Diflazon, 150mg capsules, 1pc

Composition

1 capsule contains:

Active ingredient:

fluconazole 150 mg;

Auxiliary substances:

lactose monohydrate;

corn starch;

colloidal anhydrous silicon dioxide;

sodium lauryl sulfate;

magnesium stearate.

Pharmacological action

Pharmaceutical group:

antifungal agent.

Pharmaceutical action:

Diflazone is an antifungal drug. Fluconazole, a member of the class of triazole antifungal agents, is a powerful selective inhibitor of the fungal enzyme 14-α-demethylase. The drug prevents the transition of lanosterol to ergosterol, the main component of fungal cell membranes.

Active against pathogens of opportunistic mycoses, including those caused by Candida spp. (Candida albicans, Candida tropicalis), Cryptococcus neoformans, Microsporum spp., Trichophyton spp. The activity of fluconazole has also been shown in models of endemic mycoses, including infections caused by Blastomyces dermatitidis, Coccidioides immitis and Histoplasma capsulatum.

Pharmacokinetics:  

Absorption After oral use, fluconazole is well absorbed. Bioavailability is 90%. After oral use of the drug on an empty stomach at a dose of 150 mg, Cmax is 90% of the plasma content with intravenous use of the drug at a dose of 2.5-3.5 mg/l. Simultaneous food intake does not affect oral absorption. Cmax is reached 0.5-1.5 hours after taking fluconazole. The plasma concentration is directly proportional to the dose taken.

The distribution of 90% Css is achieved by day 4-5 of treatment with the drug (when taken 1 time/day). The introduction of a shock dose (on day 1),2 times higher than the average daily dose, allows you to reach 90% of the Css level by day 2. The apparent Vd approximates the total body water content. Protein binding is 11-12%. Fluconazole penetrates well into all body fluids, including the cerebrospinal fluid. The concentration of fluconazole in saliva and sputum is similar to its level in plasma. In patients with fungal meningitis, the levels of fluconazole in the cerebrospinal fluid are about 80% of its plasma levels.

In the stratum corneum, epidermis, dermis and sweat fluid, high concentrations are achieved that exceed serum levels.

Metabolism Less than 5% of fluconazole is metabolized during the” first pass ” through the liver. No metabolites of fluconazole were detected in the blood.

Elimination Long T1 / 2 allows the use of a single dose of the drug for the treatment of vaginal candidiasis and provides the drug 1 time/day. for other indications. Fluconazole is mainly excreted by the kidneys; approximately 80% of the administered dose is excreted unchanged by the kidneys. The clearance of fluconazole is proportional to creatinine clearance.

Indications

• Cryptococcosis, including cryptococcal meningitis and other localization of the infection (including the lungs, skin), as in patients with normal immune response and in patients with various forms of immunosuppression (including patients with AIDS, organ transplant);
• prevention of cryptococcal infections in AIDS patients;
• generalized candidiasis, including candidemia, disseminated candidiasis and other forms of invasive Candida infections (infection of the peritoneum, endocardium, eyes, respiratory and urinary tract). The treatment may be performed in patients with malignant tumors, patients in intensive care and undergoing cytotoxic or immunosuppressive therapy, and the presence of other predisposing factors to the development of Candida;
• candidiasis of the mucous membranes, including the oral cavity and pharynx (including atrophic oral candidiasis associated with wearing dentures), esophagus, non-invasive bronchopulmonary candidiasis, candiduria, candidiasis of the skin;
• prevention of relapse of oropharyngeal candidiasis in patients with AIDS,
• genital candidiasis: vaginal candidiasis (acute and chronic recurrent), prophylactic use to reduce the frequency of recurrences of vaginal candidiasis (3 or more episodes per year);
• candidal balanitis;
• prevention of fungal infections in patients with malignancies who are predisposed to such infections as a result of chemotherapy with cytostatics or radiation therapy;
• fungal skin infections, including athlete’s foot, body, groin;
• tinea versicolor;
• onychomycosis;
• candidiasis of the skin;
• deep endemic mycoses, including coccidioidomycosis, paracoccidioidomycosis, sporotrichosis and histoplasmosis in patients with normal immune systems.

Use during pregnancy and lactation

The use of Diflazone during pregnancy is not advisable, except for severe or life-threatening forms of fungal infections, if the intended benefit to the mother exceeds the possible risk to the fetus.

Fluconazole is found in breast milk at the same concentration as in plasma, so the appointment of the drug during lactation is not recommended.

Contraindications

• Hypersensitivity to fluconazole, other components of Diflazone or other azole compounds;
• simultaneous use of terfenadine (against the background of constant use of fluconazole at a dose of 400 mg / day or more), cisapride or astemizole and other drugs that prolong the QT interval and increase the risk of severe rhythm disorders;
• lactation period.

Side effects

From the digestive system:  nausea, diarrhea, flatulence, vomiting, abdominal pain, taste changes, rarely-increased activity of liver enzymes and impaired liver function (jaundice, hyperbilirubinemia, increased activity of ALT, ACT and alkaline phosphatase, hepatitis, hepatocellular necrosis, including with fatal outcome).

Nervous system disorders:  headache, dizziness; rarely-convulsions.

From the side of hematopoietic organs:  rarely-agranulocytosis, neutropenia. Patients with severe fungal infections may have hematological changes (leukopenia and thrombocytopenia).

From the cardiovascular system:  increased duration of the QT interval on the electrocardiogram (ECG), ventricular fibrillation/flutter.

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

Interaction

When using fluconazole with warfarin, an increase in prothrombin time by 12% was noted. Therefore, it is recommended to monitor prothrombin time in patients receiving Diflazone in combination with coumarin anticoagulants.

When used concomitantly, fluconazole increases T 1/2 of oral hypoglycemic drugs – derivatives of sulfonylureas (chlorpropamide, glibenclamide, glipizide and tolbutamide) in healthy volunteers. Concomitant use of fluconazole and oral hypoglycemic drugs is allowed, but the possibility of hypoglycemia should be taken into account.

Concomitant use of fluconazole and phenytoin may be accompanied by a clinically significant increase in the concentration of phenytoin. If the combined use of two drugs is required, it is necessary to monitor the level of phenytoin and select its dose to ensure therapeutic concentration in serum.

Concomitant use of fluconazole and rifampicin resulted in a 25% decrease in AUC and a 20% shortening of T 1/2 of fluconazole. Patients receiving concomitant rifampicin should consider increasing the dose of fluconazole.

It is recommended to monitor the concentration of cyclosporine in the blood of patients receiving fluconazole, because when using fluconazole and cyclosporine in patients with a transplanted kidney, taking fluconazole at a dose of 200 mg / day slowly increased the concentration of cyclosporine.

Patients receiving high doses of theophylline, or who are likely to develop theophylline intoxication, should be monitored for early detection of symptoms of overdose of theophylline, since simultaneous use of fluconazole leads to a decrease in the average rate of clearance of theophylline from plasma.

Concomitant use of fluconazole and cisapride has been associated with cases of adverse cardiac reactions, including paroxysms of ventricular tachycardia ( pirouette-type arrhythmia).

There are reports of interaction between fluconazole and rifabutin, accompanied by an increase in serum levels of the latter. Cases of uveitis have been reported with concomitant use of fluconazole and rifabutin. Patients receiving rifabutin and fluconazole concomitantly should be carefully monitored.

With the simultaneous use of zidovudine and fluconazole, there is an increase in the concentration of zidovudine in plasma, which is caused by a decrease in the conversion of the latter to the main metabolite, so we should expect an increase in the side effects of zidovudine.

How to take it, course of use and dosage

Adults with cryptococcal meningitis and cryptococcal infections of other localization are prescribed 400 mg on the first day, and then continue treatment at a dose of 200-400 mg once a day. The duration of treatment for cryptococcal infections depends on the clinical efficacy confirmed by mycological examination; for cryptococcal meningitis, therapy is usually continued for at least 6-8 weeks.

To prevent recurrence of cryptococcal meningitis in AIDS patients, after completing the full course of primary treatment, fluconazole therapy at a dose of 200 mg / day can be continued for a very long period of time.

For candidaemia, disseminated candidiasis, and other invasive candida infections, the average dose is 400 mg on the first day, followed by 200 mg/day. In case of insufficient clinical efficacy, the dose can be increased to 400 mg / day. The duration of therapy depends on the clinical efficacy.

For oropharyngeal candidiasis, the drug is prescribed on average 50-100 mg once a day; the duration of therapy is 7-14 days. If necessary, in patients with a pronounced decrease in immunity, treatment can be longer.

In case of atrophic candidiasis of the oral cavity associated with wearing dentures, the drug is prescribed in an average dose of 50 mg 1 time a day for 14 days in combination with local antiseptics for the treatment of the prosthesis.

For other candida infections (with the exception of genital candidiasis), such as esophagitis, non-invasive bronchopulmonary lesions, candiduria, candidiasis of the skin and mucous membranes, the effective dose is on average 50-100 mg / day with a treatment duration of 14-30 days.

To prevent relapses of oropharyngeal candidiasis in AIDS patients after completing a full course of primary therapy, fluconazole can be prescribed 150 mg once a week.

With vaginal candidiasis, fluconazole is taken once orally at a dose of 150 mg. To reduce the frequency of relapses of vaginal candidiasis, the drug can be used at a dose of 150 mg once a month. The duration of therapy is determined individually; it varies from 4 to 12 months. Some patients may require more frequent use.

When balanitis caused by Candida, fluconazole is prescribed once in a dose of 150 mg orally.

For the prevention of candidiasis, the recommended dose of fluconazole is 50-400 mg once a day, depending on the degree of risk of fungal infection. If there is a high risk of generalized infection, for example, in patients with expected severe or long-term persistent neutropenia, the recommended dose is 400 mg once a day. Fluconazole is prescribed a few days before the expected occurrence of neutropenia; after an increase in the number of neutrophils more than 1000/µl, treatment is continued for another 7 days.

For mycoses of the skin, including mycoses of the feet, smooth skin, groin area and candidiasis of the skin, the recommended dose is 150 mg once a week or 50 mg once a day. The duration of therapy in normal cases is 2-4 weeks, but with mycoses of the feet, longer therapy may be required (up to 6 weeks).

For pityriasis versicolor, the recommended dose is 300 mg once a week for 2 weeks; some patients require a third dose of 300 mg per week, while in some cases a single dose of 300-400 mg is sufficient. An alternative treatment regimen is the use of the drug 50 mg once a day for 2-4 weeks.

For onychomycosis, the recommended dose is 150 mg once a week. Treatment should be continued until the infected nail is replaced (uninfected nail regrowth). It normally takes 3-6 months and 6-12 months, respectively, for the nails to regrow on the fingers and feet.

Deep endemic mycoses may require the use of the drug at a dose of 200-400 mg / day for up to 2 years. The duration of therapy is determined individually; it is 11-24 months for coccidioidomycosis,2-17 months for paracoccidioidomycosis,1-16 months for sporotrichosis and 3-17 months for histoplasmosis.

In children, as with similar infections in adults, the duration of treatment depends on the clinical and mycological effect. In children, the drug should not be used in a daily dose exceeding that of adults. Diflazone is used daily 1 time/day.

For mucosal candidiasis, the recommended dose of fluconazole is 3 mg / kg / day. On the first day, a shock dose of 6 mg/kg may be prescribed in order to achieve constant equilibrium concentrations more quickly.

For the treatment of generalized candidiasis and cryptococcal infection, the recommended dose is 6-12 mg / kg / day, depending on the severity of the disease.

For the prevention of fungal infections in children with reduced immunity, in whom the risk of infection is associated with neutropenia, which develops as a result of cytotoxic chemotherapy or radiation therapy, the drug is prescribed at 3-12 mg / kg / day, depending on the severity and duration of preservation of induced neutropenia.

In children with impaired renal function, the daily dose of the drug should be reduced (in the same proportion as in adults), in accordance with the severity of renal failure.

In elderly patients with no signs of renal failure, the usual dosage regimen should be followed.

In patients with renal insufficiency (CC

), Fluconazole is mainly excreted unchanged in the urine. With a single dose, no dose change is required. When re-administered to patients with impaired renal function, a shock dose of 50 mg to 400 mg should be administered.

For creatinine clearance>50 ml / min, the average recommended dose of the drug is used; for creatinine clearance from 11 to 50 ml / min, a dose of 50% of the recommended dose is used. Patients who are regularly on hemodialysis, one dose of the drug is administered after each hemodialysis session.

Overdose

Symptoms: hallucinations, paranoid behavior.

Treatment: gastric lavage and symptomatic therapy are recommended. Since fluconazole is excreted in the urine, forced diuresis increases its excretion. Hemodialysis for 3 hours reduces the concentration of fluconazole in plasma by 50%.

Special instructions

Treatment can be initiated in the absence of results of seeding or other laboratory tests, but if they are available, appropriate correction of fungicide therapy is recommended.

Form of production

Capsules

Storage conditions

At a temperature not exceeding 25 °C

Shelf life

5 years

Active ingredient

Fluconazole

Conditions of release from pharmacies

By prescription

Dosage form

Capsules

Purpose

Children as prescribed by a doctor, For adults, Children over 3 years of age

Indications

Thrush, Fungus