Drug Criteria & Outcomes

New FDA Approvals

FDA recently announced these approvals: The first generic versions of Novartis' anticonvulsant Trileptal® (oxcarbazepine) have been approved by FDA for use alone or in combination with other medications in treating partial seizures in adults and children ages four and older.

Oxcarbazepine tablets in 150 mg, 300 mg, and 600 mg strengths are being manufactured by Roxane Laboratories, Inc., Glenmark Pharmaceuticals Limited, and Sun Pharmaceutical Industries Limited.

FDA said labeling of the generic products may differ from Trileptal because parts of the Trileptal labeling are protected by patents and/or exclusivity.

Serious skin reactions have been reported in children and adults associated with Trileptal use. Common side effects reported with Trileptal include dizziness and drowsiness.

FDA has approved Johnson & Johnson's Doribax (doripenem injection, 500 mg intravenous infusion) for treating complicated urinary tract and intra-abdominal infections. The agency said Doribax has been shown to be active against several strains of bacteria.

In several multicenter, multinational studies, doripenem was shown to have a cure rate comparable to the currently prescribed medications levofloxacin (Ortho-McNeil's Levaquin®), for complicated urinary tract infections, and meropenem (AstraZeneca's Merrem®), for complicated intra-abdominal infections.

The most common adverse reactions reported were headache, nausea, diarrhea, rash, and phlebitis. Also, allergic reactions have occurred and some may require immediate treatment.

FDA said doripenem's safety and effectiveness in pediatric patients have not been established. And it has not been studied in pregnant women and should only be used during pregnancy if clearly needed.

Bristol-Myers Squibbs' intravenous infusion Ixempra (ixabepilone), a new cancer treatment, has been approved by FDA for use in patients with metastatic or locally advanced breast cancer who have not responded to certain other cancer drugs. FDA evaluated ixabepilone under priority six-month review. It was approved for use in combination with capecitabine (Roche's Xeloda®) in patients who no longer benefit from two other chemotherapy treatments, including an anthracycline such as doxorubicin or epirubicin, and a taxane such as paclitaxel or docetaxel.

Ixabepilone also was approved for use alone in patients who no longer benefit from an anthracycline, a taxane, and capecitabine.

FDA said ixabepilone has been shown to bind to cancer cell microtubules, structures within cells that help to support and shape them and also play a role in cell division.

The drug's safety and effectiveness in combination with capecitabine were evaluated in 752 patients in a randomized clinical trial comparing the combination to capecitabine alone. The combination therapy demonstrated improvements in delaying cancer progression or death compared to capecitabine alone, the agency said. Safety and efficacy of ixabepilone administered alone were evaluated in a study of 126 patients. Clinically significant tumor shrinkage occurred in 12% of the patients.

Ixabepilone's significant side effects include peripheral neuropathy and bone marrow suppression. Other commonly observed toxicities included constipation, nausea, vomiting, muscle pain, joint pain, fatigue, and general weakness. Ixabepilone should not be taken by women who have had severe allergic reactions to drugs that contain cremophor or its derivatives, or by women who have had baseline bone marrow suppression determined by low white blood cell or platelet count.

The combination of ixabepilone and capecitabine should not be given to patients with moderate or severe liver impairment due to increased risk of toxicity and death.

FDA has approved Merck's Isentress (raltegravir) tablets for treating HIV-1 infection in combination with other antiretroviral agents in treatment-experienced adult patients who have evidence of viral replication and HIV-1 strains resistant to multiple antiretroviral agents.

FDA said raltegravir is the first agent of a drug class known as HIV integrase strand transfer inhibitors. It is designed to interfere with the enzyme that HIV-1 needs to multiply.

When used with other anti-HIV medicines, raltegravir may reduce the amount of HIV in the blood and may increase white blood cells to help fight off other infections. Agency approval of raltegravir is based on data from two studies in 699 HIV-1 infected patients with histories of extensive antiretroviral use. A greater proportion of the patients who received raltegravir in combination with other anti-HIV drugs experienced reductions in the amount of HIV in the blood, compared with patients who received placebo in combination with other anti-HIV drugs.

The most common adverse events reported with raltegravir were diarrhea, nausea, and headache. Blood tests also showed abnormal elevated levels of a muscle enzyme in some patients receiving the drug.

Patients taking raltegravir may still develop infections, including opportunistic infections or other conditions that may develop in patients living with HIV-1 infection. Its long-term effects are not known and its safety and effectiveness in children younger than age 16 have not been studied. It also has not been studied in pregnant women. FDA said women who are taking HIV medications when they get pregnant are advised to talk with their doctor or other health care professional about use of this drug during pregnancy and about registering with the antiviral pregnancy registry if they use it.