Milnacipran Hydrochloride

Indications

Milnacipran Hydrochloride is used for: Depression, Fibromyalgia

Adult Dose

Oral Fibromyalgia Adult: Day 1: 12.5 mg once Days 2-3: 25 mg/day (12.5 mg twice daily) Days 4-7: 50 mg/day (25 mg twice daily) After Day 7: 100 mg/day (50 mg twice daily) Based on individual patient response, the dose may be increased to 200 mg/day (100 mg twice daily). Depression Adult: 50 mg bid. Hepatic impairment Mild or moderate (Child-Pugh A or B): No dosage adjustment required Severe (Child-Pugh C): Caution advised

Child Dose

<17 years: Safety and efficacy not established

Renal Dose

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

Administration

Should be taken with food. Preferably taken during meals.

Contra Indications

Uncontrolled narrow-angle glaucoma. Concomitant use w/ MAOI or w/in 2 wk after withdrawal of MAOI.

Precautions

Patient w/ major depressive disorder or other psychiatric disorders, history of dysuria, controlled narrow-angle glaucoma, pre-existing HTN, tachyarrhythmias or other CV disease, history of seizure disorder or condition predisposing to seizures (e.g. brain damage, alcoholism). Avoid abrupt withdrawal. Severe hepatic and moderate to severe renal impairment including ESRD. Pregnancy and lactation. 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-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

Interactions

Increased risk of bleeding w/ aspirin, NSAIDs, warfarin and other drugs that affect coagulation. Increased CNS effects w/ centrally-acting drugs (e.g. clomipramine). Increased risk of serotonin syndrome and NMS-like reactions w/ serotonergic drugs (e.g. tramadol), SSRIs, other selective serotonin-norepinephrine reuptake inhibitors, 5-HT1 receptor agonists (e.g. sumatriptan), antipsychotic agents and other dopamine antagonists. May inhibit antihypertensive effect of clonidine. May potentiate adverse haemodynamic effects w/ digoxin. Paroxysmal HTN and cardiac arrhythmia may occur when taken concurrently w/ epinephrine or norepinephrine. Potentially Fatal: Increased risk of serotonin syndrome and NMS-like reactions w/ MAOIs (e.g. linezolid, IV methylene blue).

Adverse Effects

Side effects of Milnacipran Hydrochloride : >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 Potentially Fatal: Serotonin syndrome or neuroleptic malignant syndrome (NMS)-like reactions, suicidal thinking/behaviour.

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.