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milnacipran

N06AX17

Forms & Strengths

Oral tablets: 25 mg
Oral tablets: 50 mg
Oral tablets: 100 mg
Extended‑release capsules (Savella): 50 mg
Extended‑release capsules (Savella): 100 mg

Adult Dosing

MDD: start 25 mg PO twice daily (BID); increase to 50 mg BID after ≥2 days; target 100 mg BID (max 200 mg/day)
Fibromyalgia: start 12.5 mg PO BID; increase to 25 mg BID after 1 week; target 50 mg BID (max 100 mg/day)
Renal impairment (CrCl 30‑60 mL/min): reduce dose by 50 %
Severe hepatic impairment: avoid or use 50 % dose reduction

Pediatric Dosing

Not approved for patients <18 years; safety and efficacy not established

Indications

Major depressive disorder (adults)
Fibromyalgia (adults)

Mechanism of Action

Reversible inhibition of serotonin (5‑HT) and norepinephrine (NE) reuptake
Greater potency for NE than 5‑HT (SNRI)
Increases synaptic 5‑HT and NE, enhancing mood and descending pain inhibition

Contraindications

Concomitant MAOI therapy or within 14 days of MAOI discontinuation
Known hypersensitivity to milnacipran or any excipient
Use with pimozide (risk of QT prolongation)

Adverse Reactions

Nausea
Headache
Constipation
Dry mouth
Insomnia
Increased heart rate
Hypertension
Dizziness
Sweating
Sexual dysfunction (e.g., ejaculation disorder)
Urinary retention

Drug Interactions

MAOIs (risk of serotonin syndrome)
Other serotonergic agents (SSRIs, SNRIs, tramadol, triptans) – additive serotonin syndrome risk
CYP3A4 inhibitors (ketoconazole, erythromycin) – ↑ milnacipran levels
CYP3A4 inducers (rifampin, carbamazepine) – ↓ milnacipran levels
Antihypertensives – additive hypotensive effect
QT‑prolonging drugs (pimozide) – increased arrhythmia risk
NSAIDs/anticoagulants – enhanced bleeding risk

Curated Content: Needs Vetting Before Put to Clinical Use