CEFIXIME- cefixime_powder, for suspension

Cefixime is a semisynthetic cephalosporin antibacterial drug [see Microbiology ( 12. 4 Cefixime tablets and 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 produces an average peak serum concentration of approximately 2 mcg/mL (range 1 to 4 mcg/mL); a single 400 mg tablet produces an average peak concentration of approximately 3. 7 mcg/mL (range 1. The oral suspension produces average peak concentrations approximately 25% to 50% higher than the tablets, when tested in normal adult adult adult [see Dosage and Administration ( 2 The 400 mg capsule is bioequivalent to the 400 mg 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 tablet or 400 mg of cefixime suspension. Peak serum concentrations occur between 2 and 5 hours following a single administration of 200 mg of suspension. Peak serum concentrations occur between 3 and 8 hours following oral administration of a single 400 mg 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 tablet or 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. Metabolism and Excretion There is no evidence of metabolism of cefixime in vivo. Special Populations Geriatrics: Pharmacokinetic Parameters (mean +/- SD) for Cefixime in Both Young & Elderly Subjects Pharmacokinetic parameter Young Elderly C max 4. 83 T max * 3. 4 C ave * 1. 75 * However, these increases were not clinically significant [see Dosage and Administration ( 2 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 [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.

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 To reduce the development of drug-resistant bacteria and maintain the effectiveness of cefixime and other antibacterial drugs, cefixime for oral suspension and cefixime capsules should be used only to treat infections that are proven or strongly suspected to be caused by bacteria. 6 Cefixime for oral suspension and cefixime capsule 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 Cefixime for oral suspension and cefixime capsule 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 Streptococcus pyogenes Streptococcus pyogenes Note: For patients with otitis media caused by Streptococcus pneumoniae [see Clinical Studies ( 14 Cefixime for oral suspension and cefixime capsule 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. (Note: Penicillin is the usual drug of choice in the treatment of Streptococcus pyogenes infections. Cefixime for oral suspension and cefixime capsule is generally effective in the eradication of Streptococcus pyogenes from the nasopharynx; however, data establishing the efficacy of cefixime for oral suspension and cefixime capsule in the subsequent prevention of rheumatic fever is not available. ) Cefixime for oral suspension and cefixime capsule 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 Cefixime for oral suspension and cefixime capsule 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 cefixime and other antibacterial drugs, cefixime for oral suspension and cefixime capsule 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 cefixime is 400 mg daily. This may be given as a 400 mg capsule daily. For the treatment of uncomplicated cervical/urethral gonococcal infections, a single oral dose of 400 mg is recommended. The capsule 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 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 cefixime for oral suspension is available in two different concentrations (100 mg/5 mL and 200 mg/5 mL). Suggested Doses for Pediatric Patients PEDIATRIC DOSAGE CHART Cefixime for Oral Suspension 100 mg / 5 mL 200 mg / 5 mL Patient Weight ( kg ) Dose / Day ( mg ) Dose / Day ( mL ) Dose / Day ( mL ) 5 to 7. 6 to 10 80 4 2 10. 6 to 28 200 10 5 28. 1 to 33 250 12. 1 to 40 300 15 7. 1 to 45 350 17. 1 or greater 400 20 10 Children weighing more than 45 kg or older than 12 years should be treated with the recommended adult dose. Otitis media should be treated with the suspension. Clinical trials of otitis media were conducted with the suspension, and the suspension results in higher peak blood levels than the tablet when administered at the same dose. Therefore, the tablet or capsule should not be substituted for the suspension in the treatment of otitis media [see Clinical Pharmacology ( 12. 3 In the treatment of infections due to Streptococcus pyogenes Cefixime 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 forAdults withRenalImpairment Renal Dysfunction Cefixime for Oral Suspension Creatinine Clearance (mL/min) 100 mg/5 mL 200 mg/5 mL Dose/Day (mL) Dose/Day (mL) 60 or greater Normal dose Normal dose 21 to 59 * * 13 6. 5 20 or less 8. 4 * Strength Bottle Size Reconstitution Directions 200 mg/5 mL 75 mL To reconstitute, suspend with 51 mL water 100 mg/5 mL and 200 mg/5 mL 50 mL To reconstitute, suspend with 34 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 Pharmaceuticals, Inc. 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 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 cefixime. 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 [ s ee Dosage And Administration ( 2 10.

Contraindicated in patients with known allergy to cefixime or other cephalosporins. ( 4 Cefixime is contraindicated in patients with known allergy to cefixime or other cephalosporins.

Pregnancy: Cefixime should be used during pregnancy only if clearly needed. 1 Nursing Mothers: Consideration should be given to discontinuing nursing temporarily during treatment with cefixime. 3 Children: Efficacy and safety in infants aged less than six months 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: Cefixime 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 Pregnancy Category B Reproduction studies have been performed in mice and rats at doses up to 40 times the human dose and have revealed no evidence of harm to the fetus due to cefixime. There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Cefixime has not been studied for use during labor and delivery. Treatment should only be given if clearly needed. It is not known whether cefixime is excreted in human milk. Consideration should be given to discontinuing nursing temporarily during treatment with this drug. Safety and effectiveness of cefixime in children aged less than six months old have not been established. The incidence of gastrointestinal adverse reactions, including diarrhea and loose stools, in the pediatric patients receiving the 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 cefixime is administered concomitantly. 1 Increased prothrombin time, with or without clinical bleeding, has been reported when cefixime is administered concomitantly with warfarin and anticoagulants. 2 Elevated carbamazepine levels have been reported in postmarketing experience when cefixime 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 cefixime 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 cefixime may result in a false-positive reaction for glucose in the urine using Clinitest registered** registered** registered** ** Clinitest registered registered registered.

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
CLINICAL STUDIES
Comparative clinical trials of otitis media were conducted in nearly 400 children 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 (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 BID Cefixime ( a ) 8 mg / kg QD 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%)

CEFIXIME- cefixime_capsule

CEFIXIME- cefixime_powder, for suspension Product manual source documgent