Itraconazole haloperidol

Clinically important, potentially hazardous interactions with amiodarone, astemizole, bepridil, carbamazepine, chloroquine, cisapride, clarithromycin, dihydroergotamine, disopyramide, ergotamine, grapefruit juice, halofantrine, haloperidol, itraconazole, ketoconazole, methadone, moxifloxacin, phenobarbital, phenytoin, pimozide, procainamide, quinidine, rifampicin, ritonavir, sotalol, St John s wort, telithromycin, terfenadine, voriconazole... 

Drugs that may be affected by itraconazole include alfentanil, almotriptan, alprazolam, amphotericin B, aripiprazole, benzodiazepines, buspirone, busulfan, calcium blockers, carbamazepine, cilostazol, cisapride, corticosteroids, cyclosporine, digoxin, disopyramide, docetaxel, dofetilide, eletriptan, epierenone, ergot alkaloids, haloperidol, HMG-CoA reductase inhibitors, hydantoins (phenytoin), hypoglycemic agents, oral midazolam, phosphodiesterase type 5 inhibitors, pimozide, polyenes, protease inhibitors, quinidine, rifamycins, sirolimus, tacrolimus, tolterodine, triazolam, trimetrexate, vinca alkaloids, warfarin, and zolpidem. 

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. 

Adverse effects can result from increased plasma concentrations of haloperidol during itraconazole treatment. This has been observed in 13 schizophrenic patients treated with haloperidol 12 or 24 mg/day who took itraconazole 200 mg/day for 7 days (51). Plasma concentrations of haloperidol were significantly increased and neurological adverse effects were more common. Itraconazole is a potent inhibitor of CYP3A4. 

Yasui N, Kondo T, Otani K, Furukori H, Mihara K, Suzuki A, Kaneko S, Inoue Y. Effects of itraconazole on the steady-state plasma concentrations of haloperidol and its reduced metabolite in schizophrenic patients in vivo evidence of the involvement of CYP3A4 for haloperidol metabolism. J Clin Psychopharmacol 1999 19(2) 149-54. 

The effects of itraconazole 200 mg/day for 7 days on the steady-state plasma concentrations of haloperidol and its reduced metabolite have been investigated in schizophrenic patients receiving haloperidol 12 or 24 mg/day (101). Itraconazole significantly increased trough plasma concentrations of both haloperidol and reduced haloperidol... 

Drugs that inhibit cytochrome P450 3A4 (e.g., verapamil, dUtiazem, itraconazole, fluvoxamine, nefazodone, and erythromycin) can increase buspirone levels. Rifampin caused a 10-fold reduction in buspirone levels. Buspirone reportedly increases haloperidol levels and elevates blood pressure in patients taking a monoamine oxidase inhibitor (MAOI). 

ANTICOAGULANTS - ORAL 5. ANTIDEPRESSANTS - mianserin, paroxetine 6. ANTIDIABETIC DRUGS - repaglinide, sulphonylureas 7. ANTIEMETICS - aprepi-tant 5-HT3-antagonists 8. ANTIFUN-GALS - fluconazole, itraconazole, ketoconazole, voriconazole 9. ANTIPSY-CHOTICS - apiprazole, chlorpromazine, haloperidol 10. BETA-BLOCKERS-metoprolol, propanolol, timolol... 

Desipramine, doxepin, flurazepam, haloperidol, tamoxifen Itraconazole... 

Itraconazole increases the plasma levels of haloperidol, and its metabolite, reduced haloperidol Bromperidol may be similarly affected. 

It is likely that itraconazole inhibited the metabolism of bromperidol and haloperidol by CYP3A4. The wide variation in results may be attributed to interindividual variation in CYP3A4 activity. 

The clinical significance of the raised levels is unclear, although one study found an increase in neurological adverse effects with haloperidol. It may be prudent to monitor concurrent use, decreasing the haloperidol or bromperidol dose if adverse effects become troublesome. This interaction may be of more importance in those patients have less active CYP2D6, the predominant isoenzyme involved in the metabolism of haloperidol, as CYP3A4, which is inhibited by itraconazole, will then become more important. It is likely that other azoles that are potent inhibitors of CYP3A4, such as ketoconazole, would interact similarly, but this needs confirmation. 

Park J-Y, Shon J-H, Kim K-A, Jung H-J, Shim J-C, Yoon Y-R, Cha I-J, Shin J-G. Combined effects of itraconazole and CYP2D6 10 genetic polymorphism on the pharmacokinetics and pharmacocfynamics of haloperidol in healtiiy subjects. J Clin Psychopharmacol (2006) 26, 135-42. 

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