New FDA Approvals

New indication for celecoxib (Celebrex) by Pfizer. The FDA has approved the selective COX-2 inhibitor celecoxib (Celebrex) for a new indication, the relief of the signs and symptoms associated with ankylosing spondylitis.

The FDA also finalized the prescribing instructions for celecoxib for all approved uses, including additional warnings about potential cardiovascular and gastrointestinal risks. The label recommends that celecoxib be prescribed at the lowest effective dose for the shortest duration consistent with individual patient treatment goals. The recommended dose for celecoxib is 200 mg daily for osteoarthritis and 200 mg to 400 mg daily for adult rheumatoid arthritis. For the management of the signs and symptoms of ankylosing spondylitis, the recommended dose of celecoxib is 200 mg daily in single or divided twice per day doses. If no effect is seen after six weeks, a trial of 400 mg daily may be worthwhile. If no effect is observed after six weeks on 400 mg daily, a response is not likely and consideration should be given to alternate treatment options. The approved dose for the prevention of intestinal polyps associated with familial adenomatous polyposis is 800 mg daily.

Pediatric indication for levetiracetam (Keppra) by UCB Pharma. The FDA has approved the anti-epilepsy drug levetiracetam (Keppra) as add-on therapy in the treatment of partial-onset seizures in children 4 years of age and older with epilepsy. The FDA approved this new pediatric indication for levetiracetam under a six-month priority review.

The approval of levetiracetam for children was based on findings from one multicenter, randomized, double-blind, placebo-controlled pivotal study conducted at 60 sites in North America, in 198 children 4-16 years of age with partial-onset seizures with or without secondary generalization uncontrolled by standard antiepileptic drugs (AEDs). Study participants were taking one or two other AEDs at entry. The study consisted of an eight-week baseline period and a four-week titration period, followed by a 10-week evaluation period.

When measuring efficacy, those taking levetiracetam had a significantly larger reduction (26.8%) in weekly seizure frequency over placebo, on average. Additionally, responder rates (the portion of patients achieving a 50% or greater reduction in seizures) for patients taking levetiracetam were 44.6% vs. 19.6% for placebo (both with a P = 0.0002 compared to placebo).

In pediatric patients, 4-16 years of age, the most common adverse events associated with levetiracetam in combination with other AEDs were somnolence, accidental injury, hostility, nervousness, and asthenia. Levetiracetam is associated with somnolence, fatigue, and behavioral abnormalities as well as hematological abnormalities.

Levetiracetam is available in 250 mg, 500 mg, and 750 mg tablets and a grape-flavored (100 mg/mL) oral solution for patients who prefer a solution or have difficulty swallowing tablets. Levetiracetam dosing must be individualized according to renal function status. 

New indication for pregabalin (Lyrica) by Pfizer. The FDA has approved pregabalin (Lyrica) for adjunctive treatment of partial-onset seizures in adults with epilepsy. The FDA approved pregabalin in December 2004 for the management of diabetic peripheral neuropathy and postherpetic neuralgia. Pregabalin is an alpha-2-delta ligand with a newly defined mechanism of action that is believed to work by calming hyperexcited neurons.

The efficacy of pregabalin was established in three double-blind, controlled trials involving 1,052 patients. At the start of treatment with pregabalin, patients experienced approximately 10 seizures a month despite taking one to three other antiepileptic medications. Patients receiving adjunctive treatment with pregabalin experienced a reduction in the frequency of partial seizures by up to 51%. Pregabalin can be given to patients two times or three times a day.

Pregabalin will be designated a controlled substance, recommended for classification in the category with lowest potential for abuse or misuse relative to controlled substances in other categories.

New indication for moxifloxacin HCl (Avelox) by Schering-Plough. The FDA has approved the once-daily antibiotic moxifloxacin HCl (Avelox) for the treatment of complicated skin and skin structure infections (cSSSI) in adults caused by methicillin-susceptible Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, or Enterobacter cloacae.

The FDA approval to treat cSSSI is the fifth indication for moxifloxacin, which is currently approved in the United States to treat acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis, community-acquired pneumonia, and uncomplicated skin and skin structure infections.

Moxifloxacin generally is well tolerated, with adverse events similar to standard therapy. The most common side effects caused by moxifloxacin, which usually are mild, include dizziness, nausea, and diarrhea.

New indication for valsartan (Diovan) by Novartis Pharmaceuticals Corp. The FDA has approved valsartan (Diovan) for a new indication to reduce cardiovascular death in patients at high risk following a heart attack. The FDA also expanded the drug’s heart failure labeling. Valsartan now can be prescribed in a broader range of heart failure patients and no longer is limited to those intolerant of ACE inhibitors.

The FDA approval is based on the results of the VALIANT study, which compared valsartan vs. captopril, an ACE inhibitor, vs. the combination of both in 14,703 patients at high risk for death following a heart attack. In the trial, valsartan was reported to improve survival and reduce cardiovascular events including recurrent heart attack and hospitalizations for heart failure in these patients. There were no differences observed in overall mortality among the treatment groups.

The recommended starting dose for post-myocardial infarction (MI) therapy is 20 mg twice daily (½ 40 mg scored tablet) followed by titration to 40 mg twice daily, with subsequent titrations to a target maintenance dose of 160 mg twice daily, as tolerated by the patient. If symptomatic hypotension or renal dysfunction occurs, consideration should be given to a dosage reduction.

The most common side effects in heart failure patients taking valsartan were dizziness, hypotension, and diarrhea. The most common side effects in post-MI patients that caused them to stop taking the drug were hypotension, cough, rash, and an increase in serum creatinine levels. Because of the risk of hypotension, caution should be observed when initiating therapy in heart failure or post-MI patients. Evaluation of heart failure or post-MI patients should always include assessment of renal function.