Drugs
Ketoconazole DS - contains ketoconazole, which is an imidazole derivative. It is an antifungal drug. It is a generic active ingredient for preparations containing the same active ingredient.
Composition
Active ingredient: ketoconazole - 200.0 mg; Excipients: lactose monohydrate - 40.0 mg, corn starch - 25.0 mg, povidone - 12.5 mg, pregelatinized starch - 12.0 mg, microcrystalline cellulose - 7.5 mg, magnesium stearate - 5.0 mg, sodium carboxymethyl starch - 10.0 mg
Indications / Application Notes
Ketoconazole should be used only if other effective antifungal therapy is unavailable or intolerant, if the expected benefit outweighs the possible risk of use. Ketoconazole is indicated for the treatment of the following systemic fungal infections in patients in whom other methods of therapy have proved ineffective or intolerable: blastomycosis, coccidioidomycosis, histoplasmosis, chromomycosis and paracoccidioidomycosis. It is not recommended to use ketoconazole for fungal meningitis because ketoconazole penetrates little into the cerebrospinal fluid.
Contraindications
• Hypersensitivity to ketoconazole and other components of the drug;
• Acute or chronic liver disease;
• Children under 3 years old.
• Simultaneous use of CYP3A4 isoenzymes with a number of substrates, such as dofetilide, quinidine, cisapride and pimozide, since such use can lead to an increase in the concentration of these drugs in blood plasma, to an increase or prolongation of both therapeutic and side effects and the development of a potentially dangerous condition , for example, to a prolongation of the QT interval and the development of ventricular tachycardia (including polymorphic ventricular tachycardia of the "pirouette" type, which is a potential threat to life) (see sections "Interaction with other drugs" and "Special instructions niya ").
• In addition, concomitant use with the following drugs is contraindicated: methadone, disopyramide, dronedarone, ranolazine, ergot alkaloids (eg dihydroergotamine, ergometrine, ergotamine, me-tilergometrine), irinotecan, lurasidone; oral midazolam, alprazolam, triazolam; felodipine, nisoldipine, ranolazine, tolvaptan, eplerenone, lovastatin, simvastatin, colchicine (in the treatment of patients with impaired liver and kidney function) (see sections "Interaction with other medicinal products" and "Special instructions").
• Lactase deficiency, lactose intolerance, glucose-galactose malabsorption.
Mode of application
Inside, during meals (to improve drug absorption) Adults. 1 tablet once a day. If no improvement occurs when taking the indicated dose, the dose should be increased to 2 tablets 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
The following adverse reactions have been identified in clinical studies:
Immune system disorders: anaphylactoid reactions.
Endocrine Disorders: Gynecomastia
Metabolic and nutritional disorders: alcohol intolerance, anorexia, hyperlipidemia, increased appetite.
Mental disorders: insomnia, nervousness.
Disturbances from the nervous system: headache, dizziness, paresthesia, drowsiness.
Disorders from the senses: photophobia.
Disturbances from the cardiovascular system: orthostatic decrease in blood pressure.
Respiratory, chest, and mediastinal disorders: epistaxis.
Disorders from the gastrointestinal tract: vomiting, diarrhea, nausea, constipation, abdominal pain, pain in the upper abdomen, dry mouth, taste changes, dyspepsia, flatulence, discoloration of the tongue.
Liver and biliary tract disorders: hepatitis, jaundice, abnormal liver function
Skin and subcutaneous tissue disorders: erythema, skin rash, dermatitis, urticaria, pruritus, alopecia, dry skin.
Musculoskeletal and connective tissue disorders: myalgia.
Genital and breast disorders: menstrual irregularities
General disorders: asthenia, fatigue, "hot flashes" of blood, malaise, hyperthermia, chills, peripheral edema,
Laboratory indicators: a decrease in the number of platelets.
In the post-registration period, the following adverse reactions were identified:
Disorders of the blood and lymphatic system: thrombocytopenia.
Immune system disorders: allergic conditions, including anaphylactic shock, anaphylactic reactions, angioedema.
Endocrine system disorders: adrenal insufficiency.
Nervous system disorders: A reversible increase in intracranial pressure (eg, swelling of the optic discs, swelling of the fontanelle in young children).
Liver and biliary tract disorders: severe hepatotoxicity, including cholestatic hepatitis, hepatonecrosis, cirrhosis of the liver, liver failure (including cases of transplantation and death).
Skin and subcutaneous tissue disorders: acute generalized exanthematous pustulosis, photosensitivity.
Musculoskeletal and connective tissue disorders: arthralgia.
Violations of the genitals and mammary gland: erectile dysfunction, azoospermia (at doses exceeding therapeutic doses of 200 or 400 mg per day).
Special instructions
Because of the risk of hepatotoxicity, ketoconazole should be used only when the potential benefit outweighs the potential risk, given the availability of other effective antifungal agents. Before starting treatment, it is necessary to assess liver function to exclude acute or chronic diseases. During treatment, it is necessary to regularly monitor the peripheral blood picture, the functional state of the liver and kidneys in patients in order not to miss the first signs of hepatotoxicity. While taking oral forms of ketoconazole, rare cases of hepatotoxicity have been reported, including cases with a fatal outcome or cases requiring liver transplantation. Changes in the state of the liver were observed in patients with the use of high doses of ketoconazole in a short course, and with the use of therapeutic doses for a long time. In this regard, it is recommended to regularly monitor liver function in patients receiving ketoconazole therapy. If liver dysfunctions are detected, treatment is stopped. It is very important to familiarize the patient who needs long-term treatment with ketoconazole with the symptoms of liver disease (increased fatigue, weakness, fever, dark urine, discoloration of feces, jaundice). If symptoms of hepatitis appear or if liver function tests confirm liver disease, treatment should be stopped immediately. In women over 50 years old, with a history of liver disease, drug intolerance, taking hepatotoxic drugs, and also if the duration of treatment with ketoconazole exceeds 2 weeks, it is necessary to monitor liver function before starting treatment, after 2 weeks of treatment and then monthly since in these categories of patients, the risk of toxic effects of the drug on the liver increases. It is necessary to assess the ratio of the expected benefit and the possible risk in the case of use for non-life-threatening diseases requiring long-term treatment. When using ketoknazole at a dose of 400 mg or more, a decrease in the “cortisol response” to stimulation of the pituitary adrenocorticotropic hormone (ACTH) was found. For this reason, the function of the adrenal glands should be monitored in patients with adrenal insufficiency or with borderline states, as well as in patients undergoing significant stress (major surgical interventions, etc.) The absorption of ketoconazole worsens with a decrease in the acidity of gastric juice. Patients taking medicines that suppress gastric acid secretion should preferably take ketoconazole with acidic drinks. Ketoconazole is prescribed with caution to alcohol abusers. while taking the drug with alcohol, a disulfiram-like reaction may occur, characterized by "hot flashes", rash, edema, nausea and headache. A history of hypersensitivity to ketoconazole is a contraindication for use. Concomitant use with a number of substrates of CYP3A4 isoenzymes, such as dofetilide, quinidine, cisapride, pimozide, methadone, disopyramide, dronedarone and ranolazine, since such use can lead to an increase in the concentration of these drugs in blood plasma, to an increase or prolongation of both therapeutic and and side effects and the development of potentially dangerous conditions, for example, to prolongation of the QT interval and the development of ventricular tachyarrhythmias (including polymorphic ventricular tachycardia of the "pirouette" type, which is a potential threat to life). The combined use of ketoconazole with midazolam, triazolam or alprazolam leads to an increase in the plasma concentration of these drugs. This can increase and prolong the sedative effect of these drugs, especially with repeated or prolonged use. With the simultaneous use of atorvastatin, lovastatin and simvastatin with ketoconazole, the plasma concentration of these drugs may increase, which may increase the risk of skeletal muscle damage, including rhabdomyolysis. In clinical studies, it has been found that ketoconazole can reduce testosterone concentration. Clinical manifestations may include gynecomastia, impotence, and oligospermia. Patients should be informed about the possible effects of ketoconazole. The use of ketoconazole in children is not recommended and is allowed only if no other alternative is available. Drugs that are contraindicated or not recommended for use or should be used with caution are listed in the section "Interaction with other medicinal products".
Release form
Tablets 200 mg. 10 tablets in a blister strip made of polyvinyl chloride film and aluminum foil or aluminum foil, laminated with oriented polyamide film and polyvinyl chloride film and aluminum foil. 1 or 2 blister packs with instructions for medical use in a cardboard box.
Storage conditions
In a dry, dark place at a temperature not exceeding 30°C. Keep out of the reach of children.
Shelf life
3 years. Do not use after the expiration date.
Manufacturer
ZiO-Zdorovye CJSC, Russia, 142103, Moscow region, Podolsk, st. Railway, 2