Difluzol
Difluzol: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. In case of impaired renal function
- 12. For violations of liver function
- 13. Use in the elderly
- 14. Drug interactions
- 15. Analogs
- 16. Terms and conditions of storage
- 17. Terms of dispensing from pharmacies
- 18. Reviews
- 19. Price in pharmacies
Latin name: Difluzol
ATX code: J02AC01
Active ingredient: fluconazole (fluconazole)
Manufacturer: PJSC Kievmedpreparat (Ukraine)
Description and photo update: 2019-19-08
Difluzol is an antimycotic (antifungal) drug with a wide spectrum of action.
Release form and composition
Dosage form of Difluzol - capsules for oral administration: (0.05 g or 0.1 g - 7 pieces in a package; 0.15 g each - 1 piece in a package).
The active substance is fluconazole, in 1 capsule - 0.05 g, 0.1 g or 0.15 g.
Auxiliary components: sodium starch glycolate, calcium stearate.
Pharmacological properties
Pharmacodynamics
The active ingredient of Difluzol is fluconazole - a substance that is an antifungal agent from the group of triazole derivatives, a powerful selective inhibitor of sterol synthesis in the fungal cell.
In vitro and in clinical studies, the drug has demonstrated activity against the following microorganisms: Candida tropicalis, Candida albicans, Candida parapsilosis, Candida glabrata (many strains are moderately sensitive), Cryptococcus neoformans. In vitro, the efficacy of fluconazole against Candida guilliermondii, Candida lusitaniae, Candida kefyr, Candida dubliniensis was also canceled, but the clinical significance of this activity is still unknown.
When taken orally and intravenously, fluconazole is active in opportunistic mycoses, including those caused by Trichophyton spp., Microsporum spp., Cryptococcus neoformans (including intracranial infections), Candida spp. (including generalized candidiasis in immunosuppressed patients). Also, activity was established in models of endemic mycoses, including infections caused by Histoplasma capsulatum, Coccidioides immitis (including intracranial infections), Blastomyces dermatitidis.
Resistance to fluconazole can develop in the following cases: a quantitative or qualitative change in the enzyme lanosteril-14-α-demethylase (which is a target for fluconazole), a decrease in drug access to the target, or a combination of these mechanisms.
Point mutations in the ERG11 gene, which encodes the target enzyme, lead to a modification of the target and a decrease in the affinity for azoles. In the case of an increase in the expression of this gene, high concentrations of the target enzyme are produced, which makes it necessary to increase the concentration of fluconazole in the intracellular fluid (and, therefore, its prescribed dose) to suppress all enzyme molecules in the cell.
Overexpression of the MDR (multidrug resistance) gene leads to resistance to fluconazole, while overexpression of the CDR genes (resistance of Candida fungi to azoles antimycotics) can lead to the development of resistance to various azoles. For strains in which the minimum inhibitory concentration is defined as intermediate (from 16 to 32 μg / ml), it is recommended to use fluconazole in maximum doses.
Candida krusei is considered to be resistant to fluconazole, the mechanism of its resistance is due to the reduced sensitivity of the target enzyme to the inhibitory effect of Difluzol.
Pharmacokinetics
After oral administration, fluconazole is well absorbed in the gastrointestinal tract. Food intake does not affect the absorption of the substance.
The plasma concentration of the drug is proportional to the dose taken. The maximum concentration in blood plasma is determined 0.5–1.5 hours after taking Difluzol on an empty stomach. Equilibrium concentration (C ss) at 90% is achieved by 4–5 days of therapy with repeated administration of the drug once a day. Achieving 90% C ss by the 2nd day of therapy is possible if a loading dose is taken on the first day (2 times higher than the standard dose).
Fluconazole is characterized by a low binding to plasma proteins - 11-12%. The volume of distribution is close to the total body water content.
The drug penetrates well into all body fluids. Its concentration in sputum and saliva is approximately the same as in blood plasma. With fungal meningitis, the concentration of fluconazole in the cerebrospinal fluid is about 80% of the plasma level.
Higher than in blood serum concentrations of the drug are achieved in the skin - the stratum corneum, dermis and epidermis. In the stratum corneum, fluconazole accumulates, its concentration when taken in a dose of 50 mg 1 time per day on the 12th day of treatment is 73 μg / g, 7 days after the end of therapy - 5.8 μg / g; when taking a dose of 150 mg once a week on the 7th day of treatment - 23.4 μg / g, 7 days after taking the second dose - 7.1 μg / g.
The concentration of fluconazole in the nail plate after 4 months of therapy at a dose of 150 mg once a week was: in healthy nails - 4.05 μg / g, in the affected nails - 1.8 μg / g. 6 months after the end of the course of treatment, the drug was still detected in the nail plates.
The drug is excreted mainly by the kidneys. About 80% of the received dose of fluconazole unchanged is found in urine. No circulating metabolites were found. Fluconazole clearance is proportional to creatinine clearance.
The plasma half-life is approximately 30 hours. Due to the length of this period, Difluzol can be taken 1 time per day for vaginal candidiasis, 1 time per week - for other indications.
Changes in pharmacological parameters in elderly patients are probably associated with decreased renal function.
Indications for use
According to the instructions, Difluzol is used in the treatment of fungal infections:
- Endemic deep mycosis;
- Cryptococcosis, including cryptococcal meningitis;
- Bronchopulmonary candidiasis;
- Atrophic candidiasis of the oral cavity caused by wearing dentures;
- Genital candidiasis;
- Disseminated candidiasis;
- Mycosis of the skin of the feet, trunk, groin;
- Onychomycosis;
- Fungal balanitis;
- Candiduria;
- Pityriasis versicolor.
Prophylactic intake of Difluzol is prescribed for patients with malignant neoplasms, taking cytostatic, immunosuppressive drugs, and during radiation therapy.
Contraindications
- Breastfeeding period;
- Hypersensitivity to drug components.
It is not recommended to prescribe when treating children under 6 years of age.
Difluzol is prescribed with caution: in case of impaired liver function; with immunodeficiency states; during pregnancy - use is possible only for vital clinical indications and if the expected therapeutic effect for the mother outweighs the potential harm to the fetus.
Instructions for the use of Difluzol: method and dosage
Difluzol capsules are taken orally, regardless of food intake, with water.
The doctor prescribes the dose and the period of treatment individually based on clinical indications.
Recommended dosage for the treatment of adult patients:
- Candidiasis of the mucous membranes of the body, including thrush: 0.05-0.1 g 1 time per day, for 14-30 days;
- Cryptococcosis: a single dose - 0.4 g on the first day, then 0.2-0.4 g per day. The course of treatment depends on the severity of the disease and the effect of therapy; in the treatment of meningitis, it can be from 6 to 8 weeks;
- Mycosis: 0.05 g 1 time per day or 0.15 g per week, the course of therapy is up to 6 weeks;
- Pityriasis versicolor: 0.05 g 1 time per day, treatment period - 2-6 weeks.
A single dose of Difluzol in the treatment of children depends on the weight of the child and is determined by calculation:
- Fungal diseases of the mucous membranes: 0.003 g per 1 kg;
- Candidiasis and cryptococcosis: 0.006-0.012 g per 1 kg of body weight.
Side effects
The use of Difluzol can cause side effects:
- From the digestive tract: manifestations of hepatotoxicity, vomiting, flatulence, diarrhea, pain syndrome;
- From the side of the nervous system: dizziness, change in taste, convulsions, headache;
- From the hematopoietic system: thrombocytopenia, agranulocytosis (inhibition of leukopoiesis), neutropenia;
- Possibly: allergic reactions such as itching, urticaria, facial edema, anaphylactic shock; arrhythmia; sometimes - skin rashes, hypokalemia, hypercholesterolemia, alopecia.
Overdose
In case of overdose, diarrhea, nausea, vomiting usually occur. In severe cases, convulsions are possible. Gastric lavage, forced diuresis, and hemodialysis are recommended (a 3-hour session can reduce the plasma concentration of fluconazole by about 50%). To eliminate the violations that have arisen, symptomatic therapy is prescribed.
There is one report of an overdose of fluconazole (following an oral dose of 8200 mg) in a 42-year-old patient infected with the human immunodeficiency virus, developing paranoid behavior and hallucinations. The patient was hospitalized and his condition returned to normal within 48 hours.
special instructions
For elderly patients, in the absence of absolute contraindications, Difluzol is prescribed according to the standard scheme.
In case of registration of an increase in bilirubin, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) indices, it is necessary to assess the feasibility of continuing the therapeutic use of the drug.
If rashes appear on the skin, Difluzol should be canceled.
Influence on the ability to drive vehicles and complex mechanisms
Due to the risk of dizziness and seizures during the use of Difluzol while performing potentially hazardous activities, caution should be exercised.
Application during pregnancy and lactation
Adequate and strictly controlled studies on the effect of fluconazole on pregnant and breastfeeding women have not been conducted.
The literature describes several cases of the formation of multiple developmental disorders in newborns, whose mothers received fluconazole in high daily doses (400-800 mg) during the entire first trimester or most of it. Defects such as cleft palate, impaired formation of the cranial vault, impaired development of the facial part of the skull, brachycephaly, arthrogryposis, thinning and lengthening of the ribs, curvature of the femur, congenital heart defects were noted. There is no evidence of the relationship between the described developmental anomalies with the use of low-dose fluconazole (150 mg once for vulvovaginal candidiasis) in the first trimester of pregnancy. Taking Difluzol during pregnancy is contraindicated, except in cases of severe and potentially life-threatening fungal infections,when the expected benefit from taking the drug to the mother is definitely higher than the likely risks to the fetus.
In breast milk, the concentration of fluconazole is close to the plasma concentration, therefore, the use of Difluzol is not recommended during lactation.
Pediatric use
Due to the dosage form of Difluzol, children can be prescribed the drug from an age when they are able to safely swallow the capsule. This is usually possible from about 6 years old.
With impaired renal function
With caution, Difluzol should be used for impaired renal function.
In renal failure (glomerular filtration rate less than 20 ml / min), the half-life of fluconazole increases from 30 hours to 98 hours. In this regard, this category of patients is recommended to reduce the dose of the drug.
For violations of liver function
In case of impaired hepatic function, Difluzol should be used with caution.
Use in the elderly
In the absence of signs of impaired renal function, the usual adult dose is prescribed for the elderly.
Drug interactions
The half-life of fluconazole is shortened when combined with rifampicin.
With the simultaneous use of Difluzol: increases the level of concentration in the blood of cyclosporine, cidovudine; enhances the effect of diphenin, hydrochlorothiazide, anticoagulant and hypoglycemic agents.
The absorption of Difluzol is not affected by the food intake, the combination with antacids and cimetidine.
Difluzol does not affect the effectiveness of oral contraceptives.
Analogs
Analogues of Difluzol are: Diflucan, Diflazon, Mikosist, Miconil, Medoflucon, Mikomax, Mikoflucan, Nofung, Flucostat, Flucosan, Flucoside, Fluconazole, Fungolone, Flukomycid, Flucoral, Flukorem, Fluciak, Forcan, Fucan
Terms and conditions of storage
Store at temperatures between 15 and 25 ° C. Keep out of the reach of children.
Shelf life is 4 years.
Terms of dispensing from pharmacies
Available without a prescription.
Reviews about Difluzol
Most of the reviews about Difluzol are positive. It is characterized as an effective and fast-acting remedy for thrush: for its treatment, as a rule, just a single capsule intake at a dosage of 150 mg is sufficient. The effectiveness of the drug is also noted in the treatment of other mycoses.
The price of Difluzol in pharmacies
The price of Difluzol is currently unknown, since the drug is not available in the Russian pharmacy chain. The cost of its popular analogue Diflucan: 750-860 rubles. for 7 capsules of 50 mg, 370-460 rubles. for 1 capsule 150 mg, 840-960 rubles. for 4 capsules of 150 mg, 1920-2280 for 12 capsules of 150 mg.
Maria Kulkes Medical journalist About the author
Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
