Clinical implications and management of drug-drug interactions between antiretroviral agents and psychotropic medications

Medications used in the treatment of human immunodeficiency virus (HIV) often have drug-drug interactions which complicate treatment of psychiatric illnesses in HIV-infected patients. Protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) are the two classes of HIV medications most likely to be involved with interactions, with the majority occurring via the cytochrome P450 (CYP450) system. These interactions can result in either increased or decreased exposure to psychotropic and antiretroviral medications, often requiring dosage adjustments and increased monitoring. This article reviews some of the major drug interactions with antiretroviral agents.

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Clarithromycin lowers plasma zidovudine levels in persons with human immunodeficiency virus infection.

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.41.8.1709 ◽

1997 ◽

Vol 41 (8) ◽

pp. 1709-1714 ◽

Cited By ~ 29

Author(s):

M A Polis ◽

S C Piscitelli ◽

S Vogel ◽

F G Witebsky ◽

P S Conville ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Virus Infection ◽

Human Immunodeficiency Virus Infection ◽

Drug Interactions ◽

Maximum Concentration ◽

Opportunistic Infections ◽

Simultaneous Administration ◽

Time Curve ◽

Antiretroviral Agents ◽

Immunodeficiency Virus

The use of antiretroviral agents and drugs for the treatment and prophylaxis of opportunistic infections has lengthened the survival of persons with AIDS. In the era of multidrug therapy, drug interactions are important considerations in designing effective and tolerable regimens. Clarithromycin has had a significant impact on the treatment of disseminated Mycobacterium avium complex infection, and zidovudine is the best-studied and one of the most widely used antiretroviral agents in this population. We conducted a study to determine the maximally tolerated dose of clarithromycin and the pharmacokinetics of clarithromycin and zidovudine individually and in combination. Mixing studies were conducted to simulate potential interaction in the gastric environment. The simultaneous administration of zidovudine and clarithromycin had little impact on the pharmacokinetics of clarithromycin or of its major metabolite. However, coadministration of zidovudine and clarithromycin at three doses (500 mg orally [p.o.] twice daily [b.i.d.], 1,000 mg p.o. b.i.d., and 2,000 mg p.o. b.i.d.) reduced the maximum concentration of zidovudine by 41% (P < 0.005) and the area under the concentration-time curve from 0 to 4 h for zidovudine by 25% (P < 0.05) and increased the time to maximum concentration of zidovudine by 84% (P < 0.05), compared with zidovudine administered alone. Mixing studies did not detect the formation of insoluble complexes due to chelation, suggesting that the decrease in zidovudine concentrations results from some other mechanism. Simultaneous administration of zidovudine and clarithromycin appears to decrease the levels of zidovudine in serum, and it may be advisable that these drugs not be given at the same time. Drug interactions should be carefully evaluated in persons with advanced human immunodeficiency virus infection who are receiving multiple pharmacologic agents.

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Anti-Human Immunodeficiency Virus Interactions of SCH-C (SCH 351125), a CCR5 Antagonist, with Other Antiretroviral Agents In Vitro

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.46.5.1336-1339.2002 ◽

2002 ◽

Vol 46 (5) ◽

pp. 1336-1339 ◽

Cited By ~ 68

Author(s):

Cécile L. Tremblay ◽

Françoise Giguel ◽

Christopher Kollmann ◽

Yongbiao Guan ◽

Ting-Chao Chou ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Reverse Transcriptase ◽

Protease Inhibitors ◽

Reverse Transcriptase Inhibitors ◽

Antiretroviral Agents ◽

Synergistic Interactions ◽

Immunodeficiency Virus ◽

Anti Hiv ◽

Hiv 1

ABSTRACT SCH-C (SCH 351125) is a small-molecule antagonist of the human immunodeficiency virus type 1(HIV-1) coreceptor CCR5. It has in vitro activity against R5 viruses with 50% inhibitory concentrations ranging from 1.0 to 30.9 nM. We have studied anti-HIV-1 interactions of SCH-C with other antiretroviral agents in vitro. Synergistic interactions were seen with nucleoside reverse transcriptase inhibitors (zidovudine and lamivudine), nonnucleoside reverse transcriptase inhibitors (efavirenz), and protease inhibitors (indinavir) at all inhibitory concentrations evaluated. We have also studied antiviral interactions between the HIV-1 fusion inhibitor T-20 and SCH-C against a panel of R5 HIV-1 isolates. We found synergistic interactions against all the viruses tested, some of which harbored resistance mutations to reverse transcriptase and protease inhibitors. Anti-HIV-1 synergy was also observed between SCH-C and another R5 virus inhibitor, aminooxypentane-RANTES. These findings suggest that SCH-C may be a useful anti-HIV drug in combination regimens and that a combination of chemokine coreceptor/fusion inhibitors may be useful in the treatment of multidrug-resistant viruses.

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