Ludiomil

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Ludiomil

Classes

Tetracyclic Antidepressants

Administration
Oral Administration

Maprotiline is administered orally.
To reduce daytime sedation and improve sleep, may administer entire daily dose at bedtime. In the minority of patients that experience stimulation and insomnia with bedtime dosing, the dose should be given in the morning or administered in divided doses over the course of the day.

Adverse Reactions
Severe

seizures / Delayed / 1.0-1.0
ileus / Delayed / 0-1.0
stroke / Early / Incidence not known
torsade de pointes / Rapid / Incidence not known
AV block / Early / Incidence not known
myocardial infarction / Delayed / Incidence not known
ventricular tachycardia / Early / Incidence not known
heart failure / Delayed / Incidence not known
suicidal ideation / Delayed / Incidence not known
ocular hypertension / Delayed / Incidence not known
toxic epidermal necrolysis / Delayed / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
agranulocytosis / Delayed / Incidence not known

Moderate

urinary retention / Early / 1.0-10.0
constipation / Delayed / 6.0-6.0
blurred vision / Early / 4.0-4.0
ataxia / Delayed / 0-1.0
akathisia / Delayed / 0-1.0
peripheral neuropathy / Delayed / 0-1.0
dysarthria / Delayed / 0-1.0
stomatitis / Delayed / 0-1.0
dysphagia / Delayed / 0-1.0
galactorrhea / Delayed / 0-1.0
impotence (erectile dysfunction) / Delayed / 0-1.0
elevated hepatic enzymes / Delayed / 0-1.0
QT prolongation / Rapid / Incidence not known
hypotension / Rapid / Incidence not known
hypertension / Early / Incidence not known
PR prolongation / Rapid / Incidence not known
orthostatic hypotension / Delayed / Incidence not known
palpitations / Early / Incidence not known
sinus tachycardia / Rapid / Incidence not known
EEG changes / Delayed / Incidence not known
confusion / Early / Incidence not known
memory impairment / Delayed / Incidence not known
hallucinations / Early / Incidence not known
mania / Early / Incidence not known
psychosis / Early / Incidence not known
depression / Delayed / Incidence not known
jaundice / Delayed / Incidence not known
edema / Delayed / Incidence not known
hyperglycemia / Delayed / Incidence not known
hypoglycemia / Early / Incidence not known
testicular swelling / Early / Incidence not known
thrombocytopenia / Delayed / Incidence not known
eosinophilia / Delayed / Incidence not known
pneumonitis / Delayed / Incidence not known

Mild

xerostomia / Early / 22.0-22.0
drowsiness / Early / 16.0-16.0
dizziness / Early / 8.0-8.0
headache / Early / 4.0-4.0
fatigue / Early / 4.0-4.0
weakness / Early / 4.0-4.0
tremor / Early / 3.0-3.0
anxiety / Delayed / 3.0-3.0
insomnia / Early / 2.0-2.0
agitation / Early / 2.0-2.0
nausea / Early / 2.0-2.0
paresthesias / Delayed / 0-1.0
tinnitus / Delayed / 0-1.0
weight gain / Delayed / 0-1.0
vomiting / Early / 0-1.0
tongue discoloration / Delayed / 0-1.0
dysgeusia / Early / 0-1.0
abdominal pain / Early / 0-1.0
diarrhea / Early / 0-1.0
weight loss / Delayed / 0-1.0
breast enlargement / Delayed / 0-1.0
gynecomastia / Delayed / 0-1.0
libido increase / Delayed / 0-1.0
libido decrease / Delayed / 0-1.0
increased urinary frequency / Early / 0-1.0
nasal congestion / Early / 0-1.0
syncope / Early / Incidence not known
nightmares / Early / Incidence not known
restlessness / Early / Incidence not known
mydriasis / Early / Incidence not known
hypersalivation / Early / Incidence not known
photosensitivity / Delayed / Incidence not known
fever / Early / Incidence not known
hyperhidrosis / Delayed / Incidence not known
pruritus / Rapid / Incidence not known
alopecia / Delayed / Incidence not known
rash / Early / Incidence not known
flushing / Rapid / Incidence not known
petechiae / Delayed / Incidence not known
purpura / Delayed / Incidence not known

Boxed Warning
Children, suicidal ideation

Safety and efficacy of maprotiline have not been established in pediatric patients less than 18 years of age. In a pooled analysis of placebo-controlled trials of antidepressants (n = 4,500 pediatrics and 77,000 adults), there was an increased risk for suicidal thoughts and behaviors in children, adolescent and young adult patients 24 years of age and younger receiving an antidepressant versus placebo, with considerable variation in the risk of suicidality among drugs. The difference in absolute risk of suicidal thoughts and behaviors across different indications was highest in those with major depression. The need for an antidepressant in children, adolescents, or young adults for any use must be weighed against the risk of suicidality; it is unknown if this risk extends to long-term use. All patients should be monitored for symptom worsening or suicidality, especially at treatment initiation or after dose changes. Caregivers and/or patients should immediately notify the prescriber of changes in behavior or suicidal ideation. A change to the treatment regimen or discontinuation of maprotiline may be necessary in patients with emerging suicidality or worsening depression. If use of maprotiline is required in a pediatric patient, caution is advisable when there is a known family history of heart disease or during use of other medications that might prolong the QTc interval. QTc interval prolongation, tachycardia, and other side effects have been reported in children who have taken cyclic antidepressants; there are rare reports of deaths due to cardiovascular side effects. Routine cardiovascular monitoring has been suggested for children receiving cyclic antidepressants due to the potential of these agents to produce adverse cardiac effects.

Common Brand Names

Ludiomil

Dea Class

Rx

Description

Tetracyclic antidepressant of dibenzo-bicyclo-octadiene derivation; efficacy is similar to the TCAs for depression; occasionally administered for other indications.

Dosage And Indications
For the treatment of depression. Oral dosage Adults 60 years and younger

Initially, 75 mg/day PO as a single dose or in divided doses for outpatients with mild to moderate depression. An initial dosage of 25 mg PO daily may be used in certain populations, such as debilitated patients. Maintain the initial dose for 2 weeks. Then may increase gradually in 25 mg increments as needed and tolerated. A maximum of 150 mg/day will result in therapeutic efficacy in most outpatients; do not exceed except in the most severely depressed patients, who may receive up to 225 mg/day PO. Severely depressed hospitalized patients should be given an initial dose of 100 to 150 mg/day, which may be gradually increased as required and tolerated. Most hospitalized patients with moderate to severe depression respond to 150 mg/day; up to 225 mg may be required in some cases. For prolonged maintenance therapy, use the lowest effective dosage. Usual maintenance dose range: 75 to 150 mg/day PO, with subsequent adjustment based on therapeutic response.

Geriatric Adults older than 60 years

In general, low doses are recommended (e.g., initially, 25 mg PO daily). The initial dose should be maintained for 2 weeks. May gradually increase in increments of 25 mg as required and tolerated. Doses of 50 to 75 mg/day PO are usually satisfactory as maintenance therapy for elderly patients who do not tolerate higher doses. Most hospitalized adults with moderate to severe depression respond to a daily dose of 150 mg/day. Usual Max: 150 mg/day PO.

Dosing Considerations
Hepatic Impairment

Specific guidelines for dosage adjustments in hepatic impairment are not available; but dosage adjustment may be needed. Maprotiline is metabolized in the liver to active metabolite and inactive metabolites. Enterohepatic circulation of both active drug and metabolites occurs.

Renal Impairment

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Drug Interactions

Abarelix: (Major) Since abarelix can cause QT prolongation, abarelix should be used cautiously, if at all, with other drugs that are associated with QT prolongation including maprotiline.
Abiraterone: (Moderate) Monitor for an increase in maprotiline-related adverse reactions if coadministration with abiraterone is necessary. Maprotiline is a CYP2D6 substrate and abiraterone is a moderate CYP2D6 inhibitor.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Additive anticholinergic effects may be seen when maprotiline is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects, such as diphenhydramine, a sedating H1-blocker.
Acetaminophen; Caffeine; Dihydrocodeine: (Major) Concomitant use of opioid agonists with maprotiline may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking maprotiline. Limit the use of opioid pain medications with maprotiline to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Acetaminophen; Caffeine; Pyrilamine: (Moderate) Additive anticholinergic effects may be seen when maprotiline is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects including sedating h1-blockers.
Acetaminophen; Chlorpheniramine: (Moderate) Additive anticholinergic effects may be seen when maprotiline is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects including sedating h1-blockers.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Additive anticholinergic effects may be seen when maprotiline is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects including sedating h1-blockers.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Additive anticholinergic effects may be seen when maprotiline is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects including sedating h1-blockers. (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Additive anticholinergic effects may be seen when maprotiline is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects including sedating h1-blockers. (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Additive anticholinergic effects may be seen when maprotiline is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects including sedating h1-blockers. (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Acetaminophen; Codeine: (Major) Concomitant use of opioid agonists with maprotiline may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking maprotiline. Limit the use of opioid pain medications with maprotiline to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Additive anticholinergic effects may be seen when maprotiline is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects including sedating h1-blockers.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Acetaminophen; Dichloralphenazone; Isometheptene: (Moderate) Additive anticholinergic and CNS effects may be seen when maprotiline is used concomitantly with dichloralphenazone. (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Acetaminophen; Diphenhydramine: (Moderate) Additive anticholinergic effects may be seen when maprotiline is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects, such as diphenhydramine, a sedating H1-blocker.
Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Acetaminophen; Hydrocodone: (Major) Concomitant use of opioid agonists with maprotiline may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking maprotiline. Limit the use of opioid pain medications with maprotiline to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Acetaminophen; Oxycodone: (Major) Concomitant use of opioid agonists with maprotiline may cause excessive sedation and somnolence. Limit the use of opioid pain medications with maprotiline to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Acetaminophen; Pamabrom; Pyrilamine: (Moderate) Additive anticholinergic effects may be seen when maprotiline is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects including sedating h1-blockers.
Acetaminophen; Phenylephrine: (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Acetaminophen; Pseudoephedrine: (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Acrivastine; Pseudoephedrine: (Moderate) Additive anticholinergic effects may be seen when maprotiline is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects including sedating h1-blockers. (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Adagrasib: (Major) Avoid concomitant use of adagrasib and maprotiline due to the potential for increased maprotiline exposure and additive risk for QT/QTc prolongation and torsade de pointes (TdP). If use is necessary, monitor for maprotiline-related adverse effects; a dosage reduction may be required. Additionally, consider taking steps to minimize the risk for QT prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring. Maprotiline is a CYP2D6 substrate, adagrasib is a moderate CYP2D6 inhibitor, and both medications have been associated with QT interval prolongation.
Alfentanil: (Major) Consider alternative therapy or reduce the dose of one or both drugs if alfentanil is used with another CNS depressant, such as maprotiline. The magnitude and duration of CNS and cardiovascular effects may be enhanced. Monitor patients for hypotension or prolonged respiratory depression and sedation. The respiratory depressant effect of alfentanil may persist longer than the measured analgesic effect; consider the total dose of all opioid agonists before ordering opioid analgesics during recovery from anesthesia.
Alfuzosin: (Moderate) Use caution when administering alfuzosin with maprotiline due to the potential for QT prolongation. Alfuzosin may prolong the QT interval in a dose-dependent manner. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Alosetron: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like maprotiline, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Alprazolam: (Moderate) Benzodiazepines or other CNS depressants should be combined cautiously with maprotiline because they could cause additive depressant effects and possible respiratory depression or hypotension. The combination of benzodiazepines and maprotiline is commonly used clinically and is considered to be safe as long as patients are monitored for excessive adverse effects from either agent. Maprotiline may lower the seizure threshold, so when benzodiazepines are used for anticonvulsant effects the patient should be monitored for desired clinical outcomes.
Amantadine: (Moderate) Amantadine may exhibit anticholinergic activity. Medications with significant anticholinergic activity, such as maprotiline, may potentiate the anticholinergic effects of amantadine. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, neurologic function, and temperature regulation.
Amiodarone: (Major) If possible, avoid coadministration of amiodarone and drugs known to prolong the QT interval. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs. Additionally, amiodarone may also inhibit the CYP2D6 metabolism of maprotiline. The need to coadminister maprotiline with amiodarone should be done with a careful assessment of risk versus benefit; consider alternative therapy to maprotiline.
Amisulpride: (Major) Monitor ECGs for QT prolongation when amisulpride is administered with maprotiline. Amisulpride causes dose- and concentration- dependent QT prolongation. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Amitriptyline: (Contraindicated) The use of maprotiline with tricyclic antidepressants (TCAs) is not generally recommended, due to the duplicative nature of therapy and the risk for side effects. Additive cardiac effects (e.g., prolonged QT interval), CNS effects, or antimuscarinic effects may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Amlodipine; Celecoxib: (Moderate) A dosage adjustment may be warranted for maprotiline if coadministered with celecoxib due to the potential for celecoxib to enhance the exposure and toxicity of maprotiline. Celecoxib is a CYP2D6 inhibitor, and maprotiline is a CYP2D6 substrate.
Amobarbital: (Major) Monitor for excessive sedation and somnolence during coadministration maprotiline and barbiturates. Concurrent use may result in additive CNS depression.
Amoxapine: (Contraindicated) The use of amoxapine with chemically-related cyclic antidepressants like maprotiline or tricyclic antidepressants (TCAs) is not generally recommended, due to the duplicative nature of therapy and the risk for side effects. Additive cardiac effects (e.g., prolonged QT interval), CNS effects, or antimuscarinic effects may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering clarithromycin with maprotiline. Administration of clarithromycin has resulted in prolongation of the QT interval and TdP. Maprotiline has also been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs, such as clarithromycin.
Amphetamine: (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Amphetamine; Dextroamphetamine: (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Anagrelide: (Major) Torsades de pointes (TdP) and ventricular tachycardia have been reported during post-marketing use of anagrelide. A cardiovascular examination, including an ECG, should be obtained in all patients prior to initiating anagrelide therapy. Monitor patients during anagrelide therapy for cardiovascular effects and evaluate as necessary. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with anagrelide include maprotiline.
Anxiolytics; Sedatives; and Hypnotics: (Moderate) CNS depressants should be combined cautiously with maprotiline because they could cause additive depressant effects and possible respiratory depression or hypotension.
Apomorphine: (Major) Exercise caution when administering apomorphine concomitantly with maprotiline as concurrent use may increase the risk of QT prolongation and CNS depression. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Dopaminergic agents like apomorphine have been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Aprepitant, Fosaprepitant: (Moderate) Use caution if maprotiline and aprepitant, fosaprepitant are used concurrently and monitor for an increase in maprotiline-related adverse effects for several days after administration of a multi-day aprepitant regimen. Maprotiline is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of maprotiline. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important.
Aripiprazole: (Major) QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs. Aripiprazole should be used cautiously with maprotiline.
Arsenic Trioxide: (Major) If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with arsenic trioxide include maprotiline. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Artemether; Lumefantrine: (Major) Artemether; lumefantrine is an inhibitor of and maprotiline is partially metabolized by the CYP2D6 isoenzyme; therefore, coadministration may lead to increased maprotiline concentrations. Furthermore, although there are no studies examining the effects of artemether; lumefantrine in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation. Concomitant use of artemether; lumefantrine with drugs that may prolong the QT interval, such as maprotiline, should be avoided. Consider ECG monitoring if maprotiline must be used with or after artemether; lumefantrine treatment.
Articaine; Epinephrine: (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Asenapine: (Major) Asenapine has been associated with QT prolongation. According to the manufacturer, asenapine should hould be avoided in combination with other agents also known to have this effect (e.g., maprotiline). Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Aspirin, ASA; Butalbital; Caffeine: (Major) Monitor for excessive sedation and somnolence during coadministration maprotiline and barbiturates. Concurrent use may result in additive CNS depression.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Skeletal muscle relaxants should be combined cautiously with cyclic antidepressants like maprotiline because they could cause additive CNS depressant effects. Depending on the specific agent (e.g., cyclobenzaprine, and orphenadrine), additive anticholinergic effects may also be seen. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Patients should be monitored for excessive adverse effects from either agent.
Aspirin, ASA; Carisoprodol: (Moderate) Skeletal muscle relaxants should be combined cautiously with cyclic antidepressants like maprotiline because they could cause additive CNS depressant effects. Depending on the specific agent (e.g., cyclobenzaprine, and orphenadrine), additive anticholinergic effects may also be seen. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Patients should be monitored for excessive adverse effects from either agent.
Aspirin, ASA; Carisoprodol; Codeine: (Major) Concomitant use of opioid agonists with maprotiline may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking maprotiline. Limit the use of opioid pain medications with maprotiline to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Moderate) Skeletal muscle relaxants should be combined cautiously with cyclic antidepressants like maprotiline because they could cause additive CNS depressant effects. Depending on the specific agent (e.g., cyclobenzaprine, and orphenadrine), additive anticholinergic effects may also be seen. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Patients should be monitored for excessive adverse effects from either agent.
Aspirin, ASA; Oxycodone: (Major) Concomitant use of opioid agonists with maprotiline may cause excessive sedation and somnolence. Limit the use of opioid pain medications with maprotiline to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Atazanavir: (Moderate) Atazanavir competitively inhibits the enzymes CYP3A4, CYP1A2 and CYP2C9. Concentrations of drugs that are substrates of these enzymes (e.g., tricyclic antidepressants) may be increased with concomitant atazanavir use. According to the manufacturer of atazanavir, coadministration of atazanavir in a patient on a tricyclic antidepressant (TCA) may result in increased serum concentrations of the TCA, and the two drugs should be coadministered with caution due to a potential for serious adverse events. Monitor the patient for anticholinergic effects (e.g., sedation, confusion, constipation) associated with TCA use. The manufacturer recommends TCA concentration monitoring if atazanavir is used concomitantly with a TCA. Maprotiline is related to the tricyclic antidepressants, and until more data is available, similar caution is advised when using maprotiline with atazanavir.
Atazanavir; Cobicistat: (Major) The plasma concentrations of maprotiline may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects is recommended during coadministration. Maprotiline serum concentration monitoring may be useful to guide dosage adjustments and prevent toxicity. Cobicistat is a CYP2D6 inhibitor, while maprotiline is a CYP2D6 substrate. (Moderate) Atazanavir competitively inhibits the enzymes CYP3A4, CYP1A2 and CYP2C9. Concentrations of drugs that are substrates of these enzymes (e.g., tricyclic antidepressants) may be increased with concomitant atazanavir use. According to the manufacturer of atazanavir, coadministration of atazanavir in a patient on a tricyclic antidepressant (TCA) may result in increased serum concentrations of the TCA, and the two drugs should be coadministered with caution due to a potential for serious adverse events. Monitor the patient for anticholinergic effects (e.g., sedation, confusion, constipation) associated with TCA use. The manufacturer recommends TCA concentration monitoring if atazanavir is used concomitantly with a TCA. Maprotiline is related to the tricyclic antidepressants, and until more data is available, similar caution is advised when using maprotiline with atazanavir.
Atomoxetine: (Minor) Use caution when administering atomoxetine with maprotiline as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Atropine: (Moderate) The anticholinergic effects of atropine may be enhanced when combined with other commonly used drugs with moderate to significant anticholinergic effects including maprotiline.
Atropine; Difenoxin: (Moderate) Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as maprotiline, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. (Moderate) The anticholinergic effects of atropine may be enhanced when combined with other commonly used drugs with moderate to significant anticholinergic effects including maprotiline.
Azelastine: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including maptrotiline.
Azelastine; Fluticasone: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including maptrotiline.
Azithromycin: (Major) Avoid coadministration of azithromycin with maprotiline due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Baclofen: (Moderate) Skeletal muscle relaxants should be combined cautiously with cyclic antidepressants like maprotiline because they could cause additive CNS depressant effects. Depending on the specific agent (e.g., cyclobenzaprine, and orphenadrine), additive anticholinergic effects may also be seen. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Patients should be monitored for excessive adverse effects from either agent.
Barbiturates: (Major) Monitor for excessive sedation and somnolence during coadministration maprotiline and barbiturates. Concurrent use may result in additive CNS depression.
Bedaquiline: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering bedaquiline with maprotiline. Bedaquiline has been reported to prolong the QT interval. Prior to initiating bedaquiline, obtain serum electrolyte concentrations and a baseline ECG. An ECG should also be performed at least 2, 12, and 24 weeks after starting bedaquiline therapy. Maprotiline has also been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation.
Belladonna; Opium: (Major) Concomitant use of opioid agonists with maprotiline may cause excessive sedation and somnolence. Limit the use of opioid pain medications with maprotiline to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Benzhydrocodone; Acetaminophen: (Major) Concomitant use of opioid agonists with maprotiline may cause excessive sedation and somnolence. Limit the use of opioid pain medications with maprotiline to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Benzodiazepines: (Moderate) Benzodiazepines or other CNS depressants should be combined cautiously with maprotiline because they could cause additive depressant effects and possible respiratory depression or hypotension. The combination of benzodiazepines and maprotiline is commonly used clinically and is considered to be safe as long as patients are monitored for excessive adverse effects from either agent. Maprotiline may lower the seizure threshold, so when benzodiazepines are used for anticonvulsant effects the patient should be monitored for desired clinical outcomes.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Additive anticholinergic effects may be seen when hyoscyamine is used concomitantly with other drugs with moderate to significant anticholinergic effects including maprotiline. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. (Moderate) Maprotiline should be used cautiously with intravenous methylene blue. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin and norepinephrine in the brain (MAO-A). Maprotiline is a selective norepinephrine reuptake inhibitor. Therefore, the potential for serotonin syndrome during coadministration of maprotiline and methylene blue is unclear. Monitoring for potential increases in blood pressure is advised.
Benzphetamine: (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Benztropine: (Moderate) Additive anticholinergic effects may be seen when benztropine is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects including maprotiline. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Berotralstat: (Moderate) Monitor for an increase in maprotiline-related adverse reactions if coadministration with berotralstat is necessary; a dose reduction of maprotiline may be necessary. Concurrent use may increase exposure of maprotiline. Maprotiline is a CYP2D6 substrate and berotralstat is a CYP2D6 inhibitor.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and maprotiline may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Bismuth Subsalicylate: (Moderate) Antidiarrheals decrease GI motility. Agents that inhibit intestinal motility or prolong intestinal transit time have been reported to induce toxic megacolon. The concomitant administration of maprotiline may produce additive effects.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Antidiarrheals decrease GI motility. Agents that inhibit intestinal motility or prolong intestinal transit time have been reported to induce toxic megacolon. The concomitant administration of maprotiline may produce additive effects. (Moderate) Concomitant use of metronidazole and maprotiline may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Brexpiprazole: (Moderate) Due to the CNS effects of brexpiprazole, caution is advisable when brexpiprazole is given in combination with other centrally-acting medications including heterocyclic antidepressants.
Brompheniramine: (Moderate) Additive anticholinergic effects may be seen when maprotiline is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects including sedating h1-blockers.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Additive anticholinergic effects may be seen when maprotiline is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects including sedating h1-blockers. (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Brompheniramine; Phenylephrine: (Moderate) Additive anticholinergic effects may be seen when maprotiline is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects including sedating h1-blockers. (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Brompheniramine; Pseudoephedrine: (Moderate) Additive anticholinergic effects may be seen when maprotiline is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects including sedating h1-blockers. (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Additive anticholinergic effects may be seen when maprotiline is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects including sedating h1-blockers. (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) Additive anticholinergic effects may be seen when glycopyrrolate is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects including maprotiline.
Bupivacaine; Epinephrine: (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Buprenorphine: (Moderate) Concomitant use of buprenorphine with other CNS depressants can lead to additive CNS depressive effects. Hypotension, profound sedation, coma, respiratory depression, or death may occur; examples of other CNS depressants can include maprotiline. Prior to concurrent use of buprenorphine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. A dose reduction of one or both drugs may be warranted. It is recommended that the injectable buprenorphine dose be halved for patients who receive other drugs with CNS depressant effects; for the buprenorphine transdermal patch, start with the 5 mcg/hour patch. Monitor patients for sedation or respiratory depression.
Buprenorphine; Naloxone: (Moderate) Concomitant use of buprenorphine with other CNS depressants can lead to additive CNS depressive effects. Hypotension, profound sedation, coma, respiratory depression, or death may occur; examples of other CNS depressants can include maprotiline. Prior to concurrent use of buprenorphine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. A dose reduction of one or both drugs may be warranted. It is recommended that the injectable buprenorphine dose be halved for patients who receive other drugs with CNS depressant effects; for the buprenorphine transdermal patch, start with the 5 mcg/hour patch. Monitor patients for sedation or respiratory depression.
Bupropion: (Major) Concurrent administration of maprotiline with bupropion should be undertaken only with extreme caution due to the potential for increased risk of seizures from the lowering of seizure threshold. In addition, bupropion inhibits the hepatic isozyme CYP2D6 and thus may reduce the clearance of maprotiline leading to a potential for increased Cmax, AUC and half-life. Maprotiline appears to be metabolized via CYP2D6. Low initial dosing and gradual dose increases of both drugs should be employed. If bupropion is added to a regimen of a patient already receiving maprotiline, the need to reduce the maprotiline dosage should be considered.
Bupropion; Naltrexone: (Major) Concurrent administration of maprotiline with bupropion should be undertaken only with extreme caution due to the potential for increased risk of seizures from the lowering of seizure threshold. In addition, bupropion inhibits the hepatic isozyme CYP2D6 and thus may reduce the clearance of maprotiline leading to a potential for increased Cmax, AUC and half-life. Maprotiline appears to be metabolized via CYP2D6. Low initial dosing and gradual dose increases of both drugs should be employed. If bupropion is added to a regimen of a patient already receiving maprotiline, the need to reduce the maprotiline dosage should be considered.
Buspirone: (Moderate) CNS depressants should be combined cautiously with maprotiline because they could cause additive depressant effects and possible respiratory depression or hypotension.
Butabarbital: (Major) Monitor for excessive sedation and somnolence during coadministration maprotiline and barbiturates. Concurrent use may result in additive CNS depression.
Butalbital; Acetaminophen: (Major) Monitor for excessive sedation and somnolence during coadministration maprotiline and barbiturates. Concurrent use may result in additive CNS depression.
Butalbital; Acetaminophen; Caffeine: (Major) Monitor for excessive sedation and somnolence during coadministration maprotiline and barbiturates. Concurrent use may result in additive CNS depression.
Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Concomitant use of opioid agonists with maprotiline may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking maprotiline. Limit the use of opioid pain medications with maprotiline to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Major) Monitor for excessive sedation and somnolence during coadministration maprotiline and barbiturates. Concurrent use may result in additive CNS depression.
Butalbital; Aspirin; Caffeine; Codeine: (Major) Concomitant use of opioid agonists with maprotiline may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking maprotiline. Limit the use of opioid pain medications with maprotiline to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Major) Monitor for excessive sedation and somnolence during coadministration maprotiline and barbiturates. Concurrent use may result in additive CNS depression.
Butorphanol: (Moderate) Pain medications such as buprenorphine; butorphanol; nalbuphine; pentazocine; should be combined cautiously with maprotiline because they could cause additive depressant effects and possible respiratory depression or hypotension.
Cabotegravir; Rilpivirine: (Moderate) Caution is advised when administering rilpivirine with maprotiline as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Maprotiline has also been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Cannabidiol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and maprotiline. CNS depressants can potentiate the effects of cannabidiol.
Capsaicin; Metaxalone: (Moderate) Skeletal muscle relaxants should be combined cautiously with cyclic antidepressants like maprotiline because they could cause additive CNS depressant effects. Depending on the specific agent (e.g., cyclobenzaprine, and orphenadrine), additive anticholinergic effects may also be seen. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Patients should be monitored for excessive adverse effects from either agent.
Carbamazepine: (Moderate) Maprotiline, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions. Monitor patients on anticonvulsants carefully when maprotiline is used concurrently. Because of the lowering of seizure threshold, an alternative antidepressant may be a more optimal choice for patients taking drugs for epilepsy.
Carbidopa; Levodopa: (Moderate) Maprotiline exhibits antimuscarinic activity and can decrease gastric motility, decreasing the bioavailability of levodopa. In addition, severe hypertension occurred in a limited number of patients who received levodopa in combination with a tricyclic antidepressant.
Carbidopa; Levodopa; Entacapone: (Moderate) Maprotiline exhibits antimuscarinic activity and can decrease gastric motility, decreasing the bioavailability of levodopa. In addition, severe hypertension occurred in a limited number of patients who received levodopa in combination with a tricyclic antidepressant.
Carbinoxamine: (Moderate) Additive anticholinergic effects may be seen when maprotiline is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects including sedating h1-blockers.
Cariprazine: (Moderate) Due to the CNS effects of cariprazine, caution is advisable when cariprazine is given in combination with other centrally-acting medications including heterocyclic antidepressants.
Carisoprodol: (Moderate) Skeletal muscle relaxants should be combined cautiously with cyclic antidepressants like maprotiline because they could cause additive CNS depressant effects. Depending on the specific agent (e.g., cyclobenzaprine, and orphenadrine), additive anticholinergic effects may also be seen. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Patients should be monitored for excessive adverse effects from either agent.
Celecoxib: (Moderate) A dosage adjustment may be warranted for maprotiline if coadministered with celecoxib due to the potential for celecoxib to enhance the exposure and toxicity of maprotiline. Celecoxib is a CYP2D6 inhibitor, and maprotiline is a CYP2D6 substrate.
Celecoxib; Tramadol: (Major) Concomitant use of opioid agonists with maprotiline may cause excessive sedation and somnolence. Use of tramadol may also increase the risk of seizures in patients receiving other drugs associated with seizures such as maprotiline. Limit the use of opioid pain medications with maprotiline to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and seizures. (Moderate) A dosage adjustment may be warranted for maprotiline if coadministered with celecoxib due to the potential for celecoxib to enhance the exposure and toxicity of maprotiline. Celecoxib is a CYP2D6 inhibitor, and maprotiline is a CYP2D6 substrate.
Cenobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cenobamate and maprotiline. Concurrent use may result in additive CNS depression.
Ceritinib: (Major) Avoid coadministration of ceritinib with maprotiline if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Cetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with heterocyclic antidepressants should generally be avoided. Coadministration may increase the risk of anticholinergic and CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive anticholinergic effects, sedation, and somnolence.
Cetirizine; Pseudoephedrine: (Moderate) Concurrent use of cetirizine/levocetirizine with heterocyclic antidepressants should generally be avoided. Coadministration may increase the risk of anticholinergic and CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive anticholinergic effects, sedation, and somnolence. (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Additive anticholinergic effects may be seen when maprotiline is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects including sedating h1-blockers. (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Chlorcyclizine: (Moderate) Additive anticholinergic effects may be seen when maprotiline is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects including sedating h1-blockers.
Chlordiazepoxide: (Moderate) Benzodiazepines or other CNS depressants should be combined cautiously with maprotiline because they could cause additive depressant effects and possible respiratory depression or hypotension. The combination of benzodiazepines and maprotiline is commonly used clinically and is considered to be safe as long as patients are monitored for excessive adverse effects from either agent. Maprotiline may lower the seizure threshold, so when benzodiazepines are used for anticonvulsant effects the patient should be monitored for desired clinical outcomes.
Chlordiazepoxide; Amitriptyline: (Contraindicated) The use of maprotiline with tricyclic antidepressants (TCAs) is not generally recommended, due to the duplicative nature of therapy and the risk for side effects. Additive cardiac effects (e.g., prolonged QT interval), CNS effects, or antimuscarinic effects may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. (Moderate) Benzodiazepines or other CNS depressants should be combined cautiously with maprotiline because they could cause additive depressant effects and possible respiratory depression or hypotension. The combination of benzodiazepines and maprotiline is commonly used clinically and is considered to be safe as long as patients are monitored for excessive adverse effects from either agent. Maprotiline may lower the seizure threshold, so when benzodiazepines are used for anticonvulsant effects the patient should be monitored for desired clinical outcomes.
Chlordiazepoxide; Clidinium: (Moderate) Additive anticholinergic and CNS effects may be seen when maprotiline is used concomitantly with clidinium. (Moderate) Benzodiazepines or other CNS depressants should be combined cautiously with maprotiline because they could cause additive depressant effects and possible respiratory depression or hypotension. The combination of benzodiazepines and maprotiline is commonly used clinically and is considered to be safe as long as patients are monitored for excessive adverse effects from either agent. Maprotiline may lower the seizure threshold, so when benzodiazepines are used for anticonvulsant effects the patient should be monitored for desired clinical outcomes.
Chloroquine: (Major) Avoid coadministration of chloroquine with maprotiline due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Chloroquine is associated with an increased risk of QT prolongation and torsade de pointes (TdP); the risk of QT prolongation is increased with higher chloroquine doses. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Chlorpheniramine: (Moderate) Additive anticholinergic effects may be seen when maprotiline is used concomitantly with other commonly used drugs with moderate to significant anticholinergi

c effects including sedating h1-blockers.
Chlorpheniramine; Codeine: (Major) Concomitant use of opioid agonists with maprotiline may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking maprotiline. Limit the use of opioid pain medications with maprotiline to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Moderate) Additive anticholinergic effects may be seen when maprotiline is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects including sedating h1-blockers.
Chlorpheniramine; Dextromethorphan: (Moderate) Additive anticholinergic effects may be seen when maprotiline is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects including sedating h1-blockers.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Additive anticholinergic effects may be seen when maprotiline is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects including sedating h1-blockers. (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Additive anticholinergic effects may be seen when maprotiline is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects including sedating h1-blockers. (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Major) Concomitant use of opioid agonists with maprotiline may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking maprotiline. Limit the use of opioid pain medications with maprotiline to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Moderate) Additive anticholinergic effects may be seen when maprotiline is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects including sedating h1-blockers. (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Chlorpheniramine; Hydrocodone: (Major) Concomitant use of opioid agonists with maprotiline may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking maprotiline. Limit the use of opioid pain medications with maprotiline to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Moderate) Additive anticholinergic effects may be seen when maprotiline is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects including sedating h1-blockers.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Additive anticholinergic effects may be seen when maprotiline is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects including sedating h1-blockers. (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Chlorpheniramine; Phenylephrine: (Moderate) Additive anticholinergic effects may be seen when maprotiline is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects including sedating h1-blockers. (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Chlorpheniramine; Pseudoephedrine: (Moderate) Additive anticholinergic effects may be seen when maprotiline is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects including sedating h1-blockers. (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Chlorpromazine: (Major) Phenothiazines have been reported to prolong the QT interval. Because maprotiline is associated with a possible risk for QT prolongation and torsade de pointes (TdP), concurrent use with chlorpromazine should be approached with caution. If coadministration is considered necessary, and the patient has known risk factors for cardiac disease or arrhythmia, then close monitoring is essential. In addition, additive anticholinergic effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity such as maprotiline. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive hypotension or CNS effects such as drowsiness may also occur.
Chlorthalidone; Clonidine: (Major) Concurrent use of clonidine with maprotiline should be avoided when possible, due to multiple possible interactions. Clonidine's antihypertensive effect can be reduced by cyclic antidepressants, such as maprotiline. If coadministration of maprotiline with clonidine cannot be avoided, the patient should be closely monitored for increased blood pressure and clonidine dosages adjusted as needed.
Chlorzoxazone: (Moderate) Skeletal muscle relaxants should be combined cautiously with cyclic antidepressants like maprotiline because they could cause additive CNS depressant effects. Depending on the specific agent (e.g., cyclobenzaprine, and orphenadrine), additive anticholinergic effects may also be seen. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Patients should be monitored for excessive adverse effects from either agent.
Cholinergic agonists: (Major) Maprotiline may antagonize some of the effects of parasympathomimetics. However, bethanechol has occasionally been used therapeutically to offset some of the adverse antimuscarinic effects of cyclic antidepressants. Due to their anticholinergic actions, some cyclic antidepressants like maprotiline may potentially antagonize the therapeutic actions of the cholinesterase-inhibitors used for the treatment of dementia.
Cimetidine: (Moderate) Cimetidine can inhibit the systemic clearance of drugs that undergo oxidative metabolism, such as maprotiline, resulting in increased plasma levels of the antidepressant. Patients should be monitored for maprotiline-related side effects and toxicity if cimetidine is added; when possible, choose an alternative H2-blocker for treatment.
Cinacalcet: (Moderate) Monitor for an increase in maprotiline-related adverse reactions if coadministration with cinacalcet is necessary; a dose reduction of maprotiline may be necessary. Concurrent use may increase exposure of maprotiline. Maprotiline is a CYP2D6 substrate and cinacalcet is a CYP2D6 inhibitor.
Ciprofloxacin: (Major) Concomitant use of ciprofloxacin and maprotiline increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Cisapride: (Contraindicated) Cisapride exhibits many important drug interactions that affect its safety and efficacy profile; the manufacturer only offers cisapride therapy through an investigational limited access program due to the need to appropriately screen for eligible patients. Cisapride has been implicated as a cause of QT prolongation, particularly in patients with known risk factors or when cisapride has been combined with drugs that increase cisapride serum concentrations or exhibit additive effects on cardiac repolarization. Maprotiline is related to the tricyclic antidepressants and has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Due to the potential for serious cardiac side effects, maprotiline is contraindicated for use along with cisapride. In addition to adverse cardiac effects, the antimuscarinic effects of maprotiline may hinder the therapeutic actions of cisapride on GI motility.
Citalopram: (Major) Because citalopram and maprotiline are associated with a possible risk for QT prolongation and torsade de pointes (TdP), these combinations should be used cautiously and with close monitoring. Monitoring of the ECG is recommended in patients receiving citalopram with other drugs that may prolong the QT interval such as maprotiline. CYP2D6, the primary isoenzyme responsible for the metabolism of maprotiline, is inhibited to some extent by citalopram. Patients receiving maprotiline should be monitored closely for toxicity if an SSRI is added.
Clarithromycin: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering clarithromycin with maprotiline. Administration of clarithromycin has resulted in prolongation of the QT interval and TdP. Maprotiline has also been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs, such as clarithromycin.
Clemastine: (Moderate) Additive anticholinergic effects may be seen when maprotiline is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects including sedating h1-blockers.
Clobazam: (Moderate) These drugs may be used together with caution. You may feel drowsy or more tired when taking these drugs together. Do not drive or operate machinery until you know how these drugs affect you. Notify your health care provider if you notice that your medication is not working as well for you, or if you experience confusion, dizziness, falls, unsteadiness, or other troublesome side effects. A dosage reduction of CYP2D6 substrates, such as maprotiline, may be necessary during co-administration of clobazam. Limited in vivo data suggest that clobazam is an inhibitor of CYP2D6. If these agents are used in combination, it is advisable to monitor the patient for maprotiline-related adverse reactions.
Clofazimine: (Moderate) Concomitant use of clofazimine and maprotiline may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Clomipramine: (Contraindicated) The use of maprotiline with tricyclic antidepressants (TCAs) is not generally recommended, due to the duplicative nature of therapy and the risk for side effects. Additive cardiac effects (e.g., prolonged QT interval), CNS effects, or antimuscarinic effects may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Clonazepam: (Moderate) Benzodiazepines or other CNS depressants should be combined cautiously with maprotiline because they could cause additive depressant effects and possible respiratory depression or hypotension. The combination of benzodiazepines and maprotiline is commonly used clinically and is considered to be safe as long as patients are monitored for excessive adverse effects from either agent. Maprotiline may lower the seizure threshold, so when benzodiazepines are used for anticonvulsant effects the patient should be monitored for desired clinical outcomes.
Clonidine: (Major) Concurrent use of clonidine with maprotiline should be avoided when possible, due to multiple possible interactions. Clonidine's antihypertensive effect can be reduced by cyclic antidepressants, such as maprotiline. If coadministration of maprotiline with clonidine cannot be avoided, the patient should be closely monitored for increased blood pressure and clonidine dosages adjusted as needed.
Clorazepate: (Moderate) Benzodiazepines or other CNS depressants should be combined cautiously with maprotiline because they could cause additive depressant effects and possible respiratory depression or hypotension. The combination of benzodiazepines and maprotiline is commonly used clinically and is considered to be safe as long as patients are monitored for excessive adverse effects from either agent. Maprotiline may lower the seizure threshold, so when benzodiazepines are used for anticonvulsant effects the patient should be monitored for desired clinical outcomes.
Clozapine: (Major) Caution is recommended during concurrent treatment of clozapine with heterocyclic antidepressants including amoxapine or maprotiline. Treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death. Amoxapine and maprotiline have a possible risk of QT prolongation and TdP. The manufacturer of clozapine recommends caution during concurrent use with medications known to cause QT prolongation. Additive anticholinergic effects may be seen when clozapine is used concomitantly with other drugs known to possess antimuscarinic activity like amoxapine or maprotiline. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive hypotension or sedation is also possible when clozapine is combined with these drugs. In addition, clozapine is metabolized by CYP1A2 and CYP2D6 isoenzymes; maprotiline is also metabolized via CYP2D6 and could compete for the same metabolic pathway.
Cobicistat: (Major) The plasma concentrations of maprotiline may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects is recommended during coadministration. Maprotiline serum concentration monitoring may be useful to guide dosage adjustments and prevent toxicity. Cobicistat is a CYP2D6 inhibitor, while maprotiline is a CYP2D6 substrate.
Cocaine: (Moderate) Monitor patients for increased CNS stimulation during coadministration of cocaine and maprotiline. Concurrent use of cocaine and cyclic antidepressants may increase the risk for excessive sympathetic CNS activity leading to symptoms such as tachycardia, hypertension, diaphoresis, agitation, cardiac arrythmias, or convulsions.
Codeine: (Major) Concomitant use of opioid agonists with maprotiline may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking maprotiline. Limit the use of opioid pain medications with maprotiline to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Codeine; Guaifenesin: (Major) Concomitant use of opioid agonists with maprotiline may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking maprotiline. Limit the use of opioid pain medications with maprotiline to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Codeine; Guaifenesin; Pseudoephedrine: (Major) Concomitant use of opioid agonists with maprotiline may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking maprotiline. Limit the use of opioid pain medications with maprotiline to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Codeine; Phenylephrine; Promethazine: (Major) Concomitant use of opioid agonists with maprotiline may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking maprotiline. Limit the use of opioid pain medications with maprotiline to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Moderate) Promethazine carries a risk of QT prolongation and should be used cautiously with drugs that may prolong the QT interval and have additive anticholinergic properties such as maprotiline. Additive drowsiness and sedation are also possible. Clinicians should note that additive anticholinergic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Codeine; Promethazine: (Major) Concomitant use of opioid agonists with maprotiline may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking maprotiline. Limit the use of opioid pain medications with maprotiline to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Moderate) Promethazine carries a risk of QT prolongation and should be used cautiously with drugs that may prolong the QT interval and have additive anticholinergic properties such as maprotiline. Additive drowsiness and sedation are also possible. Clinicians should note that additive anticholinergic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
COMT inhibitors: (Major) COMT inhibitors should be given cautiously with other agents that cause CNS depression, such as heterocyclic antidepressants, due to the possibility of additive sedation. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Crizotinib: (Major) Avoid coadministration of crizotinib with maprotiline due to the risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib if QT prolongation occurs. Crizotinib has been associated with concentration-dependent QT prolongation. Maprotiline has also been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Cyclizine: (Moderate) Additive anticholinergic effects may be seen when maprotiline is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects including sedating h1-blockers.
Cyclobenzaprine: (Major) Concurrent use of cyclobenzaprine should generally be avoided in patients taking maprotiline due to the additive risk of similar pharmacology and side-effect profiles. Cyclobenzaprine possesses antimuscarinic properties, which can cause dry mouth, urinary difficulties and slowing of gastrointestinal motility. If used with other drugs with antimuscarinic properties, such as maprotiline, anticholinergic side effects can be additive. Particular attention should be paid to GI problems because of the possible development of paralytic ileus. Patients should be monitored for excessive adverse effects from either agent.
Cyproheptadine: (Moderate) Additive anticholinergic effects may be seen when maprotiline is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects including sedating h1-blockers.
Dacomitinib: (Moderate) Monitor for increased toxicity of maprotiline, such as increased anticholinergic effects, if coadministered with dacomitinib. Coadministration may increase serum concentrations of maprotiline. Maprotiline is a CYP2D6 substrate; dacomitinib is a strong CYP2D6 inhibitor.
Dantrolene: (Moderate) Skeletal muscle relaxants should be combined cautiously with cyclic antidepressants like maprotiline because they could cause additive CNS depressant effects. Depending on the specific agent (e.g., cyclobenzaprine, and orphenadrine), additive anticholinergic effects may also be seen. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Patients should be monitored for excessive adverse effects from either agent.
Darifenacin: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like darifenacin are used concomitantly with maprotiline.
Darunavir: (Major) The plasma concentrations of maprotiline may be elevated when administered concurrently with darunavir. Clinical monitoring for adverse effects is recommended during coadministration. Maprotiline serum concentration monitoring may be useful to guide dosage adjustments and prevent toxicity. Darunavir is a CYP2D6 inhibitor, while maprotiline is a CYP2D6 substrate.
Darunavir; Cobicistat: (Major) The plasma concentrations of maprotiline may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects is recommended during coadministration. Maprotiline serum concentration monitoring may be useful to guide dosage adjustments and prevent toxicity. Cobicistat is a CYP2D6 inhibitor, while maprotiline is a CYP2D6 substrate. (Major) The plasma concentrations of maprotiline may be elevated when administered concurrently with darunavir. Clinical monitoring for adverse effects is recommended during coadministration. Maprotiline serum concentration monitoring may be useful to guide dosage adjustments and prevent toxicity. Darunavir is a CYP2D6 inhibitor, while maprotiline is a CYP2D6 substrate.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) The plasma concentrations of maprotiline may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects is recommended during coadministration. Maprotiline serum concentration monitoring may be useful to guide dosage adjustments and prevent toxicity. Cobicistat is a CYP2D6 inhibitor, while maprotiline is a CYP2D6 substrate. (Major) The plasma concentrations of maprotiline may be elevated when administered concurrently with darunavir. Clinical monitoring for adverse effects is recommended during coadministration. Maprotiline serum concentration monitoring may be useful to guide dosage adjustments and prevent toxicity. Darunavir is a CYP2D6 inhibitor, while maprotiline is a CYP2D6 substrate.
Dasatinib: (Moderate) Due to a possible risk for QT prolongation and torsade de pointes (TdP), dasatinib and maprotiline should be used together cautiously. In vitro studies have shown that dasatinib has the potential to prolong cardiac ventricular repolarization (prolong QT interval). Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Degarelix: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving maprotiline as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy (i.e., degarelix) may prolong the QT/QTc interval. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Delavirdine: (Moderate) Delavirdine inhibits CYP2D6 and may increase concentrations of other drugs metabolized by this enzyme including maprotiline. A dosage adjustment of maprotiline may be needed when given concurrently with delavirdine.
Desflurane: (Major) Halogenated anesthetics can prolong the QT interval. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously and with close monitoring with halogenated anesthetics include maprotiline.
Desipramine: (Contraindicated) The use of maprotiline with tricyclic antidepressants (TCAs) is not generally recommended, due to the duplicative nature of therapy and the risk for side effects. Additive cardiac effects (e.g., prolonged QT interval), CNS effects, or antimuscarinic effects may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Desloratadine; Pseudoephedrine: (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Deutetrabenazine: (Moderate) Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs. Deutetrabenazine may prolong the QT interval, but the degree of QT prolongation is not clinically significant when deutetrabenazine is administered within the recommended dosage range. Monitor for signs and symptoms of neuroleptic malignant syndrome (NMS), restlessness, and agitation. If NMS is diagnosed, immediately discontinue deutetrabenazine, and provide intensive symptomatic treatment and medical monitoring. Recurrence of NMS has been reported with resumption of drug therapy. If akathisia or parkinsonism develops during treatment, the deutetrabenazine dose should be reduced; discontinuation may be required. Deutetrabenazine is a reversible, dopamine depleting drug and neuroleptic malignant-like syndrome has been reported with maprotiline. Monitor for excessive sedation and somnolence during coadministration of maprotiline and deutetrabenazine. Concurrent use may result in additive CNS depression.
Dexbrompheniramine; Pseudoephedrine: (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Dexchlorpheniramine: (Moderate) Additive anticholinergic effects may be seen when maprotiline is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects including sedating h1-blockers.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Additive anticholinergic effects may be seen when maprotiline is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects including sedating h1-blockers. (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Dexmedetomidine: (Minor) QT/QTc prolongation can occur with concomitant use of dexmedetomidine and maprotiline although the risk of developing torsade de pointes (TdP) is low. Additional steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, may be considered in patients with additional risk factors for TdP.
Dexmethylphenidate: (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Dextroamphetamine: (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Dextromethorphan; Bupropion: (Major) Concurrent administration of maprotiline with bupropion should be undertaken only with extreme caution due to the potential for increased risk of seizures from the lowering of seizure threshold. In addition, bupropion inhibits the hepatic isozyme CYP2D6 and thus may reduce the clearance of maprotiline leading to a potential for increased Cmax, AUC and half-life. Maprotiline appears to be metabolized via CYP2D6. Low initial dosing and gradual dose increases of both drugs should be employed. If bupropion is added to a regimen of a patient already receiving maprotiline, the need to reduce the maprotiline dosage should be considered.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Additive anticholinergic effects may be seen when maprotiline is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects, such as diphenhydramine, a sedating H1-blocker. (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Dextromethorphan; Quinidine: (Contraindicated) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine include maprotiline.
Diazepam: (Moderate) Benzodiazepines or other CNS depressants should be combined cautiously with maprotiline because they could cause additive depressant effects and possible respiratory depression or hypotension. The combination of benzodiazepines and maprotiline is commonly used clinically and is considered to be safe as long as patients are monitored for excessive adverse effects from either agent. Maprotiline may lower the seizure threshold, so when benzodiazepines are used for anticonvulsant effects the patient should be monitored for desired clinical outcomes.
Dicyclomine: (Moderate) Additive anticholinergic effects may be seen when dicyclomine is used concomitantly with other drugs that possess anticholinergic properties, such as maprotiline. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur.
Diethylpropion: (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Difelikefalin: (Moderate) Monitor for dizziness, somnolence, mental status changes, and gait disturbances if concomitant use of difelikefalin with CNS depressants is necessary. Concomitant use may increase the risk for these adverse reactions.
Dimenhydrinate: (Moderate) Additive anticholinergic effects may be seen when maprotiline is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects including sedating h1-blockers.
Diphenhydramine: (Moderate) Additive anticholinergic effects may be seen when maprotiline is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects, such as diphenhydramine, a sedating H1-blocker.
Diphenhydramine; Ibuprofen: (Moderate) Additive anticholinergic effects may be seen when maprotiline is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects, such as diphenhydramine, a sedating H1-blocker.
Diphenhydramine; Naproxen: (Moderate) Additive anticholinergic effects may be seen when maprotiline is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects, such as diphenhydramine, a sedating H1-blocker.
Diphenhydramine; Phenylephrine: (Moderate) Additive anticholinergic effects may be seen when maprotiline is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects, such as diphenhydramine, a sedating H1-blocker. (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Diphenoxylate; Atropine: (Moderate) Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as maprotiline, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. (Moderate) The anticholinergic effects of atropine may be enhanced when combined with other commonly used drugs with moderate to significant anticholinergic effects including maprotiline.
Disopyramide: (Major) Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs. Disopyramide is associated with a possible risk for QT prolongation and TdP and should be used cautiously with maprotiline. In addition to effects on the EKG, disopyramide also has significant anticholinergic effects that are additive to those of maprotiline.
Disulfiram: (Moderate) The combination of cyclic antidepressants with disulfiram can produce transient delirium. Pharmacokinetic interactions have been noted between disulfiram and tricyclic antidepressants, but the clinical significance is uncertain. Disulfiram is known to inhibit some of the hepatic cytochrome P450 isoenzymes involved in cyclic antidepressant metabolism.
Dobutamine: (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Dofetilide: (Major) Coadministration of dofetilide and maprotiline is not recommended as concurrent use may increase the risk of QT prolongation. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Dolasetron: (Moderate) Administer dolasetron with caution in combination with maprotiline as concurrent use may increase the risk of QT prolongation. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Dolutegravir; Rilpivirine: (Moderate) Caution is advised when administering rilpivirine with maprotiline as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Maprotiline has also been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Donepezil: (Moderate) Use donepezil with caution in combination with maprotiline as concurrent use may increase the risk of QT prolongation; the efficacy of donepezil may also be reduced. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs. Maprotiline may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of donepezil. Donepezil inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine.
Donepezil; Memantine: (Moderate) Use donepezil with caution in combination with maprotiline as concurrent use may increase the risk of QT prolongation; the efficacy of donepezil may also be reduced. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs. Maprotiline may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of donepezil. Donepezil inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine.
Dopamine: (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Doxapram: (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Doxepin: (Contraindicated) The use of maprotiline with tricyclic antidepressants (TCAs) is not generally recommended, due to the duplicative nature of therapy and the risk for side effects. Additive cardiac effects (e.g., prolonged QT interval), CNS effects, or antimuscarinic effects may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Doxylamine: (Moderate) Additive anticholinergic effects may be seen when maprotiline is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects including sedating h1-blockers.
Doxylamine; Pyridoxine: (Moderate) Additive anticholinergic effects may be seen when maprotiline is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects including sedating h1-blockers.
Dronabinol: (Moderate) Use caution if the use of maprotioline is necessary with dronabinol, and monitor for additive dizziness, confusion, somnolence, and other CNS effects.
Dronedarone: (Contraindicated) Concomitant use of dronedarone and maprotiline is contraindicated. Dronedarone is an inhibitor of CYP2D6. Maprotiline is a substrate for CYP2D6. Coadministration of dronedarone and maprotiline may result in elevated plasma concentrations of maprotiline. In addition, maprotiline has been established to have a possible risk of QT prolongation and Torsade de Pointes (TdP). Dronedarone administration is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 milliseconds at doses of 1600 mg twice daily. Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation.
Droperidol: (Major) Droperidol should be administered with extreme caution to patients receiving other agents that may prolong the QT interval. Droperidol administration is associated with an established risk for QT prolongation and torsades de pointes (TdP). Any drug known to have potential to prolong the QT interval should not be coadministered with droperidol. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with droperidol include maprotiline.
Duloxetine: (Major) Documentation is not available on the concurrent use of duloxetine with many CNS agents. Caution should be observed when administering duloxetine with other CNS-active drugs in the absence of clinical data regarding combined use. Examples of these drugs include the maprotiline. In addition, duloxetine is a moderate inhibitor of CYP2D6, and maprotiline appears to be metabolized by this isozyme. It is possible that duloxetine could increase the risk of cyclic-antidepressant-induced side effects or toxicity.
Efavirenz: (Moderate) Consider alternatives to efavirenz when coadministering with maprotiline as concurrent use may increase the risk of QT prolongation. QTc prolongation has been observed with the use of efavirenz. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Consider alternatives to efavirenz when coadministering with maprotiline as concurrent use may increase the risk of QT prolongation. QTc prolongation has been observed with the use of efavirenz. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Consider alternatives to efavirenz when coadministering with maprotiline as concurrent use may increase the risk of QT prolongation. QTc prolongation has been observed with the use of efavirenz. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation.
Elbasvir; Grazoprevir: (Moderate) Administering maprotiline with elbasvir; grazoprevir may result in elevated maprotiline plasma concentrations. Maprotiline is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.
Eliglustat: (Major) Coadminister maprotiline and eliglustat cautiously and with close monitoring; there may be an increased risk of QT prolongation and/or antidepressant-associated adverse effects. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). In addition, coadministration may result in increased concentrations of the antidepressant. If eliglustat and maprotiline are used together, consider reducing the dosage of maprotiline and titrating to clinical effect. Eliglustat is a CYP2D6 inhibitor, and maprotiline is a CYP2D6 substrate.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) The plasma concentrations of maprotiline may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects is recommended during coadministration. Maprotiline serum concentration monitoring may be useful to guide dosage adjustments and prevent toxicity. Cobicistat is a CYP2D6 inhibitor, while maprotiline is a CYP2D6 substrate.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) The plasma concentrations of maprotiline may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects is recommended during coadministration. Maprotiline serum concentration monitoring may be useful to guide dosage adjustments and prevent toxicity. Cobicistat is a CYP2D6 inhibitor, while maprotiline is a CYP2D6 substrate.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Caution is advised when administering rilpivirine with maprotiline as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Maprotiline has also been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is advised when administering rilpivirine with maprotiline as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Maprotiline has also been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Encorafenib: (Major) Avoid coadministration of encorafenib and maprotiline due to the potential for additive QT prolongation. If concurrent use cannot be avoided, monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia and hypomagnesemia prior to treatment. Encorafenib is associated with dose-dependent prolongation of the QT interval. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation.
Entrectinib: (Major) Avoid coadministration of entrectinib with maprotiline due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Ephedrine: (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Ephedrine; Guaifenesin: (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Epinephrine: (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Eribulin: (Major) Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with maprotiline include eribulin. ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
Erythromycin: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering erythromycin with maprotiline. Erythromycin is associated with prolongation of the QT interval and TdP. Maprotiline has also been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. In addition, erythromycin is sometimes used to stimulate GI motility, for example, in patients with diabetic gastroparesis. In patients requiring erythromycin to enhance GI motility, some cyclic antidepressants with substantial antimuscarinic properties may counteract erythromycin's effectiveness.
Escitalopram: (Moderate) Concomitant use of escitalopram and maprotiline may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors fo r TdP.
Esketamine: (Moderate) Closely monitor patients receiving esketamine and maprotiline for sedation and other CNS depressant effects. Instruct patients who receive a dose of esketamine not to drive or engage in other activities requiring alertness until the next day after a restful sleep.
Estazolam: (Moderate) Benzodiazepines or other CNS depressants should be combined cautiously with maprotiline because they could cause additive depressant effects and possible respiratory depression or hypotension. The combination of benzodiazepines and maprotiline is commonly used clinically and is considered to be safe as long as patients are monitored for excessive adverse effects from either agent. Maprotiline may lower the seizure threshold, so when benzodiazepines are used for anticonvulsant effects the patient should be monitored for desired clinical outcomes.
Ethanol: (Major) Advise patients to avoid alcohol consumption while taking CNS depressants. Alcohol consumption may result in additive CNS depression.
Ethosuximide: (Moderate) Maprotiline, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions. Monitor patients on anticonvulsants carefully when maprotiline is used concurrently. Because of the lowering of seizure threshold, an alternative antidepressant may be a more optimal choice for patients taking drugs for epilepsy.
Etomidate: (Moderate) General anesthetics may produce additive CNS depression when used in patients taking maprotiline.
Everolimus: (Moderate) Monitor for an increase in maprotiline-related adverse reactions if coadministration with everolimus is necessary; consider reducing the dose of maprotiline if clinically appropriate. Maprotiline is a CYP2D6 substrate and everolimus is a CYP2D6 inhibitor; concomitant use may increase plasma concentrations of maprotiline.
Fedratinib: (Moderate) Monitor for an increase in maprotiline-related adverse reactions if coadministration with fedratinib is necessary; a dose reduction of maprotiline may be necessary. Fedratinib is a moderate CYP2D6 inhibitor. Because of the pharmacologic similarity of maprotiline hydrochloride to the tricyclic antidepressants, the plasma concentration of maprotiline may be increased when the drug is given concomitantly with hepatic enzyme inhibitors.
Felbamate: (Major) Maprotiline, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions. Monitor patients carefully.
Fenfluramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of fenfluramine and maprotiline. Concurrent use may result in additive CNS depression.
Fentanyl: (Major) Concomitant use of opioid agonists with maprotiline may cause excessive sedation and somnolence. Limit the use of opioid pain medications with maprotiline to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Fesoterodine: (Moderate) Coadministration of fesoterodine and other drugs with moderate to significant anticholinergic effects such as maprotiline may increase the frequency and/or severity of anticholinergic effects such as blurred vision, constipation, xerostomia, and urinary retention. Additive effects may be seen on GI smooth muscle, bladder function, the CNS, the eye, and temperature regulation.
Fexofenadine; Pseudoephedrine: (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Fingolimod: (Moderate) Exercise caution when administering fingolimod concomitantly with maprotiline as concurrent use may increase the risk of QT prolongation. Fingolimod initiation results in decreased heart rate and may prolong the QT interval. Fingolimod has not been studied in patients treated with drugs that prolong the QT interval, but drugs that prolong the QT interval have been associated with cases of TdP in patients with bradycardia. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation.
Flavoxate: (Moderate) Additive anticholinergic and CNS effects may be seen when maprotiline is used concomitantly with flavoxate.
Flecainide: (Major) Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with maprotiline include flecainide, Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or torsades de pointes (TdP); flecainide increases the QT interval, but largely due to prolongation of the QRS interval.
Fluconazole: (Moderate) Concomitant use of fluconazole and maprotiline may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Flumazenil: (Major) Particular caution is necessary when using flumazenil in cases of mixed drug overdosage since the toxic effects (such as convulsions and cardiac dysrhythmias) of other drugs taken in overdose (especially cyclic antidepressants like maprotiline) may emerge with the reversal of the benzodiazepine effect by flumazenil. The reversal of benzodiazepine effects may be associated with the onset of seizures in certain high-risk populations; concurrent cyclic antidepressant poisoning is a risk factor for seizures. Flumazenil is not recommended in cases of serious cyclic antidepressant poisoning, as manifested by motor abnormalities (twitching, rigidity, focal seizure), dysrhythmia (wide QRS, ventricular dysrhythmia, heart block), anticholinergic signs (mydriasis, dry mucosa, hypoperistalsis), and cardiovascular collapse at presentation. In such cases flumazenil should be withheld and the patient should be allowed to remain sedated (with ventilatory and circulatory support as needed) until the signs of antidepressant toxicity have subsided. Treatment with flumazenil has no known benefit to the seriously ill mixed-overdose patient other than reversing sedation and should not be used in cases where seizures (from any cause) are likely.
Fluoxetine: (Moderate) Concomitant use of fluoxetine and maprotiline may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Fluphenazine: (Moderate) Fluphenazine, a phenothiazine, is associated with a possible risk for QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with fluphenazine include maprotiline. CNS effects, orthostatic hypotension, antimuscarinic effects) may occur during coadministration because maprotiline and phenothiazines are metabolized via similar pathways (CYP2D6), have structural similarities, and produce similar pharmacologic effects, like antimuscarinic activity. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Flurazepam: (Moderate) Benzodiazepines or other CNS depressants should be combined cautiously with maprotiline because they could cause additive depressant effects and possible respiratory depression or hypotension. The combination of benzodiazepines and maprotiline is commonly used clinically and is considered to be safe as long as patients are monitored for excessive adverse effects from either agent. Maprotiline may lower the seizure threshold, so when benzodiazepines are used for anticonvulsant effects the patient should be monitored for desired clinical outcomes.
Fluvoxamine: (Major) There may be an increased risk for QT prolongation and torsade de pointes (TdP) during concurrent use of fluvoxamine and maprotiline. In addition, these medications may be duplicate treatment for some conditions. Cases of QT prolongation and TdP have been reported during postmarketing use of fluvoxamine. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with elevated serum concentrations from high dose therapy. Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in commonly prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT prolonging drugs. Therefore, coadministration with fluvoxamine should be avoided if possible. In addition, fluvoxamine is a CYP2D6 inhibitor and maprotiline is a substrate for CYP2D6. In several cases, symptoms of toxicity, including seizures, have been reported when selective serotonin reuptake inhibitors (SSRIs) and cyclic antidepressants were used together. Patients receiving maprotiline should be monitored closely for toxicity if fluvoxamine is added.
Food: (Major) Advise patients to avoid cannabis use while taking CNS depressants due to the risk for additive CNS depression and potential for other cognitive adverse reactions.
Foscarnet: (Major) When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as maprotiline. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs. If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment.
Fostemsavir: (Moderate) Use maprotiline and fostemsavir together with caution due to the potential for QT prolongation. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs. Supratherapeutic doses of fostemsavir (2,400 mg twice daily, four times the recommended daily dose) have been shown to cause QT prolongation. Fostemsavir causes dose-dependent QT prolongation.
Gabapentin: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and maprotiline. Concomitant use of gabapentin with maprotiline may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
Galantamine: (Moderate) Due to their anticholinergic actions, some cyclic antidepressants, including mapotiline, may antagonize the therapeutic actions of the cholinesterase-inhibitors such as galantamine, which are used for the treatment of dementia. Consider alternatives if concurrent therapy is needed. If alternative therapy is not possible, monitor for deceased efficacy of galantamine.
Gemifloxacin: (Moderate) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering maprotiline with gemifloxacin. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs. Gemifloxacin may prolong the QT interval in some patients, with the maximal change in the QTc interval occurring approximately 5 to 10 hours following oral administration. The likelihood of QTc prolongation may increase with increasing dose of gemifloxacin; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher.
Gemtuzumab Ozogamicin: (Major) Use gemtuzumab ozogamicin and maprotiline together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Gilteritinib: (Moderate) Use caution and monitor for additive QT prolongation if concurrent use of gilteritinib and maprotiline is necessary. Gilteritinib has been associated with QT prolongation. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation.
Givosiran: (Major) Avoid concomitant use of givosiran and maprotiline due to the risk of increased maprotiline-related adverse reactions. If use is necessary, consider decreasing the maprotiline dose. Maprotiline is a CYP2D6 substrate. Givosiran may moderately reduce hepatic CYP2D6 enzyme activity because of its pharmacological effects on the hepatic heme biosynthesis pathway.
Glasdegib: (Major) Avoid coadministration of glasdegib with maprotiline due to the potential for additive QT prolongation. If coadministration cannot be avoided, monitor patients for increased risk of QT prolongation with increased frequency of ECG monitoring. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Glycopyrrolate: (Moderate) Additive anticholinergic effects may be seen when glycopyrrolate is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects including maprotiline.
Glycopyrrolate; Formoterol: (Moderate) Additive anticholinergic effects may be seen when glycopyrrolate is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects including maprotiline.
Goserelin: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., goserelin) outweigh the potential risks of QT prolongation in patients receiving maprotiline. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Androgen deprivation therapy may also prolong the QT/QTc interval. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Granisetron: (Moderate) Use granisetron with caution in combination with maprotiline due to the risk of QT prolongation and torsade de pointes (TdP). Granisetron has been associated with QT prolongation. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Guaifenesin; Hydrocodone: (Major) Concomitant use of opioid agonists with maprotiline may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking maprotiline. Limit the use of opioid pain medications with maprotiline to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Guaifenesin; Phenylephrine: (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Guaifenesin; Pseudoephedrine: (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Guanfacine: (Major) Cyclic antidepressants like maprotiline can inhibit the hypotensive effects of guanfacine, causing an increase in blood pressure if given concomitantly. Increased dosages of guanfacine may be required in patients who are receiving maprotiline concurrently. In addition, concurrent maprotiline use may enhance the potential for rebound hypertension following guanfacine discontinuation. If guanfacine is withdrawn in the presence of maprotiline or other cyclic antidepressants, guanfacine should be tapered gradually and the patient should be monitored for potential hypertension.
Guselkumab: (Moderate) Clinically relevant drug interactions may occur when guselkumab is administered with sensitive substrates of CYP2D6, such as maprotiline. Monitor maprotiline concentrations if guselkumab is initiated or discontinued; the maprotiline dose may need to be adjusted. During chronic inflammation, increased levels of certain cytokines can alter the formation of CYP450 enzymes. Thus, the formation of CYP2D6 could be normalized during guselkumab administration.
Halogenated Anesthetics: (Major) Halogenated anesthetics can prolong the QT interval. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously and with close monitoring with halogenated anesthetics include maprotiline.
Haloperidol: (Major) Haloperidol can potentiate the actions of other CNS depressants such as cyclic antidepressants. Caution should be exercised with simultaneous use of these agents due to potential excessive CNS effects. Limited data suggest that haloperidol may inhibit the metabolism of some tricyclic antidepressants, however, the clinical significance of this interaction and the effect on maprotiline is uncertain. Haloperidol is an inhibitor of hepatic CYP2D6, and coadministration with maprotiline (CYP2D6 substrate) may lead to elevated maprotiline serum concentrations, potentiating toxicity. Haloperidol has also been associated with a possible risk for QT prolongation and/or torsades de pointes, particularly when excessive doses are used or in overdose. Haloperidol should be used cautiously with other agents that may have this effect (e.g., maprotiline).
Histrelin: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving maprotiline. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Androgen deprivation therapy may also prolong the QT/QTc interval. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Homatropine; Hydrocodone: (Major) Concomitant use of opioid agonists with maprotiline may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking maprotiline. Limit the use of opioid pain medications with maprotiline to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Moderate) Additive anticholinergic effects may be seen when maprotiline is used concomitantly with other drugs known to possess relatively significant antimuscarinic properties including maprotiline and should be used together cautiously.
Hydantoins: (Moderate) Maprotiline, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold. Ethotoin, phenytoin or fosphenytoin may increase antidepressant metabolism. Monitor patients on anticonvulsants carefully when maprotiline is used concurrently. Because of the lowering of seizure threshold, an alternative antidepressant may be a more optimal choice for patients taking drugs for epilepsy.
Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) Maprotiline, as a cyclic antidepressant, can block the action of methyldopa, preventing or significantly reducing the expected antihypertensive effects. Avoid use of maprotiline concurrently with this antihypertensive drug when possible.
Hydrocodone: (Major) Concomitant use of opioid agonists with maprotiline may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking maprotiline. Limit the use of opioid pain medications with maprotiline to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Hydrocodone; Ibuprofen: (Major) Concomitant use of opioid agonists with maprotiline may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking maprotiline. Limit the use of opioid pain medications with maprotiline to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Hydrocodone; Pseudoephedrine: (Major) Concomitant use of opioid agonists with maprotiline may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking maprotiline. Limit the use of opioid pain medications with maprotiline to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Hydromorphone: (Major) Concomitant use of opioid agonists with maprotiline may cause excessive sedation and somnolence. Limit the use of opioid pain medications with maprotiline to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Hydroxychloroquine: (Major) Avoid coadministration of maprotiline and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Hydroxyzine: (Moderate) Caution is recommended if hydroxyzine is administered with maprotiline due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, additive anticholinergic effects and CNS depression may also occur. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Hyoscyamine: (Moderate) Additive anticholinergic effects may be seen when hyoscyamine is used concomitantly with other drugs with moderate to significant anticholinergic effects including maprotiline. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Additive anticholinergic effects may be seen when hyoscyamine is used concomitantly with other drugs with moderate to significant anticholinergic effects including maprotiline. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. (Moderate) Maprotiline should be used cautiously with intravenous methylene blue. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin and norepinephrine in the brain (MAO-A). Maprotiline is a selective norepinephrine reuptake inhibitor. Therefore, the potential for serotonin syndrome during coadministration of maprotiline and methylene blue is unclear. Monitoring for potential increases in blood pressure is advised.
Ibuprofen; Oxycodone: (Major) Concomitant use of opioid agonists with maprotiline may cause excessive sedation and somnolence. Limit the use of opioid pain medications with maprotiline to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Ibuprofen; Pseudoephedrine: (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Ibutilide: (Major) Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP should be used cautiously with ibutilide. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Idelalisib: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with maprotiline, a CYP3A substrate, as maprotiline toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Iloperidone: (Major) Iloperidone has been associated with QT prolongation; however, torsade de pointes (TdP) has not been reported. According to the manufacturer, since iloperidone may prolong the QT interval, it should be avoided in combination with other agents also known to have this effect, such as maprotiline.
Imatinib: (Major) Imatinib, STI-571 is a potent inhibitor of CYP2D6 and may increase concentrations of other drugs metabolized by this enzyme. Caution is recommended when administering imatinib with other CYP2D6 substrates, such as maprotiline, that have a narrow therapeutic range or where large increases in serum concentrations may be associated with severe adverse reactions.
Imipramine: (Contraindicated) The use of maprotiline with tricyclic antidepressants (TCAs) is not generally recommended, due to the duplicative nature of therapy and the risk for side effects. Additive cardiac effects (e.g., prolonged QT interval), CNS effects, or antimuscarinic effects may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Indacaterol; Glycopyrrolate: (Moderate) Additive anticholinergic effects may be seen when glycopyrrolate is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects including maprotiline.
Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with maprotiline due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Iobenguane I 131: (Major) Discontinue maprotiline for at least 5 half-lives before the administration of the dosimetry dose or a therapeutic dose of iobenguane I-131. Do not restart maprotiline until at least 7 days after each iobenguane I-131 dose. Drugs that reduce catecholamine uptake or deplete catecholamine stores, such as maprotiline, may interfere with iobenguane I-131 uptake into cells and interfere with dosimetry calculations resulting in altered iobenguane I-131 efficacy.
Isavuconazonium: (Moderate) Concomitant use of isavuconazonium with maprotiline may result in increased serum concentrations of maprotiline. Maprotiline is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Isocarboxazid: (Contraindicated) Concurrent use of isocarboxazid, a non-selective monoamine oxidase inhibitor (MAOI), and maprotiline, a selective norepinephrine reuptake inhibitor, is contraindicated. The noradrenergic effects of both maprotiline and isocarboxazid may result in hypertensive crisis. A washout period of at least 14 days is required after discontinuing treatment with isocarboxazid before initiating maprotiline. After stopping maprotiline, a washout period of at least 7 days is required, at which time isocarboxazid may be initiated at half of the normal starting dose for at least the first week of treatment.
Isoflurane: (Major) Halogenated anesthetics can prolong the QT interval. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously and with close monitoring with halogenated anesthetics include maprotiline.
Isoproterenol: (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Itraconazole: (Moderate) Use itraconazole with caution in combination with maprotiline as concurrent use may increase the risk of QT prolongation. The plasma concentration of maprotiline may also be increased; a maprotiline dosage adjustment may be necessary. Itraconazole is a strong CYP3A4 inhibitor that has been associated with prolongation of the QT interval. Maprotiline is a CYP3A4 substrate that has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Ivosidenib: (Major) Avoid coadministration of ivosidenib with maprotiline due to an increased risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. An interruption of therapy and dose reduction of ivosidenib may be necessary if QT prolongation occurs. Prolongation of the QTc interval and ventricular arrhythmias have been reported in patients treated with ivosidenib. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Ketamine: (Moderate) General anesthetics may produce additive CNS depression when used in patients taking maprotiline.
Ketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and maprotiline due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Labetalol: (Moderate) An increased incidence of labetalol-induced tremor has been reported in patients being treated concurrently with tricyclic antidepressants. Similar interactions would be expected with the related cyclic antidepressant maprotiline.
Lacosamide: (Moderate) Maprotiline, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions. Monitor patients on anticonvulsants carefully when maprotiline is used concurrently. Because of the lowering of seizure threshold, an alternative antidepressant may be a more optimal choice for patients taking drugs for epilepsy.
Lamotrigine: (Moderate) Maprotiline, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions. Monitor patients on anticonvulsants carefully when maprotiline is used concurrently. Because of the lowering of seizure threshold, an alternative antidepressant may be a more optimal choice for patients taking drugs for epilepsy.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering clarithromycin with maprotiline. Administration of clarithromycin has resulted in prolongation of the QT interval and TdP. Maprotiline has also been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs, such as clarithromycin.
Lapatinib: (Moderate) Monitor for evidence of QT prolongation if lapatinib is administered with maprotiline. Lapatinib has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and torsade de pointes (TdP) have been reported in postmarketing experience with lapatinib. Maprotiline has also been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Lasmiditan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and maprotiline. Concurrent use may result in additive CNS depression.
Lefamulin: (Major) Avoid coadministration of lefamulin with maprotiline as concurrent use may increase the risk of QT prolongation. If coadministration cannot be avoided, monitor ECG during treatment. Lefamulin has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Lemborexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and maprotiline. Dosage adjustments of lemborexant and maprotiline may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Lenvatinib: (Major) Avoid coadministration of lenvatinib with maprotiline due to the risk of QT prolongation. Prolongation of the QT interval has been reported with lenvatinib therapy. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Leuprolide: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving maprotiline. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Androgen deprivation therapy may also prolong the QT/QTc interval. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Leuprolide; Norethindrone: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving maprotiline. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Androgen deprivation therapy may also prolong the QT/QTc interval. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Levetiracetam: (Moderate) Maprotiline, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions. Monitor patients on anticonvulsants carefully when maprotiline is used concurrently. Because of the lowering of seizure threshold, an alternative antidepressant may be a more optimal choice for patients taking drugs for epilepsy.
Levocetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with heterocyclic antidepressants should generally be avoided. Coadministration may increase the risk of anticholinergic and CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive anticholinergic effects, sedation, and somnolence.
Levodopa: (Moderate) Maprotiline exhibits antimuscarinic activity and can decrease gastric motility, decreasing the bioavailability of levodopa. In addition, severe hypertension occurred in a limited number of patients who received levodopa in combination with a tricyclic antidepressant.
Levofloxacin: (Moderate) Concomitant use of levofloxacin and maprotiline may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Levoketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and maprotiline due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Levorphanol: (Major) Concomitant use of opioid agonists with maprotiline may cause excessive sedation and somnolence. Limit the use of opioid pain medications with maprotiline to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Reduce the initial dose of levorphanol by approximately 50% or more. Educate patients about the risks and symptoms of excessive CNS depression.
Lidocaine; Epinephrine: (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Linezolid: (Moderate) Maprotiline should be used cautiously with linezolid. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO), an enzyme responsible for the catabolism of serotonin, norepinephrine, and dopamine in the brain. Maprotiline is a selective norepinephrine reuptake inhibitor. Therefore, the potential for serotonin syndrome during coadministration of maprotiline and linezolid is unclear. Monitoring for potential increases in blood pressure is advised due to the potential for additive noradrenergic activity.
Lisdexamfetamine: (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Lithium: (Major) Coadministration of maprotiline and lithium may increase the risk of QT prolongation; therefore, caution and close monitoring are recommended during coadministration. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Lithium has been associated with QT prolongation.
Lofexidine: (Major) Monitor the ECG if lofexidine is coadministered with maprotiline due to the potential for additive QT prolongation and torsade de pointes (TdP). Lofexidine may prolong the QT interval, and TdP has been reported during postmarketing use. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Loperamide: (Moderate) Concomitant use of loperamide and maprotiline may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Loperamide; Simethicone: (Moderate) Concomitant use of loperamide and maprotiline may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Lopinavir; Ritonavir: (Major) Avoid coadministration of lopinavir with maprotiline due to the potential for additive QT prolongation. If use together is necessary, obtain a baseline ECG to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Lopinavir is associated with QT prolongation. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs. (Moderate) Ritonavir potently inhibits the CYP2D6 and CYP3A4 isozymes, and thus may inhibit the metabolism of maprotiline. Since the magnitude of the interaction with the maprotiline is difficult to predict but may be significant, monitor patients receiving ritonavir and maprotiline concurrently closely. Adjust the dosage of maprotiline based on therapeutic response. Maprotiline serum concentration monitoring may be useful to guide adjustments and prevent toxicity.
Loratadine; Pseudoephedrine: (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Lorazepam: (Moderate) Benzodiazepines or other CNS depressants should be combined cautiously with maprotiline because they could cause additive depressant effects and possible respiratory depression or hypotension. The combination of benzodiazepines and maprotiline is commonly used clinically and is considered to be safe as long as patients are monitored for excessive adverse effects from either agent. Maprotiline may lower the seizure threshold, so when benzodiazepines are used for anticonvulsant effects the patient should be monitored for desired clinical outcomes.
Loxapine: (Moderate) Additive anticholinergic effects may be seen when maprotiline is used concomitantly with other drugs known to possess relatively significant antimuscarinic properties including loxapine.
Lumateperone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lumateperone and maprotiline. Concurrent use may result in additive CNS depression.
Macimorelin: (Major) Avoid concurrent administration of macimorelin with drugs that prolong the QT interval, such as maprotiline. Use of these drugs together may increase the risk of developing torsade de pointes-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Meclizine: (Moderate) Additive anticholinergic effects may be seen when maprotiline is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects, such as meclizine.
Mefloquine: (Moderate) Mefloquine should be used with caution in patients receiving maprotiline as concurrent use may increase the risk of QT prolongation. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Meperidine: (Major) Concomitant use of opioid agonists with maprotiline may cause excessive sedation and somnolence. Limit the use of opioid pain medications with maprotiline to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Metaxalone: (Moderate) Skeletal muscle relaxants should be combined cautiously with cyclic antidepressants like maprotiline because they could cause additive CNS depressant effects. Depending on the specific agent (e.g., cyclobenzaprine, and orphenadrine), additive anticholinergic effects may also be seen. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Patients should be monitored for excessive adverse effects from either agent.
Methadone: (Major) Concomitant use of opioid agonists with maprotiline may cause excessive sedation and somnolence. Limit the use of opioid pain medications with maprotiline to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Methamphetamine: (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Moderate) Additive anticholinergic effects may be seen when hyoscyamine is used concomitantly with other drugs with moderate to significant anticholinergic effects including maprotiline. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. (Moderate) Maprotiline should be used cautiously with intravenous methylene blue. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin and norepinephrine in the brain (MAO-A). Maprotiline is a selective norepinephrine reuptake inhibitor. Therefore, the potential for serotonin syndrome during coadministration of maprotiline and methylene blue is unclear. Monitoring for potential increases in blood pressure is advised.
Methohexital: (Major) Monitor for excessive sedation and somnolence during coadministration maprotiline and barbiturates. Concurrent use may result in additive CNS depression.
Methscopolamine: (Moderate) Additive anticholinergic effects may be seen when methscopolamine is used concomitantly with other drugs with moderate to significant antimuscarinic effects including maprotiline.
Methsuximide: (Moderate) Maprotiline, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions. Monitor patients on anticonvulsants carefully when maprotiline is used concurrently. Because of the lowering of seizure threshold, an alternative antidepressant may be a more optimal choice for patients taking drugs for epilepsy.
Methyldopa: (Moderate) Maprotiline, as a cyclic antidepressant, can block the action of methyldopa, preventing or significantly reducing the expected antihypertensive effects. Avoid use of maprotiline concurrently with this antihypertensive drug when possible.
Methylene Blue: (Moderate) Maprotiline should be used cautiously with intravenous methylene blue. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin and norepinephrine in the brain (MAO-A). Maprotiline is a selective norepinephrine reuptake inhibitor. Therefore, the potential for serotonin syndrome during coadministration of maprotiline and methylene blue is unclear. Monitoring for potential increases in blood pressure is advised.
Methylphenidate: (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Metronidazole: (Moderate) Concomitant use of metronidazole and maprotiline may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients . Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Metyrapone: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as maprotiline, should be used with caution. Additive drowsiness and/or dizziness is possible.
Midazolam: (Moderate) Benzodiazepines or other CNS depressants should be combined cautiously with maprotiline because they could cause additive depressant effects and possible respiratory depression or hypotension. The combination of benzodiazepines and maprotiline is commonly used clinically and is considered to be safe as long as patients are monitored for excessive adverse effects from either agent. Maprotiline may lower the seizure threshold, so when benzodiazepines are used for anticonvulsant effects the patient should be monitored for desired clinical outcomes.
Midodrine: (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Midostaurin: (Major) The concomitant use of midostaurin and maprotiline may lead to additive QT interval prolongation. If these drugs are used together, consider electrocardiogram monitoring. In clinical trials, QT prolongation has been reported in patients who received midostaurin as single-agent therapy or in combination with cytarabine and daunorubicin. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation.
Mifepristone: (Major) Concomitant use of maprotiline and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Minocycline: (Minor) Injectable minocycline contains magnesium sulfate heptahydrate. Because of the CNS-depressant effects of magnesium sulfate, additive central-depressant effects can occur following concurrent administration with CNS depressants such as heterocyclic antidepressants (i.e., amoxapine, maprotiline, mirtazapine, and trazodone). Caution should be exercised when using these agents concurrently.
Mirabegron: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as maprotiline may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Mirtazapine: (Major) Concomitant use of maprotiline and mirtazapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Mitotane: (Moderate) Use caution if mitotane and maprotiline are used concomitantly, and monitor for decreased efficacy of maprotiline and a possible change in dosage requirements. Mitotane is a strong CYP3A4 inducer and maprotiline is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of maprotiline.
Mobocertinib: (Major) Concomitant use of mobocertinib and maprotiline increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Molindone: (Moderate) Antipsychotics are associated with anticholinergic effects; therefore, additive effects may be seen during concurrent use of molindone and other drugs having anticholinergic activity such as maprotiline. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or other CNS effects may also occur.
Morphine: (Major) Concomitant use of opioid agonists with maprotiline may cause excessive sedation and somnolence. Limit the use of opioid pain medications with maprotiline to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. For extended-release morphine tablets, start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of excessive CNS depression.
Morphine; Naltrexone: (Major) Concomitant use of opioid agonists with maprotiline may cause excessive sedation and somnolence. Limit the use of opioid pain medications with maprotiline to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. For extended-release morphine tablets, start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of excessive CNS depression.
Moxifloxacin: (Major) Concurrent use of maprotiline and moxifloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Moxifloxacin has been associated with prolongation of the QT interval. Additionally, post-marketing surveillance has identified very rare cases of ventricular arrhythmias including TdP, usually in patients with severe underlying proarrhythmic conditions. The likelihood of QT prolongation may increase with increasing concentrations of moxifloxacin, therefore the recommended dose or infusion rate should not be exceeded. Maprotiline has also been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation.
Nabilone: (Moderate) Nabilone or other CNS depressants should be combined cautiously with heterocyclic antidepressants because they could cause additive depressant effects and possible respiratory depression or hypotension.
Nalbuphine: (Moderate) Nalbuphine should be combined cautiously with maprotiline because it could cause additive depressant effects and possible respiratory depression or hypotension.
Naproxen; Pseudoephedrine: (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Neostigmine: (Major) Maprotiline may antagonize some of the effects of neostigmine.
Neostigmine; Glycopyrrolate: (Major) Maprotiline may antagonize some of the effects of neostigmine. (Moderate) Additive anticholinergic effects may be seen when glycopyrrolate is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects including maprotiline.
Nilotinib: (Major) Avoid the concomitant use of nilotinib and maprotiline; significant prolongation of the QT interval may occur. Sudden death and QT prolongation have been reported in patients who received nilotinib therapy. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Niraparib; Abiraterone: (Moderate) Monitor for an increase in maprotiline-related adverse reactions if coadministration with abiraterone is necessary. Maprotiline is a CYP2D6 substrate and abiraterone is a moderate CYP2D6 inhibitor.
Nirmatrelvir; Ritonavir: (Moderate) Ritonavir potently inhibits the CYP2D6 and CYP3A4 isozymes, and thus may inhibit the metabolism of maprotiline. Since the magnitude of the interaction with the maprotiline is difficult to predict but may be significant, monitor patients receiving ritonavir and maprotiline concurrently closely. Adjust the dosage of maprotiline based on therapeutic response. Maprotiline serum concentration monitoring may be useful to guide adjustments and prevent toxicity.
Nitroglycerin: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as heterocyclic antidepressants. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with these antidepressants.
Non-Ionic Contrast Media: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering the use of intrathecal radiopaque contrast agents. Maprotiline should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Norepinephrine: (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Nortriptyline: (Contraindicated) The use of maprotiline with tricyclic antidepressants (TCAs) is not generally recommended, due to the duplicative nature of therapy and the risk for side effects. Additive cardiac effects (e.g., prolonged QT interval), CNS effects, or antimuscarinic effects may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Ofloxacin: (Moderate) Concomitant use of ofloxacin and maprotiline may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Olanzapine: (Major) Coadministration may result in additive effects on the QT interval. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval. Maprotiline has also been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. In addition, additive anticholinergic effects may be seen with coadministration. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Olanzapine; Fluoxetine: (Major) Coadministration may result in additive effects on the QT interval. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval. Maprotiline has also been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. In addition, additive anticholinergic effects may be seen with coadministration. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. (Moderate) Concomitant use of fluoxetine and maprotiline may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Olanzapine; Samidorphan: (Major) Coadministration may result in additive effects on the QT interval. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval. Maprotiline has also been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. In addition, additive anticholinergic effects may be seen with coadministration. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Oliceridine: (Major) Concomitant use of oliceridine with maprotiline may cause excessive sedation and somnolence. Limit the use of oliceridine with maprotiline to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Ondansetron: (Major) Concomitant use of ondansetron and maprotiline increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Do not exceed 16 mg of IV ondansetron in a single dose; the degree of QT prolongation associated with ondansetron significantly increases above this dose.
Orphenadrine: (Moderate) Skeletal muscle relaxants should be combined cautiously with cyclic antidepressants like maprotiline because they could cause additive CNS depressant effects. Depending on the specific agent (e.g., cyclobenzaprine, and orphenadrine), additive anticholinergic effects may also be seen. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Patients should be monitored for excessive adverse effects from either agent.
Osilodrostat: (Moderate) Monitor for an increase in maprotiline-related adverse reactions if coadministration with osilodrostat is necessary; a dose reduction of maprotiline may be necessary. Concurrent use may increase exposure of maprotiline. Additionally, consider more frequent ECG monitoring due to the risk of additive QT prolongation. Maprotiline is a CYP2D6 substrate that has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Osilodrostat is a CYP2D6 inhibitor that is associated with dose-dependent QT prolongation.
Osimertinib: (Major) Avoid coadministration of maprotiline with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Maprotiline has also been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Oxaliplatin: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of maprotiline with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. QT prolongation and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in postmarketing experience. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Oxazepam: (Moderate) Benzodiazepines or other CNS depressants should be combined cautiously with maprotiline because they could cause additive depressant effects and possible respiratory depression or hypotension. The combination of benzodiazepines and maprotiline is commonly used clinically and is considered to be safe as long as patients are monitored for excessive adverse effects from either agent. Maprotiline may lower the seizure threshold, so when benzodiazepines are used for anticonvulsant effects the patient should be monitored for desired clinical outcomes.
Oxybutynin: (Moderate) Additive anticholinergic effects may be seen when oxybutynin is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects including maprotiline. Clinicians should note that anticholinergic effects might be seen not only on bladder smooth muscle, but also on GI function, the eye, and temperature regulation. Additive drowsiness may also occur.
Oxycodone: (Major) Concomitant use of opioid agonists with maprotiline may cause excessive sedation and somnolence. Limit the use of opioid pain medications with maprotiline to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Oxymorphone: (Major) Concomitant use of opioid agonists with maprotiline may cause excessive sedation and somnolence. Limit the use of opioid pain medications with maprotiline to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Reduce the initial oxymorphone dosage by 1/3 to 1/2. Educate patients about the risks and symptoms of excessive CNS depression.
Ozanimod: (Contraindicated) Do not use maprotiline in patients taking MAOIs or within 14 days of stopping them. An active metabolite of ozanimod inhibits MAO-B, and interactions with maprotiline may manifest as serotonin syndrome, hypertensive crisis, QT prolongation or other serious side effects. Hyperpyretic crises, severe convulsions, and deaths have occurred in patients receiving cyclic antidepressants and MAO inhibiting drugs simultaneously. Consider an alternative to maprotiline. Ozanimod is a monoamine oxidase inhibitor that may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Pacritinib: (Major) Concomitant use of pacritinib and maprotiline increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Paliperidone: (Major) Paliperidone has been associated with QT prolongation; torsade de pointes (TdP) and ventricular fibrillation have been reported in the setting of overdose. According to the manufacturer, since paliperidone may prolong the QT interval, it should be avoided in combination with other agents also known to have this effect, such as maprotiline. However, if coadministration is necessary and the patient has known risk factors for cardiac disease or arrhythmias, close monitoring is essential.
Panobinostat: (Major) QT prolongation has been reported with panobinostat therapy in patients with multiple myeloma in a clinical trial; use of panobinostat with other agents that prolong the QT interval is not recommended. Obtain an electrocardiogram at baseline and periodically during treatment. Hold panobinostat if the QTcF increases to >= 480 milliseconds during therapy; permanently discontinue if QT prolongation does not resolve. Drugs with a possible risk for QT prolongation and torsade de pointes that should be used cautiously and with close monitoring with panobinostat include maprotiline.
Paroxetine: (Major) Paroxetine is a potent inhibitor of CYP2D6, the primary isoenzyme responsible for the metabolism of maprotiline. In several cases, symptoms of toxicity, including seizures, have been reported when SSRIs and cyclic antidepressants have been used together. In addition, because maprotiline is a CYP2D6 substrate and has a possible risk of QT prolongation and torsade de pointes, concurrent use of a potent CYP2D6 inhibitor such as paroxetine may increase the risk of such events. Patients receiving maprotiline should be monitored closely for toxicity if paroxetine is added.
Pasireotide: (Moderate) Use caution when using pasireotide in combination with maprotiline as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Pazopanib: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and the other drug must be continued, closely monitor the patient for QT interval prolongation. Drugs with a possible risk for QT prolongation and TdP that should be avoided with pazopanib include maprotiline.
Peginterferon Alfa-2b: (Moderate) Monitor for adverse effects associated with increased exposure to maprotiline if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while maprotiline is a CYP2D6 substrate.
Pentamidine: (Major) Pentamidine has been associated with QT prolongation. Drugs with a possible risk for QT prolongation and torsades de pointes (TdP) that should be used cautiously with pentamidine include maprotiline. Maprotiline may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP have been described with maprotiline, but rarely occur at normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Pentazocine: (Moderate) Use pentazocine with caution in any patient receiving medication with CNS depressant and/or anticholinergic activity. Coadministration of pentazocine with maprotiline may result in additive respiratory and CNS depression and anticholinergic effects, such as urinary retention and constipation.
Pentazocine; Naloxone: (Moderate) Use pentazocine with caution in any patient receiving medication with CNS depressant and/or anticholinergic activity. Coadministration of pentazocine with maprotiline may result in additive respiratory and CNS depression and anticholinergic effects, such as urinary retention and constipation.
Pentobarbital: (Major) Monitor for excessive sedation and somnolence during coadministration maprotiline and barbiturates. Concurrent use may result in additive CNS depression.
Perampanel: (Moderate) Co-administration of perampanel with CNS depressants, including ethanol, may increase CNS depression. The combination of perampanel (particularly at high doses) with ethanol has led to decreased mental alertness and ability to perform complex tasks (such as driving), as well as increased levels of anger, confusion, and depression; similar reactions should be expected with concomitant use of other CNS depressants, such as maprotiline. In addition, maprotiline, when used concomitantly with anticonvulsants may lower the seizure threshold, leading to pharmacodynamic interactions.
Perphenazine: (Moderate) Perphenazine, a phenothiazine, is associated with a possible risk for QT prolongation. Theoretically, perphenazine may increase the risk of QT prolongation if coadministered with drugs with a possible risk for QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with perphenazine include maprotiline. In addition to additive cardiac effects, additive anticholinergic effects are also possible. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or other additive CNS effects may also occur.
Perphenazine; Amitriptyline: (Contraindicated) The use of maprotiline with tricyclic antidepressants (TCAs) is not generally recommended, due to the duplicative nature of therapy and the risk for side effects. Additive cardiac effects (e.g., prolonged QT interval), CNS effects, or antimuscarinic effects may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. (Moderate) Perphenazine, a phenothiazine, is associated with a possible risk for QT prolongation. Theoretically, perphenazine may increase the risk of QT prolongation if coadministered with drugs with a possible risk for QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with perphenazine include maprotiline. In addition to additive cardiac effects, additive anticholinergic effects are also possible. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or other additive CNS effects may also occur.
Phendimetrazine: (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Phenelzine: (Contraindicated) Concurrent use of phenelzine, a non-selective monoamine oxidase inhibitor (MAOI), and maprotiline, a selective norepinephrine reuptake inhibitor, is contraindicated by the manufacturer of maprotiline. The noradrenergic effects of both maprotiline and phenelzine may result in hypertensive crisis. A minimum of 14 days should elapse after discontinuation of phenelzine before treatment with maprotiline is initiated. After stopping treatment with maprotiline, a time period of 4 to 5 half-lives of maprotiline and any active metabolites should elapse before starting treatment with phenelzine. The product labeling for phenelzine states that use with maprotiline should be avoided if possible; if the decision is made to administer phenelzine with maprotiline or within less than 10 days after discontinuation of maprotiline, the patient should be cautioned regarding the possibility of an interaction.
Phenobarbital: (Major) Monitor for excessive sedation and somnolence during coadministration maprotiline and barbiturates. Concurrent use may result in additive CNS depression.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Monitor for excessive sedation and somnolence during coadministration maprotiline and barbiturates. Concurrent use may result in additive CNS depression. (Moderate) Additive anticholinergic effects may be seen when hyoscyamine is used concomitantly with other drugs with moderate to significant anticholinergic effects including maprotiline. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. (Moderate) Additive anticholinergic effects may be seen when scopolamine is used concomitantly with other drugs with moderate to significant anticholinergic effects including maprotiline. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. (Moderate) The anticholinergic effects of atropine may be enhanced when combined with other commonly used drugs with moderate to significant anticholinergic effects including maprotiline.
Phentermine: (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Phentermine; Topiramate: (Moderate) Maprotiline, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions. Monitor patients on anticonvulsants carefully when maprotiline is used concurrently. Because of the lowering of seizure threshold, an alternative antidepressant may be a more optimal choice for patients taking drugs for epilepsy. (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Phenylephrine: (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Pimavanserin: (Major) Pimavanserin may cause QT prolongation and should generally be avoided in patients receiving other medications known to prolong the QT interval, such as maprotiline. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs, but coadministration may increase the risk for QT prolongation.
Pimozide: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of maprotiline with pimozide is contraindicated.
Pitolisant: (Major) Avoid coadministration of pitolisant with maprotiline as concurrent use may increase the risk of QT prolongation. Pitolisant prolongs the QT interval. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Ponesimod: (Major) In general, do not initiate ponesimod in patients taking maprotiline due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ponesimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ponesimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Porfimer: (Major) Avoid coadministration of porfimer with maprotiline due to the risk of increased photosensitivity. All patients treated with porfimer will be photosensitive. Concomitant use of other photosensitizing agents like maprotiline may increase the risk of a photosensitivity reaction.
Posaconazole: (Moderate) Use posaconazole with caution in combination with maprotiline as concurrent use may increase the risk of QT prolongation. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes (TdP). Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Pramipexole: (Moderate) Pramipexole may cause additive drowsiness when combined with maprotiline.
Pregabalin: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and maprotiline. Concomitant use of pregabalin with maprotiline may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
Prilocaine; Epinephrine: (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Primaquine: (Moderate) Exercise caution when administering primaquine in combination with maprotiline as concurrent use may increase the risk of QT prolongation. Primaquine is associated with QT prolongation. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Primidone: (Major) Monitor for excessive sedation and somnolence during coadministration maprotiline and barbiturates. Concurrent use may result in additive CNS depression.
Procainamide: (Major) Maprotiline should be used cautiously with procainamide. Procainamide is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Procarbazine: (Major) Concurrent use of drugs with MAO-inhibiting activity, such as procarbazine, with maprotiline can cause hyperpyrexia, hypertension, or seizures. The combination should be avoided whenever possible and is considered contraindicated.
Prochlorperazine: (Moderate) Prochlorperazine, a phenothiazine, is associated with a possible risk for QT prolongation. Because maprotiline is associated with a possible risk for QT prolongation and torsade de pointes (TdP), concurrent use with prochlorperazine should be approached with caution. If coadministration is considered necessary, and the patient has known risk factors for cardiac disease or arrhythmia, then close monitoring is essential. In addition, additive anticholinergic effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity such as maprotiline. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive hypotension or CNS effects such as drowsiness may also occur.
Promethazine: (Moderate) Promethazine carries a risk of QT prolongation and should be used cautiously with drugs that may prolong the QT interval and have additive anticholinergic properties such as maprotiline. Additive drowsiness and sedation are also possible. Clinicians should note that additive anticholinergic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Promethazine; Dextromethorphan: (Moderate) Promethazine carries a risk of QT prolongation and should be used cautiously with drugs that may prolong the QT interval and have additive anticholinergic properties such as maprotiline. Additive drowsiness and sedation are also possible. Clinicians should note that additive anticholinergic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Promethazine; Phenylephrine: (Moderate) Promethazine carries a risk of QT prolongation and should be used cautiously with drugs that may prolong the QT interval and have additive anticholinergic properties such as maprotiline. Additive drowsiness and sedation are also possible. Clinicians should note that additive anticholinergic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Propafenone: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering propafenone with maprotiline. The need to coadminister these drugs should be done with a careful assessment of risk versus benefit; consider alternative therapy. Propafenone is a Class IC antiarrhythmic which increases the QT interval largely due to prolongation of the QRS interval. Maprotiline has also been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Additionally, propafenone may inhibit the CYP2D6 metabolism of maprotiline.
Propantheline: (Moderate) Additive anticholinergic effects may be seen when propantheline is used concomitantly with other drugs with moderate to significant anticholinergic effects including maprotiline.
Propofol: (Moderate) General anesthetics may produce additive CNS depression when used in patients taking maprotiline.
Protriptyline: (Contraindicated) The use of maprotiline with tricyclic antidepressants (TCAs) is not generally recommended, due to the duplicative nature of therapy and the risk for side effects. Additive cardiac effects (e.g., prolonged QT interval), CNS effects, or antimuscarinic effects may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Pseudoephedrine: (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Pseudoephedrine; Triprolidine: (Major) Additive anticholinergic effects may be seen when maprotiline is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects including sedating h1-blockers. (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Pyridostigmine: (Major) Maprotiline may antagonize some of the effects of pyridostigmine.
Pyrilamine: (Moderate) Additive anticholinergic effects may be seen when maprotiline is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects including sedating h1-blockers.
Quazepam: (Moderate) Benzodiazepines or other CNS depressants should be combined cautiously with maprotiline because they could cause additive depressant effects and possible respiratory depression or hypotension. The combination of benzodiazepines and maprotiline is commonly used clinically and is considered to be safe as long as patients are monitored for excessive adverse effects from either agent. Maprotiline may lower the seizure threshold, so when benzodiazepines are used for anticonvulsant effects the patient should be monitored for desired clinical outcomes.
Quetiapine: (Major) Concomitant use of quetiapine and maprotiline increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Quinidine: (Contraindicated) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine include maprotiline.
Quinine: (Major) Concurrent use of quinine and maprotiline should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Maprotiline has also been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. In addition, concentrations of maprotiline may be increased with concomitant use of quinine. Maprotiline is a CYP2D6 substrate and quinine is a CYP2D6 inhibitor.
Quizartinib: (Major) Concomitant use of quizartinib and maprotiline increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Racepinephrine: (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Ranolazine: (Major) Ranolazine and/or metabolites are moderate inhibitors of CYP2D6 isoenzymes. Based on drug interaction studies with metoprolol, a CYP2D6 substrate, ranolazine may theoretically increase plasma concentrations of CYP2D6 substrates, such as maprotiline, and could lead to toxicity for drugs that have a narrow therapeutic range. Lower doses of some CYP2D6 substrates than are usually prescribed may be needed during therapy with ranolazine; monitor therapeutic response during coadministration. In addition, maprotiline is associated with QT prolongation. Ranolazine should be used cautiously with drugs that prolong the QT interval. The need to coadminister maprotiline with ranolazine should be done with a careful assessment of risk versus benefit; consider alternative therapy to maprotiline.
Rasagiline: (Major) It is recommended to avoid concurrent use of rasagiline and antidepressants, including maprotiline. Severe CNS toxicity with hyperpyrexia has been reported during concurrent use of antidepressants and selective or non-selective MAOIs. During postmarketing use of rasagiline, non-fatal cases of serotonin syndrome have been reported during concomitant antidepressant administration. At least 2 weeks should elapse between stopping rasagiline treatment and beginning therapy with an antidepressant. Conversely, when discontinuing an antidepressant, it is advisable to wait the length of 4 to 5 half-lives of the individual agent being discontinued prior to initiation with rasagiline.
Relugolix: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents. Androgen deprivation therapy (i.e., relugolix) may prolong the QT/QTc interval. Maprotiline has also been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Relugolix; Estradiol; Norethindrone acetate: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents. Androgen deprivation therapy (i.e., relugolix) may prolong the QT/QTc interval. Maprotiline has also been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Remifentanil: (Major) Consider alternative therapy or reduce the dose of one or both drugs if remifentanil is used with another CNS depressant, such as maprotiline. Limit the use of opioid pain medications with maprotiline to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Remimazolam: (Moderate) Benzodiazepines or other CNS depressants should be combined cautiously with maprotiline because they could cause additive depressant effects and possible respiratory depression or hypotension. The combination of benzodiazepines and maprotiline is commonly used clinically and is considered to be safe as long as patients are monitored for excessive adverse effects from either agent. Maprotiline may lower the seizure threshold, so when benzodiazepines are used for anticonvulsant effects the patient should be monitored for desired clinical outcomes.
Ribociclib: (Major) Avoid coadministration of ribociclib with maprotiline due to an increased risk for QT prolongation and torsade de pointes (TdP). Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Maprotiline has also been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs. Concomitant use may increase the risk for QT prolongation.
Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib with maprotiline due to an increased risk for QT prolongation and torsade de pointes (TdP). Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Maprotiline has also been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs. Concomitant use may increase the risk for QT prolongation.
Rilpivirine: (Moderate) Caution is advised when administering rilpivirine with maprotiline as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Maprotiline has also been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Risperidone: (Moderate) Use risperidone and maprotiline together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Ritonavir: (Moderate) Ritonavir potently inhibits the CYP2D6 and CYP3A4 isozymes, and thus may inhibit the metabolism of maprotiline. Since the magnitude of the interaction with the maprotiline is difficult to predict but may be significant, monitor patients receiving ritonavir and maprotiline concurrently closely. Adjust the dosage of maprotiline based on therapeutic response. Maprotiline serum concentration monitoring may be useful to guide adjustments and prevent toxicity.
Rivastigmine: (Moderate) Concurrent use of maprotiline and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Maprotiline may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Rolapitant: (Major) Use caution if maprotiline and rolapitant are used concurrently, and monitor for maprotiline-related adverse effects. Maprotiline is a CYP2D6 substrate and rolapitant is a moderate CYP2D6 inhibitor; the inhibitory effect of rolapitant is expected to persist beyond 28 days for an unknown duration. Exposure to another CYP2D6 substrate, following a single dose of rolapitant increased about 3-fold on Days 8 and Day 22. The inhibition of CYP2D6 persisted on Day 28 with a 2.3-fold increase in the CYP2D6 substrate concentrations, the last time point measured.
Romidepsin: (Moderate) Consider monitoring electrolytes and ECGs at baseline and periodically during treatment if romidepsin is administered with maprotiline as concurrent use may increase the risk of QT prolongation. Romidepsin has been reported to prolong the QT interval. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Ropinirole: (Moderate) Ropinirole may cause additive drowsiness when combined with maprotiline.
Safinamide: (Contraindicated) According to the manufacturer of safinamide, the concurrent use of safinamide and heterocyclic antidepressants, such as maprotiline, is contraindicated due to the risk of serotonin syndrome. At least 14 days should elapse between the discontinuation of safinamide and the initiation of maprotiline.
Saquinavir: (Major) Concurrent use of maprotiline and saquinavir should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If no acceptable alternative therapy is available, perform a baseline ECG prior to initiation of concomitant therapy and carefully follow monitoring recommendations. Saquinavir boosted with ritonavir increases the QT interval in a dose-dependent fashion, which may increase the risk for serious arrhythmias such as TdP. Maprotiline is related to the tricyclic antidepressants and has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
Scopolamine: (Moderate) Additive anticholinergic effects may be seen when scopolamine is used concomitantly with other drugs with moderate to significant anticholinergic effects including maprotiline. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Secobarbital: (Major) Monitor for excessive sedation and somnolence during coadministration maprotiline and barbiturates. Concurrent use may result in additive CNS depression.
Selegiline: (Contraindicated) Concurrent use of selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), and maprotiline, a selective norepinephrine reuptake inhibitor, is contraindicated due to the potential for severe or life-threatening reactions such as hypertensive crisis. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with maprotiline. After stopping treatment with maprotiline, a time period equal to 4 to 5 half-lives of maprotiline or any active metabolite should elapse before starting therapy with selegiline.
Selpercatinib: (Major) Monitor ECGs more frequently for QT prolongation if coadministration of selpercatinib with maprotiline is necessary due to the risk of additive QT prolongation. Concentration-dependent QT prolongation has been observed with selpercatinib therapy. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome an d torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Serdexmethylphenidate; Dexmethylphenidate: (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Sertraline: (Moderate) Concomitant use of sertraline and maprotiline may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with sertraline is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 2 times the maximum recommended dose.
Sevoflurane: (Major) Halogenated anesthetics can prolong the QT interval. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously and with close monitoring with halogenated anesthetics include maprotiline.
Siponimod: (Major) In general, do not initiate treatment with siponimod in patients receiving maprotiline due to the potential for QT prolongation. Consult a cardiologist regarding appropriate monitoring if siponimod use is required. Siponimod therapy prolonged the QT interval at recommended doses in a clinical study. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Sodium Stibogluconate: (Moderate) Concomitant use of sodium stibogluconate and maprotiline may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Solifenacin: (Major) Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with maprotiline include solifenacin. Additive anticholinergic effects may also be seen.
Sorafenib: (Major) Avoid coadministration of sorafenib with maprotiline due to the risk of additive QT prolongation. If concomitant use is unavoidable, monitor electrocardiograms and correct electrolyte abnormalities. An interruption or discontinuation of sorafenib therapy may be necessary if QT prolongation occurs. Sorafenib is associated with QTc prolongation. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Sotalol: (Major) Concomitant use of sotalol and maprotiline increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Stiripentol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and maprotiline. CNS depressants can potentiate the effects of stiripentol.
Sufentanil: (Major) Concomitant use of opioid agonists with maprotiline may cause excessive sedation and somnolence. Limit the use of opioid pain medications with maprotiline to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Sunitinib: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with maprotiline. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs. Sunitinib can prolong the QT interval.
Sympathomimetics: (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity.
Tacrolimus: (Moderate) Consider ECG and electrolyte monitoring periodically during treatment if tacrolimus is administered with maprotiline. Tacrolimus may prolong the QT interval and cause torsade de pointes (TdP). Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Tamoxifen: (Major) Concomitant use of tamoxifen and maprotiline increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Tapentadol: (Major) Concomitant use of opioid agonists with maprotiline may cause excessive sedation and somnolence. Limit the use of opioid pain medications with maprotiline to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Telavancin: (Moderate) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering telavancin with maprotiline. Telavancin has been associated with QT prolongation. Maprotiline has also been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Temazepam: (Moderate) Benzodiazepines or other CNS depressants should be combined cautiously with maprotiline because they could cause additive depressant effects and possible respiratory depression or hypotension. The combination of benzodiazepines and maprotiline is commonly used clinically and is considered to be safe as long as patients are monitored for excessive adverse effects from either agent. Maprotiline may lower the seizure threshold, so when benzodiazepines are used for anticonvulsant effects the patient should be monitored for desired clinical outcomes.
Terbinafine: (Moderate) In vitro studies have shown systemic terbinafine to inhibit hepatic isoenzyme CYP2D6, and thus may inhibit the clearance of drugs metabolized by this isoenzyme, such as maprotiline.
Tetrabenazine: (Major) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc such as maprotiline, particularly when given in excessive doses or overdosage. Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. In addition, concurrent use should generally be avoided since the risk of adverse effects such as drowsiness, sedation, dizziness, or orthostatic hypotension may be increased.
Thioridazine: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Thioridazine is considered contraindicated for use along with agents that, when combined with a phenothiazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension. Maprotiline is rarely associated with QT prolongation. Additionally, additive toxicities (e.g., cardiac effects, CNS effects, orthostatic hypotension, and antimuscarinic effects) may occur because maprotiline and thioridazine are both metabolized via similar pathways (CYP2D6), have structural similarities, and produce similar pharmacologic effects (antimuscarinic activity). Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Thyroid hormones: (Minor) Thyroid hormones may increase receptor sensitivity and enhance the effects of maprotiline.
Tiagabine: (Moderate) Maprotiline, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions. Monitor patients on anticonvulsants carefully when maprotiline is used concurrently. Because of the lowering of seizure threshold, an alternative antidepressant may be a more optimal choice for patients taking drugs for epilepsy.
Tolterodine: (Major) Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with maprotiline include tolterodine. Also, additive anticholinergic effects may be seen when maprotiline is used concomitantly with other drugs with moderate to significant anticholinergic effects including tolterodine.
Topiramate: (Moderate) Maprotiline, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions. Monitor patients on anticonvulsants carefully when maprotiline is used concurrently. Because of the lowering of seizure threshold, an alternative antidepressant may be a more optimal choice for patients taking drugs for epilepsy.
Toremifene: (Major) Avoid coadministration of maprotiline with toremifene if possible due to the risk of additive QT prolongation. If concomitant use is unavoidable, closely monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia or hypomagnesemia prior to administration of toremifene. Toremifene has been shown to prolong the QTc interval in a dose- and concentration-related manner. Maprotiline has also been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Tramadol: (Major) Concomitant use of opioid agonists with maprotiline may cause excessive sedation and somnolence. Use of tramadol may also increase the risk of seizures in patients receiving other drugs associated with seizures such as maprotiline. Limit the use of opioid pain medications with maprotiline to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and seizures.
Tramadol; Acetaminophen: (Major) Concomitant use of opioid agonists with maprotiline may cause excessive sedation and somnolence. Use of tramadol may also increase the risk of seizures in patients receiving other drugs associated with seizures such as maprotiline. Limit the use of opioid pain medications with maprotiline to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and seizures.
Tranylcypromine: (Contraindicated) Concurrent use of tranylcypromine, a non-selective monoamine oxidase inhibitor (MAOI), and maprotiline, a selective norepinephrine reuptake inhibitor, is contraindicated. The noradrenergic effects of both maprotiline and tranylcypromine may result in hypertensive crisis. A minimum of 14 days should be allowed to elapse after discontinuation of tranylcypromine before treatment with maprotiline is initiated. After stopping treatment with maprotiline, a time period of 4 to 5 half-lives of maprotiline and any active metabolites should elapse before starting treatment with tranylcypromine.
Trazodone: (Major) Concomitant use of trazodone and maprotiline increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Triazolam: (Moderate) Benzodiazepines or other CNS depressants should be combined cautiously with maprotiline because they could cause additive depressant effects and possible respiratory depression or hypotension. The combination of benzodiazepines and maprotiline is commonly used clinically and is considered to be safe as long as patients are monitored for excessive adverse effects from either agent. Maprotiline may lower the seizure threshold, so when benzodiazepines are used for anticonvulsant effects the patient should be monitored for desired clinical outcomes.
Triclabendazole: (Moderate) Concomitant use of triclabendazole and maprotiline may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Tricyclic antidepressants: (Contraindicated) The use of maprotiline with tricyclic antidepressants (TCAs) is not generally recommended, due to the duplicative nature of therapy and the risk for side effects. Additive cardiac effects (e.g., prolonged QT interval), CNS effects, or antimuscarinic effects may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Trifluoperazine: (Moderate) Trifluoperazine, a phenothiazine, is associated with a possible risk of QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with drugs with a possible risk for QT prolongation. Because maprotiline is associated with a possible risk for QT prolongation, concurrent use with trifluoperazine should be approached with caution. Depending on the specific agent, additive anticholinergic effects may also be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity, such as maprotiline. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or other additive CNS effects may also occur.
Trihexyphenidyl: (Moderate) Anticholinergic effects may be seen when drugs with antimuscarinic properties like trihexyphenidyl are used concomitantly with other antimuscarinics.
Trimipramine: (Contraindicated) The use of maprotiline with tricyclic antidepressants (TCAs) is not generally recommended, due to the duplicative nature of therapy and the risk for side effects. Additive cardiac effects (e.g., prolonged QT interval), CNS effects, or antimuscarinic effects may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Triprolidine: (Major) Additive anticholinergic effects may be seen when maprotiline is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects including sedating h1-blockers.
Triptorelin: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving maprotiline. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Androgen deprivation therapy may also prolong the QT/QTc interval. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Trospium: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like trospium are used concomitantly with other drugs with moderate to significant anticholinergic effects including maprotiline.
Valproic Acid, Divalproex Sodium: (Major) Maprotiline, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions. Monitor patients on anticonvulsants carefully when maprotiline is used concurrently. Because of the lowering of seizure threshold, an alternative antidepressant may be a more optimal choice for patients taking drugs for epilepsy.
Vandetanib: (Major) Avoid coadministration of vandetanib with maprotiline due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Vardenafil: (Moderate) Concomitant use of vardenafil and maprotiline may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Vemurafenib: (Major) Vemurafenib has been associated with QT prolongation. If vemurafenib and another drug, such as maprotiline, that is associated with a possible risk for QT prolongation and torsade de pointes (TdP) must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Also, maprotiline is a CYP2D6 substrate, while vemurafenib is a CYP2D6 inhibitor; therefore, increased concentrations of maprotiline may occur.
Venlafaxine: (Major) Concomitant use of venlafaxine and maprotiline increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Verteporfin: (Moderate) Use caution if coadministration of verteporfin with maprotiline is necessary due to the risk of increased photosensitivity. Verteporfin is a light-activated drug used in photodynamic therapy; all patients treated with verteporfin will be photosensitive. Concomitant use of other photosensitizing agents like maprotiline may increase the risk of a photosensitivity reaction.
Vigabatrin: (Moderate) Maprotiline, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions. Monitor patients on anticonvulsants carefully when maprotiline is used concurrently. Because of the lowering of seizure threshold, an alternative antidepressant may be a more optimal choice for patients taking drugs for epilepsy.
Viloxazine: (Moderate) Monitor for an increase in maprotiline-related adverse reactions if coadministration with viloxazine is necessary; a dose reduction of maprotiline may be necessary. Concurrent use may increase exposure of maprotiline. Maprotiline is a CYP2D6 substrate and viloxazine is a CYP2D6 inhibitor.
Voclosporin: (Moderate) Concomitant use of voclosporin and maprotiline may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering clarithromycin with maprotiline. Administration of clarithromycin has resulted in prolongation of the QT interval and TdP. Maprotiline has also been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs, such as clarithromycin.
Voriconazole: (Major) Caution is advised when administering voriconazole with drugs that are known to prolong that QT interval and are metabolized by CYP3A4, such as maprotiline. Voriconazole has been associated with QT prolongation and rare cases of torsades de pointes (TdP), cardiac arrest, and sudden death. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs. In addition, coadministration of voriconazole (a CYP3A4 inhibitor) with maprotiline (a CYP3A4 substrate) may result in elevated maprotiline plasma concentrations and could increase the risk for adverse events, including QT prolongation. If these drugs are given together, closely monitor for prolongation of the QT interval. Rigorous attempts to correct any electrolyte abnormalities (i.e., potassium, magnesium, calcium) should be made before initiating concurrent therapy.
Vorinostat: (Major) Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs. Vorinostat therapy is associated with a risk of QT prolongation and should be used cautiously with maprotiline.
Ziconotide: (Moderate) Due to potentially additive effects, dosage adjustments may be necessary if ziconotide is used with a drug that has CNS depressant effects such as maprotiline. Coadministration of CNS depressants may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Ziprasidone: (Major) Concomitant use of ziprasidone and maprotiline should be avoided due to the potential for additive QT prolongation. Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of torsade de pointes (TdP) in patients with multiple confounding factors. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Zonisamide: (Moderate) Maprotiline, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions. Monitor patients on anticonvulsants carefully when maprotiline is used concurrently. Because of the lowering of seizure threshold, an alternative antidepressant may be a more optimal choice for patients taking drugs for epilepsy.

How Supplied

Ludiomil/Maprotiline Hydrochloride Oral Tab: 25mg, 50mg, 75mg

Maximum Dosage
Adults

225 mg/day PO.

Geriatric

225 mg/day PO.

Adolescents

Safety and efficacy have not been established.

Children

Safety and efficacy have not been established.

Mechanism Of Action

Mechanism of Action: Maprotiline selectively inhibits the reuptake of norepinephrine at the neuronal membrane. Maprotiline shares many of the actions of the tricyclic antidepressants although, unlike tricyclic antidepressants, maprotiline does not affect the reuptake of serotonin. Recent evidence suggests that the upset of monoamine output seen in depressed patients may be regulated by antidepressants following long-term treatment due to their action on beta-adrenergic receptors. This action on beta-receptors may be a better explanation than the reuptake theory of their antidepressant effects.Maprotiline does not inhibit monoamine oxidase or interfere with dopamine reuptake. Maprotiline appears to produce sedation in depressed patients. The seizure threshold can be lowered, and anticholinergic activity is present. Cardiac dysrhythmias can result from the direct quinidine-like effect on cardiac function in combination with anticholinergic activity and the potentiation of norepinephrine. The effect of maprotiline on the endocrine system has not been evaluated but may be similar to that of the tricyclic antidepressants.

Pharmacokinetics

Maprotiline is administered orally. Maprotiline distributes widely throughout the body. A steady-state plasma concentration is achieved in about 7 days. The drug is about 88% protein-bound. Maprotiline is metabolized slowly in the liver to produce the active metabolite desmethylmaprotiline, which is known to be distributed into breast milk. Desmethylmaprotiline formation in vivo is expected to be mediated primarily by CYP2D6, with some contribution by CYP1A2. The half-life of elimination averages 51 hours. There may be enterohepatic circulation of both unchanged drug and metabolites. Primary excretion is in the urine; about 60% of a dose is excreted as metabolites within 3 weeks. About 30% is excreted via the feces.
 
Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: CYP2D6, CYP1A2
The formation of the active metabolite of maprotiline appears to be mediated via CYP2D6 and CYP1A2, with primary contribution by CYP2D6. It is possible that inhibitors of this enzyme could increase maprotiline concentrations.

Oral Route

Following oral administration, maprotiline is absorbed slowly, but completely, from the GI tract. The mean time to peak concentration (Tmax) is 12 hours. Mean plasma concentrations prior to a morning dose at steady state (maprotiline dose of 50 mg PO 3 times per day) are 181 to 295 ng/mL.

Pregnancy And Lactation
Pregnancy

Maprotiline is a tetracyclic antidepressant. Animal studies with maprotiline have failed to demonstrate teratogenicity, carcinogenicity, mutagenicity, or impairment of fertility. Because there are no adequate and well controlled studies in pregnant women, maprotiline should only be used in pregnancy if the benefits to the mother clearly outweigh the possible risks to the fetus. There are reports of complications in neonates after in utero exposure to cyclic antidepressants including hypoglycemia, respiratory diagnoses, developmental delays, and jaundice. In addition, neonatal withdrawal symptoms have been reported following in utero exposure to some antidepressants. More studies are needed. A prospective trial evaluating the effects of in utero exposure to cyclic antidepressants in infants 15 to 71 months of age compared to similar non-exposed controls found that exposure to antidepressants did not adversely affect IQ, language, behavior, or temperament. The effects of maprotiline during labor and obstetric delivery are unknown. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to maprotiline; information about the registry can be obtained at womensmentalhealth.org/research/pregnancyregistry or by calling 1866-961-2388.