Diflucan - instructions for use, reviews, analogs and formulations (capsules 50 mg, 100 mg, 150 mg, suspension powder, ampoules) of the drug for treatment of candidiasis (thrush) in adults, children and pregnancy

In this article, you can read the instructions for using the drug Diflucan. There are reviews of visitors to the site - consumers of this medication, as well as opinions of doctors of specialists on the use of Diflucan in their practice. A big request is to actively add their feedback on the drug: the medicine helped or did not help get rid of the disease, which were observed complications and side effects, possibly not declared by the manufacturer in the annotation. Analogues of Diflucan in the presence of existing structural analogs. Use to treat candidiasis (thrush) and other mycoses in adults, children, as well as during pregnancy and lactation. Medicinal forms in the form of candles and tablets - really exist?

Diflucan antifungal drug. Fluconazole (active ingredient of Diflucan) is a representative of the class of triazole antifungal agents, it is a potent selective inhibitor of the synthesis of sterols in the fungal cell.

When administered orally and with intravenous administration, fluconazole was active 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 animals with reduced immunity; Cryptococcus neoformans, including intracranial infections; Microsporum spp. and Trychoptyton spp. The activity of fluconazole was also established in the models of endemic mycoses in animals, including infections caused by Blastomyces dermatitidis, Coccidioides immitis, including intracranial infections, and Histoplasma capsulatum in animals with normal and reduced immunity.

Fluconazole is highly specific for fungal enzymes that are dependent on cytochrome P450. Therapy with fluconazole at 50 mg per day for up to 28 days did not affect testosterone plasma concentrations in men or the concentration of steroids in women of childbearing age. Fluconazole at a dose of 200-400 mg per 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.

A single or multiple administration of fluconazole at a dose of 50 mg does not affect the metabolism of antipyrin when they are taken concomitantly.

There have been reports of cases of superinfection caused by Candida strains other than Candida albicans, which often do not show sensitivity to fluconazole (for example, Candida krusei). In such cases, alternative antifungal therapy may be required.

Pharmacokinetics

The pharmacokinetics of fluconazole is similar for intravenous administration and for oral administration. After oral administration, fluconazole is well absorbed, its plasma levels (and total bioavailability) exceed 90% of fluconazole levels in blood plasma when administered iv. Simultaneous food intake does not affect absorption during ingestion. Fluconazole well penetrates into all body fluids. The levels of fluconazole in saliva and sputum are similar to those in plasma. In patients with fungal meningitis, fluconazole levels in the cerebrospinal fluid are about 80% of its levels in the blood plasma. In the stratum corneum, the epidermis or the dermis and the sweat fluid, high concentrations are reached that exceed the serum levels.Fluconazole is excreted mainly by the kidneys; approximately 80% of the administered dose is detected in the urine unchanged. No circulating metabolites were detected.

Indications

• cryptococcosis, including cryptococcal meningitis and infections of other locations (eg, lungs, skin), incl. in patients with normal immune response and in AIDS patients, recipients of transplanted organs and patients with other forms of immunodeficiency; Supportive therapy for the prevention of recurrence of cryptococcosis in AIDS patients;
• generalized candidiasis, including candidemia, disseminated candidiasis and other forms of invasive candidiasis infection, such as peritoneal, endocardial, eye, respiratory and urinary tract infections, incl. in patients with malignant tumors in intensive care units, patients receiving cytotoxic or immunosuppressive agents, as well as in patients with other factors predisposing to the development of candidiasis;
• Candidiasis of the mucous membranes, including mucous membranes of the oral cavity and pharynx, esophagus, non-invasive bronchopulmonary infections, candiduria, mucocutaneous and chronic atrophic candidiasis of the oral cavity (associated with wearing dentures), incl.in patients with normal and suppressed immune function; prevention of recurrence of oropharyngeal candidiasis in AIDS patients;
• genital candidiasis; acute or recurrent vaginal candidiasis; prevention to reduce the frequency of recurrence of vaginal candidiasis (3 or more episodes a year); Candidiasis balanitis;
• prevention of fungal infections in patients with malignant tumors, predisposed to the development of such infections as a result of cytotoxic chemotherapy or radiation therapy;
• mycosis of the skin, including mycosis of the feet, body, inguinal region, pityriasis, onychomycosis and cutaneous candidiasis infections;
• deep endemic mycoses in patients with normal immunity, coccidioidomycosis, paracoccidioidomycosis, sporotrichosis and histoplasmosis.

Forms of release

Capsules 50 mg, 100 mg and 150 mg.

Powder for the preparation of a suspension for oral administration 50 mg / 5 ml and 200 mg / 5 ml.

Solution for intravenous administration (in injections) 2 mg / ml.

Medicinal form of Diflucane in the form of candles or tablets does not exist. Perhaps the drug in such forms under this brand is a fake.

Instructions for use and dosing regimen

Treatment can begin before the results of sowing and other laboratory studies. However, 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 is effective. In infections requiring repeated use of an antifungal drug, treatment should continue until the disappearance of clinical or laboratory signs of a fungal infection. Patients with AIDS and cryptococcal meningitis or recurrent oropharyngeal candidiasis usually need maintenance therapy to prevent recurrence of the infection.

Adults with cryptococcal meningitis and cryptococcal infections of other localization on the first day are prescribed an average 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 a clinical and mycological effect; In cryptococcal meningitis, treatment usually lasts at least 6-8 weeks.

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

With candidemia, disseminated candidiasis and other invasive candidiasis infections, the average dose is 400 mg on the first day, and then 200 mg per day. Depending on the severity of the clinical effect, the dose can be increased to 400 mg per day. The duration of therapy depends on clinical effectiveness.

With oropharyngeal candidiasis, the drug is prescribed on average 50-100 mg once a day for 7-14 days. If necessary, in patients with a marked decrease in immunity, treatment can be continued for a longer time. With atrophic candidiasis of the oral cavity associated with the wearing of dentures, the drug is prescribed at an average dose of 50 mg once a day for 14 days in combination with local antiseptic agents to treat the prosthesis.

In other candidal infections of the mucous membranes (with the exception of genital candidiasis), for example, esophagitis, noninvasive bronchopulmonary infections, candiduria, candidiasis of the skin and mucous membranes, the effective dose is on the average 50-100 mg per day with a treatment duration of 14-30 days.

To prevent the recurrence of oropharyngeal candidiasis in AIDS patients after completion of the full course of primary therapy, fluconazole can be administered at 150 mg once a week.

With vaginal candidiasis, fluconazole is taken once inside at a dose of 150 mg.

To reduce the frequency of recurrences of vaginal candidiasis, the drug can be applied at 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. The use of the drug in a single dose in children under the age of 18 and patients older than 60 years without a doctor's appointment is not recommended.

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

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

For skin infections, including mycosis of the feet, smooth skin, inguinal area and candidiasis infections, the recommended dose is 150 mg 1 time / week. or 50 mg once a day. The duration of therapy in usual cases is 2-4 weeks, however, with foot mycoses, longer therapy (up to 6 weeks) may be required.

With pityriasis, the recommended dose is 300 mg 1 time / week. within 2 weeks; some patients require a third dose of 300 mg / week, while for some patients a single dose of 300-400 mg is sufficient. An alternative treatment regimen is the use of the drug at 50 mg once a day for 2-4 weeks.

With onychomycosis the recommended dose is 150 mg 1 time / week. Treatment should continue until the replacement of the infected nail (growth of uninfected nail). For the repeated growth of nails on the fingers and toes, it usually takes 3-6 months and 6-12 months, respectively. However, the growth rate can vary widely among different people, and also depending on age. After successful treatment of long-lasting chronic infections, the shape of the nails is sometimes observed.

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

In children, as with similar infections in adults, the duration of treatment depends on the clinical and mycological effect. The daily dose for children should not exceed that for adults. Fluconazole is used daily once a day.

In candidiasis of mucous membranes, the recommended dose of fluconazole is 3 mg / kg per day. On the first day, a shock dose of 6 mg / kg may be prescribed to achieve a more rapid equilibrium equilibrium concentration.

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

For the prevention of fungal infections in patients with reduced immunity, where the risk of infection is associated with neutropenia, resulting from cytotoxic chemotherapy or radiation therapy, the drug is prescribed at 3-12 mg / kg per day, depending on the severity and duration of preservation of induced neutropenia.

When using the drug in children at the age of 4 weeks or less, it should be borne in mind that in newborns fluconazole is withdrawn slowly. In the first 2 weeks of life, the drug is administered at the same dose (in mg / kg) as for older children, but at an interval of 72 hours. Children aged 3 and 4 weeks of age are given the same dose at intervals of 48 hours.

In elderly patients, in the absence of signs of renal insufficiency, the drug is prescribed in an average dose.

Fluconazole can be taken orally (in the form of capsules and suspension) or administered intravenously (in the form of a solution for intravenous administration) by infusion at a rate of no more than 10 ml / min; the choice of route of administration depends on the clinical condition of the patient. When transferring the patient from / to the introduction of taking the drug inside or vice versa, changes in the daily dose are not required.

Capsules should be swallowed whole.

When preparing the suspension for oral administration, add 24 ml of water to the contents of one vial and shake thoroughly. Before each use, the suspension should be shaken.

Solution of the drug for intravenous administration contains 0.9% solution of sodium chloride; in each 200 mg (vial per 100 ml) contains 15 mmol of Na + and Cl-,therefore, in patients who require a restriction of sodium or liquid intake, the rate of fluid administration must be considered.

Side effect

• headache;
• dizziness;
• convulsions;
• change in taste;
• abdominal pain;
• diarrhea;
• flatulence;
• nausea;
• dyspepsia;
• vomiting;
• fibrillation / flutter of the ventricles;
• rash;
• leukopenia, including neutropenia and agranulocytosis, thrombocytopenia;
• increased cholesterol and triglycerides in plasma;
• hypokalemia;
• anaphylactic reactions (including angioedema, edema of the face, urticaria, pruritus).

Contraindications

• simultaneous application of cisapride;
• simultaneous application of terfenadine during multiple use of fluconazole at a dose of 400 mg per day or more;
• hypersensitivity to fluconazole, other components of the drug, or azole substances with a fluconazole-like structure.

Application in pregnancy and lactation

Adequate and controlled studies of drug safety in pregnant women have not been conducted. Cases of multiple congenital malformations in newborns are described,whose mothers received fluconazole therapy at high dose (400-800 mg / day) for 3 or more months for coccidioidomycosis. The relationship between these disorders and the use of fluconazole has not been established.

Avoid the use of fluconazole in pregnancy, except in cases of severe and potentially life-threatening fungal infections, when the expected benefit of treatment exceeds the possible risk to the fetus. Therefore, women of childbearing age should use reliable contraception.

Fluconazole is found in breast milk in concentrations close to plasma, so do not recommend Diflucan during lactation (breastfeeding).

special instructions

In rare cases, the use of fluconazole was accompanied by toxic changes in the liver, incl. with a fatal outcome, mainly in patients with serious concomitant diseases. There was no apparent dependence of hepatotoxic effects of fluconazole on total daily dose, duration of therapy, sex and age of the patient. The hepatotoxic effect of fluconazole was usually reversible; signs of it disappeared after discontinuation of therapy.It is necessary to observe patients who, during treatment with fluconazole, are disturbed by liver function tests, in order to identify signs of more serious liver damage. If there are clinical signs or symptoms of liver damage that may be associated with fluconazole, the drug should be discontinued.

During treatment with fluconazole, exfoliative skin reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis, rarely developed in patients. Patients with AIDS are more likely to develop severe skin reactions with many drugs. When a patient who is receiving treatment for a superficial fungal infection, a rash that can be associated with the use of fluconazole, the drug should be discarded. When rashes appear in patients with invasive / systemic fungal infections, fluconazole should be carefully monitored and discarded when bullous lesions or erythema multiforme occur.

As with other azoles, fluconazole in rare cases can cause anaphylactic reactions.

Simultaneous use of Diflukane in doses less than 400 mg per day and terfenadine should be carried out under close supervision.

Like other azoles, fluconazole may cause an increase in the QT interval on the ECG. With fluconazole, an increase in the QT interval and fibrillation / flutter of the ventricles were very rare in patients with multiple risk factors, such as organic heart disease, electrolyte imbalance, and concomitant therapy that promoted the development of such disorders. Therefore, in such patients with potentially proarrhythmic conditions, fluconazole should be used with caution.

Patients with liver, heart and kidney disease before using Diflucan are advised to consult a doctor. When fluconazole 150 mg is used for vaginal candidiasis, patients should be warned that symptom improvement usually occurs after 24 hours, but it often takes several days to completely disappear. If symptoms persist for several days, you should consult your doctor.

Impact on the ability to drive vehicles and manage mechanisms

The experience with fluconazole indicates that it is unlikely that the ability to drive and drive the drug will be impaired.

Drug Interactions

Anticoagulants: like other antifungal agents - derivatives of azole, fluconazole with simultaneous application with Warfarin increases prothrombin time (by 12%), which is why bleeding can develop (hematomas, nosebleeds and digestive tract, hematuria, melena). Patients receiving coumarin anticoagulants should constantly monitor prothrombin time.

Azithromycin: with simultaneous administration of fluconazole in a single dose of 800 mg with Azithromycin in a single dose of 1200 mg, no pronounced pharmacokinetic interaction is established.

Benzodiazepines (short-acting): after ingestion of midazolam, Diflucan significantly increases the concentration of midazolam and psychomotor effects, and this effect is more pronounced after fluconazole is ingested than when it is administered iv. If concomitant therapy with benzodiazepines is required, patients taking fluconazole should be monitored to appropriately reduce the dose of benzodiazepine.

Cisapride: when fluconazole and cisapride are used concomitantly, unwanted reactions from the heart are possible, including. fibrillation / flutter of the ventricles (arrhythmia of the "pirouette" type).The use of fluconazole at a dose of 200 mg 1 time per day and cisapride in a dose of 20 mg 4 leads to a marked increase in plasma concentrations of cisapride and an increase in the QT interval on the ECG. Simultaneous administration of cisapride and fluconazole is contraindicated.

Cyclosporin: in patients after kidney transplantation, the use of fluconazole at a dose of 200 mg per day leads to a slow increase in the concentration of cyclosporine. However, with repeated administration of fluconazole at a dose of 100 mg per day, changes in the concentration of cyclosporin in bone marrow recipients were not observed. With the simultaneous use of fluconazole and cyclosporine, it is recommended to monitor the concentration of cyclosporine in the blood.

Hydrochlorothiazide: Multiple application of hydrochlorothiazide simultaneously with fluconazole leads to an increase in the concentration of fluconazole in plasma by 40%. The effect of this degree of expression does not require a change in the dosage regimen of fluconazole in patients receiving diuretics at the same time, but this should be taken into account.

Oral contraceptives: with simultaneous application of a combined oral contraceptive with fluconazole at a dose of 50 mg, there is no significant effect on hormone levels,whereas with the daily intake of 200 mg fluconazole, the AUC of ethinyl estradiol and levonorgestrel increased by 40% and 24%, respectively, and with the administration of 300 mg of fluconazole once a week, the AUC of ethinyl estradiol and norethindrone increased by 24% and 13%, respectively. Thus, the repeated use of fluconazole at these doses is unlikely to affect the effectiveness of the combined oral contraceptive.

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

Rifabutin: simultaneous application of fluconazole and rifabutin may lead to an increase in serum concentrations of the latter. With the simultaneous use of fluconazole and rifabutin, cases of uveitis are described. Patients who are simultaneously receiving rifabutin and fluconazole should be carefully monitored.

Rifampicin: simultaneous application of fluconazole and rifampicin leads to a 25% decrease in AUC and a fluconazole T1 / 2 of 20%. In patients taking rifampicin simultaneously, it is necessary to consider the advisability of increasing the dose of fluconazole.

Sulfonylurea preparations: fluconazole with simultaneous administration leads to an increase in T1 / 2 oral sulfonylureas (chlorpropamide, glibenclamide, glipizide and tolbutamide). Patients with diabetes can be co-administered fluconazole and oral sulfonylureas, but the possibility of developing hypoglycemia should be considered.

Tacrolimus: simultaneous application of fluconazole and tacrolimus leads to an increase in serum concentrations of the latter. Cases of nephrotoxicity are described. Patients taking tacrolimus and fluconazole simultaneously should be carefully monitored.

Terfenadine: with the simultaneous use of azole antifungal agents and terfenadine, serious arrhythmias may occur as a result of an increase in the QT interval. When taking fluconazole at a dose of 200 mg per day, there is no increase in the QT interval, but the use of fluconazole at doses of 400 mg per day and higher causes a significant increase in the concentration of terfenadine in plasma.The simultaneous administration of fluconazole at doses of 400 mg per day or more with terfenadine is contraindicated. Treatment with fluconazole at doses less than 400 mg per day in combination with terfenadine should be carefully monitored.

Theophylline: with simultaneous application with fluconazole at a dose of 200 mg for 14 days, the average plasma clearance rate of theophylline is reduced by 18%. In the administration of fluconazole, patients receiving high-dose theophylline or patients at increased risk of developing the toxic effect of theophylline should be monitored for symptoms of theophylline overdose and, if necessary, adjust the therapy accordingly.

Zidovudine: with simultaneous application with fluconazole, there is an increase in zidovudine concentrations, which is probably due to a decrease in the metabolism of the latter to its main metabolite. Before and after treatment with fluconazole at a dose of 200 mg / day for 15 days, AIDS patients and ARC (AIDS-related complex) had a significant increase in zidovudine AUC (20%).

When zidovudine is used in HIV-infected patients at a dose of 200 mg every 8 hours for 7 days in combination with fluconazole at a dose of 400 mg per day or without it at an interval of 21 days between the two regimens,A significant increase in AUC zidovudine (74%) with simultaneous application with fluconazole. Patients receiving this combination should be observed to identify side effects of zidovudine.

The simultaneous use of fluconazole with astemizole or other drugs metabolized by isoenzymes of the cytochrome P450 system may be accompanied by an increase in the serum concentrations of these agents. With the simultaneous administration of fluconazole, in the absence of reliable information, care must be taken. Patients should be carefully observed.

Investigations of the interaction of oral forms of fluconazole with its simultaneous administration with food, cimetidine, antacids, and after total irradiation of the body for bone marrow transplantation showed that these factors do not have a clinically significant effect on the absorption of fluconazole.

The above interactions were established with repeated application of fluconazole; interactions with drugs as a result of a single dose of fluconazole are unknown.

It should be noted that interaction with other drugs has not been specifically studied, but it is possible.

Diflucan - a solution for intravenous 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.

Analogues of the drug Diflucan

Structural analogs for the active substance:

• Vero-Fluconazole;
• Disorel-Sanovel;
• Diflason;
• Mikonil;
• Medoflucon;
• Mycomomax;
• Mycosyst;
• Mycoflucan;
• Nofung;
• Procanazole;
• Fangifflu;
• Flucosan;
• Flukoside;
• Flukomabol;
• Flucomycid SEDIKO;
• Fluconazole;
• Fluconazole Hexal;
• Fluconazole STADA;
• Fluconazole-LEXM;
• Fluconazole-Teva;
• Flukonorm;
• Flukoral;
• Flukoreem;
• Flucostat;
• Forkan;
• Fungolon;
• Ciscan.

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