milnacipran

Contraindicated in:

Concurrent use of MAO inhibitors or MAO-like drugs (linezolid or methylene blue);
End-stage renal disease;
Significant history of alcohol use/abuse;
Chronic liver disease;
Lactation: Lactation.

Use Cautiously in:

May ↑ risk of suicide attempt/ideation especially during early treatment or dose adjustment; this risk appears to be greater in adolescents or children
;
History of seizures;
Hypertension;
Moderate to severe renal impairment (↓ dose);
Severe hepatic impairment;
Obstructive uropathy (↑ risk of adverse genitourinary effects);
Angle-closure glaucoma;
OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
Pedi: Safety and effectiveness not established in children;
Geri: Appears on Beers list. May worsen or cause syndrome of inappropriate antidiuretic hormone (SIADH) secretion and/or hyponatremia in older adults. Use with caution in older adults and closely monitor sodium concentrations when starting therapy or ↑ dose.

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypertension, tachycardia

Derm: ↑sweating, hot flush

Endo: SIADH

F and E: hyponatremia

GI: ↑liver enzymes, constipation, dry mouth, nausea, PANCREATITIS, vomiting

GU: ↓libido, delayed/absent orgasm, ejaculatory delay/failure, erectile dysfunction

Hemat: BLEEDING

Neuro: dizziness, headache, insomnia, NEUROLEPTIC MALIGNANT SYNDROME, SUICIDAL THOUGHTS/BEHAVIORS

Misc: SEROTONIN SYNDROME

Interactions ⬆ ⬇

Drug-drug:

Concurrent use with MAO inhibitors may result in serious, potentially fatal reactions; wait ≥14 days following discontinuation of MAO inhibitor before initiation of milnacipran. Wait ≥5 days after discontinuing milnacipran before initiation of MAO inhibitor.
Concurrent use with MAO-inhibitor-like drugs, such as linezolid or methylene blue, may ↑ risk of serotonin syndrome; concurrent use contraindicated; do not start therapy in patients receiving linezolid or methylene blue; if linezolid or methylene blue need to be started in a patient receiving milnacipran, immediately discontinue milnacipran and monitor for signs/symptoms of serotonin syndrome for 5 days or until 24 hr after last dose of linezolid or methylene blue, whichever comes first (may resume milnacipran therapy 24 hr after last dose of linezolid or methylene blue).
Drugs that affect serotonergic neurotransmitter systems, including tricyclic antidepressants, SNRIs, fentanyl, lithium, buspirone, tramadol, meperidine, methadone, amphetamines, and triptans, may ↑ risk of serotonin syndrome.
↑risk of bleeding with NSAIDs, aspirin, clopidogrel, prasugrel, ticagrelor, dabigatran, apixaban, edoxaban, rivaroxaban, or warfarin.
May ↓ antihypertensive effectiveness of clonidine.
↑risk of hypertension and arrhythmias with epinephrine or norepinephrine.
↑risk of euphoria and hypotension when switching from clomipramine.
Concurrent use with digoxin may result in adverse hemodynamics, including hypotension and tachycardia; avoid concurrent use with IV digoxin.

Drug-Natural Products:

St. John's wort may ↑ risk of serotonin syndrome.

Availability ⬆ ⬇

(Generic available)

Tablets (contain tartrazine): 12.5 mg; 25 mg; 50 mg; 100 mg

Route/Dosage ⬆ ⬇

PO (Adults ): Day 1: 12.5 mg; Day 2–3: 12.5 mg twice daily; Day 4–7: 25 mg twice daily; After Day 7: 50 mg twice daily. Some patients may require up to 100 mg twice daily depending on response.

Renal Impairment

PO (Adults ): CCr 5–29 mL/min: Maintenance dose is 25 mg twice daily; some patients may require up to 50 mg twice daily depending on response.

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Inhibits neuronal reuptake of norepinephrine and serotonin.

Therapeutic effects:

Decreased pain associated with fibromyalgia.

Classifications ⬆ ⬇

Therapeutic Classification: antifibromyalgia agents

Pharmacologic Classification: selective norepinephrine reuptake inhibitors

Pharmacokinetics ⬆ ⬇

Absorption: 85–90% absorbed following oral administration.

Distribution: Unknown.

Metabolism/Excretion: Mostly excreted in urine as unchanged drug (55%) and inactive metabolites.

Half-Life: D: isomer 8–10 hr; L: isomer 4–6 hr.

Time/Action Profile ⬆ ⬇

(↓ in pain)

ROUTE	ONSET	PEAK	DURATION
PO	1 wk	unknown	unknown

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication. Advise patient to read Patient Information before starting therapy.
Instruct patient to take missed doses as soon as possible unless time for next dose. Do not stop abruptly; must be ↓ gradually.
Encourage patient to maintain routine follow-up visits with health care provider to determine effectiveness.
Advise patient to immediately notify health care provider for signs of serotonin syndrome (agitation, hallucinations, tachycardia, labile BP, dizziness, diaphoresis, flushing, tremor, rigidity, myoclonus, hyperreflexia, incoordination, seizure, nausea, vomiting, diarrhea).
Advise patient, family, and caregivers to look for suicidality, especially during early therapy or dose changes. Notify health care provider immediately if thoughts about suicide or dying, attempts to commit suicide, new or worse depression or anxiety, agitation or restlessness, panic attacks, insomnia, new or worse irritability, aggressiveness, acting on dangerous impulses, mania, or other changes in mood or behavior.
Encourage patient and family to be alert for emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, or mania, especially during early antidepressant therapy. Changes may be abrupt. If symptoms occur, notify health care provider immediately.
May cause dizziness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care provider before taking other medications, especially St. John's wort. Avoid use of aspirin, NSAIDs, and warfarin due to ↑ risk for bleeding.
Instruct patient to notify health care provider if signs of liver damage (pruritus, dark urine, jaundice, right upper quadrant tenderness, unexplained flu-like symptoms) or hyponatremia (headache, difficulty concentrating, memory impairment, confusion, weakness, unsteadiness, falls), or rash occur.
Advise patient to avoid taking alcohol during therapy.
Inform patient that milnacipran may cause symptoms of sexual dysfunction. In men, ejaculatory delay or failure, ↓ libido, and erectile dysfunction may occur. In women, may result in ↓ libido and delayed or absent orgasm. Advise patient to notify health care provider if symptoms occur.
Rep: Instruct women of reproductive potential to notify health care provider if pregnancy is planned or suspected or if breastfeeding. May be associated with an ↑ risk of postpartum hemorrhage. Neonates exposed to milnacipran late in the 3rd trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding; can arise immediately upon delivery. Symptoms may include respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. Monitor infants exposed to milnacipran for agitation, irritability, poor feeding, and poor weight gain. Encourage patients who become pregnant during therapy to enroll in the Savella pregnancy registry by calling 1-800-643-3010 or visiting www.savellapregnancyregistry.com.

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Indications ⬇

Contraind./Precautions ⬆ ⬇