AIDS TREATMENT NEWS #139, November 22, 1991
Denny Smith
On November 1, Abbott Laboratories announced that the Food and Drug Administration (FDA) had approved clarithromycin, an oral antibiotic which Abbott will market under the trade name "Biaxin." Three days later, Pfizer Inc announced FDA approval of a related antibiotic, azithromycin. Pfizer's drug will be marketed as "Zithromax," and will also be administered orally.
Each drug is approved to treat skin and respiratory infections, and azithromycin is also indicated for uncomplicated chlamydial infections. Both drugs were developed from the macrolide class of antibiotics, which includes the commonly used erythromycin. Because of azithromycin's exceptional tissue- penetration properties, Pfizer considers it the prototype of a new class called azalides.
Neither drug was approved specifically to treat AIDS-related infections, though one or both have shown activity in lab studies or clinical trials against toxoplasmosis, Mycobacterium avium complex (MAC), and possibly cryptosporidiosis. For background information, see AIDS TREATMENT NEWS #113.
The approvals are of course good news, because they allow physicians to prescribe the drugs at their discretion, for any diagnosis. But since the indications which won FDA clearance do not cover infections specific to AIDS, insurance companies may balk at paying for such use. Another uncertainty concerns the optimal dosing for treating AIDS infections, assuming one or both of the drugs is indeed effective.
Looking for the current consensus, we contacted three physicians known to be experienced with the research or clinical use of these drugs in treating opportunistic infections.
Jack Remington, M. D., a Professor of Medicine at Stanford University, is widely known as a prominent authority on Toxoplasma infections, and was among the first to call for studies of azithromycin. When we spoke by phone, he cautioned that not only are these drugs not officially approved to treat toxoplasmosis, but they are not yet medically proven -- they lack solid data demonstrating efficacy against this infection in humans. But he acknowledged that people with AIDS and their physicians will likely begin using one or both of the drugs anyway.
In that light, Dr. Remington expects neither drug would be sufficient by itself against toxoplasmosisPthat either will have to be combined with pyrimethamine. He added that azithromycin was more active against Toxoplasma in mice studies.
Even with those qualifications, the drugs may represent a critical option in many situations when the standard combinations -- pyrimethamine with sulfadiazine, or pyrimethamine with clindamycin -- either cannot be tolerated or fail to control the infection.
Lowell Young, M. D., is Director of the Kuzell Institute of Arthritis and Infectious Diseases in San Francisco. For some time Dr. Young has been investigating the drugs' value against MAC infections, and recent results of his work appear in last week's issue of the Lancet. He told us that when used alone, 500 mg of azithromycin daily obtained a good response in 75% of MAC patients.
In animal studies, azithromycin worked even better when combined with ethambutol and clofazimine. Dr. Young suggested that a possible approach for newly diagnosed patients would be to start them on all three drugs, discontinue the clofazimine after one month, and continue the remaining two indefinitely.
The most common side effect to watch for with azithromycin is loose stools. He noted that clarithromycin may be just as effective for treating MAC, but that four times as much drug is needed. In other words, two grams of clarithromycin would be needed to approximate the value of 500 mg of azithromycin.
Robert Thomas, M. D., maintains a large HIV practice in Washington, D. C., and has had clinical experience with at least one of the drugs for treating three different infections.
He said that azithromycin alone worked very effectively on three of his patients who were failing the standard drugs for toxoplasmosis. The dose was 1.2 grams daily until the infection was reversed, followed by maintenance at 600 mg daily. He is convinced that this is a viable option for treating this infection.
Some of Dr. Thomas' patients with MAC had a fairly good initial response to 2 grams of clarithromycin daily, but symptoms tended to return. Because of this, he doubts that the drug will be used alone, except maybe as a prophylactic agent for people at risk for active MAC.
Cryptosporidiosis largely failed to respond to either azithromycin or clarithromycin. This seems in line with most anecdotal reports our readers have shared with AIDS TREATMENT NEWS. Dr. Thomas has seen much better control of cryptosporidial diarrhea with paromomycin and Sandostatin.
We are grateful to these physicians for sharing information and experience which necessarily depend on some anecdote and guesswork. Abbott and Pfizer are expected to continue investigating their products in AIDS-related protocols.
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