Drug Interactions Studied at ICAAC
Interactions between antiretrovirals and other drugs have been of great concern for people with HIV/AIDS, yet very little helpful information has been available until several slide sessions were presented at the 39th ICAAC.
How Does Viagra Stand Up to PIs?Pfizer, the manufacturers of Viagra (sildenafil), presented results from two studies that looked at interactions between the erectile dysfunction drug made famous by former Presidential candidate Bob Dole, and two protease inhibitors, Norvir (ritonavir) and Fortovase (saquinavir) (Abstract 659). In each of these studies, 28 HIV-negative men were randomized into the following groups:
The second study had an identical design, except Fortovase (1,200 mg three times a day) was used instead of Norvir on Days 2-8 in Study Arm A. Pharmacokinetic analysis was conducted on days 1, 7 and 8 to determine how the protease inhibitors affected Viagra and vice versa. First the good news: Viagra did not seem to significantly affect the blood levels of either protease inhibitor.
Norvir and Fortovase did, however, seem to have an effect on the pharmacokinetics of Viagra. Both protease inhibitors significantly increased blood levels of Viagra and the amount of time it takes for the body to process the drug, known as clearance. Norvir, in particular, had a more significant effect on blood levels and clearance than Fortovase, but both had enough of an effect for similar action steps to be recommended. This included a 75-percent reduction in the dosing of Viagra (25 mg) when taken with the protease inhibitors and a gap of at least 48 hours before taking Viagra again.
The Lowdown on AntidepressantsMany people with HIV take antidepressants, but studies looking at their interactions with antiretrovirals have been few and far between.
One study examined the interaction of the antidepressant Effexor (venlafaxine) with Crixivan (indinavir) (Abstract 661). The 11-day study of nine HIV-negative adults who took both Crixivan and Effexor showed variable results. While Crixivan did not appear to have a significant effect on the levels of Effexor in the blood, Effexor did appear to significantly decrease Crixivan levels, although in some individuals there was everything from a 13-percent increase to a 66-percent decrease in Crixivan levels.
This raises the question of whether or not a true drug interaction was seen or whether a normal Crixivan variability occurred. Regardless, the investigators on the study recommended that people taking Crixivan should not take Effexor and that further studies were warranted.
Is Methadone as Easy as ABC?In a Canadian pharmacokinetic study, 19 HIV-positive narcotic drug users enrolled in a Dolophine (better known as methadone) treatment program were also given Ziagen (abacavir sulfate, abbreviated ABC). During the four-week study, participants received 600 mg of Ziagen twice a day during the last two weeks, which is double the standard dose.
While the combination was well tolerated by all participants, results showed that methadone delayed the rate of Ziagen absorption, but not the extent. This did not, however, appear to affect the antiviral qualities of Ziagen.
The delay in absorption is not surprising considering that the normal profile of methadone includes gastrointestinal delays. Also, while methadone did not significantly affect Ziagen levels, Ziagen did increase the clearance of methadone. This is significant because it is important for those receiving methadone to maintain consistent levels of the analgesic.
Researchers concluded that minor dosing changes of methadone may be required, and that those receiving both methadone and Ziagen should be closely monitored. The high dose of Ziagen used in the study, however, makes it difficult to draw more conclusive conclusions.
This article has been reprinted at The Body with the permission of AIDS Project Los Angeles (APLA).
This article was provided by AIDS Project Los Angeles. It is a part of the publication Positive Living.