International Journal of Hepatology / 2012 / Article / Tab 3

Review Article

Fungal Infections: Their Diagnosis and Treatment in Transplant Recipients

Table 3

Antifungal drug interactions with other drugs. Principle adverse effects of available antifungal agents.
(a)

Drug ADrug B
Interacting drugEchinocandinsAzolesPolyenes
AnidulafunginCaspofunginMicafunginFluconazoleVoriconazolePosaconazoleAmphotericin B and lipid formulations

AmitriptylineInc A
AminoglycosidesInc nephrotoxicity
Antineoplastic drugsInc nephrotoxicity
Astemizole
Calcium channel blockersInc AInc A
CarbamazepineDec B Contraindicated Dec B
CidofovirInc nephrotoxicity
CimetidineDec B
CisaprideContraindicatedContraindicatedContraindicated
CyclosporineSlight
Inc B
Warning
Inc B
Inc A, Inc nephrotoxicityInc A, Inc nephrotoxicityInc A, Inc nephrotoxicityInc nephrotoxicity
DexamethasoneDec B
Didanosine
DigitalisInc ADrug interaction
EfavirenzDec BDec B, Inc A
Ergot AlkaloidsContraindicatedContraindicated
FlucytosineDrug interaction
FoscarnetInc nephrotoxicity
GlycosidesDrug interaction
H2 blockers, antacids, and scralfateDec B
HalofantrineContraindicated
Hydantoins, (phenytoin, Dilantin)Dec BInc A, Dec BInc A, Dec BInc A, Dec B
Isoniazid
FluconazoleDrug Interaction
ItraconazoleDrug Interaction
KetoconazoleDrug Interaction
Long acting barbitunatesContraindicated
Lovastatin/simvastatinInc A
MethadoneInc A
Midazolam/triazolam, poInc AInc AInc A
NevirapineDec B
NifedipineInc A
Oral anticoagulantsInc AInc A
Oral hypoglycemics (tolbutamide, glipizide, and glyburide)Inc AInc A
PentamidineInc nephrotoxicity
PimozideContraindicated Inc AContraindicated
Inc A
Protease inhibitorsInc A
Proton pump inhibitorsDec B, Inc A
QuinidineContraindicatedContraindicated
Ritonavir (400 mg q 12 h)Contraindicated
Rifampin/rifabutinDec BInc A, Dec BContraindicated Inc A, Dec BInc A, Dec B
SirolimusInc AContraindicated, Inc B
St. John's WortContraindicated, Dec B
TacrolimusDec AInc A, with toxicityInc A, with toxicityInc A, with toxicity
TerfenadineContraindicationContraindicated
TheophyllinesInc A
Thiazide diureticsDrug interaction
Trazodone
WarfarinInc A
ZidovudineInc ADrug interaction

(b)

AgentMajor side effectsDrug interactionsCytochrome P450 interactions

PolyenesThe following are applicable to all polyenes

(1) Amphotericin BNephrotoxicity, 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 lossAntineoplastic agents, corticosteroids and corticotropin, digitalis glycosides, flucytosine, azoles, other nephrotoxic medications, skeletal muscle relaxants, and leucocyte transfusionNo interaction in the p450 pathway

(2) AmBisomeInfusion 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 rashSame as aboveNo interaction in the p450 pathway

(3) Amphotericin B
colloidal dispersion (ABCD)
Infusion-related reaction, renal toxicity, hypotension, tachycardia, abdominal pain, hypokalemia, diarrhea, nausea vomiting, rash, dyspnea, asthma, confusion, and dizzinessAntineoplastic 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 tinnitusSame as aboveNo interaction in the p450 pathway

Azoles

(1) VoriconazoleVisual disturbances, hepatic toxicity, arrhythmia, QT prolongation, and infusion-related reactionRifampin 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 indinavirCYP2C19, CYP2C9, and CYP3A4

(2) FluconazoleHepatotoxicity, anaphylactic reaction, QT prolongation, seizures, dizziness, skin disorders, leukopenia, thrombocytopenia, hypercholesterolemia, hypokalemia, vomiting, abdominal pain, nausea, and diarrheaOral hypoglycemics, coumarin-type anticoagulants, theophylline, rifampin, warfarin, phenytoin, cyclosporine, rifabutin, terfenadine, cisapride, tacrolimus, short acting benzodiazepines, astemizole, hydrochlorothiazide, glimepiride, losartan, methadone, losartan, and cyclophosphamideMetabolized by cytochrome P450 systems, CYP2C19, CYP2C9, and CYP3A4

(3) ItraconazoleHepatotoxicity, cardiac dysrhythmias, nausea, diarrhea, vomiting, hypokalemia, bilirubinemia, and rashDigoxin, 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) PosaconazoleHepatotoxicity, diarrhea, nausea, vomiting, abdominal pain, hypokalemia, thrombocytopenia, fever, rigors, headache, fatigue, hypotension, hypertension, anemia, neutropenia, and rashRifabutin, phenytoin, cimetidine, cyclosporin, tacrolimus, midazolam, terfenadine, astemizole, pimozide, cisapride, and quinidineInhibitor of CYP3A4

Echinocandins

(1) AnidulafunginHistamine-mediated symptoms, dyspnea, and hypotensionCyclosporin (no dose adjustment needed)Not an inducer, inhibitor, or substrate of the P450 system

(2) CaspofunginHistamine-mediated symptoms, anaphylactic reaction, hyperbilirubinemia, and rashTacrolimus, cyclosporin, rifampin, efavirenz, nevirapine, phenytoin, dexamethasone, and carbamazeineIs a poor substrate for cytochrome P450 enzymes

(3) MicafunginHistamine-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 arthralgiaSirolimus (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

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