Ketoconazole dosage

Disseminated histoplasmosis Acute (Infantile) Subacute Progressive histoplasmosis (immunocompetent patients and immunosuppressed patients without AIDS) 0.02-0.05 Disseminated histoplasmosis Untreated mortality 83% to 93% relapse 5% to 23% in non-AIDS patients therapy is recommended tor all patients Nonimmunosuppressedpatients Ketoconazole 400 mj day orally x 6-12 months or amphotericin B 35 mg/kg IV Immunosuppressed patients (non-AIDS) or endocarditis or CNS disease Amphotericin B >35 mg/kg x 3 months followed by fluconazole or itraconazole 200 mg orally twice daily x 12 months Life-threatening disease Amphotericin B 0.7-1 mg/kg/day IV for a total dosage of 35 mj kg over 2-4 months once the patient is afebrile, able to take oral medications, and no longer requires blood pressure or ventilatory support therapy can be changed to itraconazole 200 mg orally twice daily for 6-18 months Non-life-threatening disease Itraconazole 200-400 mg orally daily for 6-18 months fluconazole therapy 400-800 mg daily should be reserved for patients intolerant to itraconazole, and the development of resistance can lead to relapses... 

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 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. 

Ketoconazole is a potent inhibitor of the cytochrome P450 3A4 enzyme system. Coadministration of ketoconazole with other drugs metabolized by the same enzyme system may result in increased plasma concentrations of the drugs that could increase or prolong both therapeutic and adverse effects. Unless otherwise specified, dosage adjustment may be necessary. 

Dosage with concurrent ketoconazole or itraconazole (at 400 mg/day), or indinavir. PO... 

Like fluoxetine, erythromycin and other macrolides inhibit the CYP-3A isoenzyme and increase the levels and effects of the triazolobenzodiazepines (Shader and Greenblatt, 1995 Chouinard et ah, 1999). Midazolam should be avoided or the dosage dropped by 50% in patients receiving erythromycin (Olkkola et ah, 1993). Ketoconazole and itraconazole may also interact with triazolam and midazolam, and combinations of these drugs should be avoided (Varhe et ah, 1994 Chouinard et ah, 1999). 

Aripiprazole is hepatically metabolized, mainly by two cytochrome P450 enzymes CYP 2D6 and CYP 3A4. Therefore, dosage adjustments are necessary when this medication is given with other medications that either inhibit or induce these enzymes. For example, the dose of aripiprazole should be halved when this medication is given with ketoconazole, a CYP 3A4 inhibitor, or at least decreased when given with fluoxetine, a CYP 2D6 inhibitor. When aripiprazole is given with CYP 3A4 inducers such as carbamazepine, the dose should be doubled. 

Ketoconazole has been used for the treatment of patients with Cushing s syndrome due to several causes. Dosages of 200-1200 mg/d have produced a reduction in hormone levels and clinical improvement in some patients. This drug has some hepatotoxicity and should be started at 200 mg/d and slowly increased by 200 mg/d every 2-3 days up to a total daily dose of 1000 mg. 

Ketoconazole is effective in the therapy of cutaneous infections caused by epidermophyton, microsporum, and trichophyton species. Infections of the glabrous skin often respond within 2-3 weeks to a once-daily oral dose of 200 mg. Palmar-plantar skin is slower to respond, often taking 4-6 weeks at a dosage of 200 mg twice daily. Infections of the hair and nails may take even longer before resolving, with low cure rates noted for tinea capitis. Tinea versicolor is responsive to short courses of a once-daily dose of 200 mg. 

Figure 2 Mean ( SE) plasma concentrations of triazolam (left) or alprazolam (right) in a series of healthy individuals who participated in a clinical pharmacokinetic study. In one phase of the study, they ingested a single 0.25-mg oral dose of triazolam with ketoco-nazole, 200 mg twice daily, or with placebo to match ketoconazole (control). In the second phase of the study, they took 1.0 mg of alprazolam orally, either with the same dosage of ketoconazole or with placebo to match ketoconazole (control). Note that ketoconazole increases AUC and reduces clearance of both triazolam and alprazolam. For triazolam (a high-extraction compound), the effect is evident as reduced presystemic extraction, increased Cmax, and prolonged half-life. However, for alprazolam (a low-extraction compound), the effect of ketoconazole is evident only as a prolongation of half-life. Abbreviation AUC, the plasma concentration-time curve. Source Adapted, in part, from Ref. 74.

Because ketoconazole interferes with steroid synthesis and vitamin D metabolism, ketoconazole should not be used in children. It is not approved for use in children and there is no pediatric dosage range based on pharmacokinetic information in this population. 

As the induction of hepatic microsomal oxidative activity by a lipid-soluble drug (e.g. phenobarbitone) or xenobiotic could decrease the duration of action of therapeutic agents that are mainly eliminated by microsomal oxidation, the effect of induction would be considered a form of biochemical antagonism. Drug-induced inhibition of microsomal oxidative activity, without adjustment of dosage of a concomitantly administered therapeutic agent that undergoes extensive hepatic metabolism, could lead to toxicity. Cimetidine, ketoconazole and chloramphenicol inhibit hepatic microsomal enzyme activity. 

In patients not responding to 400 mg, dosage should be increased by 200 mg increments every 4 weeks to a maximum of 800 mg daily. Therapy with ketoconazole is associated with relapses, and fluconazole therapy achieves a lower response rate than itraconazole. 

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