TreatmentUpdate57, Vol. 7, No. 3 - March 1995
Sean Hosein

The life-threatening infection PCP is one of the more common infections seen in patients in North America and Western Europe. Symptoms can include fever, shortness of breath and dry cough. Standard therapy is Bactrim(R)/Septra(R) or iv (intravenous) pentamidine. Alternatives may include clindamycin-primaquine, dapsone-trimethoprim, trimetrexate-dapsone and Mepron(R) (atovaquone, Wellvone(R)). There are problems associated with every therapy as some patients cannot tolerate sulfa drugs. Mepron is a relatively new treatment for PCP, and the manufacturer, Glaxo-Wellcome, has been conducting trials comparing it to standard therapy.

* STUDY DETAILS

In one experiment, researchers tested Mepron against iv pentamidine. Although 144 subjects (139 men and 5 women) entered the trial the company used data on 56 subjects who received Mepron and 53 who received pentamidine. Only subjects with mild-to-moderate documented PCP entered the study. Researchers assigned subjects at random to one of 2 arms of the study; either 750 mg Mepron "3 times daily with food" or one daily dose of pentamidine of either 3 or 4 mg/kg of body weight. Subjects were supposed to receive either drug for 3 weeks. Those subjects with "moderately severe PCP also received oral [corticosteroids]" to reduce inflammation. Subjects and doctors knew which drugs subjects received.

* RESULTS

According to the printed analysis,

- 57% of subjects who received Mepron and 40% of who received iv pentamidine "were successfully treated." This difference was not statistically significant. - More subjects receiving Mepron (29%) were likely not to improve than subjects receiving pentamidine (17%). This difference was not statistically significant. - Subjects given pentamidine were more likely to stop recovering because of drug toxicity than subjects given Mepron.

* SIDE EFFECTS

Among subjects who received pentamidine, serious side effects included low blood sugar, nausea and vomiting. Among subjects receiving Mepron the most serious side effect was "rash". Subjects receiving Mepron reported "increased cough."

* CONTESTED CONCLUSIONS

The study doctors concluded that "oral [Mepron compared to iv pentamidine] have similar rates for successful treatment of mild to moderate PCP..."

Doctors not associated with this study warn that

"[subjects] in this study had a treatment failure rate that was 71% higher if they received Mepron than if they received iv pentamidine." Other doctors noted that within the first 4 weeks of treatment more subjects assigned to Mepron (13%) died than subjects assigned to pentamidine (8%). This difference was not statistically significant. By the 8th week the rates of death were similar.

Although Mepron is less effective than standard treatment (Bactrim/Septra or iv pentamidine) it remains an option, particularly for patients who cannot tolerate sulfa drugs.

REFERENCES:

1. Dohn MN, Weinberg WG, Torres RA, et al. Oral atovaquone compared to iv pentamidine for Pneumocystis carinii pneumonia in patients with AIDS. Annals of Internal Medicine 1994;121(3):174-180.

2. Lederman MM, and Van der Host C; Stoeckle M and Tannenberg A. Atovaquone for Pneumocystis carinii pneumonia. Annals of Internal Medicine 1995;122(4):314-315.

3. Hughes WT. The role of atovaquone tablets in treating pneumocystis carinii pneumonia. Journal of Acquired Immunodeficiency Syndromes and Human Retrovirology 1995;8(3):247-252.

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Copyright © 1995 - TreatmentUpdate. Reproduced with permission. Reproduction of this article (other than one copy for personal reference) must be cleared through the Editor, The Canadian AIDS Treatment Information Exchange, 555 Richmond St. West, Suite 505, Box 1104, Toronto, ON, M5V 3B1 • Phone: 416-203-7122 • Toll Free: 1-800-263-1638 • Fax: 416-203-8284  http://www.catie.ca