Diflucan

Diflucan – antifungal drug.

Form of release and structure

Dosage forms of drug:

• Gelatinous solid capsules: have marking of black color in the form of the Pfizer and FLU-50 logo – on capsules No. 4 with a turquoise cover and the white case, "FLU-100" – on capsules No. 2 with a white cover and the case or "FLU-150" – on capsules No. 1 with a cover and the case of turquoise color; in capsules – powder from pale yellow till white color (the capsule No. 4 and No. 2 on 7 pieces in blisters, in a cardboard pack 1 or 4 blisters; capsules No. 1 on 1 or 4 pieces in blisters, in a cardboard pack 1 blister);
• Powder for preparation of suspension for intake: without visible contaminations, has white or almost white color (on 50 mg (powder with concentration of 10 mg / 1 ml) or on 200 mg (40 mg / 1 ml) in plastic bottles of 5 ml complete with a measured spoon, in a cardboard pack 1 set);
• Solution for intravenous (in/in) introductions: colourless, transparent liquid (on 25, 50, 100 or 200 ml in bottles from colourless glass, in a cardboard pack 1 bottle).

Active agent of each of dosage forms of Diflucan – флуконазол:

• 1 capsule – 50 mg (with marking of "FLU-50"), 100 mg ("FLU-100") or 150 mg ("FLU-150");
• 1 ml of ready suspension – 10 mg, 40 mg;
• 1 ml of solution – 2 mg.

Auxiliary components:

• Capsules: starch corn, lactose, silicon dioxide colloid, sodium lauryl sulfate, magnesium stearate;
• Powder: Natrium benzoicum, silicon dioxide colloid anhydrous, gum xanthane, sucrose, titanium dioxide (E171), citrate sodium a dihydrate, fragrance orange (consists of maltodextrin, orange essential oil and water), citric acid anhydrous;
• Solution: sodium chloride, water for injections.

In addition as a part of capsules:

• Case: gelatin, titanium dioxide (E171);
• Lid: gelatin, titanium dioxide (E171), dye blue patent (E131);
• Ink: N-butanol, shellakovy glaze, alcohol industrial metilirovanny 74OP, ferrous oxide black (E172), antifoam DC1510 component, lecithin soy.

Indications to use

• Cryptococcosis, including cryptococcal meningitis, infectious damages of lungs, skin and other bodies at patients with normal immunity, recipients of transplanted organs, at patients with various forms of an immunodeficiency and AIDS; a maintenance therapy at patients AIDS for the purpose of prevention of a recurrence of a cryptococcosis;
• Generalized candidiasis, including the disseminated candidiasis, a kandidemiya, invasive candidosis infections of eyes, peritoneums, an endocardium, uric and respiratory tracts, including at the cancer patients who are on an intensive care immunosuppressive and cytotoxic drugs and at patients with other pathologies predisposed to developing of candidiasis;
• Candidosis balanitis, genital candidiasis, vaginal candidiasis – treatment of an acute or recurrent form and prevention of decrease in frequency of a recurrence (3 and more cases a year);
• Candidiasis of mucous membranes of an organism, including an oral cavity, a throat, a gullet, noninvasive bronchopulmonary infections, a kandiduriya, the chronic skin and mucous and atrophic candidiasis of an oral cavity caused by carrying dentures, at patients with the normal and broken immune function; patients have AIDS – prevention of oropharyngeal candidiasis;
• Deep local mycoses (coccidioidomycosis, paracoccidioidomycosis, histoplasmosis and sporotrichosis) at patients with normal immunity;
• Chromophytosis, mycosis (stop, inguinal area, body skin), onychomycosis and skin candidosis infections.

Besides, use of Diflucan is shown to patients with malignant tumors for prevention of a fungal infection against the background of radiation and cytotoxic therapy.

Contraindications

• Concomitant use of a terfenadin against the background of numerous use of a flukonazol in a dose of 400 mg a day and above;
• Co-administration of a tsizaprid;
• Breastfeeding period;
• Hypersensitivity to components of drug and azolny substances with structure, similar to a flukonazol.

It is necessary to avoid use of drug during pregnancy, except for life-threatening severe forms of fungus diseases of mother when the probable advantage of treatment exceeds possible risk for a fruit.

With care appoint Diflucan: at a combination of a flukonazol in a dose less than 400 mg a day with terfenadiny; at development of functional disturbances of indicators of a liver against the background of reception of a flukonazol; the patient with superficial, invasive or system fungal infections at emergence of skin rash during treatment; at pro-arhythmic states at patients with many risk factors, including an organic heart disease, disturbance of electrolytic balance and the accompanying therapy promoting emergence of similar disturbances.

Route of administration and dosage

• Gelatinous solid capsules: accept without chewing, inside;
• Powder for suspension preparation: accept inside, having added 24 ml of water to bottle contents, carefully shaking up before each reception;
• Solution for (in/in) introductions: it is entered by infusion with a speed no more than 10 ml a minute. At appointment patients to whom restriction of liquid and consumption of sodium is shown need to consider the content of 0,9% of solution of sodium of chloride in solution.

The choice of a dosage form, dose of drug and the period of treatment depend on a clinical condition of the patient and these laboratory researches therefore are defined by the doctor individually.

In case of need replacements of one dosage form by another change of dosing is not made.

To patients of advanced age in the absence of a renal failure drug is appointed in an average dose.

Correction of the mode of dosing at repeated use of drug is necessary for patients with a renal failure, the daily dose is defined depending on laboratory indications of clearance of creatinine.

The recommended dosing of Diflucan for adult patients:

• Cryptococcal meningitis and other cryptococcal infections: in the first day of 400 mg (on average), then on 200-400 mg of 1 times a day. Duration of treatment depends on mycologic and clinical effect, at cryptococcal meningitis, usually, makes 6-8 weeks. After primary full course of therapy preventive administration of drug on 200 mg a day by patients AIDS can be continued during the long period;
• Kandidemiya, the disseminated candidiasis and other invasive candidosis infections: in the first day – 400 mg, then on 200 mg a day, increase up to 400 mg a day is in case of need possible;
• The vaginal candidiasis and balanitis caused by Candida: inside once 150 mg. For the purpose of decrease in frequency of a recurrence of vaginal candidiasis it is possible to accept on 150 mg of 1 times in 4 weeks, duration is defined individually, and can make from 16 weeks to 1 year. Single use of drug for patients aged to 18 is also more senior than 60 years without appointment of the doctor it is not recommended;
• Orofaringealny candidiasis: on 50-100 mg of 1 times a day within 7-14 days. At patients AIDS after a full course of therapy for prevention of a recurrence is appointed on 150 mg once a week, the doctor defines the period individually;
• The atrophic candidiasis of an oral cavity caused by carrying dentures: on 50 mg of 1 times a day, a course of treatment – 14 days, therapy is carried out in combination with antiseptic processing of a prosthesis;
• Noninvasive bronchopulmonary infections, esophagitis, kandiduriya, candidiasis of skin and mucous membranes (except genital candidiasis): on 50-100 mg a day within 14-30 days;
• Skin infections, including mycoses of smooth skin, feet, inguinal area and candidosis infections: on 150 mg once a week or 50 mg of 1 times a day, within 2-4 weeks, at mycosis of feet – up to 6 weeks;
• Chromophytosis: on 300 mg once a week within 2-3 weeks or on 50 mg of 1 times a day 2-4 weeks;
• Deep local mycosis: on 200-400 mg a day, duration of therapy is appointed individually, it can make at a coccidioidomycosis – 11-24 months, a paracoccidioidomycosis – from 2 to 17 months, a sporotrichosis – 1-16 months, histoplasmosis – 3-17 months;
• Onychomycosis: on 150 mg once a week. Treatment is continued before full substitution of the infected nail, the repeated growth of nails on fingers of hands usually requires 3-6 months, stop – 6-12 months;
• Prevention of candidiasis: from 50 to 400 mg of 1 times a day, reception it is necessary to begin some days before alleged development of a neutropenia.

The recommended dosing for children:

• Candidiasis of mucous membranes: in the first day – at the rate of 6 mg on 1 kg of weight of the child, further on 3 mg on 1 kg of weight a day;
• Generalized candidiasis and cryptococcal infection: on 6-12 mg on 1 kg of weight a day;
• Prevention of fungal infections: on 3-12 mg on 1 kg of weight a day, the dose depends on degree and duration of a neutropenia.

For children in the first 2 weeks of life drug is appointed with an interval of 72 hours, at the age of 3-4 weeks – 48 hours.

Side effects

Use of Diflucan can cause side effect:

• From cardiovascular system: lengthening of an interval of an electrical systole of heart (QT) on the electrocardiogram, trembling or ventricular fibrillation;
• From a nervous system: taste change, dizziness, headache, spasms;
• From the alimentary system: nausea, vomiting, an abdominal pain, a meteorism, diarrhea, dyspepsia, a hepatotoxic (sometimes with a lethal outcome), an abnormal liver function, a hepatocellular necrosis, jaundice, hepatitis, increase in level of bilirubin, an alkaline phosphatase, serumal level of alaninaminotranspherase (ALT) and aspartate aminotransferase (nuclear heating plant);
• From system of a hemopoiesis: thrombocytopenia, leukopenia (including neutropenia and agranulocytosis);
• Allergic reactions: face edema, Quincke's disease, skin itch, small tortoiseshell and other anaphylactic reactions;
• From a metabolism: a hypopotassemia, increase in a blood plasma of level of triglycerides and cholesterol;
• Dermatological reactions: an alopecia, rash, exfoliative skin pathologies, including a toxic epidermal necrolysis and Stephens-Johnson's syndrome.

Special instructions

The hepatotoxic action of drug has reversible character, after completion of therapy its signs disappear.

In case of clinical symptoms of damage of a liver during therapy, drug should be cancelled.

Women of childbearing age need to use well-tried remedies of contraception during treatment.

If the patient had a rash as side effect of a flukonazol at therapy of a superficial fungal infection, drug is recommended to be cancelled at once, and at treatment of invasive or system fungal infections it is cancelled at emergence of a mnogoformny erythema or violent defeats.

In rare instances drug can become the reason of anaphylactic reaction.

Under careful control it is necessary to carry out a concomitant use of a flukonazol in doses less than 400 mg a day and a terfenadin.

Patients with potentially pro-arhythmic states флуконазол should apply with care.

Patients with heart diseases, a liver and kidneys have to consult with the doctor before drug use.

At vaginal candidiasis improvement of a state usually occurs in 24 hours after reception of 150 mg of drug, but total disappearance of symptoms of a disease requires sometimes several days. If improvement of a state did not occur, it is necessary to see the attending physician.

Use of drug has no significant effect on ability of the patient to manage vehicles.

Medicinal interaction

Simultaneous use of a tsizaprid, terfenadin (at a dose of a flukonazol of 400 mg a day and more) and Diflucan contraindicated in connection with a high probability of undesirable effects from heart.

The combined treatment with terfenadiny at a dose of a flukonazol less than 400 mg a day perhaps at careful control of level of concentration of a terfenadin in a blood plasma.

At a concomitant use with coumarinic anticoagulants the prothrombin time raises, it can lead to development of bleedings from a nose and digestive tract, to hematomas, melenas, a hamaturia.

Drug increases concentration and psychotropic effects of benzodiazepines (short action), this influence is more expressed after reception of capsules and suspension.

At a multiple concomitant use of thiazide diuretics there is an increase in concentration of a flukonazol in a blood plasma, this effect should be considered though he does not demand review of a dose of a flukonazol from patients.

The concomitant use of Diflucan with food, antacids, Cimetidinum does not exert clinically significant impact on absorption of a flukonazol.

Prolonged use of a flukonazol in doses of 200-300 mg does not exert impact on efficiency of the combined peroral contraceptives.

Drug promotes clinically significant increase in level of concentration in blood serum of Phenytoinum, rifabutin, takrolimus, astemizol and other means which metabolism is implemented by isoenzymes of system of P450 cytochrome. In case of need these combinations, patients it is necessary to observe carefully.

Simultaneous use with rifampicin leads to decrease in pharmacokinetic parameters (AUC) and duration of an elimination half-life _(T1/2) of a flukonazol.

Diflucan promotes increase _{in T1/2} of peroral drugs of sulphonylurea (a glipizid, Glibenclamidum, Chlorproramidum and Tolbutamidum). At joint purpose of these means patients with a diabetes mellitus need to consider a possibility of development of a hypoglycemia.

Drug reduces the average speed of plasma clearance of theophylline.

Action of a flukonazol leads to significant increase in AUC of a zidovudine therefore at simultaneous use of these means it is necessary to monitor development of side effects of a zidovudine carefully.

At simultaneous use with cyclosporine it is necessary to monitor the level of its concentration in blood.

Diflucan in the form of solution can be entered into infusional system together with isotonic normal saline solution, 20% glucose solution, Ringer's solution, aminofuziny, Hartmann's solution, chloride potassium solution in glucose, solution of sodium of bicarbonate of 4,2%.

Terms and storage conditions

To store in the place, unavailable to children, at a temperature up to 30 °C. Not to freeze, store ready suspension at a temperature up to 30 °C no more than 14 days.

Period of validity:

• Capsules and solution for in/in introductions – 5 years;
• Powder for suspension preparation – 3 years.