FDA Approvals: Avelox, Avandaryl, Trileptal

Yael Waknine

December 01, 2005

Dec. 1, 2005 — The US Food and Drug Administration (FDA) has approved rosiglitazone maleate plus glimepiride tablets for first- and second-line use in the treatment of type 2 diabetes mellitus; a new indication for moxifloxacin HCl tablets and injection, allowing their use for the treatment of complicated intra-abdominal infections; and an expanded indication for oxcarbazepine tablets and oral solution, allowing their use as adjunctive therapy for partial seizures in epileptic children aged 2 to 4 years.


Rosiglitazone/Glimepiride (Avandaryl) for First- and Second-Line Treatment of Type 2 Diabetes

On November 23, the FDA approved rosiglitazone maleate plus glimepiride tablets (Avandaryl, made by SB Pharmco Puerto Rico, Inc, a GlaxoSmithKline company), for use as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus who are already receiving rosiglitazone plus a sulfonylurea or who are not adequately controlled on either drug alone.

Dosing combinations will include a 4-mg dose of rosiglitazone with 1-, 2-, and 4-mg doses of glimepiride.

The approval was based on data from 3,457 patients enrolled in ten 24- to 26-week randomized, double-blind, placebo-controlled studies and one 2-year active controlled study in elderly patients that assessed the safety and efficacy of the drug combination. No clinical trials have been conducted with the fixed-combination tablets as second-line therapy.

Results from the placebo-controlled studies showed that treatment with rosiglitazone, 4 or 8 mg (administered as a single dose or twice-daily divided doses), plus a sulfonylurea significantly reduced mean fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) compared with placebo plus a sulfonylurea or sulfonylurea uptitration (P < .0001 for all).

These findings were supported by data from the active-controlled study in patients aged 59 to 89 years, showing that adjunctive use of rosiglitazone with half-maximal doses of glipizide (20 mg/d) significantly decreased loss of glycemic control compared with glipizide uptitration (2.0% vs 28.7%).

Moreover, the study showed that rosiglitazone plus glipizide was effective for long-term maintenance of glycemic control. During the 2-year period, elderly patients receiving combination therapy achieved significant decreases from baseline in mean FPG (132 vs 157 mg/dL) and HbA1c (6.98% vs 7.72%) compared with no changes in the glipizide group.


Moxifloxacin (Avelox) for Complicated Intra-abdominal Infections

On November 22, the FDA approved a new indication for moxifloxacin HCl (Avelox tablets and injection, made by Bayer Healthcare AG), allowing its use for the treatment of complicated intra-abdominal infections (cIAI), including polymicrobial infections such as abscesses caused by Escherichia coli, Bacteroides fragilis, Streptococcus anginosus, Streptococcus constellatus, Enterococcus faecalis, Proteus mirabilis, Clostridium perfringens, Bacteroides thetaiotaomicron, or Peptostreptococcus species.

The approval was based on data from a clinical trial in 681 patients (379 of whom were clinically evaluable), showing that treatment with sequential intravenous (IV) or oral moxifloxacin was similarly effective to commonly used IV piperacillin/tazobactam given 4 times daily followed by oral amoxicillin/clavulanic acid twice daily (79.8% vs 78.1%; 95% confidence interval [CI], –7.4% to 9.3%).

An open-label international study in 595 patients (clinically evaluable, n = 511) comparing moxifloxacin to IV ceftriaxone plus metronidazole followed by oral amoxicillin/clavulanic acid yielded similar results (80.9% vs 82.3%; 95% CI, –8.9% to 4.2%). In both studies, moxifloxacin was effective at eradicating the key pathogens in cIAIs including E coli and B fragilis.

According to a company news release, benefits of moxifloxacin therapy include once-daily dosing and an adjustment-free transition to oral therapy upon discharge. Dosing adjustments are also not required for patients with renal impairment.

Moxifloxacin was previously approved for the treatment of acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis, community-acquired pneumonia, and uncomplicated and complicated skin and skin structure infections caused by susceptible strains of designated microorganisms.


Oxcarbazepine (Trileptal) for Adjunctive Use in Younger Children

On Oct. 26, the FDA approved an expanded indication for oxcarbazepine (Trileptal tablets and oral solution, made by Novartis Pharmaceuticals Corporation), allowing its use as adjunctive therapy for partial seizures in epileptic children aged 2 to 4 years.

The approval was based on data from a multicenter, rater-blind, randomized study in 238 pediatric patients, showing that the addition of high-dose oxcarbazepine (60 mg/kg/d) to 1 or 2 antiepileptic drugs (AEDs) significantly reduced partial seizures compared with use of a lower dose (10 mg/kg/d).

Both doses of oxcarbazepine were well tolerated (discontinuation rate, 3.9%). The majority of adverse events were mild in severity and appeared to be dose-related, with somnolence, ataxia, and vomiting most commonly reported.

With the exception of a higher incidence of infections and infestations in children younger than 4 years, oxcarbazepine safety profiles were similar among pediatric and adult patients.

Oxcarbazepine was previously approved for use as monotherapy or adjunctive therapy for partial seizures in epileptic adults and children aged 4 years and older.

Reviewed by Gary D. Vogin, MD

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