DIFLUCAN CAPSULES 50MG
DIFLUCAN CAPSULES 50MG - 7PCS
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Active ingredient and dosage form
Capsules: 1 capsule contains Fluconazole 50, 100 or 150 mg;
Excipients: lactose, corn starch, colloidal silicon dioxide, Magnesium stearate, sodium lauryl sulfate;
50 and 100 mg: in a blister, 7 pcs.; in a cardboard box 1 blister
150 mg: in a blister 1 pc.; in a cardboard box 1 blister
5 ml ready slurry. contain fluconazole 50 or 200 mg;
excipients: sucrose, colloidal silicon, titanium dioxide, xanthan gum, sodium citrate, citric acid, sodium benzoate, a natural orange additive;
in plastic bottles of 60 ml (the volume of the finished suspension is 35 ml) complete with a dosing spoon, in a carton pack 1 bottle.
Solution for IV administration: 1 ml contains 2 mg of fluconazole;
Excipients: sodium chloride;
in vials of 25, 50, 100 or 200 ml; in a pack of cardboard 1 bottle.
Mechanism of action
Antifungal medication. Fluconazole, a representative of a new class of triazole antifungal agents, is a powerful selective inhibitor of sterol synthesis in the cell of fungi.
When administered and with a / in the introduction of fluconazole has been effective in various models of fungal infections in animals. The activity of the drug was demonstrated in opportunistic mycoses, incl.caused by Candida spp., including generalized candidiasis in immunocompromised animals; Cryptococcus neoformans, including intracranial infections; Microsporum spp. and Trychoptyton spp. Fluconazole activity has also been shown in animal models of endemic mycoses, including infections caused by Blastomyces dermatitides, Coccidioides immitis, including intracranial infections, and Histoplasma capsulatum in animals with normal and reduced immunity.
Fluconazole therapy at 50 mg / day for up to 28 days did not affect the plasma testosterone concentration in men or the steroid concentration in women of childbearing age. Fluconazole at a dose of 200-400 mg / day did not have a clinically significant effect on the levels of endogenous steroids and their response to stimulation of ACTH in healthy male volunteers.
There have been reports of cases of superinfection caused by Candida albicans strains other than Candida albicans, which are often not sensitive to fluconazole (for example, Candida krusei). In such cases, alternative antifungal therapy may be required.
Treatment can begin before the results of seeding and other laboratory tests. However, the therapy needs to be changed accordingly when the results of these studies become known.
The daily dose of fluconazole depends on the nature and severity of the fungal infection.
With vaginal candidiasis in most cases, a single dose of the drug is effective.
For infections that require repeated use of an antifungal drug, treatment should be continued until the clinical or laboratory signs of a fungal infection disappear. Patients with AIDS and cryptococcal meningitis or recurrent oropharyngeal candidiasis usually need supportive therapy to prevent recurrence of the infection.
For adults at cryptococcal meningitis and cryptococcal infections another localization on the first day is prescribed on average 400 mg, and then continue the treatment in a dose of 200-400 mg 1 time / day. The duration of treatment of cryptococcal infections depends on the presence of clinical and mycological effect; with cryptococcal meningitis, it is usually continued for at least 6-8 weeks.
To prevent the recurrence of cryptococcal meningitis in AIDS patientsAfter completion of the full course of primary treatment, therapy with fluconazole at a dose of 200 mg / day can be continued for a very long time.
In candidaemia, disseminated candidiasis and other invasive candidal infections, the dose averages 400 mg on the first day, and then 200 mg / day. Depending on the severity of the clinical effect, the dose may be increased to 400 mg / day. The duration of therapy depends on the clinical effectiveness.
When oropharyngeal candidiasis the drug is prescribed on average 50-100 mg 1 time / day for 7-14 days. If necessary, in patients with a pronounced decrease in immunity, treatment can be continued for a longer time. In case of atrophic oral candidiasis associated with the wearing of dentures, the drug is prescribed in an average dose of 50 mg 1 time / day for 14 days in combination with local antiseptic agents for the treatment of the prosthesis.
For other candidal infections of the mucous membranes (with the exception of genital candidiasis), for example, esophagitis, non-invasive bronchopulmonary infections, candiduria, candidiasis of the skin and mucous membranes, the effective dose averages 50-100 mg / day for a duration of treatment of 14-30 days.
For the prevention of recurrence of oropharyngeal candidiasis in AIDS patients After completion of the full course of primary therapy, fluconazole can be administered 150 mg 1 time / week.
With vaginal candidiasis Fluconazole is taken once by mouth in a dose of 150 mg.
To reduce the frequency of recurrences of vaginal candidiasis the drug can be used in a dose of 150 mg 1 time / month. The duration of therapy is determined individually; it varies from 4 to 12 months. Some patients may need more frequent use.
With balanitis caused by Candida, fluconazole administered once a dose of 150 mg orally.
For the prevention of candidiasis The recommended dose of fluconazole is 50-400 mg 1 time / day, depending on the degree of risk of developing a fungal infection. If there is a high risk of generalized infection, for example, in patients with expected severe or prolonged neutropenia, the recommended dose is 400 mg 1 time / day. Fluconazole is prescribed a few days before the expected appearance of neutropenia; after an increase in the number of neutrophils of more than 1000 / μl, the treatment is continued for another 7 days.
With skin infections, including mycoses of the feet, smooth skin, inguinal area and candidal infections, the recommended dose is 150 mg 1 time / week. or 50 mg 1 time / day. The duration of therapy in normal cases is 2-4 weeks, however, with mycoses of the feet, longer therapy may be required (up to 6 weeks).
With pityriasis versicolor The recommended dose is 300 mg 1 time / week.within 2 weeks; some patients require a third dose of 300 mg / 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 1 time / day for 2-4 weeks.
With onychomycosis The recommended dose is 150 mg 1 time / week. Treatment should be continued until the infected nail is replaced (the uninfected nail grows). Normally, it takes 3-6 months and 6-12 months, respectively, to re-grow nails on the fingers and feet. However, the growth rate can vary widely among different people, as well as depending on age. After successful treatment of long-lasting chronic infections, a change in the shape of the nails is sometimes observed.
With deep endemic mycoses may require the use of the drug in 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 paracoccidiomycosis, 1–16 months for sporotrichosis and 3–17 months for histoplasmosis.
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 in excess of that in adults. Fluconazole is used daily 1 time / day.
With candidiasis of the mucous membranes The recommended dose of fluconazole is 3 mg / kg / day. On the first day, a loading dose of 6 mg / kg can be given in order to more quickly achieve constant equilibrium concentrations.
For treatment 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 reduced immunity, in which the risk of developing an infection is associated with neutropenia, developing 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 persistence of induced neutropenia.
When using the drug in children 4 weeks or less It should be borne in mind that in newborns fluconazole is eliminated slowly. In the first 2 weeks of life, the drug is prescribed in the same dose (in mg / kg) as the older children, but with an interval of 72 hours. Children at the age of 3 and 4 weeks of life are given the same dose with an interval of 48 hours.
In elderly patients in the absence of signs of renal failure, the drug is used in an average dose.
Patients with renal insufficiency (CC <50 ml / min) correction of dosing regimen required.
Fluconazole is excreted mainly in the urine unchanged. When taken once a dose change is not required. In patients (including children) with impaired renal function, with repeated use of the drug, a loading dose from 50 mg to 400 mg should be initially administered. After the administration of the loading dose, the daily dose (depending on the indication) is determined according to the following table.
|Creatinine clearance (ml / min)||The percentage of the recommended dose|
|<50 (without dialysis)||50%|
|Patients who are constantly on dialysis||100% after each dialysis session|
Fluconazole can be taken orally or administered intravenously by infusion at a rate of not more than 10 ml / min; the choice of route of administration depends on the clinical condition of the patient. When transferring a patient with a / in the introduction to the reception of the drug inside or vice versa, the change in daily dose is not required.
Capsules should be swallowed whole.
When preparing the suspension for ingestion, shake the bottle first to loosen the powder, then add 24 ml of water, then shake the bottle thoroughly again. Immediately before use, the suspension should be shaken.
The solution of the drug for on / in the introduction contains a 0.9% solution of sodium chloride; each 200 mg (100 ml bottle) contains 15 mmol of Na+ and Cl-therefore, in patients who need to limit sodium or fluid intake, it is necessary to consider the rate of fluid administration
The most common side effects that have been reported in fluconazole clinical trials.
From the side of the central nervous system: headache.
Dermatological reactions: rash.
From the digestive system: abdominal pain, diarrhea, flatulence, nausea, toxic effect on the liver (including rare cases with fatal outcome), increased levels of alkaline phosphatase, bilirubin, increased serum levels of aminotransferases (ALT and AST).
In some patients, especially with serious diseases (AIDS, malignant neoplasms),in the treatment with fluconazole and similar drugs, changes in blood parameters, kidney and liver function were observed, however, the clinical significance of these changes and their relationship to treatment have not been established.
In the process of widespread use the following side effects are additionally registered.
From the side of the central nervous system and peripheral nervous system: dizziness, convulsions.
Dermatological reactions: alopecia, exfoliative skin diseases, including Stevens-Johnson syndrome, Lyell's syndrome (toxic epidermal necrolysis).
From the digestive system: dyspepsia , vomiting, abnormal liver function, hepatitis, hepatocyte necrosis, jaundice, increased serum ALT and AST levels.
From the hemopoietic system: leukopenia, including neutropenia and agranulocytosis, thrombocytopenia.
Metabolism: increased plasma cholesterol and triglycerides, hypokalemia.
Allergic reactions: Anaphylactic reactions , angioedema, swelling of the face, itching.
Other: change in taste.
- simultaneous use of cisapride;
- simultaneous use of terfenadine and astemizole;
- Hypersensitivity to the drug or azole substances close to it in chemical structure.
The use of fluconazole during pregnancy should be avoided, except in cases of severe and potentially life-threatening fungal infections, when the expected benefit of treatment outweighs the possible risk to the fetus.
Fluconazole is found in breast milk in the same concentrations as in blood, therefore it is not recommended to use Diflucan during lactation (breastfeeding).
In rare cases, the use of fluconazole was accompanied by toxic changes in the liver, including fatal, mainly in patients with serious concomitant diseases. There is no marked dependence of the incidence of hepatotoxic effects of fluconazole on the total daily dose, duration of therapy, sex and age of the patient. The hepatotoxic effect of fluconazole has usually been reversible; his symptoms disappeared after cessation of therapy. It is necessary to observe patients in whom indicators of liver function are disturbed during treatment with fluconazole in order to detect signs of more serious liver damage. If clinical signs of liver damage appear that may be associated with fluconazole, the drug should be withdrawn.
During treatment with fluconazole, patients rarely developed exfoliative skin reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis. AIDS patients are more likely to develop severe skin reactions with the use of many drugs. When a rash appears to be associated with fluconazole in a patient receiving treatment for a superficial fungal infection, the drug should be discontinued. When a rash appears in patients with invasive / systemic fungal infections, they should be carefully monitored and fluconazole should be canceled when there is a bullous lesion or erythema multiforme.
It should be borne in mind that the use of the drug in rare cases anaphylactic reactions were noted.
Influence on ability to drive motor transport and control mechanisms
Experience with fluconazole suggests that the deterioration of the ability to drive and mechanisms associated with the drug, it is unlikely.
A case of fluconazole overdose has been described. A 42-year-old patient infected with the human immunodeficiency virus, after taking 8,200 mg of fluconazole, had hallucinations and paranoid behavior. The patient was hospitalized; his condition returned to normal within 48 hours.
Treatment: symptomatic therapy (including supportive measures and gastric lavage) can give an adequate effect.
Fluconazole is mainly excreted in the urine, so forced diuresis can probably accelerate its excretion. A 3-hour hemodialysis session reduces plasma plasma levels of fluconazole by about 50%.
Fluconazole increased the prothrombin time by 12% in healthy male volunteers who received Warfarin. Cases of bleeding (hematomas, epistaxis, bleeding in the gastrointestinal tract, hematuria, melena) associated with an increase in prothrombin time in patients taking fluconazole concurrently with warfarin have been reported. Prothrombin time in patients receiving coumarin anticoagulants should be constantly monitored.
The use of fluconazole orally after midazolam significantly increased the concentration of midazolam and psychomotor effects. This effect on midazolam was more pronounced after ingestion of fluconazole inwards, rather than in its use in / in. If concomitant benzodiazepine therapy is needed in patients taking fluconazole, careful monitoring is necessary in order to appropriately reduce the dose of benzodiazepine.
With the simultaneous use of fluconazole and cisapride, cases of adverse events of the heart are described, including paroxysmal ventricular tachycardia (torsade de pointes). Concurrent use of cisapride in patients taking fluconazole is contraindicated.
According to clinical studies in patients with a transplanted kidney, fluconazole at a dose of 200 mg / day slowly increased the concentration of cyclosporine. However, in another study with repeated administration of fluconazole at 100 mg / day, there was no change in the level of cyclosporine in bone marrow recipients. When treating with fluconazole, it is recommended to monitor the concentration of cyclosporine in the blood.
In healthy volunteers who received fluconazole, repeated use of hydrochlorothiazide led to an increase in plasma concentration of fluconazole by 40%. As a rule, the effect of this severity does not require a change in the dosage regimen of fluconazole in patients receiving diuretics simultaneously.
A study of the pharmacokinetics of the combined oral contraceptive preparation in combination with repeated administration of fluconazole was conducted in 2 studies.In one study, when taking fluconazole at a dose of 50 mg, there was no significant effect on hormone levels, while in another study, when taken daily at a dose of 200 mg, there was an increase in the area under the concentration-time curve (AUC) of ethinyl estradiol by 40% and levonorgestrel by 24%. This suggests that repeated use of fluconazole in these doses is unlikely to affect the effectiveness of the combined oral contraceptive preparation.
The simultaneous use of fluconazole and phenytoin may be accompanied by an increase in the concentration of phenytoin in a clinically significant degree. If the combined use of two drugs is required, monitoring of the level of phenytoin and the selection of its dose to ensure therapeutic serum concentrations are necessary.
There are reports of the interaction of fluconazole and rifabutin, accompanied by an increase in serum levels of the latter. With the simultaneous use of fluconazole and rifabutin, cases of development of uveitis are described. It is necessary to carefully observe patients who simultaneously receive rifabutin and fluconazole.
The simultaneous use of fluconazole and rifampicin resulted in a 25% decrease in AUC and T1/2 fluconazole by 20%. In patients receiving combined rifampicin, it is necessary to consider the feasibility of increasing the dose of fluconazole.
With the simultaneous use of fluconazole extended T1/2 oral hypoglycemic drugs - sulfonylurea derivatives (chlorpropamide, glibenclamide, glipizide and tolbutamide) in healthy volunteers.Fluconazole and oral hypoglycemic drugs - sulfonylurea derivatives can be prescribed jointly for patients with diabetes, but it should take into account the possibility of hypoglycemia.
There are reports of the interaction of fluconazole and tacrolimus, which was accompanied by an increase in serum levels of the latter. With the simultaneous use of fluconazole and tacrolimus described cases of nephrotoxicity. It is necessary to carefully monitor patients receiving tacrolimus and fluconazole at the same time.
Given the occurrence of serious arrhythmias associated with prolongation of the QT intervalwith in patients receiving azole antifungal agents in combination with terfenadine and astemizole, their combined use is contraindicated.
In a placebo-controlled study, taking 200 mg of fluconazole for 14 days resulted in a 18% decrease in the average rate of clearance of theophylline from plasma. When treating fluconazole in patients receiving theophylline in high doses, or in patients with an increased risk of the toxic action of theophylline, it is necessary to observe the symptoms of a theophylline overdose; when they appear, the therapy should be changed accordingly.
Two studies showed an increase in zidovudine levels, which was most likely caused by a decrease in the conversion of the latter to its main metabolite. In one study, zidovudine levels were determined in AIDS patients before and after fluconazole therapy at 200 mg / day for 15 days.There was a significant increase in zidovudine AUC (20%). In a second, randomized, two-step, cross-sectional study, zidovudine levels were determined in HIV-infected patients. 2 times with an interval of 21 days, patients received 200 mg zidovudine every 8 hours in combination with fluconazole at a dose of 400 mg / day or without it for 7 days. Zidovudine AUC increased (74%) with simultaneous use with fluconazole. Patients receiving such a combination should be monitored to identify side effects of zidovudine.
Studies of the interaction of dosage forms of fluconazole for oral administration when taken simultaneously with food, cimetidine, antacids, and after total body irradiation during bone marrow transplantation have shown that these factors do not have a clinically significant effect on fluconazole absorption.
A single or multiple dose of fluconazole at a dose of 50 mg did not affect the metabolism of antipyrine when they were taken at the same time.
It should be borne in mind that the interaction of fluconazole with other drugs has not been specifically studied, but it is possible.
Fluconazole for IV administration is compatible with the following solutions: 20% glucose solution, Ringer's solution, Hartmann solution, potassium chloride solution in glucose, 4.2% sodium bicarbonate solution, aminofusin, isotonic saline.
Fluconazole can be administered into the infusion system along with one of the above solutions.Although cases of specific incompatibility of fluconazole with other drugs are not described, however, it is not recommended to mix it with any other drugs before infusion.
The drug should be stored at a temperature not exceeding 30 ° C, out of the reach of children.
capsules and solution for on / in the introduction - 5 years;
- powder for suspension for oral administration - 3 years.
The shelf life of the finished suspension is 14 days; the suspension should be protected from freezing.