What are the adult and pediatric dosing regimens, contraindications, renal dose adjustments, adverse effects, pregnancy safety, drug interactions, and alternative antibiotics for cefixime?

Cefixime: Comprehensive Clinical Guide

Adult Dosing

The standard adult dose of cefixime is 400 mg orally once daily or 200 mg twice daily, with the twice-daily regimen preferred to reduce gastrointestinal adverse effects. 1, 2

• For uncomplicated urinary tract infections, acute exacerbations of chronic bronchitis, pharyngitis/tonsillitis, and otitis media: 400 mg once daily or 200 mg every 12 hours 1
• For uncomplicated gonorrhea (cervical/urethral): 400 mg as a single oral dose, though cefixime is NOT recommended as first-line therapy due to increasing resistance 3, 4
• If cefixime must be used for gonorrhea (when ceftriaxone unavailable), it MUST be combined with azithromycin 1 g orally, and a test-of-cure is mandatory at 1 week 3, 4
• Avoid cefixime for pharyngeal gonorrhea due to limited efficacy at this site 3, 4

Pediatric Dosing (≥6 months)

The FDA-approved pediatric dose is 8 mg/kg/day, administered either as a single daily dose or divided as 4 mg/kg every 12 hours. 5, 1

Weight-Based Dosing Table:

• 5-7.5 kg: 50 mg/day (2.5 mL of 100 mg/5 mL suspension) 3
• 7.6-10 kg: 80 mg/day (4 mL of 100 mg/5 mL or 2 mL of 200 mg/5 mL) 3
• 10.1-12.5 kg: 100 mg/day (5 mL of 100 mg/5 mL or 2.5 mL of 200 mg/5 mL) 3
• 12.6-20.5 kg: 150 mg/day (7.5 mL of 100 mg/5 mL or 4 mL of 200 mg/5 mL) 3
• 20.6-28 kg: 200 mg/day (10 mL of 100 mg/5 mL or 5 mL of 200 mg/5 mL) 3
• 28.1-33 kg: 250 mg/day 3
• 33.1-40 kg: 300 mg/day 3
• 40.1-45 kg: 350 mg/day (maximum 400 mg/day) 3, 4

Critical Age Restriction:

Cefixime is NOT approved for infants younger than 6 months of age; use ceftazidime or cefotaxime instead for neonates requiring third-generation cephalosporin therapy. 3

Renal Dose Adjustments

Dose reduction is required in renal impairment: 1

• CrCl 21-60 mL/min: 75% of standard dose (300 mg once daily or 150 mg twice daily)
• CrCl ≤20 mL/min or hemodialysis: 50% of standard dose (200 mg once daily)

Contraindications

Absolute contraindication: Known hypersensitivity to cefixime or other cephalosporins. 1

• Use with extreme caution in patients with penicillin allergy, particularly those with history of anaphylaxis, angioedema, or urticaria 6
• Cross-reactivity between penicillins and cephalosporins occurs in approximately 1-10% of penicillin-allergic patients 6

Critical Clinical Limitations

Cefixime should NEVER be used for serious invasive infections including bacteremia, meningitis, or endocarditis—these require parenteral cephalosporins like ceftriaxone. 3, 4

• Cefixime lacks adequate CNS penetration for meningitis 6
• Insufficient serum levels for endocarditis treatment 6
• Not appropriate for disseminated gonococcal infection (requires ceftriaxone 1 g IV/IM daily) 6

Adverse Effects

The most common adverse effect is diarrhea/loose stools, occurring in approximately 16-24% of patients, usually mild and transient. 7, 2

• Gastrointestinal effects: diarrhea (16%), stool changes, nausea, abdominal pain 1, 7
• Once-daily 400 mg dosing causes more GI adverse effects than 200 mg twice daily; therefore, divided dosing is preferred 2
• Clostridioides difficile-associated diarrhea (CDAD) can occur and may range from mild to life-threatening colitis 1
• Hypersensitivity reactions: rash, urticaria, drug fever (rare) 1
• Hematologic: transient eosinophilia, thrombocytopenia (rare) 1
• Hepatic: transient elevation of liver enzymes 1
• Drug discontinuation due to adverse effects occurs in only 1.9-2% of patients 7

Pregnancy and Lactation

Cefixime is FDA Pregnancy Category B—no evidence of fetal harm in animal studies, and it is considered safe during pregnancy. 1, 8

• Pharmacokinetic parameters remain stable during pregnancy 8
• Extremely low penetration into fetal tissues (<1% of maternal dose) 8
• Excreted in breast milk in minimal amounts (<1%); compatible with breastfeeding 1, 8
• No contraindications for use during pregnancy or lactation 8

Drug Interactions

Carbamazepine levels may increase when co-administered with cefixime; monitor carbamazepine concentrations. 1

• Warfarin and anticoagulants: Cephalosporins may enhance anticoagulant effects; monitor INR closely 1
• Probenecid increases cefixime serum concentrations by inhibiting renal tubular secretion 1
• False-positive urine glucose with copper reduction tests (Benedict's, Fehling's); use glucose oxidase methods instead 1
• False-positive direct Coombs test 1

Antimicrobial Spectrum and Resistance

Cefixime has excellent activity against Enterobacteriaceae, Haemophilus influenzae, Streptococcus pyogenes, Streptococcus pneumoniae, and Moraxella catarrhalis, and is highly resistant to many beta-lactamases. 9, 10

• Poor activity against Staphylococcus aureus 9
• No activity against Pseudomonas aeruginosa 9
• Effective against beta-lactamase-producing H. influenzae 5
• Increasing resistance in Neisseria gonorrhoeae has relegated cefixime to alternative status only 6, 3, 4

Alternative Antibiotics

For gonorrhea: Ceftriaxone 125-250 mg IM single dose (preferred) plus azithromycin 1 g orally 6

For respiratory infections in children: Cefdinir, cefpodoxime, or ceftibuten are alternatives for beta-lactamase-producing H. influenzae 5

For urinary tract infections: Co-trimoxazole, amoxicillin, or fluoroquinolones (in non-pregnant adults) 2

For pharyngitis: Amoxicillin, penicillin V, or azithromycin (if penicillin-allergic) 6

For serious invasive infections: Ceftriaxone 1-2 g IV daily or cefotaxime 1-2 g IV every 4-8 hours 6

Pharmacokinetics

Cefixime has a 3-4 hour half-life permitting once or twice daily dosing, with 40-52% oral bioavailability and approximately 20% renal excretion as active drug. 10, 2

• Peak serum concentrations achieved in 2-6 hours 10
• Protein binding approximately 65-70% (free fraction 31%) 10
• No significant drug accumulation with multiple dosing 10
• Serum and urinary concentrations exceed MIC90 for susceptible organisms 10