Antiretroviral drug Interactions

Treatment of HIV-infected patients requires polypharmacy, during which drug interactions can occur. Pharmacokinetic interactions are those that affect the absorption, distribution, metabolism, or excretion of a drug. Pharmacodynamic interactions produce antagonistic, additive, or synergistic effects. Interactions can be adverse or beneficial. This chapter provides a framework for understanding HIV-related drug interactions through the principles of pharmacology. Pharmacokinetic drug interactions Absorption Fasting, gastric pH, and enteric P-glycoprotein (PGP) expression all can affect absorption. Table 12.1 delineates drug–food interactions and lists antiretroviral drugs that may be administered without regard to food. Antacids (including the buffer in older formulations of didanosine), H2-receptor antagonists, and proton pump inhibitors increase gastric pH, impairing the bioavailability of drugs that require low pH for optimal absorption (e.g., delavirdine, indinavir, itraconazole, ketoconazole). This interaction usually can be avoided by administrating the gastric pH-raising agent 1 to 2 hours later [1–3]. Didanosine is much better absorbed in an alkaline environment because it is acid labile. The original formulation of didanosine included a buffer (calcium carbonate and magnesium hydroxide in tablets or citrate-phosphate in sachets) or had to be reconstituted in antacid. The buffer in didanosine does not affect dapsone absorption but significantly decreases ciprofloxacin absorption [4, 5]. Didanosine or antacids do not interfere with nevirapine. The new formulation of didanosine (Videx® EC) does not have significant interactions with ciprofloxacin, indinavir, or azole antifungals [6, 7]. Drug absorption also can be affected by transporters in the gut.