Diflazon

Diflazon – antifungal means.

Form of release and structure

Dosage forms:

• Gelatinous solid capsules: No. 4 – with the white case and a light blue lid, No. 2 – with the white case and a blue lid, No. 1 – with the case and a lid of light blue color, No. 0 – with the white case and a dark-violet lid; capsules contain powder of almost white or white color (No. 4 – on 7 pieces in blisters, in a cardboard pack 1 blister; No. 2 – on 7 pieces in blisters, in a cardboard pack 4 blisters; No. 1 – on 1, 2 or 4 pieces in blisters, in a cardboard pack 1 blister; No. 0 – on 7 pieces in blisters, in a cardboard pack 1 blister, or on 10 pieces in blisters, in a cardboard pack 2 blisters);
• Solution for infusions: transparent colourless liquid, without visible inclusions (on 100 ml in bottles, in a cardboard pack 1 bottle complete with the plastic holder).

Active ingredient of Diflazon – флуконазол:

• 1 capsule: No. 4 – 50 mg, No. 2 – 100 mg, No. 1 – 150 mg, No. 0 – 200 mg;
• 1 ml of solution – 2 mg.

Auxiliary components:

• Capsules: starch corn, lactoses monohydrate, silicon dioxide colloid anhydrous, magnesium stearate, sodium lauryl sulfate;
• Solution: sodium chloride, water for injections.

Structure of a cover of the capsule: gelatin, titanium dioxide (E171).

Besides, in addition as a part of a cover of capsules:

• Capsules No. 4 and No. 2: a cover – dye blue patent (E131);
• Capsules No. 1: the case and a cover – dye blue patent (E131);
• Capsules No. 0: a cover – dyes FD&C indigo carmine an azoruby (E122), blue (E132).

Indications to use

• Generalized candidiasis: a kandidemiya, the disseminated candidiasis, invasive candidosis infections of eyes, respiratory system, a peritoneum, endocardium, uric ways, including at patients of intensive care units, patients with malignant new growths or being on cytotoxic or immunosuppressive therapy, with other factors contributing development of candidiasis;
• Candidiasis of mucous membranes of a mouth (superficial and chronic atrophic candidiasis), drinks, a gullet, noninvasive bronchopulmonary candidiases, a kandiduriya, skin candidiases, including prevention of a recurrence of oropharyngeal candidiasis at patients with AIDS;
• Acute and chronic recurrent vaginal candidiasis;
• Cryptococcal meningitis and other localizations of a cryptococcosis (including skin, lungs), including at various forms of immunosuppression (AIDS, organ transplantation);
• Dermatomycoses, especially at resistance to local therapy of heavy fungal infections of skin, mycoses of smooth skin, a dermatofitiya of feet, scaly (multi-colored) depriving, the sort Candida caused by dermatophytes and mushrooms;
• Prevention of fungal infections at malignant new growths at the patients predisposed to development of such infections as a result of radiation therapy and cytotoxic chemotherapy.

Besides, use of capsules is shown:

• Candidosis balanitis, prevention of a recurrence of vaginal candidiasis in the presence of three and more episodes a year;
• Coccidioidomycosis, deep local mycoses, paracoccidioidomycosis, histoplasmosis, sporotrichosis (at patients with normal immunity);
• Prevention of a cryptococcosis at patients with AIDS.

Also Diflazon's solution is applied to prevention of candidiasis before transplantation of marrow.

Contraindications

• Simultaneous use of a tsizaprid, astemizol or terfenadin (against the background of reception of a flukonazol on 400 mg a day and above) and other means promoting lengthening of an interval of QT and increasing risk of development of the expressed disturbances of a rhythm;
• Breastfeeding period;
• Hypersensitivity to azolny compounds and components of drug.

With care it is necessary to appoint Diflazon: to patients with an invasive, system or superficial fungal infection at emergence of rash against the background of administration of drug; at a liver and renal failure, a combination with terfenadiny the flukonazola in a dose is less than 400 mg in days, potentially proaritmogenny states at the patients who are at the same time accepting medicines, defiant arrhythmias, patients with disturbance of electrolytic balance, organic heart diseases and other risk factors.

Use of a flukonazol during pregnancy is shown only in case of potential threat for the woman's life if the estimated therapeutic effect exceeds harm for a fruit.

Besides, it is contraindicated to children under 3 years to accept capsules.

With care use capsules at intolerance of acetylsalicylic acid.

Under careful observation of the doctor it is necessary to use solution at a hypochlorhydria and an achlorhydria, treatment of children aged up to 6 months and the patients having alcoholism.

Route of administration and dosage

Solution is applied for intravenous (in/in) infusions at patients who cannot accept drug orally. Infusion speed – 200 mg an hour. As soon as there is an opportunity, the patient is transferred to administration of drug inside, without changing a daily dose.

The recommended Diflazon's dosing:

• Cryptococcal meningitis and cryptococcal infections of other localization: in the first days – 400 mg, then in a dose of 200-400 mg of 1 times a day. Usually therapy lasts 6-8 weeks, its duration depends on the clinical effect confirmed with a mycologic research. At patients with AIDS prevention of a recurrence of cryptococcal meningitis carry out in a dose 200 mg a day during the long period;
• System candidiasis: in the first days – 400 mg, then on 200-400 mg of 1 times a day, depending on clinical performance and disease severity increase in a daily dose to 800 mg is possible. Treatment is continued after total disappearance of symptoms of a disease and receiving a negative hemoculture within 2 weeks;
• Candidiasis of mucous membranes: on 50-100 mg of 1 times a day within 1-2 weeks, at patients with an immunodeficiency – 3 weeks. At severe forms of mucous candidiasis appoint 100-200 mg a day. After end of a course of primary therapy at patients with AIDS for prevention of a recurrence it can be appointed флуконазол in a dose of 150 mg once a week;
• Prevention of candidiasis: 50-400 mg a day (depending on weight of a neutropenia and estimated risk of a fungal infection after a miyelotransplantation and/or before cytostatic or radiation therapy at malignant new growths). Flukonazol it is necessary to appoint some days before the expected development of a neutropenia and to continue to apply not less than 1 week after achievement of quantity of neutrophils ^{more than 1000/mm3}.

Besides, the dosing mode for capsules (capsules accept inside):

• The atrophic candidiasis of an oral cavity caused by carrying dentures: on 50 mg of 1 times a day within 2 weeks with simultaneous processing of a prosthesis antiseptic agents;
• Vaginal candidiasis: once – 150 mg. For prevention of a recurrence – on 150 mg of 1 times in 4 weeks. Duration of treatment is individual, varies within 4-12 courses;
• The balanitis caused by Candida: once – 150 mg;
• Skin mycosis, including skin candidiasis, mycoses of smooth skin, feet, inguinal area: on 150 mg once a week or on 50 mg of 1 times a day within 2-4 weeks, at mycoses of feet – 6 weeks;
• Chromophytosis: 300 mg once a week, a course of treatment – 2-3 weeks, or on 50 mg of 1 times a day within 2-4 weeks;
• Onychomycosis: 150 mg once a week during the period necessary for full substitution of the infected nail healthy;
• Deep local mycoses: 200-400 mg a day. The estimated duration of therapy at a coccidioidomycosis makes 11-24 months, at a sporotrichosis – 1-16 months, at a paracoccidioidomycosis – 2-17 months, at histoplasmosis – 3-17 months.

To children with candidiasis of mucous membranes drug is appointed in the first day at the rate of 6 mg to 1 kg of weight, then on 3 mg on 1 kg a day.

Children are recommended to appoint Diflazon's dose taking into account weight of a clinical state and the child's weight: at generalized candidiasis and a cryptococcal infection – from 6 to 12 mg on 1 kg of weight of the child a day; for prevention of fungal infections at reduced immunity after cytotoxic chemotherapy or radiation therapy – on 3-12 mg on 1 kg a day.

At the age of 5-13 years the daily dose should not exceed that at adult patients (to 400 mg).

At a single dose of capsules change of a dose with renal failures is not required from patients.

Correction of the mode of dosing is not required to patients of advanced age.

At the clearance of creatinine (CC) less than 50 ml/min. a drug dose at adult patients and children should be lowered depending on degree of a renal failure.

The patients who are on a regular hemodialysis should enter one dose of drug after each session.

Side effects

• Cardiovascular system: lengthening on the electrocardiogram of an interval of QT, trembling or ventricular fibrillation;
• Alimentary system: abdominal pain, nausea, meteorism, vomiting, diarrhea, taste change; seldom – increase in activity of liver enzymes, an abnormal liver function (a hyperbilirubinemia, jaundice, a hepatocellular necrosis, hepatitis), including with a lethal outcome;
• System of a hemopoiesis: seldom – an agranulocytosis, a neutropenia; at heavy fungal infections – thrombocytopenia, a leukopenia;
• Allergic reactions: skin rash, a mnogoformny exudative erythema (including Stephens-Johnson's syndrome), a toxic epidermal necrolysis (Lyell's disease), bronchial asthma (as a rule, at intolerance of acetylsalicylic acid), anaphylactoid reactions, including a skin itch, a face edema, a small tortoiseshell, a Quincke's disease;
• Nervous system: headache, dizziness; seldom – spasms;
• Others: seldom – an alopecia, a renal failure, a hypercholesterolemia, a hypopotassemia, a gipertriglitseridemiya.

Besides, use of solution can cause a loss of appetite and a lock.

Special instructions

Reception of capsules is possible before obtaining results of laboratory analyses, however after their receiving it is recommended to correct the dosing mode.

Treatment by repeated doses of Diflazon has to be followed by control of function of kidneys, at a renal failure it is necessary to appoint the mode of dosing taking into account KK.

It is necessary to make observation of patients with functional disorder of a liver, to regularly monitor the level of liver enzymes. At increase in their activity the doctor has to compare advantage of therapy and risk of possible toxic damage of a liver in a severe form. The hepatotoxic action usually has reversible character and after the therapy termination its symptoms disappear.

At emergence of the rash caused by reception of a flukonazol in patients with a superficial fungal infection drug should be cancelled. At patients with system or invasive fungal pathologies rash it is necessary to observe and cancel therapy in case of a mnogoformny erythema or emergence of violent changes.

At simultaneous use of a flukonazol and anticoagulants of a coumarinic row it is necessary to control a prothrombin time carefully. It is necessary to continue treatment before kliniko-hematologic remission, the premature termination of therapy can lead to a recurrence.

The E122 dye which is a part of capsules No. 0 (200 mg) can cause an allergy, including bronchial asthma.

At patients with intolerance of acetylsalicylic acid allergic reactions appear more often.

Negative influence of Diflazon on ability of the patient to control of vehicles and mechanisms is not established.

Medicinal interaction

During treatment by Diflazon simultaneous use of any medicines needs to be coordinated with the attending physician.

Terms and storage conditions

To protect from children.

To store at a temperature: capsules – to 25 °C, solution – to 30 °C.

Period of validity: capsules – 5 years, solution – 3 years.