Fluconazole-Teva, 150mg capsules 1pc

Composition

1 capsule contains: Active ingredient: fluconazole 150.00 mg; Excipients: lactose monohydrate 141.00 mg, corn starch 49.95 mg, colloidal silicon dioxide 0.3375 mg, sodium lauryl sulfate 0.3375 mg, magnesium stearate 3.375 mg

. Gelatin capsule: case: titanium dioxide (E 171) 0,91 mg, brilliant blue FCF (E 133) 0.015 mg, gelatin q. s. to 22.8/q. s. to 36.6/q. s. to 45.6 mg;cover: titanium dioxide (E 171) 0,61 mg, brilliant blue FCF (E 133) 0.010 mg, gelatin q. s. to 15.2/q. s. to 24.4/q. s. to 30.4 mg

Pharmacological action

fluconazole is a synthetic antifungal drug (antimycotic) from the group of triazole derivatives, the mechanism of action is associated with selective inhibition of the biosynthesis of ergosterol required for the formation of the cell membrane of fungi.

It is active in vitro and in clinical infections against most of the following microorganisms: Candida albicans, Candida glabrata (moderately sensitive strains), Candida pararsilosis, Candida tropicalis, Cryptococcus neoformans.

It is active in vitro against the following microorganisms, but the clinical significance of this effect is unknown: Candida dubliniensis, Candida guilliermodii, Candida kefyr, Candida lusitaniae.

When administered orally, fluconazole is active in various models of fungal infections in animals: opportunistic mycoses, including those caused by Candida spp. (including generalized candidiasis in immunocompromised animals); Cryptococcus neoformans (including intracranial infections); Microsporum spp. and Trychoptyton spp.

The activity of the drug was also established in models of endemic mycoses in animals, including infections caused by Blastomyces dermatitides, Coccidioides immitis (including intracranial infections), and Histoplasma capsulatum in animals with normal and suppressed immunity.

Fluconazole is highly specific for cytochrome P-450-dependent fungal enzymes. Fluconazole therapy at a dose of 50 mg / day for up to 28 days does not affect the concentration of testosterone in the blood plasma in men or the concentration of steroid hormones in women of childbearing age. Fluconazole at a dose of 200-400 mg / day does not have a clinically significant effect on the levels of endogenous steroids in the blood and their response to stimulation of adrenocorticotropic hormone (ACTH) in healthy male volunteers.

Mechanisms of development of resistance to fluconazole.

Resistance to fluconazole may develop in the following cases: : with a qualitative or quantitative change in the lanosteryl 14-α-demethylase enzyme that is a target for fluconazole, a decrease in access to this enzyme by fluconazole, or a combination of these mechanisms.

Point mutations in the ERG11 gene encoding the target enzyme lead to a modification of the target and a decrease in affinity for chemical compounds from the group of azoles (including triazole derivatives, which include fluconazole). An increase in the expression of the ERG11 gene leads to the formation of high concentrations of the target enzyme, which creates the need to increase the concentration of fluconazole in the intracellular fluid to suppress all enzyme molecules in the cell.

The second significant mechanism of resistance is the active elimination of fluconazole from the intracellular space due to the activation of two types of transporters involved in the active elimination (efflux) of drugs from the fungal cell.

These transporters include the main messenger encoded by MDR (multiple drug resistance) genes, and the superfamily of ATP-binding transporters encoded by CDR genes (genes for resistance of Candida fungi to azole antimycotics).

Overexpression of the MDR gene leads to resistance to fluconazole, while overexpression of CDR genes can lead to resistance to various azoles. Resistance to Candida glabrata is usually mediated by overexpression of the CDR gene, which leads to resistance to many azole antimycotics. For those strains of fungi for which the minimum inhibitory concentration (MIC) is defined as intermediate (16-32 mcg/ml), it is recommended to use maximum doses of fluconazole.

Candida krusei should be considered as resistant to fluconazole. The mechanism of resistance is associated with a reduced sensitivity of its target enzyme to the inhibitory effect of fluconazole.

Indications

Fluconazole is indicated for the treatment of the following diseases in adults:

• Cryptococcal meningitis.
• Coccidioidomycosis.
• Invasive candidiasis.
• Mucosal candidiasis, including oropharyngeal candidiasis, esophageal candidiasis, candiduria, and chronic mucocutaneous candidiasis.
• Chronic atrophic candidiasis of the oral cavity (associated with wearing dentures), when oral hygiene or topical treatment is not sufficient.
• Vaginal candidiasis, acute or recurrent, when local therapy is not applicable.
• Candidal balanitis, when local therapy is not applicable.
• Dermatomycosis, including foot dermatophytosis, trunk dermatophytosis, inguinal dermatophytosis, multi-colored lichen and skin candidiasis, when systemic treatment is indicated.
• Nail dermatophytosis (onychomycosis), when treatment with other drugs is not acceptable. Fluconazole is indicated for the prevention of the following diseases in adults:
• Relapses of cryptococcal meningitis in patients at high risk of relapse.
• Relapses of oropharyngeal candidiasis and esophageal candidiasis in HIV-infected patients with a high risk of relapse.
• To reduce the recurrence rate of vaginal candidiasis (4 or more episodes per year).
• For the prevention of candida infections in patients with long-term neutropenia (such as patients with hemoblastosis undergoing chemotherapy, or patients undergoing hematopoietic stem cell transplantation. Fluconazole is indicated for use in children.

Fluconazole is used for the treatment of mucosal candidiasis (oropharyngeal candidiasis and esophageal candidiasis), invasive candidiasis, cryptococcal meningitis and prevention of candida infections in patients with a weakened immune system. Fluconazole can be used as maintenance therapy to prevent recurrence of cryptococcal meningitis in children at high risk of relapse.

Use during pregnancy and lactation

The use of the drug in pregnant women is impractical, except for severe or life-threatening forms of fungal infections, when the potential benefit of using fluconazole for the mother significantly exceeds the risk to the fetus.

Since the concentration of fluconazole in breast milk and plasma is the same, it is contraindicated to use the drug during lactation.

Contraindications

Hypersensitivity to the drug Fluconazole-Teva; simultaneous use of terfenadine (against the background of constant use of fluconazole at a dose of 400 mg / day or more) or astemizole, as well as other drugs that prolong the interval QT;

With caution:  hepatic and/or renal failure, rash associated with the use of fluconazole in patients with superficial fungal infection and invasive/systemic fungal infections, concomitant use of terfenadine and fluconazole at a dose of less than 400 mg / day, concomitant use of potentially hepatotoxic drugs, alcoholism, potentially proarrhythmogenic conditions in patients with multiple risk factors (organic heart disease, electrolyte imbalance, concomitant use of drugs that cause arrhythmias), pregnancy.

Side effects

From the digestive system:  decreased appetite, changes in taste, abdominal pain, vomiting, nausea, diarrhea, flatulence, rarely-impaired liver function (jaundice, hepatitis, hepatonecrosis, hyperbilirubinemia, increased activity of alanine aminotransferase, aspartate aminotransferase, increased activity of alkaline phosphatase, hepatocellular necrosis), including severe.

Nervous system disorders:  headache, dizziness, excessive fatigue, rarely-convulsions.

From the side of hematopoietic organs:  rarely-leukopenia, thrombocytopenia (bleeding, petechiae), neutropenia, agranulocytosis.

Allergic reactions:  skin rash, rarely-erythema multiforme (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell’s syndrome), anaphylactoid reactions (including angioedema, facial edema, urticaria, pruritus of the skin).

From the cardiovascular system:  increased QT interval duration, ventricular fibrillation/flutter.

Other services:  rarely-impaired renal function, alopecia, hypercholesterolemia, hypertriglyceridemia, hypokalemia.

Interaction

When using fluconazole with warfarin, the PV increases (on average by 12%). In this regard, it is recommended to carefully monitor the indicators PV in patients receiving the drug in combination with coumarin anticoagulants.

Fluconazole increases the plasma half-life of oral hypoglycemic agents-sulfonylurea derivatives (chlorpropamide, glibenclamide, glipizide, tolbutamide) in healthy people. The combined use of Fluconazole and oral hypoglycemic agents in diabetic patients is allowed, but the doctor should keep in mind the possibility of hypoglycemia.

Concomitant use of Fluconazole and phenytoin may lead to an increase in the concentration of phenytoin in plasma to a clinically significant degree. Therefore, if the combined use of these drugs is necessary, it is necessary to monitor the concentration of phenytoin with dose adjustment in order to maintain the level of the drug within the therapeutic interval.

Combination with rifampicin resulted in a 25% decrease in AUC and a 20% shortening of the plasma half-life of fluconazole. Therefore, it is advisable to increase the dose of Fluconazole in patients receiving rifampicin at the same time.

It is recommended to monitor the concentration of cyclosporine in the blood of patients receiving Fluconazole, because the use of fluconazole and cyclosporine in patients with a transplanted kidney (taking Fluconazole at a dose of 200 mg/day) leads to a slow increase in the concentration of cyclosporine in plasma.

Patients who are 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 taking fluconazole leads to a decrease in the average rate of clearance of theophylline from plasma.

Concomitant use of fluconazole with terfenadine and cisapride has been associated with cases of adverse cardiac reactions, including paroxysms of ventricular tachycardia (torsades de points).

Concomitant use of fluconazole and hydrochlorothiazide may increase the plasma concentration of fluconazole by 40%.

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.

In patients receiving a combination of fluconazole and zidovudine, an increase in the concentration of zidovudine is observed, which is caused by a decrease in the conversion of the latter to its main metabolite, so an increase in the side effects of zidovudine should be expected.

Increases the concentration of midazolam, and therefore increases the risk of psychomotor effects (most pronounced when using fluconazole inside, than IV).

Increases the concentration of tacrolimus, which increases the risk of nephrotoxic effects.

How to take, course of use and dosage

Inside. Capsules are swallowed whole. Therapy can be started before receiving the results of seeding and other laboratory tests. However, antifungal therapy should be modified accordingly when the results of these studies become known. When transferring a patient from intravenous to oral use of the drug or vice versa, no change in the daily dose is required. The daily dose of fluconazole depends on the nature and severity of the fungal infection. For infections that require repeated use of the drug, treatment should be continued until the clinical or laboratory signs of active fungal infection disappear. Patients with AIDS and cryptococcal meningitis or recurrent oropharyngeal candidiasis usually require maintenance therapy to prevent recurrent infection. Use in adults 1. For cryptococcal meningitis and cryptococcal infections of other localization, the drug is usually used on the first day at a dose of 400 mg, and then continue treatment at a dose of 200-400 mg once a day. The duration of treatment for cryptococcal infections depends on the presence of clinical and mycological effects; for cryptococcal meningitis, treatment is usually continued for at least 6-8 weeks. In cases of life-threatening infections, the daily dose can be increased to 800 mg. To prevent recurrence of cryptococcal meningitis in patients with a high risk of recurrence, after completing the full course of primary treatment, fluconazole therapy at a dose of 200 mg / day can be continued for an indefinite period of time. 2. coccidioidomycosis may require the use of the drug at a dose of 200-400 mg / day. For some infections, especially those involving the meninges, a dose of 800 mg per day may be considered. The duration of therapy is determined individually, it can last up to 2 years and is 11-24 months for coccidioidomycosis,2-17 months for paracoccidioidomycosis,1-16 months for sporotrichosis and 3-17 months for histoplasmosis. 3. For candidaemia, disseminated candidiasis and other invasive candida infections, the saturating dose is 800 mg on the first day, the subsequent dose is 400 mg/day. The duration of therapy depends on the clinical efficacy. The general recommendation for the duration of treatment of candidaemia is 2 weeks after the first negative result of blood culture and the disappearance of signs and symptoms of candidaemia. 4. Treatment of mucosal candidiasis. * For oropharyngeal candidiasis, saturating dose: 200-400 mg on the first day, subsequent dose: 100-200 mg once a day for 7-21 days. If necessary, patients with severe suppression of immune function can continue treatment for a longer time. • For chronic atrophic candidiasis of the oral cavity associated with wearing dentures, the drug is usually used in a dose of 50 mg once a day for 14 days in combination with local antiseptic agents for the treatment of the prosthesis. * For candidiasis, the effective dose is usually 200-400 mg / day with a treatment duration of 7-21 days. In patients with severe immune system dysfunction, longer periods of therapy can be used. * For chronic mucocutaneous candidiasis, apply 50-100 mg per day for up to 28 days of treatment. Depending on the severity of the infection or the concomitant immune system disorder and infection, longer treatment periods may be used. * For esophageal candidiasis, a saturating dose is 200-400 mg on the first day, followed by a subsequent dose of 100-200 mg per day. The course of treatment is 14-30 days (until remission of esophageal candidiasis is achieved). If necessary, patients with severe suppression of immune function can continue treatment for a longer time. * For the prevention of relapses of oropharyngeal candidiasis in HIV-infected patients with a high risk of relapses, fluconazole is used 100-200 mg per day or 200 mg 3 times a week for an indefinite period of time in patients with chronically reduced immunity. * To prevent recurrence of esophageal candidiasis in HIV-infected patients with a high risk of recurrence, fluconazole is used 100-200 mg per day or 200 mg 3 times a week for an indefinite period of time in patients with chronically reduced immunity. 5. In acute vaginal candidiasis, candidal balanitis, fluconazole is used once inside at a dose of 150 mg. To reduce the recurrence rate of vaginal candidiasis, the drug can be used at a dose of 150 mg every three days – only 3 doses (on the 1st,4th and 7th day), then a maintenance dose of 150 mg once a week. The maintenance dose can be used for up to 6 months. 6. Treatment of dermatomycosis• For skin infections, including foot dermatophytosis, trunk dermatophytosis, inguinal dermatophytosis, and candida infections, the recommended dose is 150 mg once a week or 50 mg once a day. The duration of therapy is usually 2-4 weeks, with mycoses of the feet may require longer therapy-up to 6 weeks. * For multi-colored ringworm, the recommended dose is 300-400 mg once a week for 1-3 weeks. An alternative treatment regimen is to use 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 usually takes 3-6 months and 6-12 months, respectively, for the nails on the fingers and feet to regrow. However, the rate of growth can vary widely in different people, as well as depending on age. After successful treatment of long-term chronic infections, sometimes there is a change in the shape of the nails. 7. For the prevention of candida infections in patients with long-term neutropenia, the recommended dose of fluconazole is 200-400 mg once a day, depending on the degree of risk of fungal infection. For patients at high risk of generalized infection, such as those with severe or long-term neutropenia, the recommended dose is 400 mg once a day. Fluconazole is used a few days before the expected development of neutropenia and after an increase in the number of neutrophils more than 1000 in mm3, treatment is continued for another 7 days. Use in children As with similar infections in adults, the duration of treatment depends on the clinical and mycological effect. For children, the daily dose of the drug should not exceed that for adults. Fluconazole is used daily once a 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 can be used to achieve the equilibrium concentration more quickly. For the treatment of invasive candidiasis and cryptococcal meningitis, the recommended dose is 6-12 mg / kg / day, depending on the severity of the disease. To suppress the recurrence of cryptococcal meningitis in children with AIDS, the recommended dose of fluconazole is 6 mg / kg / day. For the prevention of fungal infections in immunocompromised children who are at risk of developing neutropenia due to cytotoxic chemotherapy or radiation therapy, the drug is used at 3-12 mg / kg / day, depending on the severity and duration of maintenance of induced neutropenia (see dose for adults; for children with renal insufficiency – see dose for patients with renal insufficiency). If the dosage form of fluconazole in the form of capsules cannot be used correctly in children, the possibility of replacing it with other dosage forms of the drug (powder for preparing a suspension for oral use or solution for intravenous use) in equivalent doses should be considered. Use in elderly peopl Ein the absence of signs of renal insufficiency, fluconazole is used in the usual dose. Patients with renal insufficiency (creatinine clearanceUse in patients with renal insufficiency. With a single dose, no dose change is required. In patients (including children) with impaired renal function with repeated use of the drug, a shock dose of 50 mg to 400 mg should be initially administered, after which the daily dose (depending on the indication) is set according to the following table:

Patients on regular dialysis should receive 100% of the recommended dose after each dialysis session. On the day when dialysis is not performed, patients should receive a reduced (depending on creatinine clearance) dose of the drug. 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.

Overdose

Symptoms: hallucinations, paranoid behavior.

Treatment: symptomatic — gastric lavage, forced diuresis. Hemodialysis for 3 hours reduces the plasma concentration by approximately 50%.

Special instructions

Treatment should be continued until clinical and hematological remission occurs. Premature discontinuation of treatment leads to relapses.

During treatment, it is necessary to monitor blood parameters, kidney and liver function. If you experience impaired renal and hepatic function, you should stop taking the drug.

In rare cases, the use of fluconazole was accompanied by toxic changes in the liver, including with a fatal outcome, mainly in patients with serious concomitant diseases. In the case of hepatotoxic effects associated with fluconazole, there was no obvious dependence on the total daily dose, duration of therapy, gender and age of the patient. The hepatotoxic effect of fluconazole was usually reversible; signs of it disappeared after discontinuation of therapy. If there are clinical signs of liver damage that may be associated with fluconazole, the drug should be discontinued.

Patients People with AIDS are more likely to develop severe skin reactions when using many medications. In cases where patients with a superficial fungal infection develop a rash and it is considered definitely associated with fluconazole, the drug should be discontinued. If a rash appears in patients with invasive / systemic fungal infections, they should be carefully monitored and discontinue fluconazole if bullous changes or erythema multiforme occur.

Caution should be exercised when taking fluconazole concomitantly with cisapride, rifabutin, or other drugs that are metabolized by the cytochrome P450 system.

Form of production

Capsules

Storage conditions

At a temperature not exceeding 30 °C

Shelf life

5 years

Active ingredient

Fluconazole

Conditions of release from pharmacies

By prescription

Dosage form

Capsules

Purpose

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

Indications

Fungus, Thrush