Pharmacology Update
Pharmacology Update
The Latest Information on New Drugs and New Indications
By William T. Elliott, MD
Cisapride (propulsid-janssen) has been the subject of a new warning from the FDA. Nearly forty deaths and numerous reports of arrhythmias, usually associated with the use of other medications, have been associated with the drug since 1993. The FDA urged physicians to use every reasonable alternative to treat gastroesophageal reflux disease before trying cicsapride. Janssen has issued a "Dear Doctor" letter to alert them to the warning. Specifically, the drug should never be used with antibiotics such as erythromycin, antidepressants, or protease inhibitors.
Direct-to-consumer (DTC) advertising has become the darling of the pharmaceutical industry. As pharmacy benefit management companies and formularies make traditional pharmaceutical sales forces less effective, companies are focusing their sizable marketing dollars on consumers of health care instead, attempting to create demand for their products. The industry is spending millions on print, television, and even radio ads, touting the relative merits of their drugs and attempting to create name recognition and consumer demand. The effect of these ads on physicians and on overall health care costs has never been assessed. Now, the AMA and the FDA have agreed that the effect of DTC advertising needs to be studied. The AMA initially asked the FDA to perform the study, but the FDA said it was not equipped to perform such a study and has kicked the issue back to the AMA for further analysis.
Are selective serotonin reuptake inhibitors (SSRIs) safer for cardiac patients than tricyclic antidepressants (TCAs)? Two recent studies seem to indicate that this may be the case. Paroxetine (Paxil) and fluoxetine (Prozac) have been shown to be relatively safe for cardiac patients in two recent studies (JAMA 1998;279:287; Am J Psychiatry 1998;155:660-665). In the latter study, fluoxetine was not found to be associated with orthostasis and/or heart rate abnormalities often seen with TCAs. This suggests that these drugs may be better choices for heart patients, particularly older heart patients, than traditional antidepressants.
What is the best regimen to eradicate H. pylori? A recent paper in the British Medical Journal suggests it may be a one-week course of omeprazole, clarithromycin, and metronidazole (BMJ 1998;316:1648-1654). This regimen had a 91% eradication rate at a reasonable cost. Follow-up studies such as breath tests, with retreatment for treatment failures, increased the eradication rate to 97% but nearly doubled the cost. Compliance with one-week courses is better than with two-week regimens, but the advent of prepackaged kits such as P&G's Helidac may improve patient compliance with longer treatment plans.
The possibility of a live attenuated HIV vaccine was dealt a setback with a report at the 12th World AIDS conference in Geneva that an attenuated simian virus similar to HIV can mutate into a strain that can cause disease. The research on monkeys has put a damper on what some researchers have felt is the best hope for an AIDS vaccine. Research at the Dana Farber Cancer Institute in Boston was reported at the conference revealing that of 15 monkeys vaccinated, four became infected and one died within three to five years. This does not affect progress on human testing of an AIDS vaccine by the San Francisco company Vaxgen. Their vaccine, recently given the green light for early trials by the FDA, does not contain live virus.
Generic drug maker Mylan continues to be in the news in the wake of the company's dramatic price increases in many of its products. One of its most popular products, lorazepam (generic Ativan), was subject to a nearly 400% price increase recently amid reports that the company had cornered the worldwide market on raw materials for the popular tranquilizer. Now the U.S. Federal Trade Commission is getting involved, issuing subpoenas to the drug maker to begin investigations regarding the pricing practices. Mylan representatives suggest that it is the brand drug industry that is forcing the generic companies to increase prices in order to stay profitable and that questionable patent protection polices supported by Congress are to blame.
Work is proceeding on vaccines for herpes viruses, both HSV-1 and HSV-2. Use of an attenuated HSV-2 virus has shown some promise, but there is a problem. The most effective site of vaccination is the genital tract. Studies in mice suggest that intravaginal immunization is most effective, inducing strong immunity against vaginal challenge infection with wild-type HSV-2. Whether this is clinically applicable to humans is yet to be seen. However, there are implications from this research that the best place to vaccinate against STDs is locally.
Grapefruit juice is known to inhibit the metabolism of many drugs through its inhibition of cytochrome P450. Known interactions include the dihydropyridine group of calcium channel blockers (nifedipine, felodipine, nimodipine, and amlodipine), midazolam, triazolam, and estrogens. Now, add some of the statins to the list. A recent study (Clin Pharmacol Ther 1998;63:397-402) shows that grapefruit juice significantly altered the pharmacokinetics of lovastatin (Mevacor), raising serum levels of the drug and some of its metabolites significantly. The effect may be the same for simvastatin (Zocor), enough so that patients taking high doses of the drugs with grapefruit juice may develop side effects. The effect of grapefruit juice on cytochrome P450 in the gut is long acting (at least several hours) so separating the timing of taking the drug and drinking the juice or even eating grapefruit will not be helpful.
Subscribe Now for Access
You have reached your article limit for the month. We hope you found our articles both enjoyable and insightful. For information on new subscriptions, product trials, alternative billing arrangements or group and site discounts please call 800-688-2421. We look forward to having you as a long-term member of the Relias Media community.