Drug Interaction Report

MONITOR: Coadministration with inducers or mixed inducer/inhibitors of certain metabolic pathways may produce clinically meaningful reductions in the plasma concentrations of caspofungin. This assumption is based on results from regression analyses of patient pharmacokinetic data derived from a small number of patients who were administered the drugs efavirenz, nelfinavir, nevirapine, phenytoin, rifampin, dexamethasone, or carbamazepine prior to and/or concurrently with caspofungin. There are no data from formal drug interaction studies to evaluate these regression analyses, and it is not known which metabolic pathway involved in caspofungin clearance may be inducible.

MANAGEMENT: Caspofungin product labeling recommends that during coadministration with efavirenz, nelfinavir, nevirapine, phenytoin, rifampin, dexamethasone or carbamazepine, an increase in the daily dosage to 70 mg (following the usual 70 mg loading dose) should be considered in patients who are not clinically responding. While data are lacking for other drugs that are known to induce hepatic enzymes, the possibility of a similar interaction should be considered.

GENERALLY AVOID: An isolated case report suggests that foods containing large amounts of tyramine may precipitate a hypertensive crisis in patients treated with St. John's wort. The mechanism of interaction is unknown, as St. John's wort is not thought to possess monoamine oxidase (MAO) inhibiting activity at concentrations achieved in vivo. The case patient was a 41-year-old man who had been taking St. John's wort for seven days prior to presentation at the emergency room with confusion and disorientation. The patient recalled last eating aged cheese and having a glass of red wine approximately 10 hours prior to admission. No other cause of delirium or hypertension could be identified. In addition, alcohol may potentiate some of the pharmacologic effects of St. John's wort. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Until further information is available, patients treated with St. John's wort should consider avoiding consumption of protein foods in which aging or breakdown of protein is used to increase flavor. These foods include cheese (particularly strong, aged or processed cheeses), sour cream, wine (particularly red wine), champagne, beer, pickled herring, anchovies, caviar, shrimp paste, liver (particularly chicken liver), dry sausage, figs, raisins, bananas, avocados, chocolate, soy sauce, bean curd, yogurt, papaya products, meat tenderizers, fava beans, protein extracts, and dietary supplements. Caffeine may also precipitate hypertensive crisis so its intake should be minimized as well. Patients should also be advised to avoid or limit consumption of alcohol.