Fluconazole is an effective remedy for combating candidiasis

Fluconazole - indications for use

His range of prescriptions is very wide, since fungal infections can bother any person in cases where he has a reduced immune system. Candidiasis of the mucous membranes and skin is not dangerous in itself and is easily treatable. For example, in mild cases of thrush, it is enough to take just one Fluconazole capsule once. But problems arise when the fungus penetrates deep into organs and tissues; in such cases we are talking about systemic mycosis. Fortunately, the generalized form is rare and is treated by hospital doctors. In this article we will list general indications and focus on the over-the-counter form of the drug Fluconazole. Despite the safety and ease of taking the drug, we still do not recommend self-medication.

• vaginal candidiasis;*
• candidiasis on the mucous membranes of the oral cavity (oropharyngeal candidiasis), esophageal candidiasis;
• chronic candidiasis of the oral cavity in patients using dentures;*
• candidal balanitis (fungal inflammation of the male genital organ);*
• invasive (systemic) candidiasis;
• candiduria - (fungi of the genus Candida in the urine);
• chronic candidiasis on the skin and mucous membranes;
• dermatomycosis, including: dermatophytosis of the feet, trunk, groin, lichen versicolor and cutaneous candidiasis, when systemic therapy is prescribed;
• dermatophytosis of the nails (onychomycosis), when therapy with other drugs is impossible;
• cryptococcal meningitis;
• coccidioidomycosis.

* when local treatment is not applicable.

In cases where the patient’s immune system cannot cope, Fluconazole is prescribed to prevent relapses:

• cryptococcal meningitis;
• candidiasis of the oral cavity and esophagus in HIV-infected patients;
• vaginal candidiasis (if symptoms of thrush appeared 4 times a year or more);
• for the prevention of candidiasis in patients with prolonged neutropenia (with hematologic malignancies undergoing chemotherapy or hematopoietic stem cell transplantation).

Flunol syrup 25mg/5ml 70.0 ml (fluconazole)

Full description

[RU]

Tradename

FLUNOL® 50

FLUNOL® 150

International nonproprietary name

Fluconazole

Dosage form

Capsules 50 mg, 150 mg

Compound

One capsule contains

active substance – fluconazole 50 mg and 150 mg,

excipients: lactose monohydrate, colloidal silicon dioxide (Aerosil 200), corn starch, magnesium stearate, sodium lauryl sulfate,

capsule shell composition:

body: titanium dioxide (E 171), gelatin,

cap for 50 mg dosage: titanium dioxide E 171, sparkling black (E151), gelatin

cap for dosage 150 mg: titanium dioxide E 171, iron oxide (III) red (E 172), gelatin

Description

Hard gelatin capsules size No. 3 with a matte white body and a matte dark blue cap (for a dosage of 50 mg).

Hard gelatin capsules size No. 1 with a matte white body and a matte pink cap (for a dosage of 150 mg).

Pharmacotherapeutic group

Antifungal drugs for systemic use. Triazole derivatives. Fluconazole.

ATX code J02AC01

Pharmacological properties

Pharmacokinetics

Fluconazole is well absorbed after oral administration, bioavailability is more than 90%. Eating does not affect the absorption of the drug. The maximum concentration is reached after 0.5 - 1.5 hours. Fluconazole penetrates well into body fluids. Levels of fluconazole in saliva and sputum approach its concentration in plasma. In patients with fungal meningitis, the level of fluconazole in the cerebrospinal fluid is about 80% of its plasma level.

In the stratum corneum of the epidermis, dermis and sweat glands, high concentrations of fluconazole are achieved, which exceed serum concentrations. Fluconazole binds poorly to plasma proteins (12%). The half-life is 30 hours. Not metabolized. No fluconazole metabolites were detected in peripheral blood. Fluconazole is excreted primarily by the kidneys; approximately 80% of the dose taken is found unchanged in the urine.

Pharmacokinetics in special clinical situations

The following pharmacokinetic parameters of fluconazole were identified in children:

In preterm infants (approximately 28 weeks of development), fluconazole was administered IV at a dose of 6 mg/kg every 3rd day for a maximum of 5 doses while the infants remained in the intensive care unit (ICU). The average T1/2 was 74 hours on day 1, decreasing on the 7th day to an average of 53 hours and on the 13th day to an average of 47 hours (range 27-68 hours).

AUC values ​​were 271 mcg x h/mL on day 1, increased to 490 mcg x h/mL on day 7, and decreased to an average of 360 mcg x h/mL by day 13.

Vd was 1183 ml/kg on day 1, then increased to an average of 1184 ml/kg on day 7 and to 1328 ml/kg on day 13.

Pharmacodynamics

Fluconazole, a member of the class of triazole antifungal agents, is a selective inhibitor of ergosterol synthesis in the fungal membrane. Increases the permeability of the cell membrane, disrupts its growth and replication. Pharmacological effect - fungicidal. It has a specific effect on fungal enzymes dependent on cytochrome P450. Does not have antiandrogenic activity. Treatment with fluconazole 50 mg/day for 28 days did not affect blood testosterone concentrations in men or steroid concentrations in women of childbearing age. Fluconazole is effective against superficial and systemic fungal infections caused by Candida spp., Cryptococcus neoformans, Coccidiodes immitis, Microsporum spp., Trichophyton spp., Blastomyces dermatitidis, Histoplasma capsulatum.

Indications for use

- genital candidiasis, acute or recurrent vaginal candidiasis, prophylaxis to reduce the frequency of relapses of vaginal candidiasis, candidal balanitis

— candidiasis of the mucous membranes, including the mucous membranes of the mouth, pharynx, esophagus, non-invasive bronchopulmonary infections, candiduria, mucocutaneous and chronic atrophic candidiasis of the oral cavity

— dermatomycosis, including mycoses of the feet, smooth skin of the trunk, limbs, pityriasis versicolor, skin candidiasis infections

- generalized candidiasis, including candidemia, disseminated candidiasis and other forms of invasive candidal infection, such as infections of the peritoneum, endocardium, respiratory and urinary tract, including in patients with malignant tumors in intensive care units and receiving cytotoxic or immunosuppressive therapy, and also in patients with other factors predisposing to the development of candidiasis

— cryptococcosis, including cryptococcal meningitis and infections of other localizations (for example, lungs, skin), incl. in patients with normal

immune response and AIDS patients, organ transplant recipients and patients with other forms of immunodeficiency; maintenance therapy to prevent relapses of cryptococcosis in patients with AIDS

- prevention of fungal infections in patients with malignant neoplasms predisposed to the development of such infections as a result of cytotoxic chemotherapy or radiation therapy

Directions for use and doses

For adults:

• for oropharyngeal candidiasis, on the first day the drug is usually prescribed at 200 mg, then continued at 100 mg once a day. Treatment is continued for 2 weeks to reduce the likelihood of relapse.
• For vaginal candidiasis, take a single dose of 150 mg orally. 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.
• For chronic recurrent vulvo-vaginal candidiasis (relapse rate 4 or more times a year), pulse therapy is recommended: 150 mg once a week for 1-3 months.
• For candidal balanitis - 150 mg once.
• For mycosis of the skin, the recommended dose is 150 mg once a week. The duration of therapy in normal cases is 2-4 weeks, however, with mycoses of the feet, longer therapy (up to 6 weeks) may be required.
• For onychomycosis, the recommended dose is 150 mg once a week. Treatment should be continued until an uninfected nail grows out. Fingernails and toenails normally take 3-6 and 6-12 months to re-grow, respectively.
• For pityriasis versicolor, 300 mg once a week for 2 weeks.

The maximum daily dose for adults should not be exceeded in children. Fluconazole is taken every day in a single dose.

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 patients with immunodeficiency, considered at risk due to neutropenia, receiving cytotoxic chemotherapy or radiation therapy, the drug is prescribed at 3-12 mg/kg/day, depending on the severity and duration of persistence of induced neutropenia.

Use in the elderly

In the absence of signs of renal failure, the drug is prescribed at the usual dose.

Use in patients with renal failure

With a single dose, no dose change is required. In patients with impaired renal function, with repeated use of the drug, a loading dose of 50 mg to 400 mg should initially be 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; on days when there is no dialysis, patients should receive a reduced dose according to their creatinine clearance.

Side effects

Common (≥1/100 to <1/10)

• headache
• abdominal pain, diarrhea, nausea, vomiting
• increased levels of alkaline phosphatase, serum levels of aminotransferases (ALT and AST)
• rash

Uncommon (≥1/1,000 to ≤1/100)

• insomnia, drowsiness
• convulsions, dizziness, paresthesia, change in taste
• vertigo
• dyspepsia, flatulence, dry mouth
• cholestasis, jaundice, increased bilirubin
• itching, urticaria, increased sweating, dermatitis
• myalgia
• fatigue, malaise, weakness, increased body temperature

Rare (≥1/10,000 to ≤1/1,000)

• agranulocytosis, leukopenia, neutropenia, thrombocytopenia
• anaphylaxis, angioedema
• hypertriglyceridemia, hypercholesterolemia, hypokalemia
• tremor

• tachycardia, ventricular fibrillation/flutter, increased QT interval
• hepatotoxicity, including rare cases of death, liver failure, hepatocellular necrosis, hepatitis, hepatocellular injury
• toxic epidermal necrolysis, Stevens-Johnson syndrome, acute generalized exanthematous pustulosis, exfoliative dermatitis, facial edema, alopecia

In patients with AIDS or cancer, changes in blood counts, renal and liver function have been observed during treatment with fluconazole and similar drugs, but the clinical significance of these changes and their relationship to treatment have not been established.

Contraindications

• hypersensitivity to fluconazole, other components of the drug or azole substances with a structure similar to fluconazole
• simultaneous use of terfenadine during repeated doses of fluconazole at a dose of 400 mg/day or more
• concomitant use of drugs that prolong the QT interval and are metabolized by the CYP3A4 enzyme, such as cisapride, astemizole, erythromycin, pimozide and quinidine
• hereditary lactose intolerance, Lapp-lactase enzyme deficiency, glucose-galactose malabsorption
• pregnancy and lactation
• children under 18 years of age

Carefully

Impaired liver function parameters due to the use of fluconazole; the appearance of a rash during the use of fluconazole in patients with superficial fungal infection and invasive/systemic fungal infections; potentially proarrhythmic conditions in patients with multiple risk factors (organic heart disease, electrolyte imbalance and concomitant therapy that contributes to the development of such disorders).

Drug interactions

With simultaneous use of FLUNOL® 50, FLUNOL® 150:

• with coumarin anticoagulants - fluconazole increases prothrombin time. Patients receiving coumarin anticoagulants should be under strict medical supervision
• with cisapride - cases of adverse cardiac events have been described, including paroxysms of ventricular tachycardia (AR)
• with cyclosporine - it is recommended to control the concentration of cyclosporine in the blood, as it may increase;
• with hydrochlorothiazide - leads to an increase in the concentration of fluconazole in the blood by 40%. However, this does not require a change in dosage regimen
• with ethinyl estradiol and levonorgestrel - fluconazole increases their areas under the concentration-time curve (AUC). However, this does not affect the effectiveness of the combined oral contraceptive drug
• with phenytoin - a significant increase in phenytoin concentrations may be observed. If it is necessary to use combined treatment with phenytoin, it is necessary to control the level of the latter and adequate dose selection to ensure therapeutic concentrations in the serum
• with rifampicin - leads to a decrease in fluconazole AUC by 25% and T1/2 by 20%. It is necessary to consider the advisability of increasing the dose of fluconazole
• with oral hypoglycemic agents (sulfonylurea derivatives) - fluconazole prolongs their half-life. Frequent monitoring of blood glucose and appropriate reduction of sulfonylurea dosage is recommended
• with antifungal drugs from the group of azole derivatives, with terfenadine and astemizole - the likelihood of developing serious arrhythmias with prolongation of the QT interval increases (if necessary, the use of such a combination requires careful medical supervision)
• with theophylline - it is possible to lengthen the half-life of theophylline from plasma and develop symptoms of its overdose;
• with zidovudine - leads to an increase in the concentration of zidovudine in plasma. Patients receiving this combination should be monitored for side effects of zidovudine.
• with antipyrine - fluconazole at a dose of 50 mg does not affect the metabolism of antipyrine
• with midazolam - fluconazole significantly increases the concentration of midazolam and psychomotor effects;
• with triazolam - increases the AUC of triazolam (single dose) by approximately 50%, Cmax by 20-32% and t½ by 25-50%, due to inhibition of triazolam metabolism. Triazolam dose adjustment may be required
• with benzodiazepines - careful monitoring is necessary in order to reduce the benzodiazepine dose accordingly
• with slow calcium channel blockers (nifedipine, isradipine, amlodipine, verapamil and felodipine) - fluconazole can significantly increase the systemic exposure of calcium channel antagonists. Frequent monitoring for drug side effects is recommended
• with non-steroidal anti-inflammatory drugs (celecoxib, flurbiprofen, ibuprofen, naproxen, lornoxicam, meloxicam, diclofenac) - increases the Cmax and AUC of NSAIDs. Frequent monitoring for NSAID-related adverse effects and toxicities is recommended. NSAID dose adjustment may be required
• with cyclophosphamide - increases the levels of bilirubin and creatinine in the blood serum. The combination may be used before there is a risk of increased serum bilirubin and creatinine levels
• with fentanyl - fluconazole significantly delays the elimination of fentanyl. Elevated concentrations of fentanyl may lead to respiratory failure
• alfentanil: with simultaneous therapy with fluconazole, a decrease in clearance and volume of distribution, as well as an extension of the elimination period of alfentanil, is observed. A possible mechanism of action is inhibition of the CYP3A4 enzyme by fluconazole. Alfentanil dose adjustment may be required
• with halofantrine - fluconazole may increase plasma concentrations of halofantrine due to an inhibitory effect on CYP3A4;
• with hydroxymethylglutaryl-A reductase (HMG-CoA reductase) inhibitors - the risk of myopathy and acute skeletal muscle necrosis (rhabdomyolysis) increases when fluconazole is prescribed concomitantly with HMG-CoA reductase inhibitors that are metabolized through CYP3A4, such as atorvastatin and simvastatin , or via CYP2C9, such as fluvastatin. If concomitant therapy is necessary, the patient should be observed for symptoms of myopathy and rhabdomyolysis, and creatine kinase levels should be monitored. HMG-CoA reductase inhibitors should be discontinued if a significant increase in creatine kinase levels is observed or if myopathy/rhabdomyolysis is diagnosed or suspected.
• with losartan - fluconazole inhibits the metabolism of losartan to its active metabolite (E-31 74), which is responsible for most of the angiotensin II receptor antagonism that occurs during treatment with losartan. Patients should constantly monitor blood pressure
• with methadone – the concentration of methadone in the blood serum increases, methadone dosage adjustment may be required
• with vinca alkaloid—may increase plasma levels of vinca alkaloid (eg, vincristine and vinblastine) and lead to neurotoxicity due to inhibitory effects on CYP3A4
• with vitamin A – close monitoring of patients is required to identify CNS-related side effects
• with voriconazole - simultaneous administration of voriconazole and fluconazole at any dose is not recommended. Concomitant use of oral voriconazole (400 mg every 12 hours on day 1, then 200 mg every 12 hours for 2.5 days) and oral fluconazole (400 mg on day 1, then 200 mg every 24 hours for 4 days) resulted in an average increase in voriconazole concentration and AUC of 57% (9% CI: 20%, 107%) and 79% (90% CI: 40%, 128%), respectively.
• with cimetidine, antacids - no clinically significant effect on the absorption of fluconazole is observed
• with prednisolone - patients on long-term treatment with fluconazole and prednisolone should be monitored for the development of adrenal insufficiency after discontinuation of fluconazole
• with rifabutin – increases serum rifabutin levels by up to 80%. Cases of uveitis have been reported in patients who were simultaneously prescribed fluconazole and rifabutin. Careful monitoring of the condition of patients receiving rifabutin and fluconazole simultaneously is necessary.
• with saquinavir - increases the AUC of saquinavir by approximately 50%, Cmax by approximately 55% and reduces the clearance of saquinavir by approximately 50% due to inhibition of the hepatic metabolism of saquinavir via CYP3A4 and inhibition of P-glycoprotein. Dose adjustments of saquinavir may be necessary;
• with sirolimus - the plasma concentration of sirolimus increases, presumably by inhibiting the metabolism of sirolimus through CYP3A4 and P-glycoprotein. This combination may be used to adjust the dose of sirolimus based on effect/concentration measurements;
• with tacrolimus - serum concentrations of tacrolimus when taken orally may increase up to 5-fold due to inhibition of the metabolism of tacrolimus in the intestine via CYP3A4. No significant pharmacokinetic changes were observed with intravenous tacrolimus. Increased tacrolimus levels have been associated with nephrotoxicity. The dosage of oral tacrolimus should be reduced depending on the drug concentration
• amitriptyline, nortriptyline: fluconazole enhances the effect of amitriptyline and nortriptyline. Concentrations of 5-nortriptyline and/or S-amitriptyline may be measured at the start of combination therapy and after one week. If necessary, the dose of amitriptyline/nortriptyline should be adjusted
• carbamazepine: fluconazole inhibits the metabolism of carbamazepine and increases the concentration of the latter in the blood serum by 30%. There is a risk of carbamazepine toxicity. Carbamazepine dosage adjustments may be necessary based on concentration/effect measurements.

special instructions

Treatment must be continued until clinical and mycological remission of the disease occurs. Premature cessation of treatment leads to relapses. Treatment can begin before receiving the results of culture or other laboratory tests, with subsequent correction of fungicidal therapy based on the results of the studies. During treatment, it is necessary to monitor blood counts, kidney and liver function. If renal or liver dysfunction occurs, you should stop taking the drug. In rare cases, the use of fluconazole was accompanied by toxic changes in the liver, including death, mainly in patients with concomitant diseases. Patients whose liver function tests are impaired during treatment with fluconazole should be monitored for signs of liver damage. If clinical signs or symptoms of liver damage appear that may be associated with the use of fluconazole, the drug should be discontinued. The hepatotoxic effect of fluconazole is usually reversible, and symptoms disappear after discontinuation of therapy. If skin rashes occur in patients with immunosuppression, careful observation is necessary, and if the skin reaction progresses, treatment should be discontinued (risk of developing Stevens-Johnson syndrome, Lyell's syndrome). People with AIDS are more likely to develop severe skin reactions. If a patient receiving treatment for a superficial fungal infection develops a rash that can be associated with fluconazole, the drug should be discontinued. If a rash appears in patients with invasive/systemic fungal infections, they should be closely monitored and fluconazole should be discontinued if bullous lesions or erythema multiforme appear. In rare cases, anaphylactic reactions have been observed.

Fluconazole may cause prolongation of the QT interval on the ECG. When using fluconazole, an increase in the QT interval and ventricular fibrillation/flutter were observed very rarely in patients with multiple risk factors, such as organic heart disease, electrolyte imbalances and concomitant therapy that contributes to the development of such disorders. Therefore, fluconazole should be used with caution in such patients with potentially proarrhythmic conditions.

Patients with liver, heart and kidney diseases are advised to consult a doctor before use.

When using Flunol® 50 mg or Flunol® 150 for vaginal candidiasis, patients should be warned that improvement in symptoms is usually observed after 24 hours, but sometimes takes several days for them to completely disappear.

Fluconazole is a strong CYP2C9 inhibitor and a moderate CYP3A4 inhibitor. Patients receiving treatment with fluconazole who are taking concomitant therapy with drugs with a narrow therapeutic window that are metabolized through CYP2C9 and CYP3A4 should be monitored.

Flunol® 50 or Flunol® 150 should be taken with caution by patients with renal dysfunction.

Pediatric population

Examples and cases of adverse events and laboratory abnormalities that were observed in children are comparable to those observed in adults.

Pregnancy and lactation

During pregnancy, the use of the drug should be avoided, except in patients with severe or potentially life-threatening fungal infection for whom fluconazole can be used if the expected benefit is higher than the possible risk to the fetus.

Use during breastfeeding

Fluconazole has been found in breast milk at plasma concentrations and is therefore not recommended for use in nursing mothers.

Features of the effect of the drug on the ability to drive a vehicle or potentially dangerous mechanisms

Patients should be informed about the hazards associated with driving vehicles, servicing mechanical equipment, and other potentially hazardous activities.

Overdose

Symptoms: hallucinations, paranoid behavior.

Treatment: supportive and symptomatic therapy is used, if necessary, gastric lavage. Since fluconazole is excreted primarily in the urine, forced diuresis is likely to increase the rate of elimination. A 3-hour hemodialysis session reduces the plasma concentration of fluconazole by approximately 50%.

Release form and packaging

7 capsules (for a dosage of 50 mg) or 1 or 2 capsules (for a dosage of 150 mg) are placed in a blister pack made of transparent polyvinyl chloride film and printed aluminum foil.

1 or 2 (for a dosage of 50 mg) or 1 (for a dosage of 150 mg) blister packs together with instructions for medical use in the state and Russian languages ​​are placed in a cardboard pack with a hologram of the manufacturer.

Storage conditions

In a dry place, protected from light, at a temperature not exceeding 25 0C.

Keep out of the reach of children!

Shelf life

4 years

Do not use after expiration date

Conditions for dispensing from pharmacies

On prescription

The Republic of Kazakhstan

Almaty, st. Shevchenko 162 E.

Registration Certificate Holder

JSC "Nobel Almaty Pharmaceutical Factory"

The Republic of Kazakhstan

Address of the organization that accepts claims from consumers regarding the quality of products (products) on the territory of the Republic of Kazakhstan:

JSC "Nobel Almaty Pharmaceutical Factory"

Republic of Kazakhstan, Almaty, st. Shevchenko 162 E.

Phone number: (+7

Fax number: (+7

E-mail address

Fluconazole - instructions for use

The capsules are swallowed with water. Patients usually ask how to take it - before or after meals? In this case it does not matter, food does not affect bioavailability.

• Chronic atrophic candidiasis of the oral cavity when wearing dentures is prescribed in a dose of 50 mg 1 time / day. for 2 weeks in combination with local antiseptic treatment.
• Acute vaginal candidiasis, balanitis, complicated by fungi of the genus Candida, Fluconazole is prescribed once orally in a dose of 150 mg. To prevent relapses of vaginal candidiasis, use 150 mg every three days - a total of 3 doses (on the 1st, 4th and 7th day), then 150 mg once a week for maintenance. Maintenance therapy, if necessary, can be carried out for up to 6 months.
• Dermatomycoses. Skin infections, including dermatophytosis of the feet, trunk, groin area, for candidal infections, the dose is 150 mg once a week or 50 mg once a day. The duration of treatment is usually 2-4 weeks; for foot infections, therapy up to 6 weeks is possible.
• Lichen versicolor - 300-400 mg 1 time/week for 1-3 weeks or 50 mg 1 time per day for 2-4 weeks (depending on the regimen, the patient buys a dosage of 150 mg or 50 mg).
• Nail fungus (onychomycosis) - 150 mg 1 time/week, treatment should continue until the infected nail is replaced with a healthy one. This may take several months.

FLUCONAZOL (Fluconazole)

Single or repeated use of fluconazole at a dose of 50 mg does not affect the metabolism of phenazone (Antipyrin) when used simultaneously.

Concomitant use of fluconazole with the following drugs is contraindicated:

Cisapride: with the simultaneous use of fluconazole and cisapride, adverse reactions from the heart are possible, incl. ventricular tachysystolic arrhythmia of the “pirouette” type (torsade de pointes). The use of fluconazole at a dose of 200 mg once a day and cisapride at a dose of 20 mg 4 times a day leads to a marked increase in plasma concentrations of cisapride and an increase in the QT interval on the ECG. The simultaneous use of cisapride and fluconazole is contraindicated.

Terfenadine: When azole antifungals are used concomitantly with terfenadine, serious arrhythmias may occur as a result of prolongation of the QT interval. When using fluconazole at a dose of 200 mg/day, an increase in the QT interval has not been established; however, the use of fluconazole at doses of 400 mg/day and above causes a significant increase in the concentration of terfenadine in the blood plasma. Concomitant use of fluconazole in doses of 400 mg/day or more with terfenadine is contraindicated (see section “Contraindications”). Treatment with fluconazole in doses less than 400 mg/day in combination with terfenadine should be carried out under close monitoring.

Astemizole: simultaneous use of fluconazole with astemizole or other drugs metabolized by the cytochrome P450 system may be accompanied by an increase in serum concentrations of these drugs. Elevated concentrations of astemizole in blood plasma can lead to prolongation of the QT interval and, in some cases, to the development of ventricular tachysystolic arrhythmia of the “pirouette” type (torsade de pointes). The simultaneous use of astemizole and fluconazole is contraindicated.

Pimozide: Although adequate in
vitro
or
in vivo ,
concomitant use of fluconazole and pimozide may result in inhibition of the metabolism of pimozide. In turn, an increase in plasma concentrations of pimozide can lead to a prolongation of the QT interval and, in some cases, to the development of ventricular tachysystolic arrhythmia of the “pirouette” type (torsade de pointes). The simultaneous use of pimozide and fluconazole is contraindicated.

Quinidine: Although adequate in
vitro
or
in vivo ,
concomitant use of fluconazole and quinidine may also result in inhibition of quinidine metabolism. The use of quinidine is associated with prolongation of the QT interval and, in some cases, with the development of ventricular tachysystolic arrhythmia of the “torsade de pointes” type. The simultaneous use of quinidine and fluconazole is contraindicated.

Erythromycin: Concomitant use of fluconazole and erythromycin potentially leads to an increased risk of cardiotoxicity (QT prolongation, torsade de pointes) and consequently sudden cardiac death. The simultaneous use of fluconazole and erythromycin is contraindicated.

The following medications are not recommended:

Halofantrine: Fluconazole may increase plasma concentrations of halofantrine due to inhibition of CYP3A4. It is possible to develop ventricular tachysystolic arrhythmia of the “pirouette” type (torsade de pointes) when used simultaneously with fluconazole, as well as with other azole antifungal drugs, so their combined use is not recommended.

Caution should be exercised when used simultaneously with fluconazole:

Amiodarone: Amiodarone has been associated with QT prolongation. Caution should be exercised when using fluconazole and amiodarone concomitantly, especially when taking a high dose of fluconazole (800 mg).

Caution and possible dosage adjustments should be used when the following drugs are used concomitantly with fluconazole:

Drugs that affect fluconazole:

Hydrochlorothiazide: repeated use of hydrochlorothiazide concomitantly with fluconazole leads to an increase in plasma concentrations of fluconazole by 40%. An effect of this magnitude does not require a change in the fluconazole dosage regimen in patients receiving concomitant diuretics, but the physician should take this into account.

Rifampicin: Concomitant use of fluconazole and rifampicin results in a 25% decrease in AUC and a 20% decrease in fluconazole half-life. In patients concomitantly taking rifampicin, the advisability of increasing the dose of fluconazole must be considered.

Drugs

,
which are affected by fluconazole:
fluconazole is a moderate inhibitor of cytochrome P450 (CYP) isoenzymes 2C9 and 3A4. Fluconazole is also an inhibitor of the CYP2C19 isoenzyme. In addition, in addition to the effects listed below, there is a risk of increased plasma concentrations of other drugs metabolized by the isoenzymes CYP2C9, CYP2C19 and CYP3A4 when used simultaneously with fluconazole. In this regard, caution should be exercised when using these drugs simultaneously, and if such combinations are necessary, patients should be under close medical supervision. It should be taken into account that the inhibitory effect of fluconazole persists for 4-5 days after discontinuation of the drug due to the long half-life.

Alfentanil: There is a decrease in clearance and volume of distribution, and an increase in the half-life of alfentanil. This may be due to inhibition of the CYP3A4 isoenzyme by fluconazole. Alfentanil dosage adjustment may be required.

Amitriptyline, nortriptyline: increased effect. Concentrations of 5-nortriptyline and/or S-amitriptyline can be measured at the start of combination therapy with fluconazole and one week after initiation. If necessary, the dose of amitriptyline/nortriptyline should be adjusted.

Amphotericin B: In studies in mice (including immunosuppressed mice), the following results were observed: small additive antifungal effect in systemic infection with C.
albicans ,
no interaction in intracranial infection with
Cryptococcus neoformans
and antagonism in systemic infection with
A. . fumigatus .
The clinical significance of these results is unclear.

Anticoagulants: like other antifungal agents (azole derivatives), fluconazole, when used simultaneously with warfarin, increases prothrombin time (by 12%), and therefore bleeding may develop (hematomas, bleeding from the nose and gastrointestinal tract, hematuria , melena). In patients receiving coumarin and indanedione anticoagulants and fluconazole, it is necessary to constantly monitor prothrombin time during therapy and for 8 days after simultaneous use. The feasibility of adjusting the dose of these anticoagulants should also be assessed.

Azithromycin: with simultaneous oral use of fluconazole in a single dose of 800 mg with azithromycin in a single dose of 1200 mg, no pronounced pharmacokinetic interaction has been established between both drugs.

Benzodiazepines (short-acting): After oral administration of midazolam, fluconazole significantly increases midazolam concentrations and psychomotor effects, and this effect is more pronounced after fluconazole is administered orally than when fluconazole is administered intravenously. If concomitant therapy with benzodiazepines is necessary, patients taking fluconazole should be monitored to assess the appropriateness of an appropriate reduction in the benzodiazepine dose. With the simultaneous use of a single dose of triazolam, fluconazole increases the AUC of triazolam by approximately 50%, Cmax by 20-32% and half-life by 25-50% due to inhibition of triazolam metabolism. Triazolam dose adjustment may be necessary.

Carbamazepine: Fluconazole inhibits the metabolism of carbamazepine and increases the serum concentration of carbamazepine by 30%. The risk of carbamazepine toxicity must be taken into account. The need for carbamazepine dose adjustment based on concentration/effect should be assessed.

Slow calcium channel blockers: Some calcium channel antagonists (nifedipine, isradipine, amlodipine, verapamil and felodipine) are metabolized by the CYP3A4 isoenzyme. Fluconazole increases the systemic exposure of calcium channel antagonists. Monitoring for the development of side effects is recommended.

Nevirapine: Coadministration of fluconazole and nevirapine increased nevirapine exposure by approximately 100% compared with control data for nevirapine alone. Due to the risk of increased excretion of nevirapine during concomitant use of drugs, some precautions and careful monitoring of patients are necessary.

Cyclosporine: In patients with a kidney transplant, the use of fluconazole at a dose of 200 mg/day leads to a slow increase in cyclosporine concentrations. However, with repeated use of fluconazole at a dose of 100 mg/day, no changes in cyclosporine concentrations were observed in bone marrow recipients. When using fluconazole and cyclosporine simultaneously, it is recommended to monitor the concentration of cyclosporine in the blood.

Everolimus: Although this interaction has not been studied in
vivo
or
in vitro ,
fluconazole may increase everolimus plasma concentrations by inhibiting CYP3A4.

Cyclophosphamide: with simultaneous use of cyclophosphamide and fluconazole, an increase in serum concentrations of bilirubin and creatinine is observed. This combination is acceptable given the risk of increased bilirubin and creatinine concentrations.

Fentanyl: There has been a report of one death possibly related to the concomitant use of fentanyl and fluconazole. The disturbances are believed to be related to fentanyl intoxication. Fluconazole has been shown to significantly prolong the clearance time of fentanyl. It should be borne in mind that an increase in the concentration of fentanyl can lead to depression of respiratory function.

HMG-CoA reductase inhibitors: When fluconazole is used concomitantly with HMG-CoA reductase inhibitors metabolized by the CYP3A4 isoenzyme (such as atorvastatin and simvastatin) or the CYP2D6 isoenzyme (such as fluvastatin), the risk of developing myopathy and rhabdomyolysis increases. If simultaneous therapy with these drugs is necessary, patients should be monitored to identify symptoms of myopathy and rhabdomyolysis. It is necessary to monitor the concentration of creatinine kinase. If there is a significant increase in creatinine kinase concentrations or if myopathy or rhabdomyolysis is diagnosed or suspected, therapy with HMG-CoA reductase inhibitors should be discontinued.

Ibrutinib: Moderate CYP3A4 inhibitors such as fluconazole increase ibrutinib plasma concentrations and may increase the risk of toxicity. If the use of drugs in combination cannot be avoided, reduce the dose of ibrutinib as indicated in the ibrutinib prescribing information and ensure close clinical monitoring.

Losartan: Fluconazole inhibits the metabolism of losartan to its active metabolite (E-31 74), which is responsible for most of the effects associated with angiotensin II receptor antagonism. Regular monitoring of blood pressure is necessary. Methadone: Fluconazole may increase plasma concentrations of methadone. Methadone dose adjustment may be necessary.

Nonsteroidal anti-inflammatory drugs (NSAIDs): Cmax and AUC of flurbiprofen increased by 23% and 81%, respectively. Similarly, the Cmax and AUC of the pharmacologically active isomer [S-(+)-ibuprofen] increased by 15% and 82%, respectively, when fluconazole was administered simultaneously with racemic ibuprofen (400 mg).

With simultaneous use of fluconazole at a dose of 200 mg/day and celecoxib at a dose of 200 mg, the Cmax and AUC of celecoxib increase by 68% and 134%, respectively. In this combination, it is possible to reduce the dose of celecoxib by half.

Although there are no targeted studies, fluconazole may increase the systemic exposure of other NSAIDs metabolized by CYP2C9 (eg, naproxen, lornoxicam, meloxicam, diclofenac). NSAID dose adjustment may be necessary.

When NSAIDs and fluconazole are used concomitantly, patients should be closely monitored medically to identify and monitor NSAID-related adverse events and toxicities.

Olaparib: Moderate CYP3A4 inhibitors, such as fluconazole, increase plasma concentrations of olaparib. Their simultaneous use is not recommended. If concomitant use cannot be avoided, reduce the dose of olaparib to 200 mg twice daily.

Oral contraceptives: with simultaneous use of a combined oral contraceptive with fluconazole at a dose of 50 mg, no significant effect on hormone levels has been established, while with daily use of 200 mg fluconazole, the AUC of ethinyl estradiol and levonorgestrel increases by 40% and 24%, respectively, and with the use of 300 mg fluconazole once weekly administration, the AUCs of ethinyl estradiol and norethindrone increased by 24% and 13%, respectively. Thus, repeated use of fluconazole at the indicated doses is unlikely to affect the effectiveness of the combined oral contraceptive.

Phenytoin: Concomitant use of fluconazole and phenytoin may be accompanied by a clinically significant increase in phenytoin concentrations. If concomitant use of both drugs is necessary, phenytoin concentrations should be monitored and the dose adjusted accordingly to ensure therapeutic serum concentrations.

Ivacaftor: When coadministered with ivacaftor, a cystic fibrosis transmembrane conductance regulator (CFTR) stimulator, there was a 3-fold increase in ivacaftor exposure and a 1.9-fold increase in hydroxymethyl-ivacaftor (Ml) exposure. For patients concomitantly taking moderate CYP3A inhibitors such as fluconazole and erythromycin, a dose reduction of ivacaftor to 150 mg once daily is recommended.

Prednisone: there is a report of the development of acute adrenal insufficiency in a patient after liver transplantation when fluconazole was discontinued after a three-month course of therapy. Presumably, discontinuation of fluconazole therapy caused an increase in the activity of the CYP3A4 isoenzyme, which led to increased metabolism of prednisone.

Patients receiving combination therapy with prednisone and fluconazole should be under close medical supervision when discontinuing fluconazole to evaluate the condition of the adrenal cortex.

Rifabutin: Concomitant use of fluconazole and rifabutin can lead to an increase in serum concentrations of the latter by up to 80%. Cases of uveitis have been described with the simultaneous use of fluconazole and rifabutin. Patients receiving rifabutin and fluconazole concomitantly should be monitored closely.

Saquinavir: AUC increases by approximately 50%, Cmax by 55%, clearance of saquinavir decreases by approximately 50% due to inhibition of hepatic metabolism of the CYP3A4 isoenzyme and inhibition of P-glycoprotein. Dose adjustment of saquinavir may be necessary.

Sirolimus: increased plasma concentrations of sirolimus, presumably due to inhibition of sirolimus metabolism through inhibition of the CYP3A4 isoenzyme and P-glycoprotein. This combination can be used with appropriate dose adjustment of sirolimus depending on the effect/concentration.

Sulfonylureas: Fluconazole, when used concomitantly, leads to an increase in the half-life of oral sulfonylureas (chlorpropamide, glibenclamide, glipizide and tolbutamide). Patients with diabetes mellitus can be prescribed the combined use of fluconazole and oral sulfonylureas, but the possibility of hypoglycemia should be taken into account, in addition, regular monitoring of blood glucose is necessary and, if necessary, dose adjustment of sulfonylureas.

Tacrolimus: simultaneous use of fluconazole and tacrolimus (orally) leads to an increase in serum concentrations of the latter by 5 times due to inhibition of the metabolism of tacrolimus occurring in the intestine through the CYP3A4 isoenzyme. No significant changes in the pharmacokinetics of the drugs were observed when tacrolimus was administered intravenously. Cases of nephrotoxicity have been described. Patients receiving oral tacrolimus and fluconazole concomitantly should be monitored closely. The dose of tacrolimus should be adjusted depending on the degree of increase in its concentration in the blood.

Theophylline: when used simultaneously with fluconazole at a dose of 200 mg for 14 days, the average rate of plasma clearance of theophylline is reduced by 18%. When prescribing fluconazole to patients taking high doses of theophylline or to patients at increased risk of theophylline toxicity, monitor for symptoms of theophylline overdose and, if necessary, adjust therapy accordingly.

Tofacitinib: The exposure of tofacitinib is increased when coadministered with drugs that are both moderate inhibitors of CYP3A4 and CYP2C19 (eg, fluconazole). Dose adjustment of tofacitinib may be necessary.

Tolvaptan: Tolvaptan exposure is significantly increased (AUC by 200%, Cmax by 80%) when tolvaptan, a CYP3A4 substrate, is coadministered with fluconazole, a moderate CYP3A4 inhibitor. At the same time, there is a risk of a significant increase in the incidence of adverse events, in particular, such as increased diuresis, dehydration and acute renal failure. If these drugs are used concomitantly, the dose of tolvaptan should be reduced and the patient's condition should be closely monitored.

Vinca alkaloid: Although focused studies are lacking, it is suggested that fluconazole may increase plasma concentrations of vinca alkaloids (e.g., vincristine and vinblastine) and thus lead to neurotoxicity, possibly due to inhibition of CYP3A4.

Vitamin A: There has been a report of one case of central nervous system (CNS) adverse reactions in the form of pseudotumor cerebri with the simultaneous use of all-trans retinoic acid and fluconazole, which disappeared after discontinuation of fluconazole. The use of this combination is possible, but one should remember the possibility of adverse reactions from the central nervous system.

Zidovudine: when used simultaneously with fluconazole, an increase in the Cmax and AUC of zidovudine is observed by 84% and 74%, respectively. This effect is probably due to a decrease in the metabolism of the latter to its main metabolite. Before and after therapy with fluconazole at a dose of 200 mg/day for 15 days in patients with AIDS and ARC (AIDS-related complex), a significant increase in the AUC of zidovudine (20%) was found.

Patients receiving this combination should be monitored for side effects of zidovudine.

Voriconazole (inhibitor of CYP2C9, CYP2C19 and CYP3A4 isoenzymes): simultaneous use of voriconazole (400 mg 2 times a day on the first day, then 200 mg twice a day for 2.5 days) and fluconazole (400 mg on the first day, then 200 mg per day for 4 days) leads to an increase in voriconazole Cmax and AUC by 57% and 79%, respectively. It has been shown that this effect persists when the dose is reduced and/or the frequency of administration of any of the drugs is reduced. Concomitant use of voriconazole and fluconazole is not recommended.

Studies of the interaction of oral forms of fluconazole when taken simultaneously with food, cimetidine, antacids, as well as after total body irradiation in preparation for bone marrow transplantation showed that these factors do not have a clinically significant effect on the absorption of fluconazole.

The listed interactions were established with repeated use of fluconazole; There are no known drug interactions resulting from a single dose of fluconazole.

Doctors should note that interactions with other drugs have not been specifically studied, but are possible.

How to take Fluconazole for thrush?

With this pathology, patients can purchase medicine without a prescription and on the advice of a pharmacist. If you visit a doctor, he will confidently prescribe Fluconazole even before receiving test results for pathogens. Later, if the examination results are available, the doctor will only need to adjust the treatment regimen, or continue the chosen tactics. Fluconazole capsules help very quickly.

When taken orally, the level of bioavailability of the drug is as high as when administered intravenously, so it is enough to take one 150 mg capsule once with water. To prevent symptoms from returning, it is possible to take the drug every three days, with a total of 3 doses - on days 1, 4 and 7.

Fluconazole can begin to work within a day. In particular, the manufacturer of the original drug Pfizer (Diflucan) specifically reports that relief occurs within 24 hours. However, it is necessary to consult a doctor in order to exclude the presence of other pathogenic agents.

Fluconazole 150 mg

Thrush itself is not a sexually transmitted infection. Candidiasis develops against a background of reduced immunity, for example, after using antibiotics, when wearing synthetic underwear, during periods of very hot weather and even under stress. During a visit to the doctor, patients must be informed about the presence of a sexual partner so that preventive or therapeutic measures can be prescribed.

Women often ask the question: can cystitis appear from thrush? In this case, only the doctor can give an objective answer. The development of cystitis against the background of thrush is a very real scenario if the patient ignores visiting a specialist. Yeast-like fungi travel from the urethra to the bladder and cause inflammation there. Symptoms of vaginal candidiasis and cystitis may be similar. In the future, the infection from the bladder can reach the kidneys and there lead to acute renal failure. Therefore, therapy must be started on time. Sometimes women do not have candidiasis, but it develops after treating cystitis with antibiotics. A doctor will help correct the unpleasant effect.

Buy Diflucan powder for oral suspension 50mg/5ml 35ml in pharmacies

Diflucan Buy Diflucan in pharmacies Diflucan in the medicine directory DOSAGE FORMS powder for the preparation of suspension for oral administration 50 mg/5 ml MANUFACTURERS Pfizer PGM (France) GROUP Antifungal agents - derivatives of imidazole and triazole COMPOSITION Active substance - fluconazole. INTERNATIONAL NON-PROPENTED NAME Fluconazole SYNONYMS Vero-Fluconazole, Diflazon, Maiconil, Medoflucon, Mikomax, Mikosist, Mikoflucan, Procanazole, Fluzol, Flucozan, Flucomabol, Flucomicide Sediko, Fluconazole, Fluconazole Hexal, Fluconazole Stada, Fluconazole -LEKSVM, Fluconazole-Teva, Fluconorm, Flucoral, Flucostat, Flumicon, Forkan, Tsiskan PHARMACOLOGICAL ACTION Pharmacological action - antifungal. Highly selectively inhibits fungal cytochrome P450; blocks the synthesis of sterols in fungal cells. Absorbed from the gastrointestinal tract quickly and quite completely. The maximum concentration is achieved 0.5-1.5 hours after administration on an empty stomach. It is excreted unchanged by the kidneys. The half-life is about 30 hours. When administered intravenously, it has similar pharmacokinetic characteristics. INDICATIONS FOR USE Candidiasis (vaginal, mucous membranes, generalized), cryptococcosis, skin mycoses, deep endemic mycoses, prevention of fungal infections in malignant neoplasms. CONTRAINDICATIONS Hypersensitivity, pregnancy, breastfeeding (stop during treatment). SIDE EFFECTS : Nausea, abdominal pain, diarrhea, flatulence, liver damage, headache, alopecia, leukopenia, thrombocytopenia (in immunocompromised individuals), skin rash. INTERACTION Enhances the effect of oral hypoglycemic drugs (sulfonylurea derivatives), coumarin anticoagulants, urinary excretion of cyclosporine and rifampicin. Hydrochlorothiazide increases blood concentrations by 40%. When used simultaneously with cisapride and zidovudine, the development of paroxysmal ventricular tachycardia is possible. METHOD OF APPLICATION AND DOSAGE Orally. Adults with cryptococcal infections - 200-400 mg per day; for generalized candidiasis - 400 mg, then 200 mg per day; for oropharyngeal candidiasis - 50-100 mg per day for 7-14 days; for vaginal candidiasis - once 150 mg; for mycoses - 150 mg once a week. For children with candidiasis of the mucous membranes - 3-6 mg/kg/day, for generalized candidiasis - 6-12 mg/kg/day, for the prevention of fungal infections - 3-12 mg/kg/day. OVERDOSE No information available. SPECIAL INSTRUCTIONS Prescribe with caution to patients with impaired renal function, newborns, and AIDS patients. It is necessary to carefully monitor blood counts and liver function. If a rash or bullous changes or erythema multiforme appear, therapy should be discontinued. STORAGE CONDITIONS List B. In a dry place, protected from light, at room temperature.

Can Fluconazole be used during breastfeeding and pregnancy?

The use of the drug during pregnancy should be avoided, with the exception of severe or life-threatening systemic fungal infections, when the expected benefit of therapy for the mother outweighs the possible risk to the fetus.

Women of childbearing age should also use reliable methods of contraception during treatment with Fluconazole and for at least a week after taking the last dose. Since there is information about cases of spontaneous abortion and the appearance of congenital pathologies in children whose mothers received Fluconazole at a dose of 150 mg once or repeatedly in the first trimester of pregnancy.

When pregnant women take increased doses for a long time in the first trimester, the number of defects in infants also increases: curvature of the femurs, impaired formation of the cranial vault, brachycephaly, impaired development of the facial part of the skull, cleft palate, thinning and elongation of the ribs, arthrogryposis and congenital heart defects.

Fluconazole passes into breast milk, so use during breastfeeding is prohibited.

Can I take Fluconazole while taking antibiotics?

Combinations of antibiotics and antifungal agents are determined only by a doctor. If after treatment with antibiotics the patient develops candidiasis, the use of Fluconazole is possible. But simultaneous use is not always possible due to the fact that the medicine actively interacts with other substances. Some antibiotics, cardiovascular drugs, psychotropic drugs and many others are at risk. Therefore, the patient must be informed about all his concomitant diseases and medications taken.