Ketokonazol

General characteristics. Structure:

Active agent: кетоконазол 200 mg

Pharmacological properties:

Pharmacodynamics. Antifungal means, has activity concerning dermatophytes, barmy mushrooms, dimorphous mushrooms and eumitset. It is active also concerning stafilokokk and streptococci. The mechanism of action consists in inhibition of synthesis of ergosterol of a membrane of mushrooms and disturbance of permeability of a cell wall. Zygomycetes is inefficient concerning Aspergillus. Reduces formation of androgens.

Pharmacokinetics. Absorption - high (especially in acid medium of a stomach). Bioavailability is in direct dependence on size of the accepted dose. Contacts proteins of plasma and erythrocytes. TCmax is 2 h. Dynamics of concentration in blood is described by a bieksponentsialny curve. It is well distributed in fabrics and liquids of an organism: gets into inflammatory exudate, saliva, bile, urine, an earwax, a secret of sebaceous glands, excrements, sinews, skin and soft tissues. In insignificant quantities gets to SMZh and testicles (does not create therapeutic concentration), gets through a placenta and into breast milk. It is metabolized in a liver (oxidizing about-dezoksilirovaniye, oxidizing degradation, an aromatic hydroxylation). Is inhibitor of isoenzymes of CYP2C19 and CYP3A4, CYP3A5, CYP3A7. It is removed in not changed look and in the form of inactive metabolites: for 4 days 70% of the accepted dose are removed (57% - with bile and 13% - kidneys). T1/2 is 2-4 h.

Indications to use:

The fungal infections caused by sensitive activators: mycoses of a GIT, eye, generative organs, chronic recurrent vaginal candidiasis, dermatomycoses (including areas of a beard and moustaches, pilar part of the head, hands), onychomycoses, milkwoman, folliculitis, trichophytosis, system fungal infections (zymonematosis, candidiasis, paracoccidioidosis, coccidioidosis, cryptococcosis, histoplasmosis, chromomycosis, sporotrichosis, paronychias, fungal sepsis, fungal pneumonia); leushmaniosis (skin and visceral); a chromophytosis, prevention of fungal infections at patients with the increased risk of their development; a prostate cancer (in high doses as auxiliary anti-androgenic therapy), Kashin-Beck's syndrome (the local deforming osteoarthrosis), a hirsutism (treatment as HP 3 or 4 lines).

Route of administration and doses:

Inside, for 1 reception, during food. At dermatomycoses and multi-colored herpes appoint on 200-400 mg/days during 1-8 weeks. At onychomycoses - 200-400 mg/days within 3-12 months before recovery, including normalization of laboratory indicators. At system mycoses - on 200-400 mg/days during 2 weeks, then - on 200 mg during 4-6 weeks, to an absolute recovery. At a vulvovaginal candidiasis - on 200-400 mg within 3-5 days. At a paronychia - on 200-400 mg/days; at fungal pneumonia, sepsis - on 0.4-1 g/days; at Kashin-Beck's syndrome - on 600-1200 mg/days; at other fungus diseases - on 200-400 mg. The maximum daily dose for adults - 1 g at system mycoses and 1.2 g at a prostate cancer (on 400 mg 3 times a day). Treatment duration at system mycoses - of 6 months and more; at a paracoccidioidosis - 3-12 months. To children of 2 years is also more senior at a vulvovaginal candidiasis, at a paronychia, fungal pneumonia, sepsis - 5-10 mg/kg once within 5 days.

Features of use:

During treatment it is regularly necessary to control a pattern of peripheral blood, a functional condition of a liver and kidneys. If treatment of skin defeats was carried out by GKS, then кетоконазол appoint not earlier than in 2 weeks after their cancellation. At patients with an achlorhydria or a hypochlorhydria because of unpredictable decrease in extent of absorption кетоконазол it can be ineffective at oral administration. The use of acid drinks increases absorption of a ketokonazol. With care. A liver and/or renal failure, a concomitant use of potentially gepatotoksichny HP, alcoholism, an achlorhydria, a hypochlorhydria, pregnancy, the lactation period, children's age (up to 2 years) (safety and efficiency of use are not established).

Side effects:

From the alimentary system: loss of appetite, nausea, vomiting, abdominal pain, locks or diarrhea, toxic hepatitis (increase in activity of "hepatic" transaminases, giperkreatininemiya).

From a nervous system: headache, dizziness, drowsiness, paresthesias.

From urinogenital system: a gynecomastia, decrease in a libido at men, an oligospermatism, impotence, a dysmenorrhea, an azoospermism.

From bodies of a hemopoiesis: thrombocytopenia, leukopenia, hemolitic anemia.

Allergic reactions: urticaria, skin rash, fever, dieback, photophobia. Other: alopecia.

Interaction with other medicines:

Ethanol, etc. hepatotoxic HP increase risk of development of damages of a hepatic parenekhima. At joint use of ethanol emergence of disulfiramopodobny reactions is possible. Increases concentration of derivatives of sulphonylurea and increases risk of emergence of a hypoglycemia. Rifampicin and an isoniazid reduce concentration of a ketokonazol in plasma. The effect of Amphotericinum of V. Povyshayet weakens concentration in plasma of cyclosporine, indirect anticoagulants, digoxin, midazolam, a triazolam and Methylprednisolonum. Increases a biodostupost of an indinavir. Reduces a promoting effect of corticotropin on adrenal glands. At a combination with terfenadiny, astemizoly and tsizapridy increases risk of developing of heavy ventricular tachycardia, including the pirouette type. Increases risk of development of bleeding of "break" at single-step use of oral contraceptives with the low content of hormones. Increases toxicity of Phenytoinum. Antiacid and anticholinergic HP, H2 blockers - histamine receptors, etc. The hp reducing acidity of a gastric juice reduce absorption of a ketokonazol.

Contraindications:

Hypersensitivity, pregnancy, lactation.

Overdose:

At overdose the supporting measures are recommended. Within the first hour after reception, vomiting can be caused, the gastric lavage is carried out and absorbent carbon is appointed. Careful control of a condition of the patient and a symptomatic treatment is necessary. There is no specific antidote.

Storage conditions:

List B. In the dry, protected from light place, at a temperature not above 25 °C. To store in the place, unavailable to children.

Issue conditions:

According to the recipe