Phenytoin with itraconazole

Low and sometimes very low serum concentrations of itraconazole have been seen during concurrent therapy of itraconazole with phenjdoin (68). At the same time, phenytoin concentrations may themselves be lowered when it is used with itraconazole (68). 

Two patients tatong phenytoin and two taking phenytoin with car-bamazepine either did not respond to treatment with itraconazole 400 mg daily for aspergillosis, coccidioidomycosis or cryptococcosis, or suffered a relapse. All of them had undetectable or substantially reduced serum itraconazole levels compared with other patients taking itraconazole alone. Two other patients also had very low itraconazole serum levels while taking phenytoin and phenobarbital."... 

The effects of buspirone are decreased when the drug is administered with fluoxetine Increased serum levels of buspirone occur if the drug is taken with erythromycin or itraconazole Should any of these combinations be required, the dosage of buspirone is decreased to 2.5 mg BID, and the patient is monitored closely. Venlafaxine blood levels increase with a risk of toxicity when administered witii MAOIs or cimetidine There is an increased risk of toxicity when trazodone is administered with the phenothiazines and decreased effectiveness of trazodone when it is administered with carbamazepine Increased serum digoxin levels have occurred when digoxin is administered with trazodone There is a risk for increased phenytoin levels when phenytoin is administered witii trazodone... 

Itraconazole has significant interactions with a number of commonly prescribed drugs, such as rifampin, phenytoin, and carbamazepine. Itraconazole raises serum digoxin and cyclosporine levels and may affect the metabolism of oral hypoglycemic agents and coumadin. Absorption of itraconazole is impaired by antacids, Hj blockers, proton pump inhibitors, and drugs that contain buffers, such as the antiretroviral agent didanosine. 

With the important exception of additive effects when combined with other CNS depressants, including alcohol, BZDs interact with very few drugs. Disulfiram (see the section The Alcoholic Patient in Chapter 14) and cimetidine may increase BZD blood levels, and diazepam may increase blood levels of digoxin and phenytoin. Antacids may reduce the clinical effects of clorazepate by hindering its biotransformation to desmethyidiazepam. Coadministration of a BZD and another drug known to induce seizures may possibly increase seizure risk, especially if the BZD is abruptly withdrawn. Furthermore, as noted earlier, important interactions have been reported among nefazodone, erythromycin, troleandomycin, and other macrolide antibiotics, as well as itraconazole. In each case, metabolism is inhibited, and triazolam levels can increase significantly. 

Although specific drug or food interactions with mifepristone have not been studied, on the basis of this drug s metabolism by CYP3A4, it is possible that ketoconazole, itraconazole, erythromycin, and grapefruit juice may inhibit its metabolism (increasing serum levels of mifepristone). Furthermore, rifampin, dexamethasone, St. John s wort, and certain anticonvulsants (e.g., phenytoin, phenobarbital, and carbamazepine) may induce mifepristone metabolism (lowering serum levels of mifepristone)... 

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. 

ITRACONAZOLE, KETOCONAZOLE, MICONAZOLE, POSACONAZOLE, VORICONAZOLE CARBAMAZEPINE, PHENYTOIN L plasma concentrations of itraconazole and of its active metabolite, ketoconazole, posaconazole and voriconazole, with risk of therapeutic failure, t phenytoin levels, but clinical significance uncertain. Carbamazepine plasma concentrations are also t These azoles are highly lipophilic, and clearance is heavily dependent upon metabolism by CYP isoenzymes. Phenytoin and carbamazepine are powerful inducers of CYP3A4 and other CYP isoenzymes (CYP2C18/19, CYP1A2) the result is veiy low or undetectable plasma levels. Phenytoin extensively 1AUC of itraconazole by more than 90%. Inhibition of P-gp T bioavailability of carbamazepine Avoid co-administration of posaconazole or voriconazole with carbamazepine. Watch for inadequate therapeutic effects and t dose of itraconazole. Higher doses of itraconazole may not overcome this interaction. Consider the use of less lipophilic fluconazole, which is less dependent on CYP metabolism. Necessaiy to monitor phenytoin and carbamazepine levels... 

Drug interactions Cimetidine is a CYP450 inhibitor and can inhibit the metabolism of phenytoin, warfarin, and theophylline. Famotidine, nizatidine, and ranitidine are unlikely to cause clinically significant drug interactions. All antagonists have the potential to interact with other drugs that require gastric acid for absorption (e.g., ketoconazole, itraconazole). 

Clinically important, potentially hazardous interactions with alprazolam, astemizole, carbamazepine, cisapride, clarithromycin, dexamethasone, diltiazem, docetaxel, ifosfamide, imatinib, irinotecan, itraconazole, ketoconazole, methylprednisolone, midazolam, nefazodone, oral contraceptives, paroxetine, phenytoin, pimozide, rifampin, ritonavir, terfenadine, tolbutamide, trabectedin, troleandomycin, vinblastine, vincristine, warfarin... 

Clinically important, potentially hazardous interactions with acenocoumarol, alfuzosin, aminophylline, anisindione, anticoagulants, buprenorphine, butorphanol, caffeine, carmustine, dobazam, cocoa, dicumarol, dofetilide, duloxetine, epirubicin, eszopiclone, fentanyl, floxuridine, fluorouracil, galantamine, gliclazide, hydromorphone, itraconazole, ketoconazole, lidocaine, meptazinol, midazolam, mizolastine, modobemide, morphine, narcotic analgesics, oxprenolol, oxycodone, pentazocine, phenytoin, posaconazole, prednisone, propranolol, sufentanil, tolazoline, warfarin, xanthines, zaleplon, zofenopril, zolmitriptan, zolpidem... 

Clinically important, potentially hazardous interactions with aminophylline, amprenavir, antacids, carbamazepine, carmustine, chlorpheniramine, clarithromycin, efavirenz, esomeprazole, imatinib, indinavir, itraconazole, ketoconazole, MAO inhibitors, midazolam, modobemide, nelfinavir, phenytoin, sucralfate, warfarin... 

Clinically important, potentially hazardous interactions with atazanavir, carbamazepine, clarithromycin, dexamethasone, erythromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, phenobarbital, phenytoin, rifampicin, ritonavir, saquinavir, St John s wort... 

Clinically important, potentially hazardous interactions with albendazole, aminoglutethimide, aspirin, bexarotene, carbamazepine, cyclophosphamide, dasatinib, diuretics, ephedrine, imatinib, itraconazole, lapatinib, live vaccines, lopinavir, methotrexate, phenobarbital, phenytoin, praziquantel, primidone, rifampicin, rifampin, temsirolimus, warfarin... 

Clinically important, potentially hazardous interactions with amprenavir, aprepitant, atazanavir, carbamazepine, chlorpheniramine, cimetidine, clarithromycin, clorazepate, CNS depressants, darunavir, delavirdine, dexamethasone, efavirenz, erythromycin, esomeprazole, fluconazole, fluoxetine, fosamprenavir, grapefruit juice, griseofulvin, imatinib, indinavir, itraconazole, ivermectin, ketoconazole, lopinavir, nelfinavir, nevirapine, phenobarbital, phenytoin, primidone, rifabutin, rifampin, ritonavir, roxithromycin, saquinavir, St John s wort, telithromycin, tipranavir... 

Clinically important, potentially hazardous interactions with aluminum, aminophylline, aspirin, chlorambucil, cimetidine, clarithromycin, cyclophosphamide, cyclosporine, dicumarol, diuretics, docetaxel, estrogens, grapefruit juice, indomethacin, influenza vaccines, itraconazole, ketoconazole, lansoprazole, live vaccines, methotrexate, montelukast, omeprazole, oral contraceptives, pancuronium, phenobarbital, phenytoin, ranitidine, rifampicin, rifampin, timolol, tolbutamide, vitamin A... 

Co-admuiistration of erythromycin, phenytoin, or valproic acid increases the rate of metabolism of carbamazepine, reducing the blood concentration. Itraconazole and grapefruit juice interfere with CyP 3A4, increasing carbamazepine levels. 

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