Efavirenz Fluconazole

Clinically important, potentially hazardous interactions with alcohol, aprepitant, clarithromycin, CNS depressants, delavirdine, digoxin, efavirenz, fluconazole, fluoxetine, fluvoxamine, grapefruit juice, indinavir, itraconazole, ivermectin, kava, ketoconazole, propoxyphene, ritonavir, saquinavir, St John s wort... 

Simultaneous didanosine, folic acid, ganciclovir, lamivudine, nevirapine, pyrazinamide, ranitidine, rifampin, stavudine, sulfamethoxazole, trimethoprim, zidovudine Noninterfering adefovir, amprenavir, delavirdine, efavirenz, fluconazole, indinavir, itraconazole, methadone, nelfinavir, oxazepam, pyrimethamine, rifampin, ritonavir, saquinavir, zalcitabine... 

Others Acetaminophen, amiodarone, carbamazepine, delavirdine, efavirenz, nevirapine, quinidine, repaglinide, sildenafil, tadalafil, trazodone, vardenafil Amiodarone, amprenavir, atazanavir, ciprofloxacin, cisapride, clarithromycin, diltiozem, erythromycin, fluconazole, fluvoxamine, grapefruit juice (in high ingestion), indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, norfloxacin, ritonavir, telithromycin, troleandomycin, verapamil, voriconazole Carbamazepine, efavirenz, glucocorticoids, macrolide antibiotics, nevirapine, phenytoin, phenobarbital, rifabutin, rifapentine, rifampin, St. John s wort... 

Nevirapine is a moderate inducer of CYP3A metabolism, resulting in decreased levels of amprenavir, indinavir, lopinavir, saquinavir, efavirenz, and methadone (Table 49-4). Drugs that induce the CYP3A system, such as tipranavir, rifampin, rifabutin, and St. John s wort, can decrease levels of nevirapine, whereas those that inhibit CYP3A activity, such as fluconazole, ketoconazole, and clarithromycin, can increase nevirapine levels. 

Since indinavir is a substrate as well as an inhibitor of CYP3 A4, numerous and complex drug interactions can occur as described above. Indinavir levels decrease with concurrent use of rifabutin, fluconazole, St. John s wort, and rifampin. Caution is advised with other 3 A4 inducers also, including phenobarbital, phenytoin, carbamezepine, and dexamethasone. Dose reduction of indinavir should be considered if coadministered with delavirdine, ketoconazole, or itraconazole, while an increase in the dose of indinavir is indicated if the drug is coadministered with efavirenz or rifabutin. 

IFOSFAMIDE 1. ANTIBIOTICS -clarithromycin, erythromycin 2. ANTIFUNGALS -fluconazole, itraconazole, ketoconazole voriconazole 3. ANTIVIRALS-efavirenz, ritonavir 4. GRAPEFRUIT JUICE 5. H2 RECEPTOR BLOCKERS - cimetidine 1 plasma concentrations of 4-hydroxyifbsfamide, the active metabolite of ifosfamide, and risk of inadequate therapeutic response Due to inhibition of the isoenzymatic conversion to active metabolites Monitor the efficacy of ifosfamide clinically and t dose accordingly... 

Because efavirenz is metabolized by cytochrome P450, several clinically significant interactions have been described. Efavirenz induces CYP3A4 (5) there was 55% mean induction at a dose of 400 mg/day and 33% at 200 mg/day. However, no significant interaction was noted with co-administration of nelfinavir, zidovudine, lamivudine, fluconazole, or azithromycin (2). 

IRINOTECAN 1. ANTIBIOTICS-clarithromycin, erythromycin 2. ANTICANCER AND IMMUNOMODULATING DRUGS - imatinib 3. ANTIFUNGALS -fluconazole, itraconazole, ketoconazole, voriconazole 4. ANTIVIRALS-efavirenz, ritonavir 5. GRAPEFRUIT JUICE 6. H2 RECEPTOR BLOCKERS - cimetidine t plasma concentrations of SN-38 (t AUC by 100%) and t toxicity of irinotecan, e.g. diarrhoea, acute cholinergic syndrome, interstitial pulmonary disease Due to inhibition of the metabolism of irinotecan by CYP3A4 isoenzymes by ketoconazole Peripheral blood counts should be checked before each course of treatment. Monitor lung function. Recommendation is to -L dose of irinotecan by 25%... 

Zidovudine (AZT) is an HIV reverse transcriptase inhibitor and chain terminator that is extensively glucuronidated (70% of the dose) primarily by UGT2B7. Metabolism of AZT is induced by rifampin (PXR), ritonavir, tipranavir, and efavirenz. Zidovudine clearance is inhibited by methadone (McCance-Katz, 1998) (opiates like codeine and morphine are UGT2B7 substrates), fluconazole Trapnell, 1998, atovaquone (Lee, 1996), and valproate (Lertora, 1994). Rifampin increased the formation clearance to AZT-glucuronide by twofold (Gallicano, 1999). 

Fluconazole doubles nevirapine exposure, and the combination should be used with caution. Fluconazole causes a minor rise in efavirenz steady-state levels, and does not alter delavirdine levels. Fluconazole levels are not altered by these NNRTIs. 

Fluconazole 400 mg daily for one day, then 200 mg daily for 6 days was given to 20 healthy subjects with efavirenz 400 mg daily. The pharmacokinetics of fluconazole were not affected, and although the AUC of efavirenz was raised by 15%, no clinically significant effects are anticipated. ... 

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