FLUCONAZOLE TABLET [REMEDYREPACK INC.] The pattern and incidence of adverse events and laboratory abnormalities recorded during pediatric clinical trials are comparable to those seen in adults. In Phase II/III clinical trials conducted in the United States and in Europe, 577 pediatric patients, ages 1 day to 17 years were treated with fluconazole at doses up to 15 mg/kg/day for up to 1,616 days. Thirteen percent of pediatric patients experienced treatment-related adverse events. The most commonly reported events were vomiting (5%), abdominal pain (3%), nausea (2%), and diarrhea (2%). Treatment was discontinued in 2.3% of patients due to adverse clinical events and in 1.4% of patients due to laboratory test abnormalities. The majority of treatment-related laboratory abnormalities were elevations of transaminases or alkaline phosphatase. Percentage of Patients With Treatment-Related Side Effects Fluconazole Comparative Agents (N=577) (N=451) With any side effect 13 9.3 Vomiting 5.4 5.1 Abdominal pain 2.8 1.6 Nausea 2.3 1.6 Diarrhea 2.1 2.2 Clinical Trials Experience in Pediatric Patients Safety in Prophylaxis of Invasive Candida Infections in Premature infants weighing less than 750 grams at birth In a Phase 3 clinical tr arrhea 2.1 2.2 Clinical Trials Experience in Pediatric Patients Safety in Prophylaxis of Invasive Candida Infections in Premature infants weighing less than 750 grams at birth In a Phase 3 clinical trial of pediatric patients (premature infants weighing less than 750 grams at birth), the incidence of intestinal perforation in infants receiving fluconazole prophylaxis was higher compared to infants receiving placebo (see PRECAUTIONS: Pediatric Use ). Safety in Pediatric Patients Receiving ECMO A cohort of 20 pediatric patients (1 day to 17 years of age) on ECMO received fluconazole in a prospective, open-label, single-center safety and PK ECMO study. The adverse reaction profile of fluconazole in these patients was similar to that of adult and pediatric non-ECMO patients (See PRECAUTIONS: Pediatric Use ). Oropharyngeal candidiasis: The recommended dosage of fluconazole tablets for oropharyngeal candidiasis in pediatric patients 6 months and older is 6 mg/kg on the first day, followed by 3 mg/kg once daily. Treatment should be administered for at least 2 weeks to decrease the likelihood of relapse. Esophageal candidiasis: For the treatment of esophageal candidiasis, the recommended dosage of fluconazole tablets in pediatric patients 6 months and older is 6 mg/kg on the first day, followed by 3 mg/kg once daily. Doses up to 12 mg/kg/day may be used, based on medical judgment of the patient’s response to therapy. Patients with esophageal candidiasis should be treated for a minimum of three weeks and for at least 2 weeks following the resolution of symptoms. Systemic Candida infections: The following dosing regimens in Table 6 are recommended for pediatric patients to achieve systemic exposures similar to adults for the treatment of systemic Candida infections, i.e., to maintain an AUC 0-24 between 400 to 800 mg*h/L. Table 6: Recommended Dosing Regimens for the Treatment of Systemic Candida Infections in Pediatric Patients Patient age Dosing regimen 3 months and older A loading dose of between 400 to 800 mg*h/L. Table 6: Recommended Dosing Regimens for the Treatment of Systemic Candida Infections in Pediatric Patients Patient age Dosing regimen 3 months and older A loading dose of 25 mg/kg on the first day (not to exceed 800 mg) followed by 12 mg/kg once daily (not to exceed 400 mg). Birth to 3 months postnatal age and gestational age 30 weeks and above 25 mg/kg on the first day, followed by 12­mg/kg once daily Birth to 3 months postnatal age and gestational age less than 30 weeks 25 mg/kg on the first day, followed by 9­mg/kg once daily Patients with systemic candidiasis should be treated for a minimum of 3 weeks and for at least 2 weeks following the resolution of symptoms. Dosing in Pediatric Patients on ECMO The recommended dosage of fluconazole in pediatric patients 3 months and older on ECMO is 35 mg/kg on the first day (not to exceed 800 mg) followed by 12 mg/kg once daily (not to exceed 400 mg). For patients from birth to 3 months postnatal age, and gestational age less than 30 weeks, a loading dose of 35 mg/kg on the first day followed by 9 mg/kg once daily is recommended. For patients from birth to 3 months postnatal age and gestational age 30 weeks an nal age less than 30 weeks, a loading dose of 35 mg/kg on the first day followed by 9 mg/kg once daily is recommended. For patients from birth to 3 months postnatal age and gestational age 30 weeks and above, a loading dose of 35 mg/kg on the first day followed by 12 mg/kg once daily is recommended Cryptococcal meningitis: For the treatment of acute cryptococcal meningitis , the recommended dosage is 12 mg/kg on the first day, followed by 6 mg/kg once daily. A dosage of 12 mg/kg once daily may be used, based on medical judgment of the patient’s response to therapy. The recommended duration of treatment for initial therapy of cryptococcal meningitis is 10 to 12 weeks after the cerebrospinal fluid becomes culture negative. For suppression of relapse of cryptococcal meningitis in pediatric patients with AIDS, the recommended dose of fluconazole tablets is 6 mg/kg once daily.