Fluxar

Fluxar

fluconazole

Manufacturer:

Novell Pharma
Full Prescribing Info
Contents
Fluconazole.
Description
Each capsule contains Fluconazole 150 mg.
Action
Pharmacology: Fluconazole, a member of a new class of triazole antifungal agents, is a potent and specific inhibitor of fungal ergosterol synthesis.
Orally administered fluconazole was active in a variety of animal fungal infection models. Activity has been demonstrated against opportunistic mycoses e.g. infections with Candida sp, including systemic candidiasis in immunocompromised animals; with Cryptococcus neoformans, including intracranial infections; with Microsporum sp; and with Trichophyton sp. Fluconazole has also been shown to be active in animal models of endemic mycoses, including infections with Blastomyces dermatitides; with Coccidioides immitis, including intracranial infection; and with Histoplasma capsulatum in normal and immunosuppressed animals. Fluconazole is highly specific for fungal cytochrome P-450 dependent enzymes. Fluconazole 50 mg daily given up to 28 days has been shown not to affect testosterone plasma concentrations in males or steroid concentrations in females of childbearing age. Fluconazole 200-400 mg daily has no clinically significant effect on endogenous steroid levels or on ACTH-stimulated response in healthy male volunteers. Interaction studies with antipyrine indicate that single or multiple doses of fluconazole 50 mg does not affect its metabolism.
Pharmacokinetics: The pharmacokinetic properties of fluconazole are similar following administration by the IV or oral route. After oral administration, fluconazole is well absorbed, and plasma levels (and systemic bioavialabilty) are >90% of the levels achieved after administration.
Oral absorption is not affected by concomitant food intake. Peak plasma concentration in the fasting state occur between 1 and 2 hours post-dose with a plasma elimination half-life of approximately 30 hrs. Plasma concentrations are proportional to dose. Ninety percent steady-state levels are reached by 4-5 days with multiple once-daily dosing.
Administration of loading dose (on day 1) of twice the usual daily dose enables plasma levels to approximately 90% steady-state levels by day 2. The apparent volume of distribution approximates to total body water. Plasma protein-binding is low (11-12%).
Fluconazole achieves good penetration into all body fluids studied. The levels of fluconazole in saliva and sputum are similar to plasma levels. In patients with fungal meningitis, fluconazole levels in CSF are approximately 80% the corresponding plasma levels.
High skin concentrations of fluconazole above serum concentrations, are achieved in the stratum corneum, epidermis and eccrine sweat. Fluconazole accumulates in the stratum corneum. At a dose of 50 mg once daily, the concentration of fluconazole after 12 days was 73 mcg/g and 7 days after cessation treatment, the concentration was still 5.8 mcg/g. At the 150 mg once-a-week dose, the concentrations of fluconazole in stratum corneum on day 7 was 23.4 mcg/g and 7 days after the 2nd dose was still 7.1 mcg/g.
The major route of excretion is renal, with approximately 80% of the administered dose appearing in the urine as unchanged drug. Fluconazole clearance is proportional to creatinine clearance. There is no evidence of circulating metabolites. The long plasma elimination half-life provides the basis for single-dose therapy for vaginal candidiasis, daily dosing, once weekly for all other indications.
Toxicology: Carcinogenicity: Fluconazole showed no evidence of carcinogenic potential in mice and rats treated orally for 24 months at doses of 2.5, 5 or 10 mg/Kg/day (approximately 2-7 times the recommended human dose). Male rats treated with 5 and 10 mg/Kg/day had an increase incidence of hepatocellular adenomas.
Mutagenicity: Fluconazole, with or without metabolic activation, was negative in tests for mutagenicity in 4 strains of S. typhimurium, and in the mouse lymphoma L5178Y system. Cytogenetic studies in vivo (murine bone marrow cells, following oral administration of fluconazole) and in vitro (human lymphocytes exposed to fluconazole at 1000 mcg/mL) showed no evidence of chromosomal mutations.
Impairment of Fertility: Fluconazole did not affect the fertility of male or female rats treated orally with daily dose of 5, 10 or 20 mg/Kg or with parenteral doses of 5, 25 or 75 mg/Kg, although the onset of parturition was slightly delayed at 20 mg/Kg orally. In an IV perinatal study in rats at 5, 20 and 40 mg/Kg, dystocia and prolongation of parturition were observed on a few dams at 20 mg/Kg (approximately 5-15 times the recommended human dose) and 40 mg/Kg, but not at 5 mg/Kg. The disturbance in parturition were reflected by a slight increase in the number of stillborn pups and decrease of neonatal survival at these dose levels. The effects of parturition in rats are consistent with the species-specific estrogen-lowering property produced by high doses of fluconazole. Such a hormone change has not been observed in women treated with fluconazole (see Pharmacology as previously mentioned).
Indications/Uses
Cryptoccocal meningitis, systemic candidiasis, orofarings and esophageal candidiasis, acute and relapse vaginal candidiasis.
Dosage/Direction for Use
Cryptococcal meningitis: Usual dose for adults: 400 mg as a single dose on the first day followed by 200-400 mg daily. Duration of treatment for cryptococcal infections will depend on the clinical and mycological response (usually at least 6-8 weeks). In patients with AIDS, fluconazole may be administered indefinitely at a once daily dose of 200 mg.
Systemic candidiasis:
Usual dose for adults: 400 mg as a single dose on the first day followed by 200 mg daily. Depending on the clinical response, the dose may be increased to 400 mg daily. Duration of treatment is based upon the clinical response.
Oropharyngeal candidiasis: Usual dose for adults: 50 mg once daily for 1-2 weeks. If necessary, treatment can be continued for maintenance. This dose is the same for esophagus candidiasis however the period of therapy takes longer (approximately 14-30 days). Maximum dose is 100 mg.
Acute vaginal candidiasis or relapse: Usual dose for adults: 150 mg as a single dose.
Use in children: use in children <16 years is not recommended, however when the treating physician considers fluconazole therapy imperative the following: Children ≥1 year with normal renal function are recommended: 1-2 mg/Kg body weight daily for superficial candidal infections and 3-6 mg/Kg body weight for systemic candidal/cryptococcal infections. Daily doses up to 12 mg/Kg body weight have been used in a small number of children provided not exceeding 400 mg/day.
Use in geriatric patients: When there is no evidence of renal impairment, normal dosage recommendations should be adopted. For patients with renal impairment (creatinine clearance <50 mL/min), the dosage schedule should be adjusted.
Contraindications
Patients with known sensitivity to fluconazole or to related azole compounds.
Special Precautions
Fluconazole should be administered carefully to patients with hepatic or renal impairment.
May cause growth of insensitive microorganisms/candida (except Candida albicans and Candida krusei). Superinfection caused by insensitive candida strain may occur hence needed alternative antifungal therapy.
Patients have rarely developed exfoliative fatal cutaneous reactions during treatment with fluconazole.
Not recommended for pregnant women or nursing mothers, except in patients with severe or potentially life-threatening fungal infections in whom fluconazole may be used if the anticipated benefit outweighs the possible risk to the fetus.
Not recommended for children <16 years (unless antifungal treatment is imperative and no suitable alternative agents exist).
In rare cases, as with other azoles, anaphylaxis has been reported.
Fluconazole should be discontinued if bullous lesions or erythema multiforme develop.
Use In Pregnancy & Lactation
Not recommended for pregnant women or nursing mothers, except in patients with severe or potentially life-threatening fungal infections in whom fluconazole may be used if the anticipated benefit outweighs the possible risk to the fetus.
Side Effects
Fluconazole is generally well tolerated. The most common side effects associated with fluconazole are symptoms related to the gastrointestinal tract. These include nausea, abdominal pain, diarrhea and flatulence. After gastrointestinal symptoms, the second most commonly observed side effect was rash. Headache has been associated with fluconazole. In some patients, particularly those with serious underlying diseases, e.g. AIDS and cancer, changes in renal and hematological function test results and hepatic abnormalities (see Precautions) have been observed during treatment with fluconazole and comparative agents, but the clinical significance and relationship to treatment is uncertain.
Exfoliative skin disorders, seizures, leukopenia, including neutropenia and agranulocytosis, thrombocytopenia and alopecia have occurred under conditions where a causal association is uncertain.
If a rash develops in patients treated for superficial fungal infection which is considered attributable to fluconazole, further therapy with this agent should be discontinued. If patients with invasive/systemic fungal infections develop rashes, they should be monitored closely and fluconazole discontinued if bullous lesions or erythema multiforme develop.
In rare cases, as with other azoles, anaphylaxis have been reported.
Drug Interactions
Fluconazole can inhibit the metabolism of some drugs when administered concomitantly by inhibiting cytochrome P450 (CYP3A4). May cause an increase in plasma concentration of phenytoin, sulfonylurea, cyclosporin, nortriptyline, tributin, tacrolimus and zidovudine and decrease the toxic metabolite production of Sulfametoxazole.
Concomitant administration with rifampicin may result in a decrease of plasma concentration of fluconazole.
Concomitant administration with terfenadine can cause ECG abnormality.
Concomitant administration with astemizole, cisapride and terfenadine should be avoided because of risk in cardiac arrhythmia.
Concomitant administration with oral anticoagulants can increase the effects of anticoagulants and decrease theophylline clearance.
Concomitant administration with sulfonylureas (chlorpropamide, glibenclamide, glipizide and tolbutamide) has been shown to prolong serum half-life. Therefore the possibility of a hypoglycemic episode should be borne in mind.
There were no relevant effects on concomitantly administered oral contraceptives.
Storage
Store at room temperature (below 30°C).
MIMS Class
ATC Classification
J02AC01 - fluconazole ; Belongs to the class of triazole derivatives. Used in the systemic treatment of mycotic infections.
Presentation/Packing
Cap 150 mg x 1 x 5's.
Register or sign in to continue
Asia's one-stop resource for medical news, clinical reference and education
Sign up for free
Already a member? Sign in