Fetzima (levomilnacipran HCl)

Dosage of levomilnacipran hydrochloride is expressed in terms of levomilnacipran.

The maximum recommended dosage of levomilnacipran should not exceed 80 mg once daily when used concurrently with strong cytochrome P-450 (CYP) 3A4 inhibitors.

Levomilnacipran hydrochloride is administered orally; it is commercially available as extended-release capsules containing 20 mg, 40 mg, 80 mg, or 120 mg of levomilnacipran.

Administer the capsules orally once daily, with or without food, at approximately the same time each day. Swallow the capsules whole; do not open, chew, or crush.

If a dose of levomilnacipran is missed, instruct patients to take the dose as soon as it is remembered, unless it is almost time for the next scheduled dose. If it is almost time for the next scheduled dose, instruct patients to skip the missed dose and take the next dose at the regularly scheduled time. Advise patients not to take 2 doses at the same time.

Store levomilnacipran capsules at 25degreesC (excursions permitted between 15-30degreesC).

No dosing information is available for this tab.

No dosing information is available for this tab.

Levomilnacipran is metabolized primarily by cytochrome P-450 (CYP) isoenzyme 3A4 with minor contributions by CYP isoenzymes 2C8, 2C19, 2D6, and 2J2. In vitro studies demonstrate that levomilnacipran does not inhibit CYP isoenzymes 1A2, 2A6, 2C8, 2C9, 2C19, 2D6, or 2E1.

Levomilnacipran is a weak substrate of P-glycoprotein (P-gp), but is not a substrate of breast cancer resistance protein (BCRP), organic anion-transporting polypeptides (OATP) 1B1 and 1B3, organic cation transporter (OCT) 2, and organic anion transporters (OAT) 1 and 3. In vitro studies demonstrate that levomilnacipran does not inhibit OATP1B1, OATP1B3, OCT2, OAT1, OAT3, or P-gp.

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

*Known hypersensitivity to levomilnacipran hydrochloride, milnacipran hydrochloride, or any ingredient in the formulation.

*Concurrent or recent (i.e., within 14 days) therapy with a monoamine oxidase inhibitor (MAOI) intended to treat psychiatric disorders. Use of an MAOI intended to treat psychiatric disorders within 7 days of levomilnacipran discontinuance.

*Initiation of levomilnacipran therapy in patients receiving MAOIs such as linezolid or IV methylene blue.

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

There are no moderate contraindications for this drug.

Adverse effects reported in >=5% of patients with major depressive disorder receiving levomilnacipran and at an incidence of at least twice that reported with placebo in controlled studies include nausea, constipation, hyperhidrosis, increased heart rate, erectile dysfunction, ejaculation disorder, tachycardia, vomiting, and palpitations.

There are no severe adverse reactions for this drug.

There are no less severe adverse reactions for this drug.

No enhanced messaging available.

The safety and effectiveness of levomilnacipran in pediatric patients for the treatment of major depressive disorder have not been established; levomilnacipran is not approved for use in pediatric patients. In 2 randomized, double-blind, placebo- and active-controlled trials in pediatric patients (7-17 years of age) with major depressive disorder, levomilnacipran was not superior to placebo in terms of change from baseline to week 8 in the Children's Depression Rating Scale-Revised (CDRS-R) total score.

An increased risk of suicidal thoughts and behaviors was observed in pediatric patients treated with antidepressants. Additionally, pediatric patients receiving levomilnacipran were more likely to develop new-onset and sustained hypertension compared to adults in clinical trials.

There is a pregnancy exposure registry that monitors pregnancy outcomes in patients exposed to antidepressants during pregnancy. Advise patients to register by calling the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or by visiting https://womensmentalhealth.org/research/pregnancyregistry/antidepressants.

Available data on levomilnacipran use in pregnant women are insufficient to assess for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. There are risks associated with untreated depression in pregnancy as well as with exposure to SNRIs, including levomilnacipran, during pregnancy.

In observational studies, exposure to SNRIs, particularly during the month before delivery, has been associated with a <2-fold increase in the risk of postpartum hemorrhage. Neonates exposed to SNRIs or SSRIs, including levomilnacipran, late in the third trimester of pregnancy have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. Clinical findings reported to date in neonates have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. These findings appear to be consistent with either a direct toxic effect of SNRIs or SSRIs or, possibly, a drug withdrawal syndrome. In some cases, the clinical picture was consistent with serotonin syndrome.

In animal reproduction studies, no malformations were observed when levomilnacipran was administered during the period of organogenesis at doses up to 8 or 16 times the maximum recommended human dose (MRHD) of 120 mg on a mg/m2 basis in rats and rabbits, respectively. However, an increase in early post-natal rat pup mortality was observed at a dose equivalent to 5 times the MRHD given during pregnancy and lactation.

There are risks associated with untreated depression in pregnancy. In a prospective longitudinal study, women who discontinued antidepressant therapy during pregnancy were more likely to experience a relapse of major depressive disorder than women who continued antidepressants. Consider the risk of untreated depression when discontinuing or changing antidepressants during pregnancy and postpartum.

It is unknown whether levomilnacipran is distributed into human milk; however, racemic milnacipran is present in human milk. The effects of levomilnacipran or milnacipran on the breast-fed infant or on milk production are also unknown.

There are reports of agitation, irritability, poor feeding, and poor weight gain in infants exposed to SSRIs or SNRIs through breast milk. Monitor infants exposed to levomilnacipran for these effects.

Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for levomilnacipran and any potential adverse effects on the breast-fed child from the drug or from the underlying maternal conditions.

Routine dosage adjustment is not necessary in geriatric patients; however, consider the renal clearance of levomilnacipran when determining the dosage in such patients.

In the 8-week clinical trials with levomilnacipran, 2.8% of patients were >=65 years of age.

According to the manufacturer, no dosage adjustment is recommended on the basis of age. However, because levomilnacipran is primarily eliminated by renal excretion, consider the renal clearance of levomilnacipran when determining the dosage in geriatric patients.

SNRIs, including levomilnacipran, have been associated with clinically important hyponatremia in geriatric patients, who may be at greater risk for this adverse effect.