Ketoconazole Imatinib

Clinically important, potentially hazardous interactions with cyclosporine, epirubicin, grapefruit juice, imatinib, ketoconazole... 

Aprepitant (Emend) [Centrally Acting Antiemetic] Uses Pre-vents N/V assoc w/ emetogenic CA chemo (eg, cisplatin) (use in combo w/ other antiemetics) Action Substance P/neurokinin l(NKi) receptor antagonist Dose 125 mg PO day 1, 1 h before chemo, then 80 mg PO qAM days 2 3 Caution [B, /-] Contra Use w/ pimozide, Disp Caps SE Fatigue, asthenia, hiccups Interactions T Effects W/ clarithromycin, diltiazem, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, troleandomycin T effects OF alprazolam, astem-izole, cisapride, dexamethasone, methylprednisolone, midazolam, pimozide, terfe-nadine, triazolam, chemo agents, eg, docetaxel, etoposide, ifosfamide, imatinib, irinotecan, paclitaxel, vinblastine, vincristine, vinorelbine i effects W/ paroxetine,... 

IMATINIB 1. ANTIBIOTICS - clarithromycin, erythromycin 2. ANTIFUNGALS -fluconazole, itraconazole, ketoconazole voriconazole 3. ANTIVIRALS -efavirenz, ritonavir 4. GRAPEFRUIT JUICE 5. H2 RECEPTOR BLOCKERS - cimetidine t imatinib levels with t risk of toxicity (e.g. abdominal pain, constipation, dyspnoea) and of neurotoxicity (e.g. taste disturbances, dizziness, headache, paraesthesia, peripheral neuropathy) Due to inhibition of CYP3A4-mediated metabolism of imatinib Monitor for clinical efficacy and for the signs of toxicity listed, along with convulsions, confusion and signs of oedema (including pulmonary oedema). Monitor electrolytes and liver function, and for cardiotoxicity... 

E Itraconazole. Imatinib is primarily metabolized by the CYP3A4 hepatic enzyme system. Drugs that may inhibit this enzyme (such as ketoconazole, itraconazole, erythromycin, clarithromycin, etc.) may impair clearance of imatinib and result in increased toxicity. Imatinib itself is also a fairly potent inhibitor of the CYP3A4 enzyme and may result in toxicity due to other drugs that are substrates for this enzyme (such as simvastatin, warfarin, benzodiazepines, etc.). The other medications iisted are uniikeiy to affect the function of 0 P3A4 or interact adversely with imatinib. 

Clinically important, potentially hazardous interactions with amiodarone, anabolic steroids, antithyroid agents, barbiturates, bivalirudin, cimetidine, clofibrate, clopidogrel, cyclosporine, delavirdine, dextrothyroxine, disulfiram, fluconazole, glutethimide, imatinib, itraconazole, ketoconazole, metronidazole, miconazole, penicillins, phenylbutazones, piperacillin, quinidine, quinine, rifabutin, rifampin, rifapentine, rofecoxib, salicylates, sulfinpyrazone, sulfonamides, testosterone, thyroid, zileuton... 

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 amiloride, aminoglycosides, amphotericin B, ampicillin, anisindione, anticoagulants, armodafinil, atorvastatin, azathioprine, azithromycin, bacampicillin, basiliximab, bezafibrate, bosentan, bupropion, carbenicillin, caspofungin, cholestyramine, clarithromycin, cloxacillin, co-trimoxazole, corticosteroids, cyclophosphamide, daclizumab, danazol, dicloxacillin, dicumarol, digoxin, diltiazem, disulfiram, echinacea, erythromycin, ethotoin, etoposide, ezetimibe, flunisolide, fluoxymesterone, fluvastatin, foscarnet, fosphenytoin, gemfibrozil, hemophilus B vaccine, HMG-CoA reductase inhibitors, imatinib, imipenem/cilastatin, influenza vaccines, ketoconazole, lanreotide, lopinavir, lovastatin, mephenytoin, methicillin, methoxsalen, methylphenidate, methylprednisolone, methyltestosterone, mezlocillin, mizolastine, mycophenolate, nafcillin, nisoldipine, NSAIDs, orlistat, oxacillin, penicillins, phellodendron, phenytoin, pravastatin, prednisolone, prednisone, pristinamycin, ranolazine, red rice yeast, rifabutin, rifampin, rifapentine, ritonavir, rosuvastatin, simvastatin, sirolimus, spironolactone, St John s wort, sulfacetamide, sulfadiazine, sulfamethoxazole, sulfisoxazole, sulfonamides, tacrolimus, telithromycin, tenoxicam, testosterone, ticarcillin, tolvaptan, trabectedin, triamterene, troleandomycin, ursodeoxycholic acid, vaccines, vecuronium, warfarin, zofenopril... 

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 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 amiodarone, amprenavir, anisindione, antacids, anticoagulants, aprepitant, atazanavir, atovaquone, beclomethasone, buprenorphine, corticosteroids, cortisone, cyclosporine, cyproterone, dabigatran, dapsone, darunavir, delavirdine, dexamethasone, dicumarol, digoxin, eszopiclone, flunisolide, fosamprenavir, gadoxetate, gestrinone, halothane, imatinib, isoniazid, itraconazole, ketoconazole, lapatinib, lorcainide, methylprednisolone, midazolam, nelfinavir, nifedipine, oral contraceptives, phenylbutazone, prednisone, protease inhibitors, pyrazinamide, ramelteon, ritonavir, saquinavir, solifenacin, sunitinib, tacrolimus, telithromycin, temsirolimus, tipranavir, tolvaptan, trabectedin, triamcinolone, triazolam, voriconazole, warfarin, zaleplon... 

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%... 

Ketoconazole raises serum imatinib levels other cytochrome P450 isoenzyme CYP3A4 inhibitors (such as other azoles and macrolides) are predicted to do the same. 

An open-label, randomised, crossover study in 14 healthy subjects found that the maximum serum levels and AUC of imatinib rose by 26% and 40%, respectively, when they were given a single 400-mg dose of ketoconazole with a single 200-mg dose of imatinib. ... 

Ketoconazole is a potent inhibitor of the cytochrome P450 isoenzyme CYP3A4, which is involved in the metabolism of imatinib. Therefore ketoconazole reduces the metabolism and clearance of imatinib and its serum levels rise accordingly. Adverse skin reactions occur frequently with imatinib and may be associated with high does of imatinib and/or increased levels due to an interaction with CYP3A4 inhibitors, such as voriconazole. ... 

The manufaeturers therefore advise caution with ketoconazole and with other CYP3A4 inhibitors (examples listed are clarithromycin, erythromycin and itraconazole), but it is not entirely clear what action should be taken beeause information about excessive serum levels is very limited. The authors of one report suggest monitoring plasma levels of imatinib to identify patients at risk of severe toxieity. ... 

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