The Clinical Guide to Supportive and Palliative Care for HIV/AIDS

A Clinical Guide to Supportive and Palliative Care for HIV/AIDS • Chapter 27: Pharmacologic Interactions of Clinical Significancemake it necessary to adjust both the doses and the dosing intervals of drugs that are mostlymetabolized through the liver, such as rifampin, isoniazid and ketoconazole, and to be selectivein the choice of such medications. Changes in the renal elimination of drugs also occur withadvancing disease and can be especially important for renally cleared antiretrovirals such aszidovudine, lamivudine, didanosine, zalcitabine and stavudine, antiviral agents such as ganciclovirand cidofovir, antifungal agents such as amphotericin B, and antibacterial agents such as theaminoglycosides.Changes in immune status that may affect drug responses to antimycobacterial medications(such as the tuberculostatics) or management of opportunistic infections such as MAC havefrequently been reported in patients with advanced disease. As a general rule, there is an increasedincidence of drug toxicity as well as drug sensitivity in patients with HIV—for example,with use of the neuroleptics (chlorpromazine and prochlorperazine)— which may necessitate adecrease from usually recommended doses in order to avoid toxicity.Signs of Drug-Drug Interaction in a Patient with HIV DiseaseAs a general rule, patients experiencing exaggerated toxicities on usual doses of medicationsor manifesting treatment failure in the absence of factors such as resistance or poor adherence/compliance may be suffering from an unidentified drug-drug interaction. A careful review of thepatient’s medication profile is necessary in order to monitor for such drug interactions. Cliniciansshould become familiar with the agents most often associated with significant drug-druginteractions and with the measures to circumvent these interactions when necessary.Regimens with enzyme inducers such as rifampin or enzyme inhibitors such as ritonavir shouldbe noted and checked against a list of other agents metabolized by those same enzyme pathways(see Table 27-14, Advice to Patients: Red Flag Medications, at the end of this chapter). Fortunately,the majority of drug-drug interactions are minor in nature and do not require extensivechanges to the patient’s drug regimen. However, the minority of drug interactions that can beclinically important can offset treatment goals and outcomes in patients if unrecognized orunaddressed, leading to patients receiving suboptimal levels of various drugs and so to treatmentsfailing, often due to emergence of drug-resistant strains of the virus.Drug-Food Interactions of Clinical SignificanceIt is well established that the presence or absence of food or certain beverages can significantlyaffect the bioavailability of a number of medications. A variety of mechanisms includingchanges in pH, formation of unabsorbable cation complexes, increased solubility of drugs andinterference with gut metabolism as well as a decrease in the motility of the gut may be at play.Table 27-1 lists some of the more common food-drug interactions with antiretroviral agents. 1552U.S. Department of Health and Human Services • Health Resources and Services Administration • HIV/AIDS Bureau