Stelazine

First Generation Antipsychotics

Oral Administration

May take oral dosage forms with or without food. If stomach upset or nausea occur, take with food.

Oral Solid Formulations

Tablets:
Administer orally as prescribed.

Oral Liquid Formulations

Oral concentrate:
Measure dose using a calibrated measuring device to ensure accurate dosage.
Dilute the concentrate just prior to administration with 60 mL (2 ounces) or more of a compatible liquid, such as tomato or fruit juice, milk, simple syrup, orange syrup, carbonated beverages, coffee, tea, or water. Semi-solid foods such as (e.g., pudding or soups) may also be used.
Avoid spilling the concentrate on the skin and clothing.

Severe

neuroleptic malignant syndrome / Delayed / Incidence not known
tardive dyskinesia / Delayed / Incidence not known
seizures / Delayed / Incidence not known
cerebral edema / Early / Incidence not known
asphyxia / Early / Incidence not known
lupus-like symptoms / Delayed / Incidence not known
aplastic anemia / Delayed / Incidence not known
pancytopenia / Delayed / Incidence not known
hemolytic anemia / Delayed / Incidence not known
agranulocytosis / Delayed / Incidence not known
exfoliative dermatitis / Delayed / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
laryngeal edema / Rapid / Incidence not known
angioedema / Rapid / Incidence not known
bronchospasm / Rapid / Incidence not known
retinopathy / Delayed / Incidence not known
corneal opacification / Delayed / Incidence not known
visual impairment / Early / Incidence not known
ileus / Delayed / Incidence not known
cardiac arrest / Early / Incidence not known
ventricular tachycardia / Early / Incidence not known
bradycardia / Rapid / Incidence not known
torsade de pointes / Rapid / Incidence not known
stroke / Early / Incidence not known
SIADH / Delayed / Incidence not known
water intoxication / Delayed / Incidence not known

Moderate

constipation / Delayed / 1.0-10.0
hepatitis / Delayed / 0-1.0
akathisia / Delayed / Incidence not known
dystonic reaction / Delayed / Incidence not known
pseudoparkinsonism / Delayed / Incidence not known
psychosis / Early / Incidence not known
myasthenia / Delayed / Incidence not known
peripheral edema / Delayed / Incidence not known
leukopenia / Delayed / Incidence not known
anemia / Delayed / Incidence not known
eosinophilia / Delayed / Incidence not known
neutropenia / Delayed / Incidence not known
thrombocytopenia / Delayed / Incidence not known
atopic dermatitis / Delayed / Incidence not known
erythema / Early / Incidence not known
contact dermatitis / Delayed / Incidence not known
blurred vision / Early / Incidence not known
dysphagia / Delayed / Incidence not known
jaundice / Delayed / Incidence not known
cholestasis / Delayed / Incidence not known
sinus tachycardia / Rapid / Incidence not known
hypotension / Rapid / Incidence not known
angina / Early / Incidence not known
orthostatic hypotension / Delayed / Incidence not known
QT prolongation / Rapid / Incidence not known
hypertension / Early / Incidence not known
urinary retention / Early / Incidence not known
hyperprolactinemia / Delayed / Incidence not known
impotence (erectile dysfunction) / Delayed / Incidence not known
ejaculation dysfunction / Delayed / Incidence not known
infertility / Delayed / Incidence not known
galactorrhea / Delayed / Incidence not known
hyperglycemia / Delayed / Incidence not known
hypoglycemia / Early / Incidence not known
glycosuria / Early / Incidence not known
hyperthermia / Delayed / Incidence not known
hyponatremia / Delayed / Incidence not known

Mild

drowsiness / Early / 1.0-10.0
xerostomia / Early / 10.0
fatigue / Early / Incidence not known
headache / Early / Incidence not known
dizziness / Early / Incidence not known
insomnia / Early / Incidence not known
lethargy / Early / Incidence not known
nasal congestion / Early / Incidence not known
fever / Early / Incidence not known
purpura / Delayed / Incidence not known
seborrhea / Delayed / Incidence not known
skin hyperpigmentation / Delayed / Incidence not known
hyperhidrosis / Delayed / Incidence not known
urticaria / Rapid / Incidence not known
photosensitivity / Delayed / Incidence not known
pruritus / Rapid / Incidence not known
mydriasis / Early / Incidence not known
miosis / Early / Incidence not known
appetite stimulation / Delayed / Incidence not known
anorexia / Delayed / Incidence not known
weight gain / Delayed / Incidence not known
nausea / Early / Incidence not known
vomiting / Early / Incidence not known
hypersalivation / Early / Incidence not known
breast enlargement / Delayed / Incidence not known
mastalgia / Delayed / Incidence not known
libido decrease / Delayed / Incidence not known
amenorrhea / Delayed / Incidence not known
menstrual irregularity / Delayed / Incidence not known
polyuria / Early / Incidence not known
gynecomastia / Delayed / Incidence not known
hypothermia / Delayed / Incidence not known
polydipsia / Early / Incidence not known

Dementia, geriatric, stroke

Geriatric patients may be more susceptible to the actions and adverse effects of phenothiazines, including tardive dyskinesia, dystonias, orthostatic hypotension, QT prolongation, anticholinergic effects, and risk for falls and fractures. Initiate treatment with lower doses followed by careful dosage titration and close monitoring. Antipsychotics are not approved for the treatment of dementia-related psychosis in geriatric patients and the use of phenothiazines in this population should be avoided if possible due to an increase in morbidity and mortality in elderly patients with dementia receiving antipsychotics. Deaths have typically resulted from heart failure, sudden death, or infections. An increased incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including fatal events, has also been reported. The Beers Criteria consider antipsychotics to be potentially inappropriate medications (PIMs) in elderly patients and should be avoided except for treating schizophrenia, bipolar disorder, or short-term antiemetic use during chemotherapy. The Beers panel recommends avoiding trifluoperazine in geriatric patients with delirium, dementia, lower urinary tract symptoms/benign prostatic hyperplasia in men, or Parkinson's disease. Non-pharmacological strategies are first-line options for treating delirium- or dementia-related behavioral problems unless they have failed or are not possible and the patient is a substantial threat to self or others. If antipsychotic use is necessary in geriatrics with a history of falls or fractures, consider reducing the use of other CNS depressants and implement other fall risk strategies. Due to the potential for antipsychotic-induced hyponatremia and SIADH, sodium levels should be closely monitored when trifluoperazine is initiated and after dose changes. According to the federal Omnibus Budget Reconciliation Act (OBRA) regulations in residents of long-term care facilities, antipsychotic therapy should only be initiated in a patient with behavioral or psychological symptoms of dementia (BPSD) when the patient is a danger to self or others or has symptoms due to mania or psychosis. For acute conditions persisting beyond 7 days, appropriate non-pharmacologic interventions must be attempted, unless clinically contraindicated and documented. OBRA provides general dosing guidance for antipsychotic treatment of BPSD. Antipsychotics are subject to periodic review for effectiveness, medical necessity, gradual dose reduction (GDR), or rationale for continued use. Refer to the OBRA guidelines for complete information.

Stelazine

Rx

Oral and parenteral piperazine phenothiazine antipsychotic; similar to fluphenazine
Used primarily as an antipsychotic
Boxed warning regarding an increased risk of death in elderly patients with dementia

For the treatment of schizophrenia. Oral dosage Adults

Initially, 2 to 5 mg PO once or twice daily. May increase gradually as needed and tolerated. Lower initial doses and slower titration are recommended in geriatric or debilitated adults. Optimum response generally occurs with 15 to 20 mg/day (in divided doses); however, some patients may require 40 mg/day or more.

Adolescents

The manufacturer does not provide specific dosage recommendations. It may be prudent to initiate dosing as for children (e.g., 1 mg PO once or twice per day). Adjust gradually as needed and tolerated to the patient's weight and the severity of the symptoms. Usual pediatric maximum: 15 mg/day. Some older children with severe symptoms may require dosages more than 15 mg/day (e.g., 10 mg PO twice daily). Do not exceed usual adult dosages.

Children 6 to 12 years

For children who are hospitalized or under close supervision, initiate with 1 mg PO once or twice daily. Adjust gradually as needed and tolerated to the weight of the child and the severity of the symptoms. Generally, the dose should not exceed 15 mg/day, in divided doses. However, some older children with severe symptoms may require dosages higher than 15 mg/day, in divided doses.

For the short-term treatment of non-psychotic generalized anxiety disorder (GAD). Oral dosage Adults

Initially, 1 or 2 mg PO once or twice per day. Do not exceed 6 mg/day PO. In general, dosages in the lower adult range are sufficient for most geriatric patients. Trifluoperazine is not considered standard therapy for GAD because safer alternatives are available. Efficacy in the treatment of non-psychotic anxiety was established in a 4-week multicenter study of outpatients with GAD. This evidence does not predict that trifluoperazine will be useful in patients with other non-psychotic conditions in which anxiety, or signs that mimic anxiety, are found (e.g., physical illness, organic mental conditions, agitated depression, character pathologies, etc.). When used for non-psychotic GAD, treatment should be limited to 12 weeks or less because use for longer intervals may cause tardive dyskinesia, which may be irreversible in some cases.

For the treatment of severe behavioral or psychological symptoms of dementia† (BPSD)†. Oral dosage Geriatric Adults

Initially, 0.5 to 1 mg PO once or twice per day. May gradually increase at weekly intervals, as needed and tolerated. Dose may range from 2 to 20 mg/day PO. Antipsychotics are not FDA-approved for this indication and the labeling of all antipsychotics contains a boxed warning noting an increased risk of death in geriatric patients being treated for behavioral problems associated with dementia. The federal Omnibus Budget Reconciliation Act (OBRA) regulates the use of antipsychotics in long-term care facility (LTCF) residents with dementia-related behavioral symptoms. OBRA Max: 8 mg/day PO in residents meeting the OBRA criteria for treatment, except when documentation is provided showing that higher doses are necessary to maintain or improve the resident's functional status. In addition, the facility must attempt a gradual dose reduction (GDR) in 2 separate quarters, at least 1 month apart, within the first year of admission to the facility or after the facility has initiated an antipsychotic, unless clinically contraindicated. After the first year, a GDR must be attempted annually unless clinically contraindicated. The GDR may be considered clinically contraindicated if the target symptoms returned or worsened after the most recent GDR attempt within the facility and the physician has documented justification for why attempting additional dose reductions at that time would likely impair the resident's function or increase distressed behavior.

†Indicates off-label use

Hepatic Impairment

Trifluoperazine is contraindicated in patients with pre-existing liver damage such as significant hepatic disease.

Renal Impairment

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

Abarelix: (Minor) Abarelix can cause QT prolongation. In a single, active-controlled, clinical study comparing abarelix to LHRH agonist plus nonsteroidal antiandrogen, periodic electrocardiograms were performed. Both therapies prolonged the mean QTc interval by >10 msec from baseline. In approximately 20% of 340 patients, the QTc increased more than 30 milliseconds from baseline or the end-of-treatment QTc values were more than 450 milliseconds. The effect of abarelix on the QT interval may be due to androgen deprivation or other variables, as similar effects were seen in men that received a gonadotropin-releasing hormone (GnRH) agonist with a nonsteroidal antiandrogen. Patients with a baseline QTc value greater than 450 milliseconds may not be appropriate candidates for abarelix receipt. Prescribers need to weigh the potential benefits and risks of abarelix use in patients with prolonged QT syndrome or in patients taking other drugs that may prolong the QT interval. Agents with a possible risk for QT prolongation and TdP include phenothiazines.
Acarbose: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Additive anticholinergic and sedative effects may be seen when Trifluoperazine is used with first generation antihistamines, such as diphenhydramine. Patients should be informed to read non-prescription allergy, sleep, and cough and cold product labels carefully for additional interacting antihistamines.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of opioid agonists with trifluoperazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking trifluoperazine. Limit the use of opioid pain medications with trifluoperazine 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 and sedative effects may be seen when trifluoperazine is used with first generation antihistamines, such as pyrilamine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
Acetaminophen; Chlorpheniramine: (Moderate) Additive anticholinergic and sedative effects may be seen when trifluoperazine is used with first generation antihistamines, such as chlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Additive anticholinergic and sedative effects may be seen when trifluoperazine is used with first generation antihistamines, such as chlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Additive anticholinergic and sedative effects may be seen when trifluoperazine is used with first generation antihistamines, such as chlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. (Moderate) Other non-cardiovascular drugs with alpha-blocking activity such as phenothiazines, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Additive anticholinergic and sedative effects may be seen when trifluoperazine is used with first generation antihistamines, such as chlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Additive anticholinergic and sedative effects may be seen when trifluoperazine is used with first generation antihistamines, such as chlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. (Moderate) Other non-cardiovascular drugs with alpha-blocking activity such as phenothiazines, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
Acetaminophen; Codeine: (Moderate) Concomitant use of opioid agonists with trifluoperazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking trifluoperazine. Limit the use of opioid pain medications with trifluoperazine 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 and sedative effects may be seen when trifluoperazine is used with first generation antihistamines, such as doxylamine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Other non-cardiovascular drugs with alpha-blocking activity such as phenothiazines, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Other non-cardiovascular drugs with alpha-blocking activity such as phenothiazines, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
Acetaminophen; Dichloralphenazone; Isometheptene: (Moderate) Phenothiazines can potentiate the CNS-depressant action of other drugs such as dichloralphenazone. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Acetaminophen; Diphenhydramine: (Moderate) Additive anticholinergic and sedative effects may be seen when Trifluoperazine is used with first generation antihistamines, such as diphenhydramine. Patients should be informed to read non-prescription allergy, sleep, and cough and cold product labels carefully for additional interacting antihistamines.
Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) Other non-cardiovascular drugs with alpha-blocking activity such as phenothiazines, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
Acetaminophen; Hydrocodone: (Moderate) Concomitant use of opioid agonists with trifluoperazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking trifluoperazine. Limit the use of opioid pain medications with trifluoperazine 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 oxycodone with phenothiazines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with phenothiazines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Monitor for signs of hypotension after starting or titrating the dosage of oxycodone. There is an increased risk of severe hypotension in patients whose ability to maintain blood pressure has already been compromised by concurrent administration of phenothiazines.
Acetaminophen; Pamabrom; Pyrilamine: (Moderate) Additive anticholinergic and sedative effects may be seen when trifluoperazine is used with first generation antihistamines, such as pyrilamine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
Acetaminophen; Phenylephrine: (Moderate) Other non-cardiovascular drugs with alpha-blocking activity such as phenothiazines, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
Adagrasib: (Minor) QT/QTc prolongation can occur with concomitant use of adagrasib and trifluoperazine 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.
Alfentanil: (Moderate) Concomitant use of alfentanil with other CNS depressants, including the phenothiazines, can potentiate the effects of alfentanil on respiration, alertness, and blood pressure. A dose reduction of one or both drugs may be warranted.
Alfuzosin: (Minor) Use caution when administering alfuzosin with trifluoperazine due to the potential for QT prolongation. Alfuzosin may prolong the QT interval in a dose-dependent manner. Trifluoperazine is also associated with a possible risk for QT prolongation.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
Alogliptin: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
Alogliptin; Metformin: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted. (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. When such drugs are administered to a patient receiving metformin, observe the patient closely for loss of blood glucose control. When such drugs are withdrawn from a patient receiving metformin, observe the patient closely for hypoglycemia.
Alogliptin; Pioglitazone: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
Alosetron: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like phenothiazines, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Alpha-glucosidase Inhibitors: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
Alprazolam: (Major) Limit dosage and duration of benzodiazepines during concomitant phenothiazine use and monitor for unusual drowsiness and sedation due to the risk for additive CNS depression.
Amantadine: (Moderate) Although the mechanism of amantadine is not clear, it may potentiate the actions of dopamine. Since phenothiazines are dopamine antagonists, these drugs are best avoided when possible in patients with Parkinson's disease who require amantadine therapy. Also, the anticholinergic effects of phenothiazines can be additive to those of amantadine.
Amifampridine: (Major) Carefully consider the need for concomitant treatment with phenothiazines and amifampridine, as coadministration may increase the risk of seizures. Consider an alternative to the phenothiazine. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Phenothiazines may lower seizure threshold and should be used with caution with concomitant medications which may also affect seizure threshold.
Amikacin: (Minor) When used for the treatment of nausea and vomiting, antiemetic phenothiazines may mask symptoms that are associated with ototoxicity induced by the aminoglycosides.
Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
Aminoglycosides: (Minor) When used for the treatment of nausea and vomiting, antiemetic phenothiazines may mask symptoms that are associated with ototoxicity induced by the aminoglycosides.
Aminolevulinic Acid: (Moderate) Phenothiazines may increase the photosensitizing effects of photosensitizing agents used in photodynamic therapy. Patients should limit ultra-violet exposure.
Amiodarone: (Minor) The concomitant use of amiodarone and other drugs known to prolong the QT interval should only be done after careful assessment of risks versus benefits. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and 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. Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation.
Amisulpride: (Moderate) Monitor ECGs for QT prolongation when amisulpride is administered with trifluoperazine. Amisulpride causes dose- and concentration- dependent QT prolongation. Trifluoperazine is associated with a possible risk for QT prolongation.
Amitriptyline: (Moderate) Phenothiazines have been reported to prolong the QT interval. Because tricyclic antidepressants are associated with a possible risk for QT prolongation and TdP when given in excessive doses or overdosage, concurrent use with trifluoperazine 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. Additive anticholinergic effects or sedation may be seen when phenothiazines are used with tricyclic antidepressants.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
Amobarbital: (Moderate) Phenothiazines are CNS depressant drugs that may have cumulative effects when administered concurrently and they should be used cautiously with anxiolytic, sedative, and hypnotic type drugs, such as the barbiturates. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension. Phenothiazines can also lower the seizure threshold, which may be important in patients taking a barbiturate for the treatment of seizures. Additionally, sleep-related behaviors, such as sleep-driving, are more likely to occur during concurrent use of other CNS depressants than with the use of sedatives alone. Monitor for additive effects, unusual moods or behaviors, and warn about the potential effects to driving and other activities.
Amoxapine: (Moderate) Use caution during coadministration of amoxapine and trifluoperazine. Amoxapine exhibits some antipsychotic activity and may increase the risk of tardive dyskinesia or neuroleptic malignant syndrome (NMS) when antipsychotics are given concurrently. CNS effects, orthostatic hypotension, anticholinergic effects, and lowering of seizure threshold are potential problems with the combined use of amoxapine and antipsychotics.
Amoxicillin; Clarithromycin; Omeprazole: (Minor) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering clarithromycin with trifluoperazine. Clarithromycin is associated with an established risk for QT prolongation and TdP, while trifluoperazine (a phenothiazine) is associated with a possible risk for QT prolongation.
Anagrelide: (Minor) Torsades de pointes (TdP) and ventricular tachycardia have been reported with anagrelide. In addition, dose-related increases in mean QTc and heart rate were observed in healthy subjects. 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 that should be used cautiously with anagrelide include trifluoperazine.
Anticholinergics: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including trifluoperazine. 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.
Anxiolytics; Sedatives; and Hypnotics: (Moderate) Phenothiazines are CNS depressant drugs that may have cumulative effects when administered with other CNS depressant drugs and they should be used cautiously with anxiolytic, sedative, and hypnotics. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension. Additionally, sleep-related behaviors, such as sleep-driving, are more likely to occur during concurrent use of hypnotics and other CNS depressants than with use of a hypnotic alone.
Apomorphine: (Major) Use trifluoperazine with apomorphine with caution; avoid use if possible due to an increased risk for QT prolongation and sedation. Also, the effectiveness of either agent may be decreased due to opposing effects on dopamine; consider if an atypical antipsychotic would be a suitable alternative to trifluoperazine. Additive CNS depression is also possible. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Many phenothiazine antipsychotics are associated with a possible risk for QT prolongation.
Apraclonidine: (Minor) No specific drug interactions were identified with systemic agents and apraclonidine during clinical trials. Theoretically, apraclonidine might potentiate the effects of CNS depressant drugs such as phenothiazines.
Aripiprazole: (Moderate) Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation. Trifluoperazine may increase the risk of QT prolongation if coadministered with drugs with a possible risk for QT prolongation, such as aripiprazole. Co-administration of trifluoperazine with atypical agents (e.g., lurasidone and others) may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Arsenic Trioxide: (Minor) 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 trifluoperazine.
Artemether; Lumefantrine: (Minor) Concurrent use of trifluoperazine and artemether; lumefantrine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Consider ECG monitoring if trifluoperazine must be used with or after artemether; lumefantrine treatment. Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation. Administration of artemether; lumefantrine is also associated with prolongation of the QT interval.
Articaine; Epinephrine: (Moderate) Monitor blood pressure during concomitant epinephrine and phenothiazine use. Phenothiazines antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by a phenothiazine, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure.
Asenapine: (Moderate) Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation. According to the manufacturer, asenapine should not be used with other drugs having an association with QT prolongation. In addition, co-administration of trifluoperazine with atypical agents (e.g., aripiprazole, lurasidone and others) may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Phenothiazines are CNS depressant drugs that may have cumulative effects when administered concurrently and they should be used cautiously with anxiolytic, sedative, and hypnotic type drugs, such as the barbiturates. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension. Phenothiazines can also lower the seizure threshold, which may be important in patients taking a barbiturate for the treatment of seizures. Additionally, sleep-related behaviors, such as sleep-driving, are more likely to occur during concurrent use of other CNS depressants than with the use of sedatives alone. Monitor for additive effects, unusual moods or behaviors, and warn about the potential effects to driving and other activities.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Additive anticholinergic effects may be seen when trifluoperazine is used concomitantly with other drugs having antimuscarinic activity such as orphenadrine. Additive sedation may also occur.
Aspirin, ASA; Carisoprodol: (Moderate) Phenothiazines can potentiate the CNS-depressant action of other drugs such as skeletal muscle relaxants. Caution should be exercised during simultaneous use of these agents due to potential for additive hypotension and excessive CNS effects (sedation and dizziness), which can impair the ability to undertake tasks requiring mental alertness.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of opioid agonists with trifluoperazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking trifluoperazine. Limit the use of opioid pain medications with trifluoperazine 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) Phenothiazines can potentiate the CNS-depressant action of other drugs such as skeletal muscle relaxants. Caution should be exercised during simultaneous use of these agents due to potential for additive hypotension and excessive CNS effects (sedation and dizziness), which can impair the ability to undertake tasks requiring mental alertness.
Aspirin, ASA; Oxycodone: (Major) Concomitant use of oxycodone with phenothiazines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with phenothiazines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Monitor for signs of hypotension after starting or titrating the dosage of oxycodone. There is an increased risk of severe hypotension in patients whose ability to maintain blood pressure has already been compromised by concurrent administration of phenothiazines.
Atenolol; Chlorthalidone: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
Atomoxetine: (Minor) Use atomoxetine with caution in combination with trifluoperazine as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Trifluoperazine is associated with a possible risk for QT prolongation.
Atropine: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including trifluoperazine. 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.
Atropine; Difenoxin: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including trifluoperazine. 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. (Moderate) Diphenoxylate is a synthetic opiate derivative that appears to exert its effect locally and centrally on the smooth muscle cells of the GI tract to inhibit GI motility and slow excess GI propulsion. The effects can be additive to other agents with CNS and anticholinergic effects, such as the phenothiazines. In some cases, constipation might occur, and effects on the CNS or bladder function may also be additive.
Azelastine: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including phenothiazines.
Azelastine; Fluticasone: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including phenothiazines.
Azilsartan; Chlorthalidone: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
Azithromycin: (Major) Concomitant use of trifluoperazine and azithromycin 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.
Baclofen: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of baclofen and phenothiazines due to the risk for additive CNS depression.
Barbiturates: (Moderate) Phenothiazines are CNS depressant drugs that may have cumulative effects when administered concurrently and they should be used cautiously with anxiolytic, sedative, and hypnotic type drugs, such as the barbiturates. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension. Phenothiazines can also lower the seizure threshold, which may be important in patients taking a barbiturate for the treatment of seizures. Additionally, sleep-related behaviors, such as sleep-driving, are more likely to occur during concurrent use of other CNS depressants than with the use of sedatives alone. Monitor for additive effects, unusual moods or behaviors, and warn about the potential effects to driving and other activities.
Bedaquiline: (Minor) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering bedaquiline with trifluoperazine. 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. Trifluoperazine, a phenothiazine, is also associated with a possible risk for QT prolongation.
Belladonna; Opium: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including trifluoperazine. 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. (Moderate) Concomitant use of opioid agonists with trifluoperazine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with trifluoperazine 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.
Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
Benzhydrocodone; Acetaminophen: (Major) Concomitant use of opioid agonists with trifluoperazine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with trifluoperazine 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. If benzhydrocodone is initiated in a patient taking trifluoperazine, reduce initial dosage and titrate to clinical response. If trifluoperazine is initiated a patient taking an opioid agonist, use a lower initial dose of trifluoperazine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Benzodiazepines: (Major) Limit dosage and duration of benzodiazepines during concomitant phenothiazine use and monitor for unusual drowsiness and sedation due to the risk for additive CNS depression.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including trifluoperazine. 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.
Benztropine: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including trifluoperazine. 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.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Minor) QT/QTc prolongation can occur with concomitant use of metronidazole and trifluoperazine 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.
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 phenothiazines 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 phenothiazines may produce additive effects. (Minor) QT/QTc prolongation can occur with concomitant use of metronidazole and trifluoperazine 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.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
Brexpiprazole: (Major) Caution is advisable during concurrent use of brexpiprazole with other antipsychotics such as phenothiazines. The risk of drowsiness, dizziness, hypotension, extrapyramidal symptoms, anticholinergic effects, neuroleptic malignant syndrome, or seizures may be increased during combined use of brexpiprazole and phenothiazines; therefore, it may be advisable to initiate treatment with lower dosages if combination therapy is deemed necessary. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the coadministered antipsychotic agent, with low-potency agents (e.g., thioridazine, chlorpromazine) having an increased likelihood of causing sedation, orthostasis, and anticholinergic effects, and high-potency agents (e.g., fluphenazine) having an increased likelihood of causing extrapyramidal effects. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Bromocriptine: (Major) Avoid concurrent use of phenothiazines and bromocriptine when possible. Bromocriptine may interact with dopamine antagonists such as the phenothiazines. The phenothiazines are noted to result in a decreased efficacy of bromocriptine. The prolactin-lowering effect of bromocriptine is antagonized; the elevation in prolactin levels produced by phenothiazines persists with chronic administration. In addition, bromocriptine, a dopamine agonist, may theoretically diminish the effectiveness of central dopamine antagonists such as the phenothiazines; however, such interactions are not certain.
Brompheniramine: (Moderate) Additive anticholinergic and sedative effects may be seen when trifluoperazine is used with first generation antihistamines, such as brompheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Additive anticholinergic and sedative effects may be seen when trifluoperazine is used with first generation antihistamines, such as brompheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. (Moderate) Other non-cardiovascular drugs with alpha-blocking activity such as phenothiazines, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
Brompheniramine; Phenylephrine: (Moderate) Additive anticholinergic and sedative effects may be seen when trifluoperazine is used with first generation antihistamines, such as brompheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. (Moderate) Other non-cardiovascular drugs with alpha-blocking activity such as phenothiazines, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
Brompheniramine; Pseudoephedrine: (Moderate) Additive anticholinergic and sedative effects may be seen when trifluoperazine is used with first generation antihistamines, such as brompheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Additive anticholinergic and sedative effects may be seen when trifluoperazine is used with first generation antihistamines, such as brompheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including trifluoperazine. 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.
Bupivacaine; Epinephrine: (Moderate) Monitor blood pressure during concomitant epinephrine and phenothiazine use. Phenothiazines antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by a phenothiazine, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure.
Buprenorphine: (Moderate) Due to the potential for QT prolongation and additive CNS depressant effects, cautious use and close monitoring are advisable if concurrent use of phenothiazines and buprenorphine is necessary. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval. Phenothiazines including fluphenazine, perphenazine, prochlorperazine, and trifluoperazine are associated with a possible risk for QT prolongation. Theoretically, these phenothiazines may increase the risk of QT prolongation if co-administered with drugs with a risk of QT prolongation. Also, concomitant use of buprenorphine with other CNS depressants, such as phenothiazines, can lead to additive CNS depressive effects. Hypotension, profound sedation, coma, respiratory depression, or death may occur. 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. Evaluate the patient's use of alcohol or illicit drugs. Consider a dose reduction of one or both drugs. 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) Due to the potential for QT prolongation and additive CNS depressant effects, cautious use and close monitoring are advisable if concurrent use of phenothiazines and buprenorphine is necessary. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval. Phenothiazines including fluphenazine, perphenazine, prochlorperazine, and trifluoperazine are associated with a possible risk for QT prolongation. Theoretically, these phenothiazines may increase the risk of QT prolongation if co-administered with drugs with a risk of QT prolongation. Also, concomitant use of buprenorphine with other CNS depressants, such as phenothiazines, can lead to additive CNS depressive effects. Hypotension, profound sedation, coma, respiratory depression, or death may occur. 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. Evaluate the patient's use of alcohol or illicit drugs. Consider a dose reduction of one or both drugs. 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) Bupropion is associated with a dose-related risk of seizures and may have an additive effect with phenothiazines on lowering the seizure threshold. Low initial dosing and slow titration is recommended if this combination must be used. In addition, bupropion is a strong inhibitor of CYP2D6. Dosage reductions of trifluoperazine, a CYP2D6 substrate, may be needed during coadministration with bupropion. Increased serum concentrations of trifluoperazine may result in extrapyramidal symptoms, somnolence, or other adverse effects.
Bupropion; Naltrexone: (Major) Bupropion is associated with a dose-related risk of seizures and may have an additive effect with phenothiazines on lowering the seizure threshold. Low initial dosing and slow titration is recommended if this combination must be used. In addition, bupropion is a strong inhibitor of CYP2D6. Dosage reductions of trifluoperazine, a CYP2D6 substrate, may be needed during coadministration with bupropion. Increased serum concentrations of trifluoperazine may result in extrapyramidal symptoms, somnolence, or other adverse effects. (Moderate) Patients receiving phenothiazines and naltrexone concomitantly have had symptoms of somnolence and lethargy.
Butabarbital: (Moderate) Phenothiazines are CNS depressant drugs that may have cumulative effects when administered concurrently and they should be used cautiously with anxiolytic, sedative, and hypnotic type drugs, such as the barbiturates. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension. Phenothiazines can also lower the seizure threshold, which may be important in patients taking a barbiturate for the treatment of seizures. Additionally, sleep-related behaviors, such as sleep-driving, are more likely to occur during concurrent use of other CNS depressants than with the use of sedatives alone. Monitor for additive effects, unusual moods or behaviors, and warn about the potential effects to driving and other activities.
Butalbital; Acetaminophen: (Moderate) Phenothiazines are CNS depressant drugs that may have cumulative effects when administered concurrently and they should be used cautiously with anxiolytic, sedative, and hypnotic type drugs, such as the barbiturates. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension. Phenothiazines can also lower the seizure threshold, which may be important in patients taking a barbiturate for the treatment of seizures. Additionally, sleep-related behaviors, such as sleep-driving, are more likely to occur during concurrent use of other CNS depressants than with the use of sedatives alone. Monitor for additive effects, unusual moods or behaviors, and warn about the potential effects to driving and other activities.
Butalbital; Acetaminophen; Caffeine: (Moderate) Phenothiazines are CNS depressant drugs that may have cumulative effects when administered concurrently and they should be used cautiously with anxiolytic, sedative, and hypnotic type drugs, such as the barbiturates. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension. Phenothiazines can also lower the seizure threshold, which may be important in patients taking a barbiturate for the treatment of seizures. Additionally, sleep-related behaviors, such as sleep-driving, are more likely to occur during concurrent use of other CNS depressants than with the use of sedatives alone. Monitor for additive effects, unusual moods or behaviors, and warn about the potential effects to driving and other activities.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Concomitant use of opioid agonists with trifluoperazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking trifluoperazine. Limit the use of opioid pain medications with trifluoperazine 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) Phenothiazines are CNS depressant drugs that may have cumulative effects when administered concurrently and they should be used cautiously with anxiolytic, sedative, and hypnotic type drugs, such as the barbiturates. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension. Phenothiazines can also lower the seizure threshold, which may be important in patients taking a barbiturate for the treatment of seizures. Additionally, sleep-related behaviors, such as sleep-driving, are more likely to occur during concurrent use of other CNS depressants than with the use of sedatives alone. Monitor for additive effects, unusual moods or behaviors, and warn about the potential effects to driving and other activities.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Concomitant use of opioid agonists with trifluoperazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking trifluoperazine. Limit the use of opioid pain medications with trifluoperazine 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) Phenothiazines are CNS depressant drugs that may have cumulative effects when administered concurrently and they should be used cautiously with anxiolytic, sedative, and hypnotic type drugs, such as the barbiturates. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension. Phenothiazines can also lower the seizure threshold, which may be important in patients taking a barbiturate for the treatment of seizures. Additionally, sleep-related behaviors, such as sleep-driving, are more likely to occur during concurrent use of other CNS depressants than with the use of sedatives alone. Monitor for additive effects, unusual moods or behaviors, and warn about the potential effects to driving and other activities.
Butorphanol: (Moderate) Concomitant use of butorphanol with other CNS depressants, such as phenothiazines, can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
Cabergoline: (Moderate) Cabergoline should generally not be coadministered with phenothiazines due to mutually antagonistic effects on dopaminergic function. The dopamine antagonist action of phenothiazines may diminish the prolactin-lowering ability of cabergoline while the dopamine agonist effects of cabergoline may exacerbate a psychotic disorder, reducing the effectiveness of antipsychotics such as phenothiazines.
Cabotegravir; Rilpivirine: (Minor) Caution is advised when administering rilpivirine with trifluoperazine as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Trifluoperazine is also associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Calcium, Magnesium, Potassium, Sodium Oxybates: (Major) Additive CNS depressant effects may be possible when sodium oxybate is used concurrently with phenothiazines.
Canagliflozin: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should be closely monitored for worsening glycemic control when any of these antipsychotics is instituted.
Canagliflozin; Metformin: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should be closely monitored for worsening glycemic control when any of these antipsychotics is instituted. (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. When such drugs are administered to a patient receiving metformin, observe the patient closely for loss of blood glucose control. When such drugs are withdrawn from a patient receiving metformin, observe the patient closely for hypoglycemia.
Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
Cannabidiol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and phenothiazines. CNS depressants can potentiate the effects of cannabidiol.
Capsaicin; Metaxalone: (Moderate) Phenothiazines can potentiate the CNS-depressant action of skeletal muscle relaxants like metaxalone. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects.
Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
Carbidopa; Levodopa: (Major) Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. Due to opposing effects on central dopaminergic activity, phenothiazines and levodopa may interfere with the effectiveness of each other.
Carbidopa; Levodopa; Entacapone: (Major) Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. Due to opposing effects on central dopaminergic activity, phenothiazines and levodopa may interfere with the effectiveness of each other.
Carbinoxamine: (Moderate) Additive anticholinergic and sedative effects may be seen when trifluoperazine is used with first generation antihistamines, such as carbinoxamine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
Cariprazine: (Major) Avoid use of these drugs together due to duplicative therapeutic effects and additive risks for drowsiness, dizziness, orthostatic hypotension, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. Cariprazine, like other antipsychotics, has the potential to impair judgment, thinking, or motor skills. The use of cariprazine with other antipsychotic agents, such as the phenothiazines, would be expected to have additive risks for pharmacologic effects and adverse reactions. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during combined use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Carisoprodol: (Moderate) Phenothiazines can potentiate the CNS-depressant action of other drugs such as skeletal muscle relaxants. Caution should be exercised during simultaneous use of these agents due to potential for additive hypotension and excessive CNS effects (sedation and dizziness), which can impair the ability to undertake tasks requiring mental alertness.
Celecoxib; Tramadol: (Moderate) Concurrent use of tramadol and trifluoperazine should be avoided if possible. Antipsychotics may enhance the seizure risk of tramadol. Additive CNS depression may also be seen with the concomitant use of tramadol and trifluoperazine.
Cenobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cenobamate and a phenothiazine. Concurrent use may result in additive CNS depression.
Central-acting adrenergic agents: (Moderate) Monitor blood pressure and for unusual drowsiness or excessive sedation during concomitant central-acting adrenergic agent and phenothiazine use. Concomitant use increases the risk for additive hypotension and CNS depression.
Ceritinib: (Minor) Trifluoperazine is associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation, such a ceritinib.
Cetrorelix: (Moderate) Drugs that cause hyperprolactinemia, such as antipsychotics, should not be administered concomitantly with cetrorelix since hyperprolactinemia downregulates the number of pituitary GnRH receptors.
Charcoal: (Major) Phenothiazine absorption is reduced when coadministered with activated charcoal. Concomitant administration of phenothiazines and activated charcoal dietary supplements is not recommended. Activated charcoal may be appropriate in phenothiazine overdose situations, as charcoal absorbs the phenothiazines and also enhances drug elimination.
Chlophedianol; Dexbrompheniramine: (Moderate) Additive anticholinergic and sedative effects may be seen when trifluoperazine is used with first generation antihistamines, such as dexbrompheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Additive anticholinergic and sedative effects may be seen when trifluoperazine is used with first generation antihistamines, such as dexchlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
Chlordiazepoxide: (Major) Limit dosage and duration of benzodiazepines during concomitant phenothiazine use and monitor for unusual drowsiness and sedation due to the risk for additive CNS depression.
Chlordiazepoxide; Amitriptyline: (Major) Limit dosage and duration of benzodiazepines during concomitant phenothiazine use and monitor for unusual drowsiness and sedation due to the risk for additive CNS depression. (Moderate) Phenothiazines have been reported to prolong the QT interval. Because tricyclic antidepressants are associated with a possible risk for QT prolongation and TdP when given in excessive doses or overdosage, concurrent use with trifluoperazine 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. Additive anticholinergic effects or sedation may be seen when phenothiazines are used with tricyclic antidepressants.
Chlordiazepoxide; Clidinium: (Major) Limit dosage and duration of benzodiazepines during concomitant phenothiazine use and monitor for unusual drowsiness and sedation due to the risk for additive CNS depression. (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including trifluoperazine. 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.
Chloroquine: (Major) Avoid coadministration of chloroquine with trifluoperazine 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. Trifluoperazine is associated with a possible risk for QT prolongation.
Chlorothiazide: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
Chlorpheniramine: (Moderate) Additive anticholinergic and sedative effects may be seen when trifluoperazine is used with first generation antihistamines, such as chlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
Chlorpheniramine; Codeine: (Moderate) Additive anticholinergic and sedative effects may be seen when trifluoperazine is used with first generation antihistamines, such as chlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. (Moderate) Concomitant use of opioid agonists with trifluoperazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking trifluoperazine. Limit the use of opioid pain medications with trifluoperazine 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.
Chlorpheniramine; Dextromethorphan: (Moderate) Additive anticholinergic and sedative effects may be seen when trifluoperazine is used with first generation antihistamines, such as chlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Additive anticholinergic and sedative effects may be seen when trifluoperazine is used with first generation antihistamines, such as chlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. (Moderate) Other non-cardiovascular drugs with alpha-blocking activity such as phenothiazines, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Additive anticholinergic and sedative effects may be seen when trifluoperazine is used with first generation antihistamines, such as chlorpheniramine. Patients should be informed to read

non-prescription cough and cold product labels carefully for additional interacting antihistamines.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Additive anticholinergic and sedative effects may be seen when trifluoperazine is used with first generation antihistamines, such as chlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. (Moderate) Concomitant use of opioid agonists with trifluoperazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking trifluoperazine. Limit the use of opioid pain medications with trifluoperazine 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) Other non-cardiovascular drugs with alpha-blocking activity such as phenothiazines, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
Chlorpheniramine; Hydrocodone: (Moderate) Additive anticholinergic and sedative effects may be seen when trifluoperazine is used with first generation antihistamines, such as chlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. (Moderate) Concomitant use of opioid agonists with trifluoperazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking trifluoperazine. Limit the use of opioid pain medications with trifluoperazine 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.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Additive anticholinergic and sedative effects may be seen when trifluoperazine is used with first generation antihistamines, such as chlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
Chlorpheniramine; Phenylephrine: (Moderate) Additive anticholinergic and sedative effects may be seen when trifluoperazine is used with first generation antihistamines, such as chlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. (Moderate) Other non-cardiovascular drugs with alpha-blocking activity such as phenothiazines, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
Chlorpheniramine; Pseudoephedrine: (Moderate) Additive anticholinergic and sedative effects may be seen when trifluoperazine is used with first generation antihistamines, such as chlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
Chlorpromazine: (Moderate) Coadministration of chlorpromazine and trifluoperazine should be avoided if possible due to the risk of QT prolongation and other adverse effects. Chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and torsade de pointes (TdP). Trifluoperazine is also a phenothiazine and is associated with a possible risk for QT prolongation. Coadministration may also increase the risk of drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, tardive dyskinesia, or seizures.
Chlorpropamide: (Moderate) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted. Also, concomitant use may increase the risk for phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure.
Chlorthalidone: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
Chlorthalidone; Clonidine: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
Chlorzoxazone: (Moderate) Phenothiazines can potentiate the CNS-depressant action of other drugs such as skeletal muscle relaxants. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Ciprofloxacin: (Minor) QT/QTc prolongation can occur with concomitant use of ciprofloxacin and trifluoperazine 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.
Cisapride: (Contraindicated) Coadministration of cisapride and trifluoperazine is contraindicated due to the risk for serious adverse events, such as torsade de pointes (TdP). QT prolongation and ventricular arrhythmias, including TdP and death, have been reported with cisapride. Trifluoperazine, a phenothiazine, is also associated with a possible risk for QT prolongation and/or TdP.
Citalopram: (Minor) Citalopram causes dose-dependent QT interval prolongation. According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended. Trifluoperazine is associated with a possible risk for QT prolongation.
Clarithromycin: (Minor) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering clarithromycin with trifluoperazine. Clarithromycin is associated with an established risk for QT prolongation and TdP, while trifluoperazine (a phenothiazine) is associated with a possible risk for QT prolongation.
Clemastine: (Moderate) Additive anticholinergic and sedative effects may be seen when trifluoperazine is used with first generation antihistamines, such as clemastine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
Clindamycin; Tretinoin: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as phenothiazines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Clobazam: (Major) A dose reduction of CYP2D6 substrates, such as trifluoperazine, may be necessary during coadministration of clobazam. Clobazam is a weak inhibitor of CYP2D6. Elevated concentrations of trifluoperazine occurring through inhibition of CYP2D6 may increase the risk of extrapyramidal symptoms, somnolence, or other serious adverse effects. In addition, phenothiazines may lower the seizure threshold and reduce the effectiveness of clobazam as an anticonvulsant.
Clofazimine: (Minor) QT/QTc prolongation can occur with concomitant use of clofazimine and trifluoperazine 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.
Clomipramine: (Moderate) Phenothiazines have been reported to prolong the QT interval. Because tricyclic antidepressants are associated with a possible risk for QT prolongation and TdP when given in excessive doses or overdosage, concurrent use with trifluoperazine 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. Additive anticholinergic effects or sedation may be seen when phenothiazines are used with tricyclic antidepressants.
Clonazepam: (Major) Limit dosage and duration of benzodiazepines during concomitant phenothiazine use and monitor for unusual drowsiness and sedation due to the risk for additive CNS depression.
Clorazepate: (Major) Limit dosage and duration of benzodiazepines during concomitant phenothiazine use and monitor for unusual drowsiness and sedation due to the risk for additive CNS depression.
Clozapine: (Moderate) Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with drugs with a possible risk for QT prolongation, such as clozapine. Coadministration may also increase the risk of drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Codeine: (Moderate) Concomitant use of opioid agonists with trifluoperazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking trifluoperazine. Limit the use of opioid pain medications with trifluoperazine 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: (Moderate) Concomitant use of opioid agonists with trifluoperazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking trifluoperazine. Limit the use of opioid pain medications with trifluoperazine 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: (Moderate) Concomitant use of opioid agonists with trifluoperazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking trifluoperazine. Limit the use of opioid pain medications with trifluoperazine 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; Phenylephrine; Promethazine: (Moderate) Concomitant use of opioid agonists with trifluoperazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking trifluoperazine. Limit the use of opioid pain medications with trifluoperazine 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) Other non-cardiovascular drugs with alpha-blocking activity such as phenothiazines, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension. (Moderate) Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Promethazine should be used with caution with other phenothiazines that carry a theoretical risk of QT prolongation including trifluoperazine. In addition, coadministration may increase the risk of drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, tardive dyskinesia, or seizures.
Codeine; Promethazine: (Moderate) Concomitant use of opioid agonists with trifluoperazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking trifluoperazine. Limit the use of opioid pain medications with trifluoperazine 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, a phenothiazine, is associated with a possible risk for QT prolongation. Promethazine should be used with caution with other phenothiazines that carry a theoretical risk of QT prolongation including trifluoperazine. In addition, coadministration may increase the risk of drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, tardive dyskinesia, or seizures.
COMT inhibitors: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and COMT inhibitors may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Crizotinib: (Minor) Monitor ECGs for QT prolongation and monitor electrolytes in patients receiving crizotinib concomitantly with trifluoperazine. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib patients if QT prolongation occurs. Crizotinib has been associated with concentration-dependent QT prolongation. Trifluoperazine is associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Cyclobenzaprine: (Moderate) Additive anticholinergic effects may be seen when trifluoperazine is used concomitantly with other drugs with antimuscarinic activity such as cyclobenzaprine. Antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur.
Dantrolene: (Moderate) Phenothiazines can potentiate the CNS-depressant action of other drugs such as skeletal muscle relaxants. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Dapagliflozin: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should be closely monitored for worsening glycemic control when any of these antipsychotics is instituted.
Dapagliflozin; Metformin: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should be closely monitored for worsening glycemic control when any of these antipsychotics is instituted. (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. When such drugs are administered to a patient receiving metformin, observe the patient closely for loss of blood glucose control. When such drugs are withdrawn from a patient receiving metformin, observe the patient closely for hypoglycemia.
Dapagliflozin; Saxagliptin: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should be closely monitored for worsening glycemic control when any of these antipsychotics is instituted. (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
Dasatinib: (Minor) Monitor for evidence of QT prolongation during concurrent use of dasatinib and trifluoperazine. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Trifluoperazine is associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Degarelix: (Major) Avoid coadministration of degarelix with trifluoperazine due to the risk of reduced efficacy of degarelix; QT prolongation may also occur. Trifluoperazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; degarelix is a GnRH analog. Additionally, androgen deprivation therapy (i.e., degarelix) may prolong the QT/QTc interval. Trifluoperazine is also associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Desflurane: (Minor) Halogenated anesthetics should be used cautiously and with close monitoring with trifluoperazine. Halogenated anesthetics can prolong the QT interval. Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation. In addition, phenothiazines can potentiate the CNS-depressant action of halogenated anesthetics.
Desipramine: (Moderate) Phenothiazines have been reported to prolong the QT interval. Because tricyclic antidepressants are associated with a possible risk for QT prolongation and TdP when given in excessive doses or overdosage, concurrent use with trifluoperazine 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. Additive anticholinergic effects or sedation may be seen when phenothiazines are used with tricyclic antidepressants.
Desogestrel; Ethinyl Estradiol: (Minor) Oral contraceptives may also cause additive photosensitization with phenothiazines.
Desvenlafaxine: (Major) Dosage adjustments of some phenothiazines may be necessary during concurrent use of desvenlafaxine. Although clinical studies have shown that desvenlafaxine does not have a clinically relevant effect on CYP2D6 inhibition at doses of 100 mg/day, the manufacturer that primary substrates of CYP2D6, such as perphenazine, be dosed at the original level when co-administered with desvenlafaxine 100 mg or lower or when desvenlafaxine is discontinued. The dose of these CYP2D6 substrates should be reduced by up to one-half if co-administered with desvenlafaxine 400 mg/day.
Deutetrabenazine: (Moderate) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and trifluoperazine. 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. Trifluoperazine is associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation. 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 trifluoperazine is a dopamine antagonist. The risk for parkinsonism, NMS, or akathisia may be increased with concomitant administration. Monitor for excessive sedation and somnolence during coadministration of trifluoperazine and deutetrabenazine. Concurrent use may result in additive CNS depression.
Dexbrompheniramine: (Moderate) Additive anticholinergic and sedative effects may be seen when trifluoperazine is used with first generation antihistamines, such as dexbrompheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
Dexbrompheniramine; Pseudoephedrine: (Moderate) Additive anticholinergic and sedative effects may be seen when trifluoperazine is used with first generation antihistamines, such as dexbrompheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
Dexchlorpheniramine: (Moderate) Additive anticholinergic and sedative effects may be seen when trifluoperazine is used with first generation antihistamines, such as dexchlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Additive anticholinergic and sedative effects may be seen when trifluoperazine is used with first generation antihistamines, such as dexchlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
Dexmedetomidine: (Moderate) Consider a dosage reduction for dexmedetomidine or the phenothiazine during concomitant use due to the risk of additive CNS effects.
Dextromethorphan; Bupropion: (Major) Bupropion is associated with a dose-related risk of seizures and may have an additive effect with phenothiazines on lowering the seizure threshold. Low initial dosing and slow titration is recommended if this combination must be used. In addition, bupropion is a strong inhibitor of CYP2D6. Dosage reductions of trifluoperazine, a CYP2D6 substrate, may be needed during coadministration with bupropion. Increased serum concentrations of trifluoperazine may result in extrapyramidal symptoms, somnolence, or other adverse effects.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Additive anticholinergic and sedative effects may be seen when Trifluoperazine is used with first generation antihistamines, such as diphenhydramine. Patients should be informed to read non-prescription allergy, sleep, and cough and cold product labels carefully for additional interacting antihistamines. (Moderate) Other non-cardiovascular drugs with alpha-blocking activity such as phenothiazines, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Other non-cardiovascular drugs with alpha-blocking activity such as phenothiazines, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
Dextromethorphan; Quinidine: (Minor) Trifluoperazine and quinidine should be used cautiously due to the potential for QT prolongation. Trifluoperazine, a phenothiazine, has a possible risk for QT prolongation. Quinidine is associated with a well-established risk of QT prolongation and torsade de pointes (TdP).
Diazepam: (Major) Limit dosage and duration of benzodiazepines during concomitant phenothiazine use and monitor for unusual drowsiness and sedation due to the risk for additive CNS depression.
Dicyclomine: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including trifluoperazine. 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.
Diethylpropion: (Minor) Use of diethylpropion with phenothiazines may antagonize the anorectic effects of diethylpropion.
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 and sedative effects may be seen when trifluoperazine is used with first generation antihistamines, such as dimenhydrinate. Patients should be informed to read non-prescription motion sickness, allergy, sleep, and cough and cold product labels carefully for additional interacting antihistamines.
Dipeptidyl Peptidase-4 Inhibitors: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
Diphenhydramine: (Moderate) Additive anticholinergic and sedative effects may be seen when Trifluoperazine is used with first generation antihistamines, such as diphenhydramine. Patients should be informed to read non-prescription allergy, sleep, and cough and cold product labels carefully for additional interacting antihistamines.
Diphenhydramine; Ibuprofen: (Moderate) Additive anticholinergic and sedative effects may be seen when Trifluoperazine is used with first generation antihistamines, such as diphenhydramine. Patients should be informed to read non-prescription allergy, sleep, and cough and cold product labels carefully for additional interacting antihistamines.
Diphenhydramine; Naproxen: (Moderate) Additive anticholinergic and sedative effects may be seen when Trifluoperazine is used with first generation antihistamines, such as diphenhydramine. Patients should be informed to read non-prescription allergy, sleep, and cough and cold product labels carefully for additional interacting antihistamines.
Diphenhydramine; Phenylephrine: (Moderate) Additive anticholinergic and sedative effects may be seen when Trifluoperazine is used with first generation antihistamines, such as diphenhydramine. Patients should be informed to read non-prescription allergy, sleep, and cough and cold product labels carefully for additional interacting antihistamines. (Moderate) Other non-cardiovascular drugs with alpha-blocking activity such as phenothiazines, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
Diphenoxylate; Atropine: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including trifluoperazine. 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. (Moderate) Diphenoxylate is a synthetic opiate derivative that appears to exert its effect locally and centrally on the smooth muscle cells of the GI tract to inhibit GI motility and slow excess GI propulsion. The effects can be additive to other agents with CNS and anticholinergic effects, such as the phenothiazines. In some cases, constipation might occur, and effects on the CNS or bladder function may also be additive.
Disopyramide: (Moderate) Trifluoperazine and disopyramide should be used cautiously due to the potential for QT prolongation. Trifluoperazine, a phenothiazine, has a possible risk for QT prolongation. Disopyramide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). In addition, trifluoperazine and disopyramide have significant anticholinergic effects which may be additive during coadministration.
Dofetilide: (Minor) Trifluoperazine is associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation such as dofetilide.
Dolasetron: (Minor) Administer dolasetron with caution in combination with trifluoperazine. Trifluoperazine is associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Dolutegravir; Rilpivirine: (Minor) Caution is advised when administering rilpivirine with trifluoperazine as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Trifluoperazine is also associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Donepezil: (Minor) Use donepezil with caution in combination with trifluoperazine as concurrent use may increase the risk of QT prolongation. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Trifluoperazine is associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Donepezil; Memantine: (Minor) Use donepezil with caution in combination with trifluoperazine as concurrent use may increase the risk of QT prolongation. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Trifluoperazine is associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Dopamine: (Moderate) The vasoconstrictive properties of dopamine infusion can be decreased due to the alpha-adrenergic blocking capability of phenothiazines.
Doxepin: (Moderate) Phenothiazines have been reported to prolong the QT interval. Because tricyclic antidepressants are associated with a possible risk for QT prolongation and TdP when given in excessive doses or overdosage, concurrent use with trifluoperazine 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. Additive anticholinergic effects or sedation may be seen when phenothiazines are used with tricyclic antidepressants.
Doxylamine: (Moderate) Additive anticholinergic and sedative effects may be seen when trifluoperazine is used with first generation antihistamines, such as doxylamine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
Doxylamine; Pyridoxine: (Moderate) Additive anticholinergic and sedative effects may be seen when trifluoperazine is used with first generation antihistamines, such as doxylamine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
Dronabinol: (Moderate) Use caution if coadministration of phenothiazines with dronabinol is necessary. Administration of dronabinol with phenothiazines (e.g., prochlorperazine) has resulted in improved antiemetic efficacy as compared to either drug alone, without additional toxicity. However, it is also possible that coadministration may result in additive dizziness, confusion, somnolence, and other CNS effects.
Dronedarone: (Contraindicated) Concurrent use of trifluoperazine and dronedarone is contraindicated. Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation and/or 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: (Minor) Droperidol should be administered with extreme caution to patients receiving other agents that are known to prolong the QT interval. Droperidol administration is associated with an established risk for QT prolongation and torsades de pointes (TdP). Drugs with a possible risk for QT prolongation that should be used cautiously with droperidol include trifluoperazine. Droperidol may also cause increased CNS sedation when given with trifluoperazine.
Drospirenone; Ethinyl Estradiol: (Minor) Oral contraceptives may also cause additive photosensitization with phenothiazines.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Minor) Oral contraceptives may also cause additive photosensitization with phenothiazines.
Duloxetine: (Moderate) Caution is advisable during concurrent use of trifluoperazine and serotonin norepinephrine reuptake inhibitors (SNRIs) since elevations in plasma concentrations of trifluoperazine may occur. Phenothiazines are CYP2D6 substrates, and SNRIs including duloxetine are CYP2D6 inhibitors.
Efavirenz: (Minor) Consider alternatives to efavirenz when coadministering with trifluoperazine as concurrent use may increase the risk of QT prolongation. QTc prolongation has been observed with the use of efavirenz. Trifluoperazine is associated with a possible risk for QT prolongation.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Minor) Consider alternatives to efavirenz when coadministering with trifluoperazine as concurrent use may increase the risk of QT prolongation. QTc prolongation has been observed with the use of efavirenz. Trifluoperazine is associated with a possible risk for QT prolongation.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Minor) Consider alternatives to efavirenz when coadministering with trifluoperazine as concurrent use may increase the risk of QT prolongation. QTc prolongation has been observed with the use of efavirenz. Trifluoperazine is associated with a possible risk for QT prolongation.
Eliglustat: (Minor) Coadministration of trifluoperazine and eliglustat may result in increased concentrations of the phenothiazine and, theoretically, an increased risk of QT prolongation. If coadministration is necessary, use caution and monitor closely. Consider reducing the dosage of phenothiazine and titrating to clinical effect. Trifluoperazine is a CYP2D6 substrate associated with a possible risk for QT prolongation. Eliglustat is a CYP2D6 inhibitor that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations.
Empagliflozin: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should be closely monitored for worsening glycemic control when any of these antipsychotics is instituted.
Empagliflozin; Linagliptin: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should be closely monitored for worsening glycemic control when any of these antipsychotics is instituted. (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
Empagliflozin; Linagliptin; Metformin: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should be closely monitored for worsening glycemic control when any of these antipsychotics is instituted. (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted. (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. When such drugs are administered to a patient receiving metformin, observe the patient closely for loss of blood glucose control. When such drugs are withdrawn from a patient receiving metformin, observe the patient closely for hypoglycemia.
Empagliflozin; Metformin: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should be closely monitored for worsening glycemic control when any of these antipsychotics is instituted. (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. When such drugs are administered to a patient receiving metformin, observe the patient closely for loss of blood glucose control. When such drugs are withdrawn from a patient receiving metformin, observe the patient closely for hypoglycemia.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Minor) Caution is advised when administering rilpivirine with trifluoperazine as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Trifluoperazine is also associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Minor) Caution is advised when administering rilpivirine with trifluoperazine as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Trifluoperazine is also associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
Encorafenib: (Minor) Consider monitoring ECGs for QT prolongation and electrolytes if encorafenib and trifluoperazine are coadministered due to the potential for additive QT prolongation. Correct hypokalemia and hypomagnesemia prior to treatment. Encorafenib is associated with dose-dependent prolongation of the QT interval. Trifluoperazine is associated with a possible risk for QT prolongation.
Entrectinib: (Minor) Trifluoperazine is associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation, such as entrectinib.
Ephedrine: (Major) Avoid use of ephedrine in patients receiving phenothiazines due to the risk of paradoxical vasodilation. Phenothiazines possess potent alpha-blocking properties, making the use of vasopressors with mixed alpha- and beta-agonist properties inappropriate. If a vasopressor is required, norepinephrine and phenylephrine are most appropriate.
Ephedrine; Guaifenesin: (Major) Avoid use of ephedrine in patients receiving phenothiazines due to the risk of paradoxical vasodilation. Phenothiazines possess potent alpha-blocking properties, making the use of vasopressors with mixed alpha- and beta-agonist properties inappropriate. If a vasopressor is required, norepinephrine and phenylephrine are most appropriate.
Epinephrine: (Moderate) Monitor blood pressure during concomitant epinephrine and phenothiazine use. Phenothiazines antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by a phenothiazine, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure.
Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
Eribulin: (Minor) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval, such as trifluoperazine, must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
Ertugliflozin: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should be closely monitored for worsening glycemic control when any of these antipsychotics is instituted.
Ertugliflozin; Metformin: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should be closely monitored for worsening glycemic control when any of these antipsychotics is instituted. (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. When such drugs are administered to a patient receiving metformin, observe the patient closely for loss of blood glucose control. When such drugs are withdrawn from a patient receiving metformin, observe the patient closely for hypoglycemia.
Ertugliflozin; Sitagliptin: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should be closely monitored for worsening glycemic control when any of these antipsychotics is instituted. (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
Erythromycin: (Minor) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering erythromycin with trifluoperazine. Erythromycin is associated with prolongation of the QT interval and TdP. Trifluoperazine, a phenothiazine, is also associated with a possible risk for QT prolongation.
Escitalopram: (Minor) Use escitalopram with caution in combination with trifluoperazine as concurrent use may increase the risk of QT prolongation. Escitalopram has been associated with a risk of QT prolongation and torsade de pointes (TdP). Trifluoperazine is associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Esketamine: (Moderate) Closely monitor patients receiving esketamine and trifluoperazine 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: (Major) Limit dosage and duration of benzodiazepines during concomitant phenothiazine use and monitor for unusual drowsiness and sedation due to the risk for additive CNS depression.
Eszopiclone: (Moderate) Phenothiazines are CNS depressant drugs that may have cumulative effects when administered with other CNS depressant drugs and they should be used cautiously with anxiolytic, sedative, and hypnotics. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension. Additionally, sleep-related behaviors, such as sleep-driving, are more likely to occur during concurrent use of hypnotics and other CNS depressants than with use of a hypnotic alone.
Ethanol: (Major) Advise patients to avoid alcohol consumption while taking CNS depressants. Alcohol consumption may result in additive CNS depression.
Ethinyl Estradiol; Norelgestromin: (Minor) Oral contraceptives may also cause additive photosensitization with phenothiazines.
Ethinyl Estradiol; Norethindrone Acetate: (Minor) Oral contraceptives may also cause additive photosensitization with phenothiazines.
Ethinyl Estradiol; Norgestrel: (Minor) Oral contraceptives may also cause additive photosensitization with phenothiazines.
Ethiodized Oil: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering the use of intrathecal radiopaque contrast agents. Phenothiazines should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Ethosuximide: (Moderate) Concomitant use of ethosuximide with phenothiazines can lower the seizure threshold and reduce the effectiveness of ethosuximide as an anticonvulsant. Additive CNS effects, such as drowsiness, may also occur.
Ethynodiol Diacetate; Ethinyl Estradiol: (Minor) Oral contraceptives may also cause additive photosensitization with phenothiazines.
Etomidate: (Moderate) Etomidate potentiates the effects of CNS depressants including trifluoperazine. Additive CNS effects (e.g., oversedation, respiratory depression, and hypotension) may occur if etomidate and trifluoperazine are used concomitantly.
Etonogestrel; Ethinyl Estradiol: (Minor) Oral contraceptives may also cause additive photosensitization with phenothiazines.
Felbamate: (Moderate) The phenothiazines, when used concomitantly with anticonvulsants, can lower the seizure threshold. Adequate dosages of anticonvulsants should be continued when a phenothiazine is added.
Fenfluramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of fenfluramine and trifluoperazine. Concurrent use may result in additive CNS depression.
Fentanyl: (Moderate) Concomitant use of opioid agonists with trifluoperazine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with trifluoperazine 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.
Fingolimod: (Minor) Exercise caution when administering fingolimod concomitantly with trifluoperazine 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. Trifluoperazine is associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Flavoxate: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including trifluoperazine. 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.
Flecainide: (Minor) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering trifluoperazine with flecainide. Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation. Flecainide is a Class IC antiarrhythmic and is also associated with a possible risk for QT prolongation and/or TdP; flecainide increases the QT interval, but largely due to prolongation of the QRS interval.
Flibanserin: (Moderate) The concomitant use of flibanserin with CNS depressants, such as phenothiazines, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Fluconazole: (Minor) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering fluconazole with trifluoperazine. Fluconazole has been associated with QT prolongation and rare cases of TdP. Trifluoperazine, a phenothiazine, is also associated with a possible risk for QT prolongation.
Flucytosine: (Minor) Because of flucytosine's ability to cause significant hematologic toxicity, it should be used cautiously with all bone marrow depressants. These include: carbamazepine, clozapine, phenothiazines, zidovudine, ZDV and other blood dyscrasia-causing medications.
Fluocinolone; Hydroquinone; Tretinoin: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as phenothiazines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Fluoxetine: (Moderate) Coadministration of fluoxetine and trifluoperazine may increase the risk for QT prolongation and torsade de pointes (TdP). Additonally, fluoxetine is a potent inhibitor of CYP2D6 and may result in increases in serum trifluoperazine concentrations, leading to side effects. QT prolongation and TdP have been reported in patients treated with fluoxetine. Trifluoperazine is associated with a possible risk for QT prolongation.
Fluphenazine: (Moderate) Fluphenazine and trifluoperazine are phenothiazines that are associated with a possible risk for QT prolongation. Coadministration may represent duplicate therapy and increase the risk for QT prolongation. In addition, co-administration may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures.
Flurazepam: (Major) Limit dosage and duration of benzodiazepines during concomitant phenothiazine use and monitor for unusual drowsiness and sedation due to the risk for additive CNS depression.
Fluvoxamine: (Minor) Due to the possibility of additive effects on the QT interval, caution is advisable during concurrent use of fluvoxamine and trifluoperazine. Cases of QT prolongation and TdP have been reported during postmarketing use of fluvoxamine. Trifluoperazine is associated with a possible risk for QT prolongation, particularly in overdose settings. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
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: (Minor) When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as trifluoperazine. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). Trifluoperazine is associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation. If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment.
Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
Fosphenytoin: (Moderate) Monitor phenytoin concentrations during concomitant therapy with fosphenytoin and phenothiazines; a fosphenytoin dosage decrease may be necessary. Phenothiazines may inhibit the metabolism of fosphenytoin.
Fostemsavir: (Minor) Use trifluoperazine and fostemsavir together with caution due to the potential for QT prolongation. Trifluoperazine is associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation. 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: (Moderate) Monitor for excessive sedation and somnolence during coadministration of trifluoperazine and gabapentin. Concurrent use may result in additive CNS depression.
Ganirelix: (Moderate) In the absence of relevant data and as a precaution, drugs that cause hyperprolactinemia, such as phenothiazines, should not be administered concomitantly with ganirelix since hyperprolactinemia downregulates the number of pituitary GnRH receptors.
Gemifloxacin: (Minor) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering trifluoperazine with gemifloxacin. Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation. Gemifloxacin may also 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: (Minor) Coadministration of gemtuzumab ozogamicin with trifluoperazine may increase the potential for additive QT prolongation and risk of torsade de pointes (TdP). Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Trifluoperazine is associated with a possible risk for QT prolongation.
Gentamicin: (Minor) When used for the treatment of nausea and vomiting, antiemetic phenothiazines may mask symptoms that are associated with ototoxicity induced by the aminoglycosides.
Gilteritinib: (Minor) Use caution and monitor for additive QT prolongation if concurrent use of gilteritinib and trifluoperazine is necessary. Gilteritinib has been associated with QT prolongation. Trifluoperazine is associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Glasdegib: (Minor) Consider increased frequency of ECG monitoring if glasdegib and trifluoperazine are coadministered due to the potential for additive effects on the QT interval. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. Trifluoperazine is associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Glimepiride: (Moderate) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted. Also, concomitant use may increase the risk for phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure.
Glipizide: (Moderate) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted. Also, concomitant use may increase the risk for phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure.
Glipizide; Metformin: (Moderate) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted. Also, concomitant use may increase the risk for phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure. (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. When such drugs are administered to a patient receiving metformin, observe the patient closely for loss of blood glucose control. When such drugs are withdrawn from a patient receiving metformin, observe the patient closely for hypoglycemia.
Glyburide: (Moderate) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted. Also, concomitant use may increase the risk for phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure.
Glyburide; Metformin: (Moderate) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted. Also, concomitant use may increase the risk for phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure. (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. When such drugs are administered to a patient receiving metformin, observe the patient closely for loss of blood glucose control. When such drugs are withdrawn from a patient receiving metformin, observe the patient closely for hypoglycemia.
Glycopyrrolate: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including trifluoperazine. 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.
Glycopyrrolate; Formoterol: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including trifluoperazine. 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.
Goserelin: (Major) Avoid coadministration of goserelin with trifluoperazine due to the risk of reduced efficacy of goserelin; QT prolongation may also occur. Trifluoperazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; goserelin is a GnRH analog. Trifluoperazine is also associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation. Androgen deprivation therapy (i.e., goserelin) may also prolong the QT/Q Tc interval.
Granisetron: (Minor) Use granisetron with caution in combination with trifluoperazine due to increased risk for QT prolongation. Granisetron has been associated with QT prolongation. Trifluoperazine is associated with a possible risk for QT prolongation.
Guaifenesin; Hydrocodone: (Moderate) Concomitant use of opioid agonists with trifluoperazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking trifluoperazine. Limit the use of opioid pain medications with trifluoperazine 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) Other non-cardiovascular drugs with alpha-blocking activity such as phenothiazines, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
Guanidine: (Minor) Bone marrow suppression is associated with guanidine therapy. Avoid concomitant use of other drugs known to cause bone marrow suppression such as phenothiazines.
Halobetasol; Tazarotene: (Moderate) The manufacturer states that tazarotene should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as phenothiazines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Halogenated Anesthetics: (Minor) Halogenated anesthetics should be used cautiously and with close monitoring with trifluoperazine. Halogenated anesthetics can prolong the QT interval. Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation. In addition, phenothiazines can potentiate the CNS-depressant action of halogenated anesthetics.
Haloperidol: (Moderate) Caution is advisable when combining haloperidol concurrently with trifluoperazine as concurrent use may increase the risk of QT prolongation and other antipsychotic-related adverse effects including drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone. Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with drugs with a possible risk for QT prolongation, such as haloperidol. The likelihood of pharmacodynamic interactions varies based upon the individual properties of the coadministered antipsychotic agent.
Histrelin: (Major) Avoid coadministration of histrelin with trifluoperazine due to the risk of reduced efficacy of histrelin; QT prolongation may also occur. Trifluoperazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; histrelin is a GnRH analog. Trifluoperazine is also associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation. Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval.
Homatropine; Hydrocodone: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including trifluoperazine. 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. (Moderate) Concomitant use of opioid agonists with trifluoperazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking trifluoperazine. Limit the use of opioid pain medications with trifluoperazine 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.
Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
Hydrocodone: (Moderate) Concomitant use of opioid agonists with trifluoperazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking trifluoperazine. Limit the use of opioid pain medications with trifluoperazine 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: (Moderate) Concomitant use of opioid agonists with trifluoperazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking trifluoperazine. Limit the use of opioid pain medications with trifluoperazine 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: (Moderate) Concomitant use of opioid agonists with trifluoperazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking trifluoperazine. Limit the use of opioid pain medications with trifluoperazine 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.
Hydromorphone: (Moderate) Concomitant use of opioid agonists with trifluoperazine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with trifluoperazine 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) Concomitant use of trifluoperazine and hydroxychloroquine 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.
Hydroxyzine: (Moderate) Caution is recommended if hydroxyzine is administered with trifluoperazine 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. Trifluoperazine is associated with a possible risk for QT prolongation.
Hyoscyamine: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including trifluoperazine. 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.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including trifluoperazine. 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.
Ibuprofen; Oxycodone: (Major) Concomitant use of oxycodone with phenothiazines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with phenothiazines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Monitor for signs of hypotension after starting or titrating the dosage of oxycodone. There is an increased risk of severe hypotension in patients whose ability to maintain blood pressure has already been compromised by concurrent administration of phenothiazines.
Ibutilide: (Minor) Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation and should be used cautiously with ibutilide. Ibutilide administration can cause QT prolongation and 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.
Iloperidone: (Moderate) Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation. According to the manufacturer, iloperidone should not be used with other drugs having an association with QT prolongation. In addition, co-administration of trifluoperazine with atypical agents (e.g., aripiprazole, lurasidone and others) may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Imipramine: (Moderate) Phenothiazines have been reported to prolong the QT interval. Because tricyclic antidepressants are associated with a possible risk for QT prolongation and TdP when given in excessive doses or overdosage, concurrent use with trifluoperazine 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. Additive anticholinergic effects or sedation may be seen when phenothiazines are used with tricyclic antidepressants.
Incretin Mimetics: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
Indacaterol; Glycopyrrolate: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including trifluoperazine. 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.
Indapamide: (Moderate) Indapamide may cause electrolyte disturbances, which may increase the potential for proarrhythmic effects of selected phenothiazines.
Inotuzumab Ozogamicin: (Minor) Coadministration of inotuzumab ozogamicin with trifluoperazine may increase the potential for additive QT prolongation and risk of torsade de pointes (TdP). Inotuzumab has been associated with QT interval prolongation. Trifluoperazine is also associated with a possible risk for QT prolongation.
Insulins: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
Iodixanol: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering the use of intrathecal radiopaque contrast agents. Phenothiazines should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Iohexol: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering the use of intrathecal radiopaque contrast agents. Phenothiazines should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Iomeprol: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering the use of intrathecal radiopaque contrast agents. Phenothiazines should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Iopamidol: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering the use of intrathecal radiopaque contrast agents. Phenothiazines should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Iopromide: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering the use of intrathecal radiopaque contrast agents. Phenothiazines should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Ioversol: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering the use of intrathecal radiopaque contrast agents. Phenothiazines should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Ipecac: (Major) Phenothiazines, especially in large quantities, can cause a dystonic reaction. Due to the aspiration risk associated with emesis for a person with acute dystonia of the head or neck,avoid emesis induction for overdose cases.
Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
Isocarboxazid: (Moderate) Concurrent use of MAOIs and phenothiazines may prolong or intensify the hypotensive, anticholinergic, or sedative effects of either agent. Due to the potential for additive CNS and cardiovascular effects, MAOIs and phenothiazines should be used together cautiously.
Isoflurane: (Minor) Halogenated anesthetics should be used cautiously and with close monitoring with trifluoperazine. Halogenated anesthetics can prolong the QT interval. Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation. In addition, phenothiazines can potentiate the CNS-depressant action of halogenated anesthetics.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Rifamycins can increase the metabolism or reduce the bioavailability of phenothiazines. Dosage increases of phenothiazines may be necessary following the addition of rifampin or another rifamycin.
Isoniazid, INH; Rifampin: (Major) Rifamycins can increase the metabolism or reduce the bioavailability of phenothiazines. Dosage increases of phenothiazines may be necessary following the addition of rifampin or another rifamycin.
Isosulfan Blue: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering the use of intrathecal radiopaque contrast agents. Phenothiazines should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Itraconazole: (Minor) Use itraconazole with caution in combination with trifluoperazine as concurrent use may increase the risk of QT prolongation. Itraconazole has been associated with prolongation of the QT interval. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Ivosidenib: (Minor) Coadministration of ivosidenib with trifluoperazine may increase the risk of QT prolongation. 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. Trifluoperazine is associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Ketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and trifluoperazine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Lansoprazole; Amoxicillin; Clarithromycin: (Minor) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering clarithromycin with trifluoperazine. Clarithromycin is associated with an established risk for QT prolongation and TdP, while trifluoperazine (a phenothiazine) is associated with a possible risk for QT prolongation.
Lapatinib: (Minor) Monitor for evidence of QT prolongation if lapatinib is administered with trifluoperazine. Lapatinib has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and torsade de pointes (TdP) have been reported in postmarketing experience with lapatinib. Trifluoperazine is also associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Lasmiditan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and trifluoperazine. Concurrent use may result in additive CNS depression.
Lefamulin: (Minor) Trifluoperazine is associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation, such as lefamulin.
Lemborexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and phenothiazines. Dosage adjustments of lemborexant and the phenothiazine 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: (Minor) Use caution if coadministration of trifluoperazine with lenvatinib is necessary. Trifluoperazine is associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation such as lenvatinib.
Leuprolide: (Major) Avoid coadministration of leuprolide with trifluoperazine due to the risk of reduced efficacy of leuprolide; QT prolongation may also occur. Trifluoperazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Trifluoperazine is also associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Leuprolide; Norethindrone: (Major) Avoid coadministration of leuprolide with trifluoperazine due to the risk of reduced efficacy of leuprolide; QT prolongation may also occur. Trifluoperazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Trifluoperazine is also associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Levodopa: (Major) Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. Due to opposing effects on central dopaminergic activity, phenothiazines and levodopa may interfere with the effectiveness of each other.
Levofloxacin: (Minor) QT/QTc prolongation can occur with concomitant use of levofloxacin and trifluoperazine 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.
Levoketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and trifluoperazine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Levonorgestrel; Ethinyl Estradiol: (Minor) Oral contraceptives may also cause additive photosensitization with phenothiazines.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Minor) Oral contraceptives may also cause additive photosensitization with phenothiazines.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Minor) Oral contraceptives may also cause additive photosensitization with phenothiazines.
Levorphanol: (Moderate) Concomitant use of opioid agonists with trifluoperazine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with trifluoperazine 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.
Lidocaine; Epinephrine: (Moderate) Monitor blood pressure during concomitant epinephrine and phenothiazine use. Phenothiazines antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by a phenothiazine, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure.
Linagliptin: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
Linagliptin; Metformin: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted. (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. When such drugs are administered to a patient receiving metformin, observe the patient closely for loss of blood glucose control. When such drugs are withdrawn from a patient receiving metformin, observe the patient closely for hypoglycemia.
Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
Lithium: (Moderate) Some atypical antipsychotics are considered first-line adjunctive therapy to mood stabilizers such as lithium. Because both trifluoperazine and lithium have been associated with QT prolongation, coadminister cautiously and with close monitoring. It is also advisable to monitor patients for neurotoxicity during co-administration. Neuroleptic malignant syndrome (NMS) has been observed occasionally during concurrent use of lithium and either atypical or conventional antipsychotics. Additive extrapyramidal effects have also been noted. Early case reports described an encephalopathic syndrome consisting of delirium, tremulousness, dyskinesia, seizures, leukocytosis, weakness, hyperpyrexia, confusion, extrapyramidal symptoms, elevations in laboratory values (e.g., liver function tests, blood urea nitrogen, fasting blood sugar) and, in some cases, irreversible brain damage, during use of lithium and conventional antipsychotics, particularly haloperidol. Subsequent rare reports of NMS or NMS-like reactions have been described during co-administration of lithium and atypical antipsychotics (e.g., aripiprazole, risperidone, olanzapine, clozapine). Following resolution of NMS, there are isolated instances of re-emergence of symptoms following re-initiation of lithium as monotherapy. Lithium may be a risk factor for antipsychotic-induced NMS; however, this hypothesis has not been confirmed. In many reported cases, confounding factors have been present (e.g., previous history of NMS, high dose therapy). The ability of antipsychotics alone to precipitate NMS and the rarity of the condition further complicate assessment of lithium as a risk factor.
Lofexidine: (Moderate) Monitor for excessive hypotension and sedation during coadministration of lofexidine and trifluoperazine. Lofexidine can potentiate the effects of CNS depressants. Additionally, monitor ECG during coadministration due to the potential for additive QT prolongation. Lofexidine prolongs the QT interval. In addition, there are postmarketing reports of torsade de pointes. Trifluoperazine is associated with a possible risk for QT prolongation.
Loperamide: (Minor) QT/QTc prolongation can occur with concomitant use of loperamide and trifluoperazine 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.
Loperamide; Simethicone: (Minor) QT/QTc prolongation can occur with concomitant use of loperamide and trifluoperazine 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.
Lopinavir; Ritonavir: (Major) Avoid coadministration of lopinavir with trifluoperazine 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. Trifluoperazine is associated with a possible risk for QT prolongation.
Lorazepam: (Major) Limit dosage and duration of benzodiazepines during concomitant phenothiazine use and monitor for unusual drowsiness and sedation due to the risk for additive CNS depression.
Losartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
Loxapine: (Moderate) Caution is advisable during concurrent use of antipsychotics, including loxapine and trifluoperazine. Coadministration may increase the risk of drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, tardive dyskinesia, and seizures.
Lumateperone: (Moderate) Coadministration of antipsychotics, such as lumateperone and trifluoperazine, may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Although the incidence of tardive dyskinesia from antipsychotic combinations has not been established and data are very limited, the risk may be increased during combined use versus use of an antipsychotic alone.
Lurasidone: (Major) Similar to other antipsychotics, lurasidone administration has been associated with drowsiness, dizziness, orthostatic hypotension, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. The risk of these adverse effects may be increased during concurrent use of lurasidone with other antipsychotics. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Macimorelin: (Minor) Concurrent use of macimorelin and trifluoperazine 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. Concurrent use of macimorelin and perphenazine 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. Perphenazine is associated with a possible risk for QT prolongation. Theoretically, perphenazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Maprotiline: (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.
Meclizine: (Moderate) Additive anticholinergic and sedative effects may be seen when trifluoperazine is used with meclizine. Patients should be informed to read non-prescription product labels carefully for additional interacting motion sickness medications.
Mefloquine: (Minor) Mefloquine should be used with caution in patients receiving trifluoperazine 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. Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation.
Meglitinides: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
Melatonin: (Moderate) Monitor for unusual drowsiness and excessive duration during coadministration of melatonin and phenothiazines due to the risk for additive CNS depression.
Meperidine: (Major) Phenothiazines can potentiate the CNS-depressant action of other drugs such as meperidine. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Meprobamate: (Moderate) Phenothiazines are CNS depressant drugs that may have cumulative effects when administered with other CNS depressant drugs and they should be used cautiously with anxiolytic, sedative, and hypnotics. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension. Additionally, sleep-related behaviors, such as sleep-driving, are more likely to occur during concurrent use of hypnotics and other CNS depressants than with use of a hypnotic alone.
Metaxalone: (Moderate) Phenothiazines can potentiate the CNS-depressant action of skeletal muscle relaxants like metaxalone. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects.
Metformin: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. When such drugs are administered to a patient receiving metformin, observe the patient closely for loss of blood glucose control. When such drugs are withdrawn from a patient receiving metformin, observe the patient closely for hypoglycemia.
Metformin; Repaglinide: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. When such drugs are administered to a patient receiving metformin, observe the patient closely for loss of blood glucose control. When such drugs are withdrawn from a patient receiving metformin, observe the patient closely for hypoglycemia.
Metformin; Rosiglitazone: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted. (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. When such drugs are administered to a patient receiving metformin, observe the patient closely for loss of blood glucose control. When such drugs are withdrawn from a patient receiving metformin, observe the patient closely for hypoglycemia.
Metformin; Saxagliptin: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted. (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. When such drugs are administered to a patient receiving metformin, observe the patient closely for loss of blood glucose control. When such drugs are withdrawn from a patient receiving metformin, observe the patient closely for hypoglycemia.
Metformin; Sitagliptin: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted. (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. When such drugs are administered to a patient receiving metformin, observe the patient closely for loss of blood glucose control. When such drugs are withdrawn from a patient receiving metformin, observe the patient closely for hypoglycemia.
Methadone: (Minor) The need to coadminister methadone with drugs known to prolong the QT interval, such as trifluoperazine, should be done with extreme caution and a careful assessment of treatment risks versus benefits. Methadone is considered to be associated with an increased risk for QT prolongation and torsades de pointes (TdP), especially at higher doses (> 200 mg/day but averaging approximately 400 mg/day in adult patients). In addition, concomitant use of methadone with another CNS depressant, such as trifluoperazine, can lead to additive respiratory depression, hypotension, profound sedation, or coma. Prior to concurrent use of methadone 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. Methadone should be used with caution and in reduced dosages if used concurrently with a CNS depressant; also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including trifluoperazine. 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.
Methocarbamol: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of methocarbamol and phenothiazines due to the risk for additive CNS depression; dosage adjustments may be necessary.
Methohexital: (Moderate) Phenothiazines are CNS depressant drugs that may have cumulative effects when administered concurrently and they should be used cautiously with anxiolytic, sedative, and hypnotic type drugs, such as the barbiturates. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension. Phenothiazines can also lower the seizure threshold, which may be important in patients taking a barbiturate for the treatment of seizures. Additionally, sleep-related behaviors, such as sleep-driving, are more likely to occur during concurrent use of other CNS depressants than with the use of sedatives alone. Monitor for additive effects, unusual moods or behaviors, and warn about the potential effects to driving and other activities.
Methoxsalen: (Moderate) Use methoxsalen and phenothiazines together with caution; the risk of severe burns/photosensitivity may be additive. If concurrent use is necessary, closely monitor patients for signs or symptoms of skin toxicity.
Methscopolamine: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including trifluoperazine. 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.
Methsuximide: (Major) The phenothiazines, when used concomitantly with anticonvulsants, can lower the seizure threshold. Adequate dosages of anticonvulsants should be continued when a phenothiazine is added.
Methyclothiazide: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
Metoclopramide: (Contraindicated) Avoid metoclopramide in patients receiving phenothiazine antipsychotics due to potential for additive effects, including increased frequency and severity of tardive dyskinesia (TD), other extrapyramidal symptoms (EPS), and neuroleptic malignant syndrome (NMS). Also avoid the use of metoclopramide with phenothiazine antiemetics if possible due to these risks. Some manufacturer labels for metoclopramide contraindicate the use of these drugs together, while others state avoidance is necessary. If these agents must be used together, monitor closely for movement disorders and additive CNS effects. Discontinue these medications at the first signs of dyskinesia. Metoclopramide is a central dopamine antagonist and may cause EPS (e.g., acute dystonic reactions, pseudo-parkinsonism, akathisia, tardive dyskinesia). Tardive dyskinesia (TD) is a syndrome of potentially irreversible and disfiguring involuntary movements of the face or tongue, and sometimes of the trunk and/or extremities. Movements may be choreoathetotic in appearance. Phenothiazines are also central dopamine antagonists. In addition, both phenothiazines and metoclopramide can cause sedation, seizures, or increased prolactin levels.
Metolazone: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
Metronidazole: (Minor) QT/QTc prolongation can occur with concomitant use of metronidazole and trifluoperazine 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.
Metyrapone: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as phenothiazines, should be used with caution. Additive drowsiness and/or dizziness is possible.
Metyrosine: (Moderate) Because it also blocks central dopamine receptors, metyrosine should be avoided or used cautiously in patients receiving a phenothiazine to minimize the risk of additive adverse CNS effects. A dose reduction may be required if combination therapy is necessary.
Midazolam: (Major) Limit dosage and duration of benzodiazepines during concomitant phenothiazine use and monitor for unusual drowsiness and sedation due to the risk for additive CNS depression.
Midostaurin: (Minor) The concomitant use of midostaurin and trifluoperazine 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. Additionally, trifluoperazine is associated with a possible risk for QT prolongation. Trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Mifepristone: (Minor) Due to a possible risk for QT prolongation and torsade de pointes (TdP), mifepristone and trifluoperazine should be used together cautiously. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Drugs with a possible risk for QT prolongation and torsades de pointes that should be used cautiously with mifepristone include trifluoperazine.
Miglitol: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
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 phenothiazines. Caution should be exercised when using these agents concurrently.
Mirtazapine: (Moderate) Coadministration is contraindicated due to the potential for QT prolongation and torsade de pointes. Due to the possibility of additive effects on the QT interval, caution is advisable during concurrent use of mirtazapine and trifluoperazine. Cases of QT prolongation, TdP, ventricular tachycardia, and sudden death have been reported during postmarketing use of mirtazapine. The majority of reports have occurred in the setting of mirtazapine overdose or in patients with other risk factors for QT prolongation, including concomitant use of other medications associated with QT prolongation. Trifluoperazine is associated with a possible risk for QT prolongation, particularly in overdose settings. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation. Because both mirtazapine and trifluoperazine have CNS depressant properties, patients should be advised to avoid engaging in activities requiring mental alertness until they are aware of the effects of the combination.
Mitotane: (Moderate) Mitotane can cause sedation, lethargy, vertigo, and other CNS side effects. Concomitant administration of mitotane and CNS depressants, including opiate agonists, may cause additive CNS effects.
Mobocertinib: (Minor) QT/QTc prolongation can occur with concomitant use of mobocertinib and trifluoperazine 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.
Molindone: (Major) Close monitoring is advisable during concurrent use of molindone with other antipsychotics. Because molindone shares certain pharmacological properties with other antipsychotics, additive cardiac effects (e.g., hypotension), CNS effects (e.g., drowsiness), anticholinergic effects (e.g., constipation, xerostomia), extrapyramidal effects, neuroleptic malignant syndrome, or seizures may occur. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Monoamine oxidase inhibitors: (Moderate) Concurrent use of MAOIs and phenothiazines may prolong or intensify the hypotensive, anticholinergic, or sedative effects of either agent. Due to the potential for additive CNS and cardiovascular effects, MAOIs and phenothiazines should be used together cautiously.
Morphine: (Moderate) Concomitant use of opioid agonists with trifluoperazine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with trifluoperazine 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.
Morphine; Naltrexone: (Moderate) Concomitant use of opioid agonists with trifluoperazine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with trifluoperazine 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.
Moxifloxacin: (Minor) Concurrent use of trifluoperazine and moxifloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation. Moxifloxacin has also 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.
Nabilone: (Moderate) Concomitant use of nabilone with other CNS depressants, including phenothiazines, can potentiate the effects of nabilone on respiratory depression.
Nafarelin: (Moderate) Antipsychotics may cause hyperprolactinemia and should not be administered concomitantly with nafarelin since hyperprolactinemia down-regulates the number of pituitary GnRH receptors.
Nalbuphine: (Moderate) Concomitant use of nalbuphine with other CNS depressants, such as phenothiazines, can potentiate the effects of nalbuphine on respiratory depression, CNS depression, and sedation.
Naltrexone: (Moderate) Patients receiving phenothiazines and naltrexone concomitantly have had symptoms of somnolence and lethargy.
Neostigmine; Glycopyrrolate: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including trifluoperazine. 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.
Nilotinib: (Minor) QT interval prolongation may be additive if nilotinib and trifluoperazine are coadministered. Sudden death and QT prolongation have been reported in patients who received nilotinib therapy. Trifluoperazine is associated with a possible risk of QT prolongation.
Nitroglycerin: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as phenothiazines. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with phenothiazines.
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. Phenothiazines should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Norepinephrine: (Minor) The alpha-adrenergic effects of norepinephrine can be blocked during concurrent administration of phenothiazines. This blockade can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction. Patients taking phenothiazines can possibly have reduced pressor response to ephedrine, phenylephrine, or norepinephrine, but these drugs are preferred over epinephrine if a vasopressor agent is required. According to the manufacturers of the various phenothiazines, norepinephrine or phenylephrine may be used if a vasopressor is needed.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Minor) Oral contraceptives may also cause additive photosensitization with phenothiazines.
Norethindrone; Ethinyl Estradiol: (Minor) Oral contraceptives may also cause additive photosensitization with phenothiazines.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Minor) Oral contraceptives may also cause additive photosensitization with phenothiazines.
Norgestimate; Ethinyl Estradiol: (Minor) Oral contraceptives may also cause additive photosensitization with phenothiazines.
Nortriptyline: (Moderate) Phenothiazines have been reported to prolong the QT interval. Because tricyclic antidepressants are associated with a possible risk for QT prolongation and TdP when given in excessive doses or overdosage, concurrent use with trifluoperazine 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. Additive anticholinergic effects or sedation may be seen when phenothiazines are used with tricyclic antidepressants.
Ofloxacin: (Minor) QT/QTc prolongation can occur with concomitant use of ofloxacin and trifluoperazine 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.
Olanzapine: (Moderate) Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation. Trifluoperazine may increase the risk of QT prolongation if coadministered with drugs with a possible risk for QT prolongation, such as olanzapine. Coadministration may also increase the risk of drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Olanzapine; Fluoxetine: (Moderate) Coadministration of fluoxetine and trifluoperazine may increase the risk for QT prolongation and torsade de pointes (TdP). Additonally, fluoxetine is a potent inhibitor of CYP2D6 and may result in increases in serum trifluoperazine concentrations, leading to side effects. QT prolongation and TdP have been reported in patients treated with fluoxetine. Trifluoperazine is associated with a possible risk for QT prolongation. (Moderate) Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation. Trifluoperazine may increase the risk of QT prolongation if coadministered with drugs with a possible risk for QT prolongation, such as olanzapine. Coadministration may also increase the risk of drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Olanzapine; Samidorphan: (Moderate) Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation. Trifluoperazine may increase the risk of QT prolongation if coadministered with drugs with a possible risk for QT prolongation, such as olanzapine. Coadministration may also increase the risk of drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Oliceridine: (Moderate) Concomitant use of oliceridine with trifluoperazine may cause excessive sedation and somnolence. Limit the use of oliceridine with trifluoperazine 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.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
Omeprazole; Amoxicillin; Rifabutin: (Major) Rifamycins can increase the metabolism or reduce the bioavailability of phenothiazines. Dosage increases of phenothiazines may be necessary following the addition of rifampin or another rifamycin.
Ondansetron: (Minor) Due to a possible risk for QT prolongation and torsade de pointes (TdP), ondansetron and trifluoperazine should be used together cautiously. Ondansetron has been associated with QT prolongation and post-marketing reports of torsade de pointes (TdP). Among 42 patients receiving a 4 mg bolus dose of intravenous ondansetron for the treatment of postoperative nausea and vomiting, the mean maximal QTc interval prolongation was 20 +/- 13 msec at the third minute after antiemetic administration (p < 0.0001). If ondansetron and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended. Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation.
Orphenadrine: (Moderate) Additive anticholinergic effects may be seen when trifluoperazine is used concomitantly with other drugs having antimuscarinic activity such as orphenadrine. Additive sedation may also occur.
Osilodrostat: (Minor) Monitor ECGs in patients receiving osilodrostat with trifluoperazine. Osilodrostat is associated with dose-dependent QT prolongation. Trifluoperazine is associated with a possible risk for QT prolongation.
Osimertinib: (Minor) Use osimertinib and trifluoperazine together with caution due to the risk of QT prolongation. The manufacturer of osimertinib recommends avoiding coadministration with other drugs that prolong the QT, if possible; if 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. Trifluoperazine is associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Oxaliplatin: (Minor) Monitor electrolytes and ECGs for QT prolongation if coadministration of trifluoperazine with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. Trifluoperazine is associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Oxazepam: (Major) Limit dosage and duration of benzodiazepines during concomitant phenothiazine use and monitor for unusual drowsiness and sedation due to the risk for additive CNS depression.
Oxybutynin: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including trifluoperazine. 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.
Oxycodone: (Major) Concomitant use of oxycodone with phenothiazines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with phenothiazines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Monitor for signs of hypotension after starting or titrating the dosage of oxycodone. There is an increased risk of severe hypotension in patients whose ability to maintain blood pressure has already been compromised by concurrent administration of phenothiazines.
Oxymorphone: (Moderate) Concomitant use of opioid agonists with trifluoperazine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with trifluoperazine 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.
Ozanimod: (Minor) Coadministration of ozanimod with trifluoperazine may increase the potential for additive QT prolongation. Ozanimod initiation 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 torsade de pointes in patients with bradycardia. Trifluoperazine is associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Pacritinib: (Minor) QT/QTc prolongation can occur with concomitant use of pacritinib and trifluoperazine 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.
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 of paliperidone, the drug should be avoided in combination with other agents also known to have this effect. Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation. In addition, coadministration may increase the risk of drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Paromomycin: (Minor) When used for the treatment of nausea and vomiting, antiemetic phenothiazines may mask symptoms that are associated with ototoxicity induced by the aminoglycosides.
Paroxetine: (Moderate) Substantial increases in concentrations of phenothiazines may occur due to CYP2D6 inhibition by paroxetine, which may increase the risk of adverse effects, including extrapyramidal symptoms or QT prolongation. Phenothiazines with a possible risk of QT prolongation include trifluoperazine. Additive anticholinergic effects are also possible.
Pasireotide: (Minor) Use caution when using pasireotide in combination with trifluoperazine as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation.
Pazopanib: (Minor) 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 trifluoperazine.
Pentamidine: (Minor) 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 trifluoperazine. Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation.
Pentazocine: (Moderate) Concomitant use of pentazocine with other CNS depressants, such as phenothiazines, can potentiate respiratory depression, CNS depression, and sedation. Pentazocine should be used cautiously with phenothiazines.
Pentazocine; Naloxone: (Moderate) Concomitant use of pentazocine with other CNS depressants, such as phenothiazines, can potentiate respiratory depression, CNS depression, and sedation. Pentazocine should be used cautiously with phenothiazines.
Pentobarbital: (Moderate) Phenothiazines are CNS depressant drugs that may have cumulative effects when administered concurrently and they should be used cautiously with anxiolytic, sedative, and hypnotic type drugs, such as the barbiturates. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension. Phenothiazines can also lower the seizure threshold, which may be important in patients taking a barbiturate for the treatment of seizures. Additionally, sleep-related behaviors, such as sleep-driving, are more likely to occur during concurrent use of other CNS depressants than with the use of sedatives alone. Monitor for additive effects, unusual moods or behaviors, and warn about the potential effects to driving and other activities.
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 phenothiazines.
Perphenazine: (Moderate) Perphenazine and trifluoperazine are associated with a possible risk for QT prolongation and the risk of QT prolongation may theoretically be increased during combined use. Coadministration may increase the risk of drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, tardive dyskinesia, or seizures.
Perphenazine; Amitriptyline: (Moderate) Perphenazine and trifluoperazine are associated with a possible risk for QT prolongation and the risk of QT prolongation may theoretically be increased during combined use. Coadministration may increase the risk of drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, tardive dyskinesia, or seizures. (Moderate) Phenothiazines have been reported to prolong the QT interval. Because tricyclic antidepressants are associated with a possible risk for QT prolongation and TdP when given in excessive doses or overdosage, concurrent use with trifluoperazine 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. Additive anticholinergic effects or sedation may be seen when phenothiazines are used with tricyclic antidepressants.
Phenelzine: (Moderate) Concurrent use of MAOIs and phenothiazines may prolong or intensify the hypotensive, anticholinergic, or sedative effects of either agent. Due to the potential for additive CNS and cardiovascular effects, MAOIs and phenothiazines should be used together cautiously.
Phenobarbital: (Moderate) Phenothiazines are CNS depressant drugs that may have cumulative effects when administered concurrently and they should be used cautiously with anxiolytic, sedative, and hypnotic type drugs, such as the barbiturates. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension. Phenothiazines can also lower the seizure threshold, which may be important in patients taking a barbiturate for the treatment of seizures. Additionally, sleep-related behaviors, such as sleep-driving, are more likely to occur during concurrent use of other CNS depressants than with the use of sedatives alone. Monitor for additive effects, unusual moods or behaviors, and warn about the potential effects to driving and other activities.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including trifluoperazine. 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. (Moderate) Phenothiazines are CNS depressant drugs that may have cumulative effects when administered concurrently and they should be used cautiously with anxiolytic, sedative, and hypnotic type drugs, such as the barbiturates. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension. Phenothiazines can also lower the seizure threshold, which may be important in patients taking a barbiturate for the treatment of seizures. Additionally, sleep-related behaviors, such as sleep-driving, are more likely to occur during concurrent use of other CNS depressants than with the use of sedatives alone. Monitor for additive effects, unusual moods or behaviors, and warn about the potential effects to driving and other activities.
Phentermine; Topiramate: (Moderate) Monitor for unusual drowsiness and excess sedation during coadministration of phenothiazines and topiramate due to the risk for additive CNS depression.
Phenylephrine: (Moderate) Other non-cardiovascular drugs with alpha-blocking activity such as phenothiazines, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
Phenytoin: (Moderate) Monitor phenytoin concentrations during concomitant therapy with phenytoin and phenothiazines; a phenytoin dosage decrease may be necessary. Phenothiazines may inhibit the metabolism of phenytoin.
Photosensitizing agents (topical): (Moderate) Phenothiazines may increase the photosensitizing effects of photosensitizing agents used in photodynamic therapy. Patients should limit ultra-violet exposure.
Pilocarpine: (Moderate) Avoid using pilocarpine in combination with other drugs known to have anticholinergic effects as the therapeutic efficacy of either agent may be reduced.
Pimavanserin: (Minor) Pimavanserin may cause QT prolongation and should be avoided in patients receiving other medications known to prolong the QT interval. Fluphenazine, perphenazine, prochlorperazine, and trifluoperazine are associated with a possible risk for QT prolongation. Theoretically, these phenothiazines may increase the risk of QT prolongation if coadministered with drugs with a risk of QT prolongation.
Pimozide: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Due to the risk of additive QT prolongation and potential for serious arrhythmias, the concurrent use of pimozide with trifluoperazine is contraindicated. Concurrent use of pimozide with phenothiazines may increase the risk of adverse effects such as drowsiness, sedation, dizziness, orthostatic hypotension, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone. Many phenothiazines are inhibitors of CYP2D6, one of the metabolic pathways of pimozide.
Pioglitazone: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
Pioglitazone; Glimepiride: (Moderate) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted. Also, concomitant use may increase the risk for phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure. (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
Pioglitazone; Metformin: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted. (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. When such drugs are administered to a patient receiving metformin, observe the patient closely for loss of blood glucose control. When such drugs are withdrawn from a patient receiving metformin, observe the patient closely for hypoglycemia.
Pitolisant: (Minor) Trifluoperazine is associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation, such as pitolisant.
Plazomicin: (Minor) When used for the treatment of nausea and vomiting, antiemetic phenothiazines may mask symptoms that are associated with ototoxicity induced by the aminoglycosides.
Ponesimod: (Minor) Concomitant use of ponesimod and trifluoperazine may increase the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). 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. Trifluoperazine is associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Porfimer: (Major) Avoid coadministration of porfimer with phenothiazines due to the risk of increased photosensitivity. Porfimer is a light-activated drug used in photodynamic therapy; all patients treated with porfimer will be photosensitive. Concomitant use of other photosensitizing agents like phenothiazines may increase the risk of a photosensitivity reaction.
Posaconazole: (Minor) Use posaconazole with caution in combination with trifluoperazine. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes. Trifluoperazine is also associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Pramipexole: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and pramipexole may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. In addition, coadministration may result in additive sedation.
Pramlintide: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
Pregabalin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of trifluoperazine and pregabalin. Concurrent use may result in additive CNS depression.
Prilocaine; Epinephrine: (Moderate) Monitor blood pressure during concomitant epinephrine and phenothiazine use. Phenothiazines antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by a phenothiazine, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure.
Primaquine: (Minor) Trifluoperazine is associated with a possible risk for QT prolongation. Theoretically, this phenothiazine may increase the risk of QT prolongation if coadministered with drugs with a risk of QT prolongation, such as primaquine. Administer these agents and drugs that can prolong the QT interval with caution.
Primidone: (Moderate) Phenothiazines are CNS depressant drugs that may have cumulative effects when administered concurrently and they should be used cautiously with anxiolytic, sedative, and hypnotic type drugs, such as the barbiturates. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension. Phenothiazines can also lower the seizure threshold, which may be important in patients taking a barbiturate for the treatment of seizures. Additionally, sleep-related behaviors, such as sleep-driving, are more likely to occur during concurrent use of other CNS depressants than with the use of sedatives alone. Monitor for additive effects, unusual moods or behaviors, and warn about the potential effects to driving and other activities.
Procainamide: (Minor) Trifluoperazine and procainamide should be used cautiously due to the potential for QT prolongation. Trifluoperazine, a phenothiazine, has a possible risk for QT prolongation. Procainamide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP).
Procarbazine: (Moderate) CNS depressants, such as phenothiazines, can potentiate the CNS depression caused by procarbazine therapy, so these drugs should be used together cautiously.
Prochlorperazine: (Moderate) Prochlorperazine and trifluoperazine are associated with a possible risk for QT prolongation; this risk may theoretically be increased during concurrent use. Coadministration of antipsychotics may also increase the risk of drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, tardive dyskinesia, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures.
Promethazine: (Moderate) Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Promethazine should be used with caution with other phenothiazines that carry a theoretical risk of QT prolongation including trifluoperazine. In addition, coadministration may increase the risk of drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, tardive dyskinesia, or seizures.
Promethazine; Dextromethorphan: (Moderate) Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Promethazine should be used with caution with other phenothiazines that carry a theoretical risk of QT prolongation including trifluoperazine. In addition, coadministration may increase the risk of drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, tardive dyskinesia, or seizures.
Promethazine; Phenylephrine: (Moderate) Other non-cardiovascular drugs with alpha-blocking activity such as phenothiazines, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension. (Moderate) Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Promethazine should be used with caution with other phenothiazines that carry a theoretical risk of QT prolongation including trifluoperazine. In addition, coadministration may increase the risk of drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, tardive dyskinesia, or seizures.
Propafenone: (Minor) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering propafenone with trifluoperazine. Propafenone is a Class IC antiarrhythmic which increases the QT interval largely due to prolongation of the QRS interval. Trifluoperazine, a phenothiazine, is also associated with a possible risk for QT prolongation.
Propantheline: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including trifluoperazine. 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.
Propranolol: (Moderate) Monitor for an increase in trifluoperazine and propranolol-related adverse effects during concomitant use. The concentrations of both medications may increase.
Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines. (Moderate) Monitor for an increase in trifluoperazine and propranolol-related adverse effects during concomitant use. The concentrations of both medications may increase.
Protriptyline: (Moderate) Phenothiazines have been reported to prolong the QT interval. Because tricyclic antidepressants are associated with a possible risk for QT prolongation and TdP when given in excessive doses or overdosage, concurrent use with trifluoperazine 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. Additive anticholinergic effects or sedation may be seen when phenothiazines are used with tricyclic antidepressants.
Pseudoephedrine; Triprolidine: (Moderate) Additive anticholinergic and sedative effects may be seen when trifluoperazine is used with first generation antihistamines, such as triprolidine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
Pyrilamine: (Moderate) Additive anticholinergic and sedative effects may be seen when trifluoperazine is used with first generation antihistamines, such as pyrilamine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
Quazepam: (Major) Limit dosage and duration of benzodiazepines during concomitant phenothiazine use and monitor for unusual drowsiness and sedation due to the risk for additive CNS depression.
Quetiapine: (Moderate) Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation. According to the manufacturer, quetiapine should not be used with other drugs having an association with QT prolongation. Co-administration of trifluoperazine with atypical agents (e.g., lurasidone and others) may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
Quinidine: (Minor) Trifluoperazine and quinidine should be used cautiously due to the potential for QT prolongation. Trifluoperazine, a phenothiazine, has a possible risk for QT prolongation. Quinidine is associated with a well-established risk of QT prolongation and torsade de pointes (TdP).
Quinine: (Major) Concurrent use of quinine and trifluoperazine 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. Trifluoperazine, a phenothiazine, is also associated with a possible risk for QT prolongation and/or TdP.
Ranolazine: (Minor) Use ranolazine with caution in combination with trifluoperazine as concurrent use may increase the risk of QT prolongation. Ranolazine is associated with dose- and plasma concentration-related increases in the QTc interval. Although there are no studies examining the effects of ranolazine in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation. Trifluoperazine is associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Rasagiline: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and rasagiline may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic to the phenothiazine, if appropriate. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Relugolix: (Minor) Trifluoperazine is associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Relugolix; Estradiol; Norethindrone acetate: (Minor) Trifluoperazine is associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Remifentanil: (Moderate) Phenothiazines can potentiate the CNS depressant action of other drugs such as opiate agonists. A dose reduction of one or both drugs may be warranted.
Remimazolam: (Major) Limit dosage and duration of benzodiazepines during concomitant phenothiazine use and monitor for unusual drowsiness and sedation due to the risk for additive CNS depression.
Ribociclib: (Minor) Trifluoperazine is associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation such as ribociclib.
Ribociclib; Letrozole: (Minor) Trifluoperazine is associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation such as ribociclib.
Rifabutin: (Major) Rifamycins can increase the metabolism or reduce the bioavailability of phenothiazines. Dosage increases of phenothiazines may be necessary following the addition of rifampin or another rifamycin.
Rifampin: (Major) Rifamycins can increase the metabolism or reduce the bioavailability of phenothiazines. Dosage increases of phenothiazines may be necessary following the addition of rifampin or another rifamycin.
Rifamycins: (Major) Rifamycins can increase the metabolism or reduce the bioavailability of phenothiazines. Dosage increases of phenothiazines may be necessary following the addition of rifampin or another rifamycin.
Rifapentine: (Major) Rifamycins can increase the metabolism or reduce the bioavailability of phenothiazines. Dosage increases of phenothiazines may be necessary following the addition of rifampin or another rifamycin.
Rilpivirine: (Minor) Caution is advised when administering rilpivirine with trifluoperazine as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Trifluoperazine is also associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Risperidone: (Moderate) Use risperidone and trifluoperazine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, coadministration may also increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation.
Romidepsin: (Minor) Consider monitoring electrolytes and ECGs at baseline and periodically during treatment if romidepsin is administered with trifluoperazine as concurrent use may increase the risk of QT prolongation. Romidepsin has been reported to prolong the QT interval. Trifluoperazine is associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Ropinirole: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and ropinirole may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Rosiglitazone: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
Rotigotine: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and rotigotine may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. In addition, coadministration may result in additive sedation.
Safinamide: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and safinamide may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine if appropriate. If coadministration cannot be avoided, monitor for changes in movements, moods, or behaviors.
Saquinavir: (Minor) Coadministration may increase the risk of QT prolongation. If concurrent use is necessary, perform a baseline ECG prior to initiation of concomitant therapy and carefully follow monitoring recommendations. Trifluoperazine is associated with a possible risk for QT prolongation; saquinavir boosted with ritonavir increases the QT interval in a dose-dependent fashion, which may increase the risk for serious arrhythmias such as torsade de pointes (TdP).
Saxagliptin: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
Scopolamine: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including trifluoperazine. 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.
Secobarbital: (Moderate) Phenothiazines are CNS depressant drugs that may have cumulative effects when administered concurrently and they should be used cautiously with anxiolytic, sedative, and hypnotic type drugs, such as the barbiturates. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension. Phenothiazines can also lower the seizure threshold, which may be important in patients taking a barbiturate for the treatment of seizures. Additionally, sleep-related behaviors, such as sleep-driving, are more likely to occur during concurrent use of other CNS depressants than with the use of sedatives alone. Monitor for additive effects, unusual moods or behaviors, and warn about the potential effects to driving and other activities.
Segesterone Acetate; Ethinyl Estradiol: (Minor) Oral contraceptives may also cause additive photosensitization with phenothiazines.
Selegiline: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of phenothiazines and selegiline due to the risk for additive CNS depression. It is also possible that dopamine antagonists, such as phenothiazines, could diminish the effectiveness of selegiline.
Selpercatinib: (Minor) Monitor ECGs more frequently for QT prolongation if coadministration of selpercatinib with trifluoperazine is necessary due to the risk of additive QT prolongation. Concentration-dependent QT prolongation has been observed with selpercatinib therapy. Trifluoperazine is associated with a possible risk for QT prolongation.
Sertraline: (Minor) Sertraline's FDA-approved labeling recommends avoiding concomitant use with drugs known to prolong the QTc interval, such as trifluoperazine; however, the risk of sertraline-induced QT prolongation is generally considered to be low in clinical practice. Its effect on QTc interval is minimal (typically less than 5 msec), and the drug has been used safely in patients with cardiac disease (e.g., recent myocardial infarction, unstable angina, chronic heart failure). If use together is necessary, use caution and monitor patients for QT prolongation. In addition, CYP2D6 substrates such as trifluoperazine may require lower doses during concurrent use with sertraline, due to CYP2D6 inhibition by sertraline and the potential for arrhythmias or other adverse reactions associated with antipsychotics such as extrapyramidal symptoms.
Sevoflurane: (Minor) Halogenated anesthetics should be used cautiously and with close monitoring with trifluoperazine. Halogenated anesthetics can prolong the QT interval. Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation. In addition, phenothiazines can potentiate the CNS-depressant action of halogenated anesthetics.
SGLT2 Inhibitors: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should be closely monitored for worsening glycemic control when any of these antipsychotics is instituted.
Siponimod: (Minor) In general, do not initiate treatment with siponimod in patients receiving trifluoperazine 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. Trifluoperazine is associated with a possible risk for QT prolongation.
Sitagliptin: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
Sodium Oxybate: (Major) Additive CNS depressant effects may be possible when sodium oxybate is used concurrently with phenothiazines.
Sodium Stibogluconate: (Minor) QT/QTc prolongation can occur with concomitant use of sodium stibogluconate and trifluoperazine 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.
Solifenacin: (Moderate) Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation. Theoretically, trifluoperazine 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 trifluoperazine include solifenacin. Additive anticholinergic effects may also be seen with any antimuscarinics. 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. Drowsiness or other additive CNS effects may also occur in some patients.
Sorafenib: (Minor) Use caution if coadministration of sorafenib with trifluoperazine is necessary due to the risk of additive QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation. Sorafenib is also associated with QTc prolongation; the manufacturer of sorafenib recommends avoiding coadministration with other drugs that cause QT prolongation.
Sotagliflozin: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should be closely monitored for worsening glycemic control when any of these antipsychotics is instituted.
Sotalol: (Minor) Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation and should be used cautiously with sotalol. Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
Stiripentol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and trifluoperazine. CNS depressants can potentiate the effects of stiripentol.
Streptomycin: (Minor) When used for the treatment of nausea and vomiting, antiemetic phenothiazines may mask symptoms that are associated with ototoxicity induced by the aminoglycosides.
Sufentanil: (Moderate) Phenothiazines can potentiate the CNS depressant action of other drugs such as opiate agonists. A dose reduction of one or both drugs may be warranted.
Sulfonylureas: (Moderate) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted. Also, concomitant use may increase the risk for phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure.
Sunitinib: (Minor) Monitor patients for QT prolongation if coadministration of trifluoperazine with sunitinib is necessary. Sunitinib can cause dose-dependent QT prolongation. Trifluoperazine is associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Tacrolimus: (Minor) Consider ECG and electrolyte monitoring periodically during treatment if tacrolimus is administered with trifluoperazine. Tacrolimus may prolong the QT interval and cause torsade de pointes (TdP). Trifluoperazine is also associated with a possible risk for QT prolongation.
Tamoxifen: (Minor) Caution is advised with the concomitant use of tamoxifen and trifluoperazine due to an increased risk of QT prolongation. Tamoxifen has been reported to prolong the QT interval, usually in overdose or when used in high doses. Rare case reports of QT prolongation have also been described when tamoxifen is used at lower doses. Trifluoperazine is associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Tapentadol: (Moderate) Concomitant use of opioid agonists with trifluoperazine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with trifluoperazine 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.
Tazarotene: (Moderate) The manufacturer states that tazarotene should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as phenothiazines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Telavancin: (Minor) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering telavancin with trifluoperazine. Telavancin has been associated with QT prolongation. Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation.
Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
Temazepam: (Major) Limit dosage and duration of benzodiazepines during concomitant phenothiazine use and monitor for unusual drowsiness and sedation due to the risk for additive CNS depression.
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 trifluoperazine. Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation. In addition, concurrent use of these medications and tetrabenazine should generally be avoided since the risk of adverse effects such as drowsiness, sedation, dizziness, orthostatic hypotension, neuroleptic malignant syndrome, or extrapyramidal symptoms may be increased.
Thalidomide: (Major) Avoid the concomitant use of thalidomide with opiate agonists; antihistamines; antipsychotics; anxiolytics, sedatives, and hypnotics; and other central nervous system depressants due to the potential for additive sedative effects.
Thiazide diuretics: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
Thiazolidinediones: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
Thioridazine: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation and TdP. In addition, coadministration may increase the risk of drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, tardive dyskinesia, or seizures.
Thiothixene: (Major) Caution is advisable during concurrent use of thiothixene and the phenothiazine antipsychotics. Thiothixene use has been associated with adverse events such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. These effects may be potentiated during concurrent use of phenothiazines and other antipsychotics. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone. Administration of thiothixene with antipsychotics that are metabolized by CYP2D6, such as phenothiazines, should be approached with great caution. Thiothixene has been shown to inhibit CYP2D6 in vitro and serum concentrations of phenothiazines may increase.
Tiagabine: (Moderate) The phenothiazines, when used concomitantly with anticonvulsants, can lower the seizure threshold. Adequate dosages of anticonvulsants should be continued when a phenothiazine is added.
Tobacco: (Major) Advise patients to avoid smoking tobacco while taking phenothiazines. Tobacco smoking may increase the clearance of phenothiazines, which may reduce their efficacy.
Tobramycin: (Minor) When used for the treatment of nausea and vomiting, antiemetic phenothiazines may mask symptoms that are associated with ototoxicity induced by the aminoglycosides.
Tolazamide: (Moderate) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted. Also, concomitant use may increase the risk for phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure.
Tolbutamide: (Moderate) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted. Also, concomitant use may increase the risk for phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure.
Tolterodine: (Moderate) Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation. Theoretically, trifluoperazine 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 trifluoperazine include solifenacin and tolterodine. Additive anticholinergic effects may be seen with any antimuscarinics. 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. Drowsiness or other additive CNS effects may also occur in some patients.
Topiramate: (Moderate) Monitor for unusual drowsiness and excess sedation during coadministration of phenothiazines and topiramate due to the risk for additive CNS depression.
Toremifene: (Minor) Use toremifene and trifluoperazine together with caution due to the risk of QT prolongation. The manufacturer of toremifene recommends avoiding toremifene with other drugs that prolong the QT, if possible. Trifluoperazine is associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation. Toremifene has also been shown to prolong the QTc interval in a dose- and concentration-related manner.
Tramadol: (Moderate) Concurrent use of tramadol and trifluoperazine should be avoided if possible. Antipsychotics may enhance the seizure risk of tramadol. Additive CNS depression may also be seen with the concomitant use of tramadol and trifluoperazine.
Tramadol; Acetaminophen: (Moderate) Concurrent use of tramadol and trifluoperazine should be avoided if possible. Antipsychotics may enhance the seizure risk of tramadol. Additive CNS depression may also be seen with the concomitant use of tramadol and trifluoperazine.
Tranylcypromine: (Moderate) Concurrent use of MAOIs and phenothiazines may prolong or intensify the hypotensive, anticholinergic, or sedative effects of either agent. Due to the potential for additive CNS and cardiovascular effects, MAOIs and phenothiazines should be used together cautiously.
Trazodone: (Minor) Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation. Trazodone can prolong the QT/QTc interval at therapeutic doses. In addition, there are post-marketing reports of torsade de pointes (TdP). Therefore, the manufacturer recommends avoiding trazodone in patients receiving other drugs that increase the QT interval; if the drugs must be used together, use with caution. In addition, phenothiazines should be used cautiously in patients receiving trazodone because of additive CNS-depressant effects, including possible respiratory depression or hypotension.
Tretinoin, ATRA: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as phenothiazines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Tretinoin; Benzoyl Peroxide: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as phenothiazines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
Triazolam: (Major) Limit dosage and duration of benzodiazepines during concomitant phenothiazine use and monitor for unusual drowsiness and sedation due to the risk for additive CNS depression.
Triclabendazole: (Minor) QT/QTc prolongation can occur with concomitant use of triclabendazole and trifluoperazine 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.
Tricyclic antidepressants: (Moderate) Phenothiazines have been reported to prolong the QT interval. Because tricyclic antidepressants are associated with a possible risk for QT prolongation and TdP when given in excessive doses or overdosage, concurrent use with trifluoperazine 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. Additive anticholinergic effects or sedation may be seen when phenothiazines are used with tricyclic antidepressants.
Trihexyphenidyl: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including trifluoperazine. 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.
Trimethobenzamide: (Moderate) Trimethobenzamide has CNS depressant effects and may cause drowsiness. The concurrent use of trimethobenzamide with other medications that cause CNS depression such as the phenothiazines may potentiate drowsiness or other common side effects of either medication. In addition, the administration of trimethobenzamide to patients who have recently received CNS-depressive drugs has resulted in opisthotonus, seizures, coma, and extrapyramidal symptoms.
Trimipramine: (Moderate) Phenothiazines have been reported to prolong the QT interval. Because tricyclic antidepressants are associated with a possible risk for QT prolongation and TdP when given in excessive doses or overdosage, concurrent use with trifluoperazine 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. Additive anticholinergic effects or sedation may be seen when phenothiazines are used with tricyclic antidepressants.
Triprolidine: (Moderate) Additive anticholinergic and sedative effects may be seen when trifluoperazine is used with first generation antihistamines, such as triprolidine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
Triptorelin: (Major) Avoid coadministration of triptorelin with trifluoperazine due to the risk of reduced efficacy of triptorelin; QT prolongation may also occur. Trifluoperazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; triptorelin is a GnRH analog. Trifluoperazine is also associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation. Androgen deprivation therapy (i.e., triptorelin) may also prolong the QT/QTc interval.
Trospium: (Moderate) Additive anticholinergic effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity, such as trospium.
Valproic Acid, Divalproex Sodium: (Moderate) The phenothiazines, when used concomitantly with various anticonvulsants, such as valproic acid, can increase CNS depression and also can lower the seizure threshold. Adequate dosages of anticonvulsants should be continued when a phenothiazine is added; patients should be monitored for clinical evidence of loss of seizure control or the need for dosage adjustments of either the phenothiazine or the anticonvulsant.
Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
Vandetanib: (Minor) If concomitant use of vandetanib with trifluoperazine is necessary, 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. Trifluoperazine is also associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Vardenafil: (Minor) Use vardenafil with caution in combination with trifluoperazine as concurrent use may increase the risk of QT prolongation. Trifluoperazine is associated with a possible risk for QT prolongation. Vardenafil is associated with QT prolongation. Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval.
Vemurafenib: (Minor) Vemurafenib has been associated with QT prolongation. If vemurafenib and another drug 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. Drugs with a possible risk for QT prolongation that should be used cautiously with vemurafenib include trifluoperazine.
Venlafaxine: (Moderate) Caution is advisable during concurrent use of trifluoperazine and serotonin norepinephrine reuptake inhibitors (SNRIs) since elevations in plasma concentrations of trifluoperazine may occur. Phenothiazines are CYP2D6 substrates, and SNRIs including duloxetine and venlafaxine are CYP2D6 inhibitors. In addition, both venlafaxine and trifluoperazine are associated with a possible risk of QT prolongation; therefore, additive cardiac effects are possible. Although clinical studies have shown that desvenlafaxine does not have a clinically relevant effect on CYP2D6 inhibition at doses of 100 mg/day, the manufacturer recommends that doses of medications that are primary substrates of CYP2D6 be reduced by one-half during co-administration of desvenlafaxine doses of 400 mg/day.
Verteporfin: (Moderate) Use caution if coadministration of verteporfin with phenothiazines 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 phenothiazines may increase the risk of a photosensitivity reaction.
Vigabatrin: (Major) Vigabatrin should not be used with phenothiazines, which is associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Vincristine Liposomal: (Major) Trifluoperazine inhibits P-glycoprotein (P-gp), which is a mechanism of resistance to naturally occurring (non-synthetic) chemotherapy agents; vincristine is a P-gp substrate. Coadministration could increase exposure to vincristine; however, trifluoperazine must be given in toxic doses to achieve this effect.
Vincristine: (Major) Trifluoperazine inhibits P-glycoprotein (P-gp), which is a mechanism of resistance to naturally occurring (non-synthetic) chemotherapy agents; vincristine is a P-gp substrate. Coadministration could increase exposure to vincristine; however, trifluoperazine must be given in toxic doses to achieve this effect.
Voclosporin: (Minor) Concomitant use of voclosporin and trifluoperazine 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. Trifluoperazine is associated with a possible risk for QT prolongation.
Vonoprazan; Amoxicillin; Clarithromycin: (Minor) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering clarithromycin with trifluoperazine. Clarithromycin is associated with an established risk for QT prolongation and TdP, while trifluoperazine (a phenothiazine) is associated with a possible risk for QT prolongation.
Voriconazole: (Minor) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering voriconazole with trifluoperazine. Voriconazole has been associated with prolongation of the QT interval and rare cases of arrhythmias, including TdP. Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation.
Vorinostat: (Minor) Vorinostat therapy is associated with a risk of QT prolongation. Drugs with a possible risk for QT prolongation that should be used cautiously with vorinostat include trifluoperazine. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with drugs with a possible risk for QT prolongation.
Zaleplon: (Moderate) Phenothiazines are CNS depressant drugs that may have cumulative effects when administered with other CNS depressant drugs and they should be used cautiously with anxiolytic, sedative, and hypnotics. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension. Additionally, sleep-related behaviors, such as sleep-driving, are more likely to occur during concurrent use of hypnotics and other CNS depressants than with use of a hypnotic alone.
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 phenothiazines. Coadministration of CNS depressants may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Ziprasidone: (Major) Concomitant use of ziprasidone and trifluoperazine should be avoided if possible. Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of torsade de pointes (TdP) in patients with multiple confounding factors. Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation and may theoretically increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation. In addition, coadministration of ziprasidone with phenothiazines may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the coadministered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Zolpidem: (Moderate) Phenothiazines are CNS depressant drugs that may have cumulative effects when administered with other CNS depressant drugs and they should be used cautiously with anxiolytic, sedative, and hypnotics. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension. Additionally, sleep-related behaviors, such as sleep-driving, are more likely to occur during concurrent use of hypnotics and other CNS depressants than with use of a hypnotic alone.
Zonisamide: (Moderate) The phenothiazines, when used concomitantly with anticonvulsants, can lower the seizure threshold. Adequate dosages of anticonvulsants should be continued when a phenothiazine is added. Zonisamide may also cause decreased sweating (oligohidrosis), elevated body temperature (hyperthermia), heat intolerance, or heat stroke. The manufacturer recommends caution in using concurrent drug therapies that may predispose patients to heat-related disorders such as antipsychotic phenothiazines. Monitor patients for decreased efficacy of the anticonvulsant, heat intolerance, decreased sweating, or increased body temperature if zonisamide is used with any of these agents.

Stelazine/Trifluoperazine/Trifluoperazine Hydrochloride Oral Tab: 1mg, 2mg, 5mg, 10mg

Adults

40 mg/day PO. Debilitated patients require lower dosages.

Geriatric

40 mg/day PO. Debilitated patients require lower dosages.

Adolescents

Usual pediatric maximum is 15 mg/day PO, though older children with severe symptoms may require 20 mg/day PO.

Children

6 to 12 years: 15 mg/day PO is the usual pediatric maximum.
Less than 6 years: Safety and efficacy have not been established.

Infants

Not indicated.

Trifluoperazine blocks postsynaptic dopamine receptors in the mesolimbic system and increases dopamine turnover by blockade of the dopamine D2 somatodendritic autoreceptor. After about 12 weeks of chronic therapy, depolarization blockade of dopamine tracts occurs. The decrease in dopamine neurotransmission has been found to correlate to the antipsychotic effects. This D2 blockade is also responsible for the strong extrapyramidal effects observed with this drug. Dopamine blockade in the chemoreceptor trigger zone accounts for the antiemetic effects. Trifluoperazine possesses weak anticholinergic and alpha-adrenergic receptor blocking effects. Blockade of alpha1-adrenergic receptors produces sedation, muscle relaxation, and cardiovascular effects such as hypotension, reflex tachycardia, and minor changes in ECG patterns.

Trifluoperazine is administered orally; an intramuscular formulation is no longer marketed. Antipsychotic effects are gradual, with considerable individual patient variation, and peak therapeutic effects may not occur for weeks to months. Phenothiazines are distributed widely into body tissues and fluids, and cross the blood-brain barrier. Trifluoperazine is highly plasma protein-bound (90% to 99%), predominantly to alpha1-acid glycoprotein. Metabolism is extensive and some enterohepatic circulation may occur. Most of the metabolites formed are pharmacologically inactive. The elimination half-life in adults is 3 to 12 hours. There is some conjugation with glucuronides, and these, along with unconjugated metabolites, account for most of the drug found in urine; only a small amount is excreted as unchanged drug. Some excretion may occur via the biliary tract and feces.
 
Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: CYP1A2
Trifluoperazine is a primary substrate of CYP1A2. Trifluoperazine is also a known substrate for UGT1A4, although the clinical significance of this finding is unknown.

Oral Route

Trifluoperazine is rapidly absorbed following oral administration, with peak plasma concentrations occurring 1.5 to 6 hours after a dose. There is considerable individual patient variation in peak plasma concentrations because the drug undergoes metabolism in the gastric mucosa and during first-pass through the liver.

Pregnancy

According to the manufacturer of trifluoperazine, phenothiazines are excreted into breast milk, and a decision should be made to discontinue trifluoperazine or discontinue breast-feeding, taking into account the importance of the drug to the mother. In some instances, maternal use of phenothiazines has been associated with drowsiness, lethargy, and developmental delays in the nursing infant. The physiology of the infant should be considered when evaluating the risk of exposure to phenothiazines. Phenothiazines may also induce elevated prolactin concentrations and galactorrhea, and thus may interfere with proper lactation. The American Academy of Pediatrics (AAP) classifies trifluoperazine as a drug for which the effects on a nursing infant are unknown but may be of concern. Chlorpromazine, a related phenothiazine, is similarly classified due to drowsiness or lethargy in the infant, a decline in developmental scores, and drug-induced galactorrhea in the mother. Due to individual variability in response to antipsychotics, it may be prudent to continue the existing regimen if ongoing treatment is deemed necessary during breast-feeding; however, alternate medications for consideration include atypical agents such as olanzapine or quetiapine. It should be noted that data regarding the safety of atypical antipsychotics during breast-feeding are limited and chronic administration of any antipsychotic during breast-feeding should be avoided if possible. Regardless of the antipsychotic used, the nursing infant should be closely monitored for excessive drowsiness, lethargy, and developmental delays. Combination treatment with antipsychotics may increase the risk of these adverse events. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.