Diflucan (Fluconazole)

Instructions for Diflucan

Each capsule Diflucan contains:

active substance: fluconazole 150 mg;
excipients: lactose 149.123 mg, corn starch 49.5 mg, colloidal silicon dioxide 0.352 mg, magnesium stearate 3.173 mg, sodium lauryl sulfate 0.352 mg; capsule shell: titanium dioxide (E171) 1.47%, blue dye patented (E 131) 0.03%, gelatin up to 100%.
Ink for marking capsules 50 mg, 100 mg and 150 mg: shellac glaze 63%, black iron oxide (E172) 25%, N-butyl alcohol 8.995%, industrial methylated alcohol 74 OR 2%, soya lecithin 1%, anti-foam component DC 1510 0.005%.

general description Diflucan:
Antifungal agent

Special conditions Diflucan Pill:

Cases of superinfection caused by Candida strains other than Candida albicans, which often have natural resistance to fluconazole (e.g., Candida krusei), have been reported. In such cases, alternative antifungal therapy may be required.
During pregnancy, the use of Diflucan should be avoided, except in cases of severe and potentially life-threatening fungal infections, when the expected benefits of treatment for the mother outweigh the possible risk to the fetus.
It is necessary to consider effective methods of contraception in women of childbearing age throughout the entire period of treatment and approximately a week (5-6 half-lives) after taking the last dose of the drug (see section "Use during pregnancy and during breast-feeding"). In rare cases the use of Fluconazole was accompanied by toxic changes in the liver, including fatal outcomes, mainly in patients with serious concomitant diseases. In the case of hepatotoxic effects associated with the use of fluconazole, there is no obvious dependence on the total daily dose of the drug, duration of therapy, gender and age of the patient. The hepatotoxic effect of the Diflucan was usually reversible; his signs disappeared after discontinuation of therapy. Patients in whom liver function indicators are impaired during drug treatment should be monitored to identify signs of more serious liver damage. If there are clinical signs or symptoms of liver damage that may be associated with the use of Diflucan, the drug should be discontinued.

As with other azoles, Diflucan in rare cases can cause anaphylactic reactions.
During Diflucan treatment, patients rarely developed exfoliative skin lesions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis. AIDS patients are more likely to develop severe skin reactions when using many drugs. If a patient develops a rash during the treatment of superficial fungal infection, which can be associated with the use of fluconazole, the drug should be discontinued. If a rash appears in patients with invasive or systemic fungal infections, they should be carefully monitored and the drug should be discontinued if bullous lesions or erythema multiforme occur.
The simultaneous use of Diflucan in doses of less than 400 mg / day and terfenadine should be carried out under close monitoring (see the section "Interaction with other drugs").

Like other azoles, fluconazole can cause an increase in the QT interval on the ECG. When using fluconazole, an increase in the QT interval and ventricular fibrillation or flutter were very rare in patients with severe diseases with multiple risk factors, such as organic heart disease, electrolyte imbalance and concomitant therapy conducive to the development of such disorders. Therefore, in such patients with potentially proarrhythmic conditions, Diflucan should be used with caution.
Patients with diseases of the liver, heart and kidneys are advised to consult a doctor before using the drug. When using fluconazole 150 mg for vaginal candidiasis, patients should be warned that symptom improvement is usually observed after 24 hours, but sometimes it takes several days to completely disappear. If symptoms persist for several days, consult a doctor.
Influence on the ability to drive vehicles and control mechanisms
When using the drug, it is necessary to take into account the possibility of developing dizziness and seizures.

Drug Interactions Diflucan:

A single or multiple administration of fluconazole at a dose of 50 mg does not affect the metabolism of phenazone (Antipyrine) when taken at the same time.
The simultaneous use of Diflucan with the following drugs is contraindicated:
Cisapride: with the simultaneous use of fluconazole and cisapride, undesirable reactions from the heart are possible, including ventricular arrhythmia tachysystolic type "pirouette" (torsadede pointses). 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. Concomitant use of cisapride and fluconazole is contraindicated.
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 Diflucan at a dose of 200 mg / day, an increase in the QT interval has not been established, however, the use of fluconazole in doses of 400 mg / day and higher causes a significant increase in the concentration of terfenadine in blood plasma. The simultaneous use of Diflucan 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 monitored closely.
Astemizole: the 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 agents. Elevated plasma concentrations of astemizole can lead to a prolonged QT interval and, in some cases, to the development of ventricular arrhythmias of the tachysystolic pirouette type (torsade de pointes). The simultaneous use of astemizole and Diflucan is contraindicated.
Pimozide: although no in vitro or in vivo studies have been conducted, the simultaneous use of fluconazole and pimozide can lead to inhibition of pimozide metabolism. In turn, an increase in plasma concentrations of pimozide can lead to a prolongation of the QT interval and, in some cases, the development of ventricular arrhythmias of the tachysystolic “pirouette” type (torsade de pointses). The simultaneous use of pimozide and fluconazole is contraindicated.
Quinidine: although no in vitro or in vivo studies have been conducted, the simultaneous use of fluconazole and quinidine can also lead to inhibition of quinidine metabolism. The use of quinidine is associated with a prolongation of the QT interval and, in some cases, with the development of ventricular arrhythmias of the tachysystolic pirouette type (torsade de pointses). The simultaneous use of quinidine and fluconazole is contraindicated.
Erythromycin: the simultaneous use of Diflucan and erythromycin potentially leads to an increased risk of cardiotoxicity (prolongation of the QT interval, torsade de pointes) and, consequently, sudden cardiac death. The simultaneous use of fluconazole and erythromycin is contraindicated.
Amiodarone: The combined use of fluconazole and amiodarone can lead to inhibition of amiodarone metabolism. The use of amiodarone has been associated with a prolongation of the QT interval. The simultaneous use of fluconazole and amiodarone is contraindicated (see section "Contraindications").
Caution should be exercised and, possibly, dose adjusted while using the following drugs and fluconazole:
Drugs that affect Diflucan:

Hydrochlorothiazide: repeated use of hydrochlorothiazide simultaneously with Diflucan leads to an increase in the concentration of fluconazole in blood plasma by 40%. The effect of this severity does not require a change in the dosage regimen of fluconazole in patients receiving diuretics at the same time, but the doctor should take this into account.
Rifampicin: the simultaneous use of fluconazole and rifampicin leads to a decrease in AUC by 25% and a half-life of fluconazole by 20%. In patients taking rifampicin at the same time, the feasibility of increasing the dose of fluconazole should be considered.
Drugs affected by Diflucan:
Diflucan is a potent inhibitor of the CYP2C9 isoenzyme and CYP2C19 of the cytochrome P450 and a moderate inhibitor of the CYP3A4 isoenzyme. In addition, in addition to the effects listed below, there is a risk of increasing plasma concentrations of other drugs metabolized by the isoenzymes CYP2C9, CYP2C19 and CYP3A4 while taking Diflucan. In this regard, caution should be exercised with the simultaneous use of the listed drugs, and if necessary, such combinations should be under careful medical supervision. It should be borne in mind 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, an increase in the half-life of alfentanil. Perhaps this is due to inhibition of the CYP3A4 isoenzyme by fluconazole. Dose adjustment may be required.

Carbamazepine: fluconazole inhibits the metabolism of carbamazepine and increases the serum concentration of carbamazepine by 30%. The risk of developing carbamazepine toxicity must be considered. The need to adjust the dose of carbamazepine depending on the concentration / effect should be assessed.
Calcium channel blockers: some calcium channel antagonists (nifedipine, isradipine, amlodipine, verapamil and felodipine) are metabolized by the isoenzyme CYP3A4. Diflucan increases the systemic exposure of calcium channel antagonists. Recommended control of the development of side effects.
Nevirapine: co-administration of Diflucan and nevirapine increases the exposure of nevirapine by approximately 100% compared with control data for a single use of nevirapine. Due to the risk of increased release of nevirapine with the concomitant use of drugs, some precautions and careful monitoring of patients are necessary.
Cyclosporin: in patients with a transplanted kidney, the use of fluconazole at a dose of 200 mg / day leads to a slow increase in the concentration of cyclosporine. However, with repeated administration of fluconazole at a dose of 100 mg / 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 control the concentration of cyclosporin in the blood.
Cyclophosphamide: with the simultaneous use of cyclophosphamide and Diflucan, an increase in serum concentrations of bilirubin and creatinine is noted. This combination is acceptable given the risk of increased concentrations of bilirubin and creatinine.
Fentanyl: There is a reported one death, possibly associated with the simultaneous administration of fentanyl and fluconazole. Disorders are believed to be associated with fentanyl intoxication. Fluconazole has been shown to significantly lengthen fentanyl elimination time. It should be borne in mind that an increase in the concentration of fentanyl can lead to inhibition of respiratory function.

Halofantrine: Diflucan may increase the concentration of halofantrine in blood plasma in connection with the inhibition of the CYP3A4 isoenzyme. It is possible to develop arrhythmias of the ventricular tachysystolic “pirouette” type (torsade de pointes) with simultaneous use with fluconazole, as well as with other antifungal drugs of the azole series, therefore their combined use is not recommended.
HMG-CoA reductase inhibitors: with the simultaneous use of fluconazole 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. If simultaneous therapy with these drugs is necessary, patients should be observed in order to identify symptoms of myopathy and rhabdomyolysis. It is necessary to control the concentration of creatinine kinase. In the event of a significant increase in creatinine kinase concentration, or if a diagnosis of myopathy or rhabdomyolysis is diagnosed or suspected, therapy with HMG-CoA reductase inhibitors should be discontinued.

Losartan: Diflucan inhibits the metabolism of losartan to its active metabolite (E-31 74), which is responsible for most of the effects associated with the antagonism of angiotensin-II receptors. Regular monitoring of blood pressure is required.

Methadone: Fluconazole may increase the plasma concentration of methadone. A dose adjustment of methadone may be needed.
Nonsteroidal anti-inflammatory drugs (NSAIDs): Cmax and AUC of flurbiprofen increase by 23% and 81%, respectively. Similarly, Cmax and AUC of the pharmacologically active isomer [S - (+) - ibuprofen] increased by 15% and 82%, respectively, with the simultaneous use of Diflucan with racemic ibuprofen (400 mg).
With the simultaneous use of fluconazole at a dose of 200 mg / day and celecoxib at a dose of 200 mg, Cmax and AUC of celecoxib increase by 68% and 134%, respectively. In this combination, it is possible to halve the dose of celecoxib.

Despite the lack of targeted studies, fluconazole can increase the systemic exposure of other NSAIDs metabolized by the CYP2C9 isoenzyme (e.g., naproxen, lornoxicam, meloxicam, diclofenac). NSAID dosage adjustment may be needed.
With the simultaneous use of NSAIDs and Diflucan, patients should be under close medical supervision in order to identify and control adverse events and toxicity associated with NSAIDs.
Oral contraceptives: with the simultaneous use of a combined oral contraceptive with fluconazole at a dose of 50 mg, there is no significant effect on hormone levels, while with 200 mg of fluconazole AUC of ethinyl estradiol and levonorgestrel daily increase by 40% and 24%, respectively, and with 300 mg of fluconazole once a week, the AUCs of ethinyl estradiol and norethindrone increase by 24% and 13%, respectively. Thus, repeated use of Diflucan in the indicated doses is unlikely to affect the effectiveness of the combined oral contraceptive

Theophylline: with simultaneous use with fluconazole at a dose of 200 mg for 14 days, the average plasma clearance rate of theophylline decreases by 18%. When Diflucan is prescribed to patients taking theophylline in high doses, or to patients with an increased risk of developing the toxic effects of theophylline, the symptoms of theophylline overdose should be monitored and, if necessary, adjust therapy accordingly.

Tofacitinib: exposure to tofacitinib increases when used together with drugs that are both moderate inhibitors of the CYP3A4 isoenzyme and potent inhibitors of the CYP2C19 isoenzyme (e.g. fluconazole). A dose adjustment of tofacitinib may be necessary.
Vinca alkaloid: despite the lack of targeted research, it is believed that fluconazole can increase the concentration of vinca alkaloids (e.g. vincristine and vinblastine) in the blood plasma and, thus, lead to neurotoxicity, which may be associated with inhibition of the CYP3A4 isoenzyme.

Vitamin A: there is a report of one case of the development of adverse reactions from the central nervous system (CNS) in the form of a pseudotumor of the brain with the simultaneous use of completely transretinoic acid and fluconazole, which disappeared after the withdrawal of fluconazole. The use of this combination is possible, but you should remember about the possibility of undesirable reactions from the central nervous system.
Zidovudine: with simultaneous use with fluconazole, there is an increase in Cmax and AUCzidovudine 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, patients with AIDS and ARC (the complex associated with AIDS) found a significant increase in the AUC of zidovudine (20%).
Patients receiving this combination Diflucan should be observed in order to identify side effects of zidovudine.
Voriconazole (an inhibitor of the isoenzymes CYP2C9, CYP2C19 and CYP3A4): 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 the concentration and AUC of voriconazole by 57% and 79%, respectively. It was shown that this effect persists with a decrease in dose and / or a decrease in the frequency of administration of any of the drugs. The simultaneous use of voriconazole and

Diflucan is not recommended.
Studies of the interaction of oral forms of Diflucan when it is taken with food, cimetidine, antacids, as well as after total body irradiation to prepare 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; interactions with drugs resulting from a single dose of fluconazole are not known.
Doctors should consider that the interaction with other drugs has not been specifically studied, but it is possible.

Pharmacodynamics Diflucan:

Diflucan, a triazole antifungal agent, is a potent selective inhibitor of sterol synthesis in the fungal cell.
Fluconazole has been shown to be active in vitro and in clinical studies against most of the following microorganisms: Candida albicans, Candida glabrata (many strains are moderately sensitive), Candida parapsilosis, Candida tropicalis, Cryptococcus neoformans.
The activity of fluconazole in vitro against the following microorganisms was shown, however, the clinical significance of this is unknown: Candida dubliniensis, Candida guilliermondii, Candida kefyr, Candida lusitaniae.
When taken internally, Diflucan is active on various models of fungal infections in animals. The activity of the drug with opportunistic mycoses, including those caused by Candida spp, was demonstrated. (including generalized candidiasis in immunocompromised animals), Cryptococcus neoformans (including intracranial infections), Microsporum spp. and Trychophyton spp. Fluconazole activity has also been established 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 suppressed immunity.
Fluconazole is highly specific for fungal enzymes dependent on cytochrome P450. Diflucan therapy at a dose of 50 mg / day for up to 28 days does not affect the concentration of testosterone in blood plasma in men or the concentration of steroids in women of childbearing age. Diflucan at a dose of 200-400 mg / day does not have a clinically significant effect on endogenous steroid levels and their response to stimulation of adrenocorticotropic hormone (ACTH) in healthy male volunteers.
Mechanisms for the development of fluconazole resistance

Diflucan resistance can develop in the following cases: a qualitative or quantitative change in the enzyme that is the target for fluconazole (lanosteril 14 -? - demethylase), decreased access to the target of Diflucan, or a combination of these mechanisms.
Point mutations in the ERG11 gene encoding a target enzyme lead to a modification of the target and a decrease in affinity for azoles. Increased expression of the ERG11 gene leads to the production of high concentrations of the target enzyme, which creates a need to increase the concentration of fluconazole in the intracellular fluid to suppress all enzyme molecules in the cell.
The second significant resistance mechanism is the active removal of fluconazole from the intracellular space through the activation of two types of transporters involved in the active removal (efflux) of drugs from the fungal cell. Such transporters include the main mediator encoded by the MDR (multidrug resistance) genes and the superfamily of the ATP-binding transporter cassette encoded by the CDR genes (Candida fungal resistance genes to azole antimycotics).

Overexpression of the MDR gene leads to resistance to fluconazole, while overexpression of the CDR genes can lead to resistance to various azoles.

Candida glabrata resistance is usually mediated by overexpression of the CDR gene, which leads to resistance to many azoles. For those strains in which the minimum inhibitory concentration (MIC) is defined as intermediate (16-32 μg / ml), it is recommended to use the maximum dose of Diflucan.
Candida krusei should be considered resistant to fluconazole. The resistance mechanism is associated with a reduced sensitivity of the target enzyme to the inhibitory effect of fluconazole.

Pharmokinetics Diflucan:

The pharmacokinetics of fluconazole are similar when given intravenously and orally. After oral administration, fluconazole is well absorbed, its plasma concentrations (and total bioavailability) exceed 90% of those with intravenous administration. Simultaneous eating does not affect the absorption of fluconazole. The concentration Diflucan in the blood plasma is proportional to the dose and reaches a maximum (Cmax) after 0.5-1.5 hours after taking Diflucan on an empty stomach, and the half-life is about 30 hours. 90% of the equilibrium concentration is reached by the 4-5th day after the start of therapy ( with multiple doses of the drug once a day). The maximum concentration of fluconazole in saliva when taking the capsule is reached after 4 hours.
The introduction of a loading dose (on the 1st day), twice the usual daily dose, makes it possible to achieve 90% equilibrium concentration by the 2nd day. The volume of distribution approaches the total water content in the body. Plasma protein binding is low (11-12%).

Fluconazole penetrates well into all body fluids. Fluconazole concentrations in saliva and sputum are similar to its plasma concentrations. In patients with fungal meningitis, the concentration of Diflucan in the cerebrospinal fluid is about 80% of its plasma concentrations.
In the stratum corneum, epidermis, dermis and sweat, high concentrations are reached that exceed serum. Fluconazole accumulates in the stratum corneum. When taken at a dose of 50 mg once a day, the concentration of fluconazole after 12 days is 73 μg / g, and 7 days after discontinuation of treatment, only 5.8 μg / g. When applied at a dose of 150 mg once a week, the concentration of fluconazole in the stratum corneum on the 7th day is 23.4 μg / g, and 7 days after taking the second dose - 7.1 μg / g.
The concentration of fluconazole in nails after 4-month use at a dose of 150 mg once a week is 4.05 μg / g in healthy and 1.8 μg / g in affected nails; 6 months after completion of therapy, Diflucan is still determined in the nails.
The Diflucan drug is excreted mainly by the kidneys; approximately 80% of the administered dose is found in the urine unchanged. Fluconazole clearance is proportional to creatinine clearance. No circulating metabolites were found.
A long half-life from blood plasma allows you to take fluconazole once with vaginal candidiasis and once a day or once a week for other indications.

Pharmacokinetics in children Diflucan

In children, the following pharmacokinetic parameters were obtained (see instructions)
Pharmacokinetics in elderly patients
It was found that with a single use of Diflucan at a dose of 50 mg orally in elderly patients aged 65 years and older, some of whom were simultaneously taking diuretics, Cmax was achieved 1.3 hours after administration and amounted to 1.54 μg / ml, average values AUC - 76.4 ± 20.3 μg · h / ml, and an average half-life of 46.2 hours. The values of these pharmacokinetic parameters are higher than in young patients, which is probably due to reduced renal function characteristic of the elderly . The simultaneous administration of diuretics did not cause a pronounced change in AUC and Cmax.
Creatinine clearance (74 ml / min), the percentage of fluconazole excreted by the kidneys unchanged (0 - 24 h, 22%) and renal fluconazole clearance (0.124 ml / min / kg) in elderly patients are lower than in younger patients.

Indications Diflucan:

• Diflucan is indicated for the treatment of the following diseases in adults
• cryptococcal meningitis
• coccidioidomycosis
• invasive candidiasis
• mucous candidiasis
• including oropharyngeal candidiasis
• esophageal candidiasis
• candiduria and chronic mucocutaneous candidiasis
• chronic atrophic candidiasis of the oral cavity (associated with the wearing of dentures), when the observance of oral hygiene or local treatment is not enough
• vaginal candidiasis
• acute or recurring
• when local therapy is not applicable
• Candida balanitis, when local therapy is not applicable
• dermatomycoses
• including foot dermatophytosis
• trunk dermatophytosis
• inguinal dermatophytosis
• multicolored lichen and skin candidiasis
• when systemic treatment is indicated
• dermatophytosis of nails (onychomycosis)

Diflucan is indicated for the prevention of the following diseases in adults:

• relapses of cryptococcal meningitis in patients with a high risk of relapse
• relapses of oropharyngeal candidiasis and candidiasis of the esophagus in HIV-infected patients with a high risk of relapse
• to reduce the recurrence rate of vaginal candidiasis (4 or more episodes per year
• or the prevention of candidal infections in patients with prolonged neutropenia (such as patients with hemoblastoses undergoing
• chemotherapy, or patients undergoing 
• hematopoietic stem cell transplantation)

Diflucan is indicated for the treatment of children.

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

Contraindications Diflucan:

- Hypersensitivity to fluconazole, other components of the drug or azole substances with a similar structure to fluconazole;
- simultaneous administration of terfenadine during repeated use of Diflucan at a dose of 400 mg / day or more (see section "Interaction with other drugs");
- simultaneous use with Diflucan drugs that increase the QT interval and are metabolized using the CYP3A4 isoenzyme, such as cisapride, astemizole, erythromycin, pimozide, quinidine and amiodarone (see the section "Interaction with other drugs");
- galactose intolerance, lactase deficiency and malabsorption of glucose / galactose;
- children's age up to 3 years (for this dosage form).
Carefully:
- Liver failure;
- renal failure;
- the appearance of a rash on the background of the use of fluconazole in patients with superficial fungal infection and invasive / systemic fungal infections;
- the simultaneous use of terfenadine and fluconazole in a dose of less than 400 mg / day;
- potentially proarrhythmic conditions in patients with multiple risk factors (organic heart disease, electrolyte imbalance and concomitant therapy conducive to the development of such disorders).

Pregnancy and lactation:
Adequate and well-controlled studies of the use of fluconazole in pregnant women have not been conducted.
During pregnancy, the use of Diflucan should be avoided, except in cases of severe and potentially life-threatening fungal infections, when the expected benefits of treatment for the mother outweigh the possible risk to the fetus.
It is necessary to consider effective methods of contraception in women of childbearing age throughout the entire period of treatment and approximately a week (5-6 half-lives) after taking the last dose of the drug (see section Pharmacokinetics Diflucan).
Cases of spontaneous abortion and the development of congenital abnormalities in infants whose mothers received fluconazole in a dose of 150 mg once or repeatedly in the first trimester of pregnancy have been reported. Cases of multiple congenital malformations are described in newborns whose mothers received fluconazole therapy at a high dose (400-800 mg / day) for most or the entire first trimester. The following developmental disorders were noted: brachycephaly, impaired development of the facial part of the skull, impaired formation of the cranial vault, cleft palate, curvature of the femur, thinning and lengthening of the ribs, arthrogryposis, and congenital heart defects.
Fluconazole is found in breast milk in concentrations close to plasma, so its use in women during breastfeeding is not recommended.

Overdose Diflucan:

There are reports of an overdose of Diflucan and in one case, a 42-year-old patient infected with human immunodeficiency virus, after taking 8200 mg of the drug, hallucinations and paranoid behavior appeared. The patient was hospitalized; his condition returned to normal within 48 hours.
In case of an overdose, symptomatic treatment (including supportive measures and gastric lavage) can give an adequate effect.
Fluconazole is excreted mainly through the kidneys, so forced diuresis can probably accelerate the elimination of the drug. A 3-hour hemodialysis session reduces the level of fluconazole in blood plasma by about 50%.

Diflucan Side Effects:

Frequency assessment criteria: very frequent ³ 10%; frequent ³ 1% and <10%; infrequent ³ 0.1% and <1%; rare> 0.01% and <0.1%; very rare <0.01%, frequency unknown - cannot be determined based on available data.
Drug tolerance is usually very good.
In clinical and post-marketing (*) studies of Diflucan, the following adverse reactions were noted:
From the nervous system: frequent - headache; infrequent - dizziness *, convulsions *, taste change *, paresthesia, insomnia, drowsiness; rare - tremor.
From the digestive system: frequent - abdominal pain, diarrhea, nausea, vomiting *; infrequent - flatulence, dyspepsia *, dry oral mucosa, constipation.
From the hepatobiliary system: frequent - increased serum activity of aminotransferases (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)), alkaline phosphatase; infrequent - cholestasis, jaundice *, increased bilirubin concentration; rare - hepatotoxicity, in some cases fatal, impaired liver function *, hepatitis *, hepatocellular necrosis *, hepatocellular damage.

From the skin: frequent - rash; infrequent - skin itching, urticaria, sweating, drug rash; rare - exfoliative skin lesions *, including Stevens-Johnson syndrome and toxic epidermal necrolysis, acute generalized exanthematous pustulosis, facial edema, alopecia *.
Hematopoietic organs and lymphatic system *: rare - leukopenia, including neutropenia and agranulocytosis, thrombocytopenia, anemia.
From the immune system *: anaphylaxis (including angioedema).
From the cardiovascular system *: rare - an increase in the QT interval on the ECG, ventricular tachysystolic arrhythmia, type “pirouette” (torsade de pointes) (see section “Special instructions”).

From the side of metabolism *: rare - increased plasma cholesterol and triglycerides, hypokalemia.
From the musculoskeletal system: infrequent - myalgia.
Other: infrequent - weakness, asthenia, increased fatigue, fever, vertigo.
In some patients, especially those suffering from serious diseases, such as AIDS or cancer, during treatment with Diflucan® and similar drugs, changes in blood counts, kidney and liver function were observed (see the section “Special instructions”), however, the clinical significance of these changes and their relationship with treatment not established.

Ways of application Diflucan:

Inside. Capsules are swallowed whole.

Therapy can be started Diflucan before the results of culture and other laboratory tests. However, antifungal therapy must be modified accordingly when the results of these studies become known.

When transferring a patient from intravenous to oral administration of the drug or vice versa, changes in the daily dose are not required.

The daily dose of Diflucan depends on the nature and severity of the fungal infection. In case of infections requiring repeated administration of the drug, treatment should be continued until the clinical or laboratory signs of active fungal infection disappear. Patients with AIDS and cryptococcal meningitis or recurrent oropharyngeal candidiasis usually need supportive care to prevent recurrence of the infection.

Adult use Diflucan:

1. For cryptococcal meningitis and cryptococcal infections of a different location, 400 mg is usually used on the first day, and then treatment is continued at a dose of 200-400 mg once a day. The duration Diflucan of treatment for cryptococcal infections depends on the presence of a clinical and mycological effect; with cryptococcal meningitis, treatment usually lasts at least 6-8 weeks. In cases of treatment of life-threatening infections, the daily dose can be increased to 800 mg.

To prevent relapse of cryptococcal meningitis in patients at high risk of relapse, after completion of the full course of primary treatment, treatment with Diflucan at a dose of 200 mg / day can be continued for an indefinite period of time.

2. With coccidioidomycosis, it may be necessary to use the drug in a dose of 200-400 mg / day. For some infections, especially those with damage to the meninges, a dose of 800 mg per day may be considered. The duration of therapy Diflucan is determined individually, it can last up to 2 years; it is 11-24 months for coccidioidomycosis, 2-17 months for paracoccidioidomycosis, 1-16 months for sporotrichosis and 3-17 months for histoplasmosis.

3. For candidaemia, disseminated candidiasis and other invasive candidiasis infections, the saturating dose is 800 mg on the first day, the subsequent dose is 400 mg / day. The duration of therapy depends on clinical efficacy. The general recommendation for the duration of treatment for candidaemia is 2 weeks after the first negative result of blood culture and the disappearance of signs and symptoms of candidaemia.

Treatment of mucous candidiasis

With oropharyngeal candidiasis, the saturating dose is 200-400 mg on the first day, the subsequent dose: 100-200 mg once a day for 7-21 days. If necessary, patients with severe suppression of immune function can continue treatment for a longer time. In case of atrophic candidiasis of the oral cavity associated with wearing dentures, the drug is usually used at a dose of 50 mg once a day for 14 days in combination with local antiseptic agents for treating the prosthesis.

With candididuria, the effective dose is usually 200-400 mg / day with a treatment duration of 7-21 days. In patients with severely impaired immune system function, longer periods of therapy can be used.

In chronic mucocutaneous candidiasis, 50-100 mg per day is used up to 28 days of treatment. Depending on the severity of treatment of the infection or concomitant violation of the immune system and infection, longer periods of therapy can be used.

With esophageal candidiasis, the saturating dose of 200-400 mg on the first day, the subsequent dose: 100-200 mg per day. The course of treatment is 14-30 days (until remission of esophageal candidiasis is achieved). If necessary, patients with severe suppression of immune function can continue treatment for a longer time.

For the prevention of relapse of oropharyngeal candidiasis in HIV-infected patients with a high risk of relapse, the drug is used 100-200 mg per day or 200 mg 3 times a week for an indefinite period of time in patients with chronic

Antifungal drug Diflucan