Mycomax, 150 mg capsules 3 pcs

MIKOMAX is an antifungal.

Pharmacodynamics

Fluconazole, representative of the class of triazole antifungal agents, is a potent selective inhibitor of sterol synthesis in the fungal cell.

The drug is effective in opportunistic mycoses, including those caused by Candida spp., Cryptococcus neoformans, Microsporum spp., Trichophyton spp. Fluconazole activity has also been shown in models of endemic mycoses, including infections caused by Blastomyces dermatitidis, Coccidiodes immitis and Histoplasma capsulatum.

Pharmacokinetics

Fluconazole is well absorbed after oral administration, its bioavailability is 90%. Cmax after oral administration on an empty stomach at a dose of 150 mg is 90% of plasma content when administered in the IV dose of 2.5-3.5 mg/l. Simultaneous intake of food has no effect on absorption of the drug taken orally. Cmax in plasma is reached 0.5-1.5 hours after administration.

The T1/2 of fluconazole is about 30 hours. Plasma concentrations are in direct proportion to the dose. The 90% level of equilibrium concentration is reached by 4-5 days of treatment with the drug (when taken once daily).

The administration of a shock dose (on the first day), 2 times the usual daily dose, allows to reach the level corresponding to 90% of the equilibrium concentration by the second day. The apparent volume of distribution approaches the total body water content. Binding to plasma proteins is 11-12%.

Fluconazole penetrates well into all body fluids. Concentrations of the drug in saliva and sputum are similar to its levels in plasma. In patients with fungal meningitis the content of fluconazole in the cerebrospinal fluid reaches 80% of its level in plasma.

In the stratum corneum, epidermis, dermis and sweat fluid high concentrations are achieved that exceed serum levels.

Fluconazole is mainly excreted by the kidneys; approximately 80% of the administered dose is excreted unchanged in the urine. Fluconazole clearance is proportional to creatinine clearance. No fluconazole metabolites were detected in peripheral blood.

Indications

Active ingredient

Composition

1 capsule contains:

Active substance:

fluconazole150 mg;

Associates:

Lactose monohydrate;

Pregelatinized starch;

colloidal silicon dioxide;

magnesium stearate;

sodium lauryl sulfate.

How to take, the dosage

Ingestion.

In adults with cryptococcal meningitis and cryptococcal infections of other localizations, 400 mg is usually prescribed on the first day and then treatment is continued at a dose of 200-400 mg once daily. The duration of treatment in cryptococcal infections depends on clinical efficacy confirmed by mycological examination; in cryptococcal meningitis it is usually continued for at least 6-8 weeks.

In order to prevent relapse of cryptococcal meningitis in AIDS patients, after completion of the full course of primary treatment, fluconazole is prescribed at a dose of 200 mg/day for an extended period of time.

In candidemia, disseminated candidiasis, and other invasive candidiasis infections, the dose is usually 400 mg the first day and 200 mg thereafter. In case of insufficient clinical efficacy, the drug dose may be increased to 400 mg/day. The duration of therapy depends on clinical effectiveness.

In oropharyngeal candidiasis the drug is usually prescribed 50-100 mg once daily; therapy duration is 7-14 days. If necessary, in patients with a marked decrease in immunity, treatment may be longer.

In atrophic oral candidiasis associated with the wearing of dentures, fluconazole is usually prescribed 50 mg once daily for 14 days in combination with local antiseptics for denture treatment.

In other localizations of candidiasis (except genital candidiasis), such as esophagitis, non-invasive bronchopulmonary lesions, candiduria, candidiasis of skin and mucous membranes, etc., the effective dose is usually 50-100 mg/day with treatment duration of 14-30 days. For prevention of oropharyngeal candidiasis relapses in patients with AIDS after completion of a full course of primary therapy, the drug may be prescribed 150 mg once a week.

For vaginal candidiasis, fluconazole is taken once orally in a dose of 150 mg. To reduce the recurrence rate of vaginal candidiasis, the drug may be used in a dose of 150 mg once a month. The duration of therapy is determined individually; it varies from 4 to 12 months. Some patients may require more frequent use.

Fluconazole is given as a single oral dose of 150 mg for balanitis caused by Candida.

For prevention of candidiasis, the recommended dose of fluconazole is 50-400 mg once daily, depending on the risk of fungal infection. If there is a high risk of generalized infection, such as in patients with expected severe or prolonged neutropenia, the recommended dose is 400 mg once daily. Fluconazole is administered several days before the expected appearance of neutropenia; after an increase in neutrophil count above 1000/mm3, treatment is continued for another 7 days.

In mycoses of the skin, including mycoses of the feet, skin of the groin, and candidiasis of the skin, the recommended dose is 150 mg once weekly or 50 mg once daily. Duration of therapy in common cases is 2-4 weeks, but in case of mycoses of feet a longer therapy (up to 6 weeks) may be required.

In rubella, 300 mg once a week for 2 weeks, some patients need a third dose of 300 mg a week, while in some cases a single dose of 300-400 mg is sufficient; an alternative therapy regimen is 50 mg once a day for 2-4 weeks.

In onychomycosis, the recommended dose is 150 mg once weekly. Treatment should be continued until the infected nail is replaced (the uninfected nail grows back). It normally takes 3-6 and 6-12 months, respectively, for re-growth of nails on fingers and feet.

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

In children, as well as in 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 that would exceed that of adults. The drug is used daily once a day.

In mucosal candidiasis, the recommended dose of fluconazole is 3 mg/kg/day. A shock dose of 6 mg/kg may be administered on the first day in order to achieve steady-state equilibrium concentrations more quickly.

For the treatment of generalized candidiasis or 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 immunocompromised children whose risk of infection is associated with neutropenia resulting from cytotoxic chemotherapy or radiation therapy, the drug is prescribed at 3-12 mg/kg/day depending on the severity and duration of the maintenance of induced neutropenia.

In children with impaired renal function the daily dose of the drug should be reduced (in the same proportional relationship as in adults) according to the severity of renal failure.

In elderly patients in the absence of renal impairment, the usual dosing regimen of the drug should be followed. In patients with renal impairment (creatinine Cl – <50 ml/min) the dosing regimen should be adjusted as indicated below.

The use of the drug in patients with impaired renal function

Fluconazole is mainly excreted unchanged in the urine. There is no need to change the dose when taking it once. When re-administration of the drug in patients with impaired renal function a shock dose of 50 to 400 mg should be administered first. If creatinine Cl is >50 ml/min, the usual dose of the drug is used (100% of the recommended dose). If creatinine Cl is 11 to 50 mL/min, a dose equal to 50% of the recommended dose is used. For patients who are regularly on dialysis, one dose of the drug is used after each session of hemodialysis.

Interaction

The use of fluconazole with warfarin increases PV (by 12% on average). In this regard, it is recommended to carefully monitor the PV in patients receiving the drug in combination with coumarin anticoagulants.

Fluconazole increases plasma elimination half-life of oral hypoglycemic sulfonylurea derivatives (chlorpropamide, glibenclamide, glipizide, tolbutamide) in healthy subjects. Concomitant use of fluconazole and oral hypoglycemic agents in diabetic patients is permitted, but the physician should consider the possibility of hypoglycemia.

The concomitant use of fluconazole and phenytoin may increase plasma concentrations of phenytoin to a clinically significant degree. Therefore, if co-administration of these drugs is necessary, phenytoin concentrations should be monitored with dose adjustments to maintain drug levels within the therapeutic interval.

Combination with rifampicin decreases AUC by 25% and decreases T1/2 of fluconazole from plasma by 20%. Therefore, in patients receiving rifampicin concomitantly, it is reasonable to increase fluconazole dose.

It is recommended to monitor the blood concentration of cyclosporine in patients receiving fluconazole, because the use of fluconazole and cyclosporine in patients with renal transplantation (while taking fluconazole at a dose of 200 mg/day) leads to a slow increase in plasma concentration of cyclosporine.

Patients who receive high doses of theophylline or who are likely to develop theophylline intoxication should be monitored for early detection of symptoms of theophylline overdose, because fluconazole administration leads to decreased mean plasma clearance rate of theophylline.

In concomitant use of fluconazole with terfenadine, cisapride there have been described cases of adverse reactions in the heart, including paroxysmal ventricular tachycardia (torsades de pointes).

The concomitant use of fluconazole and hydrochlorothiazide may increase fluconazole plasma concentrations by 40%.

There have been reports of interaction between fluconazole and rifabutin accompanied by increased serum levels of the latter. There have been cases of uveitis during concomitant use of fluconazole and rifabutin. Patients receiving rifabutin and fluconazole concomitantly should be closely monitored.

In patients receiving a combination of fluconazole and zidovudine there is an increase in concentration of zidovudine that is caused by a decrease in conversion of the latter to its main metabolite, therefore an increase in side effects of zidovudine should be expected.

Special Instructions

In rare cases, the use of Mycomax was accompanied by toxic effects on the liver, including with fatal outcome, mainly in patients with serious comorbidities.

Liver function should be monitored during treatment.

If there are signs of liver damage that may be associated with fluconazole administration, the drug should be discontinued.

Contraindications

With caution: hepatic and/or renal insufficiency, concomitant use of potentially hepatotoxic drugs, alcoholism.

Side effects

Digestive system disorders: changes in taste, vomiting, nausea, diarrhea, flatulence, abdominal pain, rarely – liver function disorders (jaundice, hepatitis, hepatonecrosis, hyperbilirubinemia, increased ALT, AST, ALP activity).

Nervous system disorders: headache, dizziness, rarely – seizures.

Hematopoietic organs: rarely – leukopenia, thrombocytopenia, neutropenia, agranulocytosis.

Allergic reactions: skin rash, rarely – erythema malignant exudative (Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell syndrome), anaphylactoid reactions.

Other: rarely – renal dysfunction, alopecia, hypercholesterolemia, hypertriglyceridemia, hypokalemia.

Overdose

Symptoms: hallucinations, paranoid behavior.

Treatment: symptomatic, gastric lavage, forced diuresis. Hemodialysis for 3 h reduces plasma concentrations by approximately 50%.

Similarities