Compound
- 1 Ketoconazole suppository contains 200 mg of ketoconazole . Additional substances: semi-synthetic glycerides (up to a total mass of the candle of 2000 mg), butylated hydroxyanisole.
- 1 g of Ketoconazole cream contains 200 mg of the drug substance of the same name, ketoconazole . Additional substances: labrafil M, emulsir 61, nipagin, vaseline oil, water.
- One tablet of the drug Ketoconazole contains 200 mg of ketoconazole . Additional substances: lactose, corn starch, magnesium stearate, silicon dioxide, low molecular weight PVP.
Release form
- Homogeneous white cream with a yellowish tint. 10, 15 or 25 grams of cream in an aluminum tube, one tube in a pack of paper.
- White, cylindrical vaginal suppositories with a yellowish tint; the presence of an air rod or a funnel-shaped depression is allowed on the cut. 5 candles in a contour package, 1 cell package in a paper pack.
- White round tablets with a yellowish tint, with a cross-shaped notch on one side. 10 tablets in a blister, 1 or 2 blisters in a paper pack.
Pharmacodynamics and pharmacokinetics
Pharmacodynamics
Ketoconazole is a man-made imidazole . Has fungistatic and fungicidal effects. It inhibits the biosynthesis of ergosterol and disrupts the normal lipid composition of the cell wall of fungi.
It acts on Epidermophyton floccosum, dermatophytes of the genera Microsporum, Trichophyton, as well as fungi of the genus Pityrosporum and Candida.
Pharmacokinetics of the cream
When applied locally, the active substance is practically not subject to systemic absorption; with prolonged use, its content in the blood is not determined.
Pharmacokinetics of suppositories
Absorption into the systemic circulation when administered intravaginally is extremely low.
Pharmacokinetics of tablets
The bioavailability of ketoconazole reaches its greatest values when consumed with food. If this condition is met, the maximum content of the drug in the blood is achieved after 1-2 hours. Absorption of the active substance is reduced in persons with reduced acidity of gastric juice and achlorhydria .
Reaction with blood proteins reaches 99%. Widely distributed in organs and tissues, except for the cerebrospinal fluid. Metabolized in the liver with the release of a large number of inactive derivatives. The main routes of biotransformation are: aromatic hydroxylation, cleavage and oxidation of piperazine and imidazole rings, oxidative O-dealkylation. The half-life is approximately 10 hours.
It is excreted mainly in bile and feces.
Pharmacological properties of the drug Ketoconazole
Ketoconazole is a synthetic derivative of imidazoledioxolane. It has a fungicidal and fungistatic effect against dermatophytes, yeasts (genera Candida , Pityrosporum , Torulopsis , Cryptococcus ), dimorphic and higher fungi (eumycetes). Less sensitive to ketoconazole are Aspergillus spp ., Sporothrix schenckii , some Dermatiaceae , Mucor spp . and other fucomycetes, with the exception of Entomophthrales . Pharmacological properties are due to the ability to have a damaging effect on the cell membrane of fungi. By interacting with the enzyme 14-α demethylase, ketoconazole inhibits the biosynthesis of ergosterol, an essential membrane component, from lanosterol. Like other azole compounds, the mechanisms of antifungal action of ketoconazole include inhibition of cellular respiration processes, interaction with membrane phospholipids, disruption of the transformation of yeast fungi into filamentous forms, suppression of purine uptake, disruption of the biosynthesis of triglycerides and/or phospholipids. At high concentrations, ketoconazole can have a direct physicochemical effect on fungal membranes, exhibiting a fungicidal effect. Secondary resistance to ketoconazole does not develop. In the acidic environment of the stomach, it quickly dissolves to form hydrochloride, which is quickly absorbed. The bioavailability of ketoconazaole depends on the acid-producing function of the stomach. Coadministration with food may increase the absorption of ketoconazole. The maximum concentration in blood plasma is achieved 1–4 hours after oral administration. Widely distributed in most body fluids. Binding to blood plasma proteins is 84–99%, mainly with albumin. Elimination from blood plasma is biphasic. The half-life in the first phase is about 2 hours, in the terminal phase - about 8 hours. Partially metabolized by oxidation, dealkylation and aromatic hydroxylation. Most of ketoconazole and its metabolites are excreted in the bile and then excreted in the feces (57% within 4 days, of which 20–65% unchanged), the remainder is excreted in the urine (13% within 4 days, of which 2–4 % unchanged). When used externally, it is not subject to significant resorption. Systematic topical application in the form of 2% shampoo leads to the accumulation of ketoconazole in the hair keratin. When administered intravaginally, small amounts of ketoconazole enter the systemic circulation. The maximum plasma concentration in women after intravaginal use of 400 mg of ketoconazole ranges from 0–20.7 ng/ml.
Indications for use
Indications for use of Ketoconazole cream
- athlete's foot inguinal ;
- dermatomycosis of smooth skin;
- athlete's foot and hands;
- pityriasis versicolor;
- candidiasis ;
- seborrheic dermatitis caused by Pityrosporum ovale.
Indications for the use of Ketoconazole suppositories
Treatment of vaginal recurrent candidiasis , both acute and chronic.
Prevention of the development of fungal infections of the vagina with reduced protective function of the body and during therapy with antibacterial agents and other drugs that alter the normal microflora.
Indications for the use of Ketoconazole tablets
Therapy and prevention of mycoses provoked by drug-sensitive microorganisms:
- infectious lesions of the mucous membranes of the digestive tract;
- severe lesions of the skin, nails and hair: onychomycosis , dermatophytosis , pityriasis versicolor and others;
- vaginal recurrent candidiasis of a chronic nature with ineffective local treatment;
- systemic mycoses: paracoccidioidomycosis , candidiasis , coccidioidomycosis , histoplasmosis , blastomycosis .
Prevention of fungal infections in weakened patients, including those suffering from immunodeficiency .
Indications for use of the drug Ketoconazole
Infections of the skin and nails caused by dermatophytes and/or yeast-like fungi (dermatophytosis, onychomycosis, paronychia caused by candida, pityriasis versicolor, folliculitis caused by Pityrosporum , chronic candidiasis of the mucous membranes and skin); infections of the digestive tract caused by yeast-like fungi; candidal vulvovaginitis. Oral administration is prescribed in cases where infections cannot be treated locally due to localization, extensive or deep skin lesions, in the absence of effect from previous local treatment, as well as for generalized fungal infections (candidiasis, paracoccidioidomycosis, blastomycosis, histoplasmosis, coccidioidomycosis). For prophylactic purposes, it is prescribed for primary and secondary immunodeficiency conditions and an increased risk of fungal infections.
Contraindications
Contraindications to the use of cream
- hypersensitivity to the components of the drug;
- violation of the integrity of the skin in the areas where the cream is intended to be used.
Contraindications to the use of suppositories
- first trimester of pregnancy;
- hypersensitivity to the components of the drug;
- age less than 12 years.
Ketoconazole suppositories are used with caution during lactation, in the second and third trimesters of pregnancy and in children over 12 years of age.
Contraindications to the use of tablets
- liver diseases of an acute and chronic nature;
- pregnancy or lactation;
- age under 3 years;
- hypersensitivity to the components of the drug.
Concomitant use with the following drugs that are degraded by the CYP3A4 isoenzyme ; it is possible to increase the concentration of these drugs in the blood, leading to increased therapeutic and side effects and to prolongation of the QT segment and the development of arrhythmias :
- analgesics: Methadone , Levacetylmethadol ;
- antiarrhythmics: Dronedarone , Disopyramide , Dofetilide , Quinidine ;
- anthelmintic and antiprotozoal agents: Halofantrine ;
- antihistamines: Mizolastine , Astemizole , terfenadine ;
- drugs for the treatment of migraine: Ergometrine , ergotamine , dihydroergotamine , methylergometrine ;
- antitumor agents: Irinotecan ;
- calcium channel blockers: lercanidipine , felodipine , bepridil , nisoldipine ;
- antipsychotics and hypnotics, anxiolytics: Sertindole , Lurasidone , Pimozide , midazolam , Triazolam ;
- lipid-lowering drugs: Simvastatin , Lovastatin ;
- cardiovascular drugs: ranolazine , ivabradine ;
- immunosuppressants: Everolimus ;
- diuretics: Eplerenone ;
- gastrointestinal agents: Domperidone , cisapride ;
- other means: Colchicine in the treatment of patients with liver and kidney disorders.
Description of the drug KETOCONAZOLE
With simultaneous use of ketoconazole with antacids (aluminum hydroxide, histamine H2 receptor blockers, proton pump inhibitors), the absorption of ketoconazole from the gastrointestinal tract decreases. With these combinations, the antifungal activity of ketoconazole should be monitored and its dose adjusted if necessary.
When ketoconazole is used simultaneously with strong inducers of the CYP3A4 isoenzyme, the bioavailability of ketoconazole may decrease, which can cause a significant decrease in its effectiveness. These drugs include isoniazid, rifabutin, rifampicin, carbamazepine, phenytoin, efavirenz, nevirapine. If these combinations cannot be avoided, then the antifungal activity of ketoconazole should be monitored and, if necessary, its dose should be increased.
With simultaneous use of ketoconazole with strong inhibitors of the CYP3A4 isoenzyme (for example, antivirals, including ritonavir, ritonavir-boosted darunavir and ritonavir-boosted fosamprenavir), the bioavailability of ketoconazole may increase. With these combinations, the patient's condition should be monitored to identify symptoms of increased intensity and duration of action of ketoconazole, the concentration of ketoconazole in the blood plasma and, if necessary, reduce its dose.
With simultaneous use, ketoconazole is able to inhibit CYP3A4-mediated drug metabolism, as well as the transport of active substances due to P-glycoprotein. This may lead to increased plasma concentrations of these drugs and/or their active metabolites, causing an increase in the intensity and duration of therapeutic or side effects of concomitantly administered drugs.
The simultaneous use of the following drugs with ketoconazole is not recommended:
- tamsulosin, fentanyl, rifabutin, rivaroxaban, carbamazepine, dasatinib, nilotinib, trabectedin, salmeterol. If these combinations cannot be avoided, then clinical monitoring of the patient's condition should be provided to identify symptoms of increasing intensity or duration of therapeutic and/or side effects, monitor the concentration of the drug in the blood plasma and, if necessary, reduce the dose of the appropriate drug or suspend its use.
Ketoconazole should be used with caution concomitantly with the following drugs:
- alfentanil, buprenorphine (IV and sublingual), oxycodone, digoxin, coumarins, cilostazol, repaglinide, saxagliptin, praziquantel, ebastine, eletriptan, bortezomib, busulfan, docetaxel, erlotinib, imatinib, ixabepilone, lapatinib, trimetrexate, vinca alkaloids, alprazolam , aripiprazole, brotizolam, buspirone, haloperidol, midazolam (iv), perospirone, quetiapine, ramelterone, risperidone, maraviroc, indinavir, saquinavir, nadolol, verapamil, aliskiren, aprepitant, budesonide, ciclesonide, cyclosporine, dexamethasone, fluticasone, methylprednisolone, sirolim with , tacrolimus, temsirolimus, atorvastatin, reboxetine, fesoterodine, imidafenacin, sildenafil, solifenacin, tadalfil, tolterodine, alitretinoin (oral dosage form), cinacalcet, mozavaptan, tolvaptan. When used together, careful monitoring of the patient’s clinical condition is recommended, if necessary, monitoring the concentration of the drug in the blood plasma and, if necessary, reducing its dose.
In isolated cases, a disulfiram-like reaction is possible when drinking alcohol while taking ketoconazole.
Side effects
Side effects after using the cream
- Skin irritation, itching, burning at the site of application, and skin rash are possible, which disappear immediately after discontinuation of the cream.
Side effects after using suppositories
- Local reactions: vaginal itching, irritation of the vaginal mucous membranes.
- Allergic reactions: urticaria , skin rash.
Side effects after using the tablets
- Reactions from nervous activity: dizziness, drowsiness, paresthesia , headache, excitability, anxiety, insomnia , weakness, reversible increase in intracranial pressure.
- Metabolic reactions: anorexia , alcohol intolerance, increased appetite, hyperlipidemia .
- Digestive reactions: nausea, diarrhea , abdominal pain, dyspepsia , liver dysfunction, constipation , vomiting, dysgeusia , dry mouth, discoloration of the tongue, bloating, toxic hepatitis , jaundice, increased activity of liver enzymes, cholestatic hepatitis , cirrhosis liver , hepatonecrosis , liver failure .
- Reactions from the musculoskeletal system: pain in muscles and joints.
- Respiratory reactions: nosebleeds.
- Skin reactions: dermatitis , alopecia , erythema , itching, xeroderma , rash, hot flashes, acute exanthematous pustulosis of a generalized type , photosensitivity .
- Circulatory reactions: orthostatic hypotension .
- Reactions from the hormonal sphere: deficiency of adrenal function, gynecomastia testosterone levels in the blood is possible (this indicator returns to normal within 24 hours after administration).
- Reactions from laboratory data: decrease in the amount of thrombocytopenia .
- Sensory reactions: fear of sunlight.
- Reactions from the genital area: azoospermia , erectile dysfunction .
- Immune reactions: urticaria , rash , angioedema , anaphylactic shock , pseudoanaphylactic shock .
- General reactions: peripheral edema, fever , chills .
Side effects of the drug Ketoconazole
When applied topically, a burning sensation and itching are possible, especially in the first days of treatment. When taken orally, in some cases, diarrhea, nausea, headache, dizziness, photophobia, paresthesia, thrombocytopenia, exanthema, itching may occur, and very rarely - alopecia, urticaria, rash and other manifestations of allergic reactions. When using ketoconazole in doses higher than recommended, reversible gynecomastia and oligospermia have been observed in rare cases. With a daily therapeutic dose of 200 mg (in 1 dose), a transient decrease in the level of testosterone in the blood plasma may develop; normalization of levels occurs less than 24 hours after taking ketoconazole. Patients with liver disease or hypersensitivity to ketoconazole very rarely develop hepatitis. In this case, ketoconazole is immediately discontinued. The risk of this complication increases in women over the age of 50 years, as well as after treatment with griseofulvin or hepatotoxic drugs. Sometimes there is a slight increase in the activity of transaminases or alkaline phosphatase, which does not require discontinuation of treatment with ketoconazole.
Instructions for use of Ketoconazole (Method and dosage)
Ketoconazole cream, instructions for use
In the treatment of dermatomycosis of the skin , athlete's foot (feet, hands and groin area), pityriasis versicolor and skin candidiasis , ketoconazole cream is applied to the affected and surrounding tissues once a day.
When treating seborrheic dermatitis, the ointment is applied to the desired area up to 2 times a day, depending on the severity of the disease. Maintenance therapy for this pathology is carried out up to two times a week. Treatment is continued for several more days after the symptoms of the disease have subsided or negative results of mycological examination of the skin have been recorded.
The duration of treatment is determined by the attending physician. The standard duration of treatment with cream for inguinal athlete's foot is 15-30 days, for dermatomycosis of the skin - 20-30 days, for pityriasis versicolor - 15-20 days, for athlete's foot and hands - 30-45 days, for seborrheic dermatitis - 15-30 days , for skin candidiasis – 15-20 days,
Instructions for candles
Suppositories are used intravaginally. Having freed the suppository from its packaging in advance, it is inserted into the vagina as deeply as possible in a horizontal position. Use one suppository per day for 3-5 days, depending on the severity of the disease.
When treating chronic candidiasis, treatment is carried out for 10 days while maintaining the specified frequency of administration.
Ketoconazole tablets, instructions for use
Ketoconazole tablets are taken orally with meals.
Children weighing more than 30 kg and adults are recommended to take 200 mg of medication once a day. The duration of treatment for lichen versicolor is 10 days, for candidiasis of the skin and oral cavity - 15-20 days, for onychomycosis - from 6 months to a year, for dermatomycosis - up to 30 days, for systemic mycoses - 30-60 days.
If significant positive changes in the course of the disease are not observed during the use of the drug (200 mg per day), then the daily dosage is allowed to be increased to 400 mg.
When treating vaginal candidiasis, the dosage is 400 mg per day, and the duration of administration is 5 days. To prevent fungal infections, adult patients are prescribed 400 mg of the drug per day.
Use of the drug Ketoconazole
For candidiasis and pityriasis versicolor, the cream is applied to the skin at the affected area once a day; for seborrheic dermatitis - 1-2 times a day (depending on the severity of the disease). Treatment should be continued for several days after all symptoms of the disease disappear. Maintenance therapy for inflammation of the sebaceous glands is carried out 1–2 times a week. If no improvement in the patient's condition is observed during 4 weeks of therapy, ketoconazole cream should be discontinued. For adults with skin infections, it is prescribed orally at a dose of 200 mg/day once; if there is no effect, the daily dose should be increased to 400 mg once. Children weighing 15–30 kg are prescribed 100 mg 1 time per day; with a body weight of more than 30 kg - 200 mg/day in 1 dose. For vulvovaginal candidiasis, 1 tablet (200 mg) is prescribed intravaginally 2 times a day for 5 days. To prevent fungal infections in patients with immunodeficiency, the following is prescribed: adults - 400 mg of ketoconazole per day in 1 dose; children - 4–8 mg/kg per day. To ensure maximum absorption, ketoconazole should be taken orally with food. Treatment must be continued for at least 1 week after symptoms disappear or until negative results of mycological examination are obtained. The average duration of treatment for skin mycoses caused by dermatophytes is about 4 weeks; for pityriasis versicolor - 10 days; for candidiasis of the oral cavity and skin - 2-3 weeks; for onychomycosis - 6–12 months, depending on the rate of nail growth (the affected nail must grow completely); for systemic candidiasis - 1–2 months; for paracoccidioidomycosis, histoplasmosis, coccidioidomycosis - several months. Shampoo with warm water is applied to the scalp and left on the surface of the skin for 3-5 minutes, then rinsed off. For pityriasis versicolor, shampoo is used once a day, the course of treatment is 5 days. For seborrheic dermatitis and scalp lichen, use shampoo 2 times a week for 2–4 weeks. To prevent pityriasis versicolor, shampoo is used once a day for 3 days, seborrheic dermatitis and dandruff - once every 1-2 weeks. The average duration of treatment is 1–2 months. Use 1 suppository per day for 3–5 days, depending on the dynamics of the disease. If necessary, the course of treatment is repeated until complete clinical recovery, confirmed by laboratory tests.
Overdose
Overdose when using cream or suppositories
Since these forms of drug release do not reach the systemic bloodstream, signs of overdose are unlikely.
If cream or suppositories are swallowed, the stomach should be lavaged and symptomatic treatment should be started.
Overdose of pills
In case of an overdose of tablets, increased side effects are expected. Treatment of overdose: gastric lavage, symptomatic therapy.
Interaction
When used according to the instructions, Ketoconazole suppositories and cream (ointment) are almost not absorbed into the systemic circulation and interaction with other drugs is unlikely.
When Ketoconazole is used together with antacids (H2-histamine receptor blockers, aluminum hydroxide , proton pump inhibitors), the absorption of the former from the intestine is reduced. With these combinations, it is necessary to monitor the effectiveness of treatment with the drug and, if necessary, adjust its doses.
When Ketoconazole is used together with strong activators of the CYP3A4 isoenzyme ( Rifabutin , Isoniazid , Efavirenz , Rifampicin , phenytoin , Carbamazepine , Nevirapine ), a decrease in the bioavailability of the former is possible, which can result in a significant decrease in its effectiveness. If these combinations cannot be avoided, then it is necessary to monitor the effectiveness of the drug described and, if necessary, increase its dose.
When ketoconazole is used together with substances that suppress the CYP3A4 isoenzyme (antiviral and other drugs), the bioavailability of ketoconazole may increase. With these combinations, it is necessary to monitor the patient’s condition in order to identify signs of increased effect of Ketoconazole and, if necessary, reduce its dose.
When used simultaneously, Ketoconazole tablets can block CYP3A4-mediated drug transformation, as well as P-glycoprotein -mediated transport of substances. This leads to an increase in the concentrations of these drugs in the blood, which in turn causes an increase in their therapeutic or side effects.
Concomitant use of the following drugs with Ketoconazole is not recommended: Fentanyl , Tamsulosin , Rifabutin , Carbamazepine , rivaroxaban , Dasatinib , Trabectedin , Nilotinib , Salmeterol.
Ketoconazole tablets should be used with caution with the following drugs: buprenorphine , Alfentanil , Oxycodone , coumarins, Saxagliptin , Cilostazol , Digoxin , Repaglinide , Eletriptan , praziquantel , Ebastine , docetaxel , bortezomib , Imatinib , Busulfan , Ixabepilone , Erlotinib , Trimetrex at , Alprazolam , Lapatinib , vinca alkaloids, Buspirone , Aripiprazole , midazolam , Brotizolam , Haloperidol , Perospirone , Ramelterone , Quetiapine , Risperidone , indinavir , Maraviroc , Nadolol , Saquinavir , Aliskiren , Verapamil , Budesonide , Aprepitant , Cyclosporine , Ciclesonide , Dexamet azone , methylprednisolone , fluticasone , Tacrolimus , Sirolimus , Atorvastatin , Temsirolimus , Reboxetine , Imidafenacin , Fesoterodine , Solifenacin , Mozavaptan , Sildenafil , Tadalfil , Tolterodine , Cinacalcet , Alitretinoin , Tolvaptan .
KETOCONAZOLE DS
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; therefore, when taken together, it is necessary to reduce the dose of ketoconazole.
The effect of ketoconazole on the metabolism of other drugs.
Ketoconazole may enhance or prolong the effect of drugs metabolized by cytochrome P 450, especially from the CYP3A group. The following should not be prescribed during a course of treatment with ketoconazole:
- terfenadine, astemizole, mizolastine, cisapride, dofetilide, quinidine, pimozide, bepridil, disopyramide, halofantrine, levacetylmethadol, domperidone and sertindole. The risk of severe ventricular tachycardia increases, incl. "pirouette" type;
- midazolam and triazolam (oral forms), HMG-CoA reductase inhibitors metabolized by the CYP3A4 isoenzyme, such as simvastatin and lovastatin, ergot alkaloids (dihydroergotamine, ergometrine, ergotamine, methylergometrine), nisoldipine, eplerenone, irinotecan, everolimus. The effects, including side effects, of these drugs are enhanced.
Drugs, when prescribed, it is necessary to monitor their concentration in the blood plasma, the severity of therapeutic effects and side effects
(their dose when taken together with ketoconazole should be reduced if necessary):
- indirect anticoagulants;
- HIV protease inhibitors, such as indinavir, saquinavir;
- some anticancer drugs, such as Vinca rosea
, busulfan, docetaxel, erlotinib, imatinib;
- blockers of “slow” calcium channels of the dihydropyridine series, metabolized by the CYP3A4 isoenzyme and, possibly, verapamil;
- some immunosuppressive drugs: cyclosporine, tacrolimus, sirolimus;
- sildenafil, tolterodine;
- some HMG-CoA reductase inhibitors, for example, atorvastatin;
- some glucocorticosteroids, such as budesonide, fluticasone, dexamethasone and methylprednisolone;
- other drugs: digoxin, carbamazepine, buspirone, alfentanil, alprazolam, brotizolam, rifabutin, trimetrexate, ebastine, reboxetine, quetiapine, solifenacin, cilostazol, eletriptan, fentanyl, repaglinide.
Ethanol and other hepatotoxic drugs increase the risk of developing damage to the liver parenchyma. When combined with ethanol, disulfiram-like reactions may occur.
Weakens the effect of amphotericin B.
Reduces the stimulating effect of corticotropin on the adrenal glands.
Increases the risk of breakthrough bleeding with simultaneous use of oral contraceptives with low hormone content.
Increases the toxicity of phenytoin.
Antacid and anticholinergic drugs, H2-histamine receptor blockers and other drugs that reduce gastric acidity reduce the absorption of ketoconazole.
special instructions
The cream is not intended for use in ophthalmic practice; it is also recommended to avoid contact with the eyes.
When using the cream immediately after long-term use of external glucocorticosteroids, skin irritation is possible, to relieve which it is recommended to continue treatment with local glucocorticosteroids in the morning and apply ketoconazole cream in the evening. Over the next 3 weeks, it is necessary to reduce the dose of the corticosteroid until it is completely discontinued.
For fungal infections of the scalp, it may be more preferable to use shampoo with Ketoconazole.
In very rare cases, when using suppositories, it is possible to develop a local allergy of the external genitalia in a partner.
To reduce the risk of relapse of the disease when using suppositories, it is recommended to simultaneously carry out therapy with a sexual partner.
The use of suppositories can reduce the reliability of barrier contraception.
The use of tablet forms of the drug is not advisable in the treatment of fungal meningitis , because ketoconazole does not pass through the blood-brain barrier poorly.
Due to the high risk of developing hepatotoxicity, the drug tablets should be used only in special cases when indicated and prescribed by a doctor.
Before starting tablet therapy, it is necessary to assess the level of liver function in order to exclude diseases, and during therapy it is necessary to regularly monitor blood counts, the condition of the kidneys, adrenal glands and liver, so as not to miss the appearance of signs of hepatotoxicity.
If glucocorticosteroids were used to treat skin diseases, then Ketoconazole tablets are prescribed only 14 days after their complete withdrawal.
Consuming acidic drinks increases the absorption of ketoconazole.
The drug Ketoconazole does not affect the ability to drive vehicles.
Special instructions for the use of the drug Ketoconazole
When using the cream immediately after long-term treatment with topical corticosteroids, skin irritation may occur. It is recommended to continue topical corticosteroid therapy in the morning and take ketoconazole in the evening. Then gradually reduce the dose of the steroid over 2–3 weeks until complete withdrawal. If you previously used a strong steroid drug, then it should be replaced with a drug with a weaker effect and the dose should be reduced according to the same scheme. Ketoconazole reduces the cortisol response to ACTH, so it is necessary to monitor adrenal function in patients with insufficiency of these glands, as well as in patients exposed to prolonged stress (complex surgery, intensive care). When taking ketoconazole for more than 2 weeks in a row, it is necessary to monitor liver function (before treatment, 2 weeks after the start of treatment and then monthly). When drinking alcohol during ketoconazole therapy, in exceptional cases, a disulfiram-like reaction to alcohol is observed, characterized by hyperemia, rash, peripheral edema, nausea and headache. The cream can be used during pregnancy and breastfeeding; oral administration is contraindicated.
Ketoconazole analogs
Level 4 ATX code matches:
Gainomax
Sertaconazole
Ornisis
Metrogil Plus
Livarol
Flagyl
Ginofort
Zalain
Candide B6
Candide
Gyno-Travogen Ovulum
Kanizon
Metromicon-Neo
Lomexin
Klion-D 100
Neo-Penotran
Gyno-Pevaril
Ginesol
Antifungol
- Dermazol
- Mycozoral
- Mikoket
- Mikanisal
- Nizoral
- Livarol
- Oronazole
- Dandruff
- Fungavis
- Sebozol
- Funginok
- Fungistab
Reviews about Ketoconazole
Reviews of ointments (creams) and suppositories with ketoconazole characterize them on the positive side. There are rare cases of side effects when using them. Reviews of shampoo with ketoconazole characterize it even better in the treatment of fungal infections of the scalp.
Tablets of the same name are prescribed extremely rarely due to their high ability to provoke side effects, so it is impossible to get a complete picture of the effectiveness of this form of release of the drug based on reviews.
Drug interactions Ketoconazole
The simultaneous use of drugs that reduce the acidity of gastric contents (anticholinergics and antacids, H2 receptor blockers) should be avoided. If such drugs are indicated, they should be taken no earlier than 2 hours after taking ketoconazole. With the simultaneous use of rifampicin and ketoconazole, the concentration of the latter in the blood decreases, and therefore these two drugs should not be taken simultaneously. Ketoconazole inhibits the activity of certain liver oxidases and may slow down the inactivation of drugs whose metabolism depends on the action of these enzymes. Increased levels of drugs prescribed in parallel with ketoconazole may increase the incidence of side effects. This applies to drugs such as cyclosporine, terfenadine, anticoagulants, methylprednisolone and probably busulfan. When co-administered with ketoconazole, the doses of these drugs should be reduced. Ketoconazole should not be co-administered with astemizole. After treatment with griseofulvin, it is recommended to take a break for 1 month and then begin treatment with ketoconazole.
Ketoconazole price, where to buy
The price of Ketoconazole ointment 15 g in Russia is about 50 rubles. In Ukraine, cream in such packaging can be bought for an average of 30 hryvnia.
The price of Ketoconazole suppositories in standard packaging in Russia averages about 400 rubles, in Ukraine their average price is about 100 hryvnia.
The price of Ketoconazole tablets No. 10 in Russia is about 150 rubles.
- Online pharmacies in RussiaRussia
- Online pharmacies in UkraineUkraine
ZdravCity
- Ketoconazole suppositories vaginal.
400 mg 5 pcs. LLC Avexima Siberia 282 rub. order - Ketoconazole suppositories vaginal. 400 mg 10 pcs. Avexima LLC Avexima Siberia
RUR 451 order
- Ketoconazole sup. vag. 0.4g 5pcs YuzhPharm LLC
RUB 218 order
- Ketoconazole sup. vag. 0.4g 10pcs YuzhPharm LLC
380 rub. order
Pharmacy Dialogue
- Ketoconazole (supp. vag. 400 mg No. 10) Avexima Siberia LLC
452 rub. order
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Pharmacy24
- Ketoconazole Fitofarm 25 g cream PRAT "Fitofarm", Ukraine
38 UAH. order - Ketoconazole 2% 15 g cream PRAT "Fitofarm", Ukraine
23 UAH order
Ketoconazole sup vag 400 mg x10
Trade name: Ketoconazole
International name: Ketoconazole&, (Ketoconazole)
Pharmacological group: antifungal agent
Pharmacological group for ATC: J02AB02. Ketoconazole
Pharmacological action: antifungal, antimicrobial
Pharmacodynamics:
Antifungal agent, has activity against dermatophytes, yeast fungi, dimorphic fungi and eumycetes. Also active against staphylococci and streptococci.
The mechanism of action is to inhibit the synthesis of ergosterol in the fungal membrane and disrupt the permeability of the cell wall.
Ineffective against Aspergillus, Zygomycetes. Reduces the formation of androgens.
Pharmacokinetics:
Absorption is high (especially in the acidic environment of the stomach). Bioavailability is directly dependent on the dose taken. Binds to plasma proteins and red blood cells. TCmax - 2 hours. The dynamics of concentration in the blood is described by a biexponential curve. It is well distributed in tissues and body fluids: penetrates into inflammatory exudate, saliva, bile, urine, earwax, sebaceous gland secretions, feces, tendons, skin and soft tissues. In small quantities it enters the CSF and testicles (does not create therapeutic concentrations), penetrates the placenta and into breast milk.
Metabolized in the liver (oxidative o-deoxylation, oxidative degradation, aromatic hydroxylation). It is an inhibitor of the isoenzymes CYP2C19 and CYP3A4, CYP3A5, CYP3A7.
It is excreted unchanged and in the form of inactive metabolites: 70% of the dose taken is excreted in 4 days (57% with bile and 13% with the kidneys). T1/2 - 2-4 hours.
Indications for use:
Fungal infections caused by sensitive pathogens: mycoses of the gastrointestinal tract, eyes, genital organs, chronic recurrent vaginal candidiasis, dermatomycosis (including the beard and mustache area, scalp, hands), onychomycosis, thrush, folliculitis, trichophytosis, systemic fungal infections (blastomycosis, candidiasis, paracoccidioidosis, coccidioidosis, cryptococcosis, histoplasmosis, chromomycosis, sporotrichosis, paronychia, fungal sepsis, fungal pneumonia), leishmaniasis (cutaneous and visceral), pityriasis versicolor, prevention of fungal infections in patients at increased risk of developing them, prostate cancer (in high doses as an auxiliary antiandrogen therapy), Kashin-Beck syndrome (endemic deforming osteoarthritis), hirsutism (treatment as a 3rd or 4th line drug).
Contraindications:
Hypersensitivity
lactation period.
Carefully:
Liver failure, simultaneous use of potentially hepatotoxic drugs, alcoholism, achlorhydria, hypochlorhydria,
pregnancy
children's age (up to 2 years) (safety and effectiveness of use have not been established).
Dosage regimen:
Inside, in 1 dose, during meals.
For ringworm and lichen versicolor, 200-400 mg/day is prescribed for 1-8 weeks.
For onychomycosis - 200-400 mg/day for 3-12 months until recovery, including normalization of laboratory parameters.
For systemic mycoses - 200-400 mg/day for 2 weeks, then 200 mg for 4-6 weeks, until complete recovery.
For vulvovaginal candidiasis - 200-400 mg for 3-5 days.
For paronychia - 200-400 mg/day, for fungal pneumonia, sepsis - 0.4-1 g/day, for Kashin-Beck syndrome - 600-1200 mg/day, for other fungal diseases - 200-400 mg .
The maximum daily dose for adults is 1 g for systemic mycoses and 1.2 g for prostate cancer (400 mg 3 times a day). The duration of treatment for systemic mycoses is 6 months or more, for paracoccidioidosis - 3-12 months.
CHILDREN:
Children aged 2 years and older with vulvovaginal candidiasis, paronychia, fungal pneumonia, sepsis - 5-10 mg/kg once for 5 days.
Side effects:
From the digestive system: loss of appetite, nausea, vomiting, abdominal pain, diarrhea, toxic hepatitis (increased activity of liver transaminases or alkaline phosphatase, hypercreatininemia).
From the nervous system: headache, dizziness, drowsiness, paresthesia, reversible increase in intracranial pressure.
From the genitourinary system: decreased libido in men, oligospermia, impotence, dysmenorrhea.
From the hematopoietic organs: thrombocytopenia, leukopenia, hemolytic anemia.
Allergic reactions: urticaria, skin rash, fever, photophobia.
Other: alopecia, gynecomastia (reversible), temporary decrease in the concentration of testosterone in the blood plasma (normalized less than 24 hours after administration).
Overdose:
Treatment: gastric lavage, activated charcoal, symptomatic therapy, monitoring the patient's condition.
Interaction:
Ethanol and other hepatotoxic drugs increase the risk of developing damage to the hepatic parenchyma. When combined with 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 plasma concentrations 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. like a pirouette.
Increases the risk of breakthrough bleeding with simultaneous use of low-hormone oral contraceptives.
Increases the toxicity of phenytoin.
Antacid and anticholinergic drugs, H2-histamine receptor blockers and other drugs that reduce the acidity of gastric juice reduce the absorption of ketoconazole.
Special instructions:
During treatment, it is necessary to regularly monitor the peripheral blood picture, the functional state of the liver and kidneys.
If treatment of skin lesions was carried out with corticosteroids, then ketoconazole is prescribed no earlier than 2 weeks after their discontinuation.
In patients with achlorhydria or hypochlorhydria, ketoconazole may not be effective when taken orally due to an unpredictable decrease in absorption. Drinking acidic drinks increases the absorption of ketoconazole.
When used at a dose of 400 mg or more, there is a decrease in the cortisol response when stimulating the adrenal glands with ACTH, so during the treatment period it is necessary to monitor adrenal function in patients with adrenal insufficiency, as well as in patients exposed to significant stress (including extensive surgical interventions) .
Description connected via INN
Instruction update date 10/27/2015
Manufacturer: Aarti Drugs Ltd., India
Marketing Authorization Holder: Aarti Drugs Ltd, India
Release form: substance
State data registration: FS-000507 dated 03/19/2013
Registration certificate status: valid
Pharmaceutical article number: FS 000507-120717
Manufacturer: Nanjing Baijingyu Pharmaceutical Co.Ltd, China
Marketing Authorization Holder: Nanjing Baijingyu Pharmaceutical Co.Ltd, China
Release form: substance-powder, two-layer polyethylene bags
Ingredients: ketoconazole
Shelf life: 4 years
State data registration: LS-001508 dated 04/14/2006
Registration certificate status: valid
Pharmaceutical article number: LS-001508-291211
Manufacturer: Piramal Enterprises Limited, India
Marketing Authorization Holder: Piramal Enterprises Limited, India
Release form: substance-powder 25 kg\, double plastic bags
State data registration: FS-000008 dated 10/20/2010
Registration certificate status: valid
Pharmaceutical article number: FS 000008-201010
Manufacturer: Ultratech India Ltd., India
Registration certificate holder: N.C.Pharm LLC, Russia
Release form: substance-powder, plastic bags
State data registration: FS-000243 dated 11/21/2011
Registration certificate status: valid
Pharmaceutical article number: FS 000243-211111
Manufacturer: Avexima Sibir LLC, Russia
Registration certificate holder: Avexima LLC, Russia
Release form: vaginal suppositories 400 mg, contour cell packaging
Conditions of release: without prescription
State data registration: LP-000760 dated 09.29.2011
Date of re-registration of the RU: 04/27/2017
Registration certificate status: valid
Pharmaceutical article number: LP 000760-290911
Manufacturer: Anzhero-Sudzhensky Chemical and Pharmaceutical Plant LLC, Russia
Registration certificate holder: Avexima LLC, Russia
Release form: vaginal suppositories 400 mg, contour cell packaging
Conditions of release: without prescription
State data registration: LP-000760 dated 09.29.2011
Date of re-registration of the RU: 04/27/2017
Registration certificate status: valid
Pharmaceutical article number: LP 000760-290911
Manufacturer: Public Joint Stock Company "Biokhimik" (PJSC "Biokhimik"), Russia
Registration certificate holder: Promomed Rus LLC, Russia
Release form: vaginal suppositories 400 mg, contour cell packaging
Conditions of release: without prescription
State data registration: LP-004655 dated 01/25/2018
Status of the registration certificate: expiration date 01/25/2023
Pharmaceutical article number: LP 004655-250118
Manufacturer: Pharmaprim LLC, Republic of Moldova
Marketing authorization holder: Pharmaprim LLC, Republic of Moldova
Release form: vaginal suppositories 400 mg, contour cell packaging
Conditions of release: without prescription
State data registration: LP-000760 dated 09.29.2011
Date of re-registration of the RU: 04/27/2017
Status of the registration certificate: expiration date 09/29/2016
Pharmaceutical article number: LP 000760-290911
Manufacturer: ZiO-Zdorovye CJSC, Russia
Registration certificate holder: ZiO-Zdorovye CJSC, Russia
Release forms: tablets 200 mg, blister packs, tablets 200 mg, polymer jars, tablets 200 mg, double-layer plastic bags
Dispensing conditions: by prescription
State data registration: LS-001734 dated 06/30/2006
Status of the registration certificate: expiration date 06/30/2011
Pharmaceutical article number: FSP 42-0513-7111-05
Manufacturer: Vertex JSC, Russia
Registration certificate holder: Vertex JSC, Russia
Release form: medicinal shampoo 2%, bottles
Conditions of release: without prescription
State data registration: LP-004646 dated 01/18/2018
Status of the registration certificate: expiration date 01/18/2023
Pharmaceutical article number: LP 004646-180118
