DESCRIPTION
SPL UNCLASSIFIED SECTION
DESCRIPTION
Cefuroxime axetil tablets contain cefuroxime as cefuroxime axetil. Cefuroxime axetil is a semisynthetic, broad-spectrum cephalosporin antibiotic for oral administration. Chemically, cefuroxime axetil, the 1-(acetyloxy) ethyl ester of cefuroxime, is (RS )-1-hydroxyethyl (6R,7R)-7-[2-(2-furyl)glyoxyl-amido]-3-(hydroxymethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]-oct-2-ene-2-carboxylate, 72-(Z)-(O-methyl-oxime), 1-acetate 3-carbamate. Its molecular formula is C20H22N4O10S, and it has a molecular weight of 510.48. Cefuroxime axetil is in the amorphous form and has the following structural formula:
Cefuroxime axetil tablets are uncoated and contain the equivalent of 125, 250 or 500 mg of cefuroxime as cefuroxime axetil. Cefuroxime axetil tablets contain the inactive ingredients colloidal silicon dioxide, croscarmellose sodium, hydrogenated vegetable oil, microcrystalline cellulose and sodium lauryl sulfate.
CLINICAL PHARMACOLOGY
Absorption and Metabolism: After oral administration, cefuroxime axetil is absorbed from the gastrointestinal tract and rapidly hydrolyzed by nonspecific esterases in the intestinal mucosa and blood to cefuroxime. Cefuroxime is subsequently distributed throughout the extracellular fluids. The axetil moiety is metabolized to acetaldehyde and acetic acid.Pharmacokinetics: Approximately 50%of serum cefuroxime is bound to protein. Serum pharmacokinetic parameters for cefuroxime axetil tablets are shown in Table 1.
| Dose†(CefuroximeEquivalent) | Peak PlasmaConcentration(mcg/mL) | Time of PeakPlasma Concentration (hr) | Mean EliminationHalf-Life (hr) | AUC(mcg-hr mL) |
| 125 mg | 2.1 | 2.2 | 1.2 | 6.7 |
| 250 mg | 4.1 | 2.5 | 1.2 | 12.9 |
| 500 mg | 7 | 3 | 1.2 | 27.4 |
| 1,000 mg | 13.6 | 2.5 | 1.3 | 50 |
| MIC (mcg/mL) | Interpretation |
| ≤4 | (S) Susceptible |
| 8-16 | (I) Intermediate |
| ≥32 | (R) Resistant |
| Microorganism | MIC (mcg/mL) |
| Escherichia coli ATCC 25922 | 2-8 |
| Staphylococcus aureus ATCC 29213 | 0.5-2 |
| Zone Diameter (mm) | Interpretation |
| ≥23 | (S) Susceptible |
| 15-22 | (I) Intermediate |
| ≤14 | (R) Resistant |
| Microorganism | Zone Diameter (mm) |
| Escherichia coli ATCC 25922 | 20-26 |
| Staphylococcus aureus ATCC 25923 | 27-35 |
INDICATIONS AND USAGE
To reduce the development of drug-resistant bacteria and maintain the effectiveness of cefuroxime axetil and other antibacterial drugs, cefuroxime axetil should be used only to treat or prevent 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 antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. NOTE: CEFUROXIME AXETIL TABLETS AND CEFUROXIME AXETIL FOR ORAL SUSPENSION ARE NOT BIOEQUIVALENT AND ARE NOT SUBSTITUTABLE ON A MILLIGRAM-PER-MILLIGRAM BASIS (SEE CLINICAL PHARMACOLOGY). Cefuroxime Axetil Tablets: Cefuroxime axetil tablets are indicated for the treatment of patients with mild to moderate infections caused by susceptible strains of the designated microorganisms in the conditions listed below: 1. Pharyngitis/Tonsillitis caused by Streptococcus pyogenes. NOTE: The usual drug of choice in the treatment and prevention of streptococcal infections, including the prophylaxis of rheumatic fever, is penicillin given by the intramuscular route. Cefuroxime axetil tablets are generally effective in the eradication of streptococci from the nasopharynx; however, substantial data establishing the efficacy of cefuroxime in the subsequent prevention of rheumatic fever are not available. Please also note that in all clinical trials, all isolates had to be sensitive to both penicillin and cefuroxime. There are no data from adequate and well-controlled trials to demonstrate the effectiveness of cefuroxime in the treatment of penicillin-resistant strains of Streptococcus pyogenes. 2. Acute Bacterial Otitis Media caused by Streptococcus pneumoniae, Haemophilus influenzae (including beta-lactamase–producing strains), Moraxella catarrhalis (including beta-lactamase–producing strains), or Streptococcus pyogenes. 3. Acute Bacterial Maxillary Sinusitis caused by Streptococcus pneumoniae or Haemophilus influenzae (non-beta-lactamase–producing strains only). (See CLINICAL STUDIES section.) NOTE: In view of the insufficient numbers of isolates of beta-lactamase–producing strains of Haemophilus influenzae and Moraxella catarrhalis that were obtained from clinical trials with cefuroxime axetil tablets for patients with acute bacterial maxillary sinusitis, it was not possible to adequately evaluate the effectiveness of cefuroxime axetil tablets for sinus infections known, suspected, or considered potentially to be caused by beta-lactamase–producing Haemophilus influenzae or Moraxella catarrhalis. 4. Acute Bacterial Exacerbations of Chronic Bronchitis and Secondary Bacterial Infections of Acute Bronchitis caused by Streptococcus pneumoniae, Haemophilus influenzae (beta-lactamase negative strains), or Haemophilus parainfluenzae (beta-lactamase negative strains). (See DOSAGE AND ADMINISTRATION section and CLINICAL STUDIES section.) 5. Uncomplicated Skin and Skin-Structure Infections caused by Staphylococcus aureus (including beta-lactamase–producing strains) or Streptococcus pyogenes. 6. Uncomplicated Urinary Tract Infections caused by Escherichia coli or Klebsiella pneumoniae. 7. Uncomplicated Gonorrhea, urethral and endocervical, caused by penicillinase-producing and non-penicillinase–producing strains of Neisseria gonorrhoeae and uncomplicated gonorrhea, rectal, in females, caused by non-penicillinase–producing strains of Neisseria gonorrhoeae. 8. Early Lyme Disease (erythema migrans) caused by Borrelia burgdorferi.
CONTRAINDICATIONS
Cefuroxime axetil products are contraindicated in patients with known allergy to the cephalosporin group of antibiotics.
WARNINGS
CEFUROXIME AXETIL TABLETS AND CEFUROXIME AXETIL FOR ORAL SUSPENSION ARE NOT BIOEQUIVALENT AND ARE THEREFORE NOT SUBSTITUTABLE ON A MILLIGRAM-PER-MILLIGRAM BASIS (SEE CLINICAL PHARMACOLOGY). BEFORE THERAPY WITH CEFUROXIME AXETIL PRODUCTS IS INSTITUTED, CAREFUL INQUIRY SHOULD BE MADE TO DETERMINE WHETHER THE PATIENT HAS HAD PREVIOUS HYPERSENSITIVITY REACTIONS TO CEFUROXIME AXETIL PRODUCTS, OTHER 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 ANTIBIOTICS HAS BEEN CLEARLY DOCUMENTED AND MAY OCCUR IN UP TO 10%OF PATIENTS WITH A HISTORY OF PENICILLIN ALLERGY. IF A CLINICALLY SIGNIFICANT ALLERGIC REACTION TO CEFUROXIME AXETIL PRODUCTS OCCURS, DISCONTINUE THE DRUG AND INSTITUTE APPROPRIATE THERAPY. SERIOUS ACUTE HYPERSENSITIVITY REACTIONS MAY REQUIRE TREATMENT WITH EPINEPHRINE AND OTHER EMERGENCY MEASURES, INCLUDING OXYGEN, INTRAVENOUS FLUIDS, INTRAVENOUS ANTIHISTAMINES, CORTICOSTEROIDS, PRESSOR AMINES, AND AIRWAY MANAGEMENT, AS CLINICALLY INDICATED. Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including cefuroxime, 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 strains 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 antibiotic 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 antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.
PRECAUTIONS
ADVERSE REACTIONS
CEFUROXIME AXETIL TABLETS IN CLINICAL TRIALS: Multiple-Dose Dosing Regimens: 7 to 10 Days Dosing: Using multiple doses of cefuroxime axetil tablets, 912 patients were treated with cefuroxime axetil (125 to 500 mg twice daily). There were no deaths or permanent disabilities thought related to drug toxicity. Twenty (2.2%) patients discontinued medication due to adverse events thought by the investigators to be possibly, probably, or almost certainly related to drug toxicity. Seventeen (85%) of the 20 patients who discontinued therapy did so because of gastrointestinal disturbances, including diarrhea, nausea, vomiting, and abdominal pain. The percentage of cefuroxime axetil tablet-treated patients who discontinued study drug because of adverse events was very similar at daily doses of 1,000, 500, and 250 mg (2.3%, 2.1%, and 2.2%, respectively). However, the incidence of gastrointestinal adverse events increased with the higher recommended doses. The following adverse events were thought by the investigators to be possibly, probably, or almost certainly related to cefuroxime axetil tablets in multiple-dose clinical trials (n = 912 cefuroxime axetil-treated patients).
| Incidence ≥1% | Diarrhea/loose stools 3.7% Nausea/vomiting 3% Transient elevation in AST 2% Transient elevation in ALT 1.6% Eosinophilia 1.1% Transient elevation in LDH 1% |
| Incidence <1%but >0.1% | Abdominal pain Abdominal cramps Flatulence Indigestion Headache Vaginitis Vulvar itch Rash Hives Itch Dysuria Chills Chest pain Shortness of breath Mouth ulcers Swollen tongue Sleepiness Thirst Anorexia Positive Coombs test |
| Incidence ≥1% | Nausea/vomiting 6.8% Diarrhea 4.2% |
| Incidence <1%but >0.1% | Abdominal pain Dyspepsia Erythema Rash Pruritus Vaginal candidiasis Vaginal itch Vaginal discharge Headache Dizziness Somnolence Muscle cramps Muscle stiffness Muscle spasm of neck Tightness/pain in chest Bleeding/pain in urethra Kidney pain Tachycardia Lockjaw-type reaction |
OVERDOSAGE
Overdosage of cephalosporins can cause cerebral irritation leading to convulsions. Serum levels of cefuroxime can be reduced by hemodialysis and peritoneal dialysis.
DOSAGE AND ADMINISTRATION
NOTE: CEFUROXIME AXETIL TABLETS AND CEFUROXIME AXETIL FOR ORAL SUSPENSION ARE NOT BIOEQUIVALENT AND ARE NOT SUBSTITUTABLE ON A MILLIGRAM-PER-MILLIGRAM BASIS (SEE CLINICAL PHARMACOLOGY).
| Population/Infection | Dosage | Duration (days) |
| Adolescents and Adults (13 years and older) | ||
| Pharyngitis/tonsillitis | 250 mg b.i.d. | 10 |
| Acute bacterial maxillary sinusitis | 250 mg b.i.d. | 10 |
| Acute bacterial exacerbations ofchronic bronchitis | 250 or 500 mg b.i.d. | 10* |
| Secondary bacterial infectionsof acute bronchitis | 250 or 500 mg b.i.d. | 5-10 |
| Uncomplicated skin andskin-structure infections | 250 or 500 mg b.i.d. | 10 |
| Uncomplicated urinarytract infections | 250 mg b.i.d. | 7-10 |
| Uncomplicated gonorrhea | 1,000 mg once | single dose |
| Early Lyme disease | 500 mg b.i.d. | 20 |
| Pediatric Patients (who can swallow tablets whole) | ||
| Acute otitis media | 250 mg b.i.d. | 10 |
| Acute bacterial maxillary sinusitis | 250 mg b.i.d. | 10 |
HOW SUPPLIED
Cefuroxime Axetil Tablets, USP 250 mg of cefuroxime (as cefuroxime axetil), are white to off-white, uncoated, capsule-shaped tablets with “A33” debossed on one side and plain on the other side.
Cefuroxime Axetil Tablets, USP 500 mg of cefuroxime (as cefuroxime axetil), are white to off-white, uncoated, capsule-shaped tablets with “A34” debossed on one side and plain on the other side.
Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Replace cap securely after each opening.
| Bottles of 20 | NDC 54868-4987-0 |
| Bottles of 30 | NDC 54868-4987-1 |
| Bottles of 15 | NDC 54868-5022-2 |
| Bottles of 20 | NDC 54868-5022-1 |
| Bottles of 30 | NDC 54868-5022-0 |
| Bottles of 60 | NDC 54868-5022-3 |
CLINICAL STUDIES
Cefuroxime Axetil Tablets: Acute Bacterial Maxillary Sinusitis: One adequate and well-controlled study was performed in patients with acute bacterial maxillary sinusitis. In this study each patient had a maxillary sinus aspirate collected by sinus puncture before treatment was initiated for presumptive acute bacterial sinusitis. All patients had to have radiographic and clinical evidence of acute maxillary sinusitis. As shown in the following summary of the study, the general clinical effectiveness of cefuroxime axetil tablets was comparable to an oral antimicrobial agent that contained a specific betalactamase inhibitor in treating acute maxillary sinusitis. However, sufficient microbiology data were obtained to demonstrate the effectiveness of cefuroxime axetil tablets in treating acute bacterial maxillary sinusitis due only to Streptococcus pneumoniae or non-beta-lactamase–producing Haemophilus influenzae. An insufficient number of beta-lactamase–producing Haemophilus influenzae and Moraxella catarrhalis isolates were obtained in this trial to adequately evaluate the effectiveness of cefuroxime axetil tablets in the treatment of acute bacterial maxillary sinusitis due to these 2 organisms. This study enrolled 317 adult patients, 132 patients in the United States and 185 patients in South America. Patients were randomized in a 1:1 ratio to cefuroxime axetil 250 mg twice daily or an oral antimicrobial agent that contained a specific beta-lactamase inhibitor. An intent-to-treat analysis of the submitted clinical data yielded the following results:
| U.S. Patients* | South American Patients† | |||
| Cefuroxime Axetil(n = 49) | Control(n = 43) | Cefuroxime Axetil (n = 87) | Control(n = 89) | |
| Clinical success(cure + improvement) | 65% | 53% | 77% | 74% |
| Clinical cure | 53% | 44% | 72% | 64% |
| Clinical improvement | 12% | 9% | 5% | 10% |
| Part I (1 Month Posttreatment)* | Part II (1 Year Posttreatment)† | |||
| Cefuroxime Axetil (n = 125) | Doxycycline (n = 108) | Cefuroxime Axetil (n = 105‡) | Doxycycline (n = 83‡) | |
| Satisfactory clinical outcome§ | 91% | 93% | 84% | 87% |
| Clinical cure/success | 72% | 73% | 73% | 73% |
| Clinical improvement | 19% | 19% | 10% | 13% |
| CAE-516 andCAE-517* | CAEA4001 andCAEA4002† | |||
| 5 day(n = 127) | 10 day(n = 139) | 5 day(n = 173) | 10 day(n = 192) | |
| Clinical success(cure + improvement) | 80% | 87% | 84% | 82% |
| Clinical cure | 61% | 70% | 73% | 72% |
| Clinical improvement | 19% | 17% | 11% | 10% |
REFERENCES
- National Committee for Clinical Laboratory Standards. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically. 3rd ed. Approved Standard NCCLS Document M7-A3, Vol. 13, No. 25. Villanova, Pa: NCCLS; 1993.
- National Committee for Clinical Laboratory Standards. Performance Standards for Antimicrobial Disk Susceptibility Tests. 4th ed. Approved Standard NCCLS Document M2-A4, Vol. 10, No. 7. Villanova, Pa: NCCLS; 1990.