Composition, form of production and packaging
? Hard gelatin capsules, size 2, with a white body and a pink lid; the contents of the capsules are white or almost white powder.
1 caps.
fluconazole 150 mg
Excipients: lactose - 27.8 mg, starch - 75 mg, silicon dioxide colloid - 0.25 mg, sodium lauryl sulfate - 0.25 mg, magnesium stearate - 1.7 mg.
The composition of the capsule shell: dye Floxin B - 0.138 mg, dye sunset yellow - 0.021 mg, titanium dioxide - 2.16 mg, gelatin - 60 mg.
1 PC. - blisters (1) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2014.
PHARMACHOLOGIC EFFECT
Antifungal agent, has a highly specific effect, inhibiting the activity of enzymes of fungi, dependent on cytochrome P450. Blocking the conversion of lanosterol of fungal cells to ergosterol; increases the permeability of the cell membrane, disrupts its growth and replication.
Fluconazole, being highly selective for cytochrome P450 fungi, practically does not inhibit these enzymes in the human body (in comparison with itraconazole, clotrimazole, econazole and ketoconazole less inhibits oxidative processes dependent on cytochrome P450 in human liver microsomes). Does not have antiadrogenic activity.
Active with opportunistic fungal infections, incl. caused by Candidaspp. (including generalized forms of candidiasis on the background of immunodepression), Cryptococcus neoformans and Coccidioides immitis (including intracranial infections), Microsporum spp. and Trichophyton spp; with endemic mycoses caused by Blastomyces dermatidis, Histoplasma capsulatum (including with immunodepression).
PHARMACOKINETICS
Absorption is high (food does not affect the rate of absorption), bioavailability is 90%. T max in the plasma after oral administration of 150 mg - 0.5-1.5 h and the maximum concentration of C max in the plasma with oral administration is 90% of the concentration in the plasma with IV in the dose of 2.5-3.5 mg / kg.
The connection with plasma proteins is 11-12%. The concentration in the plasma is in direct proportion to the dose. Css in the blood is reached by the 4-5 day of admission (when taken 1 time / day). The introduction of the "shock" dose (on the first day), which is 2 times higher than the usual daily dose, allows reaching a concentration corresponding to 90% Css by day 2. Well penetrates into all body fluids. The concentration of the active substance in breast milk, articular fluid, saliva, sputum and peritoneal fluid is similar to that in plasma. Constant values ​​in the vaginal secretion are reached 8 hours after ingestion and are held at this level for at least 24 hours. It penetrates well into the cerebrospinal fluid (CSF); in fungal meningitis, the concentration in the CSF is about 85% of that in the plasma. In the fluid, epidermis and stratum corneum (selective accumulation), concentrations exceeding serum levels are achieved. After ingestion of 150 mg on day 7, the concentration in the stratum corneum is 23.4 μg / g, and 1 week after the second dose, 7.1 μg / g; concentration in the nails after 4 months of application at a dose of 150 mg once a week - 4.05 μg / g in healthy and 1.8 μg / g in the affected nails. The volume of distribution approximates the total water content in the body.
T 1/2 - 30 hours. It is an inhibitor of the isoenzyme CYP2C9 in the liver. It is excreted mainly by the kidneys (80% - unchanged, 11% - in the form of metabolites). The clearance of fluconazole is proportional to the clearance of creatinine (CC). The pharmacokinetics of fluconazole significantly depends on the functional state of the kidneys, and there is an inverse relationship between T 1/2 and KK. After hemodialysis for 3 hours the concentration of fluconazole in plasma is reduced by 50%.
INDICATIONS
- systemic lesions caused by Cryptococcus fungi, including meningitis, sepsis, lung and skin infections, both in patients with normal immune response, and in patients with various forms of immunodepression (including AIDS patients, organ transplantation);
- prevention of cryptococcal infection in AIDS patients;
- generalized candidiasis: candidemia, disseminated candidiasis (with endocardial damage, abdominal organs, respiratory organs, eyes and urogenital organs), incl. in patients receiving a course of cytostatic or immunosuppressive therapy, as well as in the presence of other factors predisposing to their development - treatment and prevention;
- candidiasis of mucous membranes: oral cavity, pharynx, esophagus, non-invasive bronchopulmonary candidiasis, candiduria, mucocutaneous and chronic oral atrophic candidosis (associated with wearing dentures);
- genital candidiasis: vaginal (acute and recurrent), balanitis;
- prevention of fungal infections in patients with malignant tumors on the background of chemo- or radiation therapy;
- prevention of recurrence of oropharyngeal candidiasis in AIDS patients;
- mycosis of the skin: stop, body, inguinal area, onychomycosis, pityriasis, skin candidiasis infections;
- Deep endemic mycoses (coccidioidosis, sporotrichosis and histoplasmosis) in patients with normal immunity.
DOSING MODE
The drug Fangiflu should be taken internally. Adults , with cryptococcal infections, candidemia, disseminated candidiasis, other invasive candidiasis infections , 400 mg are prescribed on day 1, then 200-400 mg once a day. The duration of treatment depends on the clinical and mycological response ( with cryptococcal meningitis is at least 6-8 weeks).
For the prevention of cryptococcal meningitis in AIDS patients, therapy at a dose of 200 mg / day can be continued for a long time.
With oropharyngeal candidiasis - 50-100 mg 1 time / day for 7-10 days, in patients with immunosuppression - 14 days or more.
To prevent the recurrence of oropharyngeal candidiasis in AIDS patients after completing the full course of primary therapy - 150 mg 1 time / week.
With atrophic oral candidiasis associated with wearing dentures - 50 mg 1 time / day for 14 days in combination with local antiseptic drugs for prosthesis treatment.
In other candidiasis of the mucous membranes (with the exception of genital candidiasis) - 50-100 mg / day, the duration of treatment - 14-30 days.
With vaginal candidiasis - 150 mg once. To reduce the frequency of relapses, use 1 time / month for 150 mg for 4-12 months, sometimes more frequent use may be required.
With balanitis caused by Candida - 150 mg / day once.
For the prevention of candidiasis, the recommended dose of the drug is 50-400 mg / day, depending on the degree of risk of fungal infection. If there is a high risk of generalized infection, for example, in patients with expected severe or persistent neutropenia , the recommended dose is 400 mg / day. The drug Fangiflu is prescribed several days before the expected appearance of neutropenia; after the increase in the number of neutrophils more than 1 thousand / Ојl treatment is continued for another 7 days . For skin lesions, including mycosis of the feet, skin of the inguinal region, and candidiasis , 150 mg once a week or 50 mg once a day, the duration of treatment is 2-4 weeks (up to 6 weeks with foot mycoses).
With pityriiform lichen - 300 mg 1 time / week. for 2 weeks, some patients require a third dose of 300 mg / week, while in some cases it is sufficient to receive a single dose of 300-400 mg; an alternative treatment regimen is to apply 50 mg 1 time / day for 2-4 weeks.
With onychomycosis - 150 mg 1 time / week; Treatment continues until the infected nail is replaced. To re-grow the nails on the fingers and toes, it normally takes 3-6 months and 6-12 months, respectively.
At deep endemic mycoses - 200-400 mg / day for up to 2 years. The duration of therapy is determined individually; it can be 11-24 months with coccidioidomycosis , 2-17 months with paracoccidioidomycosis, 1-16 months with sporotrichosis and 3-17 months with histoplasmosis .
In children , as with similar infections in adults, the duration of treatment depends on the clinical and mycological effect. In children, the drug should not be used in a daily dose that would exceed that of adults. The drug is used daily 1 time / day (use special dosage forms for children). Children with esophageal candidiasis are prescribed 3 mg / kg per day once for at least 3 weeks and for 2 weeks after regression of symptoms; at candidiasis of mucous membranes - 3 mg / kg per day once for at least 3 weeks; in the treatment of generalized candidiasis and cryptococcal infection (including meningitis) - 6-12 mg / kg per day for 10-12 weeks (before laboratory confirmation of the absence of pathogens in the cerebrospinal fluid).
For the prevention of fungal infections in children with reduced immunity , the risk of infection is associated with neutropenia, resulting from cytotoxic chemotherapy or radiation therapy, 3-12 mg / kg / day, depending on the severity and duration of preservation of induced neutropenia.
For newborn infants, the interval between injections is 72 hours, for children 2-4 weeks of age, the same dose is administered at intervals of 48 hours.
In children with impaired renal function, the daily dose of the drug should be reduced (in the same proportional relationship as in adults) according to the degree of renal insufficiency.
In elderly patients in the absence of violations of kidney function should follow the usual dosage regimen. Patients with renal insufficiency (CC less than 50 ml / min) dosage regimen should be adjusted, as indicated below.
In chronic renal failure, a "shock" dose of 50-400 mg is initially administered; with QC more than 50 ml / min, the usual daily dose is prescribed, with KK 11-50 ml / min - 50% of the recommended dose or usual dose 1 time in 2 days; patients on hemodialysis - 1 dose after each dialysis.
SIDE EFFECT
On the part of the digestive system: nausea, diarrhea, flatulence, abdominal pain, taste change, vomiting, rarely - impaired liver function (jaundice, hyperbilirubinemia, increased ALT activity, ACT and APF, hepatitis, hepatocellular necrosis), incl. with a lethal outcome.
From the nervous system: headache, dizziness, rarely - convulsions.
On the part of the organs of hematopoiesis: rarely - leukopenia, thrombocytopenia, neutropenia, agranulocytosis.
Allergic reactions: skin rash, rarely - multiforme exudative erythema (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome), anaphylactoid reactions (including angioedema, face swelling, hives, itching of the skin) .
From the cardiovascular system: an increase in the duration of the QT interval, flicker / flutter of the ventricles.
Other: rarely - a violation of kidney function, alopecia, hypercholesterolemia, hypertriglyceridemia, hypokalemia.
CONTRAINDICATIONS
- hypersensitivity (including other azole antifungal drug in history);
- simultaneous reception of terfenadine (against the background of a constant intake of fluconazole at a dose of 400 mg / day or more) and astemizole;
lactation period.
With caution: liver failure; the appearance of rashes on the background of fluconazole in patients with superficial fungal infection and invasive / systemic fungal infections; simultaneous reception of terfenadine and fluconazole in a dose of less than 400 mg per day; potentially proaritmogenic states in patients with multiple risk factors (organic heart disease, electrolyte balance disorders, concurrent use of drugs that cause arrhythmias); pregnancy.
PREGNANCY AND LACTATION
Use with caution during pregnancy.
Contraindicated during lactation.
APPLICATION FOR FUNCTIONS OF THE LIVER
In chronic renal failure, a "shock" dose of 50-400 mg is initially administered; with QC more than 50 ml / min, the usual daily dose is prescribed, with KK 11-50 ml / min - 50% of the recommended dose or usual dose 1 time in 2 days; patients on hemodialysis - 1 dose after each dialysis.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
With caution: liver failure.
APPLICATION FOR CHILDREN
In children , as with similar infections in adults, the duration of treatment depends on the clinical and mycological effect. In children, the drug should not be used in a daily dose that would exceed that of adults. The drug is used daily 1 time / day (use special dosage forms for children). Children with esophageal candidiasis are prescribed 3 mg / kg per day once for at least 3 weeks and for 2 weeks after regression of symptoms; at candidiasis of mucous membranes - 3 mg / kg per day once for at least 3 weeks; in the treatment of generalized candidiasis and cryptococcal infection (including meningitis) - 6-12 mg / kg per day for 10-12 weeks (before laboratory confirmation of the absence of pathogens in the cerebrospinal fluid).
For the prevention of fungal infections in children with reduced immunity , the risk of infection is associated with neutropenia, resulting from cytotoxic chemotherapy or radiation therapy, 3-12 mg / kg / day, depending on the severity and duration of preservation of induced neutropenia.
For newborn infants, the interval between injections is 72 hours, for children 2-4 weeks of age, the same dose is administered at intervals of 48 hours.
In children with impaired renal function, the daily dose of the drug should be reduced (in the same proportional relationship as in adults) according to the degree of renal insufficiency.
APPLICATION IN ELDERLY PATIENTS
In elderly patients in the absence of violations of kidney function should follow the usual dosage regimen of the drug
SPECIAL INSTRUCTIONS
Treatment should continue until the appearance of clinical-hematologic remission. Premature termination of treatment leads to relapse.
Treatment can be started in the absence of seeding results or other laboratory tests, but if appropriate, a suitable correction of fungicidal therapy is recommended. In the course of treatment, it is necessary to monitor blood counts, kidney and liver function. If there are violations of kidney and liver function, stop taking the drug. The hepatotoxic effect of fluconazole is usually reversible, the symptoms disappear after discontinuation of therapy.
Against the background of taking the drug in patients, there were rare cases of development of exfoliative skin reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis. Patients with AIDS and malignant neoplasms are more likely to develop severe skin reactions with many drugs. If the patient develops a superficial fungal infection of the rash during treatment, which can be associated with the use of fluconazole, the drug should be discontinued. If rashes appear in patients with invasive / systemic fungal infections, fluconazole should be carefully monitored and discarded when bullous lesions or erythema multiforme occur.
It is necessary to control the prothrombin index while using the coumarinic anticoagulants simultaneously.
It is recommended that the concentration of cyclosporin in the blood be monitored in patients receiving fluconazole. in patients with kidney transplantation, fluconazole administration at a dose of 200 mg / day leads to a slow increase in the concentration of cyclosporine in the plasma.
OVERDOSE
Symptoms: hallucinations, paranoid behavior.
Treatment: symptomatic - gastric lavage, forced diuresis. Hemodialysis within 3 hours reduces the plasma concentration by approximately 50%.
DRUG INTERACTION
Increases the effectiveness of coumarin anticoagulants (an increase in prothrombin time when using warfarin - an average of 12%), zidovudine concentration (an increase in side effects of zidovudine), cyclosporine (with fluconazole 200 mg / day), rifabutin (with simultaneous application described cases of uveitis) and phenytoin in a clinically significant degree (with combined use, it is necessary to monitor the concentration of phenytoin in the plasma).
Lengthens T 1/2 theophylline and increases the risk of intoxication (it is necessary to correct its dose).
Increases the concentration of midazolam - increased risk of psychomotor effects (more pronounced when fluconazole is administered orally than intravenously);tacrolimus - risk of nephrotoxicity.
When taking sulfonylurea (chlorpropamide, glibenclamide, glipizide and tolbutamide) simultaneously, you should periodically monitor the blood glucose concentration and, if necessary, correct the dose of hypoglycemic drugs (as fluconazole extends T 1/2 ).
Hydrochlorothiazide increases the concentration of fluconazole in plasma by 40%, rifampicin reduces T 1/2 by 20% and the area under the concentration-time curve (AUC) by 25%. Terfenadine and cisapride increase the risk of arrhythmias, including paroxysms of ventricular tachycardia (torsades de pointes).
TERMS OF RELEASE FROM PHARMACY
Without recipe.
TERMS AND CONDITIONS OF STORAGE
Keep out of the reach of children, dry and protected from light at a temperature not exceeding 25 В° C.
Shelf life - 2 years. Do not use after the expiration date printed on the package.
