Midazolam Fluconazole

Midazolam Fluconazole Grapefruit juice Ketoconazole Troleandomy ci n Verapamil... 

Acenocoumarol, amiodarone, celecoxib, coumadin, dexamethasone, diclofenac, etoposide, fluconazole, fluoxetine, fluvas-tatin, fluvoxamine, ghmepiride, ghpizide, glyburide, ibuprofen, irbesartan, isoniazid, losartan, midazolam, phenylbutazone, phenytoin, rifampin, teniposide, tenoxicam, thiotepa, tolbutamide, torsemide, vitamin D, warfarin... 

Values were back calculated from actual in vivo DDI data for fluconazole and S-warfarin (fee, CYP2C9 = 0.91), fluvoxamine and theophylline (fcL,CYPiA2 = 0.8), fluvoxamine and S-mephenytoin (fcL,CYP2C9 = 1). ketoconazole and midazolam fcL,CYP3A,hepatic = 0.93), and quinidine and desipramine (fcL,CYP2D6 = 0.9). 

The importance of these enzymes for drug interactions is that enzyme inducers and inhibitors may preferentially affect certain isoforms and consequently may only affect the metabolism of selected drugs. For example, ketoconazole has the potential to inhibit the metabolism of drugs metabolised to a great extent by the sub-family 3A (e.g. midazolam) but not of those metabolised by sub-family 1A (e.g. theophylline), 2C (e.g. diazepam), or 2D (e.g. metaprolol). In contrast, although fluconazole is a weaker inhibitor of the sub-family 3A than ketoconazole, it also inhibits the sub-family 2C, and so the interactions of fluconazole differ from those of ketoconazole. 

Olkkola KT, Ahonen J, Neuvonen PJ. The effect of systemic antimycotics, itraconazole and fluconazole, on the pharmacokinetics and pharmacodynamics of intravenous and oral midazolam. Anesth Analg 1996 82 511-516. 

In an in vitro study of midazolam biotransformation using human liver microsomes, midazolam metabolism was competitively inhibited by the antifungal azoles keto-conazole, itraconazole, and fluconazole, and the antidepressant fluoxetine and its metabolite norfluoxetine (55). The degree of inhibition was consistent with the inhibition reported in pharmacokinetic studies, and suggests that in vitro assay is useful for predicting significant interactions. 

The protease inhibitor saquinavir, propofol, and fluconazole (53,58,59) increased the systemic availability and peak plasma concentrations and prolonged the half-life of midazolam, thus increasing its sedative effects. The dosage of midazolam should be reduced in patients taking these drugs. 

Ahonen J, Olkkola KT, Takala A, Neuvonen PJ. Interaction between fluconazole and midazolam in intensive care patients. Acta Anaesthesiol Scand 1999 43(5) 509-14. 

Fluconazole increased blood concentrations of midazolam (77) and triazolam (78). 

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 alcohol, anticoagulants, antihistamines, betamethasone, brompheniramine, buclizine, buprenorphine, chlorpheniramine, darunavir, dasatinib, delavirdine, dexamethasone, dicumarol, ethanolamine, fesoterodine, fluconazole, flunisolide, fosamprenavir, hydrocortisone, imatinib, influenza vaccines, lacosamide, lapatinib, lopinavir, meperidine, methylprednisolone, midazolam, nilotinib, piracetam, pizotifen, prednisolone, prednisone, rivaroxaban, rufinamide, solifenacin, telithromycin, temsirolimus, teniposide, trabectedin, triamcinolone, warfarin... 

CYP3A4 Alfentanil Alprazolam Astern izole Carbamazepine Cisapride Cyclosporine Diltiazem Erythromycin Felodipine Fluconazole Itraconazole Ketoconazole Lidocaine Lova statin Midazolam Nifedipine Quinidine Simvastatin Tacrolimus Terfenadine Verapamil... 

Fluconazole, itraconazole and ketoconazole very markedly increase the serum levels of midazolam and triazolam, thereby increasing and prolonging their sedative and amnesic effects. Similar but smaller effects are seen with itraconazole or ketoconazole and alprazolam and with itraconazole and brotizolam. Even less effect is seen with etizolam and itraconazole and no important interaction occurs between estazolam and itraconazole. Small effects are found with the non-benzodiazepine hypnotic, zolpidem, with ketoconazole and even less effects with zopiclone and itraconazole. 

Ahonen J, OUdcola KT, Neuvonen PJ. Effect ofrouteofadministration of fluconazole on the interaction between fluconazole and midazolam. EurJ Clin Pharmacol (1997) 51,415-19. 

Class 1 (High Permeability, High Solubihty) Albuterol, Allopurinol, Amlodipine (Amlo), AmoxicilUn, Antipyiine, Dexamethasone, Diltiazem, Zidovudine, Isosoibide mononitrate, Ketoprofen, Lamivudine, Levonoigestiel, Levofloxa-cin. Metronidazole, Midazolam, Minocycline, Morphine, Nifedipine, Ofloxacin, Prednisolone, Propylthiouracil, Stavudine, Phenobaibital, Fluconazole, Chiiiin, Enalapril, Acetaminophen, Diazepam, Lsoniazid, Levodopa, Metoprolol, Paracetamol, Pyrazinamide, Salicylic add, Ethirtylestradiol. ... 

---