Ketozoral

General characteristics. Structure:

Active ingredient: 200 mg of a ketokonazol in each tablet.

Excipients: lactose monohydrate, starch corn, croscarmellose sodium, povidone, magnesium stearate.

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. The maximum concentration of drug in a blood plasma (Cmax) through - 2 hours. 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 cerebrospinal fluid 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: in 4 days 70% of the accepted dose are removed (57% - with bile and 13% - kidneys). A drug elimination half-life - 2-4 hours.

Indications to use:

• Treatment of a dermatophytosis and folliculitis, the caused Malassezia (which is earlier called by Pityrosporum) in case of impossibility of use of local forms of antifungal medicines because of localization or prevalence of defeat, and also in case of deep infectious damage of skin patients resistant or at patients with intolerance have a flukonazola, a terbinafina and an itrakonazola.

• Treatment of chronic candidiasis of skin and mucous membranes, and also orofarengialny candidiasis in case of impossibility of use of local forms of antifungal medicines because of localization or prevalence of defeat, and also in case of deep infectious damage of skin patients resistant or at patients with intolerance have a flukonazola and an itrakonazola.

Route of administration and doses:

Inside, for 1 reception, during food, on 200-400 mg/days within no more than 10 days.

Reception courses lasting more than 10 days have to be appointed only after careful assessment of degree of the therapeutic answer, and also correlation of risk and advantage at prolonged use.

To children of 3 years is also more senior – 5-10 mg/kg once within 5 days.

Features of use:

Ketokonazol in tablets is not choice drug in treatment of superficial mycoses.

Purpose of a ketokonazol has to be made by the specialist having experience in treatment of fungal infections.

Ketokonazol is appointed only if the potential advantage exceeds the expected risk taking into account the available alternative effective antifungal drugs.

The risk of manifestation of hepatotoxic properties increases when lengthening a course of reception of a ketokonazol.

It is necessary to control a pattern of peripheral blood regularly; functional parameters of a liver at the time of the beginning of therapy, in 2 and 4 weeks of reception with the subsequent monthly control. Treatment has to be stopped immediately in case of exceeding (at least one of functional parameters of a liver) norms more than by 3 times.

If treatment of skin defeats was carried out by glucocorticosteroids, 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.

At use in a dose of 400 mg decrease in "the kortizolovy answer" at stimulation of adrenal glands by adrenocorticotropic hormones therefore during treatment it is necessary to control function of adrenal glands at patients with adrenal insufficiency, and also at the patients who are exposed to considerable stressful influences is also more observed (including extensive surgical interventions).

Side effects:

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

From a nervous system: headache, dizziness, drowsiness, paresthesias, reversible increase in intracranial pressure.

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

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

Allergic reactions: urticaria, skin rash, fever, photophobia.

Others: an alopecia, a gynecomastia (reversible), temporary decrease in concentration of testosterone in a blood plasma (it is normalized less, than in 24 hours after reception); anaphylactoid and anfilaktichesky reactions, Quincke's disease, adrenal insufficiency, cirrhosis.

Interaction with other medicines:

Ethanol and other hepatotoxic medicines increase risk of development of damages of a hepatic parenchyma. 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 isoniazid reduce concentration of a ketokonazol in plasma.

Weakens effect of Amphotericinum of Century.

Increases 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 medicines, H2 blockers - histamine receptors and other medicines reducing acidity of a gastric juice reduce absorption of a ketokonazol.

Ketokonazol is contraindicated for co-administration with the following medicines: Disopyramidum, сертиндол, нисолдипин, эплеренон, with medicines on the basis of ergot alkaloids (dihydroergotamine, ergometrine, ergotamine and methylergometrine).

Contraindications:

Hypersensitivity, pregnancy, breastfeeding.

Precautionary measures. With care appoint at a liver failure, a concomitant use of potentially gepatotoksichny medicines, alcoholism, an achlorhydria, a hypochlorhydria, pregnancy, to children up to 3 years (safety and efficiency of use are not established).

Overdose:

Symptoms: nausea, vomiting, dizziness and headache.

Treatment: gastric lavage, absorbent carbon, symptomatic therapy, control of a condition of the patient.

Storage conditions:

In the place protected from light and moisture, at a temperature not over 25 ºС. To store in the place, unavailable to children. A period of validity - 2 years. Not to apply medicine after the termination of a period of validity.

Issue conditions:

According to the recipe

Packaging:

On 10 tablets in a blister strip packaging, on 2 planimetric packagings together with a leaf insert in a pack.