Fluoxetine

Monoamine Oxidase Inhibitors (MAOIs): (2.9 , 2.10 , 4.1 , 5.2 ) Drugs Metabolized by CYP2D6: Fluoxetine is a potent inhibitor of CYP2D6 enzyme pathway (7.7) Tricyclic Antidepressants (TCAs): Monitor TCA levels during coadministration with fluoxetine or when fluoxetine has been recently discontinued (5.2 , 7.7) CNS Acting Drugs: Caution should be used when taken in combination with other centrally acting drugs (7.2) Benzodiazepines: Diazepam - increased t½, alprazolam – further psychomotor performance decrement due to increased levels (7.7) Antipsychotics: Potential for elevation of haloperidol and clozapine levels (7.7) Anticonvulsants: Potential for elevated phenytoin and carbamazepine levels and clinical anticonvulsant toxicity (7.7) Serotonergic Drugs: (2.9 , 2.10 , 4.1 , 5.2) Drugs that Interfere with Hemostasis (e.g., NSAIDs, Aspirin, Warfarin): May potentiate the risk of bleeding (7.4) Drugs Tightly Bound to Plasma Proteins: May cause a shift in plasma concentrations (7.6 , 7.7) Olanzapine: When used in combination with fluoxetine, also refer to the Drug Interactions section of the package insert for Symbyax (7.7) Drugs that Prolong the QT Interval: Do not use fluoxetine with thioridazine or pimozide. Coadministration of alprazolam and fluoxetine has resulted in increased alprazolam plasma concentrations and in further psychomotor performance decrement due to increased alprazolam levels.

Monoamine Oxidase Inhibitors (MAOIs): (2.9 , 2.10 , 4.1 , 5.2 ) Drugs Metabolized by CYP2D6: Fluoxetine is a potent inhibitor of CYP2D6 enzyme pathway (7.7) Tricyclic Antidepressants (TCAs): Monitor TCA levels during coadministration with fluoxetine or when fluoxetine has been recently discontinued (5.2 , 7.7) CNS Acting Drugs: Caution should be used when taken in combination with other centrally acting drugs (7.2) Benzodiazepines: Diazepam - increased t½, alprazolam – further psychomotor performance decrement due to increased levels (7.7) Antipsychotics: Potential for elevation of haloperidol and clozapine levels (7.7) Anticonvulsants: Potential for elevated phenytoin and carbamazepine levels and clinical anticonvulsant toxicity (7.7) Serotonergic Drugs: (2.9 , 2.10 , 4.1 , 5.2) Drugs that Interfere with Hemostasis (e.g., NSAIDs, Aspirin, Warfarin): May potentiate the risk of bleeding (7.4) Drugs Tightly Bound to Plasma Proteins: May cause a shift in plasma concentrations (7.6 , 7.7) Olanzapine: When used in combination with fluoxetine, also refer to the Drug Interactions section of the package insert for Symbyax (7.7) Drugs that Prolong the QT Interval: Do not use fluoxetine with thioridazine or pimozide. Benzodiazepines — The half-life of concurrently administered diazepam may be prolonged in some patients [see Clinical Pharmacology (12.3) ] .

Contraindicated combination with fluoxetine due to risk of serotonin syndrome.

Serious, sometimes fatal reactions reported when used concomitantly with MAO inhibitors.

Do not use fluoxetine with pimozide due to QT interval prolongation risk.

Do not use fluoxetine with thioridazine due to QT interval prolongation risk.

Inhibits CYP450 2D6, elevating thioridazine levels and augmenting QTc prolongation, risking serious cardiac arrhythmias including Torsades de pointes.

Contraindicated due to risk of clinically significant adverse reactions. Minimum 5-week washout period required before starting tranylcypromine due to fluoxetine's long half-life.

Contraindicated due to risk of clinically significant adverse reactions. Minimum 5-week washout period required before starting tranylcypromine due to fluoxetine's long half-life.

CYP2D6 inhibitor that increases codeine plasma concentration but decreases morphine concentration, potentially causing reduced analgesic efficacy or opioid withdrawal symptoms. Discontinuation may cause increased morphine levels and potentially fatal respiratory depression.

Concurrent use may potentiate risk of upper gastrointestinal bleeding due to interference with serotonin-mediated hemostasis.

Fluoxetine inhibits P450 2D6 and may increase amitriptyline levels; caution advised with coadministration. Allow at least 5 weeks after fluoxetine discontinuation before initiating amitriptyline.

Increases risk of serotonin syndrome. Monitor patients for signs and symptoms during treatment initiation and dosage increases.

Concomitant use increases risk of serotonin syndrome and increases amphetamine exposure via CYP2D6 inhibition.

Strong CYP2D6 inhibitor increases aripiprazole exposure. Reduce aripiprazole dosage.

Strong CYP2D6 inhibitor that increases aripiprazole exposure. Avoid concomitant use because dosage cannot be modified.

CYP2D6 inhibitor that increases atomoxetine steady-state plasma concentrations 6- to 8-fold AUC and 3- to 4-fold Cmax in extensive metabolizers.

CYP2D6 inhibitor that increases atomoxetine steady-state plasma concentrations 6- to 8-fold in extensive metabolizers, with C max increased 3- to 4-fold.

Concomitant use with fluoxetine increases the risk of serotonin syndrome.

Fluoxetine may elevate carbamazepine levels and cause clinical anticonvulsant toxicity.

Inhibits P450 2D6 and may increase clomipramine plasma levels, potentially causing toxicity in normal metabolizers.

SSRI inhibitor of P450 2D6 that may increase desipramine plasma concentrations. At least 5 weeks required before initiating desipramine after fluoxetine withdrawal due to long half-life.

Strong CYP2D6 inhibitor that increases systemic exposure to active dihydro-metabolites of deutetrabenazine by approximately 3-fold. Maximum recommended dose should not exceed 36 mg per day.

CYP2D6 inhibitor and serotonergic drug; increases dextroamphetamine exposure and serotonin syndrome risk. Use lower doses and monitor.

CYP2D6 inhibitor and serotonergic drug that increases amphetamine exposure and risk of serotonin syndrome. Initiate with lower doses and monitor for serotonin syndrome.

CYP2D6 inhibitor and serotonergic drug that increases dextroamphetamine exposure and risk of serotonin syndrome. Initiate with lower doses and monitor for serotonin syndrome.

SSRI that inhibits CYP2D6 with long half-life. Caution advised; at least 5 weeks must elapse before initiating doxepin after fluoxetine withdrawal.

Potent CYP2D6 inhibitor; expected to increase duloxetine concentrations similar to paroxetine.

Potent CYP2D6 inhibitor expected to increase duloxetine concentrations similarly to paroxetine.

SSRI inhibitor of P450 2D6 that increases imipramine plasma concentration. At least 5 weeks must elapse when switching from fluoxetine to imipramine due to long half-life. Monitoring of TCA plasma levels recommended.

May increase the risk of hypoglycemia. Dose adjustment and increased glucose monitoring may be required.

May increase risk of hypoglycemia. Dosage reductions and increased glucose monitoring may be required.

May increase risk of hypoglycemia. Dosage reductions and increased glucose monitoring may be required.

May increase risk of hypoglycemia. Dosage reductions and increased glucose monitoring may be required.

May increase the risk of hypoglycemia; dose adjustment and increased glucose monitoring required.

Concomitant use with fluoxetine increases the risk of serotonin syndrome.

Methylene blue can cause serotonin syndrome; fluoxetine must be stopped at least 5 weeks before methylene blue treatment due to its longer half-life.

Strong CYP2D6 inhibitor that increases metoclopramide plasma concentrations and risk of extrapyramidal symptoms exacerbation. Dosage reduction recommended.

Strong CYP2D6 inhibitor increasing metoclopramide plasma concentrations with risk of exacerbation of extrapyramidal symptoms; dosage reduction recommended.

Strong CYP2D6 inhibitor that doubles metoprolol concentrations, decreasing cardioselectivity. Close monitoring required.

Strong CYP2D6 inhibitor that doubles metoprolol concentrations, decreasing cardioselectivity and requiring close monitoring.

Strong CYP2D6 inhibitor that doubles metoprolol plasma concentrations, decreasing cardioselectivity. Close monitoring required.

Strong CYP2D6 inhibitor that doubles metoprolol concentrations, decreasing cardioselectivity. Close monitoring required.

Strong CYP2D6 inhibitor that doubles metoprolol concentrations, decreasing cardioselectivity.

SSRI that increases risk of serotonin syndrome with mirtazapine. Monitor for symptoms during initiation and dose increases.

CYP3A inhibitor that may increase nifedipine exposure. Careful monitoring and dose adjustment necessary; consider lowest dose.

Inhibits P450 2D6 and may increase nortriptyline plasma concentrations. At least 5 weeks must elapse after fluoxetine withdrawal before initiating nortriptyline due to long half-life.

Concurrent use with fluoxetine may potentiate risk of upper gastrointestinal bleeding due to fluoxetine's effect on platelet serotonin.

Concomitant use increases risk of serotonin syndrome; monitor for signs and symptoms.

Fluoxetine inhibits cytochrome P450 2D6 and has a long half-life; at least 5 weeks must elapse before initiating amitriptyline after fluoxetine withdrawal.

Fluoxetine may elevate phenytoin levels and cause clinical anticonvulsant toxicity.

Increases S-propafenone and R-propafenone exposure by 39-71%, potentially increasing adverse reactions.

Concomitant use increases risk of serotonin syndrome. Monitor for signs and symptoms, particularly during treatment initiation and dosage increases.

Fluoxetine is a potent CYP2D6 inhibitor that increases TCA levels. Monitor TCA levels during coadministration and after fluoxetine discontinuation.

Strong CYP2D6 inhibitor that markedly increases exposure to tetrabenazine metabolites. Dose reduction necessary; maximum daily dose 50 mg, maximum single dose 25 mg.

CYP2D6 inhibitor that increases tramadol plasma concentration and decreases M1 concentration, resulting in increased risk of seizures, serotonin syndrome, and opioid withdrawal symptoms.

CYP2D6 inhibitor may increase tramadol plasma concentration and decrease M1 concentration, resulting in increased risk of seizures, serotonin syndrome, and opioid withdrawal or toxicity.

CYP2D6 inhibitor that increases tramadol plasma concentration and decreases M1 concentration, risking seizures, serotonin syndrome, opioid withdrawal, and respiratory depression.

CYP2D6 inhibitor may increase tramadol plasma concentration and decrease M1 concentration, resulting in increased risk of seizures, serotonin syndrome, and opioid withdrawal or toxicity.

Fluoxetine inhibits P450 2D6, potentially increasing trimipramine plasma concentrations and causing toxicity. Sufficient time must elapse when switching from fluoxetine to trimipramine due to fluoxetine's long half-life.

Increases risk of serotonin syndrome. Monitor patients for signs and symptoms during treatment initiation and dosage increases.

Concomitant use with fluoxetine increases the risk of serotonin syndrome.

Fluoxetine may potentiate bleeding risk through serotonin reuptake inhibition affecting platelet hemostasis.

Coadministration increased alprazolam maximum plasma concentration by 46%, decreased clearance by 21%, increased half-life by 17%, and decreased psychomotor performance.

Fluoxetine inhibits P450 2D6; caution is indicated in co-administration with tricyclic antidepressants. At least 5 weeks must elapse before initiating TCA treatment after fluoxetine withdrawal due to long half-life.

Strong CYP2D6 inhibitor that increases aripiprazole exposure. Reduce aripiprazole dosage when used concomitantly.

Strong CYP2D6 inhibitor that increases brexpiprazole exposure. Dosage adjustment may be needed depending on clinical context.

CYP2D6 substrate; bupropion inhibits CYP2D6 and increases fluoxetine concentrations; consider dose reduction.

Bupropion inhibits CYP2D6 and can increase fluoxetine concentrations; consider dose reduction of fluoxetine.

CYP2D6 substrate antidepressant. Bupropion inhibits CYP2D6, increasing fluoxetine exposure. Dose reduction may be necessary.

CYP2D6 substrate. Bupropion inhibits CYP2D6 and can increase fluoxetine concentrations. Consider dose reduction of fluoxetine when used with bupropion.

CYP2D6-metabolized antidepressant. Bupropion inhibits CYP2D6 and can increase fluoxetine concentrations. Consider dose reduction.

CYP2D6 inhibitor expected to increase blood levels of carvedilol R(+) enantiomer, potentially increasing vasodilating effects and dizziness.

Potent CYP2D6 inhibitor expected to increase carvedilol R(+) enantiomer blood levels, potentially causing dizziness and vasodilation.

Other SSRIs increase risk of serotonin syndrome when used with citalopram. Monitor for signs and symptoms of serotonin syndrome.

Other SSRIs increase risk of serotonin syndrome when used concomitantly with citalopram. Monitor for signs and symptoms of serotonin syndrome.

Fluoxetine may increase plasma levels of clomipramine; close supervision and dosage adjustment recommended.

Potential for elevation of clozapine levels.

CYP2D6 inhibitor; no dosing adjustments recommended for darifenacin when co-administered with fluoxetine.

Co-administration resulted in increased plasma concentrations of desloratadine and 3-hydroxydesloratadine, but no clinically relevant changes in safety profile.

Weakness, hyperreflexia, and incoordination may occur rarely with coadministration of selective serotonin reuptake inhibitors.

Potent CYP2D6 inhibitor expected to increase duloxetine concentrations similarly to paroxetine.

Weak CYP3A4 inhibitor; concomitant use of multiple weak inhibitors may increase risk of adverse reactions.

May increase phenytoin serum levels; monitoring of phenytoin levels recommended.

Gilteritinib may reduce the effects of fluoxetine. Avoid concomitant use unless essential for patient care.

May potentiate hypoglycemic action of glyburide. Patient should be observed closely for hypoglycemia when administered and for loss of control when withdrawn.

Highly protein-bound drug that may increase glucose-lowering effect of glimepiride, increasing susceptibility to hypoglycemia.

May increase glucose-lowering effect of glipizide and susceptibility to hypoglycemia; monitor closely.

Potential for elevation of haloperidol levels.

Combined CYP3A4 and CYP2D6 inhibitor that increases haloperidol plasma concentrations; monitor for increased adverse effects including QTc prolongation.

Combined CYP3A4 and CYP2D6 inhibitor that increases haloperidol plasma concentrations, raising risk of adverse events including QTc prolongation.

Strong CYP2D6 inhibitor that increased iloperidone AUC 2-3 fold and metabolite P88 levels, decreased P95 metabolite. Dose reduction required.

SSRI that inhibits P450 2D6 and hepatic enzymes, increasing imipramine plasma concentrations. At least 5 weeks may be necessary before initiating imipramine after fluoxetine withdrawal due to long half-life.

May increase risk of hypoglycemia. Dose adjustment and increased glucose monitoring may be required.

May increase risk of hypoglycemia; dosage reductions and increased glucose monitoring may be required.

May increase risk of hypoglycemia. Dosage reductions and increased glucose monitoring may be required.

May increase the risk of hypoglycemia. Dose reductions and increased frequency of glucose monitoring may be required.

May increase risk of hypoglycemia. Dosage reductions and increased frequency of glucose monitoring may be required.

May increase risk of hypoglycemia. Dose adjustment and increased glucose monitoring may be required.

May increase risk of hypoglycemia; dose adjustment and increased glucose monitoring may be required.

May increase risk of hypoglycemia. Dose reductions and increased glucose monitoring may be required.

May increase risk of hypoglycemia. Dose reductions and increased glucose monitoring may be required.

Concurrent use has resulted in both increased and decreased serum lithium concentrations; close monitoring required.

Less potent CYP 3A4 inhibitor; should be administered with caution due to potential vasospastic effects.

Strong CYP2D6 inhibitor that doubles metoprolol concentrations and decreases cardioselectivity; close monitoring required.

Hypomanic symptoms reported in a patient on fluoxetine who smoked marijuana; symptoms resolved after 4 days.

CYP2D6 inhibitor that may increase nebivolol levels; use caution when co-administered.

CYP2D6 inhibitor may increase nebivolol levels. Use caution when co-administered.

Moderate CYP3A4 inhibitor that may increase nimodipine plasma concentration and blood pressure lowering effect. Blood pressure monitoring and dose reduction of nimodipine may be necessary.

When used in combination with fluoxetine, refer to package inserts for both drugs.

CYP2D6 inhibitor that increases oliceridine plasma concentration, resulting in increased or prolonged opioid effects. May require less frequent dosing and close monitoring for respiratory depression.

Paroxetine is a strong CYP2D6 inhibitor that may increase fluoxetine concentrations. Use caution and monitor.

Fluoxetine inhibits P450 2D6, increasing perphenazine plasma concentrations. Close monitoring is essential and dose reduction may be necessary to avoid toxicity.

May increase phenytoin serum levels; monitoring of phenytoin levels recommended.

May increase susceptibility to hypoglycemia when coadministered with SYMLIN. Use with caution.

Exerts noncompetitive inhibition of 5-methyltetrahydrofolate active transport in the intestine.

Increases S-propafenone Cmax and AUC by 39% and 50%, and R-propafenone Cmax and AUC by 71% and 50%.

CYP2D6 and CYP2C19 substrate/inhibitor that may increase blood levels and/or toxicity of propranolol.

May increase risk of hypoglycemia. Repaglinide dose reductions and increased glucose monitoring may be required.

CYP2D6 enzyme inhibitor increases plasma concentrations of risperidone. Reduce initial dose and do not exceed 8 mg per day of risperidone.

Other SSRIs increase risk of serotonin syndrome; monitor for signs and symptoms.

Potent CYP2D6 inhibitor that significantly inhibited tolterodine metabolism, resulting in 4.8-fold increase in tolterodine AUC in extensive metabolizers. No dose adjustment required.

Potent CYP2D6 inhibitor that significantly inhibits tolterodine metabolism, resulting in 4.8-fold increase in tolterodine AUC in extensive metabolizers. No dose adjustment required.

Fluoxetine inhibits P450 2D6 and increases trimipramine maleate concentrations. Caution is indicated in co-administration. Sufficient time must elapse before initiating trimipramine in patients withdrawn from fluoxetine.

Strong CYP2D6 inhibitor increases plasma concentrations of vortioxetine. Reduce TRINTELLIX dose by half when coadministered.

Multiple doses increase zolpidem half-life by 17% with no additive effect on psychomotor performance observed.

Fluoxetine does not affect the pharmacokinetics of clonazepam.

CYP2D6 inhibitor; no dosing adjustments recommended.

Co-administration results in increased plasma concentrations of desloratadine but no clinically relevant changes in safety profile.

Fluoxetine causes small decrease in olanzapine clearance with minimal change in steady-state concentrations; dose modification not routinely recommended.

Increases zolpidem half-life by 17% after multiple doses, but no evidence of additive effect on psychomotor performance.

These include: specific antipsychotics (e.g., ziprasidone, iloperidone, chlorpromazine, mesoridazine, droperidol); specific antibiotics (e.g., erythromycin, gatifloxacin, moxifloxacin, sparfloxacin); Class 1A antiarrhythmic medications (e.g., quinidine, procainamide); Class III antiarrhythmics (e.g., amiodarone, sotalol); and others (e.g., pentamidine, levomethadyl acetate, methadone, halofantrine, mefloquine, dolasetron mesylate, probucol or tacrolimus).

These include: specific antipsychotics (e.g., ziprasidone, iloperidone, chlorpromazine, mesoridazine, droperidol); specific antibiotics (e.g., erythromycin, gatifloxacin, moxifloxacin, sparfloxacin); Class 1A antiarrhythmic medications (e.g., quinidine, procainamide); Class III antiarrhythmics (e.g., amiodarone, sotalol); and others (e.g., pentamidine, levomethadyl acetate, methadone, halofantrine, mefloquine, dolasetron mesylate, probucol or tacrolimus).

Additionally, in vitro studies have shown ketoconazole, a potent inhibitor of CYP3A4 activity, to be at least 100 times more potent than fluoxetine or norfluoxetine as an inhibitor of the metabolism of several substrates for this enzyme, including astemizole, cisapride, and midazolam.

Additionally, in vitro studies have shown ketoconazole, a potent inhibitor of CYP3A4 activity, to be at least 100 times more potent than fluoxetine or norfluoxetine as an inhibitor of the metabolism of several substrates for this enzyme, including astemizole, cisapride, and midazolam.

These include: specific antipsychotics (e.g., ziprasidone, iloperidone, chlorpromazine, mesoridazine, droperidol); specific antibiotics (e.g., erythromycin, gatifloxacin, moxifloxacin, sparfloxacin); Class 1A antiarrhythmic medications (e.g., quinidine, procainamide); Class III antiarrhythmics (e.g., amiodarone, sotalol); and others (e.g., pentamidine, levomethadyl acetate, methadone, halofantrine, mefloquine, dolasetron mesylate, probucol or tacrolimus).

These include: specific antipsychotics (e.g., ziprasidone, iloperidone, chlorpromazine, mesoridazine, droperidol); specific antibiotics (e.g., erythromycin, gatifloxacin, moxifloxacin, sparfloxacin); Class 1A antiarrhythmic medications (e.g., quinidine, procainamide); Class III antiarrhythmics (e.g., amiodarone, sotalol); and others (e.g., pentamidine, levomethadyl acetate, methadone, halofantrine, mefloquine, dolasetron mesylate, probucol or tacrolimus).

These include: specific antipsychotics (e.g., ziprasidone, iloperidone, chlorpromazine, mesoridazine, droperidol); specific antibiotics (e.g., erythromycin, gatifloxacin, moxifloxacin, sparfloxacin); Class 1A antiarrhythmic medications (e.g., quinidine, procainamide); Class III antiarrhythmics (e.g., amiodarone, sotalol); and others (e.g., pentamidine, levomethadyl acetate, methadone, halofantrine, mefloquine, dolasetron mesylate, probucol or tacrolimus).