The Latest Information on New Drugs and New Indications
By William T. Elliott, MD, FACP
Duramed has received approval to market a new synthetic conjugated estrogen compound under the trade name Cenestin. Initially proposed as a generic form of Wyeth-Ayerst’s Premarin, the FDA was convinced by Wyeth that the drugs were not identical, and Duramed was denied generic status for the drug. Subsequently, Duramed petitioned the FDA to approve Cenestin as a unique new drug, with approval granted in late March. Cenestin is synthetic and contains nine estrogen compounds that are derived from plant sources. Premarin is derived from pregnant mares’ urine.
Searle’s COX-2 inhibitor celecoxib (Celebrex) has been linked to 10 deaths and 11 cases of gastrointestinal hemorrhage since it was released in January. But the FDA is quick to point out that this is based on a denominator of 2.5 million prescriptions in the first three months, a rate that the agency feels is not excessive. The FDA is also looking at reports of dispensing errors associated with the drug. There have been more than 50 errors reported, some of them involving confusion over trade names, especially with the antidepressant Celexa and the anti-seizure medication Cerebyx, both marketed by Warner-Lambert. The irony is that Searle changed the name of celecoxib from Celebra to Celebrex just prior to approval to avoid such confusion. Searle is contemplating another name change for the drug, an option that will become unlikely once the company’s aggressive direct-to-consumer advertising campaign begins within the next two months. In other COX-2 news, Merck’s refocoxib (Vioxx) received a recommendation for approval by the FDA’s Arthritis Drugs Advisory Committee on April 20, paving the way for full approval by this summer. Merck is seeking, and will likely receive, approval for the treatment of osteoarthritis like Searle’s celecoxib, but unlike celecoxib, refocoxib is also likely to get an indication for pain. The committee also said that Merck cannot claim that the drug is less damaging to the GI tract than standard NSAIDs. It has been shown to cause less GI irritation than ibuprofen, but the committee made the recommendation because the drug has not been compared to other NSAIDs.
What is the best approach to the patient with new nonvalvular atrial fibrillation? A recent review looked at the long-term health and economic outcomes of treatments designed to restore and maintain sinus rhythm compared with rate control and anticoagulation with warfarin or aspirin.1 An initial attempt at cardioversion is always the preferred treatment. If patients relapse, those at moderate or high risk of stroke should undergo repeat cardioversion and treatment with low-dose amiodarone to maintain sinus rhythm. Patients at low risk for stroke may be allowed to fibrillate if they relapse, but daily aspirin therapy should be initiated.
The FDA has given Hoffman-LaRoche approval to market orlistat (Xenical). The drug is a lipase inhibitor that reduces absorption of dietary fat in the intestine by blocking gastro-intestinal lipases from breaking down ingested fat. Orlistat reduces the absorption of dietary fat by 30%. Unabsorbed fats pass from the small bowel to the colon and, eventually, are excreted in feces. The steatorhea that results can be bothersome to some patients. Other side effects include fecal incontinence, explosive diarrhea, and abdominal cramping. When dietary counseling and a low-calorie diet were combined with Orlistat, 57% of patients lost 5% of their baseline weight after one year compared with 31% for placebo. However, the magnitude of weight loss was not great. The average weight loss was 19.3 lb with Orlistat and 12.8 lb with placebo.
The diagnostic accuracy of colonscopy is only as good as the prep, but many patients complain that current liquid electrolyte purgative agents are worse than the actual test. InKine Pharmaceuticals of Pennsylvania is reporting favorable phase III results with their tablet purgative agent (Diacol). Their data indicate that the prep is as good as liquid agents, and patient acceptance was much higher. The tablets caused less nausea and vomiting than the electrolyte liquid preps. InKine will file for final FDA approval later this year.
The effects of estrogen on the central nervous system of postmenopausal women is the subject of two new studies. Researchers from New York looked at the records of women with early Parkinson’s disease. Estrogen users were found to have a slower progression of the disease and significantly lower scores on the Unified Parkinson’s Disease rating scale compared to non users of estrogen.2 Saunders-Pullman and collegues conclude that estrogen should not be avoided in Parkinson’s disease, and may be beneficial. In a second study, brain activation studies were evaluated by functional magnetic resonance imaging (MRI) exams in women both on and off conjugated estrogen. While women were taking estrogen, changes were seen in several areas of the brain including areas associated with verbal memory, suggesting that the drug may have a direct effect on the central nervous system.3
Despite studies demonstrating similar results using either nebulized bronchodilators or metered dose inhalers (MDI) with spacers, most hospitals and emergency departments (ED) continue to use only nebulized treatments in the setting of acute asthma. A new study again demonstrates the equivalency of these treatments and even suggests better long-term results with MDIs. Researchers in England looked at children older than 3 years who were brought into emergency departments with acute asthma attacks. The children were randomized to receive salbutamol via nebulizer or MDI with a large volume spacer. The children treated with MDIs had shorter ED stays and showed continued improvement at two weeks, presumably because they were instructed in MDI use during their ED visit. Overall costs were also slightly lower in the MDI group.4
1. Catherwood E, et al. Ann Int Med 1999;130:625-636.
2. Saunders-Pullman R, et al. Neurology 1999;52:1417-1421.
3. Shaywitz SE, et al. JAMA 1999;281:1197-1202.
4. Dewar AL, et al. Arch Dis Child 1999;80:421-423.