st ®** , benedict's solution, or fehling's solution. it is recommended that glucose tests based on enzymatic glucose oxidase reactions (such as clinistix ®** or testape ®** ) 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. ** clinitest ® and clinistix ® are registered trademarks of ames division, miles laboratories, inc. tes-tape ® is a registered trademark of eli lilly and company.

fixime 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 , and streptococcus pyogenes . (efficacy for streptococcus pyogenes in this organ system was studied in fewer than 10 infections.) note: for patients with otitis media caused by streptococcus pneumoniae , overall response was approximately 10% lower for cefixime than for the comparator [see clinical studies ( 14 )] . 1.3 pharyngitis and tonsillitis 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.) 1.4 acute exacerbations of chronic bronchitis 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 and haemophilus influenzae . 1.5 uncomplicated gonorrhea (cervical/urethral) 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 (penicillinase-and non-penicillinase-producing isolates). 1.6 usage 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.

ed diarrhea (cdad) has been reported with use of nearly all antibacterial agents, including cefixime, and may range in severity from mild diarrhea to fatal colitis. treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of c. difficile. c. difficile produces toxins a and b which contribute to the development of cdad. hypertoxin producing isolates of c. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. cdad must be considered in all patients who present with diarrhea following antibacterial drug use. careful medical history is necessary since cdad has been reported to occur over two months after the administration of antibacterial agents. if cdad is suspected or confirmed, ongoing antibacterial drug use not directed against c. difficile may need to be discontinued. appropriate fluid and electrolyte management, protein supplementation, antibacterial drug treatment of c. difficile, and surgical evaluation should be instituted as clinically indicated. 5.3 dose adjustment in renal impairment 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 )] . 5.4 coagulation effects cephalosporins, including cefixime, may be associated with a fall in prothrombin activity. those at risk include patients with renal or hepatic impairment, or poor nutritional state, as well as patients receiving a protracted course of antimicrobial therapy, and patients previously stabilized on anticoagulant therapy. prothrombin time should be monitored in patients at risk and exogenous vitamin k administered as indicated. 5.5 development of drug-resistant bacteria prescribing cefixime in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

ations (100 mg/5 ml and 200 mg/5 ml). table 1. suggested doses for pediatric patients pediatric dosage chart doses are suggested for each weight range and rounded for ease of administration 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 7.5 50 2.5 -- 7.6 to 10 80 4 2 10.1 to 12.5 100 5 2.5 12.6 to 20.5 150 7.5 4 20.6 to 28 200 10 5 28.1 to 33 250 12.5 6 33.1 to 40 300 15 7.5 40.1 to 45 350 17.5 9 45.1 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 , a therapeutic dosage of cefixime should be administered for at least 10 days. 2.3 renal impairment 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. table 2. doses for adults with renal impairment 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 the preferred concentration of oral suspension to use is 200 mg/5 ml for patients with this renal dysfunction or renal hemodialysis 13 6.5 20 or less or continuous peritoneal dialysis 8.6 4.4 2.4 reconstitution directions for oral suspension strength bottle size reconstitution directions 200 mg/5 ml 75 ml to reconstitute, suspend with 51 ml water . method: tap the bottle several times to loosen powder contents prior to reconstitution. add approximately half the total amount of water for reconstitution and shake well. add the remainder of water and shake well. 100 mg/5 ml and 200 mg/5 ml 50 ml to reconstitute, suspend with 34 ml water . method: tap the bottle several times to loosen powder contents prior to reconstitution. add approximately half the total amount of water for reconstitution and shake well. add the remainder of water and shake well. 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.

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. 6.2 post-marketing experience 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 ) and overdosage ( 10 )] . if seizures associated with drug therapy occur, the drug should be discontinued. anticonvulsant therapy can be given if clinically indicated.

st ®** , benedict's solution, or fehling's solution. it is recommended that glucose tests based on enzymatic glucose oxidase reactions (such as clinistix ®** or testape ®** ) 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. ** clinitest ® and clinistix ® are registered trademarks of ames division, miles laboratories, inc. tes-tape ® is a registered trademark of eli lilly and company.

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. 8.2 labor and delivery cefixime has not been studied for use during labor and delivery. treatment should only be given if clearly needed. 8.3 nursing mothers it is not known whether cefixime is excreted in human milk. consideration should be given to discontinuing nursing temporarily during treatment with this drug. 8.4 pediatric use 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. 8.5 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. a pharmacokinetic study in the elderly detected differences in pharmacokinetic parameters [see clinical pharmacology ( 12.3 )] . these differences were small and do not indicate a need for dosage adjustment of the drug in the elderly. 8.6 renal impairment 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 ( 2.3 )] .

ea under the time versus concentration curve (auc) is greater by approximately 10% to 25% with the oral suspension than with the tablet after doses of 100 to 400 mg, when tested in normal adult volunteers. this increased absorption should be taken into consideration if the oral suspension is to be substituted for the tablet. because of the lack of bioequivalence, tablets should not be substituted for oral suspension in the treatment of otitis media [see dosage and administration ( 2 )] . cross-over studies of tablet versus suspension have not been performed in children. 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. 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. special populations geriatrics: average aucs at steady state in elderly patients are approximately 40% higher than average aucs in other healthy adults. differences in the pharmacokinetic parameters between 12 young and 12 elderly subjects who received 400 mg of cefixime once daily for 5 days are summarized as follows: pharmacokinetic parameters ( mean ± sd ) for cefixime in both young & elderly subjects pharmacokinetic parameter young elderly c m a x (mg/l) 4.74 ± 1.43 5.68 ± 1.83 t m a x (h) difference between age groups was significant. (p<0.05) 3.9 ± 0.3 4.3 ± 0.6 auc (mg.h/l) 34.9 ± 12.2 49.5 ± 19.1 t ½ (h) 3.5 ± 0.6 4.2 ± 0.4 c a v e (mg/l) 1.42 ±0.50 1.99 ± 0.75 however, these increases were not clinically significant [see dosage and administration ( 2 )] . renal impairment: in subjects with moderate impairment of renal function (20 to 40 ml/min creatinine clearance), the average serum half-life of cefixime is prolonged to 6.4 hours. in severe renal impairment (5 to 20 ml/min creatinine clearance), the half-life increased to an average of 11.5 hours. the drug is not cleared significantly from the blood by hemodialysis or peritoneal dialysis. however, a study indicated that with doses of 400 mg, patients undergoing hemodialysis have similar blood profiles as subjects with creatinine clearances of 21 to 60 ml/min. 12.4 microbiology 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 and neisseria gonorrhoeae is most often associated with alterations in penicillin-binding proteins (pbps). cefixime may have limited activity against enterobacteriaceae producing extended spectrum beta-lactamases (esbls). pseudomonas species, enterococcus species, strains of group d streptococci, listeria monocytogenes, most strains of staphylococci (including methicillin-resistant strains), most strains of enterobacter species, most strains of bacteroides fragilis, and most strains of clostridium species are resistant to cefixime. 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 data are available, but their clinical significance is unknown. at least 90 percent of the following bacteria exhibit an in vitro minimum inhibitory concentration (mic) less than or equal to the susceptible breakpoint for cefixime against isolates of similar genus or organism group. however, the efficacy of cefixime in treating clinical infections caused by these bacteria has not been established in adequate and well-controlled clinical trials. gram-positive bacteria streptococcus agalactiae gram-negative bacteria citrobacter amalonaticus citrobacter diversus haemophilus parainfluenzae klebsiella oxytoca klebsiella pneumoniae pasteurella multocida proteus vulgaris providencia species salmonella species serratia marcescens shigella species 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.fda.gov/stic.

doses of 100 to 400 mg, when tested in normal adult volunteers. this increased absorption should be taken into consideration if the oral suspension is to be substituted for the tablet. because of the lack of bioequivalence, tablets should not be substituted for oral suspension in the treatment of otitis media [see dosage and administration ( 2 )] . cross-over studies of tablet versus suspension have not been performed in children. 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. 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. special populations geriatrics: average aucs at steady state in elderly patients are approximately 40% higher than average aucs in other healthy adults. differences in the pharmacokinetic parameters between 12 young and 12 elderly subjects who received 400 mg of cefixime once daily for 5 days are summarized as follows: pharmacokinetic parameters ( mean ± sd ) for cefixime in both young & elderly subjects pharmacokinetic parameter young elderly c m a x (mg/l) 4.74 ± 1.43 5.68 ± 1.83 t m a x (h) difference between age groups was significant. (p<0.05) 3.9 ± 0.3 4.3 ± 0.6 auc (mg.h/l) 34.9 ± 12.2 49.5 ± 19.1 t ½ (h) 3.5 ± 0.6 4.2 ± 0.4 c a v e (mg/l) 1.42 ±0.50 1.99 ± 0.75 however, these increases were not clinically significant [see dosage and administration ( 2 )] . renal impairment: in subjects with moderate impairment of renal function (20 to 40 ml/min creatinine clearance), the average serum half-life of cefixime is prolonged to 6.4 hours. in severe renal impairment (5 to 20 ml/min creatinine clearance), the half-life increased to an average of 11.5 hours. the drug is not cleared significantly from the blood by hemodialysis or peritoneal dialysis. however, a study indicated that with doses of 400 mg, patients undergoing hemodialysis have similar blood profiles as subjects with creatinine clearances of 21 to 60 ml/min.

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 resistant to the control drug and who received the control antibacterial drug) were considered to be treatment failures. by the 2 to 4 week follow-up, a total of 30%-31% of patients had evidence of either treatment failure or recurrent disease. (a)number eradicated/number isolated. (b)an additional 20 beta-lactamase positive isolates of haemophilus influenzae were isolated, but were excluded from this analysis because they were resistant to the control antibacterial drug. in nineteen of these, the clinical course could be assessed and a favorable outcome occurred in 10. when these cases are included in the overall bacteriological evaluation of therapy with the control drugs, 140/185 (76%) of pathogens were considered to be eradicated. 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 beta-lactamase negative 24/34 (71%) 13/17 (76%) 23/34 (68%) haemophilus influenzae beta-lactamase positive 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%)

on. keep tightly closed. cefixime capsules, 400 mg is size "0" capsule with pink opaque cap and pink opaque body, imprinted with "lu" on cap and "u43" on body in black ink, containing white to yellowish white granular powder containing 400 mg of cefixime as the trihydrate and is supplied as follows: ndc 68180-423-08 - bottle of 50 capsules ndc 68180-423-11 - unit dose package of 10 (1 blister of 10 capsules) store at 20 to 25°c (68 to 77°f) [see usp controlled temperature].

or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibacterial drug. if this occurs, patients should contact their physician as soon as possible. manufactured for: lupin pharmaceuticals, inc. baltimore, maryland 21202 united states manufactured by: lupin limited mandideep 462 046 india revised: july 2019 id#: 259077