Eskalith CR

Antidepressant Augmentation Agents
Mood Stabilizers

Oral Administration

May administer with or without food. If stomach upset or nausea occur, administer with food.

Oral Solid Formulations

Extended-release products: Administer intact; do not chew, crush, or cut in half.

Oral Liquid Formulations

Oral solution: To improve the taste, may be diluted with fruit juice or other flavored beverage before administering. Do not mix with an antipsychotic (especially chlorpromazine concentrate) or antidepressant liquid since an insoluble citrate salt may be formed.

Severe

diabetes insipidus / Delayed / 1.0-10.0
seizures / Delayed / 0-1.0
serotonin syndrome / Delayed / 0-1.0
neuroleptic malignant syndrome / Delayed / 0-1.0
nephrotic syndrome / Delayed / 0-1.0
renal failure (unspecified) / Delayed / 0-1.0
glomerulonephritis / Delayed / 0-1.0
proteinuria / Delayed / 0-1.0
coma / Early / Incidence not known
papilledema / Delayed / Incidence not known
new primary malignancy / Delayed / Incidence not known
cardiac arrest / Early / Incidence not known
AV block / Early / Incidence not known
bradycardia / Rapid / Incidence not known
arrhythmia exacerbation / Early / Incidence not known
teratogenesis / Delayed / Incidence not known
interstitial nephritis / Delayed / Incidence not known
oliguria / Early / Incidence not known
renal tubular acidosis (RTA) / Delayed / Incidence not known
angioedema / Rapid / Incidence not known
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / Incidence not known

Moderate

ataxia / Delayed / 13.0-13.0
hypothyroidism / Delayed / 1.0-10.0
goiter / Delayed / 1.0-10.0
blurred vision / Early / 9.0-9.0
hyperthyroidism / Delayed / 0-1.0
memory impairment / Delayed / 10.0
fecal incontinence / Early / Incidence not known
hallucinations / Early / Incidence not known
hyperreflexia / Delayed / Incidence not known
confusion / Early / Incidence not known
dysarthria / Delayed / Incidence not known
pseudotumor cerebri / Delayed / Incidence not known
dystonic reaction / Delayed / Incidence not known
myoclonia / Delayed / Incidence not known
EEG changes / Delayed / Incidence not known
impaired cognition / Early / Incidence not known
myasthenia / Delayed / Incidence not known
choreoathetosis / Delayed / Incidence not known
nystagmus / Delayed / Incidence not known
palpitations / Early / Incidence not known
QT prolongation / Rapid / Incidence not known
hypotension / Rapid / Incidence not known
ST-T wave changes / Rapid / Incidence not known
glycosuria / Early / Incidence not known
urinary incontinence / Early / Incidence not known
impotence (erectile dysfunction) / Delayed / Incidence not known
dehydration / Delayed / Incidence not known
hyperchloremic acidosis / Delayed / Incidence not known
psoriasis / Delayed / Incidence not known
skin ulcer / Delayed / Incidence not known
scotomata / Delayed / Incidence not known
exophthalmos / Delayed / Incidence not known
peripheral edema / Delayed / Incidence not known
hyperglycemia / Delayed / Incidence not known
hyponatremia / Delayed / Incidence not known
hypercalcemia / Delayed / Incidence not known

Mild

nausea / Early / 57.0-57.0
vomiting / Early / 57.0-57.0
fatigue / Early / 26.0-26.0
dizziness / Early / 23.0-23.0
rash / Early / 13.0-13.0
diarrhea / Early / 1.0-10.0
anorexia / Delayed / 9.0-9.0
weight gain / Delayed / 10.0
drowsiness / Early / 10.0
tremor / Early / 10.0
leukocytosis / Delayed / 10.0
polyuria / Early / 10.0
polydipsia / Early / 10.0
xerosis / Delayed / 10.0
metallic taste / Early / Incidence not known
flatulence / Early / Incidence not known
dysgeusia / Early / Incidence not known
weight loss / Delayed / Incidence not known
hypersalivation / Early / Incidence not known
xerostomia / Early / Incidence not known
dental caries / Delayed / Incidence not known
abdominal pain / Early / Incidence not known
restlessness / Early / Incidence not known
psychomotor impairment / Early / Incidence not known
headache / Early / Incidence not known
vertigo / Early / Incidence not known
lethargy / Early / Incidence not known
tinnitus / Delayed / Incidence not known
syncope / Early / Incidence not known
folliculitis / Delayed / Incidence not known
pruritus / Rapid / Incidence not known
acne vulgaris / Delayed / Incidence not known
alopecia / Delayed / Incidence not known
arthralgia / Delayed / Incidence not known
fever / Early / Incidence not known
cheilitis / Delayed / Incidence not known

Initial treatment, serum lithium concentration monitoring

The clinician should ensure that facilities are available for prompt and accurate evaluation of lithium concentrations before the initial treatment of a patient with lithium.[54241] [47399] Routine serum lithium concentration monitoring should be performed throughout treatment. Lithium has a narrow therapeutic index, and serum lithium concentrations are closely correlated with the toxicity of the drug; a concentration above 1.5 mEq/L is likely to produce some degree of toxicity. Signs of toxicity may range from mild neurological effects such as fine tremor, lightheadedness, incoordination, and weakness, to moderate reactions including giddiness, apathy, drowsiness, hyperreflexia, muscle twitching, ataxia, blurred vision, tinnitus, and slurred speech. Severe manifestations of lithium toxicity include clonus, confusion, seizures, coma, and death. Rarely, neurological complications may persist despite discontinuation of lithium treatment and may be associated with cerebellar atrophy. Involvement of other organ systems includes cardiovascular (e.g., ECG changes such as prolonged QT interval, ST and T-wave changes, myocarditis), renal (e.g., urine concentration defect, nephrogenic diabetes insipidus, renal failure), respiratory (e.g., dyspnea, aspiration pneumonia, respiratory failure), and gastrointestinal (e.g., nausea, vomiting, diarrhea, bloating). Avoid lithium concentrations above 1.5 mEq/L whenever possible.[41087] [41097] Serum lithium concentrations should not be permitted to exceed 2 mEq/L.[54241] A concentration above 3 mEq/L is considered a medical emergency; serum concentrations above 3 mEq/L may be associated with multiple organ involvement, changes in mental status, coma, and eventually death. Following initiation of treatment, a serum lithium concentration should be obtained after 3 days, drawn 12 hours after the last oral dose and then regularly until patient is stabilized. After that, monitor the clinical status of the patient and serum lithium concentrations regularly, and adjust the dosage according to response, tolerability, and serum lithium concentrations. Some patients may be abnormally sensitive to lithium and may exhibit toxic signs at lithium concentrations that are within the usual therapeutic range (e.g., elderly patients). Symptoms of acute toxicity may be delayed since lithium may take up to 24 hours to distribute into brain tissue. The clinician and patient should be familiar with factors which can alter lithium concentrations thereby producing toxicity including recent onset of febrile illness, acute ingestion, impaired renal function, volume depletion, dehydration, significant cardiac disease, concurrent use of some prescription and over-the-counter (OTC) medications, changes in sodium intake, or changes in electrolyte concentrations (especially sodium and potassium). Advise patients and caregivers to watch for signs of early toxicity and to discontinue lithium and immediately inform their health care provider if they occur. The patient should be instructed to contact a health care provider for further evaluation if they experience potential symptoms of toxicity including nausea/vomiting, diarrhea, confusion, coarse tremor, delirium, hallucinations, muscle fasciculations, seizures, or ataxia.[54241] [47399]

Eskalith, Eskalith CR, Lithobid

Rx

Oral monovalent cation with a narrow therapeutic range
Approved for manic episodes and as maintenance treatment for Bipolar I Disorder adult and pediatric patients 7 years and older (dependent on formulation chosen); used off-label as an adjunct for adults with refractory major depression
Due to risk for toxicity, requires close monitoring of serum lithium concentrations, fluid status, electrolytes, and renal function

For the treatment of bipolar disorder (bipolar I disorder), including acute treatment of mania and mixed episodes. For the acute treatment of mania and mixed episodes associated with bipolar I disorder. Oral dosage (immediate-release tablets or capsules) Adults

300 mg PO 3 times daily, initially. Adjust dose by 300 mg every 3 days based on clinical response, tolerability, and serum lithium concentration. Usual dose: 600 mg PO 2 to 3 times daily.

Children and Adolescents 7 to 17 years and weighing more than 30 kg

300 mg PO 3 times daily, initially. Adjust dose by 300 mg every 3 days based on clinical response, tolerability, and serum lithium concentration. Usual dose: 600 mg PO 2 to 3 times daily.

Children and Adolescents 7 to 17 years and weighing 20 to 30 kg

300 mg PO 2 times daily, initially. Adjust dose by 300 mg weekly based on clinical response, tolerability, and serum lithium concentration. Usual dose: 600 to 1,500 mg/day in 2 to 3 divided doses.. Alternatively, an approximate pediatric weight-based dose range of 10 to 30 mg/kg/day PO has been suggested.

Oral dosage (lithium citrate syrup containing 8 mEq of lithium, equivalent to 300 mg of lithium carbonate) Adults

8 mEq PO 3 times daily, initially. Adjust dose by 8 mEq every 3 days based on clinical response, tolerability, and serum lithium concentration. Usual dose: 16 mEq PO 2 to 3 times daily.

Children and Adolescents 7 to 17 years and weighing more than 30 kg

8 mEq PO 3 times daily, initially. Adjust dose by 8 mEq every 3 days based on clinical response, tolerability, and serum lithium concentration. Usual dose: 16 mEq PO 2 to 3 times daily.

Children and Adolescents 7 to 17 years and weighing 20 to 30 kg

8 mEq PO 2 times daily, initially. Adjust dose by 8 mEq weekly based on clinical response, tolerability, and serum lithium concentration. Usual dose: 16 to 40 mEq/day in 2 to 3 divided doses.

Oral dosage (extended-release) Adults

900 mg PO 2 times daily or 600 mg PO 3 times daily, initially. Adjust dose based on clinical response, tolerability, and serum lithium concentration. Usual dose: 1,800 mg/day.

Children and Adolescents 12 to 17 years

900 mg PO 2 times daily or 600 mg PO 3 times daily, initially. Adjust dose based on clinical response, tolerability, and serum lithium concentration. Usual dose: 1,800 mg/day.

For the maintenance treatment of bipolar I disorder. Oral dosage (immediate-release tablets and capsules) Adults

300 mg PO 3 times daily, initially. Adjust dose by 300 mg every 3 days based on clinical response, tolerability, and serum lithium concentration. Usual dose: 300 to 600 mg PO 2 to 3 times daily.

Children and Adolescents 7 to 17 years and weighing more than 30 kg

300 mg PO 3 times daily, initially. Adjust dose by 300 mg every 3 days based on clinical response, tolerability, and serum lithium concentration. Usual dose: 300 to 600 mg PO 2 to 3 times daily.

Children and Adolescents 7 to 17 years and weighing 20 to 30 kg

300 mg PO 2 times daily, initially. Adjust dose by 300 mg weekly based on clinical response, tolerability, and serum lithium concentration. Usual dose: 600 to 1,200 mg/day in 2 to 3 divided doses.. Alternatively, an approximate pediatric weight-based dose range of 10 to 30 mg/kg/day PO in divided doses has been suggested.

Oral dosage (lithium citrate syrup containing 8 mEq of lithium, equivalent to 300 mg of lithium carbonate) Adults

8 mEq PO 3 times daily, initially. Adjust dose by 8 mEq every 3 days based on clinical response, tolerability, and serum lithium concentration. Usual dose: 8 to 16 mEq PO 2 to 3 times daily.

Children and Adolescents 7 to 17 years and weighing more than 30 kg

8 mEq PO 3 times daily, initially. Adjust dose by 8 mEq every 3 days based on clinical response, tolerability, and serum lithium concentration. Usual dose: 8 to 16 mEq PO 2 to 3 times daily.

Children and Adolescents 7 to 17 years and weighing 20 to 30 kg

8 mEq PO 2 times daily, initially. Adjust dose by 8 mEq weekly based on clinical response, tolerability, and serum lithium concentration. Usual dose: 16 to 32 mEq/day in 2 to 3 divided doses.

Oral dosage (extended-release) Adults

450 or 600 mg PO 2 times daily or 400 mg PO 3 times daily, initially. Adjust dose based on clinical response, tolerability, and serum lithium concentration. Usual dose: 900 to 1,200 mg/day in 2 to 3 divided doses.

Children and Adolescents 12 to 17 years

450 or 600 mg PO 2 times daily or 400 mg PO 3 times daily, initially. Adjust dose based on clinical response, tolerability, and serum lithium concentration. Usual dose: 900 to 1,200 mg/day in 2 to 3 divided doses.

For use as an augmentation agent in the treatment of major depression†. Oral dosage (immediate-release tablets, capsules, or lithium oral solution or syrups) Adults

600 mg PO 3 times per day or 10 mL (16 mEq) oral solution PO 3 times per day. Consider lower initial doses in patients at risk for lithium toxicity. For use as an adjunctive agent only. Geriatric patients often respond to reduced dosage, and may exhibit signs of toxicity at serum lithium concentrations ordinarily tolerated by younger adults.

†Indicates off-label use

Hepatic Impairment

Specific recommendations for dosage adjustment in patients with hepatic impairment are not available, use caution. Dosage adjustment will be needed if renal dysfunction is also present. Many factors can affect renal lithium clearance including hyponatremia or hypernatremia, dehydration, and diuretic use, some conditions may be present in the patient with hepatic impairment.

Renal Impairment

CrCl at least 90 mL/min: No dosage adjustments are necessary.
CrCl 30 mL/min to 89 mL/min: Start with a dosage that is less than in patients with normal renal function and titrate slowly with frequent monitoring for lithium toxicity.
CrCl less than 30 mL/min: Avoid use.

Acarbose: (Moderate) Lithium may cause variable effects on glycemic control when used in patients receiving antidiabetic agents. Monitor blood glucose concentrations closely if lithium is coadministered with antidiabetic agents. Dosage adjustments of antidiabetic agents may be necessary.
Acetaminophen; Aspirin, ASA; Caffeine: (Major) Caffeine appears to reduce serum lithium concentrations. Adverse reactions to lithium have also been noted to increase simultaneously with a reduction in caffeine intake. Patients taking lithium should be counseled regarding their intake of caffeine.
Acetaminophen; Caffeine: (Major) Caffeine appears to reduce serum lithium concentrations. Adverse reactions to lithium have also been noted to increase simultaneously with a reduction in caffeine intake. Patients taking lithium should be counseled regarding their intake of caffeine.
Acetaminophen; Caffeine; Dihydrocodeine: (Major) Caffeine appears to reduce serum lithium concentrations. Adverse reactions to lithium have also been noted to increase simultaneously with a reduction in caffeine intake. Patients taking lithium should be counseled regarding their intake of caffeine. (Moderate) If concomitant use of dihydrocodeine and lithium is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Acetaminophen; Caffeine; Pyrilamine: (Major) Caffeine appears to reduce serum lithium concentrations. Adverse reactions to lithium have also been noted to increase simultaneously with a reduction in caffeine intake. Patients taking lithium should be counseled regarding their intake of caffeine. (Moderate) Because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including the sedating antihistamines.
Acetaminophen; Chlorpheniramine: (Moderate) Because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including the sedating antihistamines.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including the sedating antihistamines.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including the sedating antihistamines.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including the sedating antihistamines.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including the sedating antihistamines.
Acetaminophen; Codeine: (Moderate) If concomitant use of codeine and lithium is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Acetaminophen; Dichloralphenazone; Isometheptene: (Moderate) Because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including anxiolytics, sedatives, and hypnotics.
Acetaminophen; Hydrocodone: (Moderate) If concomitant use of hydrocodone and lithium is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Acetaminophen; Oxycodone: (Moderate) If concomitant use of oxycodone and lithium is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Acetaminophen; Pamabrom; Pyrilamine: (Moderate) Because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including the sedating antihistamines.
Acrivastine; Pseudoephedrine: (Moderate) Because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including the sedating antihistamines.
Acyclovir: (Moderate) Consider starting with a lower lithium dose and monitor lithium concentrations and for signs and symptoms of lithium toxicity during concomitant acyclovir use. The risk of lithium toxicity is increased with concomitant use of medications that affect kidney function, such as acyclovir.
Adagrasib: (Major) Concomitant use of adagrasib and lithium 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.
Aldesleukin, IL-2: (Moderate) Aldesleukin may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psychotropic activity, such as lithium. Use with caution.
Alfentanil: (Moderate) If concomitant use of alfentanil and lithium is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Alfuzosin: (Moderate) Concomitant use of lithium and alfuzosin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Aliskiren: (Minor) In theory, direct renin inhibitors, such as aliskiren, have the potential to interact with lithium; therefore, the combination should be used cautiously and with careful monitoring of lithium levels. Related drug classes, such as ACE inhibitors, may substantially increase lithium levels, sometimes resulting in lithium toxicity. Because aliskerin has demonstrated significant natriuresis, increased renal tubular reabsorption of lithium may be possible. If alternative therapies are not possible, monitoring for lithium toxicity (e.g., nausea, vomiting, anorexia, drowsiness, dysarthria, tremor, confusion, lethargy, EKG changes, etc.) is advisable. More frequent assessments of lithium levels and adjustment of lithium dosage may be needed.
Aliskiren; Hydrochlorothiazide, HCTZ: (Minor) In theory, direct renin inhibitors, such as aliskiren, have the potential to interact with lithium; therefore, the combination should be used cautiously and with careful monitoring of lithium levels. Related drug classes, such as ACE inhibitors, may substantially increase lithium levels, sometimes resulting in lithium toxicity. Because aliskerin has demonstrated significant natriuresis, increased renal tubular reabsorption of lithium may be possible. If alternative therapies are not possible, monitoring for lithium toxicity (e.g., nausea, vomiting, anorexia, drowsiness, dysarthria, tremor, confusion, lethargy, EKG changes, etc.) is advisable. More frequent assessments of lithium levels and adjustment of lithium dosage may be needed.
Alkalinizing Agents: (Major) Avoid the administration of Alkalinizing agents to patients who are being treated with lithium, especially patients who are stabilized on lithium, as urinary alkalinization increases the renal clearance of lithium. If coadministration can not be avoided, monitor lithium serum concentrations and patient clinical response very closely. Also of note, lithium clearance is increased if hypernatremia occurs.
Alogliptin: (Moderate) Lithium may cause variable effects on glycemic control when used in patients receiving antidiabetic agents. While early reports of hyperglycemia in patients treated with lithium have not been confirmed by more recent studies, it may be prudent to monitor blood glucose concentrations closely if lithium is coadministered with antidiabetic agents. Dosage adjustments of antidiabetic agents may be necessary.
Alogliptin; Metformin: (Moderate) Lithium may cause variable effects on glycemic control when used in patients receiving antidiabetic agents. While early reports of hyperglycemia in patients treated with lithium have not been confirmed by more recent studies, it may be prudent to monitor blood glucose concentrations closely if lithium is coadministered with antidiabetic agents. Dosage adjustments of antidiabetic agents may be necessary.
Alogliptin; Pioglitazone: (Moderate) Lithium may cause variable effects on glycemic control when used in patients receiving antidiabetic agents. While early reports of hyperglycemia in patients treated with lithium have not been confirmed by more recent studies, it may be prudent to monitor blood glucose concentrations closely if lithium is coadministered with antidiabetic agents. Dosage adjustments of antidiabetic agents may be necessary.
Alpha-glucosidase Inhibitors: (Moderate) Lithium may cause variable effects on glycemic control when used in patients receiving antidiabetic agents. Monitor blood glucose concentrations closely if lithium is coadministered with antidiabetic agents. Dosage adjustments of antidiabetic agents may be necessary.
Amiodarone: (Major) Concomitant use of amiodarone and lithium 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. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after drug discontinuation.
Amisulpride: (Major) Monitor ECGs for QT prolongation when amisulpride is administered with lithium. Amisulpride causes dose- and concentration- dependent QT prolongation. Lithium has been associated with QT prolongation.
Amlodipine: (Moderate) Monitor for neurologic adverse reactions during concomitant use of lithium and calcium channel blockers. Concomitant use may increase the risk of neurologic adverse reactions, such as ataxia, tremors, nausea, vomiting, diarrhea, and/or tinnitus.
Amlodipine; Atorvastatin: (Moderate) Monitor for neurologic adverse reactions during concomitant use of lithium and calcium channel blockers. Concomitant use may increase the risk of neurologic adverse reactions, such as ataxia, tremors, nausea, vomiting, diarrhea, and/or tinnitus.
Amlodipine; Benazepril: (Moderate) Monitor for neurologic adverse reactions during concomitant use of lithium and calcium channel blockers. Concomitant use may increase the risk of neurologic adverse reactions, such as ataxia, tremors, nausea, vomiting, diarrhea, and/or tinnitus.
Amlodipine; Celecoxib: (Moderate) Monitor for neurologic adverse reactions during concomitant use of lithium and calcium channel blockers. Concomitant use may increase the risk of neurologic adverse reactions, such as ataxia, tremors, nausea, vomiting, diarrhea, and/or tinnitus.
Amlodipine; Olmesartan: (Moderate) Monitor for neurologic adverse reactions during concomitant use of lithium and calcium channel blockers. Concomitant use may increase the risk of neurologic adverse reactions, such as ataxia, tremors, nausea, vomiting, diarrhea, and/or tinnitus.
Amlodipine; Valsartan: (Moderate) Monitor for neurologic adverse reactions during concomitant use of lithium and calcium channel blockers. Concomitant use may increase the risk of neurologic adverse reactions, such as ataxia, tremors, nausea, vomiting, diarrhea, and/or tinnitus.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for neurologic adverse reactions during concomitant use of lithium and calcium channel blockers. Concomitant use may increase the risk of neurologic adverse reactions, such as ataxia, tremors, nausea, vomiting, diarrhea, and/or tinnitus.
Amobarbital: (Moderate) Because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including anxiolytics, sedatives, and hypnotics.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Concomitant use of lithium and clarithromycin 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.
Amphetamine; Dextroamphetamine Salts: (Moderate) Coadministration of amphetamines and lithium may increase the risk of serotonin syndrome. At high doses, amphetamines can increase serotonin release, as well as act as serotonin agonists. Lithium has central serotonergic effects. Inform patients of the possible increased risk and monitor for serotonin syndrome, particularly during treatment initiation, after a dose increase, or the addition of other serotonergic medications. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Anagrelide: (Major) Lithium should be used cautiously and with close monitoring with anagrelide. Lithium has been associated with QT prolongation. 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.
Angiotensin II receptor antagonists: (Moderate) Monitor serum lithium concentrations during concomitant angiotensin II receptor blocker use; reduce the lithium dose based on serum lithium concentration and clinical response. Concomitant use may increase steady-state lithium concentrations.
Angiotensin-converting enzyme inhibitors: (Moderate) Monitor serum lithium concentrations during concomitant angiotensin-converting enzyme inhibitor use; reduce the lithium dose based on serum lithium concentration and clinical response. Concomitant use may increase steady-state lithium concentrations.
Anxiolytics; Sedatives; and Hypnotics: (Moderate) Because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including anxiolytics, sedatives, and hypnotics.
Apomorphine: (Moderate) Concomitant use of lithium and apomorphine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Argatroban: (Moderate) Moderate to significant dietary sodium changes, or changes in sodium and fluid intake, may affect lithium excretion. Systemic sodium chloride administration may result in increased lithium excretion and therefore, decreased serum lithium concentrations. In addition, high fluid intake may increase lithium excretion. For patients receiving sodium-containing intravenous fluids, symptom control and lithium concentrations should be carefully monitored. It is recommended that patients taking lithium maintain consistent dietary sodium consumption and adequate fluid intake during the initial stabilization period and throughout lithium treatment. Supplemental oral sodium and fluid should be only be administered under careful medical supervision.
Aripiprazole: (Moderate) Concomitant use of aripiprazole and lithium may increase the risk of neuroleptic malignant syndrome (NMS) and QT/QTc prolongation and torsade de pointes (TdP) in some patients. Monitor for neurotoxicity during concomitant use and consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. NMS has been observed during concurrent use of lithium and antipsychotics.
Arsenic Trioxide: (Major) Lithium should be used cautiously and with close monitoring with arsenic trioxide. Lithium has been associated with QT prolongation. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use. Avoid concomitant use of arsenic trioxide with other drugs that may cause QT interval prolongation; discontinue or select an alternative drug that does not prolong the QT interval prior to starting arsenic trioxide therapy. If concomitant drug use is unavoidable, frequently monitor electrocardiograms.
Artemether; Lumefantrine: (Major) Lithium should be avoided with artemether; lumefantrine. Lithium has been associated with QT prolongation. The administration of artemether; lumefantrine is associated with prolongation of the QT interval. Although there are no studies examining the effects of artemether; lumefantrine in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation and should be avoided. Consider ECG monitoring if other QT prolonging drugs must be used with or after artemether; lumefantrine treatment.
Asenapine: (Major) Some atypical antipsychotics, including asenapine, are indicated as adjunctive therapy to mood stabilizers such as lithium. Because both asenapine and lithium have been associated with QT prolongation, they should be combined 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., 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. Asenapine does not have an effect on the pharmacokinetic parameters of lithium.
Aspirin, ASA; Butalbital; Caffeine: (Major) Caffeine appears to reduce serum lithium concentrations. Adverse reactions to lithium have also been noted to increase simultaneously with a reduction in caffeine intake. Patients taking lithium should be counseled regarding their intake of caffeine. (Moderate) Because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including anxiolytics, sedatives, and hypnotics.
Aspirin, ASA; Caffeine: (Major) Caffeine appears to reduce serum lithium concentrations. Adverse reactions to lithium have also been noted to increase simultaneously with a reduction in caffeine intake. Patients taking lithium should be counseled regarding their intake of caffeine.
Aspirin, ASA; Caffeine; Orphenadrine: (Major) Caffeine appears to reduce serum lithium concentrations. Adverse reactions to lithium have also been noted to increase simultaneously with a reduction in caffeine intake. Patients taking lithium should be counseled regarding their intake of caffeine.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) If concomitant use of codeine and lithium is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Aspirin, ASA; Oxycodone: (Moderate) If concomitant use of oxycodone and lithium is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Atomoxetine: (Moderate) Concomitant use of atomoxetine and lithium may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Azithromycin: (Major) Concomitant use of azithromycin and lithium 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.
Barbiturates: (Moderate) Because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including anxiolytics, sedatives, and hypnotics.
Bedaquiline: (Major) Lithium should be used cautiously and with close monitoring with bedaquiline. Lithium has been associated with QT prolongation. 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. Coadministration with other QT prolonging drugs may result in additive or synergistic prolongation of the QT interval.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) Theoretically, concurrent use of methylene blue and lithium may increase the risk of serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and lithium is thought to increase central serotonin effects by various mechanisms. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other psychiatric serotonergic agents with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death. If serotonin syndrome is suspected, serotonergic agents should be discontinued and appropriate medical treatment should be implemented.
Benzphetamine: (Moderate) Coadministration of amphetamines and lithium may increase the risk of serotonin syndrome. At high doses, amphetamines can increase serotonin release, as well as act as serotonin agonists. Lithium has central serotonergic effects. Inform patients of the possible increased risk and monitor for serotonin syndrome, particularly during treatment initiation, after a dose increase, or the addition of other serotonergic medications. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Major) The interaction between lithium and tetracycline appears variable. Both lithium toxicity and reduction in lithium concentrations have been reported during concurrent administration of tetracycline. Use of an alternative antibiotic should be considered in patients receiving lithium; however, if concurrent use of tetracycline is necessary, close monitoring of lithium levels and clinical response is recommended. (Moderate) Concomitant use of lithium and metronidazole may increase serum lithium concentrations and increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Monitor serum lithium concentrations; reduce the lithium dose based on lithium serum concentrations and clinical response. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) The interaction between lithium and tetracycline appears variable. Both lithium toxicity and reduction in lithium concentrations have been reported during concurrent administration of tetracycline. Use of an alternative antibiotic should be considered in patients receiving lithium; however, if concurrent use of tetracycline is necessary, close monitoring of lithium levels and clinical response is recommended. (Moderate) Concomitant use of lithium and metronidazole may increase serum lithium concentrations and increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Monitor serum lithium concentrations; reduce the lithium dose based on lithium serum concentrations and clinical response. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Bivalirudin: (Moderate) Moderate to significant dietary sodium changes, or changes in sodium and fluid intake, may affect lithium excretion. Systemic sodium chloride administration may result in increased lithium excretion and therefore, decreased serum lithium concentrations. In addition, high fluid intake may increase lithium excretion. For patients receiving sodium-containing intravenous fluids, symptom control and lithium concentrations should be carefully monitored. It is recommended that patients taking lithium maintain consistent dietary sodium consumption and adequate fluid intake during the initial stabilization period and throughout lithium treatment. Supplemental oral sodium and fluid should be only be administered under careful medical supervision.
Blinatumomab: (Moderate) No drug interaction studies have been performed with blinatumomab. The drug may cause a transient release of cytokines leading to an inhibition of CYP450 enzymes. The interaction risk with CYP450 substrates is likely the highest during the first 9 days of the first cycle and the first 2 days of the second cycle. Monitor patients receiving concurrent CYP450 substrates that have a narrow therapeutic index (NTI) such as lithium. The dose of the concomitant drug may need to be adjusted.
Brexpiprazole: (Moderate) Although some atypical antipsychotics are considered first-line adjunctive therapy to mood stabilizers such as lithium, it is advisable to monitor patients for neurotoxicity during co-administration of lithium and brexpiprazole. 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. 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.
Brompheniramine: (Moderate) Because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including the sedating antihistamines.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including the sedating antihistamines.
Brompheniramine; Phenylephrine: (Moderate) Because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including the sedating antihistamines.
Brompheniramine; Pseudoephedrine: (Moderate) Because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including the sedating antihistamines.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including the sedating antihistamines.
Buprenorphine: (Major) Due to the potential for QT prolongation, cautious use and close monitoring are advisable if concurrent use of lithium and buprenorphine is necessary. Lithium may cause QT interval prolongation and a risk for torsade de pointes (TdP); buprenorphine caused QT prolongation in some patients during clinical trials. In addition, concurrent use of opioids with other drugs that modulate serotonergic function, such as lithium, has resulted in serotonin syndrome in some cases. Patients should be carefully observed, particularly during treatment initiation and during dose adjustments. Discontinue the serotonergic medications if serotonin syndrome is suspected.
Buprenorphine; Naloxone: (Major) Due to the potential for QT prolongation, cautious use and close monitoring are advisable if concurrent use of lithium and buprenorphine is necessary. Lithium may cause QT interval prolongation and a risk for torsade de pointes (TdP); buprenorphine caused QT prolongation in some patients during clinical trials. In addition, concurrent use of opioids with other drugs that modulate serotonergic function, such as lithium, has resulted in serotonin syndrome in some cases. Patients should be carefully observed, particularly during treatment initiation and during dose adjustments. Discontinue the serotonergic medications if serotonin syndrome is suspected.
Buspirone: (Moderate) Coadministration of buspirone with lithium may increase the risk of serotonin syndrome. Both medications have central serotonergic properties. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. If serotonin syndrome is suspected, all serotonergic agents should be discontinued and appropriate medical treatment should be implemented.
Butabarbital: (Moderate) Because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including anxiolytics, sedatives, and hypnotics.
Butalbital; Acetaminophen: (Moderate) Because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including anxiolytics, sedatives, and hypnotics.
Butalbital; Acetaminophen; Caffeine: (Major) Caffeine appears to reduce serum lithium concentrations. Adverse reactions to lithium have also been noted to increase simultaneously with a reduction in caffeine intake. Patients taking lithium should be counseled regarding their intake of caffeine. (Moderate) Because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including anxiolytics, sedatives, and hypnotics.
Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Caffeine appears to reduce serum lithium concentrations. Adverse reactions to lithium have also been noted to increase simultaneously with a reduction in caffeine intake. Patients taking lithium should be counseled regarding their intake of caffeine. (Moderate) Because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including anxiolytics, sedatives, and hypnotics. (Moderate) If concomitant use of codeine and lithium is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Butalbital; Aspirin; Caffeine; Codeine: (Major) Caffeine appears to reduce serum lithium concentrations. Adverse reactions to lithium have also been noted to increase simultaneously with a reduction in caffeine intake. Patients taking lithium should be counseled regarding their intake of caffeine. (Moderate) Because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including anxiolytics, sedatives, and hypnotics. (Moderate) If concomitant use of codeine and lithium is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Cabotegravir; Rilpivirine: (Moderate) Concomitant use of lithium and rilpivirine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Caffeine: (Major) Caffeine appears to reduce serum lithium concentrations. Adverse reactions to lithium have also been noted to increase simultaneously with a reduction in caffeine intake. Patients taking lithium should be counseled regarding their intake of caffeine. (Major) Caffeine appears to reduce serum lithium concentrations. In 11 coffee-drinking patients stabilized on lithium, serum lithium concentrations increased during 2 weeks when coffee was withheld and fell when coffee was resumed. Lithium ADRs have also been noted to increase simultaneously with a reduction in caffeine intake. Patients taking lithium should be counseled regarding their intake of caffeine. Clinicians should note, however, that coffee, not pure caffeine, was the variable in this study. Other beverages that contain significant amounts of caffeine include green tea, other teas, and cola. Because guarana contains a substantial caffeine content, this herb should be avoided in patients taking lithium.
Caffeine; Sodium Benzoate: (Major) Caffeine appears to reduce serum lithium concentrations. Adverse reactions to lithium have also been noted to increase simultaneously with a reduction in caffeine intake. Patients taking lithium should be counseled regarding their intake of caffeine.
Calcitonin: (Moderate) Reduced serum lithium concentrations have been observed in previously stabilized patients who initiated daily calcitonin salmon subcutaneous injections for osteoporosis. The mechanism is not clear, but serum lithium concentrations were reduced to 30% of the baseline value in all patients studied, and fell below normal therapeutic ranges. Increased urinary lithium clearance is a proposed mechanism for the interaction.
Calcium: (Moderate) Monitor serum calcium concentrations closely if concomitant use of calcium and lithium is necessary. Concomitant use may increase the risk of hypercalcemia.
Calcium-channel blockers: (Moderate) Monitor for neurologic adverse reactions during concomitant use of lithium and calcium channel blockers. Concomitant use may increase the risk of neurologic adverse reactions, such as ataxia, tremors, nausea, vomiting, diarrhea, and/or tinnitus.
Canagliflozin: (Moderate) Concomitant use of sodium-glucose cotransporter 2 (SGLT2) inhibitors with lithium may decrease serum lithium concentrations. Monitor serum lithium concentration more frequently during SGLT2 inhibitor initiation and dosage changes.
Canagliflozin; Metformin: (Moderate) Concomitant use of sodium-glucose cotransporter 2 (SGLT2) inhibitors with lithium may decrease serum lithium concentrations. Monitor serum lithium concentration more frequently during SGLT2 inhibitor initiation and dosage changes.
Capreomycin: (Moderate) Partial neuromuscular blockade has been reported with capreomycin after the administration of large intravenous doses or rapid intravenous infusion. Lithium could potentiate the neuromuscular blocking effect of capreomycin by impairing transmission of impulses at the motor nerve terminals. If these drugs are used in combination, monitor patients for increased adverse effects.
Carbamazepine: (Moderate) Monitor for neurologic adverse reactions during concomitant use of lithium and calcium carbamazepine. Concomitant use may increase the risk of neurologic adverse reactions, such as ataxia, tremors, nausea, vomiting, diarrhea, and/or tinnitus.
Carbinoxamine: (Moderate) Because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including the sedating antihistamines.
Carbonic anhydrase inhibitors: (Moderate) Carbonic anhydrase inhibitors interfere with lithium reabsorption at the proximal tubule, the primary site of lithium reabsorption. Thus, lithium serum concentrations are likely to decrease during administration of carbonic anhydrase inhibitors. In one small study evaluating the pharmacokinetic effects of several different medications on a single 600 mg dose of lithium carbonate, administration of acetazolamide resulted in a 31% increase in lithium clearance. If carbonic anhydrase inhibitor therapy is needed during lithium administration, monitoring of lithium concentrations is recommended, along with clinical monitoring for evidence of a decrease in lithium efficacy. Patients should promptly report persistent changes in moods or behaviors.
Celecoxib; Tramadol: (Moderate) If concomitant use of tramadol and lithium is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Ceritinib: (Major) Avoid coadministration of ceritinib with lithium if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. Lithium is also associated with QT prolongation.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including the sedating antihistamines.
Chlorcyclizine: (Moderate) Because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including the sedating antihistamines.
Chloroquine: (Major) Concomitant use of lithium and chloroquine 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.
Chlorpheniramine: (Moderate) Because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including the sedating antihistamines.
Chlorpheniramine; Codeine: (Moderate) Because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including the sedating antihistamines. (Moderate) If concomitant use of codeine and lithium is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Chlorpheniramine; Dextromethorphan: (Moderate) Because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including the sedating antihistamines.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including the sedating antihistamines.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including the sedating antihistamines.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including the sedating antihistamines. (Moderate) If concomitant use of dihydrocodeine and lithium is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Chlorpheniramine; Hydrocodone: (Moderate) Because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including the sedating antihistamines. (Moderate) If concomitant use of hydrocodone and lithium is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including the sedating antihistamines.
Chlorpheniramine; Phenylephrine: (Moderate) Because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including the sedating antihistamines.
Chlorpheniramine; Pseudoephedrine: (Moderate) Because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including the sedating antihistamines.
Chlorpromazine: (Major) Some atypical antipsychotics are considered first-line adjunctive therapy to mood stabilizers such as lithium. Because both chlorpromazine 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.
Cimetidine: (Moderate) Moderate to significant dietary sodium changes, or changes in sodium and fluid intake, may affect lithium excretion. Systemic sodium chloride administration may result in increased lithium excretion and therefore, decreased serum lithium concentrations. In addition, high fluid intake may increase lithium excretion. For patients receiving sodium-containing intravenous fluids, symptom control and lithium concentrations should be carefully monitored. It is recommended that patients taking lithium maintain consistent dietary sodium consumption and adequate fluid intake during the initial stabilization period and throughout lithium treatment. Supplemental oral sodium and fluid should be only be administered under careful medical supervision.
Ciprofloxacin: (Moderate) Concomitant use of ciprofloxacin and lithium may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Cisapride: (Contraindicated) Avoid concomitant use of lithium and cisapride due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Cisplatin: (Moderate) Closely monitor renal function, and monitor for signs and symptoms of lithium toxicity if coadministration with cisplatin is necessary. Cisplatin can cause nephrotoxicity. Lithium is renally eliminated; concomitant use of drugs that affect kidney function can increase lithium serum concentrations.
Citalopram: (Major) Concomitant use of citalopram and lithium 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. Monitor patients for signs and symptoms of serotonin syndrome during concomitant use, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome.
Clarithromycin: (Major) Concomitant use of lithium and clarithromycin 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.
Clemastine: (Moderate) Because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including the sedating antihistamines.
Clevidipine: (Moderate) Monitor for neurologic adverse reactions during concomitant use of lithium and calcium channel blockers. Concomitant use may increase the risk of neurologic adverse reactions, such as ataxia, tremors, nausea, vomiting, diarrhea, and/or tinnitus.
Clindamycin: (Moderate) Moderate to significant dietary sodium changes, or changes in sodium and fluid intake, may affect lithium excretion. Systemic sodium chloride administration may result in increased lithium excretion and therefore, decreased serum lithium concentrations. In addition, high fluid intake may increase lithium excretion. For patients receiving sodium-containing intravenous fluids, symptom control and lithium concentrations should be carefully monitored. It is recommended that patients taking lithium maintain consistent dietary sodium consumption and adequate fluid intake during the initial stabilization period and throughout lithium treatment. Supplemental oral sodium and fluid should be only be administered under careful medical supervision.
Clofazimine: (Moderate) Concomitant use of clofazimine and lithium may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Clozapine: (Major) Some atypical antipsychotics are considered first-line adjunctive therapy to mood stabilizers such as lithium. However, it is 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. Furthermore, lithium has been associated with QT prolongation. Treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death. The manufacturer of clozapine recommends caution during concurrent use with medications known to cause QT prolongation.
Codeine: (Moderate) If concomitant use of codeine and lithium is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Codeine; Guaifenesin: (Moderate) If concomitant use of codeine and lithium is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) If concomitant use of codeine and lithium is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of lithium and promethazine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. (Moderate) If concomitant use of codeine and lithium is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Codeine; Promethazine: (Moderate) Concomitant use of lithium and promethazine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. (Moderate) If concomitant use of codeine and lithium is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Colistin: (Moderate) Lithium can potentiate the neuromuscular blocking effect of colistimethate sodium by impairing transmission of impulses at the motor nerve terminals. If these drugs are used in combination, monitor patients for increased adverse effects. Neuromuscular blockade may be associated with colistimethate sodium, and is more likely to occur in patients with renal dysfunction.
Crizotinib: (Major) Avoid coadministration of crizotinib with lithium due to the risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib if QT prolongation occurs. Crizotinib has been associated with concentration-dependent QT prolongation. Lithium has also been associated with QT prolongation.
Cyclizine: (Moderate) Because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including the sedating antihistamines.
Dapagliflozin: (Moderate) Concomitant use of sodium-glucose cotransporter 2 (SGLT2) inhibitors with lithium may decrease serum lithium concentrations. Monitor serum lithium concentration more frequently during SGLT2 inhibitor initiation and dosage changes.
Dapagliflozin; Metformin: (Moderate) Concomitant use of sodium-glucose cotransporter 2 (SGLT2) inhibitors with lithium may decrease serum lithium concentrations. Monitor serum lithium concentration more frequently during SGLT2 inhibitor initiation and dosage changes.
Dapagliflozin; Saxagliptin: (Moderate) Concomitant use of sodium-glucose cotransporter 2 (SGLT2) inhibitors with lithium may decrease serum lithium concentrations. Monitor serum lithium concentration more frequently during SGLT2 inhibitor initiation and dosage changes. (Moderate) Lithium may cause variable effects on glycemic control when used in patients receiving antidiabetic therapy. Blood glucose concentrations should be closely monitored if lithium is taken by the patient. Dosage adjustments may be necessary.
Dasatinib: (Moderate) Concomitant use of lithium and dasatinib may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Degarelix: (Moderate) Concomitant use of lithium and androgen deprivation therapy (i.e., degarelix) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Desmopressin: (Moderate) The antidiuretic response to desmopressin may be reduced in patients receiving lithium concomitantly. Caution should be used when coadministering these agents.
Desvenlafaxine: (Major) Lithium is an effective augmenting agent to antidepressants in treatment-resistant depression; however, lithium has been reported to have central serotonin-enhancing effects and may interact pharmacodynamically with desvenlafaxine to cause serotonin syndrome. Serotonin syndrome is chara

cterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Patients should be informed of the possible increased risk of serotonin syndrome. If serotonin syndrome occurs, desvenlafaxine and lithium should be discontinued and symptomatic treatment should be initiated. One systematic review and meta-analysis of lithium augmentation of tricyclic and second generation antidepressants in major depression found no difference in discontinuation rate due to adverse events between the lithium and placebo groups. However, some data indicate that the elderly may have increased susceptibility to neurotoxicity (e.g., fine tremor, ataxia, severe memory impairment, and/or gait disturbances) from concurrent use of lithium and antidepressants, despite therapeutic lithium concentrations.
Deutetrabenazine: (Moderate) Use lithium with caution in combination with deutetrabenazine. Lithium has been associated with QT prolongation. 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.
Dexchlorpheniramine: (Moderate) Because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including the sedating antihistamines.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including the sedating antihistamines.
Dexmedetomidine: (Moderate) Concomitant use of dexmedetomidine and lithium may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Dextran: (Moderate) Moderate to significant dietary sodium changes, or changes in sodium and fluid intake, may affect lithium excretion. Systemic sodium chloride administration may result in increased lithium excretion and therefore, decreased serum lithium concentrations. In addition, high fluid intake may increase lithium excretion. For patients receiving sodium-containing intravenous fluids, symptom control and lithium concentrations should be carefully monitored. It is recommended that patients taking lithium maintain consistent dietary sodium consumption and adequate fluid intake during the initial stabilization period and throughout lithium treatment. Supplemental oral sodium and fluid should be only be administered under careful medical supervision.
Dextromethorphan; Quinidine: (Major) Concomitant use of quinidine and lithium 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.
Diltiazem: (Moderate) Monitor for neurologic adverse reactions during concomitant use of lithium and calcium channel blockers. Concomitant use may increase the risk of neurologic adverse reactions, such as ataxia, tremors, nausea, vomiting, diarrhea, and/or tinnitus.
Disopyramide: (Major) Concomitant use of lithium and disopyramide 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.
Disulfiram: (Major) Because lithium has the potential to impair cognitive and motor skills, it is advisable to avoid ethanol ingestion during treatment with lithium. In addition, some formulations of lithium solution contain alcohol; therefore, disulfiram should be avoided in patients receiving these products.
Dofetilide: (Major) Concomitant use of lithium and dofetilide 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.
Dolasetron: (Moderate) Administer dolasetron with caution in combination with lithium as concurrent use may increase the risk of QT prolongation; the risk of serotonin syndrome may also increase. Lithium has been associated with QT prolongation. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. If serotonin syndrome occurs, discontinue all serotonergic agents and initiate appropriate medical treatment.
Dolutegravir; Rilpivirine: (Moderate) Concomitant use of lithium and rilpivirine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Donepezil: (Major) Concomitant use of lithium and donepezil 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.
Donepezil; Memantine: (Major) Concomitant use of lithium and donepezil 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.
Dronabinol: (Major) Use caution if coadministration of dronabinol with lithium is necessary, and monitor for an increase in lithium plasma concentrations and lithium-related adverse effects. Additive dizziness, confusion, somnolence, and other CNS effects may also occur. Dronabinol is highly bound to plasma proteins, and may displace and increase the free fraction of other concomitantly administered protein-bound drugs; caution is recommended with other drugs with a narrow therapeutic index.
Dronedarone: (Contraindicated) Avoid concomitant use of lithium and dronedarone due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Droperidol: (Major) Lithium should be used cautiously and with close monitoring with droperidol. Lithium has been associated with QT prolongation. Droperidol should be administered with extreme caution to patients receiving other agents that may prolong the QT interval. Droperidol administration is associated with an established risk for QT prolongation and torsades de pointes (TdP). In December 2001, the FDA issued a black box warning regarding the use of droperidol and its association with QT prolongation and potential for cardiac arrhythmias based on post-marketing surveillance data. According to the revised 2001 labeling for droperidol, any drug known to have potential to prolong the QT interval should not be coadministered with droperidol.
Duloxetine: (Moderate) Lithium is an effective augmenting agent to antidepressants in treatment-resistant depression; however, lithium has central serotonin-enhancing effects and may increase the risk of serotonin syndrome when combined with SNRIs like duloxetine. Inform patients of the possible increased risk and monitor for serotonin syndrome, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, serotonergic agents should be discontinued and symptomatic treatment should be initiated.
Dupilumab: (Moderate) Coadministration of dupilumab may result in altered exposure to lithium. During chronic inflammation, increased levels of certain cytokines can alter the formation of CYP450 enzymes. Thus, the formation of CYP450 enzymes could be normalized during dupilumab administration. Clinically relevant drug interactions may occur with CYP450 substrates that have a narrow therapeutic index such as lithium. Monitor lithium concentrations if dupilumab is initiated or discontinued in a patient taking lithium; lithium dose adjustments may be needed.
Efavirenz: (Moderate) Concomitant use of lithium and efavirenz may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Concomitant use of lithium and efavirenz may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Concomitant use of lithium and efavirenz may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Eliglustat: (Major) Lithium should be used cautiously and with close monitoring with eliglustat. Lithium has been associated with QT prolongation. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations.
Empagliflozin: (Moderate) Concomitant use of sodium-glucose cotransporter 2 (SGLT2) inhibitors with lithium may decrease serum lithium concentrations. Monitor serum lithium concentration more frequently during SGLT2 inhibitor initiation and dosage changes.
Empagliflozin; Linagliptin: (Moderate) Concomitant use of sodium-glucose cotransporter 2 (SGLT2) inhibitors with lithium may decrease serum lithium concentrations. Monitor serum lithium concentration more frequently during SGLT2 inhibitor initiation and dosage changes.
Empagliflozin; Linagliptin; Metformin: (Moderate) Concomitant use of sodium-glucose cotransporter 2 (SGLT2) inhibitors with lithium may decrease serum lithium concentrations. Monitor serum lithium concentration more frequently during SGLT2 inhibitor initiation and dosage changes.
Empagliflozin; Metformin: (Moderate) Concomitant use of sodium-glucose cotransporter 2 (SGLT2) inhibitors with lithium may decrease serum lithium concentrations. Monitor serum lithium concentration more frequently during SGLT2 inhibitor initiation and dosage changes.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Concomitant use of lithium and rilpivirine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Concomitant use of lithium and rilpivirine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Encorafenib: (Major) Avoid coadministration of encorafenib and lithium due to QT prolongation. If concurrent use cannot be avoided, monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia and hypomagnesemia prior to treatment. Encorafenib is associated with dose-dependent prolongation of the QT interval. Lithium has also been associated with QT prolongation.
Entrectinib: (Major) Concomitant use of lithium and entrectinib 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.
Eplerenone: (Major) Although no drug interaction studies are known to have been conducted with eplerenone and lithium to date, lithium toxicity has been reported in patients receiving lithium concomitantly with diuretics (e.g., thiazides, spironolactone, triamterene) and ACE inhibitors. Through its effects on aldosterone, eplerenone promotes natruresis and therefore may stimulate a reflex increase in lithium and sodium reabsorption in the kidney. Therefore, if eplerenone is administered concomitantly with lithium, serum lithium levels should be monitored frequently.
Ergotamine; Caffeine: (Major) Caffeine appears to reduce serum lithium concentrations. Adverse reactions to lithium have also been noted to increase simultaneously with a reduction in caffeine intake. Patients taking lithium should be counseled regarding their intake of caffeine.
Eribulin: (Major) Concomitant use of lithium and eribulin 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.
Ertugliflozin: (Moderate) Concomitant use of sodium-glucose cotransporter 2 (SGLT2) inhibitors with lithium may decrease serum lithium concentrations. Monitor serum lithium concentration more frequently during SGLT2 inhibitor initiation and dosage changes.
Ertugliflozin; Metformin: (Moderate) Concomitant use of sodium-glucose cotransporter 2 (SGLT2) inhibitors with lithium may decrease serum lithium concentrations. Monitor serum lithium concentration more frequently during SGLT2 inhibitor initiation and dosage changes.
Ertugliflozin; Sitagliptin: (Moderate) Concomitant use of sodium-glucose cotransporter 2 (SGLT2) inhibitors with lithium may decrease serum lithium concentrations. Monitor serum lithium concentration more frequently during SGLT2 inhibitor initiation and dosage changes.
Erythromycin: (Major) Concomitant use of erythromycin and lithium 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.
Escitalopram: (Moderate) Coadministration of escitalopram and lithium may increase the risk for QT prolongation and serotonin syndrome. Lithium has been associated with QT prolongation and escitalopram also has this potential. Lithium is an effective augmenting agent to antidepressants in treatment-resistant depression; however, lithium has central serotonin-enhancing effects and may increase the risk of serotonin syndrome when combined with selective serotonin reuptake inhibitors (SSRIs) such as escitalopram. Inform patients of the possible increased risk and monitor for serotonin syndrome, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, serotonergic agents should be discontinued and symptomatic treatment should be initiated.
Felodipine: (Moderate) Monitor for neurologic adverse reactions during concomitant use of lithium and calcium channel blockers. Concomitant use may increase the risk of neurologic adverse reactions, such as ataxia, tremors, nausea, vomiting, diarrhea, and/or tinnitus.
Fenfluramine: (Moderate) Use fenfluramine and lithium with caution due to an increased risk of serotonin syndrome. Monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Fentanyl: (Moderate) If concomitant use of fentanyl and lithium is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Filgrastim, G-CSF: (Moderate) Lithium prompts the release of neutrophils and should be used with caution during filgrastim therapy. White blood cell counts above 100,000 cells/mm3 represent a medical emergency because of the risk of serious adverse effects such as brain infarction, respiratory failure, intracranial hemorrhage, retinal hemorrhage, myocardial infarction, and acute limb ischemia. Patients receiving lithium and filgrastim or pegfilgrastim should have more frequent monitoring of WBC counts.
Fingolimod: (Moderate) Concomitant use of lithium and fingolimod may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Flecainide: (Major) Concomitant use of flecainide and lithium 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.
Fluconazole: (Moderate) Concomitant use of fluconazole and lithium may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Fluoxetine: (Moderate) Coadministration of fluoxetine and lithium may increase the risk for QT prolongation and serotonin syndrome. Concurrent use of fluoxetine with lithium has also resulted in both increased and decreased serum lithium concentrations; patients should be monitored closely. QT prolongation has been reported in patients treated with fluoxetine and lithium has also been associated with QT prolongation. Lithium is an effective augmenting agent to antidepressants in treatment-resistant depression; however, lithium has central serotonin-enhancing effects and may increase the risk of serotonin syndrome when combined with selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine. Inform patients of the possible increased risk and monitor for serotonin syndrome, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, serotonergic agents should be discontinued and symptomatic treatment should be initiated.
Fluphenazine: (Moderate) Some atypical antipsychotics are considered first-line adjunctive therapy to mood stabilizers such as lithium. Because both fluphenazine 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.
Fluvoxamine: (Moderate) Concomitant use of fluvoxamine and lithium may increase the risk of serotonin syndrome and QT prolongation. Lithium has been associated with QT prolongation and there are reports of QT prolongation and TdP during postmarketing use of fluvoxamine. Lithium is an effective augmenting agent to antidepressants in treatment-resistant depression; however, lithium has central serotonin-enhancing effects and may increase the risk of serotonin syndrome when combined with selective serotonin reuptake inhibitors (SSRIs) such as fluvoxamine. Inform patients of the possible increased risk and monitor for serotonin syndrome, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, serotonergic agents should be discontinued and symptomatic treatment should be initiated.
Food: (Moderate) Excessive salt intake may result in increased lithium excretion and therefore, decreased serum lithium concentrations. In addition, high fluid intake may increase lithium excretion. It is recommended that patients taking lithium maintain consistent dietary sodium consumption and adequate fluid intake, during the initial stabilization period and throughout treatment . Moderate to significant dietary sodium changes may affect lithium excretion.
Foscarnet: (Major) When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as lithium. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). Lithium has also been associated with QT prolongation. If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment. Also, the risk of renal toxicity may be increased if foscarnet is used in conjunction with other nephrotoxic agents such as lithium.
Fosphenytoin: (Moderate) Monitor lithium and phenytoin concentrations during concomitant therapy with fosphenytoin and lithium; dosage adjustments may be necessary. Concomitant use may increase risk of adverse reactions of these drugs.
Fostemsavir: (Moderate) Concomitant use of lithium and fostemsavir may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with fostemsavir is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 4 times the recommended daily dose.
Gemcitabine: (Moderate) Moderate to significant dietary sodium changes, or changes in sodium and fluid intake, may affect lithium excretion. Systemic sodium chloride administration may result in increased lithium excretion and therefore, decreased serum lithium concentrations. In addition, high fluid intake may increase lithium excretion. For patients receiving sodium-containing intravenous fluids, symptom control and lithium concentrations should be carefully monitored. It is recommended that patients taking lithium maintain consistent dietary sodium consumption and adequate fluid intake during the initial stabilization period and throughout lithium treatment. Supplemental oral sodium and fluid should be only be administered under careful medical supervision.
Gemifloxacin: (Moderate) Concomitant use of lithium and gemifloxacin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Gemtuzumab Ozogamicin: (Moderate) Concomitant use of lithium and gemtuzumab ozogamicin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Gentamicin: (Moderate) Moderate to significant dietary sodium changes, or changes in sodium and fluid intake, may affect lithium excretion. Systemic sodium chloride administration may result in increased lithium excretion and therefore, decreased serum lithium concentrations. In addition, high fluid intake may increase lithium excretion. For patients receiving sodium-containing intravenous fluids, symptom control and lithium concentrations should be carefully monitored. It is recommended that patients taking lithium maintain consistent dietary sodium consumption and adequate fluid intake during the initial stabilization period and throughout lithium treatment. Supplemental oral sodium and fluid should be only be administered under careful medical supervision.
Gilteritinib: (Moderate) Concomitant use of lithium and gilteritinib may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Glasdegib: (Major) Avoid coadministration of glasdegib with lithium due to the potential for additive QT prolongation. If coadministration cannot be avoided, monitor patients for increased risk of QT prolongation with increased frequency of ECG monitoring. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. Lithium has also been associated with QT prolongation.
Goserelin: (Major) Concomitant use of lithium and goserelin acetate 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.
Granisetron: (Moderate) Use lithium with caution in combination with granisetron due to the risk of QT prolongation and serotonin syndrome. If serotonin syndrome is suspected, discontinue granisetron and concurrent serotonergic agents and initiate appropriate medical treatment. Both lithium and granisetron have been associated with QT prolongation.
Green Tea: (Major) Some, but not all, green tea products contain caffeine. Caffeine appears to reduce serum lithium concentrations. In 11 coffee drinking patients stabilized on lithium, serum lithium concentrations increased during 2 weeks when coffee was withheld and lithium concentrations fell when coffee consumption was resumed. Lithium ADRs have also been noted to increase simultaneously with a reduction in caffeine intake. If patients taking lithium want to change their caffeine intake, they should contact their health care professional.
Guaifenesin; Hydrocodone: (Moderate) If concomitant use of hydrocodone and lithium is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Halogenated Anesthetics: (Major) Concomitant use of lithium and halogenated anesthetics 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.
Haloperidol: (Moderate) Use lithium with caution in combination with haloperidol as concurrent use may increase the risk of QT prolongation, neuroleptic malignant syndrome (NMS), and extrapyramidal effects. Both drugs have been associated with QT prolongation. Torsade de pointes (TdP) has been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. NMS has been observed occasionally during concurrent use of lithium and either atypical or conventional antipsychotics. 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., 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.
Heparin: (Moderate) Moderate to significant dietary sodium changes, or changes in sodium and fluid intake, may affect lithium excretion. Systemic sodium chloride administration may result in increased lithium excretion and therefore, decreased serum lithium concentrations. In addition, high fluid intake may increase lithium excretion. For patients receiving sodium-containing intravenous fluids, symptom control and lithium concentrations should be carefully monitored. It is recommended that patients taking lithium maintain consistent dietary sodium consumption and adequate fluid intake during the initial stabilization period and throughout lithium treatment. Supplemental oral sodium and fluid should be only be administered under careful medical supervision.
Hetastarch: (Moderate) Moderate to significant dietary sodium changes, or changes in sodium and fluid intake, may affect lithium excretion. Systemic sodium chloride administration may result in increased lithium excretion and therefore, decreased serum lithium concentrations. In addition, high fluid intake may increase lithium excretion. For patients receiving sodium-containing intravenous fluids, symptom control and lithium concentrations should be carefully monitored. It is recommended that patients taking lithium maintain consistent dietary sodium consumption and adequate fluid intake during the initial stabilization period and throughout lithium treatment. Supplemental oral sodium and fluid should be only be administered under careful medical supervision.
Histrelin: (Moderate) Concomitant use of lithium and androgen deprivation therapy (i.e., histrelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Homatropine; Hydrocodone: (Moderate) If concomitant use of hydrocodone and lithium is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) Patients receiving lithium and methyldopa concomitantly can develop lithium toxicity. Interestingly, lithium levels may appear to be in the therapeutic range while signs of lithium toxicity are evident. Therefore, plasma lithium concentrations are not an accurate indicator of lithium toxicity in patients receiving concurrent methyldopa therapy.
Hydrocodone: (Moderate) If concomitant use of hydrocodone and lithium is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Hydrocodone; Ibuprofen: (Moderate) If concomitant use of hydrocodone and lithium is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Hydrocodone; Pseudoephedrine: (Moderate) If concomitant use of hydrocodone and lithium is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Hydromorphone: (Moderate) If concomitant use of hydromorphone and lithium is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Hydroxychloroquine: (Major) Concomitant use of hydroxychloroquine and lithium 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) Concomitant use of hydroxyzine and lithium may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Major) Theoretically, concurrent use of methylene blue and lithium may increase the risk of serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and lithium is thought to increase central serotonin effects by various mechanisms. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other psychiatric serotonergic agents with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death. If serotonin syndrome is suspected, serotonergic agents should be discontinued and appropriate medical treatment should be implemented.
Ibritumomab Tiuxetan: (Moderate) Moderate to significant dietary sodium changes, or changes in sodium and fluid intake, may affect lithium excretion. Systemic sodium chloride administration may result in increased lithium excretion and therefore, decreased serum lithium concentrations. In addition, high fluid intake may increase lithium excretion. For patients receiving sodium-containing intravenous fluids, symptom control and lithium concentrations should be carefully monitored. It is recommended that patients taking lithium maintain consistent dietary sodium consumption and adequate fluid intake during the initial stabilization period and throughout lithium treatment. Supplemental oral sodium and fluid should be only be administered under careful medical supervision.
Ibuprofen; Oxycodone: (Moderate) If concomitant use of oxycodone and lithium is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Ibutilide: (Major) Ibutilide should be used cautiously and with close monitoring with lithium. Lithium has been associated with QT prolongation. Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Iloperidone: (Major) Iloperidone and lithium are associated with QT prolongation. Coadministration may increase the risk of QT prolongation; therefore, iloperidone and lithium should be coadministered with caution and close monitoring. Some atypical antipsychotics are considered first-line adjunctive therapy to mood stabilizers such as lithium. However, it is 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., 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.
Indapamide: (Moderate) The risk of lithium toxicity may be increased in patients receiving medications that affect kidney function and sodium excretion, such as indapamide. Monitor serum lithium levels closely and adjust the lithium dosage if necessary. One case of severe lithium toxicity occurred in an adult male patient with bipolar disorder after the addition of indapamide to a prior regimen which included lithium. The baseline lithium concentration was not reported; however, after one week of treatment with indapamide, the patient presented to the emergency room with a lithium serum concentration of 3.93 mEq/Liter and symptoms of severe toxicity. The patient recovered and returned to his prior lithium regimen after receiving hemodialysis and stopping therapy with indapamide.
Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with lithium due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Both inotuzumab and lithium have been associated with QT interval prolongation.
Insulins: (Moderate) Monitor blood glucose during concomitant insulin and lithium use; an insulin dose adjustment may be necessary. Lithium may increase or decrease the blood glucose lowering effect of insulin.
Iodine; Potassium Iodide, KI: (Moderate) Lithium can precipitate goiter and/or hypothyroidism. Concomitant use of lithium and potassium iodide, KI can increase the likelihood of this adverse reaction.
Isocarboxazid: (Moderate) There is an increased risk of serotonin syndrome during concurrent use of lithium and nonselective monoamine oxidase inhibitors (MAOIs). Lithium has central serotonergic actions and MAOIs impair the metabolism of serotonin. If concurrent use is necessary, monitor for the emergence of serotonin syndrome and inform patients of the increased risk. If serotonin syndrome is suspected, serotonergic agents should be discontinued and appropriate medical treatment should be implemented.
Isradipine: (Moderate) Monitor for neurologic adverse reactions during concomitant use of lithium and calcium channel blockers. Concomitant use may increase the risk of neurologic adverse reactions, such as ataxia, tremors, nausea, vomiting, diarrhea, and/or tinnitus.
Itraconazole: (Moderate) Concomitant use of lithium and itraconazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Ivosidenib: (Major) Avoid coadministration of ivosidenib with lithium due to an increased risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. An interruption of therapy and dose reduction of ivosidenib may be necessary if QT prolongation occurs. Prolongation of the QTc interval and ventricular arrhythmias have been reported in patients treated with ivosidenib. Lithium has also been associated with QT prolongation.
Ketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and lithium due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. Lithium has been associated with QT prolongation; ketoconazole is associated with QT prolongation and TdP.
Labetalol: (Moderate) Moderate to significant dietary sodium changes, or changes in sodium and fluid intake, may affect lithium excretion. Systemic sodium chloride administration may result in increased lithium excretion and therefore, decreased serum lithium concentrations. In addition, high fluid intake may increase lithium excretion. For patients receiving sodium-containing intravenous fluids, symptom control and lithium concentrations should be carefully monitored. It is recommended that patients taking lithium maintain consistent dietary sodium consumption and adequate fluid intake during the initial stabilization period and throughout lithium treatment. Supplemental oral sodium and fluid should be only be administered under careful medical supervision.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Concomitant use of lithium and clarithromycin 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.
Lapatinib: (Moderate) Concomitant use of lithium and lapatinib may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Lasmiditan: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and lithium. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Lefamulin: (Major) Avoid coadministration of lefamulin with lithium as concurrent use may increase the risk of QT prolongation. If coadministration cannot be avoided, monitor ECG during treatment. Lefamulin has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown. Lithium has been associated with QT prolongation.
Lenvatinib: (Major) Concomitant use of lithium and lenvatinib 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.
Leuprolide: (Moderate) Concomitant use of lithium and androgen deprivation therapy (i.e., leuprolide) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Leuprolide; Norethindrone: (Moderate) Concomitant use of lithium and androgen deprivation therapy (i.e., leuprolide) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Levamlodipine: (Moderate) Monitor for neurologic adverse reactions during concomitant use of lithium and calcium channel blockers. Concomitant use may increase the risk of neurologic adverse reactions, such as ataxia, tremors, nausea, vomiting, diarrhea, and/or tinnitus.
Levetiracetam: (Moderate) Moderate to significant dietary sodium changes, or changes in sodium and fluid intake, may affect lithium excretion. Systemic sodium chloride administration may result in increased lithium excretion and therefore, decreased serum lithium concentrations. In addition, high fluid intake may increase lithium excretion. For patients receiving sodium-containing intravenous fluids, symptom control and lithium concentrations should be carefully monitored. It is recommended that patients taking lithium maintain consistent dietary sodium consumption and adequate fluid intake during the initial stabilization period and throughout lithium treatment. Supplemental oral sodium and fluid should be only be administered under careful medical supervision.
Levofloxacin: (Moderate) Concomitant use of levofloxacin and lithium may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Levoketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and lithium due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. Lithium has been associated with QT prolongation; ketoconazole is associated with QT prolongation and TdP.
Levomilnacipran: (Major) Lithium is an effective augmenting agent to antidepressants in treatment-resistant depression; however, lithium has been reported to have central serotonin-enhancing effects and may interact pharmacodynamically with levomilnacipran to cause serotonin syndrome. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Patients should be informed of the possible increased risk of serotonin syndrome. If serotonin syndrome occurs, levomilnacipran and lithium should be discontinued and symptomatic treatment should be initiated. One systematic review and meta-analysis of lithium augmentation of tricyclic and second generation antidepressants in major depression found no difference in discontinuation rate due to adverse events between the lithium and placebo groups. However, some data indicate that the elderly may have increased susceptibility to neurotoxicity (e.g., fine tremor, ataxia, severe memory impairment, and/or gait disturbances) from concurrent use of lithium and antidepressants, despite therapeutic lithium concentrations.
Levorphanol: (Moderate) If concomitant use of levorphanol and lithium is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Linezolid: (Major) There is an increased risk of serotonin syndrome during concurrent use of drugs with central serotonergic properties such as lithium and linezolid. Signs and symptoms of serotonin syndrome include autonomic instability (e.g., labile blood pressure, tachycardia, diaphoresis, dizziness, hyperthermia), mental status changes (e.g., delirium, confusion, coma), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), gastrointestinal effects (e.g., nausea, vomiting, diarrhea), seizures, and in rare cases, death. If concurrent use is necessary, monitor for the emergence of serotonin syndrome and inform patients of the increased risk. If serotonin syndrome is suspected, serotonergic agents should be discontinued and appropriate medical treatment should be implemented.
Lisdexamfetamine: (Major) Use a lower initial lisdexamfetamine dose with concomitant lithium therapy and monitor for serotonin syndrome, particularly during initation or dosage increases. If serotonin syndrome occurs, discontinue lisdexamfetamine and consider discontinuation of lithium. Concomitant use increases the risk of serotonin syndrome.
Lofexidine: (Moderate) Monitor ECG if lofexidine is coadministered with lithium due to the potential for additive QT prolongation. Lofexidine prolongs the QT interval. In addition, there are postmarketing reports of torsade de pointes. Lithium has been associated with QT prolongation.
Loop diuretics: (Moderate) Monitor serum electrolyte and lithium concentrations during concomitant loop diuretic use; reduce the lithium dose based on serum lithium concentration and clinical response. Diuretic-induced sodium loss may reduce lithium clearance and increase lithium serum concentrations.
Loperamide: (Moderate) Loperamide should be used cautiously and with close monitoring with lithium. Lithium has been associated with QT prolongation and high doses of loperamide have been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Coadministration may further increase the risk of QT prolongation and TdP.
Loperamide; Simethicone: (Moderate) Loperamide should be used cautiously and with close monitoring with lithium. Lithium has been associated with QT prolongation and high doses of loperamide have been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Coadministration may further increase the risk of QT prolongation and TdP.
Lopinavir; Ritonavir: (Major) Concomitant use of lopinavir and lithium 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.
Lorcaserin: (Moderate) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, lithium. Patients receiving this combination should be monitored for the emergence of serotonin syndrome or Neuroleptic Malignant Syndrome (NMS) like signs and symptoms.
Loxapine: (Moderate) It is advisable to monitor patients for neurotoxicity during co-administration of lithium and loxapine. Although conventional antipsychotics are considered a treatment option as adjuncts to mood stabilizers such as lithium, neuroleptic malignant syndrome (NMS) and extrapyramidal effects have been observed occasionally during concurrent use. 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., 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.
Lurasidone: (Moderate) Some atypical antipsychotics are considered first-line adjunctive therapy to mood stabilizers such as lithium. However, it is 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., 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. Lurasidone does not significantly change the pharmacokinetic parameters of lithium.
Macimorelin: (Major) Avoid concurrent administration of macimorelin with drugs that prolong the QT interval, such as lithium. Use of these drugs together may increase the risk of developing torsade de pointes-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval. Lithium has been associated with QT prolongation.
Mannitol: (Major) Concomitant use of mannitol and lithium may initially increase the elimination of lithium but may also increase the risk of lithium toxicity if the patient develops hypovolemia or renal impairment. Consider holding lithium doses during mannitol treatment. In patients requiring concomitant use, frequently monitor serum lithium concentrations and for signs of lithium toxicity.
Maprotiline: (Major) Coadministration of maprotiline and lithium may increase the risk of QT prolongation; therefore, caution and close monitoring are recommended during coadministration. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Lithium has been associated with QT prolongation.
Meclizine: (Moderate) Because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including meclizine.
Mefloquine: (Moderate) Concomitant use of lithium and mefloquine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Meglitinides: (Moderate) Lithium may cause variable effects on glycemic control when used in patients receiving antidiabetic agents. Monitor blood glucose concentrations closely if lithium is coadministered with antidiabetic agents. Dosage adjustments of antidiabetic agents may be necessary.
rong>Meperidine: (Moderate) If concomitant use of meperidine and lithium is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Metformin; Saxagliptin: (Moderate) Lithium may cause variable effects on glycemic control when used in patients receiving antidiabetic therapy. Blood glucose concentrations should be closely monitored if lithium is taken by the patient. Dosage adjustments may be necessary.
Methadone: (Major) Concomitant use of lithium and methadone 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.
Methamphetamine: (Moderate) Coadministration of amphetamines and lithium may increase the risk of serotonin syndrome. At high doses, amphetamines can increase serotonin release, as well as act as serotonin agonists. Lithium has central serotonergic effects. Inform patients of the possible increased risk and monitor for serotonin syndrome, particularly during treatment initiation, after a dose increase, or the addition of other serotonergic medications. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Major) Theoretically, concurrent use of methylene blue and lithium may increase the risk of serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and lithium is thought to increase central serotonin effects by various mechanisms. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other psychiatric serotonergic agents with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death. If serotonin syndrome is suspected, serotonergic agents should be discontinued and appropriate medical treatment should be implemented.
Methohexital: (Moderate) Because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including anxiolytics, sedatives, and hypnotics.
Methotrexate: (Major) Avoid concomitant use of methotrexate with lithium due to the risk of additive nephrotoxicity as well as an increased risk of severe methotrexate-related adverse reactions. If concomitant use is unavoidable, closely monitor for adverse reactions. Lithium and methotrexate are both nephrotoxic drugs; methotrexate is also renally eliminated. Coadministration of methotrexate with lithium may result in decreased renal function as well as increased methotrexate plasma concentrations.
Methyldopa: (Moderate) Patients receiving lithium and methyldopa concomitantly can develop lithium toxicity. Interestingly, lithium levels may appear to be in the therapeutic range while signs of lithium toxicity are evident. Therefore, plasma lithium concentrations are not an accurate indicator of lithium toxicity in patients receiving concurrent methyldopa therapy.
Methylene Blue: (Major) Theoretically, concurrent use of methylene blue and lithium may increase the risk of serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and lithium is thought to increase central serotonin effects by various mechanisms. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other psychiatric serotonergic agents with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death. If serotonin syndrome is suspected, serotonergic agents should be discontinued and appropriate medical treatment should be implemented.
Methylphenidate Derivatives: (Moderate) Monitor for serotonin syndrome, particularly during lithium initiation, during concomitant methylphenidate use. If serotonin syndrome occurs, consider discontinuation of lithium and/or methylphenidate.
Metronidazole: (Moderate) Concomitant use of lithium and metronidazole may increase serum lithium concentrations and increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Monitor serum lithium concentrations; reduce the lithium dose based on lithium serum concentrations and clinical response. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Midostaurin: (Major) Concomitant use of lithium and midostaurin 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.
Mifepristone: (Major) Concomitant use of mifepristone and lithium 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.
Miglitol: (Moderate) Lithium may cause variable effects on glycemic control when used in patients receiving antidiabetic agents. Monitor blood glucose concentrations closely if lithium is coadministered with antidiabetic agents. Dosage adjustments of antidiabetic agents may be necessary.
Milnacipran: (Major) Lithium is an effective augmenting agent to antidepressants in treatment-resistant depression; however, lithium has been reported to have central serotonin-enhancing effects and may interact pharmacodynamically with milnacipran to cause serotonin syndrome. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Patients should be informed of the possible increased risk of serotonin syndrome. If serotonin syndrome occurs, milnacipran and lithium should be discontinued and symptomatic treatment should be initiated. One systematic review and meta-analysis of lithium augmentation of tricyclic and second generation antidepressants in major depression found no difference in discontinuation rate due to adverse events between the lithium and placebo groups. However, some data indicate that the elderly may have increased susceptibility to neurotoxicity (e.g., fine tremor, ataxia, severe memory impairment, and/or gait disturbances) from concurrent use of lithium and antidepressants, despite therapeutic lithium concentrations. There does not appear to be a pharmacokinetic interaction between lithium and milnacipran.
Mirtazapine: (Moderate) Concomitant use of lithium and mirtazapine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. Monitor patients for signs and symptoms of serotonin syndrome during concomitant use, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome.
Mobocertinib: (Major) Concomitant use of mobocertinib and lithium increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Molindone: (Moderate) It is advisable to monitor patients for neurotoxicity during co-administration of lithium and molindone. Although conventional antipsychotics are considered a treatment option as adjuncts to mood stabilizers such as lithium, neuroleptic malignant syndrome (NMS) and extrapyramidal effects have been observed occasionally during concurrent use. 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., 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.
Monoamine oxidase inhibitors: (Moderate) There is an increased risk of serotonin syndrome during concurrent use of lithium and nonselective monoamine oxidase inhibitors (MAOIs). Lithium has central serotonergic actions and MAOIs impair the metabolism of serotonin. If concurrent use is necessary, monitor for the emergence of serotonin syndrome and inform patients of the increased risk. If serotonin syndrome is suspected, serotonergic agents should be discontinued and appropriate medical treatment should be implemented.
Morphine: (Moderate) If concomitant use of morphine and lithium is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Morphine; Naltrexone: (Moderate) If concomitant use of morphine and lithium is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Moxifloxacin: (Major) Concomitant use of moxifloxacin and lithium 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. (Moderate) Moderate to significant dietary sodium changes, or changes in sodium and fluid intake, may affect lithium excretion. Systemic sodium chloride administration may result in increased lithium excretion and therefore, decreased serum lithium concentrations. In addition, high fluid intake may increase lithium excretion. For patients receiving sodium-containing intravenous fluids, symptom control and lithium concentrations should be carefully monitored. It is recommended that patients taking lithium maintain consistent dietary sodium consumption and adequate fluid intake during the initial stabilization period and throughout lithium treatment. Supplemental oral sodium and fluid should be only be administered under careful medical supervision.
Nabilone: (Moderate) Concomitant use of nabilone with lithium can potentiate the effects of cannabinoids on drowsiness and CNS depression.
Nalbuphine: (Moderate) If concomitant use of nalbuphine and lithium is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Netupitant, Fosnetupitant; Palonosetron: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering palonosetron with other drugs that have serotonergic properties such as lithium. If serotonin syndrome is suspected, discontinue palonosetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
Neuromuscular blockers: (Moderate) Concomitant use of neuromuscular blockers and lithium may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Nicardipine: (Moderate) Moderate to significant dietary sodium changes, or changes in sodium and fluid intake, may affect lithium excretion. Systemic sodium chloride administration may result in increased lithium excretion and therefore, decreased serum lithium concentrations. In addition, high fluid intake may increase lithium excretion. For patients receiving sodium-containing intravenous fluids, symptom control and lithium concentrations should be carefully monitored. It is recommended that patients taking lithium maintain consistent dietary sodium consumption and adequate fluid intake during the initial stabilization period and throughout lithium treatment. Supplemental oral sodium and fluid should be only be administered under careful medical supervision. (Moderate) Monitor for neurologic adverse reactions during concomitant use of lithium and calcium channel blockers. Concomitant use may increase the risk of neurologic adverse reactions, such as ataxia, tremors, nausea, vomiting, diarrhea, and/or tinnitus.
Nifedipine: (Moderate) Monitor for neurologic adverse reactions during concomitant use of lithium and calcium channel blockers. Concomitant use may increase the risk of neurologic adverse reactions, such as ataxia, tremors, nausea, vomiting, diarrhea, and/or tinnitus.
Nilotinib: (Major) Concomitant use of lithium and nilotinib 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.
Nimodipine: (Moderate) Monitor for neurologic adverse reactions during concomitant use of lithium and calcium channel blockers. Concomitant use may increase the risk of neurologic adverse reactions, such as ataxia, tremors, nausea, vomiting, diarrhea, and/or tinnitus.
Nisoldipine: (Moderate) Monitor for neurologic adverse reactions during concomitant use of lithium and calcium channel blockers. Concomitant use may increase the risk of neurologic adverse reactions, such as ataxia, tremors, nausea, vomiting, diarrhea, and/or tinnitus.
Nonsteroidal antiinflammatory drugs: (Moderate) Monitor serum lithium concentrations during concomitant nonsteroidal anti-inflammatory (NSAID) use; reduce the lithium dose based on serum lithium concentrations and clinical response. NSAIDs decrease renal blood flow, resulting in decreased renal clearance and increased serum lithium concentrations.
Norepinephrine: (Moderate) Moderate to significant dietary sodium changes, or changes in sodium and fluid intake, may affect lithium excretion. Systemic sodium chloride administration may result in increased lithium excretion and therefore, decreased serum lithium concentrations. In addition, high fluid intake may increase lithium excretion. For patients receiving sodium-containing intravenous fluids, symptom control and lithium concentrations should be carefully monitored. It is recommended that patients taking lithium maintain consistent dietary sodium consumption and adequate fluid intake during the initial stabilization period and throughout lithium treatment. Supplemental oral sodium and fluid should be only be administered under careful medical supervision.
Ofloxacin: (Moderate) Concomitant use of ofloxacin and lithium may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Olanzapine: (Moderate) Olanzapine and lithium are associated with QT prolongation. Coadministration may increase the risk of QT prolongation; therefore, olanzapine and lithium should be coadministered with caution and close monitoring. Some atypical antipsychotics, including olanzapine, are indicated as adjunctive therapy to mood stabilizers such as lithium. However, it is 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., 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. Olanzapine does not influence the pharmacokinetics of lithium.
Olanzapine; Fluoxetine: (Moderate) Coadministration of fluoxetine and lithium may increase the risk for QT prolongation and serotonin syndrome. Concurrent use of fluoxetine with lithium has also resulted in both increased and decreased serum lithium concentrations; patients should be monitored closely. QT prolongation has been reported in patients treated with fluoxetine and lithium has also been associated with QT prolongation. Lithium is an effective augmenting agent to antidepressants in treatment-resistant depression; however, lithium has central serotonin-enhancing effects and may increase the risk of serotonin syndrome when combined with selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine. Inform patients of the possible increased risk and monitor for serotonin syndrome, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, serotonergic agents should be discontinued and symptomatic treatment should be initiated. (Moderate) Olanzapine and lithium are associated with QT prolongation. Coadministration may increase the risk of QT prolongation; therefore, olanzapine and lithium should be coadministered with caution and close monitoring. Some atypical antipsychotics, including olanzapine, are indicated as adjunctive therapy to mood stabilizers such as lithium. However, it is 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., 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. Olanzapine does not influence the pharmacokinetics of lithium.
Olanzapine; Samidorphan: (Moderate) Olanzapine and lithium are associated with QT prolongation. Coadministration may increase the risk of QT prolongation; therefore, olanzapine and lithium should be coadministered with caution and close monitoring. Some atypical antipsychotics, including olanzapine, are indicated as adjunctive therapy to mood stabilizers such as lithium. However, it is 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., 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. Olanzapine does not influence the pharmacokinetics of lithium.
Oliceridine: (Moderate) If concomitant use of oliceridine and lithium is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for neurologic adverse reactions during concomitant use of lithium and calcium channel blockers. Concomitant use may increase the risk of neurologic adverse reactions, such as ataxia, tremors, nausea, vomiting, diarrhea, and/or tinnitus.
Ondansetron: (Major) Due to the potential for QT prolongation, cautious use and close monitoring are advisable if concurrent use of lithium and ondansetron is necessary. Both medications may cause QT interval prolongation and a risk for torsade de pointes (TdP). ECG monitoring has been recommended for at-risk patients. In addition, concurrent use of ondansetron with other drugs that modulate serotonergic function, such as lithium, has resulted in serotonin syndrome in some cases. Patients should be carefully observed, particularly during treatment initiation and during dose adjustments. Discontinue the serotonergic medications if serotonin syndrome is suspected. (Moderate) Moderate to significant dietary sodium changes, or changes in sodium and fluid intake, may affect lithium excretion. Systemic sodium chloride administration may result in increased lithium excretion and therefore, decreased serum lithium concentrations. In addition, high fluid intake may increase lithium excretion. For patients receiving sodium-containing intravenous fluids, symptom control and lithium concentrations should be carefully monitored. It is recommended that patients taking lithium maintain consistent dietary sodium consumption and adequate fluid intake during the initial stabilization period and throughout lithium treatment. Supplemental oral sodium and fluid should be only be administered under careful medical supervision.
Osilodrostat: (Moderate) Concomitant use of lithium and osilodrostat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Osimertinib: (Major) Concomitant use of osimertinib and lithium 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.
Oxaliplatin: (Major) Avoid coadministration of oxaliplatin with lithium due to the risk of increased oxaliplatin-related adverse reactions; there is also an increased risk of QT prolongation. Lithium is known to be potentially nephrotoxic; because platinum-containing drugs like oxaliplatin are eliminated primarily through the kidney, oxaliplatin clearance may be decreased by coadministration with nephrotoxic agents. Additionally, lithium has been associated with QT prolongation. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
Oxycodone: (Moderate) If concomitant use of oxycodone and lithium is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Oxymorphone: (Moderate) If concomitant use of oxymorphone and lithium is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Ozanimod: (Major) In general, do not initiate ozanimod in patients taking lithium due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). Additionally, there is a potential for hypertensive crisis and serotonin syndrome. If treatment initiation is considered, seek advice from a cardiologist and monitor for hypertension and serotonergic effects. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis and serotonin syndome. There is an increased risk of serotonin syndrome during concurrent use of drugs with central serotonergic properties such as lithium and MAO inhibitors. Ozanimod may also result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Lithium is a serotonergic drug that has been associated with QT prolongation.
Pacritinib: (Major) Concomitant use of pacritinib and lithium increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Paliperidone: (Major) Paliperidone and lithium are associated with QT prolongation. Torsade de pointes (TdP) and ventricular fibrillation have been reported in the setting of paliperidone overdose. Coadministration may increase the risk of QT prolongation and neurotoxicity and close monitoring is recommended. Neuroleptic malignant syndrome (NMS) has been observed occasionally during 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 coadministration of lithium and atypical antipsychotics (e.g., 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. A pharmacokinetic interaction between lithium and paliperidone is unlikely.
Palonosetron: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering palonosetron with other drugs that have serotonergic properties such as lithium. If serotonin syndrome is suspected, discontinue palonosetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
Panobinostat: (Major) Concomitant use of panobinostat and lithium 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.
Paroxetine: (Moderate) Lithium is an effective augmenting agent to antidepressants in treatment-resistant depression; however, lithium has central serotonin-enhancing effects and may increase the risk of serotonin syndrome when combined with selective serotonin reuptake inhibitors (SSRIs) such as paroxetine. Inform patients of the possible increased risk and monitor for serotonin syndrome, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, serotonergic agents should be discontinued and symptomatic treatment should be initiated.
Pasireotide: (Moderate) Concomitant use of lithium and pasireotide may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Pazopanib: (Major) Concomitant use of pazopanib and lithium 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.
Pegfilgrastim: (Moderate) Lithium prompts the release of neutrophils and should be used with caution during filgrastim therapy. White blood cell counts above 100,000 cells/mm3 represent a medical emergency because of the risk of serious adverse effects such as brain infarction, respiratory failure, intracranial hemorrhage, retinal hemorrhage, myocardial infarction, and acute limb ischemia. Patients receiving lithium and filgrastim or pegfilgrastim should have more frequent monitoring of WBC counts.
Pentamidine: (Major) Concomitant use of pentamidine and lithium 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.
Pentobarbital: (Moderate) Because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including anxiolytics, sedatives, and hypnotics.
Perindopril; Amlodipine: (Moderate) Monitor for neurologic adverse reactions during concomitant use of lithium and calcium channel blockers. Concomitant use may increase the risk of neurologic adverse reactions, such as ataxia, tremors, nausea, vomiting, diarrhea, and/or tinnitus.
Perphenazine: (Moderate) Some atypical antipsychotics are considered first-line adjunctive therapy to mood stabilizers such as lithium. Because both perphenazine 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.
Perphenazine; Amitriptyline: (Moderate) Some atypical antipsychotics are considered first-line adjunctive therapy to mood stabilizers such as lithium. Because both perphenazine 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.
Phendimetrazine: (Moderate) Psychostimulants, such as phendimetrazine, can occasionally worsen mania in those with bipolar disorder, potentially reducing the overall effectiveness of treatment with mood stabilizers. According to some literature and the product labeling of many stimulants, lithium may antagonize the anorectic and stimulant effects of amphetamines. Despite this precaution, some data indicate a beneficial effect based upon the clinical circumstances of the patient. Further study is needed to fully assess the benefits and risks that may occur from concomitant administration of psychostimulants and lithium. Close monitoring is advisable when combination therapy is initiated or dosages are increased.
Phenelzine: (Moderate) There is an increased risk of serotonin syndrome during concurrent use of lithium and nonselective monoamine oxidase inhibitors (MAOIs). Lithium has central serotonergic actions and MAOIs impair the metabolism of serotonin. If concurrent use is necessary, monitor for the emergence of serotonin syndrome and inform patients of the increased risk. If serotonin syndrome is suspected, serotonergic agents should be discontinued and appropriate medical treatment should be implemented.
Phenobarbital: (Moderate) Because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including anxiolytics, sedatives, and hypnotics.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including anxiolytics, sedatives, and hypnotics.
Phentermine; Topiramate: (Moderate) Monitor serum lithium concentrations during concomitant high-dose topiramate use. Lithium concentrations were unaffected during treatment with topiramate 200 mg/day; however, there was an observed increase in systemic exposure of lithium (26%) after topiramate doses up to 600 mg/day.
Phenytoin: (Moderate) Monitor lithium and phenytoin concentrations during concomitant therapy; dosage adjustments may be necessary. Concomitant use may increase risk of adverse reactions of these drugs.
Pimavanserin: (Major) Concomitant use of pimavanserin and lithium 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.
Pimozide: (Contraindicated) Lithium has been associated with QT prolongation. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of lithium with pimozide is contraindicated. Additionally, some atypical antipsychotics are considered first-line adjunctive therapy to mood stabilizers such as lithium. However, it is 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.
Pitolisant: (Major) Concomitant use of pitolisant and lithium 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.
Ponesimod: (Major) In general, do not initiate ponesimod in patients taking lithium due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ponesimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ponesimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Lithium has been associated with QT prolongation.
Posaconazole: (Moderate) Concomitant use of lithium and posaconazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Potassium Chloride: (Moderate) Moderate to significant dietary sodium changes, or changes in sodium and fluid intake, may affect lithium excretion. Systemic sodium chloride administration may result in increased lithium excretion and therefore, decreased serum lithium concentrations. In addition, high fluid intake may increase lithium excretion. For patients receiving sodium-containing intravenous fluids, symptom control and lithium concentrations should be carefully monitored. It is recommended that patients taking lithium maintain consistent dietary sodium consumption and adequate fluid intake during the initial stabilization period and throughout lithium treatment. Supplemental oral sodium and fluid should be only be administered under careful medical supervision.
Potassium Iodide, KI: (Moderate) Lithium can precipitate goiter and/or hypothyroidism. Concomitant use of lithium and potassium iodide, KI can increase the likelihood of this adverse reaction.
Potassium-sparing diuretics: (Minor) The risk of lithium toxicity may be increased in patients receiving medications that affect kidney function and sodium excretion, such as diuretics. However, concurrent use of potassium-sparing diuretics (e.g., amiloride, spironolactone, triamterene) with lithium is generally regarded as safe. Lithium is primarily reabsorbed from the proximal tubules whereas potassium-sparing diuretics inhibit the endothelial sodium channel in the renal collecting duct thereby inhibiting reabsorption of sodium and lithium. In one small study evaluating concurrent use of lithium and spironolactone, lithium clearance was increased by 16%, which was not considered clinically significant. Amiloride has been safely used as a reversal agent for lithium-induced nephrogenic diabetes insipidus. There is a lack of evidence to evaluate the effect of lithium and triamterene co-administration, however, a significant interaction would not be expected due to the pharmacologic similarities with other potassium-sparing diuretics.
Pramlintide: (Moderate) Lithium may cause variable effects on glycemic control when used in patients receiving antidiabetic agents. Monitor blood glucose concentrations closely if lithium is coadministered with antidiabetic agents. Dosage adjustments of pramlintide may be necessary.
Primaquine: (Moderate) Concomitant use of lithium and primaquine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Primidone: (Moderate) Because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including anxiolytics, sedatives, and hypnotics.
Procainamide: (Major) Concomitant use of procainamide and lithium 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.
Prochlorperazine: (Moderate) Some atypical antipsychotics are considered first-line adjunctive therapy to mood stabilizers such as lithium. Because both prochlorperazine 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.
Promethazine: (Moderate) Concomitant use of lithium and promethazine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Promethazine; Dextromethorphan: (Moderate) Concomitant use of lithium and promethazine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Promethazine; Phenylephrine: (Moderate) Concomitant use of lithium and promethazine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Propafenone: (Major) Concomitant use of propafenone and lithium 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.
Pseudoephedrine; Triprolidine: (Moderate) Because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including the sedating antihistamines.
Pyrilamine: (Moderate) Because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including the sedating antihistamines.
Quetiapine: (Major) Concomitant use of lithium and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP) as well as an encephalopathic syndrome that may be similar to or the same as neuroleptic malignant syndrome. 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. Monitor for early evidence of neurologic toxicity and discontinue treatment promptly if such signs appear. An encephalopathic syndrome has occurred in a few patients treated with lithium plus a neuroleptic. In some instances, the syndrome was followed by irreversible brain damage.
Quinidine: (Major) Concomitant use of quinidine and lithium 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.
Quinine: (Major) Concomitant use of quinine and lithium 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.
Quizartinib: (Major) Concomitant use of quizartinib and lithium 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.
Ramelteon: (Moderate) Because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including anxiolytics, sedatives, and hypnotics.
Ranolazine: (Moderate) Concomitant use of lithium and ranolazine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Regular Insulin: (Moderate) Moderate to significant dietary sodium changes, or changes in sodium and fluid intake, may affect lithium excretion. Systemic sodium chloride administration may result in increased lithium excretion and therefore, decreased serum lithium concentrations. In addition, high fluid intake may increase lithium excretion. For patients receiving sodium-containing intravenous fluids, symptom control and lithium concentrations should be carefully monitored. It is recommended that patients taking lithium maintain consistent dietary sodium consumption and adequate fluid intake during the initial stabilization period and throughout lithium treatment. Supplemental oral sodium and fluid should be only be administered under careful medical supervision.
Relugolix: (Moderate) Concomitant use of lithium and androgen deprivation therapy (i.e., relugolix) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Relugolix; Estradiol; Norethindrone acetate: (Moderate) Concomitant use of lithium and androgen deprivation therapy (i.e., relugolix) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Remifentanil: (Moderate) If concomitant use of remifentanil and lithium is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Ribociclib: (Major) Concomitant use of ribociclib and lithium 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.
Ribociclib; Letrozole: (Major) Concomitant use of ribociclib and lithium 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.
Rilpivirine: (Moderate) Concomitant use of lithium and rilpivirine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Risperidone: (Moderate) Use risperidone and lithium together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, it is advisable to monitor patients for neurotoxicity. 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. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Lithium has also been associated with QT prolongation.
Romidepsin: (Moderate) Concomitant use of lithium and romidepsin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Salsalate: (Moderate) NSAIDs interfere with lithium excretion and may lead to elevated lithium serum concentrations. If NSAID therapy is started or stopped in a patient stabilized on lithium, monitor for evidence of lithium toxicity or decreased clinical effects, respectively.
Saquinavir: (Major) Lithium should avoided in combination with saquinavir. Lithium has been associated with 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 torsades de pointes (TdP). Avoid administering saquinavir boosted with ritonavir concurrently with other drugs that may prolong the QT interval. If no acceptable alternative therapy is available, perform a baseline ECG prior to initiation of concomitant therapy and carefully follow monitoring recommendations.
Sargramostim, GM-CSF: (Major) Avoid the concomitant use of sargramostim and lithium due to the risk of additive myeloproliferative effects. If coadministration of these drugs is required, frequently monitor patients for clinical and laboratory signs of excess myeloproliferative effects (e.g., leukocytosis). Sargramostim is a recombinant human granulocyte-macrophage colony-stimulating factor that works by promoting proliferation and differentiation of hematopoietic progenitor cells.
Saxagliptin: (Moderate) Lithium may cause variable effects on glycemic control when used in patients receiving antidiabetic therapy. Blood glucose concentrations should be closely monitored if lithium is taken by the patient. Dosage adjustments may be necessary.
Secobarbital: (Moderate) Because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including anxiolytics, sedatives, and hypnotics.
Selegiline: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant selegiline and lithium use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Selpercatinib: (Major) Concomitant use of selpercatinib and lithium 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.
Serotonin-Receptor Agonists: (Major) If concurrent use is necessary, monitor for the emergence of serotonin syndrome and inform patients of the increased risk. If serotonin syndrome is suspected, serotonergic agents should be discontinued and appropriate medical treatment should be implemented. There is an increased risk of serotonin syndrome during concurrent use of drugs with central serotonergic properties such as lithium and serotonin-receptor agonists. Signs and symptoms of serotonin syndrome include autonomic instability (e.g., labile blood pressure, tachycardia, diaphoresis, dizziness, hyperthermia), mental status changes (e.g., delirium, confusion, coma), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), gastrointestinal effects (e.g., nausea, vomiting, diarrhea), seizures, and in rare cases, death.
Sertraline: (Moderate) Coadministration of sertraline and lithium may increase the risk for QT prolongation and serotonin syndrome. Lithium has been associated with QT prolongation. However, the risk of sertraline-induced QT prolongation is generally considered to be low in clinical practice. The effect of sertraline on the QTc interval is minimal (typically less than 5 msec), and the drug has been used safely in patients with cardiac disease. Lithium is an effective augmenting agent to antidepressants in treatment-resistant depression; however, lithium has central serotonin-enhancing effects and may increase the risk of serotonin syndrome when combined with selective serotonin reuptake inhibitors (SSRIs) such as sertraline. Inform patients of the possible increased risk and monitor for serotonin syndrome, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, serotonergic agents should be discontinued and symptomatic treatment should be initiated.
Sevelamer: (Moderate) Although drug interaction studies have not been conducted, it may be prudent to separate the timing of administration of lithium from sevelamer. According to the manufacturer of sevelamer, clinicians should consider separating the timing of administration of sevelamer and drugs where a reduction in the bioavailability of would have a clinically significant effect on its safety or efficacy. The duration of separation should be based on the absorption characteristics of the coadministered drug. Because lithium has a narrow therapeutic index, consider monitoring clinical response and serum concentrations during concurrent use of sevelamer.
SGLT2 Inhibitors: (Moderate) Concomitant use of sodium-glucose cotransporter 2 (SGLT2) inhibitors with lithium may decrease serum lithium concentrations. Monitor serum lithium concentration more frequently during SGLT2 inhibitor initiation and dosage changes.
Siponimod: (Major) Concomitant use of siponimod and lithium 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.
Sodium Chloride: (Moderate) Moderate to significant dietary sodium changes, or changes in sodium and fluid intake, may affect lithium excretion. Systemic sodium chloride administration may result in increased lithium excretion and therefore, decreased serum lithium concentrations. In addition, high fluid intake may increase lithium excretion. For patients receiving sodium-containing intravenous fluids, symptom control and lithium concentrations should be carefully monitored. It is recommended that patients taking lithium maintain consistent dietary sodium consumption and adequate fluid intake during the initial stabilization period and throughout lithium treatment. Supplemental oral sodium and fluid should be only be administered under careful medical supervision.
Sodium Iodide: (Moderate) Concurrent administration of sodium iodide and lithium salts can potentiate the incidence of hypothyroidism and goiter. In general, this combination is not advised; however, if concomitant use is required, careful monitoring for signs and symptoms of hypothyroidism is indicated.
Sodium Polystyrene Sulfonate: (Major) Sodium polystyrene sulfonate can reduce the absorption of lithium.
Sodium Stibogluconate: (Moderate) Concomitant use of sodium stibogluconate and lithium may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Solifenacin: (Moderate) Concomitant use of lithium and solifenacin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Sorafenib: (Major) Concomitant use of sorafenib and lithium 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.
Sotagliflozin: (Moderate) Concomitant use of sodium-glucose cotransporter 2 (SGLT2) inhibitors with lithium may decrease serum lithium concentrations. Monitor serum lithium concentration more frequently during SGLT2 inhibitor initiation and dosage changes.
Sotalol: (Major) Concomitant use of lithium and sotalol 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.
St. John's Wort, Hypericum perforatum: (Moderate) Coadministration of paroxetine and lithium may increase the risk of serotonin syndrome. If serotonin syndrome occurs, all serotonergic drugs should be discontinued and appropriate medical treatment should be initiated.
Sufentanil: (Moderate) If concomitant use of sufentanil and lithium is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Sunitinib: (Moderate) Concomitant use of lithium and sunitinib may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Tacrolimus: (Moderate) Concomitant use of lithium and tacrolimus may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Tamoxifen: (Moderate) Concomitant use of tamoxifen and lithium may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Tapentadol: (Moderate) If concomitant use of tapentadol and lithium is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Tbo-Filgrastim: (Moderate) Lithium prompts the release of neutrophils and should be used with caution during filgrastim therapy. White blood cell counts above 100,000 cells/mm3 represent a medical emergency because of the risk of serious adverse effects such as brain infarction, respiratory failure, intracranial hemorrhage, retinal hemorrhage, myocardial infarction, and acute limb ischemia. Patients receiving lithium and filgrastim or pegfilgrastim should have more frequent monitoring of WBC counts.
Tedizolid: (Minor) Caution is warranted with the concurrent use of tedizolid and lithium. Tedizolid is an antibiotic that is also a weak reversible, non-selective inhibitor of MAO. Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid, which is structurally similar to tedizolid, and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity, including lithium.
Teduglutide: (Moderate) Teduglutide may increase absorption of lithium because of it's pharmacodynamic effect of improving intestinal absorption. Careful monitoring and possible dose adjustment of lithium is recommended.
Telavancin: (Moderate) Concomitant use of lithium and telavancin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Telmisartan; Amlodipine: (Moderate) Monitor for neurologic adverse reactions during concomitant use of lithium and calcium channel blockers. Concomitant use may increase the risk of neurologic adverse reactions, such as ataxia, tremors, nausea, vomiting, diarrhea, and/or tinnitus.
Tetrabenazine: (Major) Concomitant use of tetrabenazine and lithium 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.
Tetracycline: (Major) The interaction between lithium and tetracycline appears variable. Both lithium toxicity and reduction in lithium concentrations have been reported during concurrent administration of tetracycline. Use of an alternative antibiotic should be considered in patients receiving lithium; however, if concurrent use of tetracycline is necessary, close monitoring of lithium levels and clinical response is recommended.
Thalidomide: (Major) Avoid the concomitant use of thalidomide with other central nervous system depressants such as lithium due to the potential for additive sedative effects. Additionally, co-administration of thalidomide and other agents that slow cardiac conduction such as lithium may increase the potential for additive bradycardia.
Theophylline, Aminophylline: (Major) Theophylline; aminophylline can significantly increase the urinary excretion of lithium; therefore, close monitoring is recommended during concurrent use. Dosage adjustments may be necessary, particularly during initiation of theophylline therapy or following changes in theophylline dosage. It should be noted that theophylline and aminophylline have been used to treat lithium toxicity. (Moderate) Aminophylline can increase renal clearance of lithium, reducing its therapeutic effectiveness. Clinicians should be alert to loss of lithium therapeutic effectiveness if aminophylline is added.
Thiazide diuretics: (Moderate) Monitor lithium concentrations during concomitant use with thiazide diuretics; consider lower lithium starting doses and titrating slowly while frequently monitoring lithium concentrations and for signs of lithium toxicity. Thiazide diuretics reduce the renal clearance of lithium and increase the risk for lithium toxicity.
Thioridazine: (Contraindicated) Lithium has been associated with QT prolongation. Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Thioridazine is considered contraindicated for use along with agents that may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension. Because of the potential for TdP, use of lithium with thioridazine is contraindicated. Additionally, some atypical antipsychotics are considered first-line adjunctive therapy to mood stabilizers such as lithium. However, it is 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.
Thiothixene: (Moderate) It is advisable to monitor patients for neurotoxicity during co-administration of lithium and thiothixene. Although conventional antipsychotics are considered a treatment option as adjuncts to mood stabilizers such as lithium, neuroleptic malignant syndrome (NMS) and extrapyramidal effects have been observed occasionally during concurrent use. 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., 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.
Tinidazole: (Moderate) Consider monitoring serum lithium and creatinine concentrations after several days of concomitant lithium and tinidazole treatment to detect potential lithium intoxication. Another nitroimidazole has been reported to increase serum lithium concentrations.
Tobramycin: (Moderate) Moderate to significant dietary sodium changes, or changes in sodium and fluid intake, may affect lithium excretion. Systemic sodium chloride administration may result in increased lithium excretion and therefore, decreased serum lithium concentrations. In addition, high fluid intake may increase lithium excretion. For patients receiving sodium-containing intravenous fluids, symptom control and lithium concentrations should be carefully monitored. It is recommended that patients taking lithium maintain consistent dietary sodium consumption and adequate fluid intake during the initial stabilization period and throughout lithium treatment. Supplemental oral sodium and fluid should be only be administered under careful medical supervision.
Tolterodine: (Moderate) Lithium should be used cautiously with tolterodine. Lithium has been associated with QT prolongation and tolterodine has been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers. This should be taken into consideration when prescribing tolterodine to patients taking other drugs that are associated with QT prolongation.
Topiramate: (Moderate) Monitor serum lithium concentrations during concomitant high-dose topiramate use. Lithium concentrations were unaffected during treatment with topiramate 200 mg/day; however, there was an observed increase in systemic exposure of lithium (26%) after topiramate doses up to 600 mg/day.
Toremifene: (Major) Concomitant use of toremifene and lithium 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.
Tramadol: (Moderate) If concomitant use of tramadol and lithium is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Tramadol; Acetaminophen: (Moderate) If concomitant use of tramadol and lithium is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Trandolapril; Verapamil: (Moderate) Monitor for neurologic adverse reactions during concomitant use of lithium and calcium channel blockers. Concomitant use may increase the risk of neurologic adverse reactions, such as ataxia, tremors, nausea, vomiting, diarrhea, and/or tinnitus.
Tranexamic Acid: (Moderate) Moderate to significant dietary sodium changes, or changes in sodium and fluid intake, may affect lithium excretion. Systemic sodium chloride administration may result in increased lithium excretion and therefore, decreased serum lithium concentrations. In addition, high fluid intake may increase lithium excretion. For patients receiving sodium-containing intravenous fluids, symptom control and lithium concentrations should be carefully monitored. It is recommended that patients taking lithium maintain consistent dietary sodium consumption and adequate fluid intake during the initial stabilization period and throughout lithium treatment. Supplemental oral sodium and fluid should be only be administered under careful medical supervision.
Tranylcypromine: (Moderate) There is an increased risk of serotonin syndrome during concurrent use of lithium and nonselective monoamine oxidase inhibitors (MAOIs). Lithium has central serotonergic actions and MAOIs impair the metabolism of serotonin. If concurrent use is necessary, monitor for the emergence of serotonin syndrome and inform patients of the increased risk. If serotonin syndrome is suspected, serotonergic agents should be discontinued and appropriate medical treatment should be implemented.
Trazodone: (Major) Due to the risk of QT prolongation and torsade de pointes (TdP), the manufacturer of trazodone recommends avoiding use with other drugs that increase the QT interval. Lithium has been associated with a risk of QT prolongation. In addition, coadministration of trazodone and lithium may increase the risk of serotonin syndrome. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue lithium and trazodone and initiate symptomatic treatment if serotonin syndrome occurs.
Tretinoin, ATRA: (Moderate) Monitor for pseudotumor cerebri (benign intracranial hypertension) during concomitant lithium and tretinoin use due to increased risk for the condition. Both lithium and tretinoin are associated with pseudotumor cerebri.
Triclabendazole: (Moderate) Concomitant use of triclabendazole and lithium may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Tricyclic antidepressants: (Moderate) Monitor for serotonin syndrome, particularly during lithium initiation, during concomitant tricyclic antidepressant use. If serotonin syndrome occurs, consider discontinuation of lithium and/or the tricyclic antidepressant.
Trifluoperazine: (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.
Triprolidine: (Moderate) Because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including the sedating antihistamines.
Triptorelin: (Moderate) Concomitant use of lithium and androgen deprivation therapy (i.e., triptorelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Tryptophan, 5-Hydroxytryptophan: (Major) Avoid the co-use of lithium and tryptophan whenever possible. There is an increased risk of serotonin syndrome during concurrent use of drugs with central serotonergic properties such as lithium and tryptophan. Signs and symptoms of serotonin syndrome include autonomic instability (e.g., labile blood pressure, tachycardia, diaphoresis, dizziness, hyperthermia), mental status changes (e.g., delirium, confusion, coma), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), gastrointestinal effects (e.g., nausea, vomiting, diarrhea), seizures, and in rare cases, death. If concurrent use is necessary, monitor for the emergence of serotonin syndrome and inform patients of the increased risk. If serotonin syndrome is suspected, serotonergic agents should be discontinued and appropriate medical treatment should be implemented.
Urea: (Major) Diuretics that act at the proximal tubule (like injectable Urea) will increase urinary lithium excretion by interfering with the primary site of lithium tubular reabsorption. Patients receiving these agents concomitantly should be monitored very closely to ensure that the desired clinical response to lithium continues to occur. Also carefully monitor renal function during combined use. Monitor serum lithium levels closely and adjust the lithium dosage if necessary.
Valacyclovir: (Moderate) Consider starting with a lower lithium dose and monitor lithium concentrations and for signs and symptoms of lithium toxicity during concomitant valacyclovir use. The risk of lithium toxicity is increased with concomitant use of medications that affect kidney function, such as valacyclovir.
Vancomycin: (Moderate) Moderate to significant dietary sodium changes, or changes in sodium and fluid intake, may affect lithium excretion. Systemic sodium chloride administration may result in increased lithium excretion and therefore, decreased serum lithium concentrations. In addition, high fluid intake may increase lithium excretion. For patients receiving sodium-containing intravenous fluids, symptom control and lithium concentrations should be carefully monitored. It is recommended that patients taking lithium maintain consistent dietary sodium consumption and adequate fluid intake during the initial stabilization period and throughout lithium treatment. Supplemental oral sodium and fluid should be only be administered under careful medical supervision.
Vandetanib: (Major) Concomitant use of vandetanib and lithium 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.
Vardenafil: (Moderate) Concomitant use of vardenafil and lithium may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Vasopressin, ADH: (Moderate) Monitor hemodynamics and adjust the dose of vasopressin as needed when used concomitantly with drugs suspected of causing diabetes insipidus, such as lithium. Use together may decrease the pressor and antidiuretic effects of vasopressin.
Vemurafenib: (Major) Concomitant use of vemurafenib and lithium 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.
Venlafaxine: (Moderate) Concomitant use of lithium and venlafaxine may increase the risk of serotonin syndrome or QT/QTc prolongation and torsade de pointes (TdP) in some patients. Monitor for serotonin syndrome, particularly during therapy initiation and dose increases. If serotonin syndrome occurs, consider discontinuation of lithium and/or venlafaxine. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Verapamil: (Moderate) Monitor for neurologic adverse reactions during concomitant use of lithium and calcium channel blockers. Concomitant use may increase the risk of neurologic adverse reactions, such as ataxia, tremors, nausea, vomiting, diarrhea, and/or tinnitus.
Vilazodone: (Major) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering vilazodone with other drugs that have serotonergic properties such as lithium. Lithium has been reported to increase 5-hydroxytryptamine metabolites in the cerebrospinal fluid and may interact pharmacodynamically with serotonergic agents resulting in serotonin syndrome. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Patients receiving vilazodone and lithium should be monitored for the emergence of serotonin syndrome, particularly during treatment initiation and during dosage increases. Vilazodone and lithium should be discontinued if serotonin syndrome occurs and supportive symptomatic treatment should be initiated.
Voclosporin: (Moderate) Concomitant use of lithium and voclosporin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Concomitant use of lithium and clarithromycin 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.
Voriconazole: (Moderate) Concomitant use of lithium and voriconazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Vorinostat: (Moderate) Concomitant use of lithium and vorinostat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Vortioxetine: (Major) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering vortioxetine with other drugs that have serotonergic properties such as lithium. Lithium has been reported to increase 5-hydroxytryptamine metabolites in the cerebrospinal fluid and may interact pharmacodynamically with vortioxetine resulting in serotonin syndrome. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Patients receiving lithium in combination with vortioxetine should be monitored for the emergence of serotonin syndrome or other adverse effects. If serotonin syndrome is suspected, vortioxetine and concurrent serotonergic agents should be discontinued.
Ziprasidone: (Major) Concomitant use of ziprasidone and lithium should be avoided due to the potential for additive QT prolongation. Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of torsade de pointes (TdP) in patients with multiple confounding factors. Lithium has been associated with QT prolongation. Additionally, lithium may be a risk factor for antipsychotic-induced neuroleptic malignant syndrome (NMS); however, this hypothesis has not been confirmed. NMS has been observed occasionally during concurrent use of lithium and either atypical or conventional antipsychotics. 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, particularly during concurrent use of haloperidol and lithium. Subsequent rare reports of NMS or NMS-like reactions have been described during coadministration of lithium and atypical antipsychotics. Following resolution of NMS, there are isolated instances of re-emergence of symptoms following re-initiation of lithium as monotherapy. 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.

Eskalith CR/Lithium/Lithium Carbonate/Lithobid Oral Tab ER: 300mg, 450mg
Eskalith/Lithium/Lithium Carbonate Oral Cap: 150mg, 300mg, 600mg
Lithium/Lithium Carbonate Oral Tab: 300mg
Lithium/Lithium Citrate Oral Sol: 5mL, 8mEq

Adults

Maximum dosage not well defined. Individualize dosage to patient disease and response, and lithium concentrations; avoid concentration above 1.5 mEq/L. For most adults, a total daily dosage of 1,200 to 1,800 mg/day PO (in divided doses) will provide appropriate lithium concentrations.

Geriatric

Maximum dosage not well defined. Individualize dosage to patient disease and response, and lithium concentrations; avoid concentration above 1.5 mEq/L. For most adults, a total daily dosage of 1,200 to 1,800 mg/day PO (in divided doses) will provide appropriate lithium concentrations.

Adolescents

Maximum dosage not well defined. Individualize dosage to patient disease and response, and lithium concentrations; avoid concentration above 1.5 mEq/L. For most adolescents, as with adults, a total daily dosage of 1,200 to 1,800 mg/day PO (in divided doses) will provide appropriate lithium concentrations.

Children

7 to 12 years: Maximum dosage not well defined. Individualize dosage to patient disease and response, and lithium concentrations; avoid concentration above 1.5 mEq/L. In children weighing 20 to 30 kg, a total daily dosage up to 1,500 mg/day PO (in divided doses) for acute treatment and 1,200 mg/day PO (in divided doses) for maintenance therapy will provide appropriate lithium concentrations for most patients. In children weighing more than 30 kg, a total daily dosage up to 1,800 mg/day PO (in divided doses) for acute or maintenance therapy will provide appropriate lithium concentrations for most patients.
6 years: Safety and efficacy have not been established. Used off label; dosing must be individualized. One consensus guideline notes that approximate weight-based doses of 10 to 30 mg/kg/day PO (in divided doses) are needed to provide appropriate lithium concentrations. Avoid lithium concentration above 1.5 mEq/L.
Less than 6 years: Safety and efficacy have not been established.

Infants

Not indicated.

Lithium competes at cellular sites with sodium, potassium, calcium, and magnesium ions. Lithium competes with these ions at intracellular binding sites, at protein surfaces, at carrier binding sites, and at transport sites. At the cell membrane, lithium readily passes through sodium channels, and high concentrations can block potassium channels. Although the mechanism of the antimanic and antidepressant action in the CNS is not known, evidence suggests that the drug interferes with the synthesis, storage, release, and reuptake of monoamine neurotransmitters. Lithium enhances the uptake of tryptophan, increases the synthesis of serotonin, and may also enhance the release of serotonin in the CNS. Lithium does not possess sedative, depressant, or euphoriant effects. Onset of the acute antimanic effect is usually seen in 5 to 7 days, and the full therapeutic effect is established in 10 to 21 days.
 
Lithium administration increases renal sodium and potassium clearance. These effects are attenuated by a compensatory increase in aldosterone after 2 to 3 days. Lithium does not affect sodium reabsorption in either the ascending limb of the loop of Henle or in the distal tubule. A decrease in renal concentrating ability occurs in 30% to 50% of patients while receiving lithium; it often produces a mild nephrogenic diabetes insipidus manifested as polyuria. Lithium-induced diabetes insipidus is thought to be due to inhibition of vasopressin-induced adenylate cyclase activity in the medullary collecting tubule of the nephron. Since lithium is more toxic and a less reliable agent than demeclocycline, lithium should be considered a last choice for the treatment of SIADH.
 
Lithium enhances granulocyte production via stimulation of monocyte colony stimulating factor production. Lithium produces an increase in the total neutrophil pool and each of its components in the bone marrow and circulation. Leukocytosis peaks within 7 to 10 days of initiating therapy and the WBC count will return to baseline 7 to 10 days after discontinuing lithium.
 
The actions of lithium on the heart generally give rise to adverse effects. The most common electrocardiogram (ECG) changes include flattening or inversion of the T-waves. This manifestation is thought to be due to lithium-induced inhibition of potassium cellular reuptake leading to intracellular hypokalemia. Because lithium displaces potassium, an extracellular hyperkalemia is seen and, since the intracellular:extracellular potassium balance is shifted, cardiac arrest is possible at lower than usual degrees of hyperkalemia.

Lithium salts are administered orally. Lithium carbonate is most commonly used because it has a longer shelf-life and contains more lithium on a weight basis than do other salts. Lithium has negligible protein binding (15%) and the distribution space of lithium approximates that of total body water. The kinetics of lithium distribution into the brain remain largely anecdotal and there is large inter-patient variability. A review of studies using magnetic resonance spectroscopy (MRS) in humans indicated that initial brain lithium concentrations were about half those in serum, occasionally rising to 75% to 80%. Brain concentrations varied significantly over 48 hours, mirroring serum concentrations. Ten days after the last dose, lithium was not detectable in the brain. Because lithium may take up to 24 hours to distribute into brain tissue, occurrence of acute toxicity symptoms may be delayed. Lithium is concentrated into bile by a factor of 2 to 10 compared with blood concentrations. There appears to be long-term retention in the bone, from where it is eliminated over several months after discontinuation of lithium. In adults, the half-life is 18 to 36 hours. The half-life may be increased or decreased during acute episodes of mania or depression. Lithium is not metabolized and more than 95% of a dose is eliminated by the kidneys. The amount eliminated through sweat, saliva, and feces is negligible under normal circumstances. Many factors can affect lithium clearance including hyponatremia or hypernatremia, dehydration, and diuretic use. Both creatinine clearance (CrCl) and body weight are important factors in predicting lithium clearance. Lithium is freely filtered by renal glomeruli, but it also undergoes significant renal tubular reabsorption (about 80%). Renal impairment, such as a decrease in the glomerular filtration rate (GFR) will reduce lithium elimination. It was once thought that tubular reabsorption occurred only in the proximal tubule but interaction studies with HCTZ and furosemide revealed substantial lithium reabsorption also occurs in the ascending limb of the loop of Henle.
 
A serum lithium concentration between 0.6 mEq/L and 1 mEq/L is the usual range for maintenance treatment with immediate-release formulations. For sustained-release preparations, a range between 0.6 mEq/L to 1.2 mEq/L is recommended by the manufacturers. The manufacturers of the sustained-release products recommend lithium concentrations of 0.8 mEq/L to 1.5 mEq/L for the treatment of acute mania, while the manufacturers of the immediate-release formulations recommend a range of 0.8 mEq/L to 1.2 mEq/L for acute mania. The dosage should be adjusted according to efficacy and tolerability while ensuring that lithium serum concentrations are maintained in the therapeutic range. Toxicity is likely in most patients when levels exceed 1.5 mEq/L, although symptoms of lithium toxicity can appear in some patients with serum concentrations of 1 mEq/L or less. The narrow therapeutic ratio and inter-patient variations make individual monitoring and dosage adjustment essential.
 
Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: None

Oral Route

Lithium tablets, capsules, and oral solution are completely absorbed from the GI tract, and the rate of absorption is not significantly slowed by the presence of food. Peak serum concentrations after administration of lithium carbonate immediate-release formulations are reached in 0.25 to 3 hours. Absorption is complete by about 8 hours. When extended-release tablets are used, the peak lithium concentration (Cmax) is observed 4 to 6 hours after the dose. Sustained-release products produce a Cmax that is lower than the immediate-release formulations.

Pregnancy

Lithium is excreted in human milk. According to the manufacturer, breast-feeding during lithium treatment is not recommended. Closely monitor if breast-feeding is continued; monitoring of lithium levels, thyroid function, and renal function should be considered in a breastfed infant. Discontinue breast-feeding if the infant develops lithium toxicity. Signs and symptoms of lithium toxicity in breastfed infants have included hypertonia, hypothermia, cyanosis, and ECG changes. Adverse effects including increased thyroid stimulating hormone (TSH) have rarely been reported in some infants exposed to lithium via breast milk. Dehydration in a nursing infant may contribute to lithium toxicity. One-third to one-half of therapeutic maternal blood concentrations have been observed in nursing infants. In a study of 11 lactating women receiving 600 to 1500 mg/day of lithium for bipolar disorder, the estimated infant dose from milk ranged from 0 to 30% of the weight-adjusted dose of the mothers. Due to individual variability in response to mood stabilizers, it may be prudent to continue the existing regimen if ongoing treatment is deemed necessary during lactation; however, alternate medications include valproate and divalproex; carbamazepine may also be considered.