Amycasol

Amycasol

International Non-Proprietary Name
Fluconazole

Pharmaceutical Form
Solution for infusion

Ingredients
1 ml solution contains:
Active ingredient: fluconazole - 2 mg.
Auxiliary substances: sodium chloride, water for injections

Description
Colorless transparent liquid

Pharmacotherapeutic group
Antifungal agent

Pharmalogical properties

Pharmacodynamics:
Fluconazole is a triazole antifungal agent that is a selective inhibitor of sterol biosynthesis in fungal cells. The drug has an action in mycosis, caused by Candida spp., Cryptococcus neoformans. Microsporum spp., Trichophyton spp., Blastomyces dermatidis, Coccidioides immitis, and Histoplasma capsulatum.

Pharmacokinetics:
Following intravenous administration, fluconazole penetrates well into the body tissues and body fluids. The drug concentration in saliva and sputum are similar to its level in plasma. In patients with fungal meningitis the concentrations of fluconazole in the cerebrospinal fluid can reach up to 80% the ones in the plasma.
The fluconazole plasma concentrations have the direct relation to the drug dosage. Ninety percent level of the equilibrium concentration is achieved in 4-5 days after a number of administrations in the amount of one dose per day.
On the first day, administration in the dosage that twice the usual daily dose allows to achieve such plasma concentrations that approach 90% of the equilibrium concentrations values by the second day. The apparent volume of distribution approaches the total fluid volume in the body. Little portion of fluconazole (11-12%) binds to plasma proteins. Elimination half-life of the drug is extended (30 hours).
Fluconazole is excreted from the body mainly through kidneys; and approximately 80% of the administered dose is excreted unchanged. The clearance of fluconazole is directly proportional to creatinine clearance. No metabolites in peripheral blood were detected.

Indications
Used for treating the following diseases:

•  Cryptococcosis: cryptococcal meningitis, cryptococcal lung disease and cutaneous cryptococcus: prevention of cryptococcosis relapse in AIDS patients, in organ transplantation or other immunodeficiency cases.
• Generalized candidiasis: candidemia, disseminated candidiasis and other forms of Invasive candidiasis (abdominal cavity infections, endocardium infections, eye infections, as well as respiratory and urinary tract infections).
• Mucosal candidiasis: oral cavity infections, pharynx infections, esophagus infections, non-invasive bronchopulmonary infections, and candiduria.
• Vaginal candidiasis — acute vaginal or chronic recurrent vulvovaginal candidiasis.
• Prevention of fungal infections in patients with malignant tumors, who are predisposed to such infections because of cytostatic chemotherapy or radiation therapy.

Contraindications
The administration of fluconazole is contraindicated in patients with  hypersensitivity reactions to the drug or similar structure azole compounds.
Co-administration of terfenadine, astemizole, and cisapride is contraindicated.
Contraindicated during breast-feeding.

Use with caution
Hepatic insufficiency, development of rashes during treatment with fluconazole in patients with superficial fungal infection and invasive/systemic fungal infections, potential pro-arrhythmogenic disorders in patients with multiple risk factors (organic heart disease, electrolyte imbalance, concomitant use of drugs, causing cardiac arrhythmias),and pregnancy.

Pregnancy and breastfeeding
The administration of the drug is contraindicated in pregnancy, the exceptions are severe, generalized and potentially life-threatening fungal infections.

Administration and dosage
Fluconazole is a solution for injections intended for intravenous drip at a rate no more than 20 mg (10 ml) per min. When switching from intravenous administration to capsules and vice versa, there is no need to change the daily dose.
Solution for infusion is compatible with the following solvents: 20% glucose solution, Ringer’s solution, Hartmann's solution, potassium chloride in glucose, 4.2% Sodium bicarbonate solution, aminofuzin, isotonic sodium chloride solution.
Fluconazole infusions can be performed by using conventional transfusion tools with one of the above mentioned liquids.

Administration in Adults
In cryptococcal infections the usual fluconazole dose is 400 mg once a day on the first day of treatment, further - 200-400 mg once a day. Duration of treatment in patients with cryptococcal infections depends on the clinical efficiency, confirmed by mycological examination; and typically ranges from 6 to 8 weeks. In preventing the relapse of cryptococcal meningitis in AIDS patients after the completion of a full course of the primary treatment, fluconazole is administered in doses at least 200 mg per day for a prolonged period.
In candidemia, disseminated candidiasis and other invasive candida infections, the daily dose is 400 mg during the first day and increased to 200 mg on subsequent days. Depending on the clinical efficiency of the drug, the dose may be increased to 400 mg/day. The duration of treatment depends on the clinical efficiency.
In oropharyngeal candidiasis, including patients with impaired immunity, the usual dose is 50-100 mg once a day for 7-14 days. If necessary, the treatment period can be extended, especially in severe immunity disorders.
In case of other candida infections, such as esophagitis, non-invasive bronchopulmonary infections, candiduria, cutaneous candidiasis and mucosal candidiasis, the usual daily dose is 50-100 mg within 14-30 days.
In preventing fungal infections in patients with malignant tumors, the fluconazole dose should be 50 mg once a day as long as the patient under an increased risk because of cytostatic therapy or radiotherapy.

Administration in Children
As in case of similar infections in adults, the duration of treatment depends on the clinical and mycological effect. For children, the daily dose should not exceed the one administered in adults. Fluconazole is administered on a daily basis once a day.
In mucosal candidiasis, the recommended fluconazole dose is 3 mg/kg/day. On the first day, for faster achievement of permanent equilibrium concentrations, a loading dose of 6 mg/kg may be prescribed.
In treating generalized candidiasis and cryptococcal infection, the recommended dose is 6-12 mg/kg/day depending on the severity of the disease.
For prevention of fungal infections in immunosuppressed patients, in whom the risk of infection is associated with neutropenia and developed as a result of cytotoxic chemotherapy or radiation therapy, the drug is administered in the amount of 3-12 mg/kg/day, depending on the severity and duration of the induced neutropenia retention (see the dosage for adults; in children with renal insufficiency - see dosage in patients with renal insufficiency).

Administration in children aged 4 weeks and less
In newborns fluconazole is excreted slowly. During the first 2 weeks of life the drug is administered in the same dose (mg/kg) as the one for older children but with 72-hour intervals. For children aged 3 and 4 weeks the same dose should be administered every 48 hours.

Administration in Elderly
If there is no impaired renal function, one should adhere to usual drug dosage recommendations. When administered in patients with impaired renal function (creatinine clearance of < 50 ml/min), the dosage should be adjusted, as specified below.

Administration in patients with renal insufficiency
Fluconazole is excreted mainly through the kidneys unchanged. In single dose use, no dosage amendments are required. In case of repeated administration of the drug in patients (including children) with impaired renal function it is recommended to initially infuse a “loading” dose from 50 mg to 400 mg. After infusing the loading dose, the daily dose (depending on the prescription) is defined based on the following table:

Patients who are permanently on dialysis    100 % after each dialysis

Side effects
On the digestive system: nausea, diarrhea, flatulence, abdominal pain, taste disturbance, vomiting, rarely –liver function disorder (yellow sickness, hyperbilirubinemia, increased aminotransferase and alkaline phosphatase levels, hepatitis, hepatocellular necrosis), including fatal case.
On the nervous system: headache, dizziness, rarely – convulsions.
On hematopoietic organs: rarely – leukopenia, thrombocytopenia, neutropenia, agranulocytosis.
In case of overdose, a symptomatic therapy will  be sufficient.
Fluconazole is excreted primarily through the kidneys: forced diuresis can apparently accelerate the excretion of the drug from the body. After a three-hour hemodialysis, the fluconazole concentration in plasma is reduced by approximately 50%.

Interaction with other drugs
Anticoagulants: in patients receiving fluconazole and coumarin anticoagulants, careful monitoring of prothrombin time is required due to the risk of its increase.
Oral hypoglycemic agents (sulfonylurea derivatives: fluconazole may extend the period of the half-life of sulfonylurea derivatives, therefore, in case of their co-administration the possibility of hypoglycemia should be considered.

Release form
Solution for infusion 2 mg/ml. -  100 ml