KETAZOL [Ketoconazole] 200 mg Film-coated tablets
KETAZOL
instructions for medical use of the medicinal product
Tradename
Ketazol, Ketazol
International non-proprietary name
Ketoconazole, Ketoconazole
Composition
Each film-coated tablet contains:
active ingredient: etoconazole USP 200 mg
excipients: corn starch, sodium starch glycolate, hypromellose, magnesium stearate.
Dosage form
Tablets.
Pharmacotherapeutic group
Antifungal agent.
Pharmacological properties
Ketazol is an antifungal agent. The active substance is ketoconazole.
Pharmacodynamics
Ketoconazole has a fungicidal and fungistatic effect. The mechanism of action is to inhibit the synthesis of ergosterol and change the lipid composition of the membrane. It is active against the causative agent of multicolored lichen Malassezia furfur, causative agents of some dermatomycosis (Trichophyton, Epidermophyton floccosum, Microsporum), causative agents of candidiasis (Candida), as well as causative agents of systemic mycoses (Cryptococcus).
It is also active against gram-positive cocci: Staphylococcus spp., Streptococcus spp.
Pharmacokinetics
Ketoconazole is a weak dibasic compound that dissolves and is absorbed in an acidic environment. Cmax of ketoconazole in plasma is about 3.5 μg / ml and is achieved 1-2 hours after a single oral dose of 200 mg during meals. The bioavailability of ketoconazole is maximal when taken with food. The absorption of ketoconazole is reduced in patients with low gastric acidity, for example, those taking antacids such as aluminum hydroxide and antisecretory drugs such as histamine H 2 receptor blockers and proton pump inhibitors, as well as in patients with achlorhydria caused by a certain disease.
Plasma protein binding, mainly to the albumin fraction, is 99%. Ketoconazole is widely distributed in tissues, but only a small part of the drug penetrates into the cerebrospinal fluid.
After absorption from the gastrointestinal tract, ketoconazole is metabolized in the liver with the formation of a large number of inactive metabolites.
In vitro studies have shown that the CYP3A4 isoenzyme is involved in the metabolism of ketoconazole. The main metabolic pathways are oxidation and cleavage of the imidazole and piperazine rings, oxidative O-dealkylation, and aromatic hydroxylation. Ketoconazole is not an inducer of its own metabolism. Excretion from plasma is biphasic: during the first 10 hours T 1/2 is 2 hours, subsequently - 8 hours.
About 13% is excreted in the urine, of which 2-4% is unchanged. It is excreted mainly with bile in the gastrointestinal tract and about 57% is excreted in the feces.
Indications for use
Blastomycosis, coccidioidomycosis, histoplasmosis, chromomycosis, paracoccidioidomycosis .
Contraindications
Hypersensitivity to ketoconazole , acute liver disease, pregnancy, lactation.
Dosage and administration
For oral administration 1 time per day with meals.
Adults and children weighing more than 30 kg - 200-400 mg per day.
Children weighing less than 30 kg - 4-8 mg / kg per day.
Special instructions and precautions
During treatment, it is necessary to regularly monitor the picture of peripheral blood, the functional state of the liver and kidneys in patients in order not to miss the first symptoms of hepatotoxicity. Due to the risk of hepatotoxicity, Ketazol should only be used when the potential benefit outweighs the potential risk.
During treatment with Ketazol, due to incompatibility, alcohol should not be consumed.
Drinking acidic drinks increases the absorption of ketoconazole.
Influence on the ability to drive vehicles and mechanisms
When treating with Ketazol , dizziness is possible, drowsiness is recommended to refrain from engaging in potentially hazardous activities.
Use during pregnancy and during breastfeeding
Use during pregnancy and during breastfeeding is contraindicated, and women planning pregnancy should not be prescribed.
Interaction with other drugs
Ethanol and other hepatotoxic drugs increase the risk of developing hepatic parenchymal damage. With the joint use of ethanol, disulfiram-like reactions may occur. Increases the concentration of sulfonylurea derivatives and increases the risk of hypoglycemia. Rifampicin and isoniazid reduce plasma concentrations of ketoconazole. Weakens the effect of amphotericin B. Increases the plasma concentration of cyclosporine, indirect anticoagulants, digoxin, midazolam, triazolam and methylprednisolone. Increases the bioavailability of indinavir. Reduces the stimulating effect of corticotropin on the adrenal glands. When combined with terfenadine, astemizole and cisapride, it increases the risk of severe ventricular tachycardia, incl. pirouette type. Increases the risk of bleeding "breakthrough" with the simultaneous use of oral contraceptives with a low content of hormones. Enhances the toxicity of phenytoin. Antacids and anticholinergics, H2-histamine receptor blockers, and other drugs that reduce gastric acidity reduce the absorption of ketoconazole .
Side effect
From the nervous system: often - insomnia, depression, asthenia; infrequently - headache, dizziness, drowsiness; rarely - paresthesia, confusion or loss of consciousness, peripheral polyneuropathy; the frequency is unknown - convulsions, a violation of taste sensations, emotional lability.
From the senses: rarely - blurred vision, tinnitus, conjunctivitis, dryness of the mucous membrane of the eye, eye pain, hearing loss; frequency unknown - optic neuritis.
From the side of the cardiovascular system: infrequently - tachycardia; the frequency is unknown - heart failure, increased blood pressure, vasodilation.
From the respiratory system: rarely - exacerbation of bronchial asthma, nosebleeds, laryngeal edema; the frequency is unknown - bronchospasm (especially in patients with hypersensitivity to NSAIDs), rhinitis.
From the digestive system: often - nausea, vomiting, dyspepsia, pain in the abdomen, NSAID gastropathy; infrequently - constipation, diarrhea, bloating, gastritis; rarely - peptic ulcer, stomatitis; very rarely - exacerbation of ulcerative colitis or Crohn's disease, gingival, gastrointestinal, hemorrhoidal bleeding, melena, perforation of the digestive tract; frequency unknown - gastrointestinal discomfort, stomach pain.
From the side of the liver and biliary tract: rarely - hepatitis, increased activity of liver enzymes in the blood, increased concentration of bilirubin in the blood.
From the urinary system: rarely - cystitis, urethritis, hematuria; very rarely - acute renal failure, interstitial nephritis, nephrotic syndrome, abnormal values of indicators of kidney function.
From the skin and subcutaneous tissues: infrequently - skin rash, pruritus; frequency unknown - photosensitivity, alopecia, urticaria, exacerbation of chronic urticaria, angioedema, erythema, bullous rash, including Stevens-Johnson syndrome, toxic epidermal necrolysis, purpura.
Other: peripheral edema, fatigue, shortness of breath, thirst, muscle twitching.
Overdose
Symptoms: headache, dizziness, drowsiness, nausea, vomiting, diarrhea and abdominal pain.
Treatment: the patient is immediately hospitalized and symptomatic treatment is carried out. The specific antidote is unknown.
Storage conditions
Store in a dry place, at a temperature not exceeding 30º C.
Keep out of the reach of children!
Best before date
3 years. Do not use after the expiry date stated on the package.
Holiday conditions
Released by prescription.
Release form
10 tablets in an aluminum foil blister. 1 blister with instructions for use in a cardboard box.