Ketoconazole interactions

Honig PK, Wortham DC, Zamani K, et al. Terfenadine-ketoconazole interaction. Pharmacokinetic and electrocardiographic consequences. JAMA 1993 269 1513-1518. 

Mode of action Ketoconazole interacts with C-14 a-demethylase (a cytochrome P-450 enzyme) to block demethylation of lanosterol to ergosterol, the principal sterol of fungal membranes Figure 34.4). This inhibition disrupts membrane function and increases permeability. Ketoconazole acts in an additive manner with flucytosine against Candida, but antagonizes amphotericin B s antifungal activity. 

First MR, Schroeder TJ, Michael A, Hariharan S, Weiskittel P, Alexander JW. Cyclosporine-ketoconazole interaction. Long-term follow-up and preliminary results of a randomized trial. Transplantation 1993 55(5) IOOO-4. 

Ketoconazole interacts with rifampicin, and the serum concentrations of both drugs are reduced (SEDA-9, 269). 

Kriett JM, JahansouzF, Smith CM, Hayden AM, Fox KJ, Kapelanski DP, Jamieson SW. The cyclosporine-ketoconazole interaction safety and econom ic impact in lung transplantation. J HeartLimg Transplcmt( 99A) 13, S43. 

Only a small number of drug interactions have been reported with donepezil. In vitro studies show a low rate of binding of donepezil to cytochrome P-450 (CYP)3A4 or 2D6. Whether or not donepezil has the potential for enzyme induction is not known. No interactions with theophylline, cimeti-dine, warfarin, digoxin, or ketoconazole have been documented. In vitro studies show that inhibitors of CYP3A4 and 2D6 have the potential to inhibit the metabolism of donepezil. The clinical relevance of this is unknown. However, monitoring for possible increased peripheral side effects is advised... 

Khashaba et al. [34] suggested the use of sample spectrophotometric and spectrofluorimetric methods for the determination of miconazole and other antifungal drugs in different pharmaceutical formulations. The spectrophotometric method depend on the interaction between imidazole antifungal drugs as -electron donor with the pi-acceptor 2,3-dichloro-5,6-dicyano-l,4-benzoquinone, in methanol or with p-chloranilic acid in acetonitrile. The produced chromogens obey Beer s law at Amax 460 and 520 nm in the concentration range 22.5-200 and 7.9-280 pg/mL for 2,3-dichloro-5,6-dicyano-l,4-benzoquinone and p-chloranilic acid, respectively. Spectrofluorimetric method is based on the measurement of the native fluorescence of ketoconazole at 375 nm with excitation at 288 nm and/or fluorescence intensity versus concentration is linear for ketoconazole at 49.7-800 ng/mL. The methods... 

Itraconazole and ketoconazole (200-800 mg/day orally for 1 year) are effective in 74% to 86% of cases, but relapses are common fluconazole 200-400 mg daily is less effective (64%) than ketoconazole or itraconazole, and relapses are seen in 29% of responders Severe disease Amphotericin B 0.7 mg/kg/day for a minimum total dose of 35 mj kg is effective in 59% to 100% of cases and should be used in patients who require hospitalization or are unable to take itraconazole because of drug interactions, allergies, failure to absorb drug or failure to improve clinically after a minimum of 12 weeks of itiaconazole therapy... 

Drugs that may interact with isoniazid include acetaminophen, carbamazepine, chlorzoxazone, disulfiram, enflurane, hydantoins, ketoconazole, rifampin, and theophylline. 

Because trimetrexate is metabolized by a P450 enzyme system, drugs that induce or inhibit this drug metabolizing enzyme system may elicit important drug interactions that may alter trimetrexate plasma concentrations, which include erythromycin, rifampin, rifabutin, ketoconazole, fluconazole, cimetidine, nitrogen substituted imidazole drugs (eg, clotrimazole, ketoconazole, miconazole). 

Aluminum Hydroxide + Magnesium Hydroxide (Maalox) [OTC] [Antacid/Aluminum Magnesium Salts] Uses Hyper-acidity (peptic ulcer, hiatal hernia, etc) Action Neutralizes gastric acid Dose Adults. 10-20 mL or 2-4 tabs PO qid or PRN Feds. 5-15 mL PO qid or PRN Caution [C, ] Disp Tabs, susp SE May cause t Mg in renal insuff, constipation, D Interactions In addition to AlOH, X effects OF digoxin, quinolones, phenytoin, Fe supl, ketoconazole EMS None OD May cause constipation, loss of appetite, painful urination, heart rhythm changes, muscle weakness, and peripheral edema symptomatic and supportive... 

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,... 

Budesonide, Oral (Entocort EC) [Anti-inflammatory> Corticosteroid] Uses Mild-mod Crohn Dz Action Steroid, anti-inflammatory Dose Adults. Initial, 9 mg PO qAM to 8 wk max maint 6 mg PO qAM taper by 3 mo avoid grapefruit juice Contra Active TB and fungal Infxn Caution [C, /-] DM, glaucoma, cataracts, HTN, CHF Disp Caps SE HA, cough, hoarseness, Candida Infxn, epistaxis Interactions T Effects W/ erythromycin, indinavir, itraconazole, ketoconazole, ritonavir, grapefruit EMS Monitor ECG and BP for signs of electrolyte disturbances and hypovolemia OD Acute OD unlikely to cause a problem, chronic OD can reduce natural production of certain steroids symptomatic and supportive... 

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