Ketoconazole dosing

Prostatic cancer In clinical trials involving 350 patients with metastatic prostatic cancer, 11 deaths were reported within 2 weeks of starting high-dose ketoconazole (1200 mg/day). It is not known whether death was related to therapy. High ketoconazole doses are known to suppress adrenal corticosteroid secretion. Hypersensitivity reactions Anaphylaxis occurs rarely after the first dose. Hypersensitivity reactions, including urticaria, have been reported. 

Ketoconazole Dose reduction of indinavir to 600 mg every 8 hours is recommended when concurrently administering ketoconazole. 

Cmcm Cmin increased by 42% (23, 65), 21% (4, 40), and 73% (39, 114) respectively during darunavir + ritonavir and keto-conazole co-administration. Ketoconazole pharmacokinetics were unchanged by coadministration of darunavir alone. Ketoconazole AUCq—,22h> max, and Cnun increased by 212% (165, 268), 111% (81,144), and 868% (544,1355) respectively during co-administration of darunavir + ritonavir. The increase in darunavir exposure by ketoconazole was lower than that observed previously with ritonavir. A maximum ketoconazole dose of 200 mg/day is recommended if it is used concomitantly with darunavir + ritonavir, and no dose adjustments of darunavir + ritonavir is required. 

Telaprevir Three clinical studies with volunteers evahuited the effects of ketoconazole on telaprevir [62 ]. A single 400 mg ketoconazole dose increased telaprevir exposure 1.24-fold, but at steady state after repeated telaprevir dosing, the effect vanished. 

Following oral administration, approximately 75% of an administered ketoconazole dose is absorbed. However, there is considerable inter- and intrapatient variation, with oral absorption impaired when gastric acidity is decreased due to clinical pathology, e.g. achlorhydria, or due to concurrent administration of agents that decrease gastric acidity, e.g. antacids, H2-receptor antagonists or proton pump inhibitors, or whether the patient is in a fed or fasted state (absorption is enhanced in the fed state). 

Plasma levels of 3—5 p.g/mL are obtained two hours after adraiinistration of 200 mg ketoconazole. No accumulation in the bloodstream was noted after a 30-wk treatment with this dose. The half-life is approximately eight hours. When ketoconazole is taken with meals, higher plasma levels are obtained. Distribution studies using radioactive ketoconazole in rats show radioactivity mainly in the Hver and the connective tissue. Radioactivity is also present in the subcutaneous tissue and the sebaceous glands. After one dose of 200 mg in humans, ketoconazole is found in urine, saUva, sebum, and cenimen. Like miconazole, the mode of action is based on inhibition of the cytochrome P-450 dependent biosynthesis of ergosterol. This results in disturbed membrane permeabiUty and membrane-bound enzymes (8,10,23,25). 

Theoretically buprenorphine metabolism could be inhibited by itraconazole, ketoconazole, grapefruit juice, and erythromycin or any other CYP3A4 inhibitor the effects may be greater than expected for the dose of buprenorphine being given may need to decrease buprenorphine dose. 

Treatment fluconazole, itraconazole, ketoconazole, Amphotericin B Consider liposomal products decrease or stop CSA or TAC to minimize nephrotoxicity Remember to adjust doses of renally eliminated drugs (e.g., acyclovir, ganciclovir, TMP-SMX)... 

Two to three weeks of fluconazole or itraconazole solution are highly effective and demonstrate similar clinical response rates.32 Doses of 100 to 200 mg are effective in immunocompetent patients but doses up to 400 mg are recommended for immunocompromised patients. Due to variable absorption, ketoconazole and itraconazole capsules should be considered second-line therapy. In severe cases, oral azoles may prove ineffective, warranting the use of amphotericin B for 10 days. Although echinocandins and voriconazole are effective in treatment of esophageal candidiasis, experience remains limited. 

While ketoconazole is an antifungal agent, it has been used for treatment of prostate cancer. In high doses of 400 mg three times daily, ketoconazole blocks the production of testosterone. 

Selfiimited disease Amphotericin Bc 03-0.5 mg/kg/day x 2-4 weeks (total dose 500 mg) or ketoconazole 400 mg orally daily x 3-6 months can be... 

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... 

All patients with disseminated blastomycosis and those with extrapulmonary disease require therapy (ketoconazole, 400 mg/day orally for 6 months). CNS disease should be treated with amphotericin B for a total cumulative dose greater than 1 g. 

Sildenafil doses should be decreased when any potent cytochrome P450 3A4 inhibitor is used (e g., cimetidine, erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir, and saquinavir). Vardenafil doses vary accordingto which agent is used (2.5 mg q 72 h for ritonavir, 2.5 mg q 24 h for indinavir, ketoconazole 400 mg daily, and itraconazole 400 mg daily and 5 mg q 24 h for ketoconazole 200 mg daily, itraconazole200 mg daily, and erythromycin). Tadalafil doses are reduced only when it is used with the most potent cytochrome P450 3A4 inhibitors (e g., ketoconazole or ritonavir). 

Chagas disease is caused by a kinetoplastid trypanosoma parasite and affects millions of people in Latin America. The disease is currently incurable. Chemotherapy is based mainly on nitrofuran and nitroimidazole compounds and sterol biosynthesis inhibitors such as ketoconazole (337). Toxicity and high doses are the major problems for these organic drugs. Urbina et al. (338, 339) have found that com-plexation of antiparasitic organic agents such as chloroquine (78)... 

CYP3A4 inhibitors If concomitant administration with ketoconazole or any other CYP3A4 inhibitor is indicated, closely monitor patients for increased signs and/or symptoms of hypercorticism. Consider reduction in budesonide dose. 

Dosage adjustment - Consider a starting dose of 25 mg in the following patients Older than 65 years of age, hepatic impairment, severe renal impairment, and concomitant use of potent cytochrome P450 3A4 inhibitors (eg, erythromycin, ketoconazole, itraconazole, saquinavir). 

Concomitant medications - For patients taking concomitant potent inhibitors of CYP3A4 (eg, ketoconazole, ritonavir), the maximum recommended dose of tadalafil is 10 mg, not to exceed once every 72 hours. 

Concomitant mecf/caf/ons - The dosage of vardenafil may require adjustment in patients receiving certain CYP3A4 inhibitors. For ritonavir, do not exceed a single dose of 2.5 mg vardenafil in a 72-hour period. For indinavir, ketoconazole 400 mg/day, and itraconazole 400 mg/day, do not exceed a single dose of 2.5 mg vardenafil in a 24-hour period. For ketoconazole 200 mg/day, itraconazole 200 mg/day, and erythromycin, do not exceed a single dose of 5 mg vardenafil in a 24-hour period. 

A4 inhibitors - Patients receiving cytochrome P450 3A4 inhibitors, such as macrolide antibiotics (erythromycin and clarithromycin), antifungal agents (ketoconazole, itraconazole, and miconazole), or cyclosporine or vinblastine should not receive doses of tolterodine greater than 1 mg twice/day (greater than 2 mg/day for ER capsules). 

Coadministration with CYP450 inhibitors- Nhen coadministered with potent CYP3A4 inhibitors (eg, ketoconazole, itraconazole, ritonavir, nelfinavir, clarithromycin, nefazodone), do not exceed a daily dose of darifenacin 7.5 mg. 

Dose adjustment with CYP3A4 inhibitors When administered with therapeutic doses of ketoconazole or other potent CYP3A4 inhibitors, a daily dose greater than 5 mg is not recommended. 

Ketoconazole A potent inhibitor of cytochrome P450 3A4 may increase plasma levels of budesonide and fluticasone during concomitant dosing. The clinical significance is unknown. Use caution. 

Use caution when coadministering high and prolonged doses of fluticasone with ketoconazole and other known cytochrome P450 inhibitors. 

Concomitant use with potential CYP3A4 inhibitors - During coadministration of ketoconazole with aripiprazole, reduce the aripiprazole dose to one-half of the usual dose. 

Coadministration with CYP3A4 inhibitors Do not exceed a 1 mg starting dose in patients coadministered eszopiclone with potent CYP3A4 inhibitors (eg, ketoconazole). If needed, the dose can be raised to 2 mg. 

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