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milnacipran (Savella)

Indications: - fibromyalgia (FDA-approved use) - used for treatment of depression in Europe Contraindications: - do not use with 14 days of MAO inhibitor - narrow-angle glaucoma - use with caution in patient with a history of dysuria - use with caution in patient with a history of seizures - end-stage renal disease - avoid concurrent use of other antidepressants Pregnancy category: C Dosage: - start 12.5 mg PO QD - maintenance dose: 50 mg BID Tabs: 12.5, 25, 50, 100 mg film-coated, immediate release tablets Pharmacokinetics: - majority is excreted unchanged in the urine (55%) - minimal CYP450-related metabolism - low binding to plasma protein (13%) Dosage adjustment in renal failure: - decrease dose by 50% for creatinine clearance of 5-30 mL/min Monitor: - blood pressure & heart rate a) prior to initiation of therapy b) periodically thereafter Adverse effects: - nausea, headache, palpitations - hypertension: mean increase of 3 mm Hg in systolic BP - tachycardia: mean increase of 7-8 beats/min - hyponatremia due to SIADH - hepatitis (rare) - seizures (rare) - increased risk of mydriasis Drug interactions: - may increase risk of bleeding when used in combination with aspirin or other NSAIDs Laboratory: - milnacipran in blood - milnacipran in serum/plasma - milnacipran in urine Mechanism of action: - serotonin-norepinephrine reuptake inhibitor (SNRI) - allegedly more potent inhibitor of norepinephrine reuptake than the other SNRIs - about 1 in 12 patients taking Savella for 3 months will have a 50% or greater improvement in symptoms compared to placebo [1] Notes: - contains FD&C Yellow No. 5 (tartrazine)

Interactions

drug adverse effects of antidepressants

Specific

levomilnacipran (Savella)

General

serotonin & norepinephrine reuptake inhibitor (SNRI, dual-acting reuptake inhibitor)

References

  1. Prescriber's Letter 16(3): 2009 New Drug: Savella (Milnacipran) Detail-Document#: 250310 (subscription needed) http://www.prescribersletter.com
  2. Arnold LM et al. Efficacy and safety of milnacipran 100 mg/day in patients with fibromyalgia: Results of a randomized, double-blind, placebo- controlled trial. Arthritis Rheum 2010 Sep; 62:2745. PMID: 20496365 http://dx.doi.org/10.1002/art.27559