Disorel-Sanovel - instructions for use, dose, side effects, contraindications

highly specific action, inhibiting the fungal enzyme 14-alpha-demethylase. Blocking the conversion of lanosterol of fungal cells to ergosterol - the main component of cell membranes of fungi; increases the permeability of the cell membrane, disrupts its growth and replication.

Active with opportunistic fungal infections, incl. caused by Candida spp. (including generalized forms of candidiasis on the background of immunodepression), Cryptococcus neoformans, Microsporum spp. and Trichophyton spp; with endemic mycoses caused by Blastomyces dermatidis, Histoplasma capsulatum and Coccidioides immitis (including immunosuppression).

Pharmacokinetics:

After oral administration fluconazole well absorbed, food intake does not affect the absorption of fluconazole, its bioavailability is 90%.

The time of maximum concentration (TCmax) is reached in 0,5 - 1,5 hours after administration. The maximum concentration (Cmax) of fluconazole after ingestion, fasting 150 mg is 90% of the plasma concentration when given intravenously at a dose of 2.5 to 3.5 mg / kg.The connection with plasma proteins is 11-12%. Concentration in plasma

is in direct proportion to the dose. Equilibrium concentration is achieved by 4-5 days of treatment with the drug (with the administration of 1 time / day).

The introduction of the "shock dose" (on the first day), 2 times higher than the usual daily dose, allows you to reach a concentration level corresponding to 90% of the equilibrium concentration by the second day.

Fluconazole well penetrates into all body fluids, including cerebrospinal fluid. The concentration of the active substance in breast milk, articular fluid, saliva, sputum and peritoneal fluid is similar to its concentration in plasma. The equilibrium concentration in the vaginal secretion is reached 8 hours after ingestion and is kept within this value for at least 24 hours. With fungal meningitis, the fluconazole content in the cerebrospinal fluid reaches 80% of its plasma content. Concentrations exceeding serum levels are achieved in the flowing fluid, the epidermis and the stratum corneum.

The volume of distribution approximates the total water content in the body.

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). Less than 5% of fluconazole is metabolized on first passage through the liver.The clearance of fluconazole is proportional to the creatinine clearance. The half-life (T1 / 2) of fluconazole is 30 hours. Fluconazole metabolites are not found in the peripheral blood.

Indications:

-genital candidiasis: vaginal candidiasis (acute and chronic

relapsing), prophylactic use to reduce the frequency of recurrences of vaginal candidiasis (3 or more episodes per year); Candidiasis balanitis;

-prophylaxis of fungal infections in patients with malignant neoplasms that are predisposed to such infections as a result of chemotherapy with cytostatics or radiation therapy;

- mikozy skin, including mycosis of the feet, body, inguinal area; pityriasis (multicolored) lichen, onychomycosis; candidiasis of the skin.

Contraindications:

hypersensitivity to fluconazole and the components of the drug (including other azole antifungal drugs);
simultaneous reception of terfenadine (against the background of a constant intake of fluconazole 400 mg / day or more), cisapride, astemizole and other drugs that extend the Q-T interval and increase the risk of severe rhythm disturbances;
lactose intolerance;
deficiency of lactase;
glucose-galactose malabsorption;
lactation period;
Children under 3 years old (for this dosage form).

Carefully:hepatocellular and / or renal failure, the appearance of rash on the background of fluconazole in patients with superficial fungal infection and invasive / systemic fungal infections, concurrent administration of terfenadine and fluconazole at a dose of less than 400 mg / day, potentially pro-rhythmic conditions in patients with multiple risk factors (organic heart disease, electrolyte balance disorders, simultaneous intake of medications that cause arrhythmias); patients with intolerance to acetylsalicylic acid, pregnancy.

Pregnancy and lactation:

The use of the drug in pregnant women is not recommended, except for severe or life-threatening forms of fungal infections, when the potential benefit from using fluconazole for the mother is significantly higher than the risk for the fetus.

Since the concentration of fluconazole in breast milk and in plasma is the same, it is not recommended to use the drug during lactation.

Use in Pediatrics

Studies of the drug in children younger than 16 years were not conducted.In such cases, the drug is prescribed only if necessary antifungal therapy and the absence of an alternative agent.

Dosing and Administration:

Inside. The daily dose depends on the nature and severity of the fungal infection.

Adults and children over 16 years of age:

With vaginal candidiasis fluconazole taken once inside the dose of 150 mg. To reduce the frequency of recurrences of vaginal candidiasis, the drug can be used in a dose 150 mg 1 once in month. The duration of therapy is determined

individually; she is varies from 4 up to 12 months. Some patients may

more frequent use is required.

With balanitis caused by Candida spp., fluconazole is administered orally once a day at a dose of 150 mg per day.

For the prevention of candidiasis in patients with malignant neoplasms the recommended dose of fluconazole is 150-450 (1-3 capsules) mg 1 time / day, depending on the degree of risk of fungal infection.

With mycoses (including candidiasis) of the skin, including mycosis of the feet, the skin of the inguinal region, the recommended dose is 150 mg 1 once a week. Duration of therapy in usual cases is 2-4 weeks, however, with foot mycoses, longer therapy (up to 6 weeks) may be required.

With pityriasis - 300 mg (2 capsules) once a week for 2 weeks, some patients require a third dose of 300 mg per week, while in some cases it is sufficient to receive 300 mg once a day.

With onychomycosis, the recommended dose is 150 mg once a week. Treatment should continue until the replacement of the infected nail (growth of uninfected nail). For the repeated growth of the nails on the fingers and toes normally takes 3-6 months. and 6-12 months. respectively.

In elderly patients in the absence of impaired renal function, the dosage regimen described for adults should be followed.

Patients with renal insufficiency (creatinine clearance less than 50 ml / min) dosage regimen should be adjusted as indicated below.

Fluconazole is excreted mainly with urine in unchanged form. In chronic renal failure, the initial "shock" dose, for example 300 mg. If the creatinine clearance (CK) is more than 50 ml / min, the usual dose of the drug (100% of the recommended dose) is used. With SC from 11 to 50 ml / min with vaginal candidiasis, 150 mg once is used, with skin mycoses and others - 150 mg once a week.Patients regularly on dialysis, a single dose of the drug is used after each session of hemodialysis.

Side effects:

On the part of the digestive system, decreased appetite, nausea, changes in taste, vomiting, diarrhea, flatulence, abdominal pain, rarely - impaired liver function and increased activity of "liver" enzymes (jaundice, hepatitis, hyperbilirubinemia, increased activity of alanine aminotransferase, aspartate aminotransferase, increased activity of alkaline phosphatase, hepatocellular necrosis), incl. with a lethal outcome.

From the nervous system: headache, dizziness, rarely - convulsions.

From the hemopoiesis: rarely - neutropenia, agranulocytosis; In patients with severe fungal infections, hematologic changes (leukopenia, thrombocytopenia) can be noted.

Allergic reactions: skin rash, multiforme exudative erythema (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome), anaphylactoid reactions (including angioedema, facial edema, urticaria, skin itching), bronchial Asthma (more often with intolerance to acetylsalicylic acid).

From the cardiovascular system: an increase in the duration of the Q-T interval on an electrocardiogram, fibrillation / flutter of the ventricles.

Other: rarely - renal dysfunction, alopecia, hypercholesterolemia, hypertriglyceridemia, hypokalemia.

Overdose:

Symptoms: nausea, vomiting, diarrhea, severe cases of convulsions, hallucinations, paranoid behavior.

Treatment: symptomatic: gastric lavage, forced diuresis. Hemodialysis within 3 hours reduces the concentration in the plasma by 50%.

Interaction:

One-time administration of fluconazole in the treatment of vaginal candidiasis is not accompanied by significant drug interactions. However, when several or more doses of the drug are used simultaneously with other drugs, the following drug interactions are possible:

When using fluconazole with warfarin, prothrombin time increases. In this regard, it is recommended to carefully monitor the prothrombin time in patients taking fluconazole in combination with coumarin anticoagulants.
Fluconazole increases the plasma half-life of oral hypoglycemic agents- derivatives of sulfonylureas (chlorpropamide, glibenclamide, glipizide, tolbutamide) in healthy people. Joint use of fluconazole and sulfonylurea derivatives in diabetic patients is allowed, but the doctor should keep in mind the possibility of developing hypoglycemia.
With the repeated simultaneous administration of hydrochlorothiazide and fluconazole, the fluconazole concentration in the plasma is increased.
Rifampicin accelerates the metabolism of fluconazole. Therefore, patients receiving concomitantly rifampicin, it is advisable to increase the dose of fluconazole accordingly.
In patients who underwent renal transplantation, it is recommended to monitor the concentration of cyclosporine in the joint administration of fluconazole, fluconazole can increase the concentration of cyclosporine in plasma.
The interaction of fluconazole with terfenadine, cisapride and astemizole can lead to an increase in the concentration of these drugs in the plasma, which in turn can cause prolongation of the Q-T interval and lead to serious heart rhythm disturbances. Fluconazole inhibits cytochrome P450 isoenzymes in the liver, thereby reducing the metabolism of terfenadine,cisapride and astemizole. The simultaneous administration of fluconazole at a dose of 400 mg / day or more and these drugs is contraindicated.
Fluconazole increases the concentration of theophylline in plasma, therefore it is recommended to monitor the concentration of theophylline in patients simultaneously taking theophylline and fluconazole.
There have been reports of an interaction between fluconazole and rifabutin, accompanied by an increase in serum concentration of the latter. With the simultaneous use of fluconazole and rifabutin, cases of uveitis are described. It is necessary to carefully observe patients who simultaneously take rifabutin and fluconazole.
Fluconazole enhances the pharmacological effects of phenytoin at a clinically significant degree and increases its serum concentrations. It is necessary to monitor the concentrations of phenytoin in the plasma and, if necessary, adjust the dose of phenytoin.
In patients taking a combination of fluconazole and zidovudine, an increase in the concentration of zidovudine is observed, which is caused by a slowing of the metabolism of the latter, so it is necessary to observe patients who are simultaneously receiving these drugs, possibly an increase in the incidence of side effects of zidovudine.
It is possible to increase the concentration of indinavir and midazolam. With the simultaneous administration of these drugs with fluconazole, their dose should be appropriately reduced.
Increases the concentration of tacrolimus, in connection with which, the risk of nephrotoxic action increases.
Doctors should take into account that interaction with other medicines has not been specifically considered, but it is possible.

Special instructions:

Treatment can be started in the absence of seeding results or other laboratory tests, but if appropriate, appropriate correction of antifungal therapy is recommended.

Treatment should continue until the appearance of clinical and microbiological remission.

Premature termination of treatment leads to relapse.

Because of fluconazole is excreted mainly by the kidneys, caution should be exercised in patients with renal insufficiency. With long-term treatment with fluconazole, dosing should be carried out taking into account the clearance of creatinine.

Caution should be exercised when administering fluconazole to patients with impaired liver function. During treatment, it is necessary to regularly monitor the activity of "liver" enzymes and monitor the patient in order to identify possible toxic effects.When the activity of "liver" enzymes is increased, the doctor must weigh the benefits of the therapy and the risk of developing severe liver damage. 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 when using many drugs. In those cases where the rash develops in patients with superficial fungal infection and it is regarded as definitely associated with fluconazole, the drug should be discontinued.

It is necessary to monitor prothrombin time in patients simultaneously receiving fluconazole and anticoagulants of the coumarin series.

Effect on the ability to drive transp. cf. and fur:

The experience with fluconazole indicates that it is unlikely that the ability to drive and drive the drug is impaired.

Form release / dosage:Capsules 150 mg.

Packaging:1, 2 capsules in a blister of PVC-aluminum foil.1 blister in a cardboard envelope. 1 cardboard envelope is placed in a cardboard box together with an instruction for use.

Storage conditions:

In a dry place at a temperature of no higher than 30 ° C.

Keep out of the reach of children.

Shelf life:

3 years. Do not use after the time specified on the package.

Terms of leave from pharmacies:Without recipe

Registration number:LSR-003644/10

Date of registration:30.04.2010

The owner of the registration certificate:Sanovel Pharmaco-industrial trading companySanovel Pharmaco-industrial trading company Turkey

Manufacturer: & nbsp

SANOVEL PHARMACEUTICAL PRODUCTS IND., Inc. Turkey

Representation: & nbspSANOVEL branch of the company pharmaco-industrial trading companySANOVEL branch of the company pharmaco-industrial trading companyRussia

Information update date: & nbsp13.10.2015

Illustrated instructions

Instructions

Disorel-Sanovel (Disorel-Sanovel)