FDA/November

New Combination for Menopausal Symptoms

A oral combination of drospirenone and estradiol (Angeliq; Berlex) has been approved for the treatment of moderate-to-severe vasomotor symptoms associated with menopause. The agent is expected to be available in mid-2006 in a preparation containing 0.5 mg drospirenone and 1 mg estradiol. Women with liver, kidney, or adrenal disease should not take this drug (www.berlex.com).

Novel Once-Daily Pain Medication

A once-daily oral formulation of tramadol hydrochloride (brand name undisclosed; Biovail) has been approved for the treatment of moderate-to-moderately severe chronic pain in once-daily 100-, 200-, and 300-mg doses (www.biovail.com).

Combination Vaccine for Children Offers Extended Coverage

A combination of M-M-R II and Varivax in a single shot (ProQuad; Merck) for simultaneous vaccination against measles, mumps, rubella, and varicella in children 12 months to 12 years of age has been approved. The most common side effects of the combined vaccine include injection site reactions (ie, pain/tenderness/soreness, erythema, swelling, ecchymosis, and rash) (www.merck.com).

Extended-Release Version of Oral Sleep Agent

Zolpidem tartrate extended-release (Ambien CR; Sanofi-Aventis) has received a new indication for sleep maintenance in patients with insomnia. The new formulation can be used for the long term and is available in a 12.5-mg dose, recommended for adults, and a 6.25-mg dose, recommended for the elderly. This sleep aid is already approved for the short-term treatment of sleep induction in patients with insomnia (www.sanofi-aventis.us).

Atorvastatin for Stroke/MI Prevention in Diabetes

Atorvastatin calcium (Lipitor; Pfizer) has received a new indication for reducing the risk of stroke or myocardial infarction (MI) in patients with type 2 diabetes who have no evidence of heart disease but have other risk factors, as well as reducing stroke risk in patients with no evidence of coronary heart disease (CHD) but with multiple risk factors other than diabetes. This agent is already indicated for reducing risk of MI and revascularization procedures and angina in adults without clinically evident CHD but with multiple risk factors for CHD (www.pfizer.com).

Exemestane Indicated for Adjuvant Therapy in Early Breast Cancer

Exemestane (Aromasin; Pfizer) has received a new indication as adjuvant treatment in postmenopausal women with estrogen receptor-positive early breast cancer after 2 to 3 years of tamoxifen or the completion of 5 consecutive years of adjuvant hormonal therapy. Exemestane was already approved for treatment of advanced breast cancer in women whose tumors stopped responding to tamoxifen. The most common side effects include hot flashes, fatigue, and arthralgia/bone pain (www.pfizer.com).

Expanded Indications for RA Agents

• The injectable agent infliximab (Remicade; Centracor) has received new indications for reducing signs and symptoms, achieving clinical remission and mucosal healing, and eliminating corticosteroid use in patients with moderate- to-severe active ulcerative colitis who have not responded to conventional therapy.Infliximab is already approved for the treatment of Crohn's disease, rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis (www.centocor.com).

· Adalimumab (Humira; Abbott) has received new indications for reducing signs and symptoms of active arthritis in patients with psoriatic arthritis and as first-line treatment of recent-onset moderate-to-severe rheumatoid arthritis (RA). Adalimumab is already approved to treat moderate-to-severe RA in patients who have had insufficient response to ³1 disease-modifying antirheumatic drugs (www.abbott.com).

Box: Public Health Advisories

• Infusion-pump seizure. At the request of the FDA, on October 12, 2005, the US District Court for the Northern District of Illinois issued a warrant for seizure of 3 types of infusion pumps manufactured by Baxter Healthcare Corporation because FDA inspections revealed that the firm has continually failed to follow medical device manufacturing requirements. The seized products are: SYNDEO PCA Syringe Pumps, Colleague Volumetric Infusion Pumps, and Colleague CX Volumetric Infusion Pumps. The FDA alleges that none of the seized infusion pumps was manufactured under the proper controls and that the Colleague pumps have a design defect that may cause them to stop and shut down during infusion therapy. Infusion pumps were seized from Baxter's warehouses. No products were seized from health care facilities or patients. Health care facilities can continue to use pumps in their possession, guided by instructions provided previously by Baxter, but should recognize the types of problems that could occur and have a backup plan in place, especially in situations where the pump is part of a life-saving function. More detailed recommendations for users of specific pump models are available at www.Baxter.com.

• Patients with hepatic insufficiency should avoid duloxetine. The FDA has revised the prescribing information for duloxetine hydrochloride (Cymbalta; Ely Lilly), indicated for the treatment of major depressive disorder and diabetic peripheral neuropathic pain. Postmarketing reports of hepatic injury (ie, hepatitis and cholestatic jaundice) suggest that patients with preexisting liver disease who take duloxetine may have an increased risk for further liver damage. The new labeling extends the precautions with this agent to include patients with chronic liver disease. It is recommended that duloxetine not be administered to patients with any hepatic insufficiency (www.fda.gov/medwatch/safety/2005/safety05.htm#Cymbalta).

· Dispensing/Rx errors of hypertension drug and migraine/seizure drugs. Medication dispensing or prescribing errors between the oral agents metoprolol succinate extended-release (Toprol XL; AstraZeneca), indicated for the treatment of hypertension, for the long-term treatment of angina pectoris, and for heart failure New York Heart Association class II or III, and topiramate (Topamax; Ortho-McNeil), indicated for the treatment of epilepsy and migraine prophylaxis have been reported. There have also been reports of medication errors stemming from confusion between metoprolol succinate extended release and carbamazepine (Tegretol, Tegretol XR; Novartis), which is indicated for the treatment of complex partial seizures, generalized tonic-clonic seizures, and trigeminal neuralgia. Some of these errors have led to adverse events (www.fda.gov/medwatch/safety/2005/safety05.htm#Toprol).

• FDA warns of suicide risk associated with atomoxetine. The prescribing information for atomoxetine (Strattera, Eli Lilly) was changed to include a boxed warning to alert physicians of an increased risk of suicidal ideation in children and adolescents being treated with this drug. The FDA also advised that a guide informing patients of the risks associated with atomoxetine treatment should be given to patients when prescribing this agent, which is indicated for attention deficit hyperactivity disorder. Also, pediatric patients receiving atomoxetine should be closely observed for clinical worsening, as well as agitation, irritability, suicidal thinking or behavior, and unusual changes in behavior (www.fda.gov/medwatch/safety/2005/safety05.htm#Strattera).

• Major malformations in pregnant women taking paroxetine. The FDA has initiated changes to the pregnancy/precautions section of the prescribing information for paroxetine and paroxetine controlled-release (Paxil, Paxil CR; GlaxoSmithKline) tablets to describe the results of a retrospective epidemiologic study of major congenital malformations in infants born to women taking antidepressants during the first trimester of pregnancy. This study suggested an increase in the overall risk of major congenital malformations for paroxetine as compared with other antidepressants (odds ratio, 2.2%; 95% confidence interval, 1.34-3.63). Physicians are advised to carefully weigh the potential risks and benefits of paroxetine therapy in women who are pregnant and to discuss these findings, as well as treatment alternatives, with their patients (www.fda.gov/medwatch/safety/2005.safety05.htm#Paxil2).

FDA Proposes New Measures to Protect Food Supply from Mad Cow Disease

New measures to protect against the agent thought to cause bovine spongiform encephalopathy (BSE), or mad cow disease, have been proposed by the FDA. If passed, the FDA’s feed regulations for all animals would be amended to prohibit the use of certain high-risk cattle materials that can potentially carry the BSE-infectious agent. These additional measures include:

• Prohibiting the use of the brains and spinal cords form cattle ³30 months of age
• Prohibiting the use of the brains and spinal cords from cattle of any age not inspected and passed for human consumption
• Prohibiting the use of the entire carcass of cattle not inspected and passed for human consumption if the brains and spinal cords have not been removed
• Prohibiting the use of tallow that is derived from the materials prohibited by this proposed rule if the tallow contains >0.15% insoluble impurities
• Prohibiting the use of mechanically-separated beef that is derived from the materials prohibited by this proposed rule.

More information on the proposed rule can be found at: www.fda.gov.