Nizoral 200 mg Tablets

Brand name

The trade name of the drug is Nizoral. This is the registered name under which the drug is known in medical practice and is available in pharmacies.

International Nonproprietary Name (INN)

The international nonproprietary name is ketoconazole. It denotes the active active ingredient and is used in pharmacology internationally.

Form of release

Nizoral is available in several forms: 200 mg tablets packed in blisters of 10 or 30 pieces; cream 2% in tubes of 15 g or 30 g; shampoo 2% in bottles of 60 ml or 120 ml. Tablets have a white color and round shape, cream - white homogeneous consistency, and shampoo - orange-pink tint with a characteristic odor. The variety of forms allows to adapt the treatment to the type and localization of fungal infection.

Composition

Active substance

The main active ingredient is ketoconazole. One tablet contains 200 mg of ketoconazole, 1 g of cream - 20 mg, and 1 ml of shampoo - 20 mg.

Auxiliary Components

The tablets include lactose monohydrate, corn starch, microcrystalline cellulose, povidone, and magnesium stearate. The cream contains propylene glycol, cetyl alcohol, stearyl alcohol, sorbitan monostearate, polysorbate 60, and purified water. Shampoo consists of sodium laureth sulfate, cocamide DEA, sodium chloride, fragrance, colorant and water.

Pharmacologic Properties

Pharmacodynamics

Ketoconazole, the active ingredient of Nizoral, has a pronounced antifungal action, which is based on the inhibition of ergosterol synthesis, a key component of the cell membrane of fungi. It blocks the enzyme 14-alpha-demethylase involved in the biosynthesis of ergosterol, which leads to disruption of membrane integrity of fungal cells, their dysfunction and subsequent death. The drug is active against a wide range of fungi, including dermatophytes (Trichophyton, Microsporum, Epidermophyton), yeasts (Candida, Malassezia), as well as some dimorphic and mold fungi (Aspergillus).

When used systemically (tablets) Nizoral effectively eliminates deep and widespread mycoses, such as internal candidiasis or onychomycosis. When used topically (cream, shampoo), it quickly relieves the symptoms of superficial infections - itching, peeling, inflammation. The therapeutic effect is manifested in 3-7 days with topical treatment and in 1-2 weeks with systemic therapy, depending on the severity of the infection. Ketoconazole also has a weak anti-inflammatory effect, which enhances its efficacy in dermatitis associated with fungal flora.

Pharmacokinetics

Absorption

Ketoconazole is well absorbed from the gastrointestinal tract after oral administration of tablets, especially in the acidic environment of the stomach. Maximum plasma concentration is reached in 1-2 hours, and bioavailability is about 75% when taken with food rich in fat or under conditions of normal acidity. When applied topically (cream, shampoo), systemic absorption is minimal (less than 1%), which limits the action to the local area.

Distribution

Ketoconazole binds actively to blood plasma proteins (95-99%), predominantly to albumin. The volume of distribution is about 0.4 L/kg, indicating penetration into tissues, including skin, nails, mucous membranes and lungs. The drug penetrates the blood-brain barrier poorly, but passes through the placenta and is excreted into breast milk.

Metabolism

Ketoconazole is metabolized in the liver with the participation of cytochrome P450 (CYP3A4) enzymes by oxidation and cleavage of the imidazole ring. Inactive metabolites are formed, which have no antifungal activity. The process of metabolism proceeds intensively, which reduces the concentration of the original substance in the blood.

Excretion

The half-life of ketoconazole is 2-10 hours (biphasic excretion: fast phase - 2 hours, slow phase - 8-10 hours). The drug is excreted mainly through intestine (about 70% in the form of metabolites) and through kidneys (about 13%, of which 2-4% in unchanged form). Complete excretion takes about 24-48 hours.

Indications for Use

Nizoral is prescribed for the treatment of the following conditions:

• Systemic mycoses (tablets): oral candidiasis, esophageal candidiasis, chronic candidiasis of the skin and mucous membranes, blastomycosis;
• Dermatophytosis (cream, tablets): ringworm, foot fungus, onychomycosis;
• Seborrheic dermatitis and dandruff (shampoo) caused by Malassezia;
• Superficial candidiasis of the skin and mucous membranes (cream);
• Prevention of fungal infections in immunodeficient patients.

The drug is effective for the treatment of acute and chronic fungal lesions.

Contraindications

The use of Nizoral is prohibited when:

• Hypersensitivity to ketoconazole or other imidazoles;
• Severe hepatic insufficiency;
• Simultaneous administration of CYP3A4 substrates (terfenadine, astemizole, cisapride) due to the risk of QT prolongation;
• Childhood under 3 years of age (for tablets);
• Pregnancy and lactation.

Cautiously prescribe in alcoholism, adrenal dysfunction, renal failure.

Method of Administration and Dosage

How to take

Nizoral tablets are taken orally with meals, drinking water (100-150 ml) to improve absorption. Cream is applied in a thin layer on the affected areas of the skin 1-2 times a day, gently rubbing. Shampoo is used for washing the head, leaving for 3-5 minutes before rinsing, 1-2 times a week.

Dosages for adults and children

Adults

Tablets: 200 mg once a day, in severe infections - 400 mg / day, the course of 2-8 weeks. Cream: 1-2 times a day for 2-4 weeks. Shampoo: 2 times a week for 2-4 weeks, then once a week for prophylaxis.

Children over 3 years of age

Tablets: 3.3-6.6 mg/kg body weight once daily (maximum 200 mg), course determined by a doctor. Cream and shampoo: as in adults, age-appropriate.

Dose adjustment for certain conditions

Dose adjustment is not required in renal failure. In hepatic insufficiency, the dose is reduced to 100 mg/day or cancel the drug in severe disorders.

Side Effects

Possible adverse reactions include:

• GI: nausea, vomiting, abdominal pain, diarrhea;
• Liver: increased transaminases, hepatitis (rare);
• Nervous system: headache, dizziness, drowsiness;
• Skin: rash, itching, photosensitization;
• Allergic reactions: urticaria, angioedema;
• Other: decrease in testosterone levels, gynecomastia in men.

Side effects require monitoring of liver function.

Overdose

Symptoms of overdose

Doses above 800 mg/day may cause nausea, dizziness, confusion, and hepatotoxicity.

First aid measures

Stop taking, call a doctor. Wash the stomach, give activated charcoal. Symptomatic treatment is required.

Drug Interactions

Influence on the effect of other drugs

Nizoral inhibits CYP3A4, increasing the concentration of drugs (cyclosporine, warfarin, statins), which increases their toxicity. Antacids and H2-blockers reduce the absorption of ketoconazole. Rifampicin accelerates its excretion.

Compatibility with alcohol and food

Alcohol increases the risk of hepatotoxicity. Food, especially fatty foods, improves the absorption of tablets.

Special Precautions

Use in pregnancy and breastfeeding

Nizoral is contraindicated in pregnancy and lactation due to the risk of teratogenicity and penetration into milk.

Effect on driving and mechanisms

The drug may cause dizziness, which requires caution when driving.

Particularities of use in the elderly and children

In the elderly, the dose is adjusted in case of hepatic dysfunction. In children under 3 years of age tablets are not used; cream and shampoo - with caution.