milnacipran (Rx)

Brand and Other Names:Savella
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet

  • 12.5mg
  • 25mg
  • 50mg
  • 100mg

Fibromyalgia

12.5 mg PO once on day 1, then 25 mg/day divided q12hr on days 2-3, then 50 mg/day divided q12hr on days 4-7, then 100 mg/day divided q12hr thereafter; not to exceed 200 mg/day

Therapy discontinuation

  • When discontinuing antidepressant therapy that have lasted for more than 3 weeks, taper dose gradually over 2-4 weeks; this will minimize withdrawal symptoms and help detect reemerging symptoms
  • If intolerable withdrawal symptoms occur, resume previously prescribed dose; may also decrease dose at more gradual rate; patients on long-term treatment (>6 weeks) may benefit from tapering over >3 months

Switching to or from MAO inhibitors

  • Allow five or more days to elapse between milnacipran discontinuation and initiation of MAO inhibitor
  • Allow 14 days to elapse between MAO inhibitor discontinuation and initiation of milnacipran
  • Severe renal impairment: may increase to 50 mg BID if tolerated

Dosing Modifications

Renal impairment

  • Mild (CrCl 50-80 mL/min): No dosage adjustment required
  • Moderate (CrCl 30-49 mL/min): Use with caution
  • Severe (CrCl 5-29 mL/min): Reduce maintenance dosage by 50% (ie, to 50 mg/day divided q12hr)
  • End-stage renal disease (ESRD): Use not recommended

Hepatic impairment

  • Mild or moderate (Child-Pugh A or B): No dosage adjustment required
  • Severe (Child-Pugh C): Caution advised

<17 years: Safety and efficacy not established

Next:

Interactions

Interaction Checker

and milnacipran

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            Contraindicated (7)

            • iobenguane I 123

              milnacipran 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 milnacipran both increase serotonin levels. Contraindicated.

            • phenelzine

              phenelzine and milnacipran both increase serotonin levels. Contraindicated.

            • procarbazine

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

            • rasagiline

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

            • safinamide

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

            • tranylcypromine

              tranylcypromine and milnacipran both increase serotonin levels. Contraindicated.

            Serious - Use Alternative (52)

            • amitriptyline

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

            • amoxapine

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

            • apixaban

              milnacipran and apixaban both increase anticoagulation. Avoid or Use Alternate Drug.

            • bupropion

              milnacipran increases toxicity of bupropion by unspecified interaction mechanism. Avoid or Use Alternate Drug. May lower seizure threshold; keep bupropion dose as low as possible.

            • buspirone

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

            • citalopram

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

            • clomipramine

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

            • cyclobenzaprine

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

            • desipramine

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

            • desvenlafaxine

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

            • dextromethorphan

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

            • dolasetron

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

            • dosulepin

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

            • doxepin

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

            • duloxetine

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

            • epinephrine

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

            • epinephrine racemic

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

            • escitalopram

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

            • fluoxetine

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

            • fluvoxamine

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

            • granisetron

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

            • imipramine

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

            • iobenguane I 131

              milnacipran 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.

            • levomilnacipran

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

            • linezolid

              linezolid and milnacipran 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

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

            • lorcaserin

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

            • maprotiline

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

            • meperidine

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

            • methylene blue

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

            • nefazodone

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

            • netupitant/palonosetron

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

            • norepinephrine

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

            • nortriptyline

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

            • ondansetron

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

            • ozanimod

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

            • paroxetine

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

            • phentermine

              milnacipran, phentermine. Either increases toxicity of the other by Mechanism: unknown. Avoid or Use Alternate Drug. Risk of serotonin syndrome.

            • protriptyline

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

            • pseudoephedrine

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

            • selegiline

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

            • selegiline transdermal

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

            • sertraline

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

            • St John's Wort

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

            • trazodone

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

            • trimipramine

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

            • venlafaxine

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

            • vilazodone

              milnacipran, 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

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

            • warfarin

              milnacipran increases levels of warfarin by decreasing metabolism. Avoid or Use Alternate Drug.

            Monitor Closely (106)

            • 5-HTP

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

            • aceclofenac

              milnacipran, aceclofenac. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • acemetacin

              milnacipran, acemetacin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • almotriptan

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

            • aripiprazole

              milnacipran, 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

              milnacipran, 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

              milnacipran, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • aspirin rectal

              milnacipran, aspirin rectal. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • aspirin/citric acid/sodium bicarbonate

              milnacipran, aspirin/citric acid/sodium bicarbonate. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • benzhydrocodone/acetaminophen

              benzhydrocodone/acetaminophen, milnacipran. 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

              milnacipran, 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

              milnacipran, 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

              milnacipran, 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

              milnacipran, celecoxib. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • choline magnesium trisalicylate

              milnacipran, choline magnesium trisalicylate. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • clomipramine

              milnacipran, clomipramine. Mechanism: unspecified interaction mechanism. Use Caution/Monitor. Risk of euphoria, postural hypot'n when switching from clomipramine to milnacipran.

            • clonidine

              milnacipran decreases effects of clonidine by pharmacodynamic antagonism. Use Caution/Monitor.

            • clopidogrel

              milnacipran 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

              milnacipran, 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

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

            • cyproheptadine

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

            • dexfenfluramine

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

            • dextroamphetamine

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

            • diazepam intranasal

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

            • diclofenac

              milnacipran, diclofenac. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • diflunisal

              milnacipran, diflunisal. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • dihydroergotamine

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

            • dihydroergotamine intranasal

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

            • eletriptan

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

            • ergotamine

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

            • etodolac

              milnacipran, etodolac. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • fenbufen

              milnacipran, fenbufen. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • fenfluramine

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

              fenfluramine, milnacipran. 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

              milnacipran, fenoprofen. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • fish oil triglycerides

              fish oil triglycerides will increase the level or effect of milnacipran 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

              milnacipran, 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

              milnacipran, flurbiprofen. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • frovatriptan

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

            • gabapentin

              gabapentin, milnacipran. 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, milnacipran. 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.

            • green tea

              green tea, milnacipran. Other (see comment). Use Caution/Monitor. Comment: Combination may increase risk of bleeding.

            • haloperidol

              milnacipran, 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, milnacipran. 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 milnacipran 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

              milnacipran, ibuprofen. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • ibuprofen IV

              milnacipran, ibuprofen IV. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • iloperidone

              milnacipran, 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).

            • indomethacin

              milnacipran, indomethacin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • isoniazid

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

            • ketoprofen

              milnacipran, ketoprofen. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • ketorolac

              milnacipran, ketorolac. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • ketorolac intranasal

              milnacipran, ketorolac intranasal. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • L-tryptophan

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

            • lasmiditan

              lasmiditan, milnacipran. 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.

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

            • lemborexant

              lemborexant, milnacipran. 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.

            • lisdexamfetamine

              milnacipran, 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

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

            • lornoxicam

              milnacipran, lornoxicam. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • loxapine

              milnacipran, 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

              milnacipran, 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

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

            • lurasidone

              lurasidone increases effects of milnacipran by Other (see comment). Use Caution/Monitor. Comment: Potential for additive CNS effects .

              milnacipran, 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

              milnacipran, meclofenamate. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • mefenamic acid

              milnacipran, mefenamic acid. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • meloxicam

              milnacipran, meloxicam. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • mirtazapine

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

            • molindone

              milnacipran, 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

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

            • nabumetone

              milnacipran, nabumetone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • naproxen

              milnacipran, naproxen. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • naratriptan

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

            • olanzapine

              milnacipran, 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

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

            • oxaprozin

              milnacipran, oxaprozin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • paliperidone

              milnacipran, 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).

            • parecoxib

              milnacipran, parecoxib. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • pentazocine

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

            • perphenazine

              milnacipran, 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

              milnacipran, 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

              milnacipran, 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

              milnacipran, piroxicam. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • pregabalin

              pregabalin, milnacipran. 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

              milnacipran, 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).

            • remifentanil

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

            • remimazolam

              remimazolam, milnacipran. 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.

            • risperidone

              milnacipran, 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).

            • rizatriptan

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

            • salicylates (non-asa)

              milnacipran, salicylates (non-asa). Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • salsalate

              milnacipran, salsalate. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • SAMe

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

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

              milnacipran, 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.

            • sufentanil SL

              sufentanil SL, milnacipran. 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

              milnacipran, sulfasalazine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • sulindac

              milnacipran, sulindac. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • sumatriptan

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

            • sumatriptan intranasal

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

            • tapentadol

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

            • thiothixene

              milnacipran, 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).

            • tolfenamic acid

              milnacipran, tolfenamic acid. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • tolmetin

              milnacipran, tolmetin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • tramadol

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

            • trifluoperazine

              milnacipran, 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 milnacipran both increase sedation. Use Caution/Monitor.

            • vorapaxar

              milnacipran, 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 .

            • ziprasidone

              milnacipran, 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 milnacipran both increase serotonin levels. Modify Therapy/Monitor Closely.

            Minor (17)

            • almotriptan

              milnacipran, almotriptan. Mechanism: unknown. Minor/Significance Unknown. Risk of weakness, dyspnea, chest pain.

            • bumetanide

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

            • celandine

              celandine decreases effects of milnacipran by pharmacodynamic antagonism. Minor/Significance Unknown. Based on animal studies.

            • dexmethylphenidate

              dexmethylphenidate increases effects of milnacipran by decreasing metabolism. Minor/Significance Unknown.

            • eletriptan

              milnacipran, eletriptan. Mechanism: unknown. Minor/Significance Unknown. Risk of weakness, dyspnea, chest pain.

            • ethacrynic acid

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

            • frovatriptan

              milnacipran, frovatriptan. Mechanism: unknown. Minor/Significance Unknown. Risk of weakness, dyspnea, chest pain.

            • furosemide

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

            • lithium

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

            • naratriptan

              milnacipran, naratriptan. Mechanism: unknown. Minor/Significance Unknown. Risk of weakness, dyspnea, chest pain.

            • panax ginseng

              panax ginseng increases effects of milnacipran by pharmacodynamic synergism. Minor/Significance Unknown.

            • pleurisy root

              pleurisy root decreases effects of milnacipran by unspecified interaction mechanism. Minor/Significance Unknown. Theoretical interaction.

            • rizatriptan

              milnacipran, rizatriptan. Mechanism: unknown. Minor/Significance Unknown. Risk of weakness, dyspnea, chest pain.

            • sumatriptan

              milnacipran, sumatriptan. Mechanism: unknown. Minor/Significance Unknown. Risk of weakness, dyspnea, chest pain.

            • sumatriptan intranasal

              milnacipran, sumatriptan intranasal. Mechanism: unknown. Minor/Significance Unknown. Risk of weakness, dyspnea, chest pain.

            • torsemide

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

            • zolmitriptan

              milnacipran, zolmitriptan. Mechanism: unknown. Minor/Significance Unknown. Risk of weakness, dyspnea, chest pain.

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            Adverse Effects

            >10%

            Nausea (37%)

            Headache (18%)

            Constipation (16%)

            Hot flush (12%)

            Insomnia (12%)

            1-10% (selected)

            Dizziness

            Hyperhidrosis

            Hypertension

            Migraine

            Palpitations

            Tachycardia

            Vomiting

            Xerostomia

            Frequency Not Defined

            Abnormal bleeding

            Depression (worsening)

            Serotonin syndrome

            Suicidal thoughts

            Withdrawal signs or symptoms

            Postmarketing Reports

            Hematologic disorders: Leukopenia, neutropenia, thrombocytopenia

            Cardiac disorders: Supraventricular tachycardia, takotsubo cardiomyopathy

            Eye disorders: Accommodation disorder

            Endocrine disorders: Hyperprolactinemia

            Gastrointestinal disorders: Acute pancreatitis

            Hepatobiliary disorders: Hepatitis

            Metabolic and nutritional disorders: Anorexia, hyponatremia

            Musculoskeletal and connective tissue disorders: Rhabdomyolysis

            Neurologic disorders: Convulsions (including grand mal), loss of consciousness, parkinsonism

            Psychiatric disorders: Aggression, anger, delirium, hallucination, homicidal ideation

            Renal and urinary disorders: Acute renal failure

            Reproductive system and breast disorders: Galactorrhea, decreased libido, delayed or absent orgasm

            Skin disorders: Erythema multiforme, Stevens-Johnson syndrome

            Vascular disorders: Hypertensive crisis

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            Warnings

            Black Box Warnings

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

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

            In children and young adults, risks must be weighed against 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

            Patient’s family should communicate any abrupt behavioral changes to healthcare provider

            Worsening behavior and suicidal tendencies that are not part of presenting symptoms may necessitate discontinuance of therapy

            Drug is not approved for use in pediatric patients

            Contraindications

            Concomitant use of monoamine oxidase inhibitors (MAOIs), use of MAOIs within 5 days after discontinuance of milnacipran, or initiation of milnacipran within 14 days after discontinuance of MAOIs

            Patients being treated with linezolid or intravenous methylene blue

            Cautions

            Milnacipran is serotonin-norepinephrine reuptake inhibitor (SNRI) similar to those used for depression and other psychiatric disorders; monitoring and close observation for clinical worsening, suicidality, and unusual changes in behavior are necessary, especially during first few months of treatment and when dosage is increased or decreased (see Black Box Warnings)

            Potentially life-threatening serotonin syndrome has been reported with both SNRIs and selective serotonin reuptake inhibitors (SSRIs) when these agents are taken alone, but especially when they are coadministered with other serotonergic agents; thus, patient medications should be thoroughly reviewed for other serotonergic drugs (eg, tryptophan supplements, tramadol, serotonin agonists [triptans], MAOIs, tricyclic antidepressants [TCAs], SSRIs, methylene blue, buspirone, amphetamines, linezolid)

            May increase blood pressure (BP) or heart rate (HR); BP should be controlled before initiation of milnacipran; BP and HR should be monitored while patient is taking drug; consider dose reduction or discontinuation of therapy in patients with sustained hypertension or tachycardia during therapy

            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 aspirin, NSAIDs, warfarin, other anticoagulants, or other drugs known to affect platelet function may add to this risk

            Neonates exposed to SNRIs or SSRIs late in third trimester are at risk for complications such as feeding difficulties, irritability, and respiratory problems

            Prescription should be written for smallest amount consistent with good patient care; alert family members to monitor for emergence of suicidality, including panic attacks, hostility, irritability, insomnia, anxiety, agitation, mania and hypomania

            Bone fracture reported with antidepressant treatment; consider possibility of fracture in patients that present with unexplained bone pain, swelling, or bruising

            Use caution in patients with history of seizures

            Moderate renal impairment

            Avoid use in severe hepatic impairment; discontinue therapy with signs of hepatic dysfunction or jaundice; do not reinitiate therapy unless another source or cause identified

            Avoid concomitant use in patients with substantial alcohol use or chronic liver disease

            Withdrawal symptoms reported in patients when discontinuing treatment; gradual dose reduction recommended

            Pupillary dilation that occurs following use of SNRI drugs including milnacipran may trigger angle closure attack in patients with anatomically narrow angles who do not have a patent iridectomy; for patients who have not had an iridectomy for narrow-angle glaucoma risk factors, consider performing evaluation

            Patietns with history of obstructive uropathies may experience higher rates of genitourinary adverse drug reactions (ADRs)

            ESRD: Use not recommended

            Development of SIADH and hyponatremia reported with SSRIs and SNRIs, predominantly in the elderly; volume depletion and/or concurrent use of diuretics may increase risk

            May cause urinary hesitance; advise patients to report urinary symptoms or difficulties; use caution in patients with history of lower urinary tract disorders, including benign prostatic hyperplasia or prostatitis

            May worsen psychosis in patients with mood disorders; a shift to mania or hypomania reported with bipolar disorder; avoid monotherapy in patients with bipolar disorder; screen prospective patients for bipolar disorder when presenting with depressive symptoms

            Sexual 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
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            Pregnancy & Lactation

            Pregnancy category: C

            Lactation: Drug is excreted in human milk; peak breast milk concentration is observed within 4 hours after maternal dose, and estimated infant exposure is 5% of maternal dose; limited data are available regarding infant exposure, but caution is advised

            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

            SNRI; has no affinity for other neurotransmitter receptors (including gamma-aminobutyric acid [GABA], beta-adrenergic, opiate, histaminergic, and benzodiazepine receptors) and has no MAOI activity

            Absorption

            Bioavailability: 85-90%

            Peak plasma time: 2-4 hr

            Distribution

            Protein bound: 13%

            Vd: 400 L

            Metabolism

            Metabolized to several metabolites

            Elimination

            Half-life: L-isomer, 6-8 hr; D-isomer, 8-10 hr

            Excretion: Urine (55%)

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            Images

            BRAND FORM. UNIT PRICE PILL IMAGE
            Savella oral
            -
            50 mg tablet
            Savella oral
            -
            25 mg tablet
            Savella oral
            -
            12.5 mg tablet
            Savella oral
            -
            100 mg tablet
            Savella oral
            -
            12.5 mg (5)-25 mg(8)-50 mg(42) tablet

            Copyright © 2010 First DataBank, Inc.

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            Patient Handout

            Patient Education
            milnacipran oral

            MILNACIPRAN - ORAL

            (mil-NA-si-pran)

            COMMON BRAND NAME(S): Savella

            WARNING: Although not used for depression, this medication is in the same class as antidepressant medications. 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: Milnacipran is used to treat pain caused by a condition called fibromyalgia that affects the muscles, tendons, ligaments, and supporting tissues.This medication is a serotonin-norepinephrine reuptake inhibitor (SNRI) that works by helping to restore the balance of certain natural substances in the brain (neurotransmitters).

            HOW TO USE: Read the Medication Guide provided by your pharmacist before you start using milnacipran and each time you get a refill. If you have any questions, consult your doctor or pharmacist.Take this medication by mouth with or without food, usually 2 times a day or as directed by your doctor. If you have nausea, it may help to take this medication with food.Dosage is based on your medical condition and response to treatment.To reduce your risk of side effects, your doctor may start you at a low dose and gradually increase your dose. Follow your doctor's instructions carefully. Do not increase your dose or take this medication more often than prescribed. Your condition will not improve any faster, and the risk of serious side effects may be increased.If you suddenly stop using this medication, you may have withdrawal symptoms (such as mood swings, headache, tiredness, sleep changes, brief feelings similar to electric shock). To help prevent withdrawal, your doctor may lower your dose slowly. Withdrawal is more likely if you have used milnacipran for a long time or in high doses. Tell your doctor or pharmacist right away if you have withdrawal.Tell your doctor if your condition does not improve or if it worsens.

            SIDE EFFECTS: See also Warning section.Nausea, vomiting, dry mouth, constipation, loss of appetite, dizziness, increased sweating, headache, or hot flashes (flushing) may occur. If any of these effects persist or worsen, tell your doctor 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: fast/pounding heartbeat, changes in sexual ability, decreased interest in sex, painful/difficult urination, seizures, yellowing eyes/skin, dark urine, severe stomach/abdominal pain, black/bloody stools, vomit that looks like coffee grounds, easy bruising/bleeding.Get medical help right away if you have any very serious side effects, including: 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 milnacipran, tell your doctor or pharmacist if you are allergic to it; or to levomilnacipran; 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 disease, liver disease, alcohol use, personal or family history of glaucoma (angle-closure type), personal or family history of psychiatric disorders (such as bipolar/manic-depressive disorder), personal or family history of suicide attempts, high blood pressure, heart problems (such as chest pain, heart attack, fast/irregular heartbeat), seizure disorder, dehydration, stomach/intestinal ulcers, mineral imbalance (low level of sodium in the blood), painful/difficult urination (for example, due to enlarged prostate).This drug may make you dizzy. Alcohol or marijuana (cannabis) can make you more dizzy. Do not drive, use machinery, or do anything that needs alertness until you can do it safely. Avoid alcoholic beverages. Talk to your doctor if you are using marijuana (cannabis). Drinking alcohol can also increase your risk of liver problems.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 mineral imbalance (low level of sodium in the blood) while using this drug, especially if they are also taking "water pills" (diuretics) with this medication.During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor. 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.This medication passes 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: "water pills" (diuretics such as furosemide), drugs that can cause bleeding/bruising (such as "blood thinners" including warfarin/heparin, anti-platelet drugs including clopidogrel).Taking MAO inhibitors with this medication may cause a serious (possibly fatal) drug interaction. Avoid taking MAO inhibitors (isocarboxazid, linezolid, metaxalone, 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 at least 5 days after treatment with this medication. Ask your doctor when to start or stop taking this medication.Check all prescription and nonprescription medicine labels carefully since many medications contain pain relievers/fever reducers (nonsteroidal anti-inflammatory drugs-NSAIDs such as aspirin, ibuprofen, naproxen) that may increase your risk for bleeding if taken together with this drug. Low-dose aspirin should be continued if prescribed by your doctor for specific medical reasons such as heart attack or stroke prevention (usually 81-162 milligrams a day). Consult 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, other SNRIs such as duloxetine/venlafaxine), tryptophan, among others. The risk of serotonin syndrome/toxicity may be more likely when you start or increase the dose of these drugs.Milnacipran is very similar to levomilnacipran. Do not use medications containing levomilnacipran while using milnacipran.

            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. Symptoms of overdose may include: confusion, severe drowsiness/dizziness.

            NOTES: Do not share this medication with others.Laboratory and/or medical tests (such as blood pressure, heart rate, liver function) should be performed periodically to monitor your progress or 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 September 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.