Drug Interactions of Antiretroviral Agents

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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Antiviral and Cellular Metabolism Interactions between Dexelvucitabine and Lamivudine

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01543-06 ◽

2007 ◽

Vol 51 (6) ◽

pp. 2130-2135 ◽

Cited By ~ 7

Author(s):

Brenda I. Hernandez-Santiago ◽

Judy S. Mathew ◽

Kim L. Rapp ◽

Jason P. Grier ◽

Raymond F. Schinazi

Keyword(s):

Drug Interactions ◽

Human Peripheral Blood ◽

Synergistic Effects ◽

Cellular Metabolism ◽

Therapeutic Modality ◽

Nucleoside Triphosphate ◽

Antiretroviral Agents ◽

Human T Cell ◽

High Concentrations ◽

Hiv 1

ABSTRACT Studies on cellular drug interactions with antiretroviral agents prior to clinical trials are critical to detect possible drug interactions. Herein, we demonstrated that two 2′-deoxycytidine antiretroviral agents, dexelvucitabine (known as β-d-2′,3′-didehydro-2′,3′-dideoxy-5-fluorocytidine, DFC, d-d4FC, or RVT) and lamivudine (3TC), combined in primary human peripheral blood mononuclear (PBM) cells infected with human immunodeficiency virus 1 strain LAI (HIV-1LAI), resulted in additive-to-synergistic effects. The cellular metabolism of DFC and 3TC was studied in human T-cell lymphoma (CEM) and in primary human PBM cells to determine whether this combination caused any reduction in active nucleoside triphosphate (NTP) levels, which could decrease with their antiviral potency. Competition studies were conducted by coincubation of either radiolabeled DFC with different concentrations of 3TC or radiolabeled 3TC with different concentrations of DFC. Coincubation of radiolabeled 3TC with DFC at concentrations up to 33.3 μM did not cause any marked reduction in 3TC-triphosphate (TP) or any 3TC metabolites. However, a reduction in the level of DFC metabolites was noted at high concentrations of 3TC with radiolabeled DFC. DFC-TP levels in CEM and primary human PBM cells decreased by 88% and 94%, respectively, when high concentrations of 3TC (33.3 and 100 μM) were added, which may influence the effectiveness of DFC-5′-TP on the HIV-1 polymerase. The NTP levels remained well above the median (50%) inhibitory concentration for HIV-1 reverse transcriptase. These results suggest that both β-d- and β-l-2′-deoxycytidine analogs, DFC and 3TC, respectively, substrates of 2′-deoxycytidine kinase, could be used in a combined therapeutic modality. However, it may be necessary to decrease the dose of 3TC for this combination to prove effective.

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Zidovudine and other antiretroviral agents including drug interactions and toxicities

Current Opinion in Infectious Diseases ◽

10.1097/00001432-199304000-00013 ◽

1993 ◽

Vol 6 (2) ◽

pp. 210-217 ◽

Cited By ~ 3

Author(s):

Douglas L. Mayers

Keyword(s):

Drug Interactions ◽

Antiretroviral Agents

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Drug interactions between statins and antiretroviral agents

Current Opinion in HIV and AIDS ◽

10.1097/coh.0b013e3282fbaa54 ◽

2008 ◽

Vol 3 (3) ◽

pp. 247-251 ◽

Cited By ~ 4

Author(s):

David Burger ◽

Erik Stroes ◽

Peter Reiss

Keyword(s):

Drug Interactions ◽

Antiretroviral Agents

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New Options in the Treatment of Lipid Disorders in HIV-Infected Patients

The Open AIDS Journal ◽

10.2174/1874613600903010031 ◽

2009 ◽

Vol 3 (1) ◽

pp. 31-37 ◽

Cited By ~ 9

Author(s):

Erika Ferrari Rafael da Silva ◽

Giuseppe Bárbaro

Keyword(s):

Cardiovascular Risk ◽

Drug Interactions ◽

Patient Adherence ◽

Blood Cholesterol ◽

Antiretroviral Agents ◽

Lipid Disorders ◽

Lipid Guidelines ◽

Long Time ◽

Virologic Control ◽

History Of

Since the introduction of HAART, there was a remarkably change in the natural history of HIV disease, leading to a notable extension of life expectancy, although prolonged metabolic imbalances could significantly act on the longterm prognosis and outcome of HIV-infected persons, and there is an increasing concern about the cardiovascular risk in this population. Current recommendations suggest that HIV-infected perons undergo evaluation and treatment on the basis of the Third National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (NCEP ATP III) guidelines for dyslipidemia, with particular attention to potential drug interactions with antiretroviral agents and maintenance of virologic control of HIV infection. While a hypolipidemic diet and physical activity may certainly improve dyslipidemia, pharmacological treatment becomes indispensable when serum lipid are excessively high for a long time or the patient has a high cardiovascular risk, since the suspension or change of an effective antiretroviral therapy is not recommended. Moreover, the choice of a hypolipidemic drug is often a reason of concern, since expected drug-drug interactions (especially with antiretroviral agents), toxicity, intolerance, effects on concurrent HIV-related disease and decrease patient adherence to multiple pharmacological regimens must be carefully evaluated. Often the lipid goals of patients in this group are not achieved by the therapy recommended in the current lipid guidelines and in this article we describe other possibilities to treat lipid disorders in HIV-infected persons, like rosuvastatin, ezetimibe and fish oil.

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

Mental Health Clinician ◽

10.9740/mhc.n139874 ◽

2013 ◽

Vol 2 (9) ◽

pp. 274-285 ◽

Cited By ~ 1

Author(s):

Meredith G. Jernigan ◽

Gretchen M. Kipp ◽

Ashley Rather ◽

Matthew T. Jenkins ◽

Allison M. Chung

Keyword(s):

Human Immunodeficiency Virus ◽

Drug Interactions ◽

Psychotropic Medications ◽

Clinical Implications ◽

Reverse Transcriptase Inhibitors ◽

Antiretroviral Agents ◽

Psychiatric Illnesses ◽

Antiretroviral Medications ◽

Immunodeficiency Virus ◽

Major Drug

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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