SUPRAX- cefixime_tablet

Cefixime is a semisynthetic cephalosporin antibacterial drug [see Microbiology ( 12. 4 SUPRAX chewable tablets are bioequivalent to SUPRAX for oral suspension. SUPRAX tablets and SUPRAX for oral suspension, given orally, are about 40% to 50% absorbed whether administered with or without food; however, time to maximal absorption is increased approximately 0. 8 hours when administered with food. A single 200 mg tablet of cefixime SUPRAX produces an average peak serum concentration of approximately 2 mcg/mL (range 1 to 4 mcg/mL); a single 400 mg SUPRAX tablet produces an average peak concentration of approximately 3. 7 mcg/mL (range 1. The SUPRAX for oral suspension produces average peak concentrations approximately 25% to 50% higher than the tablets, when tested in normal adult adult [see Dosage and Administration (2)] The 400 mg SUPRAX capsule is bioequivalent to the 400 mg SUPRAX tablet under fasting conditions. However, food reduces the absorption following administration of the capsule by approximately 15% based on AUC and 25% based on C max Peak serum concentrations occur between 2 and 6 hours following oral administration of a single 200 mg tablet, a single 400 mg SUPRAX tablet or 400 mg of SUPRAX for oral suspension. Peak serum concentrations occur between 2 and 5 hours following a single administration of 200 mg of SUPRAX for oral suspension. Peak serum concentrations occur between 3 and 8 hours following oral administration of a single 400 mg SUPRAX capsule. Distribution Serum protein binding is concentration independent with a bound fraction of approximately 65%. In a multiple dose study conducted with a research formulation which is less bioavailable than the SUPRAX tablet or SUPRAX for oral suspension, there was little accumulation of drug in serum or urine after dosing for 14 days. Adequate data on CSF levels of cefixime are not available. Elimination Metabolism and Excretion There is no evidence of metabolism of cefixime in vivo. Approximately 50% of the absorbed dose is excreted unchanged in the urine in 24 hours. In animal studies, it was noted that cefixime is also excreted in the bile in excess of 10% of the administered dose. The serum half-life of cefixime in healthy subjects is independent of dosage form and averages 3 to 4 hours but may range up to 9 hours in some normal volunteers. Specific Populations Geriatric Patients: Table 4. Pharmacokinetic Parameters for Cefixime in Both Young and Elderly Subjects Pharmacokinetic Parameters (mean +/- SD) for Cefixime in Both Young & Elderly Subjects Pharmacokinetic parameter Young Elderly C max 4. 83 T max Difference between age groups was significant. 75 However, these increases were not clinically significant [see Dosage and Administration ( 2 Patients with Renal Impairment: Mechanism of Action As with other cephalosporins, the bactericidal action of cefixime results from inhibition of cell wall synthesis. Cefixime is stable in the presence of certain beta-lactamase enzymes. As a result, certain organisms resistant to penicillins and some cephalosporins due to the presence of beta-lactamases may be susceptible to cefixime. Resistance Resistance to cefixime in isolates of Haemophilus influenzae Neisseria gonorrhoeae Pseudomonas Enterococcus Listeria monocytogenes, Enterobacter Bacteroides fragilis, Clostridium Antimicrobial Activity Cefixime has been shown to be active against most isolates of the following microorganisms, both in vitro and in clinical infections [see Indications and Usage ( 1 Gram-positive Bacteria Streptococcus pneumoniae Streptococcus pyogenes Gram-negative Bacteria Escherichia coli Haemophilus influenzae Moraxella catarrhalis Neisseria gonorrhoeae Proteus mirabilis The following in vitro in vitro Gram-positive Bacteria Streptococcus agalactiae Gram-negative Bacteria Citrobacter amalonaticus Citrobacter diversus Haemophilus parainfluenzae Klebsiella oxytoca Klebsiella pneumoniae Pasteurella multocida Proteus vulgaris Providencia Salmonella Serratia marcescens Shigella Susceptibility Testing For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.

SUPRAX (cefixime) is a cephalosporin antibacterial drug indicated in the treatment of adults and pediatric patients six months and older with the following infections: Uncomplicated Urinary Tract Infections ( 1. 1 Otitis Media ( 1. 2 Pharyngitis and Tonsillitis ( 1. 3 Acute Exacerbations of Chronic Bronchitis ( 1. 4 Uncomplicated Gonorrhea (cervical/urethral) ( 1. 5 Usage to Reduce Development of Drug-Resistant Bacteria To reduce the development of drug-resistant bacteria and maintain the effectiveness of SUPRAX and other antibacterial drugs, SUPRAX should be used only to treat infections that are proven or strongly suspected to be caused by bacteria. 6 SUPRAX is indicated in the treatment of adults and pediatric patients six months of age or older with uncomplicated urinary tract infections caused by susceptible isolates of Escherichia coli Proteus mirabilis SUPRAX is indicated in the treatment of adults and pediatric patients six months of age or older with otitis media caused by susceptible isolates of Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pyogenes. Streptococcus pyogenes Note: For patients with otitis media caused by Streptococcus pneumoniae [see Clinical Studies ( 14 SUPRAX is indicated in the treatment of adults and pediatric patients six months of age or older with pharyngitis and tonsillitis caused by susceptible isolates of Streptococcus pyogenes. Streptococcus pyogenes Streptococcus pyogenes SUPRAX is indicated in the treatment of adults and pediatric patients six months of age or older with acute exacerbations of chronic bronchitis caused by susceptible isolates of Streptococcus pneumoniae Haemophilus influenzae. SUPRAX is indicated in the treatment of adults and pediatric patients six months of age or older with uncomplicated gonorrhea (cervical/urethral) caused by susceptible isolates of Neisseria gonorrhoeae To reduce the development of drug resistant bacteria and maintain the effectiveness of SUPRAX and other antibacterial drugs, SUPRAX should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antimicrobial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Adults: 400 mg daily ( 2. 1 Pediatric patients (6 months and older): 8 mg/kg/day ( 2. 2 The recommended dose of SUPRAX tablet or capsule is 400 mg daily. This may be given as a 400 mg tablet or capsule daily or the 400 mg tablet may be split and given as one half tablet every 12 hours. For the treatment of uncomplicated cervical/urethral gonococcal infections, a single oral dose of 400 mg is recommended. The capsule and tablet may be administered without regard to food. In the treatment of infections due to Streptococcus pyogenes The recommended dose is 8 mg/kg/day of the SUPRAX for oral suspension. This may be administered as a single daily dose or may be given in two divided doses, as 4 mg/kg every 12 hours. Note: A suggested dose has been determined for each pediatric weight range. Refer to Table 1. Ensure all orders that specify a dose in milliliters include a concentration, because SUPRAX for oral suspension is available in three different concentrations (100 mg/5 mL, 200 mg/5 mL, and 500 mg/5 mL). Suggested doses for pediatric patients PEDIATRIC DOSAGE CHART SUPRAX for oral suspension SUPRAX chewable tablet 100 mg/5 mL 200 mg/5 mL 500 mg/5 mL Patient Weight (kg) Dose/Day (mg) Dose/Day (mL) Dose/Day (mL) Dose/Day (mL) Dose 5 to 7. 5 The preferred concentrations of oral suspension to use are 100 mg/5 mL or 200 mg/5 mL for pediatric patients in these weight ranges. 5 -- -- -- 7. 6 to 10 80 4 2 -- -- 10. 5 1 1 tablet of 100 mg 12. 5 1 tablet of 150 mg 20. 6 to 28 200 10 5 2 1 tablet of 200 mg 28. 1 to 33 250 12. 5 1 tablet of 100 mg and 33. 1 to 40 300 15 7. 5 3 2 tablets of 150 mg 40. 1 to 45 350 17. 5 1 tablet of 150 mg and 45. 1 or greater 400 20 10 4 2 tablets of 200 mg Pediatric patients weighing more than 45 kg or older than 12 years should be treated with the recommended adult dose. SUPRAX chewable tablets must be chewed or crushed before swallowing. Otitis media should be treated with SUPRAX chewable tablets or for oral suspension. Clinical trials of otitis media were conducted with the chewable tablets or suspension, and the chewable tablets or suspension results in higher peak blood levels than the tablet when administered at the same dose. Therefore, the SUPRAX tablet or SUPRAX capsule should not be substituted for the SUPRAX chewable tablets or SUPRAX for oral suspension in the treatment of otitis media [see Clinical Pharmacology ( 12. 3 In the treatment of infections due to Streptococcus pyogenes SUPRAX may be administered in the presence of impaired renal function. Normal dose and schedule may be employed in patients with creatinine clearances of 60 mL/min or greater. Refer to Table 2 for dose adjustments for adults with renal impairment. Neither hemodialysis nor peritoneal dialysis removes significant amounts of drug from the body. Doses for Adults with Renal Impairment Renal Dysfunction SUPRAX for oral suspension SUPRAX Tablet SUPRAX Chewable Tablet Creatinine Clearance (mL/min) 100 mg/5 mL 200 mg/5 mL 500 mg/5 mL 400 mg 200 mg Dose/Day (mL) Dose/Day (mL) Dose/Day (mL) Dose/Day Dose/Day 60 or greater Normal dose Normal dose Normal dose Normal dose Normal dose 21 to 59 The preferred concentrations of oral suspension to use are 200 mg/5 mL or 500 mg/5 mL for patients with this renal dysfunction 13 6. 6 Not Appropriate Not Appropriate 20 or less 8. 5 tablet 1 tablet Table 3. Reconstitution Direction for SUPRAX for Oral Suspension Strength Bottle Size Reconstitution Directions 100 mg/5 mL and 100 mL To reconstitute, suspend with 68 mL water 100 mg/5 mL and 75 mL To reconstitute, suspend with 51 mL water 100 mg/5 mL and 50 mL To reconstitute, suspend with 34 mL water 200 mg/5 mL 37. 5 mL To reconstitute, suspend with 26 mL water 200 mg/5 mL 25 mL To reconstitute, suspend with 17 mL water 500 mg/5 mL 20 mL To reconstitute, suspend with 14 mL water 500 mg/5 mL 10 mL To reconstitute, suspend with 8 mL water After reconstitution, the suspension may be kept for 14 days either at room temperature, or under refrigeration, without significant loss of potency. Keep tightly closed. Shake well before using. Discard unused portion after 14 days.

Most common adverse reactions are gastrointestinal such as diarrhea (16%), nausea (7%), loose stools (6%), abdominal pain (3%), dyspepsia (3%), and vomiting. ( 6 To report SUSPECTED ADVERSE REACTIONS, contact Lupin Pharma at 1-800-399-2561 or FDA at 1-800-FDA-1088 or www. gov/medwatch. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The most commonly seen adverse reactions in U. trials of the SUPRAX tablet formulation were gastrointestinal events, which were reported in 30% of adult patients on either the twice daily or the once daily regimen. Five percent (5%) of patients in the U. clinical trials discontinued therapy because of drug-related adverse reactions. Individual adverse reactions included diarrhea 16%, loose or frequent stools 6%, abdominal pain 3%, nausea 7%, dyspepsia 3%, and flatulence 4%. The incidence of gastrointestinal adverse reactions, including diarrhea and loose stools, in pediatric patients receiving the suspension was comparable to the incidence seen in adult patients receiving tablets. The following adverse reactions have been reported following the post-approval use of SUPRAX. Incidence rates were less than 1 in 50 (less than 2%). Gastrointestinal Several cases of documented pseudomembranous colitis were identified in clinical trials. The onset of pseudomembranous colitis symptoms may occur during or after therapy. Hypersensitivity Reactions Anaphylactic/anaphylactoid reactions (including shock and fatalities), skin rashes, urticaria, drug fever, pruritus, angioedema, and facial edema. Erythema multiforme, Stevens-Johnson syndrome, and serum sickness-like reactions have been reported. Hepatic Transient elevations in SGPT, SGOT, alkaline phosphatase, hepatitis, jaundice. Renal Transient elevations in BUN or creatinine, acute renal failure. Central Nervous System Headaches, dizziness, seizures. Hemic and Lymphatic System Transient thrombocytopenia, leukopenia, neutropenia, prolongation in prothrombin time, elevated LDH, pancytopenia, agranulocytosis, and eosinophilia. Abnormal Laboratory Tests Hyperbilirubinemia. Other Adverse Reactions Genital pruritus, vaginitis, candidiasis, toxic epidermal necrolysis. Adverse Reactions Reported for Cephalosporin-class Drugs Allergic reactions, superinfection, renal dysfunction, toxic nephropathy, hepatic dysfunction including cholestasis, aplastic anemia, hemolytic anemia, hemorrhage, and colitis. Several cephalosporins have been implicated in triggering seizures, particularly in patients with renal impairment when the dosage was not reduced [see Dosage and Administration ( 2 10.

SUPRAX Contraindicated in patients with known allergy to cefixime or other cephalosporins.

Pediatric Use: Efficacy and safety in pediatric patients younger than 6 months of age have not been established. 4 Geriatric Use: Clinical studies did not include sufficient numbers of subjects aged 65 and older to determine whether they respond differently than younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. 5 Renal Impairment: SUPRAX may be administered in the presence of impaired renal function. Dose adjustment is required in patients whose creatinine clearance is less than 60 mL/min. 6 Risk Summary Available data from published observational studies, case series, and case reports over several decades with cephalosporin use, including cefixime, in pregnant women have not established drug-associated risks of major birth defects, miscarriage, or adverse maternal or fetal outcomes (see Data) (see Data The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Maternal gonorrhea may be associated with preterm birth, low neonatal birth weight, chorioamnionitis, intrauterine growth restriction, small for gestational age and premature rupture of membranes. Perinatal transmission of gonorrhea to the offspring can result in infant blindness, joint infections, and bloodstream infections. Data Human Data While available studies cannot definitively establish the absence of risk, published data from prospective cohort studies, case series, and case reports over several decades have not identified a consistent association with cephalosporin use, including cefixime, during pregnancy, and major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Available studies have methodological limitations, including small sample size, retrospective data collection, and inconsistent comparator groups. Animal Data The results of embryo-fetal development studies in mice and rats show that cefixime, at doses up to 3200 mg/kg/day administered during the period of organogenesis did not adversely affect development. In these studies, in mice and rats, cefixime did not affect postnatal development or reproductive capacity of the F 1 2 1 2 Risk Summary There are no available data on the presence of cefixime in human milk, the effects on the breast-fed infant, or the effects on milk production. Cefixime is present in animal milk (see Data) Data In a study on disposition of cefixime in pregnant and lactating rats, continuous intra-peritoneal infusion of 2. 54 mg/kg/day of 14 After 102 hours of drug infusion, total radioactivity in the body of the pups, including the stomach and intestinal contents, was 1. 5% of the 14 1 The safety and effectiveness of SUPRAX have been established in pediatric patients 6 months of age and older. Safety and effectiveness of SUPRAX in pediatric patients younger than 6 months of age have not been established. The incidence of gastrointestinal adverse reactions, including diarrhea and loose stools, in the pediatric patients receiving the SUPRAX for oral suspension, was comparable to the incidence seen in adult patients receiving tablets. Clinical studies did not include sufficient numbers of subjects aged 65 and older to determine whether they respond differently than younger subjects. A pharmacokinetic study in the elderly detected differences in pharmacokinetic parameters [see Clinical Pharmacology ( 12. 3 The dose of cefixime should be adjusted in patients with renal impairment as well as those undergoing continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD). Patients on dialysis should be monitored carefully [see Dosage and Administration ( 2.

Elevated carbamazepine levels have been reported in postmarketing experience when SUPRAX is administered concomitantly. 1 Increased prothrombin time, with or without clinical bleeding, has been reported when SUPRAX is administered concomitantly with warfarin and anticoagulants. 2 Elevated carbamazepine levels have been reported in postmarketing experience when SUPRAX is administered concomitantly. Drug monitoring may be of assistance in detecting alterations in carbamazepine plasma concentrations. Increased prothrombin time, with or without clinical bleeding, has been reported when SUPRAX is administered concomitantly. A false-positive reaction for ketones in the urine may occur with tests using nitroprusside but not with those using nitroferricyanide. The administration of SUPRAX may result in a false-positive reaction for glucose in the urine when using glucose tests based on the Benedict's solution or Fehling's solution. It is recommended that glucose tests based on enzymatic glucose oxidase reactions be used. A false-positive direct Coombs test has been reported during treatment with other cephalosporins; therefore, it should be recognized that a positive Coombs test may be due to the drug.

OVERDOSAGE
Gastric lavage may be indicated; otherwise, no specific antidote exists. Cefixime is not removed in significant quantities from the circulation by hemodialysis or peritoneal dialysis. Adverse reactions in small numbers of healthy adult volunteers receiving single doses up to 2 g of cefixime did not differ from the profile seen in patients treated at the recommended doses.
NONCLINICAL TOXICOLOGY
Lifetime studies in animals to evaluate carcinogenic potential have not been conducted. Cefixime did not cause point mutations in bacteria or mammalian cells, DNA damage, or chromosome damage in vitro in vivo In the fertility and reproductive performance study in rats, no difference between control and drug-treated animals was detected in mating behavior, pregnancy rate, or litter parameters (determined at sacrifice on day 13 of pregnancy) at oral doses up to 1000 mg/kg/day (25 times the adult therapeutic dose) administered to males (for 68 days prior to pairing and during the cohabitation period) and females (for 14 days before pairing to weaning).
CLINICAL STUDIES
Comparative clinical trials of otitis media were conducted in nearly 400 pediatric patients between the ages of 6 months to 10 years. Streptococcus pneumoniae Haemophilus influenzae Moraxella catarrhalis S. pyogenes The overall response rate of Streptococcus pneumoniae Haemophilus influenzae Moraxella catarrhalis H. influenzae In these studies, patients were randomized and treated with either cefixime at dose regimens of 4 mg/kg twice a day or 8 mg/kg once a day, or with a comparator. Sixty-nine to 70% of the patients in each group had resolution of signs and symptoms of otitis media when evaluated 2 to 4 weeks post-treatment, but persistent effusion was found in 15% of the patients. When evaluated at the completion of therapy, 17% of patients receiving cefixime and 14% of patients receiving effective comparative drugs (18% including those patients who had Haemophilus influenzae Table 5. Bacteriological Outcome of Otitis Media (a) Number eradicated/number isolated. (b) An additional 20 beta-lactamase positive isolates of Haemophilus influenzae Bacteriological Outcome of Otitis Media at Two to Four Weeks Post-Therapy Based on Repeat Middle Ear Fluid Culture or Extrapolation from Clinical Outcome Organism Cefixime(a) 4 mg/kg Twice Daily Cefixime(a) 8 mg/kg Once Daily Control(a) drugs Streptococcus pneumoniae 48/70 (69%) 18/22 (82%) 82/100 (82%) Haemophilus influenzae 24/34 (71%) 13/17 (76%) 23/34 (68%) Haemophilus influenzae 17/22 (77%) 9/12 (75%) 1/1 (b) Moraxella catarrhalis 26/31 (84%) 5/5 18/24 (75%) S. pyogenes 5/5 3/3 6/7 All Isolates 120/162 (74%) 48/59 (81%) 130/166 (78%)
REFERENCES
1. Halperin-Walega, E. Batra VK, Tonelli AP, Barr A, Yacobi A. ''Disposition of Cefixime in the Pregnant and Lactating Rat. Transfer to the Fetus and Nursing Pup''. Drug Metabolism and Disposition

SUPRAX- cefixime_capsule

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