Dosing & Uses
Dosage Forms & Strengths
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
- 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
- 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
Serious - Use Alternative
Significant - Monitor Closely
Hot flush (12%)
Frequency Not Defined
Withdrawal signs or symptoms
Hematologic disorders: Leukopenia, neutropenia, thrombocytopenia
Cardiac disorders: Supraventricular tachycardia
Eye disorders: Accommodation disorder
Endocrine disorders: Hyperprolactinemia
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
Skin disorders: Erythema multiforme, Stevens-Johnson syndrome
Vascular disorders: Hypertensive crisis
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
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
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, 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
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
History of seizures
Moderate renal impairment
Severe hepatic impairment, substantial alcohol use, 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
Patietns with history of obstructive uropathies may experience higher rates of genitourinary adverse drug reactions (ADRs)
ESRD: Use not recommended
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
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.
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
Peak plasma time: 2-4 hr
Protein bound: 13%
Vd: 400 L
Metabolized to several metabolites
Half-life: L-isomer, 6-8 hr; D-isomer, 8-10 hr
Excretion: Urine (55%)
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