New (Possible) 2nd Generation PI Hits the Market
The new protease inhibitor amprenavir (Agenerase®) manufactured by Glaxo Wellcome has been approved by the FDA. This is the fifth FDA-approved protease inhibitor (PI), and the first PI approved in 2 years. When given as part of a triple combination therapy, amprenavir is capable of significant viral suppression in both therapy-naïve patients, as well as some NRTI and NNRTI-experienced patients. In addition, amprenavir appears to help about 50% of patients who have developed viral resistance to other PIs. Preliminary trials also show it can penetrate the blood-brain barrier, reaching virus in this part of the body that no other HIV-drug has been able to kill.
Amprenavir is a gelatin capsule taken with or without food, and the standard dose is eight very large 150mg capsules taken twice daily. If taken with food, high fat meals should be avoided. It has a long half-life, with blood levels staying high for up to10 hours. This means dosage timing can be a little more relaxed than with previous PIs. Preliminary research on amprenavir shows the level in the blood varies significantly depending on the other antiretrovirals being used. Of particular concern is that when used with efavirenz (Sustiva), amprenavir levels may be decreased so much that it might have to be taken three times a day. For this reason, each patient's dose may be different, but we still do not know the interactions of all the antiretroviral drugs with amprenavir.
The most frequently reported side effects were nausea, vomiting, diarrhea, flatulence, headache and numbness and tingling around the mouth. The gastro-intestinal side effects tend to resolve after a few weeks, and generally, the drug was pretty well tolerated in clinical trials. Skin rashes were reported by 11% or more subjects, including Stevens-Johnson syndrome (1%). As with other PIs, amprenavir may be associated with acute anemia, diabetes mellitus and elevated blood sugar. However, early data suggests that amprenavir may not cause a significant increase in blood lipids, cholesterol and triglycerides. Galxo Wellcome reports no changes in fat distribution, but it is premature to predict what the results of long term use may be.
This article was provided by Seattle Treatment Education Project. It is a part of the publication STEP Perspective.