Pharmacological Effects Ketoconazole:
Ketoconazole Antifungal agent, has activity against dermatophytes, yeasts, dimorphic fungi and eumitsetov. Active also against staphylococci and streptococci. The mechanism of action is to inhibit the synthesis of ergosterol membranes of fungi and a violation of the permeability of the cell wall. Ineffective against Aspergillus, Zygomycetes. Reduces the formation of androgens.
Indications Ketoconazole:
Fungal infections caused by sensitive pathogens: fungal digestive tract, eyes, genital organs, chronic recurrent vaginal candidiasis, tinea (including area beard, scalp, hands), onychomycosis, thrush, folliculitis, trichophytosis, systemic fungal infections (blastomycosis, candidiasis, parakoktsidioidoz, koktsidioidoz, cryptococcosis, histoplasmosis, chromomycosis, sporotrichosis, paronychia, fungal sepsis, fungal pneumonia), leishmaniasis (cutaneous and visceral), pityriasis versicolor, the prevention of fungal lesions in patients with increased risk of development of prostate cancer (in high doses as an auxiliary anti-androgenic therapy), syndrome of Kashin-Beck (endemic osteoarthrosis deformans), hirsutism (drug therapy as a 3 or 4 lines).
Contra Ketoconazole:
Hypersensitivity, pregnancy, laktatsiya.C caution. Hepatic and / or renal insufficiency, concomitant use of potentially hepatotoxic drugs, alcoholism, achlorhydria, hypochlorhydria, pregnancy, lactation, childhood (up to 2 years) (safety and efficacy not established).
Side Effects Ketoconazole:
From the digestive system: loss of appetite, nausea, vomiting, abdominal pain, constipation or diarrhea, toxic hepatitis (increased activity of liver enzymes, hypercreatininemia).
The nervous system: headache, dizziness, drowsiness, paresthesia.
With the genitourinary system: gynecomastia, decreased libido in men, oligospermia, impotence, dysmenorrhea, azoospermia.
On the part of hematopoiesis: thrombocytopenia, leukopenia, hemolytic anemia.
Allergic reactions: hives, skin rash, fever, rash, photophobia.
Other: alopecia.
Dosing and Administration Ketoconazole:
Inside, for a reception during the meal. In dermatomycosis and multi-colored shingles appoint 200-400 mg / day for 8.1 weeks. In onihomikozah – 200-400 mg / day for 3-12 months to recover, including the normalization of laboratory parameters. In systemic mycosis – at 200-400 mg / day for 2 weeks, then – on 200 mg for 4-6 weeks, until complete recovery. When vulvovaginal candidiasis – at 200-400 mg for 3-5 days. When a felon – at 200-400 mg / day, with fungal pneumonia, sepsis – at 0.4-1 g / d; syndrome Kashin-Beck – to 600-1200 mg / day for other fungal diseases – by 200-400 mg . The maximum daily dose for adults – 1 g in systemic mycoses and 1.2 g of prostate cancer (400 mg 3 times daily). The duration of treatment in systemic mycosis – 6 months or more and parakoktsidioidoze – 3-12 months. Children from 2 years and older with vulvovaginal candidiasis, and paronychia, fungal pneumonia, sepsis – 5-10 mg / kg once daily for 5 days.
Special instructions Ketoconazole:
During treatment, you should regularly monitor the pattern of peripheral blood and functional state of liver and kidney. If the treatment of skin lesions was SCS, the ketoconazole appoint not less than 2 weeks after their withdrawal. In patients with achlorhydria or hypochlorhydria due to unpredictable reduce ketoconazole absorption may be ineffective when taken orally. Drinking acidic beverages increases the absorption of ketoconazole.
Interaction Ketoconazole:
Ethanol and other hepatotoxic drugs increases the risk of liver damage parenehimy. When combined use of ethanol may cause disulfiramopodobnyh reactions. Increases the concentration of sulfonylurea derivatives and increases the risk of hypoglycemia. Rifampicin and isoniazid reduce the concentration of ketoconazole in the plasma. Weakens the effect of amphotericin B. It increases plasma concentrations of cyclosporine, indirect anticoagulants, digoxin, midazolam, triazolam, and methylprednisolone. Increases biodostupost indinavir. Reduces the stimulatory effect of corticotropin on the adrenal glands. When combined with terfenadine, astemizole, and cisapride increases the risk of severe ventricular tachycardia, including Type “pirouette”. Increases the risk of bleeding “breakthrough” in the one-stage use of oral contraceptives with low hormone levels. Amplifies the toxicity of phenytoin. Antacids and anticholinergic drugs, blockers of histamine H2-receptor and other drugs that reduce gastric acidity, reduce the absorption of ketoconazole.
