Carbamazepine with itraconazole

CARBAMAZEPINE ANTIFUNGALS - ITRACONAZOLE, KETOCONAZOLE, MICONAZOLE, POSACONAZOLE, VORICONAZOLE 1 plasma concentrations of itraconazole and of its active metabolite, ketoconazole, posaconazole and voriconazole, with risk of therapeutic failure, t carbamazepine plasma concentrations These azoles are highly lipophilic, and clearance is heavily dependent upon metabolism by CYP isoenzymes. Carbamazepine is a powerful inducer of CYP3A4 and other CYP isoenzymes (CYP2C18/19, CYP1A2), and the result is very low or undetectable plasma levels. 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 use of the less lipophilic fluconazole, which is less dependent on CYP metabolism. Necessary to monitor carbamazepine levels... 

Clinically important, potentially hazardous interactions with atazanavir, carbamazepine, clarithromycin, itraconazole, ketoconazole, nefazodone, nelfinavir, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, ritonavir, saquinavir, St John s wort, troleandomycin, voriconazole, warfarin... 

About 14 days after starting carbamazepine 400 mg daily, a patient taking itraconazole 200 mg daily was noted to have low itraconazole levels (0.15 mg/L), and about 2 months later they were undetectable. About 3 weeks after stopping the carbamazepine, itraconazole levels had reached the therapeutic range (0.36 mg/L). For mention of 2 patients taking carbamazepine with phenytoin, who had undetectable or very low itraconazole levels, and who relapsed or did not respond to itraconazole therapy, see Phenytoin + Azoles , p.552. 

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. 

GFJ has been shown to increase the exposure of carbamazepine (175), cisapride (176-179), fluvoxamine (184), losartan (188), methadone (189), scopolamine (191), and sertraline (192). However, only the interaction of GFJ with carbamazepine and cisapride seems to be clinically relevant. No alteration in exposure was observed for clozapine (180,181), heophylline (195), halo-peridol (196), and omeprazole (190). Reports of increased pharmacokinetic parameters of clozapine, theophylline, and haloperidol suggest that an interaction is unlikely to be clinically relevant. Contradicting results were reported for itraconazole (185-187), digoxin (75,183), and sildenafil (193,194). An increased effect on concomitant use of diclofenac and GFJ was observed in rats (182). Overall, the clinical relevance for this drug class appears to be low. 

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)... 

Low and sometimes very low serum concentrations of itraconazole have been seen during concurrent therapy of itraconazole with carbamazepine (68). 

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 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 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 alfentanil, aminophylline, amisulpride, amoxicillin, ampicillin, anticonvulsants, astemizole, atorvastatin, benzodiazepines, bromocriptine, buprenorphine, bupropion, carbamazepine, cilostazol, ciprofloxacin, cisapride, clindamycin, colchicine, cyclosporine, dasatinib, digoxin, dihydroergotamine, diltiazem, disopyramide, enoxacin, eplerenone, ergotamine, eszopiclone, everolimus, fluconazole, fluoxetine, fluvastatin, gatifloxacin, HMG-CoA reductase inhibitors, imatinib, itraconazole, ketoconazole, lomefloxacin, lorazepam, lovastatin, methadone, methylprednisolone, methysergide, midazolam, mizolastine, moxifloxacin, nitrazepam, norfloxacin, ofloxacin, paroxetine, pimozide, pravastatin, quinolones, ranolazine, repaglinide, rupatadine, sertraline, sildenafil, simvastatin, sparfloxacin, sulpiride, tacrolimus, terfenadine, triazolam, troleandomycin, vardenafil, verapamil, vinblastine, warfarin, zaleplon, zolpidem, zuclopenthixol... 

Clinically important, potentially hazardous interactions with amlodipine, anisindione, anticoagulants, aprepitant, atorvastatin, barbiturates, benzodiazepines, butabarbital, carbamazepine, chlordiazepoxide, clarithromycin, clonazepam, dorazepate, corticosteroids, cyclosporine, dexamethasone, diazepam, dicumarol, erythromycin, ethotoin, felodipine, flurazepam, fluvastatin, fosphenytoin, isradipine, itraconazole, ketoconazole, lorazepam, lovastatin, mephenytoin, mephobarbital, midazolam, nicardipine, nifedipine, nimodipine, nisoldipine, oxazepam, pentobarbital, phenobarbital, pimozide, pravastatin, primidone, quazepam, rifampin, secobarbital, simvastatin, St John s wort, temazepam, warfarin... 

Clinically important, potentially hazardous interactions with aluminum, aminophylline, carbamazepine, carbimazole, cyclosporine, daclizumab, diuretics, etoposide, etretinate, grapefruit juice, indomethacin, isoniazid, itraconazole, ketoconazole, licorice, live vaccines, methotrexate, naproxen, oral contraceptives, pancuronium, phenobarbital, phenytoin, rifampicin, troleandomycin... 

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. 

Carbamazepine is metabolized to an active 10,11-epoxide metabolite, thus medications that inhibit 3A4 isoenzymes may result in carbamazepine toxicity (e.g., cimetidine, dUtiazem, erythromycin, fluoxetine, fluvoxamine, isoniazid, itraconazole, ketoconazole, nefa-zodone, propoxyphene, and verapamil). " When carbamazepine is combined with valproate, the carbamazepine dose should be reduced because valproate displaces carbamazepine from protein binding sites, thus increasing free levels." Combining clozapine and carbamazepine is not recommended because of the possibdity of bone marrow suppression with both agents. ... 

Ketoconazole causes a small to moderate rise in serum carbamazepine levels. A marked rise in carbamazepine levels has been seen in two patients taking fluconazole, with toxicity in one. Adverse effects were seen in another patient when carbamazepine was given with miconazole. Carbamazepine may markedly reduce the levels of itraconazole and possibly voriconazole, and is predicted to lower the levels of posaconazole. 

Note also that carbamazepine may reduce the levels of azole antifungals a marked reduction in itraconazole levels has been reported, and some manufacturers of itraconazole consequently say that concurrent use of potent enzyme inducers such as carbamazepine is not recommended. Based on the interaction with phenytoin , (p.552), which results in reduced posaconazole levels, the manufacturer of posaconazole suggests that concurrent use of posaconazole and carbamazepine should be avoided, unless the benefits outweigh the risks. If both drugs are given it would seem sensible to consider increasing the posaconazole dose, and increase monitoring of carbamazepine levels. Based on the interaction with phenytoin , (p.552), the manufacturers of voriconazole also contraindicate the concurrent use of carbamazepine and voriconazole. " ... 

The manufacturers of sertindole contraindicate the concurrent use of cimetidine, diltiazem, erythromycin, itraconazole, ketoco-nazole, terfenadine and verapamil because of an increased risk of cardiac arrhythmias. Carbamazepine and phenytoin reduce plasma sertindole levels whereas fluoxetine and paroxetine increase them. No clinically relevant interactions occur with alprazolam, antacids, food or tobacco smoking. 

---