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

Inhibition of sterol-14-demethylase (cytochrome P450 isoenzyme) of fungal cells: a disruption in the synthesis of ergosterol involved in the construction of fungal membranes; violation of accumulating 14α-methylsterols dense packing of hydrocarbon chains of phospholipids, necessary for normal functioning of membrane proteins, including respiratory chain enzymes. Have C. albicans ketoconazole inhibits the transformation of blastophores into an invasive mycelium.

Pharmacological effects

Antifungal.

Fungistatic (inhibition of proliferation).

Fungicidal (destruction of fungal cells). The effect will develop depending on the concentration.

Weak non-competitive inhibition of the liver cytochrome P450 system (CYP3A4) B3.

Anti-protozoal (presumably).

Antineoplastic.

Antiandrogenic: a reversible decrease in the level of glucocorticoids and testosterone in the blood (at a dose of 800 mg per day),complete suppression of testosterone secretion (at a dose of 1.6 g per day), decreased libido, impotence.

Spectrum of antimicrobial activity

Active against dermatophytes (Trichophyton spp., Microsporum spp., Epidermophyton floccosum, Malassezia furfur), yeast fungi Candida spp. (including C. albicans, C. glabrata, C. tropicalis), molds (Cryptococcus neoformans, Aspergillus spp., Histoplasma spp., Paracoccidioides brasiliensis, Sporothrix schenckii, Fonsecaea spp., Cladosporium spp., Blastomyces dermatitidis, Coccidioides immitis). Ineffective against bacteria, rickettsia and viruses.

Pharmacokinetics:Bioavailability is 75%. The volume of distribution is 2.4 ± 1.6 l / kg. Well penetrates into keratinocytes. Only 1% of the dose penetrates into the cerebrospinal fluid. The connection with plasma proteins is 99%. Biotransformation in the liver using cytochrome CYP3A. Inhibits CYP3A4. The half-life is 8 hours. Clearance 8,4 ± 4,1 ml / min. Elimination by the kidneys (13%) and with feces (57%).

Indications:Mycoses of the digestive tract, eyes, genital organs.

Dermatomycosis of feet, multicolored lichen; pityriasis lichen.

Onychomycosis.

Thrush, prevention and treatment of oral cavity candidiasis in cancer patients receiving radiation or chemotherapy.

Folliculitis.

Trichophytosis.

Systemic fungal infections (blastomycosis, histoplasmosis, candidiasis, paracoccidiomycosis, coccidiomycosis, chromomycosis).

Fungal sepsis, fungal pneumonia.

Leishmaniasis (cutaneous and visceral); prevention of fungal infections in people with an increased risk of their development.

Prevention of fungal lesions.

Prostate cancer (in high doses - as an auxiliary antiandrogen therapy); Kashin-Bek syndrome (endemic deforming osteoarthritis), hirsutism (treatment as a means of III or IV line).

Chronic recurrent vaginal candidiasis.

Use in children

Systemic fungal infections, severe chronic resistant mucocutaneous candidiasis, severe resistant gastrointestinal fungal infections, skin or nail infections (fingers fingers, but not the toes) caused by resistant dermatophytes.

Chronic resistant vaginal candidiasis.

Prophylaxis and maintenance therapy in children with immunosuppression.

Seborrheic dermatitis, dandruff.

Multicolored lichen.

Dermatophytosis of the feet.

Other superficial mycoses.

ICD-10

I.A30-A49.A41.9 Septicemia, unspecified

I.B35-B49.B35 Dermatophytosis

I.B35-B49.B35.0 Mycosis of the beard and head

I.B35-B49.B35.1 Mycosis of nails

I.B35-B49.B36.0 Multicolored lichen

I.B35-B49.B37.3 Candidiasis of the vulva and vagina (N77.1 *)

I.B35-B49.B37.2 Candidiasis of skin and nails

I.B35-B49.B37 Candidiasis

I.B35-B49.B38 Coccidioidomycosis

I.B35-B49.B39 Histoplasmosis

I.B35-B49.B40 Blastomycosis

I.B35-B49.B41 Paracoccidioidomycosis

I.B35-B49.B49 Mycosis, unspecified

I.B50-B64.B55.1 Cutaneous leishmaniasis

XII.L20-L30.L21 Seborrheic dermatitis

Contraindications:Hypersensitivity to ketoconazole and the components of the drug. Hepatic and / or renal insufficiency. Pregnancy, breast-feeding.

Carefully:With the simultaneous use of potentially hepatotoxic agents, alcoholism, achlorhydria, hypochlorhydria, pregnancy, in children under 2 years of age (safety and efficacy have not been established), age over 50 years (women), insufficiency of the adrenal cortex and pituitary gland.

Pregnancy and lactation:FDA recommendations in category C. Adequate and well-controlled studies in humans and animals have not been conducted. In animals, it caused toxic effects in the mother, embryotoxic and teratogenic effects. Investigations of intravaginal use (177 women, 71 fetuses) did not reveal any abnormalities on the part of the mother and newborns.

Lactation. Penetrates into breast milk. Do not use or stop breastfeeding!

Dosing and Administration:The drug is taken inwards, while eating.

Adults and children weighing more than 30 kg - 200 mg 1 time per day, with inefficiency - 400 mg once a day.

Children with a body weight of 15 to 30 kg - 100 mg once a day.

When preventive use in patients with immunodeficiency, adults are prescribed 400 mg per day, children - 4-8 mg / kg per day.

Outwardly cream or ointment is applied to the affected areas 1 time per day.

Locally - Shampoo is applied to the affected areas of the skin and hair, then after 3-5 minutes, rinse with water.

Intravaginally - 1 suppository for 3-5 days. Treatment continues for at least a week after the disappearance of all symptoms of the disease.

The maximum single dose is 400 mg.

The maximum daily dose of 1 g (with systemic fungal infections).

Dermatomycosis stop - 200 mg per day for 4 weeks, multi-colored lichen - inside 200-400 mg per day for 2-8 weeks.

Onychomycosis - inside at a dose of 200-400 mg per day for 3-12 months (before clinical recovery, including normalization of laboratory indicators).

Folliculitis - 200 mg per day for 4 weeks.

Systemic fungal infections (blastomycosis, histoplasmosis, candidiasis, paracoccidioidomycosis, coccidioidomycosis, chromomycosis) - inside of 200-400 mg a day for 2 weeks, followed by 200 mg over 4-6 weeks until complete recovery.

Fungal sepsis, fungal pneumonia - 0.4-1 g / day.

Prevention of fungal infections - 400 mg / day.

Prostate cancer (in high doses - as an auxiliary antiandrogen therapy, the maximum dose of 400 mg 3 times a day); Kashin-Bek syndrome (endemic deforming osteoarthritis) - 600-1200 mg / day.

The duration of treatment with systemic fungal infections is 6 months or more, with paracoccidioidosis - 3-12 months.

Chronic recurrent vaginal candidiasis - intravaginally 400 mg (one candle) per day for 3-5 days.

Side effects:From the nervous system and sensory organs: headache, dizziness, drowsiness, paresthesia.

On the part of the digestive system: loss of appetite, nausea, vomiting, diarrhea, abdominal pain, increased hepatic transaminases in the blood, jaundice, hepatitis (high lethality, the risk increases with more than 14 days).

From the genitourinary system: gynecomastia, decreased libido, impotence, oligospermia, menstrual cycle disorders.

Allergic reactions: urticaria, itching.

Other: photophobia, alopecia, arthralgia, fever, thrombocytopenia; local reactions - hyperemia and irritation of the mucous membrane of the vagina, itching of the vagina (suppositories); local skin irritation, burning, rash, contact dermatitis (cream, ointment); irritation, itching and burning of the skin, increased fat content or dry hair (shampoo).

Overdose:When an overdose develops symptoms of cardiopulmonary insufficiency. Treatment - symptomatic therapy, monitoring and maintenance of vital functions. Removal of the drug by hemodialysis is unlikely.

Interaction:Weaken the effect of amphotericin B.

Incompatible with terfenadine, astemizol, alcohol.

Antacids, anticholinergics, H2-blockers significantly reduce absorption.

Rifampicin and isoniazid reduce the plasma concentration of ketoconazole.

Ketoconazole inhibits microsomal oxidation of concomitantly prescribed drugs and increases their concentration, increases the toxicity of phenytoin.

Reduces the stimulating effect of corticotropin on the adrenal glands.

Simultaneous administration of oral contraceptives with a low content of hormones causes breakthrough bleeding.

Special instructions:Among the antifungal drugs, there are preparations for local and systemic use; for many superficial mycoses, both dosage forms are used.

Antifungal agents, partially or completely absorbed from the digestive tract, effectively prevent oral cavity candidiasis in cancer patients in comparison withunabsorbed drugs, but the effectiveness of treatment of developing candidiasis is low in both groups.

Antifungal agents for systemic use are relatively toxic drugs.

Monitoring: the activity of aminotransferases (before and every month in the first 3-4 months of treatment, with small deviations - withdrawal of the drug), the concentration of creatinine and potassium in the blood, cardiac activity.

In connection with the high hepatotoxicity of ketoconazole and its violation of the synthesis of steroid hormones, systemically prescribed itraconazole.

The drug begins to act not immediately, therefore, with severe and rapidly progressing infections, it is not recommended to use it (should be replaced by itraconazole).

When ingested for 4 weeks ketoconazole comparable with fluconazole, itraconazole and griseofulvin (within 4 weeks) for the effectiveness of treatment of fungal lesions of the feet (mycological cure).

When treating ketoconazole (tablets), dizziness is possible, it is recommended to refrain from engaging in potentially hazardous activities.

Cream and ointment can not be used in ophthalmic practice (only systemic application). Avoid contact with eyes.

Instructions

Ketoconazole (Ketoconazolum)