Drug Monograph

Cefuroxime (Ceftin / Zinacef)

cefuroxime axetil (oral) · cefuroxime sodium (IV/IM)

Second-Generation Cephalosporin·Oral, IV, IM
Pharmacokinetic Profile
Half-Life
~1.2–1.3 h (normal renal function)
Metabolism
Prodrug (axetil) hydrolyzed to cefuroxime; cefuroxime itself is not metabolized
Protein Binding
~50%
Bioavailability
37–52% oral (food increases); 100% IV
Volume of Distribution
Extracellular fluid; penetrates CSF, bone, synovial fluid
Clinical Information
Drug Class
Second-generation cephalosporin (beta-lactam)
Available Doses
Oral: 250 mg, 500 mg tablets; 125 mg/5 mL, 250 mg/5 mL suspension. IV/IM: 750 mg, 1.5 g, 7.5 g vials
Route
Oral, Intravenous, Intramuscular
Renal Adjustment
Yes — required when CrCl <30 mL/min
Hepatic Adjustment
None required
Pregnancy
Category B — no evidence of harm in animal studies
Lactation
Excreted in milk; use with caution
Schedule
Prescription only (not scheduled)
Generic Available
Yes
Rx

Indications

IndicationApproved PopulationFormulationStatus
Pharyngitis / tonsillitis (S. pyogenes)Adults & peds (tablets ≥13 y; suspension ≥3 mo)OralFDA Approved
Acute otitis media (S. pneumoniae, H. influenzae, M. catarrhalis, S. pyogenes)Pediatric ≥3 monthsOral (suspension)FDA Approved
Acute bacterial sinusitis (S. pneumoniae, H. influenzae)Adults & peds (tablets ≥13 y; suspension ≥3 mo)OralFDA Approved
Acute exacerbation of chronic bronchitis (S. pneumoniae, H. influenzae, H. parainfluenzae)Adults & peds ≥13 yearsOralFDA Approved
Uncomplicated skin & skin structure infections (S. aureus [MSSA], S. pyogenes)Adults & peds ≥13 yearsOralFDA Approved
Uncomplicated UTI (E. coli, K. pneumoniae)Adults & peds ≥13 yearsOralFDA Approved
Uncomplicated gonorrhea (N. gonorrhoeae)Adults & peds ≥13 yearsOral (single dose)FDA Approved
Early Lyme disease (Borrelia burgdorferi)Adults & peds ≥13 yearsOralFDA Approved
Lower respiratory tract infections (pneumonia)Adults & peds ≥3 monthsIV/IMFDA Approved
Septicemia, meningitis, bone/joint infections, perioperative prophylaxisAdults & peds ≥3 months (Zinacef)IV/IMFDA Approved

Cefuroxime is a versatile second-generation cephalosporin available in both oral (as the prodrug cefuroxime axetil) and parenteral (as cefuroxime sodium) formulations. Compared with first-generation agents, cefuroxime offers enhanced activity against beta-lactamase-producing H. influenzae and M. catarrhalis while retaining useful gram-positive coverage. It is one of the few oral cephalosporins with an FDA-approved indication for early Lyme disease and is recommended as an alternative to doxycycline by IDSA/AAN guidelines. The parenteral formulation achieves adequate CSF penetration in bacterial meningitis, which is unique among second-generation cephalosporins.

Off-Label Uses

Community-acquired pneumonia — IV-to-oral step-down: Commonly used as sequential IV cefuroxime → oral cefuroxime axetil for hospitalised patients with CAP. ATS/IDSA CAP guidelines list cefuroxime as an option for non-ICU inpatients. Evidence quality: Moderate.

Intracameral injection — post-cataract endophthalmitis prophylaxis: Cefuroxime 1 mg intracameral injection at the end of cataract surgery is supported by high-quality evidence (ESCRS trial) and is standard practice in Europe and increasingly in the US. Evidence quality: High.

Dose

Dosing

Adult Oral Dosing by Clinical Scenario (Cefuroxime Axetil Tablets)

Clinical ScenarioStarting DoseMaintenance DoseMaximum DoseNotes
Pharyngitis / tonsillitis (GAS)250 mg PO BID250 mg PO BID500 mg/day10 days; alternative to penicillin
Acute bacterial sinusitis250 mg PO BID250 mg PO BID500 mg/day10 days
Acute exacerbation of chronic bronchitis250–500 mg PO BID250–500 mg PO BID1 g/day10 days
Use 500 mg for more severe exacerbations
Uncomplicated skin/soft tissue infection250–500 mg PO BID250–500 mg PO BID1 g/day10 days
Uncomplicated UTI250 mg PO BID250 mg PO BID500 mg/day7–10 days
Uncomplicated gonorrhea1 g PO single doseN/A1 gSingle dose; not preferred per current CDC guidelines
Early Lyme disease (erythema migrans)500 mg PO BID500 mg PO BID1 g/day20 days; IDSA/AAN recommended alternative to doxycycline
Jarisch-Herxheimer reaction may occur

Adult IV/IM Dosing by Clinical Scenario (Cefuroxime Sodium — Zinacef)

Clinical ScenarioStarting DoseMaintenance DoseMaximum DoseNotes
Uncomplicated infection (UTI, SSSI, pneumonia)750 mg IV/IM Q8H750 mg IV/IM Q8H2.25 g/day5–10 days; step down to oral when able
Severe / complicated infection1.5 g IV Q8H1.5 g IV Q8H4.5 g/day5–10 days
Bone & joint infections1.5 g IV Q8H1.5 g IV Q8H4.5 g/dayMay follow with oral step-down
Life-threatening / less susceptible organisms1.5 g IV Q6H1.5 g IV Q6H6 g/dayMaximum IV dose
Bacterial meningitis1.5 g IV Q6–8H1.5 g IV Q6–8H6 g/dayAdequate CSF penetration with inflamed meninges
Pediatric: 200–240 mg/kg/day divided Q6–8H (max 9 g/day)
Surgical prophylaxis1.5 g IV750 mg IV/IM Q8H × 24–48 h1.5 g preopGive ½–1 h before incision
Open-heart: 1.5 g Q12H × 4 total doses

Renal Dose Adjustment

CrCl (mL/min)OralIV/IMSource
≥30No adjustmentNo adjustmentFDA PI
10–29Standard dose Q24H750 mg IV Q12HFDA PI / StatPearls
<10Standard dose Q48H750 mg IV Q24HFDA PI / StatPearls
HemodialysisAdditional dose after each sessionFDA PI
Clinical Pearl: Tablet vs Suspension — NOT Interchangeable

Cefuroxime axetil tablets and oral suspension are NOT bioequivalent and must not be substituted on a milligram-per-milligram basis. The suspension achieves approximately 91% of the AUC and 71% of the Cmax compared with the tablet formulation. Each formulation has independently established safety and efficacy data. Tablets can be taken with or without food (food increases absorption), while the suspension must always be administered with food (FDA PI). Avoid concurrent use of antacids, H2-receptor antagonists, or proton pump inhibitors, as these can significantly reduce oral cefuroxime bioavailability.

PK

Pharmacology

Mechanism of Action

Cefuroxime is a bactericidal beta-lactam antibiotic that inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), disrupting the final transpeptidation step of peptidoglycan cross-linking. This leads to osmotic instability and cell lysis. As a second-generation cephalosporin, cefuroxime has enhanced stability against beta-lactamases produced by common respiratory pathogens such as H. influenzae and M. catarrhalis, while retaining activity against MSSA and streptococci. Its bactericidal activity is time-dependent (% fT > MIC). The oral formulation (cefuroxime axetil) is an acetoxyethyl ester prodrug that is rapidly hydrolyzed by nonspecific esterases in the intestinal mucosa and blood to release active cefuroxime.

ADME Profile

ParameterValueClinical Implication
AbsorptionOral: prodrug hydrolyzed to cefuroxime; bioavailability ~37–52% (increases with food); Tmax ~2–3 h. IV: Cmax ~100 mcg/mL after 1.5 gFood significantly enhances oral absorption; suspension MUST be given with food; tablets may be taken with or without food but food improves absorption; avoid acid-suppressing drugs
DistributionDistributed throughout extracellular fluids; ~50% protein bound; penetrates CSF (especially inflamed meninges), bone, synovial fluid, sputum, bileCSF penetration supports meningitis use (IV formulation only); adequate bone penetration for osteomyelitis
MetabolismAxetil ester hydrolyzed to cefuroxime + acetaldehyde + acetic acid; cefuroxime itself undergoes no hepatic metabolism; no CYP involvementMinimal drug-drug interaction potential via metabolic pathways; no hepatic dose adjustment
Eliminationt½ ~1.2–1.3 h (normal renal function); ~3.5 h in elderly (CrCl ~35); oral: ~50% unchanged in urine within 12 h; IV: ~89% unchanged in urine within 8 hDose reduction required when CrCl <30 mL/min; removed by hemodialysis — give supplemental dose post-dialysis
SE

Side Effects

≥3%Very Common (Oral Tablets — Multi-Dose Regimens)
Adverse EffectIncidenceClinical Note
Diarrhea / loose stools3.7%Most common GI reaction; taking with food may reduce; distinguish from C. difficile
Nausea / vomiting3.0%Usually self-limiting; more common with suspension
Jarisch-Herxheimer reaction5.6%Occurs in early Lyme disease treatment only; fever, myalgia within 24 h of starting; self-limiting
Vaginitis5.1%Reported primarily in Lyme disease trials (20-day course); disruption of vaginal flora
1–3%Common
Adverse EffectIncidenceClinical Note
Thrombophlebitis (IV)1.7% (1 in 60)IV administration; rotate infusion sites
Transient eosinophilia~1%Usually not clinically significant
Elevated liver enzymes~1%Transient AST/ALT elevations; monitor if prolonged therapy
Positive Coombs’ test~1%Usually without hemolysis; inform blood bank
SeriousSerious (Regardless of Frequency)
Adverse EffectEstimated FrequencyTypical OnsetRequired Action
Anaphylaxis / severe hypersensitivityRareMinutes to hoursDiscontinue; epinephrine; emergency care
C. difficile-associated diarrheaUncommonDuring or up to 2 months post-therapyTest for toxin; discontinue cefuroxime; treat with vancomycin or fidaxomicin
SeizuresRare (postmarketing)Variable; higher risk with renal impairmentDiscontinue; anticonvulsant therapy; dose-adjust for renal function
Hepatitis / cholestasisRare (postmarketing)Days to weeksDiscontinue; evaluate hepatic function
Hearing loss (IV, pediatric meningitis)UncommonDuring therapyAudiometric monitoring in meningitis; usually mild-to-moderate
Stevens-Johnson syndromeVery rare1–3 weeksDiscontinue immediately; dermatology referral
DiscontinuationDiscontinuation Rates
Oral (Multi-Dose)
Low (~2–4%)
Top reasons: GI intolerance (diarrhea, nausea), hypersensitivity
IV (Zinacef)
Low
Top reasons: Phlebitis, hypersensitivity, GI effects
Management: Jarisch-Herxheimer Reaction in Lyme Disease

Up to 5.6% of patients treated for early Lyme disease may experience a Jarisch-Herxheimer reaction — an acute febrile response with myalgia, headache, and temporary worsening of symptoms — typically within the first 24 hours of antibiotic initiation. This reaction reflects spirochaetal lysis and should not be confused with drug allergy. It is self-limiting, resolves within 24–48 hours, and should not prompt discontinuation of therapy. Symptomatic management with antipyretics is appropriate (FDA PI).

Int

Drug Interactions

Cefuroxime itself undergoes no CYP-mediated metabolism, but the oral prodrug (cefuroxime axetil) is significantly affected by gastric pH, making acid-suppressing drugs a clinically important interaction.

MajorProton Pump Inhibitors / H2-Receptor Antagonists
MechanismReduced gastric acidity impairs dissolution and absorption of cefuroxime axetil
EffectSignificantly lower bioavailability, potentially subtherapeutic cefuroxime levels
ManagementAvoid concomitant use; PPIs and H2 blockers should be avoided during cefuroxime axetil therapy (FDA PI)
FDA PI
ModerateAntacids (Short-Acting)
MechanismIncreased gastric pH reduces oral absorption
EffectLower cefuroxime bioavailability
ManagementAdminister cefuroxime at least 1 h before or 2 h after short-acting antacids (FDA PI)
FDA PI
ModerateProbenecid
MechanismInhibits renal tubular secretion of cefuroxime
EffectIncreased and prolonged cefuroxime serum concentrations
ManagementCo-administration not recommended (FDA PI)
FDA PI
ModerateOral Contraceptives
MechanismAlteration of gut flora may reduce estrogen reabsorption
EffectPotentially reduced efficacy of combined oral contraceptives
ManagementAdvise patients to use supplementary non-hormonal contraception during treatment (FDA PI)
FDA PI
MinorUrine Glucose / Blood Glucose Testing
MechanismInterference with copper-reduction methods (urine) and ferricyanide test (blood)
EffectFalse-positive urine glucose (Benedict’s/Fehling’s); false-negative blood glucose (ferricyanide)
ManagementUse glucose oxidase or hexokinase methods
FDA PI
Mon

Monitoring

  • Renal FunctionBaseline; periodically
    Routine
    Assess CrCl before and during therapy. Dose adjustment required when CrCl <30 mL/min. Elderly patients likely to have impaired renal function; mean t½ increases to 3.5 h.
  • Clinical Response48–72 h
    Routine
    Evaluate for clinical improvement. For Lyme disease, assess resolution of erythema migrans. If no response, consider cultures and alternative therapy.
  • GI Symptoms / StoolIf diarrhea develops
    Trigger-based
    Test for C. difficile toxin if diarrhea is persistent, watery, or bloody, during or up to 2 months after therapy.
  • CBCIf therapy >14 days
    Trigger-based
    Monitor for eosinophilia, leukopenia, thrombocytopenia. Particularly relevant for prolonged Lyme disease courses (20 days).
  • Hearing (Pediatric Meningitis)During and after IV therapy
    Trigger-based
    Mild-to-moderate hearing loss reported in pediatric meningitis patients treated with cefuroxime. Audiometric assessment recommended.
  • IV SiteEach dose
    Routine
    Monitor for thrombophlebitis (~1.7% incidence); rotate infusion sites as needed.
CI

Contraindications & Cautions

Absolute Contraindications

  • Known hypersensitivity to cefuroxime or any member of the cephalosporin class

Relative Contraindications (Specialist Input Recommended)

  • History of penicillin allergy — cross-hypersensitivity among beta-lactams may occur in up to 10% of penicillin-allergic patients
  • MRSA infection — cefuroxime has no activity; confirm susceptibility

Use with Caution

  • Renal impairment (CrCl <30 mL/min) — dose adjustment required; risk of accumulation and seizures
  • Concurrent acid-suppressing therapy — PPIs, H2 blockers, and antacids significantly reduce oral bioavailability
  • Elderly patients — impaired renal function prolongs half-life (mean 3.5 h when CrCl ~35)
  • History of GI disease (especially colitis) — increased risk of C. difficile
  • Pediatric meningitis (IV) — risk of hearing loss; audiometric monitoring recommended
  • Pediatric patients <3 months — safety and effectiveness not established
FDA Class-Wide Safety Advisory Beta-Lactam Cross-Hypersensitivity

Cross-hypersensitivity among beta-lactam antibacterial drugs may occur in up to 10% of patients with a history of penicillin allergy. Before initiating cefuroxime therapy, inquire about previous hypersensitivity reactions to cephalosporins, penicillins, or other drugs. If an allergic reaction occurs, discontinue the drug immediately and institute appropriate treatment (FDA PI).

Pt

Patient Counselling

Purpose of Therapy

Cefuroxime is a prescription antibiotic used to treat bacterial infections of the ears, sinuses, throat, lungs, skin, urinary tract, and for early Lyme disease. The oral form (tablets or liquid) is taken at home, while the injectable form is given by a healthcare professional in a hospital or clinic. Cefuroxime does not work against viral infections.

How to Take (Oral)

Take tablets twice daily with or without food, though taking with food improves absorption. The liquid suspension must always be taken with food. Shake the liquid well before each dose. Swallow tablets whole; do not crush — crushed tablets have a strong bitter taste. Complete the full course even if symptoms improve. Store the liquid in the refrigerator and discard after 10 days.

Allergic Reactions
Tell patientInform your prescriber if you have any history of allergy to penicillin, cephalosporins, or any antibiotic. Allergic reactions including rash, hives, and swelling can occur.
Call prescriberImmediately for difficulty breathing, swelling of face or throat, or widespread rash.
Lyme Disease — Jarisch-Herxheimer Reaction
Tell patientIf you are being treated for Lyme disease, you may experience fever, chills, muscle aches, or temporary worsening of symptoms within the first day of treatment. This is a normal reaction caused by bacterial die-off, not an allergy. It resolves within 24–48 hours.
Call prescriberIf symptoms persist beyond 48 hours or are severe.
Antacids and Stomach Medications
Tell patientMedications that reduce stomach acid — including over-the-counter antacids, ranitidine, famotidine, omeprazole, and similar drugs — can significantly reduce how much cefuroxime your body absorbs, making it less effective.
Call prescriberIf you are currently taking any stomach acid reducer, so your prescriber can advise on timing or alternatives.
Diarrhea
Tell patientMild diarrhea is common with antibiotics. However, severe, persistent, or bloody diarrhea — even weeks after finishing the course — may indicate a serious gut infection and requires medical evaluation.
Call prescriberIf diarrhea is severe, bloody, or persists more than 2 days.
Contraception
Tell patientCefuroxime may reduce the effectiveness of hormonal birth control pills. Use an additional non-hormonal method of contraception (such as condoms) during the entire course of treatment.
Call prescriberIf you have concerns about contraceptive effectiveness during treatment.
Ref

Sources

Regulatory (PI / SmPC)
  1. CEFTIN (cefuroxime axetil) tablets and oral suspension prescribing information. Revised 2021. FDA LabelPrimary source for oral formulation indications, dosing, adverse reactions (including Lyme disease-specific data), PK, and drug interactions.
  2. ZINACEF (cefuroxime for injection) prescribing information. Revised 2021. FDA LabelPrimary source for IV/IM formulation indications (including meningitis, septicemia, surgical prophylaxis), dosing, PK (t½ ~80 min, ~89% renal excretion), and CSF penetration data.
  3. Cefuroxime axetil tablets prescribing information (generic). Aurobindo Pharma. DailyMedUpdated generic tablet label confirming identical clinical information to branded Ceftin product.
Key Clinical Trials
  1. Nadelman RB, Luger SW, Frank E, et al. Comparison of cefuroxime axetil and doxycycline in the treatment of early Lyme disease. Ann Intern Med. 1992;117(4):273-280. doi:10.7326/0003-4819-117-4-273Pivotal RCT establishing cefuroxime axetil 500 mg BID × 20 days as effective alternative to doxycycline for early Lyme disease.
  2. Luger SW, Paparone P, Wormser GP, et al. Comparison of cefuroxime axetil and doxycycline in treatment of patients with early Lyme disease associated with erythema migrans. Antimicrob Agents Chemother. 1995;39(3):661-667. doi:10.1128/AAC.39.3.661Second pivotal Lyme disease trial confirming comparable efficacy of cefuroxime axetil vs doxycycline; safety data for 20-day course.
Guidelines
  1. Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the IDSA. Clin Infect Dis. 2006;43(9):1089-1134. doi:10.1086/508667IDSA guideline recommending cefuroxime axetil 500 mg BID × 14–21 days as first-line alternative to doxycycline for early Lyme disease.
  2. Bratzler DW, Dellinger EP, Olsen KM, et al. Clinical practice guidelines for antimicrobial prophylaxis in surgery. Am J Health Syst Pharm. 2013;70(3):195-283. doi:10.2146/ajhp120568ASHP/IDSA/SIS/SHEA guideline recommending cefuroxime as alternative to cefazolin for surgical prophylaxis in head/neck, cardiac, and thoracic procedures.
  3. Chow AW, Benninger MS, Brook I, et al. IDSA clinical practice guideline for acute bacterial rhinosinusitis in children and adults. Clin Infect Dis. 2012;54(8):e72-e112. doi:10.1093/cid/cis370IDSA sinusitis guideline listing cefuroxime as alternative for acute bacterial sinusitis in penicillin-allergic patients.
Mechanistic / Basic Science
  1. Neu HC, Fu KP. Cefuroxime, a beta-lactamase-resistant cephalosporin with a broad spectrum of gram-positive and -negative activity. Antimicrob Agents Chemother. 1978;13(4):657-664. doi:10.1128/AAC.13.4.657Original characterisation of cefuroxime’s in vitro activity against 604 isolates demonstrating enhanced beta-lactamase stability vs first-generation cephalosporins.
Pharmacokinetics / Special Populations
  1. Sommers DK, Van Wyk M, Moncrieff J, Schoeman HS. Influence of food and reduced gastric acidity on the bioavailability of cefuroxime axetil. Br J Clin Pharmacol. 1984;18(4):535-539. doi:10.1111/j.1365-2125.1984.tb02501.xKey PK study demonstrating food-enhanced absorption and negative impact of reduced gastric acidity on cefuroxime axetil bioavailability.
  2. Scott LJ, Ormrod D, Goa KL. Cefuroxime axetil: an updated review of its use in the management of bacterial infections. Drugs. 2001;61(10):1455-1500. doi:10.2165/00003495-200161100-00008Comprehensive PK and clinical review covering oral and IV cefuroxime formulations, bioavailability data, and clinical trial efficacy across all approved indications.
  3. Foord RD. Cefuroxime: human pharmacokinetics. Antimicrob Agents Chemother. 1976;9(5):741-747. doi:10.1128/AAC.9.5.741Foundational human PK study in 44 volunteers establishing cefuroxime serum half-life (~70 min), protein binding (33%), and urinary recovery (≥95%) after IM and IV doses.