FDA Safety Changes: Keppra, Naropin, Rebetol

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FDADecember 22, 2006 — The US Food and Drug Administration (FDA) has approved safety label revisions to advise of the expected similarity of levetiracetam's safety profile in patients with juvenile myoclonic epilepsy compared with partial-onset seizures; the rare risk for cardiac arrest in patients receiving ropivacaine HCl injection for the purposes of anesthesia or peripheral nerve blockade; and the risk for dental and periodontal disorders associated with use of ribavirin in with concomitant interferon therapy.

Levetiracetam (Keppra) Linked to Somnolence and Behavior Abnormalities in JME Patients

On August 15, the FDA approved safety label changes for levetiracetam tablets and oral solution (Keppra, made by UCB, Inc) to advise of risks associated with their use as adjunctive therapy for myoclonic seizures in patients aged 12 years and older with juvenile myoclonic epilepsy (JME), a new indication.

Because clinical trials of levetiracetam included a limited number of JME patients, underreporting of certain adverse events is more likely in this population. However, the drug's safety profile is expected to be similar to that observed in the treatment of adults and adolescents with myoclonic seizures, the FDA warned. Adverse events may include including hematologic abnormalities, somnolence, and behavior abnormalities.

Although no obvious hematologic abnormalities were reported in association with levetiracetam therapy for JME, studies of adult patients with partial onset seizures revealed minor but statistically significant decreases compared with placebo in total mean red blood cell count (0.03 x 106/mm3), mean hemoglobin (0.09 g/dL), and mean hematocrit (0.38%).

In pediatric patients with partial onset seizures, minor but statistically significant decreases in white blood cell and neutrophil counts were observed in those receiving levetiracetam vs placebo (-0.4 x 109/L and -0.3 x 109/L, respectively). Mean relative lymphocyte counts increased by 1.7% vs a decrease of 4% in the placebo group.

In a double-blind, controlled trial, 11.7% of JME patients treated with levetiracetam experienced somnolence compared with 1.7% of those receiving placebo. Although the condition did not lead to any discontinuations from the study, 1.7% vs 0% of patients required reduced doses of the treatment drug or placebo, respectively.

Nonpsychotic behavioral disorders (aggression and irritability) and mood disorders (depressed mood, depression, and mood swings) also occurred more often in the levetiracetam vs placebo group (5% vs 0% and 6.7% vs 3.3%, respectively). Of the patients in the active treatment group, 5% required dose reductions or discontinuation of therapy due to anxiety, depressed mood, depression, irritability, or nervousness (vs placebo, 1.7%).

Levetiracetam is indicated as adjunctive therapy for the treatment of partial onset seizures in epileptic patients aged 4 years and older. It is also indicated as adjunctive therapy for myoclonic seizures in patients aged 12 years and older with juvenile myoclonic epilepsy.

Ropivacaine HCl Injection (Naropin) Linked to Rare Cases of Cardiac Arrest

On August 8, the FDA approved safety label changes for ropivacaine HCl injection (Naropin, made by Abraxis BioScience, Inc) to warn of the rare risk for cardiac arrest associated with its use for anesthesia or peripheral nerve blockade.

According to the FDA, the majority of the reported incidents have occurred after unintentional accidental intravascular administration in elderly patients and in patients with concomitant heart disease. Resuscitation has been difficult in some cases, and prolonged efforts may be required to improve the probability of a successful outcome in patients who experience cardiac arrest.

Ropivacaine injection is indicated for use as an epidural block for surgery, including cesarean delivery, major nerve block, and local infiltration. For acute pain management, it may be used as an epidural continuous infusion or intermittent bolus (eg, postoperative or labor; local infiltration).

Ribavirin (Rebetol)-Based Therapy Linked to Risk for Dental and Periodontal Disorders

On August 25, the FDA approved safety label changes for ribavirin capsules and oral solution (Rebetol, made by Schering Corp) to warn of the risk for dental and periodontal disorders associated with their use.

According to the FDA, these conditions have been reported in patients receiving ribavirin and interferon or peginterferon combination therapy. In addition, dry mouth from long-term treatment with ribavirin and interferon alfa-2b or pegylated interferon alfa-2b can damage a patient's teeth and oral mucous membranes.

Patients should be advised to brush their teeth thoroughly twice daily, have regular dental examinations, and rinse their mouths thoroughly after vomiting.

Ribavirin is indicated for use in combination with recombinant interferon alfa-2b injection for the treatment of chronic hepatitis C virus infection (HCV) in interferon-alpha–naive patients aged 18 years and older with compensated liver disease, and those who have relapsed after interferon-alpha therapy.

It is also indicated for use in conjunction with recombinant peginterferon alfa-2b injection for the treatment of HCV in patients aged 18 years and older with compensated liver disease who have not previously received interferon-alpha.

source - Medscape