Mycosorrhal - instructions for use, dose, side effects, contraindications

Excipients: lactose monohydrate 16 mg, potato starch 60 mg, povidone 22.6 mg, silicon dioxide colloid 12 mg, talc 6.2 mg, magnesium stearate 3.2 mg.

Description:

Tablets are white or white with a creamy or grayish hue of color, flat-cylindrical, with a facet and a risk. Presence of "marble" is admissible.

Pharmacotherapeutic group:Antifungal agent

ATX: & nbsp

J.02.A.B.02 Ketoconazole

D.01.A.C.08 Ketoconazole

Pharmacodynamics:

Ketoconazole is a synthetic imidazoledioxole derivative with fungicidal or fungistatic action against dermatophytes, yeast-like (Candida, Pityrosporum, Torulopsis, Cryptococcus), dimorphic fungi and higher fungi (eumycetes).

Less sensitive to the action of ketoconazole Aspergillus spp., Sporothrix schenckii, others Dermatiaceae, Mucor spp. and other fikomitsety, except for Enomophthorales.

It is also active against staphylococci and streptococci.

Ketoconazole inhibits the biosynthesis of ergosterol in fungi, which leads to a change in composition of the lipid components in the membranes.

Reduces the formation of androgens.

Pharmacokinetics:

Absorption is high (especially in the acidic environment of the stomach). Bioavailability is directly dependent on the value of the dose taken. The average maximum concentration of ketoconazole in plasma (3.5 μg / ml) is achieved 1-2 hours after a single oral intake of 200 mg of the drug during meals.

Connection with blood plasma proteins - 99%. Well distributed in tissues and body fluids. In small amounts, it penetrates into the spinal fluid and testicles (does not create therapeutic concentrations), penetrates the placenta and into breast milk.

Metabolized in the liver in a large number of inactive metabolites. The main metabolic pathways are oxidation and degradation of the imidazole and piperazine rings, oxidative O-dealkylation and aromatic hydroxylation. Is an inhibitor of isoenzymes CYP2C19 and CYP3A4, CYP3A5, CYP3A7.

Excretion from the plasma is biphasic: during the first 10 hours, the elimination half-life is 2 hours, and in the subsequent - 8 hours.

Output is unchanged in the form of inactive metabolites: for 4 days 70% from the accepted dose (57% - with bile and 13% - kidneys).

The pharmacokinetic characteristics of ketoconazole generally differ slightly in patients with hepatic or renal insufficiency and in patients without such.

Indications:

Ketoconazole should be used only if other effective antifungal therapy is unavailable or intolerable if the expected benefit exceeds the possible risk of use.

Ketoconazole is indicated for the treatment of the following systemic fungal infections in patients in whom other therapies have proven ineffective or intolerable: blastomycosis, coccidioidomycosis, histoplasmosis, chromomycosis, paracoccidioidomycosis.

Use ketoconazole when fungal meningitis is not recommended, because ketoconazole little penetrates into the cerebrospinal fluid.

Contraindications:

Hypersensitivity to ketoconazole or other components of the drug; acute or chronic liver disease; lactation period; children up to 3 years; lactose intolerance, lactase deficiency or glucose-galactose malabsorption.

Simultaneous reception with terfenadine, astemizole, misolastine, cisapride, dofetilide, quinidine,pimozide; bepiride, disopyramide, halofantrine, levacetylmethadol, domperidone, and sertindole; triazolam and midazolam for oral administration; metabolized through CYP3A4 inhibitors of HMG-CoA reductase (simvastatin, lovastatin); alkaloids of ergot (dihydroergotamine, ergometrine, ergotamine, methylergomethrin); nisoldipine, eplerenone, irinotecan, everolimus.

Carefully:Hepatic insufficiency, achlorhydria, hypochlorhydria, insufficiency of the adrenal cortex and pituitary gland, simultaneous reception of potentially hepatotoxic drugs, alcoholism, pregnancy, age over 50 years (women).

Pregnancy and lactation:

The drug Mikozoral® should not be given to pregnant women, unless the intended benefit to the mother exceeds the potential risk to the fetus.

Because the ketoconazole penetrates into breast milk, it is recommended to stop breastfeeding when taking the drug.

Dosing and Administration:

Mikozoral® should be taken orally, to improve the absorption of the drug - while eating.

Adults

1 tablet (200 mg) once a day.If no improvement occurs after taking this dose, you should increase the dose to 2 tablets (400 mg) once a day.

Children over 3 years old

- with a body weight of 15 to 30 kg: ½ tablet (100 mg) once a day;

- with a body weight of more than 30 kg: the doses indicated for adults.

The average duration of treatment is 6 months.

Side effects:

From the digestive system: loss of appetite, nausea, vomiting, abdominal pain, diarrhea, toxic hepatitis (increased activity of "liver" transaminases or alkaline phosphatase, hypercreatininaemia).

From the central nervous system: headache, dizziness, drowsiness, paresthesia, reversible increase in intracranial pressure.

From the sense organs: photophobia.

On the part of the organs of hematopoiesis: thrombocytopenia, leukopenia, hemolytic anemia

Allergic reactions: urticaria, skin rash, fever; very rarely - anaphylactic shock, anaphylactoid and anaphylactic reactions, angioedema.

From the genitourinary system: decreased libido in men, oligospermia, impotence, menstrual irregularities.

Other: alopecia, gynecomastia (reversible), temporary decrease in the concentration of testosterone in the blood plasma (normalized less than 24 hours after reception).

Overdose:Treatment: gastric lavage, Activated carbon, symptomatic therapy, control of the patient's condition. There is no specific antidote.

Interaction:

Medicines that affect the metabolism of ketoconazole:

- inducers of microsomal oxidation, such as rifampicin, rifabutin, carbamazepine, isoniazid, nevirapine and phenytoin significantly reduce the bioavailability of ketoconazole. The use of ketoconazole with such drugs is not recommended;

- ritonavir increases the bioavailability of ketoconazole, as a result of this, when taking together, it is necessary to reduce the dose of ketoconazole.

Effect of ketoconazole on the metabolism of other drugs

Ketoconazole may enhance or prolong the effect of drugs metabolized with cytochrome P 450, especially from group CYP3A.

It is not possible to prescribe during the course of treatment with ketoconazole:

- terfenadine, astemizole, misolastine, cisapride, dofetilide, quinidine, pimozide, bepridil, disopyramide, halofantrine, levometadil, domperidone and sertindole. The risk of severe ventricular tachycardia increases, incl. type "pirouette";

- midazolam and triazolam (oral forms) metabolized by the isoenzyme CYP3A4 HMG-CoA reductase inhibitors, such as simvastatin and lovastatin, alkaloids - ergot (dihydroergotamine, ergometrine, ergotamine, methylergomethrin), nisoldipine, eplerenone, irinotecan, everolimus. Effects, including side effects, of these drugs are increasing.

Drugs, in the appointment of which it is necessary to monitor their concentration in the blood plasma, the severity of therapeutic effects and side effects (their dosage when taken together with ketoconazole, if necessary, should be reduced):

- oral anticoagulants;

- HIV protease inhibitors, such as indinavir, saquinavir;

- Some antineoplastic agents, such as alkaloids Carbon Pink, busulfan, docetaxel, erlotinib, imatinib;

- metabolized by isoenzyme CYP3A4 blockers of "slow" calcium channels dihydropyridine series and, possibly, verapamil;

- some immunosuppressive agents: ciclosporin, tacrolimus, sirolimus;

- sildenafil, tolterodine;

- some inhibitors of HMG-CoA reductase, for example, atorvastatin;

- Some glucocorticosteroids, such as budesonide, fluticasone, dexamethasone and methylprednisolone;

- other drugs: digoxin, carbamazepine, buspirone, alfentanil, alprazolam, brotisolam, rifabutin, trimetrexate, ebastine, reboxetine, quetiapine, solifenacin, cilostazol, eletriptan, fentanyl, repaglinide.

Ethanol and other hepatotoxic drugs increase the risk of damage to the liver parenchyma. With the joint use of ethanol, disulfiram-like reactions may occur.

Reduces the effect amphotericin B.

Reduces the stimulating effect corticotropin on the adrenal glands.

Increases the risk of bleeding "breakthrough" when using one-time oral contraceptives with a low content of hormones.

Increases toxicity phenytoin.

Antacid and anticholinergic drugs, H2-histamine receptor blockers and others drugs that reduce the acidity of gastric juice, reduce the absorption of ketoconazole.

Special instructions:

Before the beginning of treatment, it is necessary to evaluate the function of the liver to exclude acute or chronic diseases during treatment, it is necessary to frequently and regularly monitor liver function in all patients in order not to miss the first signs of hepatotoxicity. The total dose of ketoconazole (for treatment) is a risk factor for severe hepatotoxicity. .

In women older than 50 years, with liver disease in history, with drug intolerance, the use of hepatotoxic drugs, and if the duration of treatment with the drug exceeds 2 weeks, it is necessary to monitor liver function before treatment, after 2 weeks of treatment and then monthly, so as in these categories of patients the risk of the toxic effect of the drug on the liver increases.

It is very important to acquaint patients who need long-term treatment with the drug, with symptoms of liver disease (fatigue, loss of strength, fever, darkening of urine, fecal decolorization, jaundice).

In case of symptoms of hepatitis or if functional liver tests confirm liver disease, treatment should be stopped immediately.

If the treatment of skin lesions was carried out by glucocorticosteroids, then ketoconazole appoint not earlier than 2 weeks after their cancellation.

Patients taking antacid preparations (for example, aluminum hydroxide) should take them no earlier than 2 hours after taking the drug.

In patients with achlorhydria or hypochlorhydria due to an unpredictable decrease in the degree of absorption ketoconazole may be ineffective when taken orally. The use of acidic drinks increases the absorption of ketoconazole.

When applied at a dose of 400 mg or more, a decrease in the "cortisol response" with stimulation of the adrenal glands by adrenocorticotropic hormone (ACTH) is observed, therefore, during the treatment it is necessary to monitor the adrenal function in patients with adrenal insufficiency, as well as in patients undergoing significant stress effects (incl. h. extensive surgical interventions).

Effect on the ability to drive transp. cf. and fur:

During the period of treatment, care must be taken when driving vehicles and engaging in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions.

Form release / dosage:

Tablets 200 mg.

Packaging:

For 10 tablets in a planar cell package.

1, 2 or 3 contour mesh packages together with instructions for use in a pack of cardboard.

Storage conditions:

In a dry, the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:P N000408 / 03

Date of registration:24.03.2009 / 22.11.2016

Expiration Date:Unlimited

The owner of the registration certificate:AKRIKHIN HFK, JSC AKRIKHIN HFK, JSC Russia

Manufacturer: & nbsp

AKRIKHIN HFK, JSC Russia

Representation: & nbspAKRIKHIN OJSC AKRIKHIN OJSC Russia

Information update date: & nbsp07.06.2018

Illustrated instructions

Instructions

Mikozoral® (Mycozoral®)