Antiretroviral drugs drug interactions

J. G. Gerber, Using pharmacokinetics to optimize antiretroviral drug-drug interactions in the treatment of human immunodeficiency virus infection. Clin Infect Dis 30 S123-129 (2000). 

Table 49-4 Clinically Significant Drug-Drug Interactions Pertaining to Two-Drug Antiretroviral Combinations.1 ...

A systematic review of antipsychotic use in patients with HIV identified one study involving the use of FGAs for the control of delirium and case reports concerning the use of SGAs [24 ]. Increased sensitivity to extrapyramidal symptoms, increased risk of metabolic and bone marrow toxicities and drug-drug interactions with antiretrovirals are discussed. 

Drug-drug interactions Eighteen patients who were given telaprevir and methadone showed no decrease in methadone concentration or any signs of opiate withdraw [55 ]. A meffl-analysis of FAERS from 1997 to 2011 showed increased risk of cardiac arrhythmias in patients on antiretroviral drugs and methadone [43 ]. 

The majority of antiretroviral medications are metabolized by the cytochrome P-450 enzyme system (CYP). Therefore, it is important to review patient medication profiles for drugs that may interact with antiretroviral drugs. 

Significant drug interactions can occur with many antiretroviral agents ... 

The latest information on drug interactions of antiretroviral drugs should be consulted. 

Protease inhibitors, a class of antiretroviral drugs used in the management of HIV infection, are associated with a high risk of drug interactions largely... 

The most common adverse effects associated with enfuvirtide therapy are local injection site reactions. Hypersensitivity reactions may rarely occur, are of varying severity, and may recur on rechallenge. Eosinophilia has also been noted. In one prospective clinical trial, an increased rate of bacterial pneumonia was noted in patients receiving enfuvirtide. No interactions have been identified that would require the alteration of the dosage of other antiretroviral drugs. 

Young B. Review mixing new cocktails drug interactions in antiretroviral regimens. AIDS Patient Care STDS. 2005 19 286-297. 

The most frequent adverse effects associated with nelfinavir are diarrhea and flatulence. Diarrhea can be dose-limiting but often responds to antidiarrheal medications. Like the other protease inhibitors, nelfinavir is an inhibitor of the CYP3A system, and multiple drug interactions may occur as described above. Interactions with antiretroviral agents are summarized in Table 49-4 others may be found in Table 4-2. 

Fichtenbaum CJ, Gerber JG. Interactions between antiretroviral drugs and drugs used for the therapy of the metabolic complications encountered during HIV infection. Clin Pharmacokinet 2002 41 1195-1211. 

The advent of highly active antiretroviral therapy (HAART) to minimize the rapid development of viral resistance in the treatment of HIV infection may result in multiple drug interactions (110-113). Both the nonnucleoside reverse transcriptase inhibitors and the protease inhibitors are substrates and inhibitors of some CYP enzymes, and some act as inducers as well (110,111). The major effects are on the CYP3A isoforms, and this has been used to advantage to increase concentrations of some HIV drugs. For example, delavirdine is a mechanism-based irreversible inhibitor of CYP3A4, and thereby is used to increase exposure to protease inhibitors (114). Ritonavir is a protease inhibitor, but it is used primarily for its ability as a potent inhibitor of CYP3A4 to increase concentrations of other protease inhibitors (115). 

An important consideration in the use of all HIV-1 protease inhibitors, but of ritonavir in particular, is their potential for drug interactions through their effects on cytochrome P450 isozymes. The various interactions of ritonavir with other antiretroviral drugs have been reviewed (139). Ritonavir, which inhibits CYP2D6, the principal pathway by which MDMA is metabolized, can also produce clinically relevant interactions with recreational drugs (140). 

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