This activity is part of an ongoing CME/CE initiative to provide information on labeling changes reported by the FDA. Activities of this nature will be posted on Medscape on a weekly basis.
June 25, 2009 — The US Food and Drug Administration (FDA) has approved safety labeling revisions to advise of fetal and neonatal risks associated with use of betaxolol HCl during pregnancy, drug interactions that raise the risk for serotonin syndrome in patients receiving treatment with sibutramine HCl, and an ivermectin drug interaction with warfarin.
Betaxolol HCl (Kerlone) Linked to Fetal and Neonatal Risks
On April 6, the FDA approved safety labeling changes for betaxolol HCl tablets (Kerlone; sanofi-aventis US, Inc) to provide additional information regarding its effects when used in pregnancy.
Betaxolol should only be used during pregnancy if the potential benefit justifies fetal risk, the FDA warned. Beta-blockers, including betaxolol, decrease placental perfusion and can cause intrauterine fetal death and immature or premature deliveries. Fetal bradycardia and hypoglycemia can also occur.
Because the effects of beta-blocker therapy persist for several days after birth, neonates born to mothers who continue betaxolol therapy remain at increased risk for postnatal cardiac and pulmonary complications; bradycardia, respiratory distress, and hypoglycemia have also been reported. Attentive surveillance of the neonate (heart rate and blood glucose for the first 3 to 5 days of life) in a specialized setting is therefore recommended.
Betaxolol is indicated alone or with other antihypertensive agents for the management of hypertension.Sibutramine HCl Monohydrate Linked to Risk for Serotonin Syndrome
The FDA approved class safety labeling revisions for sibutramine HCl monohydrate capsules to provide updated information regarding drug interactions that increase the risk for serotonin-related adverse events. Sibutramine exerts its therapeutic effects via inhibition of norepinephrine, serotonin, and dopamine reuptake. On May 5, the label for Meridia (Abbott Laboratories, Inc) was updated.
The agency previously warned of the risk for potentially life-threatening serotonin syndrome in patients receiving selective serotonin-reuptake inhibitors (SSRIs) and selective serotonin-norepinephrine reuptake inhibitors (SNRIs) in conjunction with 5-hydroxytryptamine receptor agonists (triptans).
A new section now warns that serotonin syndrome or neuroleptic malignant syndrome (NMS)–like reactions can occur with use of SSRIs and SNRIs alone, including sibutramine, but are more likely with concomitant use of serotonergic drugs (including triptans), agents that impair serotonin metabolism (including monoamine oxidase inhibitors [MAOIs]), or with antipsychotics and other dopamine antagonists.
Symptoms of serotonin syndrome may include mental status changes (eg, agitation, hallucinations, and coma), autonomic instability (eg, tachycardia, labile blood pressure, and hyperthermia), neuromuscular aberrations (eg, hyperreflexia and incoordination), and/or gastrointestinal tract symptoms (eg, nausea, vomiting, and diarrhea). Severe cases can resemble NMS, which includes hyperthermia, muscle rigidity, autonomic instability with possible rapid fluctuation of vital signs, and mental status changes.
Clinicians are reminded that as with other serotonergic agents, sibutramine should not be used concomitantly with MAOIs. A minimal 2-week interval should elapse after stopping MAOIs before initiating sibutramine therapy and between discontinuation of sibutramine and starting treatment with MAOIs.
Coadministration of sibutramine with other serotonergic agents is generally not recommended. If such a combination is clinically indicated, patients should be observed closely for the emergence of serotonin syndrome or NMS-like signs and symptoms, particularly during initiation of therapy and dose increases.
Concomitant use of sibutramine with serotonin precursors (eg, tryptophan) is not recommended. Treatment with sibutramine and any concomitant serotonergic or antidopaminergic agents, including antipsychotics, should be discontinued immediately in patients in whom symptoms of serotonin syndrome develop.
Sibutramine is indicated for the management of obesity, including weight loss and maintenance of weight loss, and should be used in conjunction with a reduced-energy diet. It is recommended for obese patients with an initial body mass index of at least 30 kg/m2 or at least 27 kg/m2 in the presence of other risk factors (eg, diabetes, dyslipidemia, controlled hypertension).
Ivermectin (Stromectol) Linked to Drug Interaction With Warfarin
On May 1, the FDA approved safety labeling revisions for ivermectin tablets (Stromectol; Merck & Co, Inc) to warn of a drug interaction with warfarin.
According to the agency, postmarketing cases of increased international normalized ratio have been reported rarely when ivermectin was coadministered with warfarin.Caution is therefore advised in patients receiving concomitant treatment with warfarin and ivermectin.
Ivermectin is an oral antihelmintic agent indicated for the treatment of strongyloidiasis of the intestinal tract caused by the nematode parasite Strongyloides stercoralis and onchocerciasis from Onchocerca volvulus.
Warfarin is indicated for the prophylaxis and/or treatment of venous thromboembolism and pulmonary embolism and thromboembolic complications associated with atrial fibrillation and/or cardiac valve replacement. It may also be used to reduce the risk for death, recurrent myocardial infarction, and thromboembolic events such as stroke or systemic embolization after myocardial infarction.
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Cite this: FDA Safety Changes: Kerlone, Meridia, Stromectol - Medscape - Jun 25, 2009.