Fluconazole tablet

Microbiology



Fluconazole exhibits in vitroactivity against Cryptococcus neoformansand Candida spp.Fungistatic activity has also been demonstrated in normal and immunocompromised animal models for systemic and intracranial fungal infections due to Cryptococcus neoformansand for systemic infections due to Candida albicans.

In common with other azole antifungal agents, most fungi show a higher apparent sensitivity to fluconazole in vivothan in vitro. Fluconazole administered orally and/or intravenously was active in a variety of animal models of fungal infection using standard laboratory strains of fungi. Activity has been demonstrated against fungal infections caused by Aspergillus flavusand Aspergillus fumigatusin normal mice. Fluconazole has also been shown to be active in animal models of endemic mycoses, including one model of Blastomyces dermatitidispulmonary infections in normal mice; one model of Coccidioides immitisintracranial infections in normal mice; and several models of Histoplasma capsulatumpulmonary infection in normal and immunosuppressed mice. The clinical significance of results obtained in these studies is unknown.

Oral fluconazole has been shown to be active in an animal model of vaginal candidiasis.

Concurrent administration of fluconazole and amphotericin B in infected normal and immunosuppressed mice showed the following results: a small additive antifungal effect in systemic infection with C. albicans, no interaction in intracranial infection with Cr. neoformans, and antagonism of the two drugs in systemic infection with Asp. fumigatus. The clinical significance of results obtained in these studies is unknown.

There have been reports of cases of superinfection with Candidaspecies other than C. albicans, which are often inherently not susceptible to fluconazole (e.g., Candida krusei). Such cases may require alternative antifungal therapy.


Warnings



1. Hepatic Injury

Fluconazole has been associated with rare cases of serious hepatic toxicity, including fatalities primarily in patients with serious underlying medical conditions. In cases of fluconazole-associated hepatotoxicity, no obvious relationship to total daily dose, duration of therapy, sex or age of the patient has been observed.

Fluconazole hepatotoxicity has usually, but not always, been reversible on discontinuation of therapy. Patients who develop abnormal liver function tests during fluconazole therapy should be monitored for the development of more severe hepatic injury. Fluconazole should be discontinued if clinical signs and symptoms consistent with liver disease develop that may be attributable to fluconazole.

2. Anaphylaxis

In rare cases, anaphylaxis has been reported.

3. Dermatologic

Patients have rarely developed exfoliative skin disorders during treatment with fluconazole. In patients with serious underlying diseases (predominantly AIDS and malignancy), these have rarely resulted in a fatal outcome. Patients who develop rashes during treatment with fluconazole should be monitored closely and the drug discontinued if lesions progress.


Pediatric use



An open-label, randomized, controlled trial has shown fluconazole to be effective in the treatment of oropharyngeal candidiasis in pediatric patients 6 months to 13 years of age (see CLINICAL STUDIES).

The use of fluconazole in pediatric patients with cryptococcal meningitis, Candidaesophagitis, or systemic Candidainfections is supported by the efficacy shown for these indications in adults and by the results from several small noncomparative pediatric clinical studies. In addition, pharmacokinetic studies in pediatric patients (see CLINICAL PHARMACOLOGY) have established a dose proportionality between pediatric patients and adults (see DOSAGE AND ADMINISTRATION).

In a noncomparative study of pediatric patients with serious systemic fungal infections, most of which were candidemia, the effectiveness of fluconazole was similar to that reported for the treatment of candidemia in adults. Of 17 subjects with culture-confirmed candidemia, 11 of 14 (79%) with baseline symptoms (3 were asymptomatic) had a clinical cure; 13/15 (87%) of evaluable patients had a mycologic cure at the end of treatment but two of these patients relapsed at 10 and 18 days, respectively, following cessation of therapy.

The efficacy of fluconazole for the suppression of cryptococcal meningitis was successful in 4 of 5 pediatric patients treated in a compassionate-use study of fluconazole for the treatment of life-threatening or serious mycosis. There is no information regarding the efficacy of fluconazole for primary treatment of cryptococcal meningitis in pediatric patients.

The safety profile of fluconazole in pediatric patients has been studied in 577 pediatric patients ages 1 day to 17 years who received doses ranging from 1 to 15 mg/kg/day for 1 to 1,616 days (see ADVERSE REACTIONS).

Efficacy of fluconazole has not been established in infants less than 6 months of age (see CLINICAL PHARMACOLOGY). A small number of patients (29) ranging in age from 1 day to 6 months have been treated safely with fluconazole.


Geriatric use



In non-AIDS patients, side effects possibly related to fluconazole treatment were reported in fewer patients aged 65 and older (9%, n=339) than for younger patients (14%, n=2240). However, there was no consistent difference between the older and younger patients with respect to individual side effects. Of the most frequently reported (less then 1%) side effects, rash, vomiting and diarrhea occurred in greater proportions of older patients. Similar proportions of older patients (2.4%) and younger patients (1.5%) discontinued fluconazole therapy because of side effects. In post-marketing experience, spontaneous reports of anemia and acute renal failure were more frequent among patients 65 years of age or older than in those between 12 and 65 years of age. Because of the voluntary nature of the reports and the natural increase in the incidence of anemia and renal failure in the elderly, it is however not possible to establish a casual relationship to drug exposure.

Controlled clinical trials of fluconazole did not include sufficient numbers of patients aged 65 and older to evaluate whether they respond differently from younger patients in each indication. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. Fluconazole is primarily cleared by renal excretion as unchanged drug. Because elderly patients are more likely to have decreased renal function, care should be taken to adjust dose based on creatinine clearance. It may be useful to monitor renal function. (See CLINICAL PHARMACOLOGYand DOSAGE AND ADMINISTRATION.)


Overdosage



There have been reports of overdosage with fluconazole. A 42-year-old patient infected with human immunodeficiency virus developed hallucinations and exhibited paranoid behavior after reportedly ingesting 8200 mg of fluconazole. The patient was admitted to the hospital, and his condition resolved within 48 hours.

In the event of overdose, symptomatic treatment (with supportive measures and gastric lavage if clinically indicated) should be instituted. Fluconazole is largely excreted in urine. A three-hour hemodialysis session decreases plasma levels by approximately 50%

In mice and rats receiving very high doses of fluconazole, clinical effects in both species included decreased motility and respiration, ptosis, lacrimation, salivation, urinary incontinence, loss of righting reflex and cyanosis; death was sometimes preceded by clonic convulsions.


Ingredients and appearance - Product information

Fluconazole tablet- Fluconazole

Product information

Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC: 49349-087
Route of Administration Oral

Active Ingredient/Active Moiety

Ingredient Name Strength
Fluconazole ( UNII: 8VZV102JFY)( Fluconazole - UNII: 8VZV102JFY ) 100 mgin 1

Inactive Ingredients

Ingredient Name Code
Silicon dioxide ( UNII: ETJ7Z6XBU4)
Starch, corn ( UNII: O8232NY3SJ)
Croscarmellose sodium ( UNII: M28OL1HH48)
Fd&c red no. 40 ( UNII: WZB9127XOA)
Lactose monohydrate ( UNII: EWQ57Q8I5X)
Magnesium stearate ( UNII: 70097M6I30)
Cellulose, microcrystalline ( UNII: OP1R32D61U)
Talc ( UNII: 7SEV7J4R1U)

Product Characteristics

Color pink Score 1
Shape OVAL (TABLET) Imprint Code 5411;100
Size 10 mm

Packaging

# Item Code Package Description Marketing Start Date
1 NDC: 49349-087-02 30 in 1 BLISTER PACK 2010/11/22

Marketing Information

Marketing Category Application Number or Monograph Citation Territorial Authority Marketing Start Date
ANDA ANDA076077 USA 2010/11/22

Labeler - REMEDYREPACK INC.( 829572556)