Agent Major side effects Drug interactions Cytochrome P450 interactions Polyenes The following are applicable to all polyenes (1) Amphotericin B Nephrotoxicity, infusion-related reaction, pain at the site of injection, phlebitis, thrombophlebitis, cardiopulmonary (cardiac arrest, hypotension, tachypnea, and arrthmia) anemia, thrombocytopenia, leukopenia, coagulation defect, anorexia, nausea, diarrhea, generalized pain, muscle, joint pain, headache, anaphylactic reaction, bronchospasm, wheezing, rash, acute liver failure, hepatitis, jaundice, convulsion, and hearing loss Antineoplastic agents, corticosteroids and corticotropin, digitalis glycosides, flucytosine, azoles, other nephrotoxic medications, skeletal muscle relaxants, and leucocyte transfusion No interaction in the p450 pathway (2) AmBisome Infusion related reaction, renal toxicity, chest pain, hypotension, tachycardia, diarrhea, nausea, vomiting, abdominal pain, bilirubinemia, liver enzymes elevation, hypokalemia, hypomagnesemia, anxiety, headache, lung disorder, pleural effusion, and rash Same as above No interaction in the p450 pathway (3) Amphotericin B Infusion-related reaction, renal toxicity, hypotension, tachycardia, abdominal pain, hypokalemia, diarrhea, nausea vomiting, rash, dyspnea, asthma, confusion, and dizziness Antineoplastic agents, corticosteroids and corticotropin, digitalis glycosides, and azoles No interaction in the p450 pathway (4) Abelcet (ABLC) Infusion-related reactions, increased serum creatinine, cardiopulmonary (hypotension, tachypnea, arrythmia, pleural effusion, anaphylactic reaction (bronchospasm, wheezing, and asthma), rash, acute liver failure, hepatitis, jaundice, nausea vomiting, abdominal pain, headache, renal toxicity dose dependent, muscle, joint pain, convulsion, and tinnitus Same as above No interaction in the p450 pathway Azoles (1) Voriconazole Visual disturbances, hepatic toxicity, arrhythmia, QT prolongation, and infusion-related reaction Rifampin and rifabutin, ritonavir, St.
John's Wort, carbamazepine and long acting barbiturates, cimetidine, macrolide antibiotics (erythromycin), sirolimus, ergot alkaloids, cyclosporine, methadone, tacrolimus, warfarin, oral coumarin, anticoagulants, statins, benzodiazepines, calcium channel blockers, sulfonylureas, vinca alkaloids, prednisolone, mycophenolic acid, rifabutin, efavirenz, phenytoin, omeprazole, oral contraceptives, other HIV protease inhibitors, other nonnucleoside reverse transcriptase inhibitors, and indinavir CYP2C19, CYP2C9, and CYP3A4 (2) Fluconazole Hepatotoxicity, anaphylactic reaction, QT prolongation, seizures, dizziness, skin disorders, leukopenia, thrombocytopenia, hypercholesterolemia, hypokalemia, vomiting, abdominal pain, nausea, and diarrhea Oral hypoglycemics, coumarin-type anticoagulants, theophylline, rifampin, warfarin, phenytoin, cyclosporine, rifabutin, terfenadine, cisapride, tacrolimus, short acting benzodiazepines, astemizole, hydrochlorothiazide, glimepiride, losartan, methadone, losartan, and cyclophosphamide Metabolized by cytochrome P450 systems, CYP2C19, CYP2C9, and CYP3A4 (3) Itraconazole Hepatotoxicity, cardiac dysrhythmias, nausea, diarrhea, vomiting, hypokalemia, bilirubinemia, and rash Digoxin, dofetilide, quinidine, disopyramide, carbamazepine, nevirapine, rifabutin, busulfan, docetaxel, vinca alkaloids, pimozide, alprazolam, diazepam, midazolam, triazolam, dihydropyridines, verapamil, cisapride, atorvastatin, cerivastatin, lovastatin, simvastatin, cyclosporin, tacrolimus, sirolimus, oral hypoglycemics, indinavir, ritonavir, saquinavir, levacetylmethadol, ergot alkaloids, halofantrine, alfentanil, buspirone, corticosteroids, budesonide, trimetrexate, cilostazol, eletriptan, warfarin, carbamazepine, phenobarbital, phenytoin, isoniazid, rifabutin, rifampine, and erythromycin, Potent CYP3A4 isoenzyme inhibitor, CYP2C9 (4) Posaconazole Hepatotoxicity, diarrhea, nausea, vomiting, abdominal pain, hypokalemia, thrombocytopenia, fever, rigors, headache, fatigue, hypotension, hypertension, anemia, neutropenia, and rash Rifabutin, phenytoin, cimetidine, cyclosporin, tacrolimus, midazolam, terfenadine, astemizole, pimozide, cisapride, and quinidine Inhibitor of CYP3A4 Echinocandins (1) Anidulafungin Histamine-mediated symptoms, dyspnea, and hypotension Cyclosporin (no dose adjustment needed) Not an inducer, inhibitor, or substrate of the P450 system (2) Caspofungin Histamine-mediated symptoms, anaphylactic reaction, hyperbilirubinemia, and rash Tacrolimus, cyclosporin, rifampin, efavirenz, nevirapine, phenytoin, dexamethasone, and carbamazeine Is a poor substrate for cytochrome P450 enzymes (3) Micafungin Histamine-mediated symptoms (rash, pruritus, facial swelling, and vasodilation), diarrhea, nausea, vomiting, pyrexia, hypokalemia, thrombocytopenia, headache, hepatocellular damage, delirium, skin disorders (skin necrosis, urticaria), convulsions, and arthralgia Sirolimus (AUC increased by 21%, no effect on micafungin), nifedipine (AUC increased by 18%, no effect on micafungin), and itraconazole (AUC increased by 22%, no effect on micafungin) Micafungin is not an inducer or inhibitor of P-glycoprotein, but is an inducer of CYP3A4
