PATIENT INFORMATION LEAFLET
INTERNATIONAL NONPROPRIETARY NAME
Description: hard gelatin capsules, size 1, with opaque light green cap and body, containing white to almost white powder.
Active ingredient: fluconazole 150 mg.
Excipients: microcrystalline cellulose, lactose monohydrate, magnesium stearate, sodium laurilsulfate.
Composition of capsule shell: black iron oxide, titanium dioxide, yellow iron oxide, gelatin.
PHARMACOLOGICAL PROPERTIES PHARMACODYNAMICS
Flucosan is an antifungal agent of triazole group. Fluconazole, drug active substance, is a strong selective inhibitor of sterol synthesis in cell fungus membranes. The mechanism of action is due to P450 cytochrome blockade. Fluconazole blocks the fungus lanosterol cell transformation in ergosterol; increases the cell memb- rane penetration, disturbs its growth and replication. Being highly selective for P450 fungal cytochrome, prac- tically doesn't inhibit these ferments in human body (comparing with itraconasole, clotrimazole, econazole and ketoconazole in less rate inhibits dependent on P450 cytochrome the oxidizing processes in human hepatic microsomes). It doesn't have antiandrogen activity.
It is active during opportunistic mycoses, including caused Candida spp. (including generalised candidiasis forms against immunodepression), Cryptococcus neoformans and Coccidioides immitis (including intracranial infections), Microsporum spp. and Trichophyton spp.; at endemic mycoses, caused by Blastomyces dermatitidis, Histoplasma capsulatum (including at immunodepression). The drug is used for prevention of fungal infections in patients with malignant neoplasms during treatment with cytostatic agents or radiation treatment, in cases of organ transplantation and in other cases of immune system suppression and the risk of fungal infection development.
The drug is quickly and almost completely absorbed from gastrointestinal tract (meal doesn't affect the absorption speed). Bioavailability - 90%. Maximum concentration is achieved in 0.5-1.5 h after fasting administration. Binding with plasma proteins is 11-12%. It well penetrates in all body fluids. Concentration of active substance in human milk, joint fluid, saliva, sputum and peritoneal fluid is similar to those in blood plasma. Constant values in vaginal secreta is achieved in 8 h after oral administration and remains on this level not less than 24 h. Concentrations, exceeding serumal (selective uptake) are achieved in sudoral fluid, epidermis and in horny layer. 80% in unchanged form are excreted with kidney, remaining part in form of metabolites. Circulating metabolites are not observed. Half-life period is about 30 h.
Pharmacokinetics of fluconazole significantly depends on renal function, and inverse proportion exists between half-life time and creatinine clearance. After hemodialysis for 3 h the concentration in blood plasma of Fluconazole is reduced by 50%.
DOSAGE AND ADMINISTRATION
Capsules for oral administration. Capsule is swallowed whole independently on meal intake. Daily dose of fluconazole depends on nature and severity of fungoid infection.
Treatment of infections demanding repeated administration of the medicine should be prolonged till clinically and laboratory confirmed disappearance of sings of fungoid infection.
Administration of the product in a single dose in children under 18 years old and in patients older than 60 years without a doctor's prescription is not recommended.
Vaginal candidiasis: 150 mg is taken orally in a single dose.
Preventive treatment of vaginal candidiasis recurrences: 150 mg once a month. Therapy duration is determined individually; it varies from 4 to 12 months. More frequent administration of the product can be required for some patient.
Balanitis, caused by Candida: 150 mg is taken orally in a single dose.
For preventive of Oropharyngeal candidiasis recurrences in patients with AIDS 150 mg of the product once a week can be prescribed after the complete course of primary therapy.
For skin mycoses (including foot mycoses, smooth skin mycoses, skin of inguinal region and candidiasis infections): 150 mg once a week. Duration of therapy in usual cases is 2-4 weeks, however, for feet mycoses - up to 6 weeks.
Onychomycosis: 150 mg once a week. Treatment course continues till complete replacement of the infected nail with healthy nail. For repeated nails growth on hand and feet fingers is normally required 3-6 months and 6-12 months accordingly.
Elderly patients without renal dysfunction may administer Flucosan according to the usual dosage regimen.
No dosage adjustment required in case of a single administration of the preparation.
Used below frequency parameters of side effects are classified in the following way:
frequently (from ≥ 1/100 to < 1/10), infrequently (from ≥ 1/1000 to < 1/100), rarely (from ≥ 1/10000 to < 1/1000). From digestive system: frequently - nausea, diarrhea, abdominal pain; infrequently - appetite reduction, con- stipation, meteorism, toothache; rarely - hepatic function disorder (scleral icterus, icterus, hyperbilirubinemia, increase in activity of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase).
From nervous system: frequently - headache; infrequently - dizziness, hypernormal fatigability; rarely - convul- sions.
From blood-formingorgans: rarely - leukocytopenia, thrombocytopenia (bleedings, petechia), neutropenia, ag- ranulocytosis.
Allergic reactions: frequently - skin rash; rarely - Erythema multiforme (including Stevens Johnson's syndro- me), toxic epidermal necrolysis (Lyell's syndrome), anaphylactoid reactions.
Other: rarely - renal function disorder, alopecia, hypercholesteremia, hypertriglyceridemia, hypokalemia.
Flucosan is prescribed with caution to patients with hypersensitivity to thiazole compounds due to possible cross-sensitivityreactions.
Treatment with fluconazole should continue till the appearance of clinical hematological remission. Premature treatment discontinuation leads to recurrences.
Treatment may be started at absence of inoculation results or other laboratorial analysis, but the appropriate correction of fungicide therapy is recommended at their presence.
Blood values, renal and hepatic functions are necessary to control during treatment. It is necessary to observe patients in which these values disorder during treatment, with purpose of revealing signs of more severe hepa- tic lesion. Drug administration should be discontinued during onset of renal function disorder. Hepatotoxic action of fluconazole is usually reversible and the symptoms disappear after stopping therapy.
At onset of cutaneous eruptions in patients it is necessary to conduct thorough observation, and in case of skin reaction progress the treatment should be stopped (danger of progress of Stevens Johnson's syndrome, toxic epidermal necrolysis, erythema multiforme).
In case of rash appearance which can be connected with fluconazole use in patient, receiving the treatment of surfactant fungal infection, the drug should be cancelled. In case of rash appearance in patients with invasive/ systemic fungal infections, they should be observed, and fluconazole should be cancelled in case of appea- rance of bullous lesions.
It is prescribed with caution in patients with renal function disorder, neonates, AIDS patients (and other status with weakened immunity), as well as to patients with potentially proarrhythmic states.
INFLUENCE ON ABILITY TO DRIVE AND OPERATE MECHANISMS
Flucosan doesn't influence on the ability to drive and for work performance, demanding a high speed of psychomotor reactions.
PREGNANCY AND LACTATION
No adequate clinical studies of fluconazole administration during pregnancy have been performed. Administration of Flucosan in pregnancy is possible only in cases when the potential benefit for the mother outweighs the risk for the fetus.
Fluconazole is found in breast milk in the same concentration as in plasma. Therefore its prescription in lac- tation period is not recommended.
Administration of the drug in children under 18 years old without doctor`s prescription is not recommended.
Fluconazole strengthens the pharmacological action of histamine preparations (astemizole, terfenadine); an- xiolytics, referring to benzodiazepine group of short action period (midazolam, triazolam); rifabutin, cisapride, phenytoin, zidovudine, tacrolimus, cyclosporine; prolongs the half-life period of theophylline and increases the development risk of intoxication, that requires the correction of its dose.
Hydrochlorothiazide increases fluconazole concentration level in plasma, at concomitant administration with rifampicin the reduction of fluconazole half-life period from blood plasma is reported.
Fluconazole increases the concentration level in blood plasma, and also increases the half-life period of oral hypoglycemic drugs, sulfonylurea derivatives (glibenclamide, glipizide, tolbutamide). During concomitant administration of these drugs, sugar level in blood should be thoroughly controlled for prevention of hypoglycemicdevelopment.
During concomitant administration of fluconazole with oral contraceptives the variability of concentration level of hormones is possible (estradiol, levonorgestrel), at concomitant administration of these drugs it is neces- sary to conduct more thorough control of female patients' status for prevention of possible side effects deve- lopment.
It increases the efficacy of coumarinic anticoagulants, increase of prothrombin time is possible, resulting in bleeding development (hematoma, nose bleeding and GIT, hematuria, melena).
The antagonist character of their interaction should be considered at concomitant administration of flucona- zole and amphotericin B, however, in practice the interaction result is determined by the substance which was injected earlier and the kind of pathogen fungus.
Symptoms: nausea, vomiting, diarrhea, in more severe cases - convulsions.
Therapy: symptomatic. Gastric lavage, artificial diuresis. Hemodialysis during 3 hours reduces concentration in plasma by about 50%.
Hard gelatin capsules. 1 or 2 capsules in a blister. 1 blister with the enclosed leaflet in a carton box.
Store at temperature not exceeding 25ºС. Keep out of reach of children!
3 years from the manufacturing date. Do not use after expiry date.
Sold without prescription.
СLARACTIVE is a product and a trade mark of "Sanolife", Great Britain.
“WORLD MEDICINE İLAÇ SAN. VE TİC. А.Ş.”, TURKEY