Микозорал®

General characteristics. Structure:

Active ingredient: 200 mg of a ketokonazol in 1 tablet.

Excipients: potato starch, sugar milk, polyvinylpirrolidone low-molecular medical, aerosil, talc, magnesium stearate.

Pharmacological properties:

Pharmacodynamics. Ketokonazol — synthetic derivative an imidazoldioksolana, possessing fungicidal or a fungistasis against dermatophytes, drozhzhepodobny (Candida, Pityrosporum, Topulopsis, Cryptococcus), dimorphous mushrooms and the highest mushrooms (eumitset). Are less sensitive to action of a ketokonazol of Aspergillus spp., Sporothrix schenckii, other Dermatiacceae, Mucor spp. and other phycomycetes, except for Entomophthorales.

Ketokonazol inhibits biosynthesis of ergosterol in mushrooms that leads to change of structure of lipidic components in membranes.

Pharmacokinetics. Average maximum concentration of a ketokonazol in plasma (3,5 mg/ml) is reached in 1-2 hours after single oral administration of 200 mg of drug during food. Removal from plasma is two-phase: within the first 10 hours the elimination half-life makes 2 hours, and in the subsequent — 8 hours.

After absorption from digestive tract кетоконазол turns into a large number of inactive metabolites. Highways of metabolism are oxidation and splitting of imidazolny and piperazinovy rings, oxidizing O-dealkylation and an aromatic hydroxylation. About 13% of a dose are removed with urine of which from 2 to 4% are made by not changed medicine.

Drug is emitted generally with bile through digestive tract. In vivo linkng with proteins of plasma, mainly with albuminous fraction, makes 99%. Only an insignificant part of drug gets into cerebrospinal fluid.

Indications to use:

- the infections of smooth skin, a pilar part of the head, nails caused by dermatophytes and/or drozhzhepodobny mushrooms (a dermatofitiya, an onychomycosis, the paronychia called by sort mushrooms Candida multi-colored deprive, dandruff, the folliculitis caused by sort Pityrosporum mushrooms, chronic candidiasis of skin and mucous membranes) when it is impossible to use topical treatment of the big size of affected areas, considerable depth of damage of skin, and also in the absence of effect of the carried-out earlier topical treatment;
- the digestive tract infections caused by drozhzhepodobny mushrooms;
- chronic recurrent vaginal candidiasis in the absence of effect of performing local therapy;
- system fungal infections, for example, system candidiasis, паракокцидиомикоз, histoplasmosis, кокцидиомикоз, zymonematosis;
- prevention of fungal infections at patients with decrease in protective forces of an organism (inborn or the caused disease or effect of medicines).

Route of administration and doses:

Mikozoral it is necessary to accept inside, for drug absorption improvement - during food.

Treatment. Adults and children with body weight more than 30 kg:
- fungal infections of skin, digestive tract and system mycoses: about 1 tablet (200 mg) is recommended to accept mikozorat in day. If the adequate answer to this dose is not observed, it is possible to increase a dose to 2 tablets (400 mg) once a day.
- vaginal candidiasis: 2 tablets (400 mg) once a day, within 5 days.

Children with the body weight from 15 to 30 kg: 1/2 tablets (100 mg) a day. Treatment according to the provided scheme has to be carried out not less than a week after disappearance of all symptoms until negative takes of microbiological researches are received.

Preventive use for patients with an immunodeficiency:
- the adult — on 2 tablets (400 mg) a day;
- to children — 4-8 mg/kg of body weight a day, but no more than 400 mg.

The average duration of treatment makes:
- vaginal candidiasis — 5 days;
- the skin mycoses caused by dermatophytes — about 4 weeks;
- multi-colored deprive — 10 days;
- candidiasis of skin and oral cavity — 2-3 weeks;
- fungal infections of a pilar part of the head — 1-2 months;
- fungal infections of nails — 6-12 months;
- system candidiasis — 1-2 months;
- паракокцидиомикоз, histoplasmosis, кокцидиомикоз — the optimum duration of treatment — 3-6 months.

Features of use:

Slight, passing asymptomatic increase of activity of hepatic transaminases or alkaline phosphotazy is in certain cases observed. This reaction is not dangerous and does not demand the obligatory termination of treatment, however, such patients have to be under special observation.

If treatment duration mikozoraly exceeds 2 weeks, it is necessary to control function of a liver: prior to treatment, in two weeks and then monthly. In case of detection of abnormal liver functions treatment has to be stopped.

It is very important to acquaint patients who need prolonged treatment mikozoraly, with liver disease symptoms (increased fatigue, breakdown, fervescence, urine darkening, decolouration a calla, jaundice). In case of symptoms of hepatitis or if functional hepatic tests confirm a liver disease, treatment has to be immediately stopped.

At patients with insufficiency of adrenal glands or borderline cases, and also at the patients who are exposed to considerable stressful influences (surgical intervention) at administration of drug in a dose of 400 mg and more it is necessary to control function of adrenal glands.

Use during pregnancy and a lactation. Researches on use of a mikozoral for pregnant women are absent therefore it is not recommended to use drug during pregnancy, the exception is made by those cases when potential advantages of treatment to mother can justify possible risk for a fruit. Mikozoral gets into breast milk, breastfeeding at administration of drug is not recommended.

Influence on driving and other mechanisms. At treatment by drug dizziness is possible, it is recommended to refrain from occupations potentially dangerous types of activity.

Side effects:

The most often found side effects connected with reception of a ketokonazol are dysfunctions of digestive tract, such as dyspepsia, nausea, abdominal pains, diarrhea. Meet less often — a headache, sleeplessness, an arthralgia, fever, reversible increase in activity of "hepatic" enzymes, frustration of a menstrual cycle, dizziness, a photophobia, paresthesias, a giperkreatininemiya and allergic reactions (urticaria, skin rash, fever), an arthralgia, a dieback.

Treat the side effects arising seldom or never — thrombocytopenia, an alopecia, impotence and reversible increase in intracranial pressure (hypostasis of optic disks, protrusion of a fontanel at children).

At use of drug in the doses exceeding recommended therapeutic (200 or 400 mg a day) the reversible gynecomastia and an oligospermatism, decrease in a libido was in rare instances noted.

At reception of a therapeutic dose of 200 mg temporary decrease in level of testosterone in a blood plasma can be observed once a day.

It was reported about developing of toxic hepatitis during reception of a ketokonazol. At the bystry termination of treatment this reaction is reversible.

Interaction with other medicines:

The medicines exerting impact on Mikozoral's metabolism:
- rifampicin, рифабутин, carbamazepine, an isoniazid and Phenytoinum considerably reduce bioavailability of a ketokonazol;
- the drugs exerting impact on acidity of a gastric juice;
- ритонавир increases bioavailability of a ketokonazol thereof at joint reception it is necessary to reduce a dose of a mikozoral.
Mikozoral can strengthen or prolong effect of the medicines which are metabolized with participation of P 450 cytochrome, especially from the SYRZA group.

Examples of such medicines are:
- Drugs which it is impossible to appoint when carrying out a course of treatment mikozoraly: терфенадин, астемизол, цизаприд, to triazoles, the peroral forms of midazolam, quinidine, Pimozidum split by SYRZA4 enzyme, inhibitors of GMG-KOA reductase such, as симвастатин and ловастатин.
- Drugs at which purpose it is necessary to watch their concentration in plasma, action, side effects. Their dosage at joint reception with mikozoraly if necessary has to be reduced:
- Peroral anticoagulants.
- HIV inhibitors - proteases, such, as индинавир, саквинавир.
- Some antineoplastic drugs, such as alkaloids of the Periwinkle pink, dotsetakset.
- The blockers of calcium channels which are metabolized with SYRZA4 enzyme participation.
- Some immunodepressive means: cyclosporine.
- Other drugs: digoxin, carbamazepine, буспирон, sildenafit, to alprazola, midazolam, рифабутин, Methylprednisolonum.

It was in exceptional cases reported about emergence of the disulfirampodobny reaction to alcohol which is characterized by reddening, rash, peripheral hypostasis, nausea and a headache. All symptoms completely disappear within several hours.

The lowered acidity: at this state absorption of drug worsens.

The patients accepting antiacid drugs, for example aluminum hydroxide should accept them not earlier than in 2 hours after reception of a mikozoral. To patients with an achlorhydria or to the patients accepting the medicines suppressing secretion of hydrochloric acid in a stomach (for example, H2 - histamine receptors or inhibitors of "the proton pump"), it is desirable to accept mikozorat with acid drinks.

Mikozoral weakens effect of Amphotericinum of Century.

Reduces a promoting effect of corticotropin on adrenal glands.

Increases risk of development of bleeding of "break" against the background of reception of oral contraceptives with the low content of hormones.

Increases toxicity of Phenytoinum.

Contraindications:

Acute and chronic diseases of a liver, kidneys, hypersensitivity to drug components.

With care - pregnancy, the lactation period, age is more senior than 50 years (woman), a concomitant use of potentially hepatotoxic drugs, insufficiency of bark of adrenal glands and a hypophysis.

Overdose:

At accidental overdose it is recommended within the first hour after poisoning to cause vomiting, to wash out a stomach and to accept absorbent carbon. Careful control of a condition of the patient and a symptomatic treatment is necessary. There is no specific antidote.

Storage conditions:

To store in the dry, protected from light place, at a temperature not above 25 °C. To store in the place, unavailable to children. Not to use drug after the expiry date specified on packaging. A period of validity - 2 years.

Issue conditions:

Without recipe

Packaging:

Tablets on 200 mg; 10 tablets in a blister strip packaging. 1,2,3 blister strip packagings in a pack.