FDA Approvals: Effexor XR, Xyrem, Antara

Yael Waknine

November 28, 2005

Nov. 28, 2005 -- The U.S. Food and Drug Administration (FDA) has approved extended-release venlafaxine HCl capsules for the treatment of adults with panic disorder; sodium oxybate oral solution for the treatment of excessive daytime sleepiness in patients with narcolepsy; and micronized fenofibrate capsules for administration with or without food.

Extended-Release Venlafaxine HCl (Effexor XR) for Panic Disorder

On November 18, the FDA approved a new indication for extended-release venlafaxine HCl (Effexor XR capsules, made by Wyeth Pharmaceuticals, Inc.), allowing its use for the treatment of adults with panic disorder (with or without agoraphobia), as defined in the Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition (DSM-IV).

The approval was based on data from two 12-week clinical trials that compared the efficacy of venlafaxine (75- or 150-mg/day; 75- or 225-mg/day) relative to placebo in adult outpatients.

Results showed that a significantly greater percentage of venlafaxine-treated patients were free of full-symptom panic attacks on the Panic and Anticipatory Anxiety Scale (PAAS). Venlafaxine was likewise associated with a significantly greater mean change from baseline on the Panic Disorder Severity Scale (PDSS) and higher response rate (much/very much improved) on the Clinical Global Impressions (CGI) improvement scale.

The FDA notes that although efficacy was established for each venlafaxine dose, a dose-response relationship for efficacy was not established in the 2 fixed-dose studies

The long-term efficacy of venlafaxine was established in a randomized long-term 26-week extension trial of patients responding to 75-, 150-, or 225-mg venlafaxine, showing that patients who continued therapy experienced a significantly longer time to relapse, relative to placebo.

Nevertheless, periodic evaluations are recommended to evaluate therapeutic efficacy in patients receiving extended treatment with the drug.

Venlafaxine extended-release capsules were previously approved for the treatment of major depressive disorder, generalized anxiety disorder, and social anxiety disorder.

Sodium Oxybate (Xyrem) to Reduce Excessive Daytime Sleepiness Associated with Narcolepsy

On Nov. 18, the FDA approved a new indication for sodium oxybate (Xyrem oral solution, made by Orphan Medical, Inc,), allowing its use for the treatment of excessive daytime sleepiness in patients with narcolepsy.

The approval was based on data from 2 multicenter, randomized, double-blind, placebo-controlled trials of sodium oxybate administered in equally divided doses at bedtime and 2.5 to 4 hours later.

Results from the first study (n = 228) showed that sodium oxybate at doses of 6- and 9-mg nightly significantly improved daytime sleepiness from baseline, as measured subjectively using the Epworth Sleepiness Scale (median change, -2.0 and -5.0 vs -0.5, P < .001).

Data from the second study demonstrated that sodium oxybate therapy with or without modafinil significantly improved daytime sleepiness from baseline, as measured objectively using the Maintenance of Wakefulness Test (12.0 and 13.2 vs 6.9 min, P < .001 for both).

Patients receiving the 6- and 9-mg doses also reported significant improvements in quality of life, with the majority rating much/very much improved on the Clinical Global Impression of Change (CGI-C) in Day and Nighttime Symptoms scale (52% and 64% vs 22%, P < .001 for both).

Treatment with sodium oxybate was well tolerated, with nausea (19%), dizziness (18%), headache (18%), vomiting (8%), somnolence (6%), urinary incontinence (6%), and nasopharyngitis (6%) most commonly reported. No serious adverse events occurred. These incidences are based on combined data from 5 clinical trials (n = 655).

Sodium oxybate should be initiated at a dose of 4.5 g/night in divided doses, and uptitrated in increments of 1.5-g to a maximum of 9-g/night. One to 2 weeks are recommended between dosage increases to evaluate clinical response and minimize adverse events.

Sodium oxybate was previously approved for the treatment of cataplexy associated with narcolepsy.

Micronized Fenofibrate 130-mg Capsules (Antara) May Be Taken Without Food

On Oct. 21, the FDA approved a new dosing regimen for micronized fenofibrate capsules (Antara, made by Reliant Pharmaceuticals, Inc.), allowing their administration with or without food.

The approval was based on clinical trial data showing that the130-mg formulation yielded comparable effects on all lipid parameters when taken with or between meals.

The study population (61% male, 39% female) included significant numbers of patients with hypertension (70%) and diabetes mellitus (32%). Diabetes is associated with higher rates of hypertriglyceridemia than that observed in the general population.

According to a company news release, the dosing option is expected to improve patient compliance with fenofibrate therapy.

Fenofibrate micronized capsules are indicated as adjunctive therapy for the treatment of primary hypercholesterolemia, mixed dyslipidemia (Fredrickson types 2a and 2b), and hypertriglyceridemia (Fredrickson types 4 and 5).

Reviewed by Gary D. Vogin, MD

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