Names and pronunciation
(mil-na′si-pran) Savella, Savella Titration Pack
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Drug reference
(mil-na′si-pran) Savella, Savella Titration Pack
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Func. class.: Antidepressant
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Chem. class.: Serotonin-norepinephrine reuptake inhibitor (SNRI)
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Do not confuse: Fetzima/Farxiga
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ACTION: May potentiate serotonergic, adrenergic activity in the CNS; is a potent inhibitor of adrenal serotonin and nor- epinephrine reuptake
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USES: Major depressive disorder in adults
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CONTRAINDICATIONS: Hyper- sensitivity, MAOI therapy Precautions: Pregnancy, breastfeeding, geriatric patients, mania, hypertension, renal/cardiac disease, seizures, increased intraocular pressure, anorexia, bleeding, dehydration, diabetes, hypotension, hypo- volemia, orthostatic hypotension, abrupt product withdrawal, alcohol intoxication, alcoholism, closed-angle glaucoma
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Black Box Warning: Children, suicidal ideation Black Box Warning: Depression: mood, sensorium, affect, suicidal tendencies, increase in psychiatric symptoms; panic; monitor children weekly face to face during first 4 wk, or dosage change, then every other week for the next 4 wk, then at 12 wk • B/P lying, standing; pulse; if systolic B/P drops 20 mm Hg, hold product, no- tify prescriber; take VS more often in patients with CV disease • Hepatic studies: AST, ALT, bilirubin baseline and periodically • Withdrawal symptoms: headache, nausea, vomiting, muscle pain, weak- ness; not common unless product is dis- continued abruptly • Avoid alcohol, rapid absorption may occur Black Box Warning: Serotonin syn- drome: nausea, vomiting, dizziness, fa- cial flush, shivering, sweating • Beers: use with caution in older adults; may exacerbate or cause SIADH; monitor for hyponatremia • Pregnancy/breastfeeding: use only if benefits outweigh fetal risk; SSRIs should not be used; do not use in 3rd trimester; do not breastfeed Black Box Warning: That clinical wors- ening and suicidal risk may occur, usu- ally worse in first few months of treat- ment; to notify prescriber immediately if suicidal thoughts/behaviors, aggres- sion, hostility, agitation, panic attacks occur • That improvement may occur in 4-8 wk or up to 12 wk (geriatric patients) • To report trouble with urination • Serotonin syndrome: to report imme diately nausea, vomiting, dizziness, facial flush, shivering, sweating • Pregnancy/breastfeeding: to notify prescriber if pregnancy is planned or sus pected or if breastfeeding
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SIDE EFFECTS CNS: Dizziness, agitation, hallucinations, seizures, drowsiness, mania, migraine, paresthesias, suicidal ideation, syncope CV: Hypertension, palpitations, dysrhyth- mia, sinus tachycardia EENT: Teeth grinding, blurred vision GI: Constipation, diarrhea, nausea, vomit- ing, anorexia, dry mouth, abdominal pain GU: Urinary retention SYST: Serotonin syndrome, Stevens- Johnson syndrome
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INTERACTIONS • Do not use with linezolid or methylene blue IV, or within 14 days of MAOIs • Increase: levomilnacipran effect— CYP34A inhibitors Increase: serotonin syndrome—SSRIs, serotonin receptor agonists, SNRIs, lithium Increase: bleeding risk—anticoagulants, antiplatelets, salicylates, NSAIDs Increase: risk of neuroleptic malignant syndrome—antipsychotics, DOPamine antagonists; avoid concurrent use Increase: bleeding risk—alfalfa, fever- few, dong quai, fish oil, ginseng, garlic, ginkgo biloba Drug/Herb • Serotonin syndrome: St. John’s wort Increase: CNS depression—kava, valerian
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DOSAGE AND ROUTES Major depressive disorder (levomilnacipran) • Adult: PO 20 mg/day × 2 days, then 40 mg/day; may increase in increments of 40 mg at intervals of at least 2 days, max 120 mg/day; max 80 mg/day (strong CYP3A4 inhibitors therapy) Major depressive disorder (milnacipran) • Adult: PO 12.5-25 mg bid, may titrate to 100 mg bid, max 200 mg/day Fibromyalgia (levomilnacipran) • Adult: PO 12.5 mg daily, increase to 12.5 mg bid on days 2 and 3, then 25 mg bid on days 4 to 7; increase to 50 mg bid after day 7; may increase to 100 mg bid as needed Fibromyalgia (milnacipran) • Adult/adolescent ≥17 yr: PO 12.5 mg once on day 1, then 12.5 mg bid on days 2-3, then 25 mg bid on days 4-7, and 50 mg bid thereafter Renal dose (levomilnacipran) • Adult: PO CCr 15-29 mL/min, max 40 mg/day; CCr 30-59 mL/min, max 80 mg/ day; CCr <15 mL/min, do not use Renal dose (milnacipran) • Adult: PO CCr 5-29 mL/min, reduce maintenance dose by 50% (25-50 mg bid)
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Available forms: Ext rel caps 20, 40, 80, 120 mg (levomilnacipran); tabs 12.5, 25, 50, 100 mg (milnacipran)
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Administer: • Swallow cap whole; do not break, crush, or chew; do not sprinkle on food or mix with liquid • Without regard to food • Give at the same time each day
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Assess: • Neuroleptic malignant syndrome: hyperthermia, rigidity, rapid fluctuations of vital signs, mental status changes; MAOIs: coadministration contraindicated within 14 days of MAOI
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Evaluate: • Therapeutic response: decreased de- pression
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CLINICAL CONSIDERATIONS
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Patient and caregiver information: • About signs and symptoms of bleeding L (GI bleeding, nosebleed, ecchymosis, bruising) • To use with caution when driving and performing other activities requiring alertness because of drowsiness and blurred vision • To avoid ingestion of alcohol, MAOIs, other CNS depressants; not to use within 14 days of MAOIs; to notify all providers of use of this product • Not to discontinue medication quickly after long-term use; may cause headache, malaise; taper • That product may be used with or without food • To swallow caps whole; do not break, crush, chew
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PHARMACOKINETICS Peak 6-8 hr metabolized (CYP2D6) in the liver; excretion 58% (urine), 22% pro- tein binding, half-life 12 hr (levomil- nacipran) 6-10 hr (milnacipran)
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• Adult: PO 20 mg/day × 2 days, then 40 mg/day; may increase in increments of 40 mg at intervals of at least 2 days, max 120 mg/day; max 80 mg/day (strong CYP3A4 inhibitors therapy) Major depressive disorder (milnacipran)
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• Adult: PO 12.5-25 mg bid, may titrate to 100 mg bid, max 200 mg/day Fibromyalgia (levomilnacipran)
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• Adult: PO 12.5 mg daily, increase to 12.5 mg bid on days 2 and 3, then 25 mg bid on days 4 to 7; increase to 50 mg bid after day 7; may increase to 100 mg bid as needed Fibromyalgia (milnacipran)
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• Adult/adolescent ≥17 yr: PO 12.5 mg once on day 1, then 12.5 mg bid on days 2-3, then 25 mg bid on days 4-7, and 50 mg bid thereafter Renal dose (levomilnacipran)
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• Adult: PO CCr 15-29 mL/min, max 40 mg/day; CCr 30-59 mL/min, max 80 mg/ day; CCr <15 mL/min, do not use Renal dose (milnacipran)
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• Adult: PO CCr 5-29 mL/min, reduce maintenance dose by 50% (25-50 mg bid)
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