Complete SPL Sections#
DESCRIPTION
Description Section
Fluconazole, the first of a new subclass of synthetic triazole antifungal agents, is available as a powder for oral suspension. Fluconazole is designated chemically as 2,4-difluoro-α,α 1 -bis(1H-1,2,4-triazol-1-ylmethyl) benzyl alcohol with an empirical formula of C 13 H 12 F 2 N 6 O and molecular weight of 306.3. The structural formula is: Fluconazole USP is a white or almost white, crystalline powder which is slightly soluble in water and saline. Fluconazole for oral suspension USP contains 350 mg or 1400 mg of fluconazole USP and the following inactive ingredients: sodium benzoate, citric acid anhydrous, sodium citrate, xanthan gum, titanium dioxide, natural orange flavor, colloidal silicon dioxide, and sucrose. After reconstitution with 24 mL of distilled water or Purified Water (USP), each mL of reconstituted suspension contains 10 mg or 40 mg of fluconazole.
CLINICAL PHARMACOLOGY
Clinical Pharmacology Section
INDICATIONS AND USAGE
Indications & Usage Section
Fluconazole for oral suspension is indicated for the treatment of: Oropharyngeal and esophageal candidiasis. In open noncomparative studies of relatively small numbers of patients, fluconazole for oral suspension was also effective for the treatment of Candida urinary tract infections, peritonitis, and systemic Candida infections including candidemia, disseminated candidiasis, and pneumonia. Cryptococcal meningitis . Before prescribing fluconazole for oral suspension for AIDS patients with cryptococcal meningitis , please see CLINICAL STUDIES section. Studies comparing fluconazole for oral suspension to amphotericin B in non-HIV infected patients have not been conducted. Prophylaxis: Fluconazole for oral suspension is also indicated to decrease the incidence of candidiasis in patients undergoing bone marrow transplantation who receive cytotoxic chemotherapy and/or radiation therapy. Specimens for fungal culture and other relevant laboratory studies (serology, histopathology) should be obtained prior to therapy to isolate and identify causative organisms. Therapy may be instituted before the results of the cultures and other laboratory studies are known; however, once these results become available, anti-infective therapy should be adjusted accordingly.
CLINICAL STUDIES
Clinical Studies Section
Cryptococcal meningitis: In a multicenter study comparing fluconazole (200 mg/day) to amphotericin B (0.3 mg/kg/day) for treatment of cryptococcal meningitis in patients with AIDS, a multivariate analysis revealed three pretreatment factors that predicted death during the course of therapy: abnormal mental status, cerebrospinal fluid cryptococcal antigen titer greater than 1:1024, and cerebrospinal fluid white blood cell count of less than 20 cells/mm 3 . Mortality among high risk patients was 33% and 40% for amphotericin B and fluconazole patients, respectively (p=0.58), with overall deaths 14% (9 of 63 subjects) and 18% (24 of 131 subjects) for the 2 arms of the study (p=0.48). Optimal doses and regimens for patients with acute cryptococcal meningitis and at high risk for treatment failure remain to be determined. (Saag, et al . N Engl J Med 1992; 326:83-9.) Pediatric Studies Oropharyngeal candidiasis: An open-label, comparative study of the efficacy and safety of fluconazole (2 to 3 mg/kg/day) and oral nystatin (400,000 I.U. 4 times daily) was conducted in immunocompromised pediatric patients from 6 months to 13 years of age with oropharyngeal candidiasis. Clinical and mycological response rates were higher in pediatric patients treated with fluconazole. Clinical cure at the end of treatment was reported for 86% of fluconazole-treated patients compared to 46% of nystatin treated patients. Mycologically, 76% of fluconazole treated patients had the infecting organism eradicated compared to 11% for nystatin treated patients. Fluconazole Nystatin * Subjects without follow-up cultures for any reason were considered nonevaluable for mycological response. Enrolled 96 90 Clinical Cure 76/88 (86%) 36/78 (46%) Mycological eradication* 55/72 (76%) 6/54 (11%) The proportion of patients with clinical relapse 2 weeks after the end of treatment was 14% for subjects receiving fluconazole and 16% for subjects receiving nystatin. At 4 weeks after the end of treatment, the percentages of patients with clinical relapse were 22% for fluconazole and 23% for nystatin.
CONTRAINDICATIONS
Contraindications Section
Fluconazole for oral suspension is contraindicated in patients who have shown hypersensitivity to fluconazole or to any of its excipients. There is no information regarding cross-hypersensitivity between fluconazole and other azole antifungal agents. Caution should be used in prescribing fluconazole for oral suspension to patients with hypersensitivity to other azoles. Coadministration of other drugs known to prolong the QT interval and which are metabolized via the enzyme CYP3A4 such as erythromycin, pimozide, and quinidine are contraindicated in patients receiving fluconazole. (See CLINICAL PHARMACOLOGY: Drug Interaction Studies and PRECAUTIONS .)
WARNINGS
Warnings Section
(1) Hepatic injury: Fluconazole should be administered with caution to patients with liver dysfunction. 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: Exfoliative skin disorders during treatment with fluconazole have been reported. Fatal outcomes have been reported in patients with serious underlying diseases. Patients with deep seated fungal infections who develop rashes during treatment with fluconazole should be monitored closely and the drug discontinued if lesions progress. Fluconazole should be discontinued in patients treated for superficial fungal infection who develop a rash that may be attributed to fluconazole. (4) Potential for fetal harm: There are no adequate and well-controlled clinical trials of fluconazole in pregnant women. Case reports describe a pattern of distinct congenital anomalies in infants exposed in utero to high dose maternal fluconazole (400 to 800 mg/day) during most or all of the first trimester. These reported anomalies are similar to those seen in animal studies. If fluconazole is used during pregnancy or if the patient becomes pregnant while taking the drug, the patient should be informed of the potential hazard to the fetus. Effective contraceptive measures should be considered in women of child-bearing potential who are being treated with fluconazole 400 to 800 mg/day and should continue throughout the treatment period and for approximately 1 week (5 to 6 half-lives) after the final dose. Epidemiological studies suggest a potential risk of spontaneous abortion and congenital abnormalities in infants whose mothers were treated with 150 mg of fluconazole as a single or repeated dose in the first trimester, but these epidemiological studies have limitations and these findings have not been confirmed in controlled clinical trials. (See PRECAUTIONS: Pregnancy . )
PRECAUTIONS
Precautions Section
ADVERSE REACTIONS
Adverse Reactions Section
Fluconazole is generally well tolerated. In some patients, particularly those with serious underlying diseases such as AIDS and cancer, changes in renal and hematological function test results and hepatic abnormalities have been observed during treatment with fluconazole and comparative agents, but the clinical significance and relationship to treatment is uncertain.
OVERDOSAGE
Overdosage Section
There have been reports of overdose with fluconazole accompanied by hallucination and paranoid behavior. 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 3-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.
DOSAGE AND ADMINISTRATION
Dosage & Administration Section
HOW SUPPLIED
How Supplied Section
Fluconazole for Oral Suspension USP, 10 mg/mL is supplied as an orange flavored white to off-white powder to provide 35 mL per bottle as follows: 35 mL Bottle NDC 16714-695-01 Fluconazole for Oral Suspension USP, 40 mg/mL is supplied as an orange flavored white to off-white powder to provide 35 mL per bottle as follows: 35 mL Bottle NDC 16714-696-01
References Section
References Section
Maalox ® is a registered trademark of Novartis Consumer Health, Inc. XELJANZ ® is a registered trademark of Pfizer Inc. LYNPARZA ® is a registered trademark of AstraZeneca group of companies. Manufactured for: Northstar Rx LLC Memphis, TN 38141. Toll free number: 1-800-206-7821 Manufactured by: Aurobindo Pharma Limited Hyderabad-500 090, India. M.L.No.: 19/HD/AP/95/F/R Revised: 08/2024
PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 10 mg/mL (35 mL Bottle)
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
Rx only NDC 16714-695-01 Fluconazole for Oral Suspension USP 10 mg/mL when reconstituted 35 mL when reconstituted NORTHSTAR ®
PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 10 mg/mL Carton Label
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
Rx only NDC 16714-695-01 Fluconazole for Oral Suspension USP 10 mg/mL when reconstituted ORANGE FLAVORED 35 mL when reconstituted NORTHSTAR ®
PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 40 mg/mL (35 mL Bottle)
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
Rx only NDC 16714-696-01 Fluconazole for Oral Suspension USP 40 mg/mL when reconstituted 35 mL when reconstituted NORTHSTAR ®
PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 40 mg/mL Carton Label
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
Rx only NDC 16714-696-01 Fluconazole for Oral Suspension USP 40 mg/mL when reconstituted ORANGE FLAVORED 35 mL when reconstituted NORTHSTAR ®
