SmithKline Beecham Issues Dear Doctor Letter’ for Ropinirole

By William T. Elliott, MD, FACP

Ropinirole (requip), smithkline beecham’s parkinson’s drug, is the subject of a "Dear Doctor" letter regarding a tendency of treated patients to suddenly fall asleep while performing various activities, even driving a car. To date, 60 cases of sudden sleep onset have been reported, and there have been reports of fatal car accidents. Similar reports have been seen with pramipexole (Mirapex), also a dopamine agonist used for the same indication. Although somnolence is a known side effect of these drugs, many patients have noted sleep onset suddenly without warning signs. The onset of these sleep episodes may occur as late as one year after starting the drug. Patients need to be assessed for safety and drowsiness during activities. Patients may need to be warned not to drive or perform other potentially hazardous activities.

Glaxo Wellcome has received FDA approval to market alosetron for the treatment of irritable bowel syndrome (IBS) in women. The drug is the first in a new class of drugs for this indication—the selective 5HT3 antagonists. Alosetron will be marketed under the trade name Lotronex. Other pharmaceutical manufacturers are rushing to develop similar drugs for this indication, which affects as many as 20% of Americans, and for which no current treatment provides consistent relief. The drug is only approved for use in women for whom diarrhea is the primary symptom. It should not be used in women with constipation as their primary symptom. It is most effective at reducing pain and urgency to defecate. Constipation is the most common side effect.

Johnson & Johnson’s levofloxacin (Levaquin) is the first agent to be approved for penicillin-resistant Streptococcus pneumonia in community- acquired pneumonia. Although it is the only drug to have received this indication, the other two new fluoroquinolones, moxifloxacin (Avelox) and gatifloxiacin (Tequin), may also be effective in this role. Because of this coverage and their coverage of gram-negative as well as atypical organisms such as mycoplasma and chlamydia, these antibiotics are becoming the drug of choice for community-acquired pneumonia over the macrolides such as azithromycin.

The FDA has approved a new proton pump inhibitor (PPI). Wyeth-Ayerst’s pantoprazole (Protonix) is the fourth entry into this competitive and lucrative drug class. The dominant PPI remains omeprazole (Prilosec) which is the top selling prescription drug in the world. Rabeprazole (Aciphex) and lansoprazole (Prevacid) round out the class. Pantoprazole may try to position itself in the market by touting its favorable drug-drug interaction profile since, unlike omeprazole, no dose adjustment is needed with concomitant administration of other drugs metabolized by the cytochrome P450 system. Pantoprazole is available as a delayed released tablet and is seeking FDA approval for an intravenous (IV) form as well.

Mifepristone, the French abortion pill, has received an "approval" letter from the FDA. However, this was a disappointment for the Population Council, the group that holds the rights to the controversial drug formerly known as RU-486. The letter raises several questions about the manufacture and use of the pill, questions that may be answered by the end of the year. Mifepristone is taken with a prostaglandin (usually misoprostol) to terminate pregnancy and is about 97% effective. It could eventually take the place of 50% of abortions in this country, as it has done in Europe where is has been available for 10 years.

Researchers from the University of Naples have reported success with fluoxetine (Prozac) in preventing migraine. Fifty-two patients with migraine without aura were randomized to 20 mg of fluoxetine or placebo for six months of therapy. Fluoxetine resulted in a significant reduction in total pain index, but only after three months of therapy. No change was noted with placebo. This suggests that serotonin disregulation may play a role in the pathogenesis of migraine (Headache 2000;39:716-719).

Based on research from the University of California at Irvine, estrogen does not appear to benefit women with Alzheimer’s disease (AD). A total of 97 women with mild to moderate AD completed the one-year study after being randomized to conjugated estrogen (0.625 mg/d or 1.25 mg/d) or placebo. The women were assessed using the Clinical Global Impression of Change 7-point scale. Estrogen showed no benefit in either primary or secondary outcomes (JAMA 2000;283:1007-1015). Despite these findings, the role of estrogen replacement therapy (ERT) in the prevention of AD is still unclear. A recent study from Columbia seems to suggest that women with low estradiol levels may be predisposed to developing AD. Fifty postmenopausal women with mild AD were compared to 93 nondemented controls, none of whom were taking ERT. The women with AD had significantly lower estradiol levels than the controls. The authors consider many potential explanations for this finding, but conclude that a cause and effect is likely, suggesting that low estradiol levels may predispose women to AD (Neurology 2000;54:833-837). Studies are ongoing to evaluate the role of estrogen in the prevention of AD.