Active substance: Fluconazole; 1 tablet contains Fluconazole 150 mg. Additional ingredients: Lactose, MCC PH 102, PVP K- 30, Sodium Starch Glycolate, Cross Carmellose Sodium, Magnesium Stearate, Purified Talc.

INDICATIONS:

Infections, caused by Candidas, including generalized candidosis, including candidemia, disseminated candidosis and other forms of invasive candidal infections (candidal infection of endocardium, eye, respiratory and urinary tract); mucous membrane candidiasis, including oral cavity, throat and esophagus; non-invasive bronchopulmonary candidal infections; candiduria; mucocutaneous and chronic atrophic candidiasis of tunica mucosa of mouth (caused by dental prosthesis wearing); genital candidiasis  vaginal candidiasis (acute or recurrent ), prophylaxis of vaginal candidiasis recurrence (in occurrence frequency of 3 or more times per year), and also of candidal balanitis; cryptococcal meningitis and infections of other localisations; dermatomycosis, including tinea pedis, tinea cruris, tinea unguium (onychomycosis), and also pityriasis versicolor; deep endemic mycosis, including coccidioidomycosis, paracoccidioidomycosis, sporotrichosis and histoplasmosis; fungal infections prophylaxis (cryptococcosis, oropharyngeal candidiasis) in patients, who receive cytostatic or radiation therapy, in patients with AIDS.

DOSAGE:

Tablets for oral use. The daily dosage depends on character and severity of fungal infection. The treatment of infections, which require repeated usage of the preparation, must be continued until clinic-laboratory effect reaching (decay of fungal infection). In candidemia, disseminated candidosis and other invasive candidosis the usual dose is 400 mg during the first day, then – 200 mg per day. The daily dose can be increased up to 400 mg per day if there is a need. For adults in oropharyngeal candidiasis it is usually administered 50-100 mg of Fluconazole 1 time per day during 7-14 days. In patients with acute depressed immunity the treatment is prolonged if it is necessary. In atrophic candidiasis of tunica mucosa of mouth caused by dental prosthesis wearing the preparation is administered in 50 mg dose 1 time per day during 14 days concurrently with local antiseptic drugs for dental prosthesis treatment. In other mucous membrane candidiasis (except generalized candidosis), for example esophagitis, non-invasive bronchopulmonary candidal infections; candiduria, cutis and mucous membrane candidiasis an effective dose is usually 50-100 mg in the treatment duration of 14-30 days. For prophylaxis of oropharyngeal candidiasis recurrence in patients with AIDS after the course of primary therapy by Fluconazole it is administered 150 mg 1 time per week. In vaginal candidiasis Fluconazole is used in 150 mg single dose per oral. For reduction of disease recurrence rate the preparation is used in 150 mg dose 1 time per month. The therapy duration is determined individually (from 4 to 12 months). In some cases usage frequency is increased. In balanitis, caused by Candida fungis, Fluconazole is administered per oral in 150 mg single dose. For candidiasis prophylaxis the recommended dose is 50-400 mg 1 time per day depending on the degree of risk of fungal infection development. In presence of high risk of generalized infection, for example in patients with foreseen marked and long-term neutropenia, the recommended dose is 400 mg 1 time per day. Fluconazole is administered before several days to foreseen neutropenia occurrence; after increased number of neutrophilic granulocytes over 1000 in 1 mm3 the treatment is prolonged for 7 days more. In cryptococcal meningitis and cryptococcal infections of other localisations it is usually administered 400 mg in the 1st day, and the treatment is continued in 200-400 mg dose 1 time per day. The treatment duration in cryptococcal meningitis is usually not less than 6-8 weeks. For prophylaxis of cryptococcal meningitis recurrence in patients with AIDS (after the end of the course of primary treatment) the therapy by Fluconazole in 200 mg dose per day can be prolonged. In dermatomycosis, including tinea pedis, tinea cruris and in candidal infections the recommended dose is 150 mg 1 time per week or 50 mg 1 time per day. The therapy duration as usual is 2–4 weeks, but in mycisis of legs it may be necessary more long-term treatment (up to 6 weeks). In pityriasis versicolor the recommended dose is 300 mg 1 time per week during 2 weeks; some patients need the 3rd dose of Fluconazole  300 mg, whereas in some cases it is enough a single dose of 300-400 mg of the preparation. Alternative treatment scheme is the preparation usage of 50 mg 1 time per day during 24 weeks. In onychomycosis (tinea unguium) the recommended dose is 150 mg 1 time per week. The treatment should be continued until change of affected nail on health one. For repeated fingernail and toenail growth it is usually necessary 3-6 and 6-12 months correspondingly, but growth rate may be varied within wide diapason in different people and in dependence on age. In deep endemic mycosis it may be necessary long-term (up to 2 years) administration of the preparation in 200-400 mg dose per day. The therapy duration is determined individually; it is usually 11-24 months in coccidioidomycosis, 2-17 months in paracoccidioidomycosis, 1-16 months in sporotrichosis and 3-17 months in histoplasmosis. For the treatment of elderly patients in absence of kidney insufficiency symptoms the preparation is used in usual dose. For patients (including children) with kidney dysfunctions in multiuse of the preparation it is necessary to use a loading dose that is from 50 to 400 mg. The daily dose is determined by the table (depending on indexes) after loading dose usage.

At the change from intravenous infusion to oral usage or contra verse it is not necessary to change the daily dose. For children less than 7 years old Fluconazole is administered by the doctor’s recommendation. The daily dose for children does not exceed the dose for adults. In mucous membrane candidiasis the recommended dose of Fluconazole for children is 3 mg/kg. In the first day it may be used a loading dose of 6 mg/kg for faster reaching of stable balanced concentration. For the treatment of generalized candidosis and cryptococcal infections the dose of Fluconazole for children is 6-12 mg/kg per day depending on the disease severity. For fungal infection prophylaxis in patients with depressed immunity in which the risk of infection development is related to neutropenia that is a result of cytostatic chemical or radiation therapy, the preparation is administered 3-12 mg/kg/day depending on severity and keeping period of induced neutropenia. The duration of the treatment by Fluconazole for children depends on results of mycological examination and clinical presentation. It is determined individually.

ADVERSE REACTIONS: Central and peripheral nervous system: headache, dizziness, convulsion, change of taste. Cardio-vascular system: QT-interval lengthening, paroxysmal ventricular tachycardia of the “pirouette” type. Gastrointestinal tract: stomach ache, diarrhoea, dyspepsia, nausea, vomiting. Liver and bile-excreting system: often – toxic hepatic impairment, including single cases of fatal outcome, increase of levels of alkaline phosphatise, bilirubin, alanine aminotransferase (ALT) and aspartate aminotransferase (AST); sometimes – hepatic incompetence, hepatitis, hepatocellular necrosis, jaundice. Laboratory data: leucopenia, including neutropenia and agranulocytosis, thrombocytopenia, hypercholesterolemia, hypertriglyceridemia and hypokaliemia. Immune system: anaphylaxis, including angioneurotic oedema, face oedema and skin itch, urticaria. Skin and its appendixes: alopecia, exfoliative skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrosis.

Drug interactions:

Patients who concurrently use other drugs must consult a doctor before the treatment start. Flutuff intensifies anticoagulants action, therefore in concurrent usage with cumarin anticoagulants it is necessary a precise control of prothrombin time. In oral Midazolame the usage of Fluconazole can cause significant increasing of Midazolame concentration and psychomotor action appearance. If patient, who receive Fluconazole treatment, need benzodiazepine administration the dose of benzodiazepine should be reduced and patient must be on precise examination. In concurrent usage of Fluconazole and Cisapride it was reported untoward cardiac reaction, including paroxysmal ventricular tachycardia of the “pirouette” type. Cisapride is contraindicated in patients, who receive Fluconazole. Flutuff increases Cyclosporine concentration in their concurrent usage. During Fluconazole treatment it is recommended to control concentration of Cyclosporine in blood. Multiuse of hydrochlorthiazide increases Fluconazole concentration in plasma approximately on 40%, but it is not necessary to change the dosage regimen of Fluconazole in patients who concurrently use diuretics. Flutuff does not influence on efficacy of combined oral contraceptives. Concurrent usage of Fluconazole and Fenitoin may be accompanied by Fenitoin concentration increase up to significant clinical level. If there is need of concurrent usage of both preparations then it should be a control of Fenitoin level and its adjustment for providing of therapeutic concentration in plasma. Rifabutin level in blood serum is increased as a result of Fluconazole and Rifabutin interaction. In concurrent usage of Fluconazole and Rifabutin it was reported about uveitis cases. In concurrent usage of Fluconazole and Rifampicin Fluconazole dosage should be increased. In concurrent usage with per oral sulfonylurea drugs (chlorpromide, glybenclamide, glipizide and tolbutamide) Flutuff prolonges their half-excretion period. Flutuff and oral sulfonylurea drugs can be concurrently used in patients with insular diabetes, but it is necessary to take into account possible hypoglikemia development. Flutuff intensifies Tacrolimus concentration in plasma. In concurrent usage of Fluconazole and Tacrolimus there were reported about cases of nephrotoxicity increasing. Terfenadine is contraindicated in patients who receive Flutuff. During Fluconazole treatment of patients, who receive high doses of Theophylline or who have an increased risk of Theophylline toxic actions, it is necessary to control appearance of symptoms of Theophylline overdosage, because Fluconazole decreases an average clearance speed of Theophylline from plasma. Zidovudine concentration in blood is increased in case of concurrent usage with Fluconazole. Usage of Fluconazole in patients, who concurrently receive astemizole or others drugs, which are metabolized by cytochrome system P450, can be accompanied by increased concentrations of these drugs in blood serum. Flutuff used simultaneously with meal, cimetidine and antacids does not change its absorption properties.

AIDS patients are more susceptible to severe skin reactions upon usage of a lot of many drugs. If skin rash, which may be associated with Fluconazole usage, appears in patients who are on the treatment of superficial fungal infection, it is necessary to contraindicate the preparation. If skin rash appears in patients with invasive/systemic fungal infections, it is necessary to observe the patients’ states and stop Fluconazole usage in a case of polymorphic erythema. In a case of successful treatment of chronic nail infection by Fluconazole it is sometimes observed a change of nail shape.

Overdose:

Symptoms: hallucinations and paranoiac behavior. Treatment: treatment is symptomatic (including gastric lavage and supporting therapy). Fluconazole is mainly excreted with urine, therefore forced diuresis can accelerate the preparation excretion. Dialysis during 3 hours decreases the concentration of the preparation in plasma approximately on 50%.

CONTRAINDICATIONS:

Flutuff should not be administered in individual hypersensitivity to Fluconazole or other agents similar to azole substance by chemical structure. Concurrent usage of Terfenadine is contraindicated in patients who use Flutuff. Cisapride is contraindicated in patients who receive Flutuff. Children age less than 7 years old. Lactation and pregnancy periods.

PHARMACOLOGICAL PROPERTIES:Pharmacodynamics: Flutuff is an antifungal agent of triazole substances. Fluconazole has an intensive antifungal action and specifically blocks fungal sterol synthesis. It has a specific action against fungal enzymes, which are depended on cytochrome P450. It is active against different Candida spp. (including visceral candidiasis), Cryptococcus neoformans (including intracranial infections), Microsporum spp. and Trichophytum spp. Fluconazole is also active against endemic mycosis: Blastomyces dermatitidis, Coccidioides immitis (including intracranial infections), Hystoplasma capsulatum. Pharmacokinetics: After per oral usage it is well absorbed in gastrointestinal tract, general bioaviability exceeds 90%. Meal does not influence on Fluconazole absorption. Maximal concentration in plasma is reached in 0.5–1.5 hours after intake. The period of half-excretion of Fluconazole from plasma is 30 hours, that allows to use it 1 time per day during the treatment course and provides the therapeutic effect in vaginal candidiasis after a single use of the preparation. The concentration of active substance in plasma is proportionate to the used dose. 11–12% of Fluconazole binds with plasma proteins. In 90% of patients the stable concentration of Fluconazole is reached on 4–5 days of everyday single usage. This effect is reached to 2nd day of the treatment after a loading dose (twice a day) in the first day of the treatment. Fluconazole well penetrates in fluids of the organism. Its concentrations in spittle and sputum are equivalent to the concentrations in plasma. The concentration of Fluconazole in spinal fluid is reached 80% from its concentration in plasma. The concentrations in epidermis, derma and sweat are reached the levels, which exceed plasma’s ones. It is excreted mainly with urine, and approximately 80% of it is excreted in unchanged form. Fluconazole clearance is directly proportional to creatinine clearance.

PHARMACEUTICAL CHARACTERISTICS:

General physic-chemical properties:

White round, flat beveled edged uncoated tablets with breack line on one side.

Shelf-life:

Shelf-life is 3 years.

Storage:

Keep it out of reach of children, in a dry, dark place at temperature below 25 °C.

Package:

4 tablet in blister. 1 blister in a carton box.

Conditions of supply:

By prescription.