Fluconazole-Teva capsules 150 mg 1 pc. in St. Petersburg

Fluconazole-Teva

Single or multiple doses of fluconazole at a dose of 50 mg do 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 fibrillation/flutter ( 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. Concomitant use of cisapride and fluconazole is contraindicated.

Terfenadite.

With the simultaneous use of azole antifungals 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/day, an increase in the QT interval has not been established. however, the use of fluconazole in doses of 400 mg/day and above causes a significant increase in plasma terfenadine concentrations. 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.
the metabolism of which is carried out 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:

despite.
Although appropriate studies have not been conducted in vitro
or
in vivo ,
the simultaneous use of fluconazole and pimozide may lead to 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 tachycardia of the “torsade de pointes ” type .
The simultaneous use of pimozide and fluconazole is contraindicated.

Quinidine:

despite.
Although appropriate in vitro
or
in vivo ,
the simultaneous use of fluconazole and quinidine may lead to inhibition of quinidine metabolism.
In turn, an increase in plasma concentrations of quinidine can lead to a prolongation of the QT interval and, in some cases, to the development of torsade de pointes ( TdP ).
The simultaneous use of quinidine and fluconazole is contraindicated.

Erythromycin:

simultaneous use of fluconazole and erythromycin potentially leads to an increased risk of cardiotoxicity (QT interval prolongation, torsades
de pointes ) and ,
consequently, sudden cardiac arrest. The simultaneous use of fluconazole and erythromycin is contraindicated.

Amiodarone:

Concomitant use of fluconazole and amiodarone may result in decreased metabolism of amiodarone and prolongation of the QT interval. The simultaneous use of fluconazole and amiodarone is contraindicated (see section "Contraindications").

Caution and possible dosage adjustments should be used when using the following drugs and fluconazole concomitantly: Drugs that affect the metabolism and effects of fluconazole:

Hydrochlorothiazide

: Repeated use of hydrochlorothiazide concomitantly with fluconazole leads to an increase in plasma concentrations of fluconazole by 40%. An effect of this severity does not require a change in the fluconazole dosage regimen in patients. receiving diuretics at the same time, however, the doctor should take this into account.

Rifampicin',

simultaneous use of fluconazole and rifampicin leads to a decrease in AUC by 25% and the half-life of fluconazole by 20%. In patients. concomitantly taking rifampicin, it is necessary to consider the advisability of increasing the dose of fluconazole.

Drugs whose action is influenced by fluconazole:

Fluconazole is an active inhibitor of the cytochrome P450 isoenzyme CYP2C9 and a moderate inhibitor of the CYP3A4 isoenzyme. In addition, there is a risk of increased plasma concentrations of other drugs metabolized by CYP2C9 and CYP3A4 isoenzymes when taken 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:

increase in 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 those with immunosuppression), the following results were observed: a small additive antifungal effect in systemic infection with
Candida albicans ,
no interaction in intracranial infection with
Cryptococcus neoformans
and antagonism in systemic infection with
Aspergillus fumigatus .
The clinical significance of these results is unclear.

Anticoagulants

: like other antifungal agents from the group of azole derivatives, fluconazole, when used simultaneously with warfarin, increases the prothrombin time (by 12%), and therefore bleeding may develop (hematomas, bleeding from the nose and gastrointestinal tract, hematuria, melena). In patients receiving coumarin or indanedione anticoagulants and fluconazole, prothrombin time should be continuously monitored during therapy and for 8 days after cessation of concomitant use. The feasibility of adjusting the dose of 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 administered intravenously. If concomitant therapy with benzodiazepines is necessary, patients taking fluconazole should be monitored for an appropriate reduction in the benzodiazepine dose. When coadministered with a single dose of triazolam, fluconazole increases the AUC of triazolam by approximately 50%, Cmax by 25-32% and T1/2 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.

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.

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.

Cyclosporine:

in patients with a transplanted kidney, the use of fluconazole at a dose of 200 mg/day leads to a slow increase in cyclosporine concentrations. However, with repeated doses 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.

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.

Halofantrine:

Fluconazole may increase plasma concentrations of halofantrine due to inhibition of the CYP3A4 isoenzyme. Concomitant use of fluconazole and halofantrine may increase the risk of cardiotoxicity (prolongation of the QT interval. “torsade de pointes”) and. hence sudden cardiac arrest. Concomitant use of fluconazole and halofantrine is not recommended.

HMG-CoA reductase inhibitors:

with 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 is increased. 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.

Losartan:

fluconazole inhibits the metabolism of losartan to its active metabolite (E-3174), 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 [8-(+)-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 AUC of celecoxib increased by 68% and 134%, respectively. In this combination, it is possible to reduce the dose of celecoxib by half.

Although focused studies are lacking, fluconazole may increase the systemic exposure of other NSAIDs. metabolized by the CYP2C9 isoenzyme (for example, 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.

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 administration of 200 mg of fluconazole, the AUC of ethinyl estradiol and levonorgestrel increases by 40% and 24%, respectively, and with 300 mg of fluconazole once a week 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:

simultaneous 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.

Prednisone:

There is a report of the development of acute adrenal insufficiency in a patient after liver transplantation while fluconazole was discontinued after a three-month course of therapy. Presumably, cessation of fluconazole therapy caused an increase in the activity of the CYP3A4 isoenzyme. resulting in 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:

simultaneous 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 increases 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:

an increase in the concentration of sirolimus in the blood plasma, presumably due to inhibition of the metabolism of sirolimus 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.

Sulfonylurea derivatives:

Fluconazole, when taken concomitantly with sulfonylurea derivatives, leads to an increase in the half-life of oral sulfonylurea drugs (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. if necessary, adjust the dose of sulfonylurea drugs.

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 tacrolimus metabolism. occurring in the intestine via 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 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 developing theophylline toxicity, the appearance of symptoms of theophylline overdose should be monitored. if necessary, adjust therapy accordingly.

Tofacitinib:

Tofacitinib exposure increases when co-administered with drugs that are both moderate CYP3A4 inhibitors and strong CYP2C19 inhibitors (for example, fluconazole). Maybe. Tofacitinib dose adjustment may be necessary.

Vinca alkaloid:

Although focused studies are lacking, it is suspected that fluconazole may increase plasma concentrations of vinca alkaloids (eg, vincristine and vinblastine) and thus lead to neurotoxicity. which may possibly 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 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:

with simultaneous use with fluconazole, an increase in the Cmax and AUC of zidovudine was 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.

When HIV-infected patients used zidovudine at a dose of 200 mg every 8 hours for 7 days in combination with fluconazole at a dose of 400 mg / day with an interval of 21 days between the two regimens, a significant increase in the AUC of zidovudine (74%) was found at simultaneous use with fluconazole. Patients receiving this combination should be monitored for side effects of zidovudine.

Voriconazole

(inhibitor of 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 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.

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 taking moderate CYP3A inhibitors concomitantly, such as fluconazole and erythromycin, a dose reduction of ivacaftor to 150 mg once daily is 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.

Fluconazole-Teva capsules 150 mg 1 pc. in St. Petersburg

Inside

regardless of food intake. Capsules should be swallowed whole with a glass of water. The daily dose of fluconazole depends on the nature and severity of the fungal infection.

Adults

Vaginal candidiasis: once 150 mg.

Candidiasis of the mucous membranes of the oral cavity and pharynx: 50 mg 1 time / day for 7-14 days. Normally, treatment should not exceed 14 days, with the exception of patients with severe immunocompromise. Chronic atrophic oral candidiasis associated with wearing dentures: 50 mg once daily for 14 days in combination with local antiseptics.

Other candidal infections of the mucous membranes (except for vaginal candidiasis described above), for example, with esophagitis, non-invasive bronchopulmonary infections, mucocutaneous candidiasis, etc.: 50 mg per day for 14-30 days.

In severe cases of candidal infections of the mucous membranes, in particular with relapses, the daily dose can be increased to 100 mg/day.

Mycoses of the skin, including mycoses of the feet, body, groin area and skin candidal infections: 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 (up to 6 weeks) may be required.

Onychomycosis: 150 mg 1 time/week. Treatment should be continued until the infected nail is replaced (the uninfected nail regrows). Fingernails and toenails typically take 3-6 and 6-12 months to re-grow, respectively. However, growth rate can vary widely between individuals and also depending on age. After successful treatment of long-standing chronic infections, a change in the shape of the nails is sometimes observed.

Pityriasis versicolor: 300 mg 1 time/week for 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 50 mg 1 time/day for 2-4 weeks.

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

Cryptococcal meningitis: on the first day, an average of 400 mg, then 200-400 mg 1 time / day. The duration of treatment for cryptococcal infections depends on the presence of clinical and mycological effect; treatment is usually continued for at least 6-8 weeks. Prevention of relapse of cryptococcal meningitis in patients with AIDS: after completion of the full course of primary treatment, fluconazole therapy at a dose of 200 mg/day can be continued for a very long period.

Prevention of candidiasis: 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 severe or long-term neutropenia after cytotoxic chemotherapy or radiation therapy, the recommended dose is 400 mg 1 time / day. Fluconazole is prescribed several days before the expected onset of neutropenia and after the number of neutrophils increases to more than 1000/μl, treatment is continued for another 7 days.

Children over 16 years old

Method of administration and dose - as with similar infections in adults, the duration of treatment depends on the clinical and mycological effect. The maximum daily dose for children is 400 mg. Fluconazole is used daily 1 time/day.

Use in children with renal impairment: See "Patients with renal impairment" below.

Elderly patents

In the absence of signs of renal failure, the drug is used in a standard dose.

Patients with impaired renal function

Fluconazole is excreted mainly in the urine unchanged. With a single dose, no dose change is required. In patients, including children, with impaired renal function, with repeated use of the drug, a “loading” dose of 50 mg to 400 mg should be initially administered, after which the daily dose is determined depending on the indications according to the following table.