levomilnacipran (Rx)

Brand and Other Names:Fetzima
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

capsule, extended-release

  • 20mg
  • 40mg
  • 80mg
  • 120mg

titration packs

  • Contains two 20mg capsules and twenty-six 40mg capsules

Major Depressive Disorders

SNRI indicated for major depressive disorders in adults

20 mg PO qDay x2 days initially; THEN

Increase to 40 mg PO qDay

Based on efficacy and tolerability, increase dose in increments of 40 mg/day at intervals of 2 or more days; not to exceed 120 mg/day

Dosage range: 40-120 mg/day

Dosage Modifications

Strong CYP3A4 inhibitors: Not to exceed 80 mg/day levomilnacipran maintenance dose

Hepatic impairment: Hepatic elimination is low, no dosage adjustment required with mild, moderate, or severe hepatic impairment

Renal impairment

  • Mild (CrCl 60-89 mL/min): No dosage adjustment required
  • Moderate (CrCl 30-59 mL/min): Not to exceed 80 mg/day maintenance dose
  • Severe (CrCl 15-29 mL/min): Not to exceed 40 mg/day maintenance dose
  • End-stage renal disease: Not recommended

Dosing Considerations

Not approved for the management of fibromyalgia

Screen for personal or family history of bipolar disorder, mania, or hypomania before initiating antidepressants

Safety and efficacy not established

Next:

Interactions

Interaction Checker

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            Contraindicated (10)

            • ethanol

              ethanol will increase the level or effect of levomilnacipran by enhancing GI absorption. Applies only to oral form of both agents. Contraindicated. Alcohol interacts with the extended-release properties of levomilnacipran capsules resulting in a pronounced accelerated drug release

            • iobenguane I 123

              levomilnacipran decreases effects of iobenguane I 123 by pharmacodynamic antagonism. Contraindicated. If clinically appropriate, discontinue drugs that decrease uptake of NE for at least 5 half-lives; may cause false-negative imaging results.

            • isocarboxazid

              isocarboxazid and levomilnacipran both increase serotonin levels. Contraindicated. Do not use MAOIs intended to treat psychiatric disorders with levomilnacipran or within 7 days of stopping levomilnacipran due to an increased risk of serotonin syndrome

            • phenelzine

              phenelzine and levomilnacipran both increase serotonin levels. Contraindicated. Do not use MAOIs intended to treat psychiatric disorders with levomilnacipran or within 7 days of stopping levomilnacipran due to an increased risk of serotonin syndrome

            • procarbazine

              procarbazine and levomilnacipran both increase serotonin levels. Contraindicated. Combination is contraindicated within 2 weeks of MAOI use.

            • rasagiline

              rasagiline and levomilnacipran both increase serotonin levels. Contraindicated. Concomitant use with MAOIs or within 14 days of discontinuing treatment with an MAOI is contraindicated.

            • safinamide

              levomilnacipran, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.

            • selegiline

              selegiline and levomilnacipran both increase serotonin levels. Contraindicated. Combination is contraindicated within 2 weeks of MAOI use

            • selegiline transdermal

              selegiline transdermal and levomilnacipran both increase serotonin levels. Contraindicated. Combination is contraindicated within 2 weeks of MAOI use

            • tranylcypromine

              tranylcypromine and levomilnacipran both increase serotonin levels. Contraindicated. Do not use MAOIs intended to treat psychiatric disorders with levomilnacipran or within 7 days of stopping levomilnacipran due to an increased risk of serotonin syndrome

            Serious - Use Alternative (61)

            • abametapir

              abametapir will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.

            • amitriptyline

              levomilnacipran and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

            • amoxapine

              levomilnacipran and amoxapine both increase serotonin levels. Avoid or Use Alternate Drug.

            • apalutamide

              apalutamide will decrease the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.

            • apixaban

              levomilnacipran, apixaban. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. SNRIs may further impair platelet activity in patients taking antiplatelet or anticoagulant drugs.

            • buspirone

              levomilnacipran and buspirone both increase serotonin levels. Avoid or Use Alternate Drug.

            • chloramphenicol

              chloramphenicol will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • citalopram

              citalopram and levomilnacipran both increase serotonin levels. Avoid or Use Alternate Drug. Combination may increase risk of serotonin syndrome or neuroleptic malignant syndrome-like reactions.

            • clomipramine

              levomilnacipran and clomipramine both increase serotonin levels. Avoid or Use Alternate Drug.

            • cobicistat

              cobicistat will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Do not esceed 80 mg levominacipram dose once daily if coadministration necessary

            • cyclobenzaprine

              levomilnacipran and cyclobenzaprine both increase serotonin levels. Avoid or Use Alternate Drug.

            • desipramine

              levomilnacipran and desipramine both increase serotonin levels. Avoid or Use Alternate Drug.

            • desvenlafaxine

              levomilnacipran and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • dexmethylphenidate

              dexmethylphenidate and levomilnacipran both increase serotonin levels. Avoid or Use Alternate Drug.

            • dextromethorphan

              levomilnacipran and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • dolasetron

              dolasetron, levomilnacipran. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

            • dosulepin

              levomilnacipran and dosulepin both increase serotonin levels. Avoid or Use Alternate Drug.

            • doxepin

              levomilnacipran and doxepin both increase serotonin levels. Avoid or Use Alternate Drug.

            • duloxetine

              duloxetine and levomilnacipran both increase serotonin levels. Avoid or Use Alternate Drug.

            • epinephrine

              levomilnacipran increases levels of epinephrine by pharmacodynamic synergism. Avoid or Use Alternate Drug. Risk of paroxysmal HTN, arrhythmia.

            • epinephrine racemic

              levomilnacipran increases levels of epinephrine racemic by pharmacodynamic synergism. Avoid or Use Alternate Drug. Risk of paroxysmal HTN, arrhythmia.

            • escitalopram

              escitalopram and levomilnacipran both increase serotonin levels. Avoid or Use Alternate Drug.

            • fexinidazole

              fexinidazole will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

            • fluoxetine

              fluoxetine and levomilnacipran both increase serotonin levels. Avoid or Use Alternate Drug.

            • fluvoxamine

              fluvoxamine and levomilnacipran both increase serotonin levels. Avoid or Use Alternate Drug.

            • granisetron

              granisetron, levomilnacipran. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

            • idelalisib

              idelalisib will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates

            • imipramine

              levomilnacipran and imipramine both increase serotonin levels. Avoid or Use Alternate Drug.

            • iobenguane I 131

              levomilnacipran will decrease the level or effect of iobenguane I 131 by Other (see comment). Avoid or Use Alternate Drug. Based on the mechanism of action of iobenguane, drugs that reduce catecholamine uptake or that deplete catecholamine stores may interfere with iobenguane uptake into cells, and thus, reduce iobenguane efficacy. Discontinue interfering drugs for at least 5 half-lives before administration of either the dosimetry or an iobenguane dose. Do not administer these drugs until at least 7 days after each iobenguane dose.

            • ivosidenib

              ivosidenib will decrease the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternative therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

            • linezolid

              linezolid and levomilnacipran both increase serotonin levels. Avoid or Use Alternate Drug. Linezolid may increase serotonin as a result of MAO-A inhibition. If linezolid must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last linezolid dose or after 2 weeks of monitoring, whichever comes first.

            • lofepramine

              levomilnacipran and lofepramine both increase serotonin levels. Avoid or Use Alternate Drug.

            • lorcaserin

              levomilnacipran and lorcaserin both increase serotonin levels. Avoid or Use Alternate Drug.

            • maprotiline

              levomilnacipran and maprotiline both increase serotonin levels. Avoid or Use Alternate Drug.

            • meperidine

              levomilnacipran and meperidine both increase serotonin levels. Avoid or Use Alternate Drug.

            • methylene blue

              methylene blue and levomilnacipran both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.

            • metoclopramide

              metoclopramide and levomilnacipran both increase serotonin levels. Avoid or Use Alternate Drug. Additive effects; increased risk for serotonin syndrome, neuroleptic malignant syndrome, dystonia, or other extrapyramidal reactions

            • mifepristone

              mifepristone will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • milnacipran

              levomilnacipran and milnacipran both increase serotonin levels. Avoid or Use Alternate Drug.

            • nefazodone

              levomilnacipran and nefazodone both increase serotonin levels. Avoid or Use Alternate Drug.

            • netupitant/palonosetron

              netupitant/palonosetron, levomilnacipran. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

            • norepinephrine

              levomilnacipran increases levels of norepinephrine by pharmacodynamic synergism. Avoid or Use Alternate Drug. Risk of paroxysmal HTN, arrhythmia.

            • nortriptyline

              levomilnacipran and nortriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

            • ondansetron

              ondansetron, levomilnacipran. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

            • ozanimod

              ozanimod increases toxicity of levomilnacipran by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Because the active metabolite of ozanimod inhibits MAO-B in vitro, there is a potential for serious adverse reactions, including hypertensive crisis. Therefore, coadministration of ozanimod with drugs that can increase norepinephrine or serotonin is not recommended. Monitor for hypertension with concomitant use.

            • palonosetron

              palonosetron, levomilnacipran. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

            • paroxetine

              levomilnacipran and paroxetine both increase serotonin levels. Avoid or Use Alternate Drug.

            • phentermine

              levomilnacipran and phentermine both increase serotonin levels. Avoid or Use Alternate Drug.

            • protriptyline

              levomilnacipran and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

            • pseudoephedrine

              levomilnacipran increases effects of pseudoephedrine by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug.

            • sertraline

              levomilnacipran and sertraline both increase serotonin levels. Avoid or Use Alternate Drug.

            • St John's Wort

              levomilnacipran and St John's Wort both increase serotonin levels. Avoid or Use Alternate Drug.

            • tedizolid

              tedizolid, levomilnacipran. Either increases effects of the other by Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. both increase serotonin levels; increased risk of serotonin syndrome.

            • trazodone

              levomilnacipran and trazodone both increase serotonin levels. Avoid or Use Alternate Drug.

            • trimipramine

              levomilnacipran and trimipramine both increase serotonin levels. Avoid or Use Alternate Drug.

            • tucatinib

              tucatinib will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.

            • venlafaxine

              levomilnacipran and venlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • vilazodone

              levomilnacipran, vilazodone. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug. Concomitant therapy should be discontinued immediately if signs or symptoms of serotonin syndrome emerge and supportive symptomatic treatment should be initiated. .

            • vortioxetine

              levomilnacipran, vortioxetine. Either increases effects of the other by serotonin levels. Avoid or Use Alternate Drug.

            • voxelotor

              voxelotor will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.

            • warfarin

              levomilnacipran, warfarin. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. SNRIs may further impair platelet activity in patients taking antiplatelet or anticoagulant drugs.

            Monitor Closely (130)

            • 5-HTP

              levomilnacipran and 5-HTP both increase serotonin levels. Modify Therapy/Monitor Closely.

            • almotriptan

              almotriptan and levomilnacipran both increase serotonin levels. Modify Therapy/Monitor Closely.

            • aripiprazole

              levomilnacipran, aripiprazole. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • asenapine

              levomilnacipran, asenapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • aspirin

              levomilnacipran, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. SNRIs may further impair platelet activity in patients taking antiplatelet or anticoagulant drugs.

            • aspirin rectal

              levomilnacipran, aspirin rectal. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. SNRIs may further impair platelet activity in patients taking antiplatelet or anticoagulant drugs.

            • aspirin/citric acid/sodium bicarbonate

              levomilnacipran, aspirin/citric acid/sodium bicarbonate. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. SNRIs may further impair platelet activity in patients taking antiplatelet or anticoagulant drugs.

            • atazanavir

              atazanavir will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Do not exceed 80 mg/day of levomilnacipran when coadministered with strong CYP3A4 inhibitors

            • benzhydrocodone/acetaminophen

              benzhydrocodone/acetaminophen, levomilnacipran. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • buprenorphine subdermal implant

              levomilnacipran, buprenorphine subdermal implant. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.

            • buprenorphine, long-acting injection

              levomilnacipran, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.

            • cariprazine

              levomilnacipran, cariprazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • celecoxib

              levomilnacipran, celecoxib. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. SNRIs may further impair platelet activity in patients taking antiplatelet or anticoagulant drugs.

            • cenobamate

              cenobamate will decrease the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.

            • choline magnesium trisalicylate

              levomilnacipran, choline magnesium trisalicylate. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. SNRIs may further impair platelet activity in patients taking antiplatelet or anticoagulant drugs.

            • clarithromycin

              clarithromycin will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Do not exceed 80 mg/day of levomilnacipran when coadministered with strong CYP3A4 inhibitors

            • clonidine

              levomilnacipran decreases effects of clonidine by pharmacodynamic antagonism. Use Caution/Monitor. Because levomilnacipran decreases reuptake of NE, it may antagonize clonidine antihypertensive effect.

            • clopidogrel

              levomilnacipran increases effects of clopidogrel by pharmacodynamic synergism. Use Caution/Monitor. SNRIs affect platelet activation; coadministration of SNRIs with clopidogrel may increase the risk of bleeding.

            • clozapine

              levomilnacipran, clozapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • cocaine

              levomilnacipran and cocaine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • conivaptan

              conivaptan will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Do not exceed 80 mg/day of levomilnacipran when coadministered with strong CYP3A4 inhibitors

            • cyproheptadine

              cyproheptadine decreases effects of levomilnacipran by pharmacodynamic antagonism. Use Caution/Monitor. Cyproheptadine may diminish the serotonergic effect of SNRIs.

            • darunavir

              darunavir will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Do not exceed 80 mg/day of levomilnacipran when coadministered with strong CYP3A4 inhibitors

            • dexfenfluramine

              levomilnacipran and dexfenfluramine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • dextroamphetamine

              levomilnacipran and dextroamphetamine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • diazepam intranasal

              diazepam intranasal, levomilnacipran. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may potentiate the CNS-depressant effects of each drug.

            • diclofenac

              levomilnacipran, diclofenac. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. SNRIs may further impair platelet activity in patients taking antiplatelet or anticoagulant drugs.

            • diflunisal

              levomilnacipran, diflunisal. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. SNRIs may further impair platelet activity in patients taking antiplatelet or anticoagulant drugs.

            • dihydroergotamine

              levomilnacipran and dihydroergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • dihydroergotamine intranasal

              levomilnacipran and dihydroergotamine intranasal both increase serotonin levels. Modify Therapy/Monitor Closely.

            • duvelisib

              duvelisib will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with duvelisib increases AUC of a sensitive CYP3A4 substrate which may increase the risk of toxicities of these drugs. Consider reducing the dose of the sensitive CYP3A4 substrate and monitor for signs of toxicities of the coadministered sensitive CYP3A substrate.

            • elagolix

              elagolix decreases levels of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.

            • eletriptan

              eletriptan and levomilnacipran both increase serotonin levels. Modify Therapy/Monitor Closely.

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

              elvitegravir/cobicistat/emtricitabine/tenofovir DF will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Do not exceed 80 mg/day of levomilnacipran when coadministered with strong CYP3A4 inhibitors

            • encorafenib

              encorafenib, levomilnacipran. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.

            • ergotamine

              levomilnacipran and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • etodolac

              levomilnacipran, etodolac. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. SNRIs may further impair platelet activity in patients taking antiplatelet or anticoagulant drugs.

            • fedratinib

              fedratinib will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • fenfluramine

              levomilnacipran and fenfluramine both increase serotonin levels. Modify Therapy/Monitor Closely.

              fenfluramine, levomilnacipran. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration with drugs that increase serotoninergic effects may increase the risk of serotonin syndrome.

            • fenoprofen

              levomilnacipran, fenoprofen. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. SNRIs may further impair platelet activity in patients taking antiplatelet or anticoagulant drugs.

            • fish oil triglycerides

              fish oil triglycerides will increase the level or effect of levomilnacipran by anticoagulation. Use Caution/Monitor. Prolonged bleeding reported in patients taking antiplatelet agents or anticoagulants and oral omega-3 fatty acids. Periodically monitor bleeding time in patients receiving fish oil triglycerides and concomitant antiplatelet agents or anticoagulants.

            • fluphenazine

              levomilnacipran, fluphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • flurbiprofen

              levomilnacipran, flurbiprofen. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. SNRIs may further impair platelet activity in patients taking antiplatelet or anticoagulant drugs.

            • fosamprenavir

              fosamprenavir will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Do not exceed 80 mg/day of levomilnacipran when coadministered with strong CYP3A4 inhibitors

            • frovatriptan

              frovatriptan and levomilnacipran both increase serotonin levels. Modify Therapy/Monitor Closely.

            • gabapentin

              gabapentin, levomilnacipran. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

            • gabapentin enacarbil

              gabapentin enacarbil, levomilnacipran. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

            • haloperidol

              levomilnacipran, haloperidol. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • hydrocodone

              hydrocodone, levomilnacipran. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • ibrutinib

              ibrutinib will increase the level or effect of levomilnacipran by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

            • ibuprofen

              levomilnacipran, ibuprofen. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. SNRIs may further impair platelet activity in patients taking antiplatelet or anticoagulant drugs.

            • ibuprofen IV

              levomilnacipran, ibuprofen IV. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. SNRIs may further impair platelet activity in patients taking antiplatelet or anticoagulant drugs.

            • iloperidone

              levomilnacipran, iloperidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • imatinib

              imatinib will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Do not exceed 80 mg/day of levomilnacipran when coadministered with strong CYP3A4 inhibitors

            • indinavir

              indinavir will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Do not exceed 80 mg/day of levomilnacipran when coadministered with strong CYP3A4 inhibitors

            • indomethacin

              levomilnacipran, indomethacin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. SNRIs may further impair platelet activity in patients taking antiplatelet or anticoagulant drugs.

            • isoniazid

              levomilnacipran and isoniazid both increase serotonin levels. Modify Therapy/Monitor Closely.

              isoniazid will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Do not exceed 80 mg/day of levomilnacipran when coadministered with strong CYP3A4 inhibitors

            • istradefylline

              istradefylline will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.

            • itraconazole

              itraconazole will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Do not exceed 80 mg/day of levomilnacipran when coadministered with strong CYP3A4 inhibitors

            • ketoconazole

              ketoconazole will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Do not exceed 80 mg/day of levomilnacipran when coadministered with strong CYP3A4 inhibitors

            • ketoprofen

              levomilnacipran, ketoprofen. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. SNRIs may further impair platelet activity in patients taking antiplatelet or anticoagulant drugs.

            • ketorolac

              levomilnacipran, ketorolac. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. SNRIs may further impair platelet activity in patients taking antiplatelet or anticoagulant drugs.

            • ketorolac intranasal

              levomilnacipran, ketorolac intranasal. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. SNRIs may further impair platelet activity in patients taking antiplatelet or anticoagulant drugs.

            • L-tryptophan

              levomilnacipran and L-tryptophan both increase serotonin levels. Modify Therapy/Monitor Closely.

            • lasmiditan

              lasmiditan, levomilnacipran. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions.

              levomilnacipran increases effects of lasmiditan by serotonin levels. Use Caution/Monitor. Coadministration may increase risk of serotonin syndrome.

            • lemborexant

              lemborexant, levomilnacipran. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects.

            • levodopa

              levomilnacipran and levodopa both increase serotonin levels. Modify Therapy/Monitor Closely.

            • lisdexamfetamine

              levomilnacipran, lisdexamfetamine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Initiate with lower doses and monitor for signs and symptoms of serotonin syndrome, particularly during initiation or dosage increase. If serotonin syndrome occurs, discontinue along with concomitant serotonergic drug(s).

            • lithium

              levomilnacipran and lithium both increase serotonin levels. Modify Therapy/Monitor Closely.

            • lopinavir

              lopinavir will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Do not exceed 80 mg/day of levomilnacipran when coadministered with strong CYP3A4 inhibitors

            • loxapine

              levomilnacipran, loxapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • loxapine inhaled

              levomilnacipran, loxapine inhaled. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • lsd

              levomilnacipran and lsd both increase serotonin levels. Modify Therapy/Monitor Closely.

            • lurasidone

              levomilnacipran, lurasidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • meclofenamate

              levomilnacipran, meclofenamate. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. SNRIs may further impair platelet activity in patients taking antiplatelet or anticoagulant drugs.

            • mefenamic acid

              levomilnacipran, mefenamic acid. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. SNRIs may further impair platelet activity in patients taking antiplatelet or anticoagulant drugs.

            • meloxicam

              levomilnacipran, meloxicam. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. SNRIs may further impair platelet activity in patients taking antiplatelet or anticoagulant drugs.

            • mirtazapine

              levomilnacipran and mirtazapine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • mitotane

              mitotane decreases levels of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments.

            • molindone

              levomilnacipran, molindone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • morphine

              levomilnacipran and morphine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • nabumetone

              levomilnacipran, nabumetone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. SNRIs may further impair platelet activity in patients taking antiplatelet or anticoagulant drugs.

            • naproxen

              levomilnacipran, naproxen. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. SNRIs may further impair platelet activity in patients taking antiplatelet or anticoagulant drugs.

            • naratriptan

              naratriptan and levomilnacipran both increase serotonin levels. Modify Therapy/Monitor Closely.

            • nefazodone

              nefazodone will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Do not exceed 80 mg/day of levomilnacipran when coadministered with strong CYP3A4 inhibitors

            • nelfinavir

              nelfinavir will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Do not exceed 80 mg/day of levomilnacipran when coadministered with strong CYP3A4 inhibitors

            • nicardipine

              nicardipine will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Do not exceed 80 mg/day of levomilnacipran when coadministered with strong CYP3A4 inhibitors

            • olanzapine

              levomilnacipran, olanzapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • oliceridine

              levomilnacipran, oliceridine. Either increases effects of the other by serotonin levels. Modify Therapy/Monitor Closely.

            • oxaprozin

              levomilnacipran, oxaprozin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. SNRIs may further impair platelet activity in patients taking antiplatelet or anticoagulant drugs.

            • paliperidone

              levomilnacipran, paliperidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • pentazocine

              levomilnacipran and pentazocine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • perphenazine

              levomilnacipran, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • pimavanserin

              levomilnacipran, pimavanserin. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • pimozide

              levomilnacipran, pimozide. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • piroxicam

              levomilnacipran, piroxicam. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. SNRIs may further impair platelet activity in patients taking antiplatelet or anticoagulant drugs.

            • posaconazole

              posaconazole will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Do not exceed 80 mg/day of levomilnacipran when coadministered with strong CYP3A4 inhibitors

            • pregabalin

              pregabalin, levomilnacipran. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

            • quetiapine

              levomilnacipran, quetiapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • quinidine

              quinidine will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Do not exceed 80 mg/day of levomilnacipran when coadministered with strong CYP3A4 inhibitors

            • remifentanil

              remifentanil increases toxicity of levomilnacipran by serotonin levels. Modify Therapy/Monitor Closely. Increases risk of serotonin syndrome.

            • remimazolam

              remimazolam, levomilnacipran. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.

            • ribociclib

              ribociclib will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • risperidone

              levomilnacipran, risperidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • ritonavir

              ritonavir will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Do not exceed 80 mg/day of levomilnacipran when coadministered with strong CYP3A4 inhibitors

            • rizatriptan

              rizatriptan and levomilnacipran both increase serotonin levels. Modify Therapy/Monitor Closely.

            • rucaparib

              rucaparib will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.

            • salsalate

              levomilnacipran, salsalate. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. SNRIs may further impair platelet activity in patients taking antiplatelet or anticoagulant drugs.

            • SAMe

              levomilnacipran and SAMe both increase serotonin levels. Modify Therapy/Monitor Closely.

            • saquinavir

              saquinavir will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Do not exceed 80 mg/day of levomilnacipran when coadministered with strong CYP3A4 inhibitors

            • sodium sulfate/potassium sulfate/magnesium sulfate/polyethylene glycol

              levomilnacipran, sodium sulfate/potassium sulfate/magnesium sulfate/polyethylene glycol. Other (see comment). Use Caution/Monitor. Comment: Caution when bowel preps are used with drugs that cause SIADH or NSAIDs; increased risk for water retention or electrolyte imbalance.

            • stiripentol

              stiripentol, levomilnacipran. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.

            • sufentanil SL

              sufentanil SL, levomilnacipran. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • sulfasalazine

              levomilnacipran, sulfasalazine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. SNRIs may further impair platelet activity in patients taking antiplatelet or anticoagulant drugs.

            • sulindac

              levomilnacipran, sulindac. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. SNRIs may further impair platelet activity in patients taking antiplatelet or anticoagulant drugs.

            • sumatriptan

              sumatriptan and levomilnacipran both increase serotonin levels. Modify Therapy/Monitor Closely.

            • sumatriptan intranasal

              sumatriptan intranasal and levomilnacipran both increase serotonin levels. Modify Therapy/Monitor Closely.

            • tapentadol

              levomilnacipran and tapentadol both increase serotonin levels. Modify Therapy/Monitor Closely.

            • tazemetostat

              tazemetostat will decrease the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tecovirimat

              tecovirimat will decrease the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.

            • thiothixene

              levomilnacipran, thiothixene. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • tipranavir

              tipranavir will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Do not exceed 80 mg/day of levomilnacipran when coadministered with strong CYP3A4 inhibitors

            • tolmetin

              levomilnacipran, tolmetin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. SNRIs may further impair platelet activity in patients taking antiplatelet or anticoagulant drugs.

            • tramadol

              levomilnacipran and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.

            • trifluoperazine

              levomilnacipran, trifluoperazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • valerian

              valerian and levomilnacipran both increase sedation. Use Caution/Monitor.

            • vorapaxar

              levomilnacipran, vorapaxar. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive antiplatelet effect may occur; SSRIs and SNRIs may cause platelet serotonin depletion .

            • voriconazole

              voriconazole will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Do not exceed 80 mg/day of levomilnacipran when coadministered with strong CYP3A4 inhibitors

            • ziprasidone

              levomilnacipran, ziprasidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • zolmitriptan

              zolmitriptan and levomilnacipran both increase serotonin levels. Modify Therapy/Monitor Closely.

            Minor (5)

            • bumetanide

              bumetanide, levomilnacipran. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Possible additive hyponatremia.

            • ethacrynic acid

              ethacrynic acid, levomilnacipran. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Possible additive hyponatremia.

            • furosemide

              furosemide, levomilnacipran. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Possible additive hyponatremia.

            • lithium

              levomilnacipran, lithium. Mechanism: unknown. Minor/Significance Unknown. Risk of neurotoxicity.

            • torsemide

              torsemide, levomilnacipran. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Possible additive hyponatremia.

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            Adverse Effects

            >10%

            Nausea (17%)

            1-10%

            Erectile dysfunction, dose-related (6-10%)

            Constipation (9%)

            Tachycardia (6%)

            Urinary hesitation, dose-related (4-6%)

            Palpitations (5%)

            Vomiting (5%)

            Hyperhidrosis (2%)

            Increased heart rate (1%)

            Increased blood pressure (1%)

            Hot flush (1%)

            Hypotension (1%)

            Decreased appetite (1%)

            <1%

            Testicular pain

            Ejaculation disorder

            Postmarketing Results

            Takotsubo cardiomyopathy

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            Warnings

            Black Box Warnings

            In short-term studies, antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults (<24 yr of age) taking antidepressants for major depressive disorders and other psychiatric illnesses

            This increase was not seen in patients aged >24 years; a slight decrease in suicidal thinking was seen in adults >65 years

            In children and young adults, risks must be weighed against the benefits of taking antidepressants

            Patients should be monitored closely for changes in behavior, clinical worsening, and suicidal tendencies; this should be done during initial 1-2 months of therapy and dosage adjustments

            The patient’s family should communicate any abrupt changes in behavior to the healthcare provider

            Worsening behavior and suicidal tendencies that are not part of the presenting symptoms may require discontinuation of therapy

            This drug is not approved for use in pediatric patients

            Contraindications

            Hypersensitivity

            MAOIs

            • Do not use MAOIs intended to treat psychiatric disorders with levomilnacipran or within 7 days of stopping levomilnacipran due to an increased risk of serotonin syndrome
            • Do not initiate levomilnacipran within 14 days of stopping an MAOI
            • Starting in a patient who is being treated with MAOIs such as linezolid or IV methylene blue is also contraindicated due to an increased risk of serotonin syndrome
            • If methylene blue or linezolid must be administered for an urgent condition to a patient currently taking a serotonergic drug, stop serotonergic drug immediately and monitor for CNS toxicity; serotonergic therapy may be resumed 24 hr after the last dose of methylene blue, or after 2 weeks of monitoring, whichever comes first

            Cautions

            All patients being treated with antidepressants should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the first few months of treatment and when increasing or decreasing the dose; consider changing therapeutic regimen, including possibly discontinuing therapy, in patients whose depression is persistently worse, or who are experiencing emergent suicidal thoughts or behaviors

            SSRIs and SNRIs may impair platelet aggregation and increase the risk of bleeding events, ranging from ecchymoses, hematomas, epistaxis, petechiae, and GI hemorrhage to life-threatening hemorrhage; concomitant use of other drugs that inhibit platelets or anticoagulants may increase this risk; inform patients about risk of bleeding associated with concomitant use of drug and NSAIDs, aspirin, or other drugs that affect coagulation

            Risk of mydriasis; may trigger angle closure attack in patients with angle-closure glaucoma with anatomically narrow angles without a patent iridectomy; pre- existing glaucoma is almost always open-angle glaucoma because angle-closure glaucoma, when diagnosed, can be treated definitively with iridectomy; open-angle glaucoma is not a risk factor for angle-closure glaucoma

            Can affect urinary hesitation or retention; caution with obstructive urinary disorders and discontinue is symptoms present; the noradrenergic effect of the drug, can affect urethral resistance; if symptoms of urinary hesitation, urinary retention, or dysuria develop during treatment, consideration should be given to possibility that they might be drug-related, and discontinuation or other appropriate medical intervention should be considered

            May activate mania/hypomania in patients with bipolar disorder; screen patients for bipolar disorder prior to initiating; use cautiously in patients with a history or family history of bipolar disorder, mania, or hypomania

            Caution with seizure disorders; not systematically evaluated in patients with seizure disorder

            Sexual dysfunction

            • Use may cause symptoms of sexual dysfunction in both male and female patients; inform patients that they should discuss any changes in sexual function and potential management strategies with their healthcare provider
            • Use of SSRIs, may cause symptoms of sexual dysfunction; in male patients, SSRI use may result in ejaculatory delay or failure, decreased libido, and erectile dysfunction
            • In female patients, SSRI/SNRI use may result in decreased libido and delayed or absent orgasm
            • Important for prescribers to inquire about sexual function prior to initiation of therapy and to inquire specifically about changes in sexual function during treatment, because sexual function may not be spontaneously reported
            • When evaluating changes in sexual function, obtaining a detailed history (including timing of symptom onset) is important because sexual symptoms may have other causes, including underlying psychiatric disorder
            • Discuss potential management strategies to support patients in making informed decisions about treatment

            Serotonin syndrome

            • Potentially life-threatening serotonin syndrome has been reported with SNRIs and SSRIs both when taken alone, but especially when coadministered with other serotonergic agents; thoroughly review patient medications for other serotonergic drugs (eg, tryptophan supplements, tramadol, 5-HT agonists [triptans], MAOIs, TCAs, SSRIs)
            • Serotonin syndrome symptoms may include mental status changes (eg, agitation, hallucinations, delirium, and coma), autonomic instability (eg, tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (eg, tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (eg, nausea, vomiting, diarrhea)
            • Monitor all patients receiving therapy for emergence of serotonin syndrome; discontinue treatment with drug and any concomitant serotonergic agents immediately if above events occur and initiate supportive symptomatic treatment; if concomitant use of drug with other serotonergic drugs is clinically warranted, inform patients of increased risk for serotonin syndrome and monitor for symptoms

            Blood pressure

            • May increase blood pressure; blood pressure should be measured prior to initiating treatment and periodically throughout treatment
            • Pre-existing hypertension should be controlled before initiating therapy
            • Use caution when treating patients with pre-existing hypertension, cardiovascular, or cerebrovascular conditions that might be compromised by increases in blood pressure
            • For patients who experience a sustained increase in blood pressure while receiving drug, discontinuation or other appropriate medical intervention should be considered

            Heart rate

            • Therapy may increase heart rate; heart rate should be measured prior to initiating treatment and periodically throughout treatment
            • Pre­existing tachyarrhythmias and other cardiac disease should be treated before starting therapy; for patients who experience a sustained increase in heart rate while receiving therapy, discontinuation or other appropriate medical intervention should be considered
            • Drug has not been systematically evaluated in patients with a cardiac rhythm disorder

            Discontinuation syndrome

            • Discontinuation symptoms (some serious) reported with abrupt withdrawal of serotonergic antidepressants
            • Some symptoms include dysphoric mood, irritability, agitation, dizziness, sensory disturbances (e.g., paresthesia, such as electric shock sensations), anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus, and seizures
            • Monitor patients for these symptoms when discontinuing therapy; reduce dose gradually whenever possible; if intolerable symptoms occur following a decrease in dose or upon discontinuation of treatment, consider resuming previously prescribed dose; subsequently, the dose may be decreased, but at a more gradual rate

            Hyponatremia

            • Hyponatremia may occur; in many cases, hyponatremia appears to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH); cases with serum sodium lower than 110 mmol/L reported
            • Elderly patients may be at greater risk of developing hyponatremia with SSRIs and SNRIs; patients taking diuretics or who are otherwise volume depleted can be at greater risk
            • Therapy should be discontinued in patients with symptomatic hyponatremia and appropriate medical intervention instituted
            • Signs and symptoms of hyponatremia include headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness, which can lead to falls
            • Signs and symptoms associated with more severe and/or acute cases have included hallucination, syncope, seizure, coma, respiratory arrest, and death

            Drug interaction overview

            • Contraindicated with an MAOI (or within 14 days of stopping an MAOI) intended to treat psychiatric disorders or within 7 days of stopping treatment with levomilnacipran; it is also contraindicated in patients treated with linezolid or IV methylene blue
            • Coadministration with strong CYP3A4 inhibitors may increase levomilnacipran levels; see Dosage Modifications
            • Avoid alcohol with levomilnacipran; concomitant use may result in accelerated release of levomilnacipran from the extended-release capsules
            • SSRIs and SNRIs may impair platelet aggregation and increase the risk of bleeding events; coadministration with other antiplatelet drug or anticoagulants may cause additive risk
            • Coadministration with other serotonergic drugs may increase risk of serotonin syndrome
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            Pregnancy & Lactation

            Pregnancy

            There is pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy; healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or visiting online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants

            Available data on pregnant women are insufficient to evaluate for drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes; there are risks associated with untreated depression in pregnancy and with exposure to SNRIs and SSRIs during pregnancy

            Clinical considerations

            • Women who discontinued antidepressants during pregnancy were more likely to experience relapse of major depression than women who continued antidepressants; consider risk of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum
            • Use of SNRIs in late pregnancy may be associated with an increased risk of postpartum hemorrhage

            Fetal/neonatal effects

            • Neonates exposed to SNRIs or SSRIs, late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding; such complications can arise immediately upon delivery
            • Reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying

            Animal data

            • In animal reproduction studies, drug was not associated with malformations in rats or rabbits when given during the period of organogenesis at doses up to 8 or 16 times maximum recommended human dose (MRHD) of 120 mg on a mg/m2 basis, respectively
            • However, an increase in early post-natal rat pup mortality was seen at a dose equivalent to 5 times the MRHD given during pregnancy and lactation

            Lactation

            There are no available data on presence of drug in human milk; however, racemic milnacipran is present in human milk; there are no reports on effects of drug or milnacipran on breastfed infant or effects on milk production; however, there are reports of agitation, irritability, poor feeding and poor weight gain in infants exposed to SSRIs or SNRIs through breast milk

            The developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed child from drug or from underlying maternal conditions

            Clinical considerations

            • Infants exposed to drug should be monitored for agitation, irritability, poor feeding and poor weight gain

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Active enantiomer milnacipran; potent inhibitor of neuronal serotonin and norepinephrine reuptake (SNRI); inhibits norepinephrine uptake with ~3-fold higher potency in vitro than serotonin without directly affecting the uptake of dopamine or other neurotransmitters

            Absorption

            Bioavailability: 92%

            Peak plasma time: 6-8 hr

            Peak plasma concentration: 341 ng/mL

            AUC: 5196 ng•h/mL

            Distribution

            Protein bound: 22%

            Vd: 387-473 L

            Metabolism

            Undergoes desethylation to form desethyl levomilnacipran and hydroxylation to form p-hydroxy-levomilnacipran; both oxidative metabolites undergo further conjugation with glucuronide to form conjugates and are inactive

            Desethylation is catalyzed primarily by CYP3A4 with minor contribution by CYP2C8, 2C19, 2D6, and 2J2

            Elimination

            Half-life, terminal: 12 hr

            Total clearance: 21-29 L/hr

            Excretion: 58% unchanged in urine; 18% N-desethyl metabolite in urine

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            Administration

            Oral Administration

            May take with or without food

            Take at approximately the same time each day

            Swallow capsules whole; do not open, chew, or crush

            Discontinuing drug

            • Avoid abrupt discontinuation if possible; gradual dose reduction recommended to avoid discontinuation symptoms associated with serotonergic drugs
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            Images

            BRAND FORM. UNIT PRICE PILL IMAGE
            Fetzima oral
            -
            80 mg capsule
            Fetzima oral
            -
            40 mg capsule
            Fetzima oral
            -
            120 mg capsule
            Fetzima oral
            -
            20 mg (2)- 40 mg (26) capsule
            Fetzima oral
            -
            20 mg capsule

            Copyright © 2010 First DataBank, Inc.

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            Patient Handout

            Patient Education
            levomilnacipran oral

            LEVOMILNACIPRAN - ORAL

            (LEE-voe-mil-NA-si-pran)

            COMMON BRAND NAME(S): Fetzima

            WARNING: Antidepressant medications are used to treat a variety of conditions, including depression and other mental/mood disorders. These medications can help prevent suicidal thoughts/attempts and provide other important benefits. However, studies have shown that a small number of people (especially people younger than 25) who take antidepressants for any condition may experience worsening depression, other mental/mood symptoms, or suicidal thoughts/attempts. It is very important to talk with the doctor about the risks and benefits of antidepressant medication (especially for people younger than 25), even if treatment is not for a mental/mood condition.Tell the doctor right away if you notice worsening depression/other psychiatric conditions, unusual behavior changes (including possible suicidal thoughts/attempts), or other mental/mood changes (including new/worsening anxiety, panic attacks, trouble sleeping, irritability, hostile/angry feelings, impulsive actions, severe restlessness, very rapid speech). Be especially watchful for these symptoms when a new antidepressant is started or when the dose is changed.

            USES: Levomilnacipran is used to treat depression. It works by helping to restore the balance of certain natural substances (serotonin and norepinephrine) in the brain. Levomilnacipran belongs to a class of drugs known as serotonin-norepinephrine reuptake inhibitors (SNRIs). It may improve your mood, sleep, and appetite and may help restore your interest in daily living.

            HOW TO USE: Read the Medication Guide and, if available, the Patient Information Leaflet provided by your pharmacist before you start taking levomilnacipran and each time you get a refill. If you have any questions, ask your doctor or pharmacist.Take this medication by mouth with or without food as directed by your doctor, usually once daily. Swallow the capsules whole. Do not open, crush or chew the capsules. Doing so can release all of the drug at once, increasing the risk of side effects.The dosage is based on your medical condition, response to treatment, and other medications you may be taking. Be sure to tell your doctor and pharmacist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).To reduce your risk of side effects, your doctor may direct you to start this medication at a low dose and gradually increase your dose. Follow your doctor's instructions carefully.Use this medication regularly to get the most benefit from it. To help you remember, take it at the same time each day.Do not increase your dose or use this drug more often or for longer than prescribed. Your condition will not improve any faster, and your risk of side effects will increase.It may take several months before you get the full benefit of this drug.Keep taking this medication even if you feel well. Do not stop taking this medication without consulting your doctor. Some conditions may become worse when this drug is suddenly stopped. Also, you may experience symptoms such as mood swings, headache, tiredness, sleep changes, and brief feelings similar to electric shock. To prevent these symptoms while you are stopping treatment with this drug, your doctor may reduce your dose gradually. Consult your doctor or pharmacist for more details. Report any new or worsening symptoms right away.Tell your doctor if your condition persists or worsens.

            SIDE EFFECTS: See also Warning section.Constipation, vomiting, increased sweating, dizziness, or nose bleeds may occur. Males may also have trouble getting/keeping an erection. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.This medication may raise your blood pressure. Check your blood pressure regularly and tell your doctor if the results are high.Tell your doctor right away if you have any serious side effects, including: pounding heartbeat, signs of stomach/intestinal bleeding (such as black/bloody stools, vomit that contains blood or looks like coffee grounds, dizziness), easy bleeding/bruising, problems beginning the flow of urine, painful/difficult urination, signs of low level of sodium in the blood (such as nausea, extreme drowsiness, mental/mood changes).Get medical help right away if you have any very serious side effects, including: seizures, eye pain/swelling/redness, widened pupils, vision changes (such as seeing rainbows around lights at night, blurred vision).This medication may increase serotonin and rarely cause a very serious condition called serotonin syndrome/toxicity. The risk increases if you are also taking other drugs that increase serotonin, so tell your doctor or pharmacist of all the drugs you take (see Drug Interactions section). Get medical help right away if you develop some of the following symptoms: fast heartbeat, hallucinations, loss of coordination, severe dizziness, severe nausea/vomiting/diarrhea, twitching muscles, unexplained fever, unusual agitation/restlessness.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

            PRECAUTIONS: Before taking levomilnacipran, tell your doctor or pharmacist if you are allergic to it; or to milnacipran; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney problems, personal or family history of glaucoma (angle-closure type), personal or family history of a certain mental/mood disorder (bipolar disorder), personal or family history of suicide attempts, high blood pressure, heart problems (such as chest pain, heart attack, fast/irregular heartbeat), poor blood flow to the brain, urinary retention or problems urinating (such as enlarged prostate), seizures, mineral imbalance (low level of sodium in the blood).This drug may make you dizzy or blur your vision. Alcohol or marijuana (cannabis) can make you more dizzy. Do not drive, use machinery, or do anything that needs alertness or clear vision until you can do it safely. Avoid alcoholic beverages. Talk to your doctor if you are using marijuana (cannabis).Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).Older adults may be at greater risk for a certain mineral imbalance (low level of sodium in the blood) while using this drug, especially if they are taking "water pills" (diuretics).During pregnancy, this medication should be used only when clearly needed. It may harm an unborn baby. Also, babies born to mothers who have used this drug during the last 3 months of pregnancy may rarely develop withdrawal symptoms such as feeding/breathing difficulties, seizures, muscle stiffness, or constant crying. If you notice any of these symptoms in your newborn, tell the doctor promptly.Since untreated mental/mood problems (such as depression) can be a serious condition, do not stop taking this medication unless directed by your doctor. If you are planning pregnancy, become pregnant, or think you may be pregnant, immediately discuss with your doctor the benefits and risks of using this medication during pregnancy.It is unknown if this medication passes into breast milk. However, similar drugs pass into breast milk. Consult your doctor before breast-feeding.

            DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.Some products that may interact with this drug include: diuretics/"water pills" (such as furosemide), other drugs that can cause bleeding/bruising (including antiplatelet drugs such as clopidogrel, NSAIDs such as ibuprofen/naproxen, "blood thinners" such as warfarin/dabigatran).Aspirin can increase the risk of bleeding when used with this medication. However, if your doctor has directed you to take low-dose aspirin for heart attack or stroke prevention (usually 81-162 milligrams a day), you should continue taking it unless your doctor instructs you otherwise. Ask your doctor or pharmacist for more details.The risk of serotonin syndrome/toxicity increases if you are also taking other drugs that increase serotonin. Examples include street drugs such as MDMA/"ecstasy," St. John's wort, certain antidepressants (including SSRIs such as fluoxetine/paroxetine, SNRIs such as duloxetine/venlafaxine), among others. The risk of serotonin syndrome/toxicity may be more likely when you start or increase the dose of these drugs.Taking MAO inhibitors with this medication may cause a serious (possibly fatal) drug interaction. Do not take any MAO inhibitors (isocarboxazid, linezolid, methylene blue, moclobemide, phenelzine, procarbazine, rasagiline, safinamide, selegiline, tranylcypromine) during treatment with this medication. Most MAO inhibitors should also not be taken for two weeks before and 7 days after treatment with this medication. Ask your doctor when to start or stop taking this medication.Levomilnacipran is very similar to milnacipran. Do not use medications containing milnacipran while using levomilnacipran.

            OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.

            NOTES: Do not share this medication with others.Medical tests (such as blood pressure, heart rate) should be performed before you start treatment, periodically to monitor your progress, or to check for side effects. Consult your doctor for more details.

            MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.

            STORAGE: Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

            Information last revised August 2021. Copyright(c) 2021 First Databank, Inc.

            IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

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            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.