151 However, investigators have shown that no interaction occurs when the itraconazole capsule is co-administered with the non-buffered enteric-coated ddI formulation that is currently marketed.152 Early studies of antacid co-administration

with posaconazole tablets suggested that elevations in gastric pH did not produce clinically significant changes in EGFR tumor posaconazole concentrations or exposure.153 However, a well-designed study using the currently marketed formulation and a proton pump inhibitor clearly demonstrates that posaconazole absorption is significantly impacted by changes in pH and food.45 Co-administration with a proton pump inhibitor reduces posaconazole Cmax and exposure Selumetinib nmr by 46% and 32% respectively.45 Food, irrespective of whether it is a solid or liquid and regardless of fat content, significantly increases the bioavailability of posaconazole.46,47,153 Indeed, the effect of food on posaconazole

pharmacokinetics is much greater than that of pH.45,153 Increases in gastric emptying caused by prokinetic agents such as metoclopramide may result in reductions in Cmax and exposure that are likely not clinically significant.45 In contrast, the co-administration of this azole with loperamide, an antikinetic agent, produces no clinically relevant effects on posaconazole pharmacokinetics.45 In patients who require acid suppression therapy and treatment with either itraconazole or posaconazole, the interactions can be managed. In patients requiring itraconazole therapy, the solution should be employed. For protracted courses of therapy, the solution may be impractical and an appropriate alternative antifungal agent should be considered. To maximise posaconazole absorption in patients requiring acid suppression therapy, the drug should be administered in divided doses with or after a high-fat meal, or at least with any meal, a nutritional supplement, or an acidic beverage.45 Induction of antifungal biotransformation.  Antifungal agents can produce additive toxicities with other

medicines and alter the distribution, metabolism and elimination of many other drugs. However, few drugs can enhance the toxicity, or decrease the Metalloexopeptidase serum concentrations or systemic exposure of antifungal agents. Medicines that affect the disposition of antifungal agents do so by inducing enzymes involved in oxidative or conjugative metabolism, or transport proteins. Interactions affecting the disposition of antifungal agents typically involve phenytoin, phenobarbital, carbamazepine, rifampin, ritonavir, efavirenz and other well-known inducers of CYP3A4. In addition, as illustrated by the interaction between rifampin and caspofungin, our understanding of the induction of transport proteins will grow as their role in drug disposition continues to evolve. The majority of interactions affecting the disposition of antifungal agents involves the induction of CYP3A4.