FLIFON [Fluconazole] 150 mg Capsules
FLIFON
instructions for medical use of the medicinal product
Tradename
Flifon, Флифон
International non-proprietary name
Fluconazole, Флуконазол
Compound:
Each capsule contains:
Fluconazole 150 mg
Excipients: l actose, microcrystalline cellulose, magnesium stearate, sodium lauryl sulfate.
Dosage form
Capsules.
Pharmacotherapeutic group
Pharmacological properties
Pharmacodynamics
Antimycotics for systemic use, triazole derivatives. Fluconazole is a triazole antifungal agent. Its main mode of action is to inhibit fungal cytochrome P -450-mediated alpha-lanosterol 14 demethylation, which is an essential step in fungal ergosterol biosynthesis. Accumulation of 14 alpha-methylstyrenes correlates with subsequent loss of ergosterol in the fungal cell membrane and may be responsible for the antifungal activity of fluconazole.
Fluconazole has been shown to be more selective for fungal cytochrome P -450 enzymes than for various mammalian cytochrome P -450 enzyme systems.
Pharmacokinetics
After oral administration, fluconazole is well absorbed, food intake does not affect the absorption rate of fluconazole, its bioavailability is 90%. Time C max after ingestion, fasting 150 mg of the drug - 0.5-1.5 hours T 1/2 fluconazole is 30 hours Plasma protein binding - 11-12%. Plasma concentration is directly related to the dose. 90% level of equilibrium concentration is achieved by 4-5 days of treatment with the drug (when taken 1 time / day).
The introduction of a "shock" dose (on the first day), 2 times the usual daily dose, allows you to reach a concentration level corresponding to 90% of the equilibrium concentration by the second day.
Fluconazole penetrates well into all body fluids. The concentration of the active substance in breast milk, joint fluid, saliva, sputum and peritoneal fluid is similar to that in blood plasma. Constant values in the vaginal secretion are reached 8 hours after ingestion and are maintained at this level for at least 24 hours. Fluconazole penetrates well into the cerebrospinal fluid (CSF), with fungal meningitis, the concentration in the CSF is about 85% of its plasma level. In the sweat fluid, epidermis and stratum corneum (selective accumulation), concentrations exceeding serum levels are achieved. After oral administration of 150 mg on day 7, the concentration in the stratum corneum is 23.4 mcg / g, and 1 week after taking the second dose - 7.1 mcg / g; concentration in nails after 4 months. application at a dose of 150 mg 1 time per week - 4.05 mcg / g in healthy and 1.8 mcg / g in affected nails. V d approaches the total water content in the body. It is an inhibitor of the CYP2C9 isoenzyme in the liver. It is excreted mainly by the kidneys (80% - unchanged, 11% - in the form of metabolites). Fluconazole clearance is proportional to creatinine clearance (CC). Fluconazole metabolites were not detected in peripheral blood. The pharmacokinetics of fluconazole significantly depends on the functional state of the kidneys, while there is an inverse relationship between T 1/2 and creatinine clearance. After hemodialysis for 3 hours, the plasma concentration of fluconazole is reduced by 50%.
Indications for use
· cryptococcosis, including cryptococcal meningitis and other localizations of this infection (including lungs, skin), both in patients with a normal immune response and in patients with various forms of immunosuppression;
· generalized candidiasis, including candidemia, disseminated candidiasis and other forms of invasive candidal infections (infections of the peritoneum, endocardium, eyes, respiratory and urinary tract);
· candidiasis of the mucous membranes, incl. oral cavity and pharynx (including atrophic candidiasis of the oral cavity associated with wearing dentures), esophagus, non-invasive bronchopulmonary candidiasis, candiduria, skin candidiasis;
· genital candidiasis: vaginal candidiasis (acute and chronic recurrent), prophylactic use to reduce the frequency of recurrence of vaginal candidiasis (3 or more episodes per year);
· candidal balanitis;
· prevention of fungal infections in patients with malignant neoplasms who are predisposed to such infections as a result of chemotherapy with cytostatics or radiation therapy;
· mycoses of the skin, including mycoses of the feet, body, inguinal region;
· pityriasis (versus versicolor) lichen;
· onychomycosis;
· skin candidiasis.
Dosage and administration
For oral administration. Capsules should be swallowed whole and with or without food.
The dose should be based on the nature and severity of the fungal infection. Treatment of infections requiring multiple doses should be continued until (so as not to relapse) until clinical symptoms or laboratory tests show that the active fungal infection has subsided.
Adults:
Genital candidiasis:
- Acute vaginal candidiasis: 150 mg as a single dose.
- Candida balanitis: 150 mg as a single dose.
- Treatment and prevention of recurrent vaginal candidiasis (4 or more episodes per year): 150 mg every three days for a total of 3 doses (days 1, 4 and 7), followed by 150 mg once a week maintenance dose.
Maintenance dose: 6 months.
Dermatomycosis:
- Mycosis of the skin, including athlete's foot, body, groin and candida infections: 150 mg once a week for 2 to 4 weeks, athlete's foot may require treatment up to 6 weeks.
- Fungal infection of the stratum corneum of the epidermis : 300-400 mg once a week for 1-3 weeks.
- Onychomycosis ( affecting the nail plate and/or nail bed ): 150 mg once a week. Treatment should be continued until a healthy nail is grown instead of the infected nail. Recovery of fingernails and toenails usually requires 3 to 6 months and 6 to 12 months, respectively. However, growth rates can vary greatly between individuals and by age.
Special Populations:
Elderly: Dosage should be adjusted based on renal function.
Children: The safety and efficacy of the indication of genital candidiasis in the pediatric population have not been established. If treatment for genital candidiasis is mandatory for adolescents (12 to 17 years of age), the dosage should be the same as for adults.
Contraindications
Flifon should not be used in patients with hypersensitivity to fluconazole or related azole compounds or any other ingredient of the drug.
Co - administration of other drugs known to prolong the QT interval and which are metabolized by the CYP3A4 enzyme , such as cisapride, astemizole, pimozide, and quinidine, is contraindicated in patients receiving fluconazole
Special instructions and precautions
Treatment should be continued until the appearance of clinical and hematological remission. Premature termination of treatment leads to relapses.
Kidney failure: There is no need for a single dose adjustment.
Patients on regular dialysis should receive 100% of the recommended dose after each dialysis; on days without dialysis, patients should receive a reduced dose according to their creatinine clearance.
Liver failure: Use with caution in patients with hepatic dysfunction. In rare cases, the use of fluconazole was accompanied by toxic liver changes . The hepatotoxic effect of fluconazole was usually reversible; its signs disappeared after cessation of therapy. Therefore, if there are clinical signs of liver damage that may be associated with fluconazole, the drug should be discontinued.
Interaction with other drugs
When using fluconazole with warfarin, the prothrombin time increases (by an average of 12%). It is recommended to control prothrombin time when fluconazole is combined with coumarin anticoagulants.
Fluconazole increases T 1/2 of the plasma of oral hypoglycemic agents - sulfonylurea derivatives (chlorpropamide, glibenclamide, glipizide, tolbutamide) in healthy people. The combined use of fluconazole and oral hypoglycemic agents in patients with diabetes mellitus is allowed, but the doctor should keep in mind the possibility of developing hypoglycemia.
The simultaneous use of fluconazole and phenytoin can lead to an increase in plasma concentrations of phenytoin to a clinically significant degree. Therefore, if it is necessary to use these drugs together, it is necessary to monitor the concentration of phenytoin with dose adjustment in order to maintain the concentration of the drug within the therapeutic interval.
The combination with rifampicin leads to a decrease in AUC by 25% and a shortening of T 1/2 of fluconazole from plasma by 20%. Therefore, in patients receiving concomitant rifampicin, it is advisable to increase the dose of fluconazole.
It is recommended to control the concentration of cyclosporine in the blood in patients receiving fluconazole, because. when using fluconazole and cyclosporine in patients with a transplanted kidney, taking fluconazole at a dose of 200 mg / day leads to a slow increase in the concentration of cyclosporine in plasma.
Patients who receive high doses of theophylline or who are likely to develop theophylline intoxication should be monitored for symptoms of theophylline overdose, tk. simultaneous administration of fluconazole leads to a decrease in the clearance of theophylline from blood plasma.
There are reports of the interaction of fluconazole and rifabutin, accompanied by an increase in the serum concentration of the latter. With the simultaneous use of fluconazole and rifabutin, cases of uveitis have been described. It is necessary to carefully monitor patients who simultaneously receive rifabutin and fluconazole.
In patients receiving a combination of fluconazole and zidovudine, there is an increase in the concentration of zidovudine, which is caused by a decrease in the conversion of the latter to its main metabolite, so an increase in the side effects of zidovudine should be expected.
With the simultaneous use of fluconazole, terfenadine and cisapride, cases of adverse reactions from the heart, including torsades de pointes, have been described.
The simultaneous use of fluconazole and hydrochlorothiazide can lead to an increase in the concentration of fluconazole by 40%.
Increases the concentration of midazolam, and therefore increases the risk of developing psychomotor effects (more pronounced when fluconazole is used orally than intravenously).
Increases the concentration of tacrolimus, and therefore increases the risk of nephrotoxicity.
Use during pregnancy or lactation
The use of the drug in pregnant women is impractical, except for severe or life-threatening forms of fungal infections, when the potential benefit from the use of fluconazole for the mother significantly outweighs the risk to the fetus.
Since the concentration of fluconazole in breast milk and in plasma is the same, it is contraindicated to use the drug during lactation.
Influence on the ability to drive a car
Patients should be warned about the possibility of dizziness while taking the drug.
Side effect
The adverse events presented below are listed depending on the anatomical and physiological classification and frequency of occurrence. The frequency of occurrence is defined as follows: often - more than 1%; infrequently - 0.1-1%; rarely - 0.01-0.1%; very rarely - less than 0.01%.
From the digestive system: loss of appetite, change in taste, nausea, diarrhea, flatulence, abdominal pain, vomiting, abdominal pain; rarely - impaired liver function (jaundice, hepatocellular necrosis, hyperbilirubinemia, increased activity of alanine aminotransferase (ALT), aspartate aminotransferase (ACT) and alkaline phosphatase (AP), hepatitis, hepatonecrosis), incl. heavy.
From the nervous system: headache, dizziness, excessive fatigue; rarely - convulsions.
On the part of the hematopoietic organs: rarely - leukopenia, thrombocytopenia (bleeding, petechiae), neutropenia, agranulocytosis.
Allergic reactions: skin rash; rarely - erythema multiforme exudative (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome), anaphylactoid reactions (including angioedema, swelling of the face, urticaria, skin itching).
From the side of the cardiovascular system: an increase in the duration of the QT interval, ventricular fibrillation / flutter.
Others: rarely - impaired renal function, alopecia, hypercholesterolemia, hypertriglyceridemia, hypokalemia.
Overdose
Symptoms: hallucinations, paranoid behavior.
Treatment: symptomatic (gastric lavage, forced diuresis). Hemodialysis in the next 3 hours reduces the concentration by 50%.
Storage conditions
Store in a dry place, at a temperature not exceeding 25°C. Keep out of the reach of children.
Best before date
3 years. Do not use after the expiry date stated on the packaging.
Holiday conditions
Released by prescription.
Release form
1 capsule in a strip pack with instructions for medical use in a cardboard box.