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Composition: 1 ml of solution contents Fluconazole 2 mg; Other ingredients: Sodium Chloride, Water for Injections.
Medicine form:
Solution for infusion.
Pharmacotherapeutic group:
Antifungal agent for systemic use. ATC code: J02A C01.
Pharmacological properties:
Pharmacodynamic
Fusys® is the antifungal medicine of general action of bis-triazole type. The mechanism of action of the medicine is following: it depressed specifically the biosynthesis of ergosterol, which is necessary for fungal membranes cells building.
Fusys® is effective against the system infections, caused by Candida and Cryptococcus neoformans. It penetrates through the hematoencephalic barrier; therefore it could be successfully used in treatment of intracranial infections. It is effective in infections, caused by Histoplasma capsulatum, Blastomyces dermatitidis, Coccidioides immitis (including intracranial infections) and in infections, caused by Miсrosporum and Trichophyton.
Pharmacokinetic
The period of the half-life of Fluconazole is approximately 30 hours, that is allows to use it 1 time per day during the course of the treatment with therapeutic effect. The concentration of the active substance in plasma is proportionate to the using dose. 11 – 12 % of Fluconazole connects with plasma proteins. In 90 % of the patients the stable concentration of Fluconazole is reached on 4 – 5 days of everyday usage.
Fluconazole penetrates well in tissues and fluids of the organism. Its concentration in human milk, synovial fluid, spittle, sputum, vaginal secret and peritoneal fluid is equivalent to the concentration in plasma. The concentration in spinal fluid is 50-90% from the plasma level without regard to the inflammation of the cerebral membranes. The concentrations in corneal layer, epidermis, derma and sweat are reached the levels, which exceed plasmas one. The excretion is realized mainly by kidney, approximately 80 % of the administered dose is excreted in unchanged form, 11 % - is excreted with urine as metabolites.
Indications for use:
Systemic infections.
Systemic candidosis: candidemia, disseminated candidosis (mycosis of endocardium, abdominal cavities organs, respiratory systems organs, urogenital organs, eyes.
Systemic infections, caused by Cryptococcus: mycosis of respiratory systems organs, skin, mucous membranes, and cryptococcal meningitis.
Administration and dosage:
Daily dose of Fluconazole is depended on the character and severity of disease.
Untimely stopping of the treatment directs to the recurrences. Cryptococcal meningitis in AIDS patients and recurrent oropharyngeal candidosis require, as usual, long treatment.
For adults in candidemia, disseminated candidosis and other invasive candidoses the usual dose is 400 mg in first day, than – 200 mg per day. Daily dose could be increased for 400 mg depending on clinical situation. The duration of the treatment is depended on patient’s state.
In cryptococcal meningitis and other cryptococcal infections 400 mg is administered in first day, than 200 – 400 mg one time per day. The duration of the course of treatment is depended on clinical and mycological reactions, in cryptococcal meningitis it is minimum of 6 – 8 weeks.
Children
The dosage and course of the treatment for children as well as for adults is indicated individually, depending on clinical and mycological effect. Daily dosage for children should not exceed maximum dose for adults.
In systemic candidosis or cryptococcal infections the recommended dose is 7 mg/kg (saturating dose), than – 3 mg/kg (maintaining dose). In a case of cryptococcal meningitis the dose should be redouble.
In a case of decreased kidney function it is necessary to decrease the daily dose for children.
Infants under 4 weeks
In first weeks of the life Fluconazole is administered as for more elder children in the same dosage (mg/kg), but every 3 days, that is the interval should be 72 hours because in infants Fluconazole is excreted slowly. For children of 3 – 4 weeks the same dose is administered every 2 days with the interval of 48 hours.
For the patients of middle age under the normal kidney function the usual dose could be administered. In a case of depressed kidney function (the clearance of kreatinine is less than 40 ml/minute) the dose should be decreased.
If the function of the kidney is depressed the dose should be decreased according to the extent of disorder (table 1). In a case of single administration (vaginal candidosis) do not change the dose. During the continuous treatment of patients with depressed kidneys function it is necessary to start the treatment from knock-out dose 50 – 400 mg. Than the rate of usage or dose should be changed according to the clearance of kreatinine, namely:
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Clearance of kreatinine, ml/minute |
Dosage: |
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>50 |
Usual dose every 24 hours.
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11 – 50 |
Usual dose every 48 hours or half of the usual dose every 24 hours.
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Regular hemodialysis |
One daily dosage after each course of hemodialysis. |
At the change from the intravenous infusion to oral usage or contra verse do not change the dose. Daily dose is not depend on the usage way. In 100 ml of infusion solution 200 mg of Fluconazole contains in 0,9 % solution of Sodium chloride that is equivalent to 15 mmol of ions of Na+ or Cl-. It is necessary to take in account in patients which are needed in limitation of administration of sodium and fluids.
Intravenous infusion is compatible with such infusion solutions as 20% Glucose solution, Ringer's solution, and solution of potassium chloride in glucose (composition: 1000 ml of the water for injections,
3,8 g of potassium chloride, 33,75 g of anhydrous glucose, 5 g of 0,1 N hydrochloric acid), solution of Sodium Bicarbonate (composition: 1000 ml of the water for injections, 13 g of Sodium Bicarbonate), isotonic solution of Sodium Chloride.In spite of the absence of the intense incompatibility it is not recommended to mix the medicine with the other infusion solution.
Side effects:
As usual Fusys® is good transmitted.
But most often it could be following side effects: headache, stomach pain, diarrhea, meteorism, nausea, vomiting, toxic liver lesion (increasing of alkaline phosphatase level, bilirubin, aminotransferase) and hepatitis appearance. It could be also dizziness, spasms, alopecia, exfoliative skin reactions, change of the leukocytes number (granulocytopenia, agranulocytosis), decreasing of platelet, allergic reactions (skin rush, itch, face edema, anaphylaxis), increasing of level of the cholesterol, triglycerides, plasma potassium; change of the taste.
Contraindications:
- Hypersensitivity to some components of the medicine.
- Periods of the pregnancy and lactation.
Overdosage:
In a case of overdosage it is recommended the symptomatic treatment. Forced diuresis intensifies the excretion of the medicine. The hemodialysis during 3 hours decreases the concentration of the medicine in plasma approximately in 50 %.
Special indications:
The treatment could be started without any results of bacterial inoculation or other laboratory data, but in presence of them it is necessary to correct the therapy.
In rare cases the anaphylaxis may take a place.
Patients, which have increasing of indexes of liver function, should be carefully obtained for determination of the possible liver disease. Although the severe hepatic reactions have took a place rare and there ware no any approval dependence with Fluconazole treatment, but in a case of the appearance of the symptoms, which indicate to liver disease it is necessary to stop Fluconazole usage. As usual hepatotoxic action of Fluconazole is reversible; the symptoms disappear after the ending of the therapy.
If during the therapy of Fluconazole in immunosuppressive patients the skin rush is appeared it is necessary to observe them carefully and in a case of the impairment of the skin reaction one should to stop the treatment by Fluconazole (because of the possibility of Stevens-Johnson syndrome, toxic epidermal necrosis, polymorphous eruption).
Drug interaction:
Oral anticoagulants of cumarine line
The prothrombin time may prolong (12 % by measuring data), therefore in patients, who receive oral anticoagulants the prothrombin time should be controlled.
Oral anti-diabetic medicines of sulfonylurea type
In combined administration Fluconazole prolongs the half-value period of these medicines in healthy volunteers. Therefore it is necessary to take in account the possibility of hypoglycemia.
Thiazide-type diuretics
In healthy volunteers hydrochlorthiazide increases the level of Fluconazole in plasma approximately in 40%. Therefore in combined administration with diuretics it is necessary to take in account this effect.
Fenitoin
The level of Fenitoin increases in plasma significantly. In synchronous administration one should contron its level in plasma.
Rifampicin
During the treatment by Fluconazole of the patients, who received the Rifampicin long time the AUC of Fluconazole absorption decreases in 25 % and the period of half-life – in 20 %. In such cases it is necessary to provide for the possibility of increasing of the Fluconazole dosage.
Cyclosporine
100 mg daily dosage of Fluconazole has not had a reliable action on the level of Cyclosporine in patients, who have had a transplantation of the marrow. According to some reports the level of Cyclosporine increases in patients after kidney transplantation in administration of 200 mg daily dosage of Fluconazole. Therefore in synchronous administration of Cyclosporine and Fluconazoleit is recommended to monitor the level of Cyclosporine in plasma.
Theophylline
In placebo-controlled trial of the interaction of Fluconazole 200 mg per day with Theophylline
during 14 days the plasma cleaners of Theophylline has decreased in 18 %. Therefore it is necessary to observe carefully the patients, who have treated by high doses of Theophylline, and in a case of the determination of toxic action the dose of the medicine should be decreased.
Oral contraceptives
50 mg of Fluconazole has not influenced on the level of combined oral contraceptives in healthy women, 200 mg of Fluconazole has increased the AUC of ethynilestradiol and levonorergosterol in 40% and 24% accordingly. Based on these investigations it is supposed that repeated dose of Fluconazole is not influenced on the effectiveness of combined oral contraceptives.
Terfenadine
Taking in consideration the appearance of severe arrhythmias in patients receiving other azole antifungal medicines synchronously with Terfenadine, it is necessary the carefully observation under the patient.
Zidovudine
It was observed the increasing of the AUC of Zidovudine in plasma in 20 - 70%. Therefore it is necessary to control the level of Zidovudine in plasma and correct its dose.
Antipyrine
50 mg of Fluconazole do not influence on the Antipyrine metabolism.
Meal, cimetidine, antacids and irradiation of the patients after marrow transplantation do not influence on the Fluconazole absorption.
There ware no any other trials, but doctor should take in account the possibility of interaction between Fluconazole and other medicines.
Storage conditions and shelf-life:
Keep at the temperature not more 250С. Keep out of reach of children in protected from the light place.
Shelf-life is 2 years.
Conditions of supply:
On prescription
Package:
50 ml or 100 ml in vial; 1 vial is in plastic sachet in carton box.
Manufacturer:
Kusum Healthcare Pvt. Ltd.
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