Cefixime

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.

• Hypersensitivity reactions including shock and fatalities have been reported with cefixime.
• Discontinue use if a reaction occurs.
• ( 5.1 ) Clostridium difficile associated diarrhea: Evaluate if diarrhea occurs.
• ( 5.2 )
• 5.1 Hypersensitivity Reactions Anaphylactic/anaphylactoid reactions (including shock and fatalities) have been reported with the use of cefixime.
• Before therapy with cefixime is instituted, careful inquiry should be made to determine whether the patient has had previous hypersensitivity reactions to cephalosporins, penicillins, or other drugs.
• If this product is to be given to penicillin-sensitive patients, caution should be exercised because cross hypersensitivity among beta-lactam antibacterial drugs has been clearly documented and may occur in up to 10% of patients with a history of penicillin allergy.
• If an allergic reaction to cefixime occurs, discontinue the drug.
• 5.2 Clostridium difficile -Associated Diarrhea Clostridium difficile associated 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).
• 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.

• 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) .
• Reproduction studies have been performed in mice and rats at doses equivalent to 40 and 80 times, respectively, the adult human recommended dose and have revealed no evidence of harm to the fetus due to cefixime (see Data ).
• The estimated 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.In the U.S. 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 generation or fetal development of the F 2 generation.
• In an embryo-fetal development study in rabbits, cefixime at doses of 3.2, 10 or 32 mg/kg given daily during the period of organogenesis (gestation days 6 through 18) resulted in abortions and/or maternal deaths at doses > 10 mg/kg (typically associated with the administration of antibiotics in this species), but no malformations were reported at lower doses.
• A pre- and post-natal development study of cefixime at oral doses up to 3200 mg/kg/day in rats demonstrated no effect on the duration of pregnancy, process of parturition, development and viability of offspring, or reproductive capacity of the F 1 generation and development of their fetuses (F 2 ).
• IN SPECIFIC POPULATIONS Pediatric Use:
• Efficacy and safety in infants younger than 6 months of age have not been established.
• ( 8.4 ) 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.
• ( 8.5 ) 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.
• ( 8.6 )
• 8.1 Pregnancy 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) .
• Reproduction studies have been performed in mice and rats at doses equivalent to 40 and 80 times, respectively, the adult human recommended dose and have revealed no evidence of harm to the fetus due to cefixime (see Data ).
• The estimated 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.In the U.S. 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 generation or fetal development of the F 2 generation.
• In an embryo-fetal development study in rabbits, cefixime at doses of 3.2, 10 or 32 mg/kg given daily during the period of organogenesis (gestation days 6 through 18) resulted in abortions and/or maternal deaths at doses > 10 mg/kg (typically associated with the administration of antibiotics in this species), but no malformations were reported at lower doses.
• A pre- and post-natal development study of cefixime at oral doses up to 3200 mg/kg/day in rats demonstrated no effect on the duration of pregnancy, process of parturition, development and viability of offspring, or reproductive capacity of the F 1 generation and development of their fetuses (F 2 ).
• 8.2 Lactation Risk Summary There are no available data on the presence of cefixime in human milk, the effects on the breastfed infant, or the effects on milk production.
• Cefixime is present in animal milk (see Data) .
• When a drug is present in animal milk, it is likely the drug will be present in human milk.
• The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for cefixime and any potential adverse effects on the breastfed infant from cefixime or from the mother's underlying condition.
• 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 C-cefixime from days 10 to 14 postpartum resulted in steady state plasma concentrations of radioactivity in the dams that were 70 times greater than in their nursing pups.
• 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 C-cefixime estimated to be in the mother's body at steady state 1 .
• 8.4 Pediatric Use Safety and effectiveness of cefixime 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 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 ) ].

• Elevated carbamazepine levels have been reported in postmarketing experience when cefixime is administered concomitantly.
• ( 7.1 ) Increased prothrombin time, with or without clinical bleeding, has been reported when cefixime is administered concomitantly with warfarin and anticoagulants.
• ( 7.2 )
• 7.1 Carbamazepine 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.
• 7.2 Warfarin and Anticoagulants Increased prothrombin time, with or without clinical bleeding, has been reported when cefixime is administered concomitantly.
• 7.3 Drug/Laboratory Test Interactions 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 ® **, 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.

• 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.