levomilnacipran

Contraindicated in:

Hypersensitivity to levomilnacipran or milnacipran;
Uncontrolled narrow-angle glaucoma;
Concurrent use of or in close temporal proximity to MAO inhibitors, linezolid, or methylene blue (↑ risk of serotonin syndrome);
Concurrent use of alcohol;
Lactation: Lactation.

Use Cautiously in:

Hypertension, cardiovascular or cerebrovascular disease (BP should be controlled prior to treatment);
Bipolar disorder (may activate mania/hypomania);
Renal impairment (dose ↓ required for CCr <60 mL/min);
OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
Pedi: ↑risk of suicidal thinking and behavior (suicidality) in adolescents and young adults up to 24 yr with major depressive disorder;
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, hypotension, palpitations, tachycardia

Derm: hot flushes, hyperhidrosis, rash

EENT: mydriasis

Endo: SIADH

F and E: hyponatremia

GI: nausea, ↓appetite, constipation, vomiting

GU: ↓libido, delayed/absent orgasm, ejaculatory delay/failure, erectile dysfunction, testicular pain, urinary hesitation/retention

Hemat: BLEEDING

Neuro: activation of mania/hypomania, SUICIDAL THOUGHTS/BEHAVIORS

Misc: SEROTONIN SYNDROME

Interactions ⬆ ⬇

Drug-drug:

Concurrent use with MAO inhibitors may result in serious, potentially fatal reactions and is contraindicated; wait at least 14 days following discontinuation of MAO inhibitor before initiation of levomilnacipran. Wait at least 7 days after discontinuing levomilnacipran 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 levomilnacipran, immediately discontinue levomilnacipran.
Drugs that affect serotonergic neurotransmitter systems, including tricyclic antidepressants, SNRIs, fentanyl, lithium, buspirone, tramadol, meperidine, methadone, amphetamines, and triptans, ↑ risk of serotonin syndrome.
Concurrent use of NSAIDs, aspirin, warfarin, or other drugs that affect coagulation may ↑ the risk of bleeding.
Strong CYP3A4 inhibitors, including ketoconazole, clarithromycin, and ritonavir, may ↑ levels and the risk of toxicity.
Concurrent use of other medications that may BP may ↑ risk of hypertension.
Concurrent use with alcohol may cause a rapid release of drug and should be avoided.

Drug-Natural Products:

Concurrent use with St. John's wort or tryptophan may ↑ the risk of serotonin syndrome; also ↑ risk of coronary vasoconstriction and hypertension.

Availability ⬆ ⬇

(Generic available)

Extended-release capsules: 20 mg; 40 mg; 80 mg; 120 mg

Route/Dosage ⬆ ⬇

PO (Adults ): 20 mg once daily for 2 days; then ↑ to 40 mg once daily; may then ↑ by 40 mg every two or more days; may ↑ up to 120 mg/day; Concurrent use of CYP3A4 inhibitors (including ketoconazole, clarithromycin, ritonavir): not to exceed 80 mg/day.

Renal Impairment

PO (Adults ): CCr 30–59 mL/min: not to exceed 80 mg/day; CCr 15–29 mL/min: not to exceed 40 mg/day.

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Inhibits neuronal reuptake of norepinephrine and serotonin in the CNS.

Therapeutic effects:

Decrease in depressive symptomatology, with fewer relapses/recurrences.

Classifications ⬆ ⬇

Therapeutic Classification: antidepressants

Pharmacologic Classification: selective serotonin and norepinephrine reuptake inhibitors-SSNRIs

Pharmacokinetics ⬆ ⬇

Absorption: Well absorbed (92%) following oral administration.

Distribution: Widely distributed.

Metabolism/Excretion: Primarily metabolized in the liver via the CYP3A4 isoenzyme. 58% eliminated unchanged in urine; 42% metabolized; metabolites are renally eliminated.

Half-Life: 12 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	6–8 hr	unknown

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of levomilnacipran to patient. Instruct them to take levomilnacipran as directed at the same time each day. Take missed doses as soon as possible unless time for next dose; do not double dose. Do not stop abruptly; must be ↓ gradually to avoid withdrawal. Abrupt discontinuation may cause dysphoric mood, irritability, agitation, dizziness, paresthesia, electric shock sensation, anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus, and seizures. Advise patient to read Medication Guide prior to therapy and with each Rx refill in case of changes.
Encourage patient to maintain routine follow-up visits with health care professional to determine effectiveness.
May cause drowsiness and may affect ability to make decisions or react quickly. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
Advise patient, family, and caregivers to look for activation of mania/hypomania and suicidality, especially during early therapy or dose changes. Notify health care professional 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, other changes in mood or behavior, or symptoms of serotonin syndrome occur.
Caution patient of the risk or serotonin syndrome (agitation, hallucinations, changes in mental status, muscle twitching, fast heartbeat, high or low BP, sweating or fever, nausea or vomiting, diarrhea, muscle stiffness or tightness), especially when taking triptans, tramadol, tryptophan supplements, or other serotonergic or antipsychotic agents.
Inform patient that levomilnacipran may cause symptoms of sexual dysfunction. In males, ejaculatory delay or failure, ↓ libido, and erectile dysfunction may occur. In female patients, may result in ↓ libido and delayed or absent orgasm. Advise patient to notify health care professional if symptoms occur.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to avoid concurrent use of Rx, OTC, and herbal products, especially St. John's wort, NSAIDs, aspirin, and warfarin, without consulting health care professional; may ↑ bleeding.
Instruct patient to notify health care professional if signs of hyponatremia (headache, difficulty concentrating, memory impairment, confusion, weakness, unsteadiness) occur.
Advise patient to avoid using alcohol during levomilnacipran therapy.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected and to avoid breastfeeding during therapy. Use of levomilnacipran in last month of pregnancy may ↑ risk of postpartum hemorrhage. Monitor infants exposed to levomilnacipran via breastfeeding for sedation, poor feeding, and poor weight gain. Encourage pregnant patients to enroll in pregnancy exposure registry that monitors outcomes of women exposed to antidepressants during pregnancy by contacting National Pregnancy Registry for Antidepressants at 1-866-961-2388 or visiting online at https://womensmentalhealth.org/research/pregnancyregistry/antidepressants/.

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Indications ⬇

Contraind./Precautions ⬆ ⬇