Fetzima by Forest Laboratories and Pierre Fabre Laboratories

The FDA has approved Fetzima (levomilnacipran extended-release capsules) for the treatment of major depressive disorder (MDD) in adult patients. Fetzima carries a boxed warning regarding the potential for an increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults and the need for close monitoring in this population. Fetzima is not approved for use in pediatric patients. The approval of Fetzima also carries the limitation that it is not approved for the management of fibromyalgia.¹

MDD is a leading cause of disability in the United States, with approximately 16 million Americans—7.3% of the adult population—affected by it. The World Health Organization expects MDD to become the second-leading cause of disability by the year 2020.

Fetzima was discovered by Pierre Fabre Laboratories and codeveloped by Forest Laboratories, Inc.²

Pharmacology and Pharmacokinetics

Fetzima is a serotonin and norepinephrine reuptake inhibitor (SNRI). Fetzima has a terminal elimination half-life of approximately 12 hours and a median time to peak concentration of 6 to 8 hours after oral administration. The elimination of Fetzima is primarily renal. The pharmacokinetics of Fetzima are not affected by age, gender, or race.¹

Dosage and Administration

The recommended dose of Fetzima is 40 to 120 mg once daily. It should be initiated as 20 mg once daily for 2 days and then increased to 40 mg once daily, with subsequent increases in 40-mg increments every 2 days or more based on efficacy and tolerability. The capsule may be taken with or without food, and it should never be opened, chewed, or crushed.

The maximum dose of Fetzima for patients with moderate renal impairment (creatinine clearance of 30 to 59 mL/min) is 80 mg per day. The maximum dose of Fetzima for patients with severe renal impairment (creatinine clearance of 15 to 29 mL/min) is 40 mg per day. Fetzima should not be used in patients with end-stage renal disease.

Whenever possible, the dose of Fetzima should be gradually reduced before discontinuing therapy and patients should be monitored closely.¹

Clinical Trials

The efficacy of Fetzima was established in three 8-week randomized, double-blind, placebo-controlled studies in a total of over 1600 patients. Studies 1 and 2 were fixed dose; study 3 was flexible dose. In each study, the primary end point evaluated the overall improvement in depressive symptoms through the change from baseline to end point in the Montgomery-Åsberg Depression Rating Scale total score. The secondary end point evaluated the improvement in functional impairment through change from baseline to end point in the Sheehan Disability Scale. A statistically significant difference was found for both end points in each study.^1,2

Contraindications, Warnings, and Precautions

Fetzima is contraindicated in patients with hypersensitivity to any of its components, uncontrolled narrow-angle glaucoma, concurrent or recent use of monoamine oxidase inhibitors, or concurrent use of linezolid or intravenous methylene blue.

As stated in the boxed warning, patients should be monitored for increased suicidal thoughts and behaviors. Fetzima is not approved for use in pediatric patients. Serotonin syndrome has been reported in patients using serotonin reuptake inhibitors and SNRIs, especially when used in combination with other serotonergic substances, such as triptans, tricyclics, fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John’s Wort. Blood pressure and heart rate should be monitored throughout treatment with Fetzima; preexisting hypertension should be controlled prior to initiation of therapy. Fetzima may increase the risk of bleeding. Patients at risk for or with elevated intraocular pressure should be monitored carefully. Urinary hesitation or retention may occur. Fetzima may activate mania or hypomania in bipolar patients. Fetzima should be used cautiously in patients with seizure disorder. Hyponatremia may occur during treatment with Fetzima.

Do not exceed 80 mg daily when Fetzima is used in combination with strong CYP3A4 inhibitors, such as ketoconazole. Fetzima is Pregnancy Category C. The most common adverse reactions (≥5%) are nausea, constipation, hyperhidrosis, increased heart rate, erectile dysfunction, tachycardia, vomiting, and palpitations.¹

Dr. Holmberg earned her PharmD from the University of Connecticut and completed an ambulatory care residency at the Phoenix VA Healthcare System. Her practice has also included pediatrics and inpatient mental health. She resides in Phoenix, Arizona.

References

• Fetzima prescribing information. www.frx.com/pi/Fetzima_pi.pdf#page=1. Accessed December 4, 2013.
• Forest Laboratories and Pierre Fabre Laboratories announce FDA approval of Fetzima for the treatment of major depressive disorder in adults. Forest Laboratories website. http://frx.investorhq.businesswire.com/press-release/corporate-news/forest-laboratories-and-pierre-fabre-laboratories-announce-fda-approval. Accessed December 4, 2013.