FDA Approvals: Clarinex, Abilify, Isovorin

Yael Waknine

March 10, 2005

March 10, 2005 — The U.S. Food and Drug Administration (FDA) has approved desloratadine 5 mg plus pseudoephedrine sulfate 240 mg extended-release tablets for the relief of seasonal allergic rhinitis symptoms in patients aged 12 and older; aripiprazole tablets and oral solution for the extended maintenance of stability in patients with bipolar I disorder after a manic or mixed episode; intravenous levofolinic acid for use with 5-fluorouracil in the treatment of colon cancer; and intravenous levofolinic acid for use in conjunction with methotrexate in the treatment of osteosarcoma.

Long-Acting Desloratadine/Pseudoephedrine (Clarinex-D 24-hour) for Seasonal Allergic Rhinitis

On March 3, the FDA approved desloratadine 5 mg plus pseudoephedrine sulfate 240 mg extended-release tablets (Clarinex-D 24-hour, made by Schering-Plough Corp.) for the relief of nasal and nonnasal symptoms associated with seasonal allergic rhinitis (including nasal congestion) in patients aged 12 years and older.

The formulation provides controlled and consistent delivery of the pseudoephedrine component over 24 hours, allowing patients to manage troublesome early-morning symptoms such as congestion.

The approval was based on the results of two 2-week randomized, parallel-group trials involving 2,852 patients aged 12 to 78 years with seasonal allergic rhinitis. The studies showed that administration of the combination was significantly more effective in reducing histaminic symptoms and congestion than use of either component alone.

The most commonly reported adverse events associated with use of the combination product (compared with desloratadine alone) included dry mouth (8% vs 2%), headache (6% vs 5%), insomnia (5% vs 1%), fatigue (3% for both), pharyngitis (3% vs 2%), and somnolence (3% vs 2%).

Use of the extended-release formulation is contraindicated in patients with narrow-angle glaucoma, urinary retention, severe hypertension or coronary artery disease, and in patients receiving monoamine oxidase inhibitor therapy. A minimum of two weeks must elapse prior to its use in patients who have discontinued MAOI treatment.

Desloratadine (Clarinex, made by Schering-Plough Corp.) was previously approved for the treatment of symptoms associated with seasonal allergic rhinitis and hives of idiopathic origin in patients aged 12 and older.

Aripiprazole (Abilify) Extends Time to Relapse of Stabilized Bipolar Disorder

On March 1, the FDA approved an expanded indication for aripiprazole tablets and oral solution (Abilify, made by Bristol-Myers Squibb Co. and Otsuka Pharmaceutical Company, Ltd.), allowing their use for maintaining efficacy in patients with bipolar I disorder after a recent manic or mixed episode who have been stabilized and maintained for at least six weeks.

The approval was based on the results of a randomized, double-blind, multicenter trial involving 161 patients who had recently experienced a manic or mixed episode and been stabilized with aripiprazole (15 or 30 mg/day) for a minimum of six weeks. All patients had a Young Mania Rating Scale (Y-MRS) total score of 10 or less and a Montgomery-Ã…sberg Depression Rating Scale (MADRS) score of 13 or less at baseline prior to randomization for further aripiprazole therapy or placebo.

Results showed that treatment with aripiprazole significantly increased the time to relapse (manic and depressive) compared with placebo (P = .020). Relapses were also less frequent in the aripiprazole group compared with placebo (25% vs 43%; P = .013).

The majority of relapses were due to manic, rather than depressive symptoms. In a news release, the company notes that there is insufficient data to demonstrate whether aripiprazole is effective in delaying time to depression in patients with bipolar I disorder.

The FDA recommends that use of aripiprazole for extended periods of time (>6 weeks) be periodically evaluated in terms of an individualized patient risk-benefit analysis.

Aripiprazole was approved in September 2004 for the treatment of acute bipolar mania, including manic and mixed episodes associated with bipolar disorder. It is also indicated for the treatment of schizophrenia.

Orphan Drug Levofolinic Acid (Isovorin) for Use With Colon Cancer and Osteosarcoma Therapies

On March 2, the FDA approved two orphan drug designations for intravenous levofolinic acid (Isovorin, made by Target Inc.), allowing its use with 5-fluorouracil (5-FU) for the treatment of colon cancer, and in conjunction with methotrexate (MTX) for osteosarcoma.

Levofolinic acid is the active levo (L) isomer of the 1:1 racemic mixture (d-, l-leucovorin) commonly used in "standard of care" 5-FU–containing regimens for the treatment of colorectal cancer, and after administration of high-dose MTX in treating certain hematologic malignancies.

It approved for use and marketed by Wyeth Pharmaceuticals, Inc., in many member states of the European Union and Japan.

Reviewed by Gary D. Vogin, MD


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