Konazole (Ketoconazole) Use, Dosage, Side Effects, FAQ - MedicinesFAQ (2023)

Konazol (ketokonazol)

Conazole (ketoconazole) interferes with triglyceride and phospholipid biosynthesis by blocking fungal CYP450, thereby altering cell membrane permeability in susceptible fungi. It also inhibits other fungal enzymes, leading to the buildup of toxic concentrations of hydrogen peroxide.

Conazole (ketoconazole), like other azole antifungals, is a fungistatic that causes the growth of fungal cells to stop, thus preventing the growth and spread of fungi throughout the body.

usos

Treatment of superficial and deep mycoses:

• Dermatophytic and/or fungal infections of the skin, hair and nails (dermatomycosis, onychomycosis, perionyx, tinea versicolor, chronic mucocutaneous candidiasis, etc.), especially when local treatment is difficult or ineffective due to the involvement of large areas of skin or lesions affecting the deeper dermal layers, nails and hair
• Fungal infections of the mouth (thrush, perleche) and gastrointestinal tract
• Vaginal candidiasis, especially chronic recurrent cases or cases that respond poorly to local treatment
• Systemic fungal infections such as systemic candidiasis, paracoccidioidomycosis, histoplasmosis, coccidioidomycosis, etc.

Maintenance treatment to prevent relapses in systemic fungal infections and chronic mucocutaneous candidiasis. Prophylactic treatment to prevent fungal infections in patients with reduced host defences, eg cancer patients, organ transplants and burns.

Conazole (Ketoconazole) is also used for the associated treatment of these conditions: bacterial vaginosis (BV), blastomycosis, systemic candidiasis, chromomycosis, chronic mucocutaneous candidiasis (CMC), coccidioidomycosis, dandruff, endogenous Cushing's syndrome, histoplasmosis, infections, fungi, Paracoccidioidomycosis, Seborrheic dermatitis, Tinea corporis caused by Epidermophyton floccosumin, Tinea corporis caused by Trichophyton mentagrophytes, Tinea corporis caused by Trichophyton rubrum, Tinea cruris caused by Epidermophyton floccosumin, Tinea cruris caused by Trichophyton mentagrophytes, Tinea cruris caused by Trichophyton rubrum, Tine a Pedis Caused by Epidermophyton floccosumin, Tinea pedis caused by Trichophyton mentagrophytes, Tinea pedis caused by Trichophyton rubrum, Vaginal candidiasis, Vulvovaginal candidiasis, Cutaneous candidiasis, Recalcitrant dermatosis, Tinea versicolor caused by Malassezia infection

How conazole (ketoconazole) works.

Conazole (ketoconazole) interacts with 14-α-sterol demethylase, a cytochrome P-450 enzyme required for the conversion of lanosterol to ergosterol. This results in inhibition of ergosterol synthesis and increased permeability of fungal cells due to the reduced amount of ergosterol present in the fungal cell membrane. This metabolic inhibition also results in the accumulation of 14α-methyl-3,6-diol, a toxic metabolite. An increase in membrane fluidity is also believed to lead to damage to membrane-bound enzyme systems, as the components become less compact.

Konazol (ketokonazol)

Structure

Dose

Dosis de conazol (ketoconazol)

Orally-

fungal infections:

• Adult:200mg once a day; it can be increased to 400 mg once daily if the clinical response is poor. Continue treatment until symptoms resolve and cultures are negative.
• Niño:≥2 years 3.3-6.6 mg/kg once daily. Duration of treatment: 1-2 weeks for candidiasis; at least 4 weeks for resistant dermatophyte infections and up to 6 months for other systemic mycoses.
• Elderly people:No dose adjustments are necessary.

Theme (For Adults)-

Pityriasis versicolor, fungal skin infections:

• As 2% cream: Apply 1-2 times a day to cover the affected area and its surroundings for at least a few days after the symptoms disappear.
• As 2% shampoo: Apply to the scalp once a day for a maximum of 5 days. For prophylaxis: Use as a 2% shampoo once a day for a maximum of 3 days before sun exposure.

Seborrheic dermatitis:

• like 2% foam: Apply to the sensitive affected area for 4 weeks.
• As shampoo 1 or 2%: Apply to the scalp twice a week for 2-4 weeks. For prophylaxis: As a 2% shampoo, use once every 1-2 weeks.

Treatment duration

• Tinnitus versicolor: 1 to 6 weeks
• Dermatomycosis: 2 to 8 weeks
• Onychomycosis: 1 to 12 months
• Mycosis of the hair and scalp: 1 to 2 months
• Chronic mucocutaneous candidiasis: 1 to 12 months
• Oral mycoses: 5 to 10 days
• Systemic candidiasis: 1 to 2 months
• Paracoccidioidomicosis, histoplasmosis
• and other systemic mycoses: 1 month to 2 years

Side effects

Konazole (ketoconazole) is very well tolerated. Occasionally, nausea and itching may occur. An idiosyncratic hepatic reaction may occur in some patients (incidence 1:10,000).

toxicity

Overdose symptoms include acute liver damage, which may include hepatocellular and cholestatic damage, followed by anorexia, fatigue, nausea, and jaundice. In case of overdose, gastric lavage with activated charcoal can be used within an hour of taking ketoconazole; otherwise, provide supportive care. If the patient shows signs of adrenal insufficiency, give hydrocortisone 100 mg once with a saline and glucose infusion and monitor the patient closely. Blood pressure and fluid and electrolyte balance should be monitored over the next several days.

a precaution

Predisposition to adrenocortical insufficiency. Apply with acid drink in patients with achlorhydria. Pregnancy and lactation.

Interaction

Decreased absorption with antimuscarinics, antacids, H2 blockers, PPIs, and sucralfate. Reduced plasma concentrations with rifampicin, isoniazid, efavirenz, nevirapine, phenytoin. It can also reduce concentrations of isoniazid and rifampicin. May reduce the effectiveness of oral contraceptives. May increase serum levels of CYP3A4 substrates, eg digoxin, oral anticoagulants, sildenafil, tacrolimus.

Interaction with food

• Avoid alcohol. Drinking alcohol while taking ketoconazole can cause liver damage.
• Avoid multivalent ions. May reduce ketoconazole concentrations.
• Take with food. Food reduces gastrointestinal irritation caused by ketoconazole.

Conazole (ketoconazole) Interaction with alcohol

[Moderate] GENERALLY AVOID:

:

Excessive use of alcohol or alcohol-containing products together with ketoconazole or levoketoconazole may increase the risk of liver damage.

Serious hepatotoxicity has been reported with levoketoconazole.

Fatal hepatotoxicity or the need for liver transplantation has been reported with oral ketoconazole, of which levoketoconazole is an enantiomer.

Some patients had no obvious risk factors for liver disease.

Additionally, excessive use of alcohol or alcohol-containing products during ketoconazole or levoketoconazole therapy may cause a disulfiram-like reaction in some patients.

In general, excessive alcohol consumption should be avoided during ketoconazole or levoketoconazole therapy.

Patients receiving ketoconazole or levoketoconazole should be instructed to contact their doctor immediately if they experience swelling, rash, itching, loss of appetite, fatigue, nausea, vomiting, abdominal pain, dark urine, pale stools, and/or yellowish discoloration. of the skin or eyes. because they can be signs and symptoms of liver damage.

Conazole (ketoconazole) drug interactions

Moderate: polyethylene glycol 3350, polyethylene glycol 3350

Unknown: aspirin, aspirin, duloxetine, duloxetine, omega-3 polyunsaturated fatty acids, omega-3 polyunsaturated fatty acids, pregabalin, pregabalin, paracetamol, paracetamol, cyanocobalamin, cyanocobalamin, ascorbic acid, ascorbic acid, cholecalciferol, cholecalciferol, cetirizine, cetirizine

Conazole (ketoconazole) interaction with pain

Address: hepatotoxicity

Moderate: QT prolongation, achlorhydria, adrenal insufficiency

volume of distribution

Conazole (ketoconazole) has an estimated volume of distribution of 25.41 L or 0.36 L/kg. It is widely distributed in tissues, reaching effective concentrations in skin, tendons, tears, and saliva. Distribution in vaginal tissue creates concentrations 2.4 times lower than in plasma. Penetration into the CNS, bone, and seminal fluid is minimal. Animal studies have shown that conazole (ketoconazole) passes into breast milk and crosses the placenta.

removal path

Conazole (ketoconazole) requires an acidic environment to become soluble in water. At pH values ​​above 3, it becomes increasingly insoluble and about 10% dissolves in 1 h. At pH less than 3, dissolution is 85% complete in 5 minutes and complete in 30 minutes. A single oral dose of 200 mg gives a Cmax of 2.5 to 3 mcg/mL with a Tmax of 1 to 4 hours. Administration of ketoconazole with food consistently increases Cmax and delays Tmax, but the literature is conflicting regarding the effect on AUC, which may be slightly reduced. A bioavailability of 76% has been reported for ketoconazole.

half life

Conazole (ketoconazole) exhibits biphasic elimination with a first phase half-life of 2 hours and a terminal half-life of 8 hours.

Descargar

Conazole (ketoconazole) has an estimated clearance of 8.66 L/h.

removal path

Only 2-4% of the ketoconazole dose is excreted unchanged in the urine. More than 95% is eliminated by metabolism in the liver.

Use in pregnancy and lactation.

Category C: Animal studies have revealed harmful effects on the fetus (teratogenic, embryocidal or other) and there are no controlled studies in women or studies in women and animals. Drugs should only be given if the potential benefit justifies the potential risk to the fetus.

Contraindication

hypersensitivity; existing liver disease. Concomitant use with CYP3A4 substrates, for example, HMG-CoA reductase inhibitors (for example, lovastatin, simvastatin), midazolam, triazolam, cisapride, dofetilide, eplerenone, nisoldipine, pimozide, quinidine, terfenadine, astemizole, ergot alkaloids (for example, ergotamine, dihydroergotamine).

special notice

Renal insufficiency: Oral: No dose adjustment required.

Liver failure:Oral method: Contraindicated.

storage condition

Store at a temperature of 15-25° C. Protect from moisture and light.

monograph of innovators

You can find a simplified version hereKonazol (ketokonazol)