Mikozoral

Mikozoral – the antifungal drug having fungicidal activity against dermatophytes, drozhzhepodobny, dimorphous and highest mushrooms is active against stafilokokk and streptococci.

Form of release and structure

Dosage forms:

• Tablets: white with a gray or cream shade or white color, a ploskotsilindrichesky form, with dividing risky and a facet, the mramornost is allowed (on 10 pieces in a blister strip packaging, in a cardboard pack 1, 2 or 3 packagings);
• Ointment for external use of 2%: white with a cream or pink shade or white color, with a light specific smell (15 g, 20 g, 30 g, 40 g or 50 g in an aluminum tuba, in a cardboard pack 1 tuba);
• Shampoo of 2%: transparent viscous liquid from orange till yellow-orange color, with a slight smell (on 60 g in a polymeric bottle, in a cardboard pack 1 bottle).

Active ingredient of Mikozoral – кетоконазол:

• 1 tablet – 0,2 g;
• 1 g of ointment – 0,02 g;
• 1 g of shampoo – 0,02 g.

Auxiliary components:

• Tablets: lactoses monohydrate, povidone, potato starch, silicon dioxide colloid, magnesium stearate, talc;
• Ointment: propylene glycol, castor oil, a karmelloz of sodium, нипагин (methylparahydroxybenzoate), monoglycerides distilled, Dibunolum (butyl hydroxytoluene) emulsifying wax, the water purified;
• Shampoo: propylene glycol, sodium laureth sulfate, sodium metabisulphite, imidourea, Acidum hydrochloricum divorced, a macrogoal глицерилкокоат, an oksipropilmetiltsellyuloza, dye yellow-orange, the water purified.

Indications to use

Tablets
Mikozoral's use in the form of tablets is shown in case of lack of clinical effect of the local therapy, and also with a considerable depth of defeat, the big size infected with dermatophytes and/or barmy mushrooms of the surface of smooth skin and a pilar part of the head:

• Multi-colored deprive;
• Dermatofitiya;
• The folliculitis caused by Pityrosporum mushrooms;
• Chronic form of candidiasis of mucous membranes (including an oral cavity, a throat, a gullet) and skin;
• Chronic form of recurrent vaginal candidiasis.

Besides, tablets are appointed at treatment of system fungal infections:

• Histoplasmosis;
• Paracoccidioidosis;
• Coccidioidosis;
• Zymonematosis.

Ointment
Local therapy of the mycoses caused by the mushrooms sensitive to drug:

• Skin candidiasis;
• Dermatomycosis of smooth skin;
• Inguinal epidermophitia;
• Chromophytosis;
• The seborrheal dermatitis caused by drozhzhepodobny mushrooms of Pityrosporum ovale;
• Epidermophitia of brushes and/or feet.

Shampoo
Prevention and treatment of dandruff, chromophytosis, seborrheal dermatitis.

Contraindications

Mikozoral patients cannot apply with hypersensitivity to a ketokonazol and other components of drug.

Tablets

• Acute or chronic form of a disease of a liver;
• Concomitant use with astemizoly, terfenadiny, mizolastiny, dofetilidy, tsizapridy, quinidine, bepridily, Pimozidum, Disopyramidum, levatsetilmetadoly, galofantriny, domperidony, sertindoly, a peroral form of a triazolam and midazolam, GMG-KOA-reduktazy inhibitors, metaboliziruyemy through CYP3A4 (ловастатин, симвастатин), ergot alkaloids (ergometrine, dihydroergotamine, methylergometrine, ergotamine), eplerenony, nisoldipiny, everolimusy, irinotekany;
• Syndrome of glyukozo-galaktozny malabsorption, deficit of lactase, lactose intolerance;
• Breastfeeding period;
• Age up to 3 years.

With care it is recommended to appoint кетоконазол inside the patient with a liver failure, a hypochlorhydria, an achlorhydria, insufficiency of bark of a hypophysis and adrenal glands, at alcoholism, simultaneous use of gepatotoksichny means, during pregnancy, to women 50 years are aged more senior.

Ointment
Putting ointment on sites with the broken integrity of an integument is contraindicated.

Route of administration and dosage

Tablets
Pill is taken orally, during food.

The recommended daily dosing with frequency rate of reception of Mikozoral of 1 times:

• Adults and children with body weight more than 30 kg: on 1 tablet, in the absence of therapeutic effect at use of the specified dose or treatment of vaginal candidiasis appoint 2 tablets;
• Children of 3 years weighing 15-30 kg: on 1/2 tablets (0,1 g).

Average duration of therapy:

• Vaginal candidiasis – 1 week;
• Multi-colored deprive – 1,5 weeks;
• Dermatofitiya – up to 4 weeks;
• Chronic candidiasis of mucous membranes and skin – 2-3 weeks;
• Coccidioidosis, paracoccidioidosis, histoplasmosis, zymonematosis – 24 weeks;
• Fungal infections of a pilar part of the head – 4-8 weeks.

Ointment
Ointment is applied locally by drawing on skin of the body parts struck and adjoining to them.

Frequency rate of use:

• Dermatomycosis of smooth skin (skin candidiasis, epidermophitia of brushes and feet, inguinal epidermophitia, chromophytosis): 1 time a day;
• Seborrheal dermatitis: 1-2 times a day depending on expressiveness of defeat.

The recommended treatment duration:

• Dermatomycosis of smooth skin: 3-4 weeks;
• Epidermophitia of feet: 4-6 weeks;
• Inguinal epidermophitia: 2-4 weeks;
• The infections caused by drozhzhepodobny mushrooms: 2-3 weeks;
• Chromophytosis: 2-3 weeks;
• Seborrheal dermatitis: 2-4 weeks.

Treatment should be continued within 2-3 days after total disappearance of symptoms of an infection.

In the absence of clinical improvement against the background of 4 weeks of use it is necessary to specify the diagnosis.

Shampoo
Shampoo is applied outwardly, applying for 3-5 minutes on affected areas of a pilar part of the head and washing away water.

The recommended frequency rate and duration of use:

• Seborrheal dermatitis of a pilar part of the head, dandruff of various genesis: treatment – 2 times a week within 3-4 weeks, prevention – 1 time in 1-2 weeks;
• Chromophytosis: treatment – 1 time a day within 5-7 days; prevention (a one-time course) – 1 time a day within 3-5 days at the end of a spring season.

Side effects

Tablets

• Nervous system: passing increase in intracranial pressure, headache, drowsiness, dizziness, paresthesias;
• Alimentary system: loss of appetite, abdominal pain, nausea, vomiting, diarrhea, toxic hepatitis (giperkreatininemiya, increase in activity of liver enzymes or alkaline phosphatase);
• Bodies of a hemopoiesis: leukopenia, thrombocytopenia, hemolitic anemia;
• Sense bodys: photophobia;
• Urinogenital system: an oligospermatism, decrease in a libido at men, impotence, disturbances of a menstrual cycle;
• Allergic reactions: skin rash, small tortoiseshell, fever; very seldom – anaphylactoid and anaphylactic reactions, an acute anaphylaxis, a Quincke's disease;
• Others: a gynecomastia (reversible), an alopecia, decrease in level of concentration of testosterone in a blood plasma (it is recovered within 24 hours after administration of drug).

Ointment

• Allergic reactions: perhaps – burning in sites of application, urticaria, skin rash;
• Dermatological reactions: seldom – contact dermatitis.

Shampoo
Shampoo is transferred usually well, except exceptional cases of emergence of fat content or a xerasia, local irritation and an itch.

Special instructions

Reception of tablets of Mikozoral should be begun after careful assessment of function of a liver. Timely diagnosis of the first symptoms of a hepatotoxic during treatment requires frequent and regular control of function of a liver from all patients.

The total dose of a ketokonazol on a course of treatment poses a threat for development of a heavy hepatotoxic.

Toxic effect of drug on a liver increases at patients with liver diseases in the anamnesis, at a concomitant use of hepatotoxic means, medicinal intolerance, duration of use of a ketokonazol more than two weeks, at women 50 years are more senior. In this case function of a liver needs to be controlled prior to therapy, in 2 weeks of use and then monthly.

The breakdown, increased fatigue, fervescence, jaundice, decolouration a calla, urine darkening belongs to symptoms of functional disorder of a liver. The patient has to be informed on need of the immediate address to the doctor at their emergence and if functional hepatic tests confirm a liver disease, Mikozoral's reception should be cancelled.

At preliminary therapy glucocorticosteroids it is possible to appoint кетоконазол in 2 weeks after their cancellation.

At the accompanying therapy antiacid means should be accepted in 2 hours after administration of drug.

For increase in absorption of a ketokonazol at an achlorhydria or a hypochlorhydria patients are recommended to take acid drinks.

Use of drug in a dose of 0,4 g and more causes decrease in the kortizolovy answer against the background of stimulation of adrenal glands adrenocorticotropic hormone therefore during considerable stressful influence (for example, extensive surgical intervention) and at patients with adrenal insufficiency it is necessary to control function of adrenal glands.

Ointment is intended only for external use with observance of the general rules of hygiene.

It is not necessary to allow hits of ointment and shampoo in eyes, at accidental hit it is necessary to wash out them water.

To avoid a withdrawal after prolonged use of local glucocorticosteroids at treatment of seborrheal dermatitis it is recommended to continue therapy in combination with shampoo with gradual (within 2-3 weeks) a dose decline of glucocorticosteroids.

At oral administration of Mikozoral it is necessary to be careful at the control of vehicles and mechanisms demanding concentration of attention and high speed of psychomotor reactions.

Medicinal interaction

At simultaneous use of tablets of Mikozoral:

• Rifampicin, Phenytoinum, рифабутин, an isoniazid, carbamazepine, not Virapinum (inductors of a microsomal oxidation) – promote considerable decrease in bioavailability of a ketokonazol therefore this combination should be avoided;
• Ritonavir – increases bioavailability of a ketokonazol (reduction of a dose of a ketokonazol at this combination is required);
• Hepatotoxic means, ethanol – increase risk of emergence of damages of a hepatic parenchyma, against the background of the use of ethanol development of disulfiramopodobny reactions is possible;
• Phenytoinum – increases the toxicity;
• B Amphotericinum – weakens the therapeutic action;
• Corticotropin – reduces the action on adrenal glands;
• Antacids, anticholinergics, blockers _{of H2-histamine} receptors and other drugs reducing acidity of a gastric juice – reduce absorption of a ketokonazol.

Against the background of use of tablets action of the means which are metabolized with the participation of _{P450 cytochrome}, in particular from the CYP3A group amplifies or lasts.

Medicines, the demanding corrections (decrease) of dosing at a combination to Mikozoral because of risk of increase in their level of contents in a blood plasma, development of side effects:

• Anticoagulants for intake;
• Antineoplastic means: иматиниб, alkaloids of a periwinkle pink, dotsetakset, бусульфан, эрлотиниб;
• HIV protease inhibitors (индинавир, саквинавир);
• Blockers of slow calcium channels of a dihydropyridinic row, metaboliziruyemy CYP3A4 isoenzyme, perhaps, verapamil;
• Tolterodin, sildenafit;
• Cyclosporine, сиролимус, такролимус (immunosuppressive means);
• Atorvastatin and other inhibitors of GMG-KOA-reduktazy;
• Digoxin, буспирон, carbamazepine, alfentanil, brotiozolam, цилостазол, рифабутин, to alprazola, триметрексат, ребоксетин, эбастин, кветиапин, солифенацин, элетриптан, репаглинид, fentanyl;
• Budesonid, dexamethasone, флутиказон, Methylprednisolonum.

Against the background of Mikozoral's reception the risk of developing of breakthrough bleedings when using peroral contraceptives with the low content of hormones increases.

Interaction of ointment at a combination to other medicines is not established.

Terms and storage conditions

To protect from children.

To store at a temperature:

• Tablets: to 25 °C in the dry, protected from light place;
• Ointment: to 15 °C in the dry place;
• Shampoo: from 15 to 25 °C in the place protected from light.

Period of validity: tablets and ointment – 3 years, shampoo – 2 years.