MICADAC

 

TRADE NAME

Micadac

 

INTERNATIONAL NONPROPRIETARY NAME

Fluconazole

 

CHEMICAL NAME

2-(2,4- difluorophenyl)-1,3-bis(1Н-1,2,4- triazol-1-yl)-2-propanol

 

PHARMACEUTICAL FORM

Capsules.

Description: hard gelatin capsules, size 1, with opaque light green cap and body, containing white to almost white powder.

 

COMPOSITION

Capsule contains

Active ingredient: fluconazole 150 mg.

Inactive ingredients: microcrystalline cellulose, lactose monohydrate, magnesium stearate, sodium laurilsulfate.

Composition of capsule shell: black iron oxide, titanium dioxide, yellow iron oxide, gelatin.

 

АТC CODE              J02AC01

 

PHARMACOTHERAPEUTIC GROUP

Antifungal agent.

 

PHARMACOLOGICAL PROPERTIES

PHARMACODYNAMICS

Micadac is an antifungal agent of triazol group. Fluconazole, drug active substance, is a strong selective inhibitor of sterol synthesis in cell fungus membranes. The mechanism of action is due to P450 cytochrome blockade. Fluconazole blocks the fungus lanosterol cell transformation in ergosterol; increases the cell membrane penetration, disturbs its growth and replication. Being highly selective for P450 fungal cytochrome, practically doesn’t inhibit these ferments in human body (comparing with itraconazole, clotrimazole, econazole and ketoconazole in less rate inhibits dependent on P450 cytochrome the oxidizing processes in human hepatic microsomes). It doesn’t have antiadrogen activity.

It is active during opportunistic mycoses, including caused Candida spp. (including generelised candidiasis forms against immunodepression), Cryptococcus neoformans and Coccidioides immitis (including intracraneal infections), Microsporum spp. and Trichophyton spp.; at endemical micoses, caused by Blastomyces dermatidis, Histoplasma capsulatum (including at immunodepression). The drug is used for prevention of fungal infections in patients with malignant neoplasms during treatment with cytostatic agents or radiation treatment, in cases of organ transplantation and in other cases of immune system suppression and the risk of fungal infection development.

PHARMACOKINETICS

The drug is quickly and enough completely absorbed from gastrointestinal tract (the meal doesn’t affect the absorption speed). Bioavailability - 90%. Maximal concentration is achieved in 0.5-1.5 h after administration fasting. The binding with plasma proteins is 11-12%. It well penetrates in all body fluids. The concentration of active substance in human milk, joint fluid, saliva, sputum and peritoneal fluid is similar to those in blood plasma. Constant values in vaginal secreta is achieved in 8 h after oral administration and remains on this level not less than 24 h. The concentrations, exceeding serumal (selective uptake) are achieved in sudoral fluid, epidermis and in horny layer. 80% unchanged is excreted with kidney, remaining part in form of metabolites. Circulating metabolites are not observed. The half-life period is about 30 h.

Fluconazole pharmacokinetics significantly depends on renal function, and inverse proportion exists between half-life time and creatinine clearance. After hemodialysis for 3 h the concentration in blood plasma of Fluconazole is reduced by 50%.

 

THERAPEUTIC INDICATIONS

- genital candidiasis; acute or recurrent vaginal candidiasis; preventive treatment to decrease the recurrence rate of vaginal candidiasis (3 and more episodes a year); candidal balanitis;

- preventive treatment of relapse oropharyngeal candidiasis for patients with acquired immune deficiency syndrome (AIDS);

- skin mycosises, including feet and body mycosises, inguinal region; branny lichen; onychomycosis; skin candida infections.

 

DOSAGE AND ADMINISTRATION

Capsules for oral administration. Capsule are swallowed completely independently on meal intake.

The daily dose of fluconazole depends on nature and severity of fungoid infection.

The treatment of other forms of disease demands repeated administration of the medicine till clinically and laboratory confirmed disappearance of active stage of fungoid infection.

The administration of the preparation in a single dose in children in the age of 18 years old and the patients older than 60 years without a doctor’s prescription is not recommended.

For adults:

Vaginal candidiasis: 150 mg is taken orally in a single dose.

Preventive treatment of vaginal candidiasis recurrences: 150 mg 1 time per month. The therapy duration is determined individually; it varies from 4 till 12 months. More frequent administration of the preparation can be required for some patient.

Balanitis, caused by Candida: 150 mg is taken orally in a single dose.

For preventive of Oropharyngeal candidiasis recurrences in patients with AIDS 150 mg of the preparation 1 time per week can be prescribed after the full course completion of primary therapy.

For skin mycosises (including foot mycosises, smooth skin mycosises, skin of inguinal region and candidiasis infections): 150 mg once a week. Duration of therapy in usual cases is 2-4 weeks, however, for feet mycosises, can be required to 6 weeks.

Onychomycosis: 150 mg 1 time per week. The treatment course continues till complete replacement of the infected nail with healthy nail. For repeated nails growth on hand and feet fingers is normally required 3-6 months and 6-12 months accordingly.

Elderly patients without renal dysfunction may administer Micadac according to the usual dosage regimen.

Administration of fluconazole in renal impairment:

No dosage adjustment required in case of a single administration of the preparation.

 

CONTRAINDICATIONS

- hypersensitivity to fluconazole;

- concomitant drug administration, lengthening QT interval (including terfenadine or asthemizole).

 

SIDE EFFECTS

The used side effects frequency parameters presented below are classified in the following way:

frequently (from ≥ 1/100 to < 1/10), infrequently (from ≥ 1/1000 to < 1/100), rarely (from ≥ 1/10000 to < 1/1000).

From digestive system: frequently – nausea, diarrhea, pain in a stomach; infrequently - appetite reduction, constipation, meteorism, toothache; rarely - hepatic function disorder (scleral icterus, icterus, hyperbilirubinemia, increase in activity of alanin aminotransferase, aspartate aminotransferase and alkaline phosphatase).

From nervous system: frequently – headache; infrequently - dizziness, hypernormal fatigability; rarely - convulsions.

From blood-forming organs: rarely - leukocytopenia, thrombocytopenia (bleedings, petechia), neutropenia, agranulocytosis.

Allergic reactions: frequently – skin rash; rarely - Erythema multiforme (including Stevens Johnson's syndrome), toxic epidermal necrolysis (Lyell's syndrome), anaphylactoid reactions.

Other: rarely - renal function disorder, alopecia, hypercholesteremia, hypertriglyceridemia, hypokaliemia.

 

SPECIAL INDICATIONS

Exercise caution prescribing Micadac to patients with hypersensitivity to thiazole compounds due to possible cross-sensitivity reactions.

Fluconazole treatment is necessary to continue till the appearance of clinical hematological remission. Premature treatment discontinuation leads to recurrences.

The treatment may be started at absence of inoculation results or other laboratorial analysis, but the appropriate correction of fungicide therapy is recommended at their presence.

Blood values, renal and hepatic functions are necessary to control during treatment. It is necessary to observe patients in which these values disorder during treatment, with purpose of revealing signs of more severe hepatic lesion. Drug administration should be discontinued during onset of renal function disorder. Hepatotoxic action of fluconazole is usually reversible and the symptoms disappear after therapy stopping.

At onset of cutaneous eruptions in patients it is necessary to conduct thorough observation, and in case of skin reaction progression the treatment should be stopped (the development risk of Stevens Johnson's syndrome, toxic epidermal necrolysis, erythema multiforme).

In case of appearance in patient, receiving the treatment of surfactant fungal infection, rash, which can be connected with fluconazole use, the drug should be cancelled. In case of rash appearance in patients with invasive/systemic fungal infections, they should be observed, and fluconazole should be cancelled in case of appearance of bullous lesions.

It is prescribed with caution in patients with renal function disorder, neonates, AIDS patients (and during the other status with weakened immunity), and also to patients with potentially proarrhythmic states.

 

INFLUENCE ON ABILITY TO DRIVE AND OPERATE OTHER MECHANISMS

Micadac doesn’t influence on the ability for driving a car and for work performance, demanding a high speed of psychomotor reactions.

 

APPLICATION DURING PREGNANCY AND LACTATION

No adequate clinical studies of fluconazole administration during pregnancy have been performed.

Administration of Micadac in pregnancy is possible only in cases when the potential benefit for the mother outweighs the risk for the fetus.

Fluconazole is found in breast milk in the same concentration as in plasma. Therefore its prescription in lactation period is not recommended.

 

PEDIATRIC USE

Administration of the drug in children under 18 years old without doctor`s prescription is not recommended.

DRUG INTERACTIONS

Fluconazole strengthens the pharmacological action of histamine preparations (astemizole, terfenadine); anxiolytics, referring to benzodiazepine group of short action period (midazolam, triazolam); rifabutin, cisapride, phenytoin, zidovudine, tacrolimus, cyclosporine; prolongs the half-life period of theophylline and increases the development risk of intoxication, that requires the correction of its dose.

Hydrochlorothiazide increases fluconazole concentration level in plasma, at concomitant administration with rifampicin the reduction of fluconazole half-life period from blood plasma is reported.

Fluconazole increases the concentration level in blood plasma, and also increases the half-life period of oral hypoglycemic drugs, sulfonylurea derivatives (glibenclamide, glipizide, tolbutamide). During concomitant administration of these drugs the sugar level in blood should be thoroughly controlled for prevention of hypoglicemy development.

During concomitant administration of fluconazole with oral contraceptives the variability of concentration level of hormones is possible (estradiol, levonorgestrel), at concomitant administration of these drugs it is necessary to conduct more thorough control of female patients’ status for prevention of possible side effects development.

It increases the efficacy of coumarinic anticoagulants, the increase of protrombin time is possible, resulting in bleeding development (hematoma, nose bleeding and GIT, hematuria, melena).

The antagonist character of their interaction should be considered at concomitant administration of fluconazole and amphotericin B, however, on practice the interaction result is determined on what substance was injected earlier and the kind of pathogen fungus.

 

OVERDOSE

Symptoms: nausea, vomiting, diarrhea, in more severe cases - convulsions.

Therapy: symptomatic. Gastric lavage, artificial diuresis. Hemodialysis during 3 hours reduces concentration in plasma by about 50%.

 

PACKAGING

Hard gelatin capsules. 1 capsule in a blister.

1 blister with the enclosed leaflet in a carton box.

 

STORAGE CONDITIONS

Store at temperature not exceeding 25ºС.

Keep out of reach of children!

 

SHELF LIFE

3 years from the manufacture date.

Do not use after expiry date.

 

SALES TERMS

Sold without prescription.

 

MANUFACTURER

The holder of trade mark and Marketing Authorization is

"DR SERTUS İLAÇ SANAYİ VE TİCARET LİMİTED ŞİRKETİ", TURKEY.

Manufactured by

“World Medicine Ilaç San. ve Tic. A.Ş.”, Turkey.

(Bağcılar İlçesi, Güneşli, Evren Mahallesi, Cami Yolu Cad. No:50 K. 1B Zemin 4-5-6, İstanbul).