Cefuroxime axetil
FULL PRESCRIBING INFORMATION: CONTENTS*
- Rx only
- CEFUROXIME AXETIL DESCRIPTION
- CLINICAL PHARMACOLOGY
- INDICATIONS & USAGE
- CEFUROXIME AXETIL CONTRAINDICATIONS
- WARNINGS
- PRECAUTIONS
- CEFUROXIME AXETIL ADVERSE REACTIONS
- OVERDOSAGE
- DOSAGE & ADMINISTRATION
- HOW SUPPLIED
- CLINICAL STUDIES
- REFERENCES
- Principal Display Panel - Cefuroxime Axetil Tablets USP 250 mg
- Principal Display Panel - Cefuroxime Axetil Tablets USP 500 mg
FULL PRESCRIBING INFORMATION
Rx only
CEFUROXIME AXETIL DESCRIPTION
RSRR2ZO2022410
CLINICAL PHARMACOLOGY
Absorption and Metabolism:
Pharmacokinetics:
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*Mean values of 12 healthy adult volunteers. †Drug administered immediately after a meal. |
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| Dose†
(Cefuroxime Equivalent) |
Peak Plasma Concentration (mcg/mL) |
Time of Peak Plasma Concentration (hr) |
Mean Elimination Half-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 |
7.0 |
3.0 |
1.2 |
27.4 |
| 1,000 mg |
13.6 |
2.5 |
1.3 |
50.0 |
Comparative Pharmacokinetic Properties: Cefuroxime axetil for oral suspension was not bioequivalent to cefuroxime axetil tablets when tested in healthy adults. The tablet and powder for oral suspension formulations are NOT substitutable on a milligram-per-milligram basis.
Food Effect on Pharmacokinetics:
Renal Excretion:
Microbiology: in vivo
in vitro INDICATIONS AND USAGE
Aerobic Gram-Positive Microorganisms:
Staphylococcus aureus
Streptococcus pneumoniae
Streptococcus pyogenes
Aerobic Gram-Negative Microorganisms:
Escherichia coli
Haemophilus influenzae
Haemophilus parainfluenzae
Klebsiella pneumoniae
Moraxella catarrhalis
Neisseria gonorrhoeae
Spirochetes:
Borrelia burgdorferi
in vitro
in vitro
Aerobic Gram-Positive Microorganisms:
Staphylococcus epidermidis
Staphylococcus saprophyticus
Streptococcus agalactiae
Listeria monocytogenesEnterococcus faecalis Streptococcus faecalis
Aerobic Gram-Negative Microorganisms:
Morganella morganii
Proteus inconstans
Proteus mirabilis
Providencia rettgeri
Pseudomonas Campylobacter Acinetobacter calcoaceticusLegionellaSerratia Proteus vulgaris Morganella morganiiEnterobacter cloacaeCitrobacter in vitro
Anaerobic Microorganisms:
Peptococcusniger
Clostridium difficile Bacteroides fragilis
Susceptibility Tests: Dilution Techniques: 1
|
MIC (mcg/mL)
|
Interpretation
|
| ≤ 4 |
(S) Susceptible |
| 8 to16 |
(I) Intermediate |
| ≥32 |
(R) Resistant |
|
Microorganism
|
MIC (mcg/mL)
|
|
Escherichia coli ATCC 25922 |
2 to 8 |
|
Staphylococcus aureus ATCC 29213 |
0.5 to 2 |
Diffusion Techniques: 2
|
Zone Diameter (mm)
|
Interpretation
|
| ≥ 23 |
(S) Susceptible |
| 15 to 22 |
(I) Intermediate |
| ≤14 |
(R) Resistant |
|
Microorganism
|
Zone Diameter (mm)
|
|
Escherichia coli ATCC 25922 |
20 to 26 |
|
Staphylococcus aureus ATCC 25923 |
27 to 35 |
INDICATIONS & USAGE
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:
1. Pharyngitis/Tonsillitis Streptococcus pyogenes.
NOTE: Streptococcus pyogenes.
2. Acute Bacterial Otitis Media Streptococcus pneumoniaeHaemophilus influenzae Moraxella catarrhalis Streptococcus pyogenes.
3. Acute Bacterial Maxillary Sinusitis Streptococcus pneumoniae Haemophilus influenzae CLINICAL STUDIES
NOTE: Haemophilus influenzae Moraxella catarrhalis Haemophilus influenzae Moraxella catarrhalis
4. Acute Bacterial Exacerbations of Chronic Bronchitis and Secondary Bacterial Infections of Acute Bronchitis Streptococcus pneumoniaeHaemophilus influenzae Haemophilus parainfluenzae DOSAGE AND ADMINISTRATIONCLINICAL STUDIES
5. Uncomplicated Skin and Skin-Structure Infections Staphylococcus aureus Streptococcus pyogenes.
6. Uncomplicated Urinary Tract Infections Escherichia coli Klebsiella pneumoniae
7. Uncomplicated Gonorrhea, Neisseria gonorrhoeae Neisseria gonorrhoeae
8. Early Lyme Disease (erythema migrans) Borrelia burgdorferi.
CEFUROXIME AXETIL CONTRAINDICATIONS
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 aC. difficile
C. difficile C. difficile
C. difficileC. difficile
PRECAUTIONS
General:
Information for Patients/Caregivers (Pediatric):
Drug/Laboratory Test Interactions: ®®
Drug/Drug Interactions:
Carcinogenesis, Mutagenesis, Impairment of Fertility: in vitroin vivo2
Pregnancy: Teratogenic Effects: 22
Labor and Delivery:
Nursing Mothers:
Pediatric Use: CLINICAL PHARMACOLOGYINDICATIONS AND USAGEADVERSE REACTIONSDOSAGE AND ADMINISTRATIONCLINICAL STUDIES
Geriatric Use:
CEFUROXIME AXETIL 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).
Table 2. Adverse Reactions – Cefuroxime Axetil Tablets
Multiple-Dose Dosing Regimens—Clinical Trials
| Incidence ≥1% |
Diarrhea/loose stools Nausea/vomiting Transient elevation in AST Transient elevation in ALT Eosinophilia Transient elevation in LDH |
3.7% 3.0% 2.0% 1.6% 1.1% 1.0% |
| 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 |
|
5-Day Experience (see CLINICAL STUDIESsection): In clinical trials using cefuroxime axetil in a dose of 250 mg twice daily in the treatment of secondary bacterial infections of acute bronchitis, 399 patients were treated for 5 days and 402 patients were treated for 10 days. No difference in the occurrence of adverse events was found between the 2 regimens.
In Clinical Trials for Early Lyme Disease With 20 Days Dosing: Two multicenter trials assessed cefuroxime axetil tablets 500 mg twice a day for 20 days. The most common drug-related adverse experiences were diarrhea (10.6% of patients), Jarisch-Herxheimer reaction (5.6%), and vaginitis (5.4%). Other adverse experiences occurred with frequencies comparable to those reported with 7 to 10 days dosing.
Single-Dose Regimen for Uncomplicated Gonorrhea: In clinical trials using a single dose of cefuroxime axetil tablets, 1,061 patients were treated with the recommended dosage of cefuroxime axetil (1,000 mg) for the treatment of uncomplicated gonorrhea. There were no deaths or permanent disabilities thought related to drug toxicity in these studies.
The following adverse events were thought by the investigators to be possibly, probably, or almost certainly related to cefuroxime axetil in 1,000 mg single-dose clinical trials of cefuroxime axetil tablets in the treatment of uncomplicated gonorrhea conducted in the United States.
Table 3. Adverse Reactions–Cefuroxime Axetil Tablets
1 g Single-Dose Regimen for Uncomplicated Gonorrhea–Clinical Trials
| Incidence ≥1% |
Nausea/vomiting Diarrhea |
6.8% 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 |
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POSTMARKETING EXPERIENCE WITH CEFUROXIME AXETIL PRODUCTS
In addition to adverse events reported during clinical trials, the following events have been identified during clinical practice in patients treated with cefuroxime axetil tablets or with cefuroxime axetil for oral suspension and were reported spontaneously. Data are generally insufficient to allow an estimate of incidence or to establish causation.
General: The following hypersensitivity reactions have been reported: anaphylaxis, angioedema, pruritus, rash, serum sickness-like reaction, urticaria.
Gastrointestinal: Pseudomembranous colitis (see WARNINGS).
Hematologic: Hemolytic anemia, leukopenia, pancytopenia, thrombocytopenia, and increased prothrombin time.
Hepatic: Hepatic impairment including hepatitis and cholestasis, jaundice.
Neurologic: Seizure.
Skin: Erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis.
Urologic: Renal dysfunction.
CEPHALOSPORIN-CLASS ADVERSE REACTIONS:
In addition to the adverse reactions listed above that have been observed in patients treated with cefuroxime axetil, the following adverse reactions and altered laboratory tests have been reported for cephalosporin-class antibiotics: toxic nephropathy, aplastic anemia, hemorrhage, increased BUN, increased creatinine, false-positive test for urinary glucose, increased alkaline phosphatase, neutropenia, elevated bilirubin, and agranulocytosis.
Several cephalosporins have been implicated in triggering seizures, particularly in patients with renal impairment when the dosage was not reduced (see DOSAGE AND ADMINISTRATIONand OVERDOSAGE). If seizures associated with drug therapy occur, the drug should be discontinued. Anticonvulsant therapy can be given if clinically indicated.
OVERDOSAGE
DOSAGE & 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) |
|---|---|---|
|
*The safety and effectiveness of cefuroxime axetil administered for less than 10 days in patients with acute exacerbations of chronic bronchitis have not been established. |
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Adolescents and Adults (13 years and older)
|
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| Pharyngitis/tonsillitis |
250 mg b.i.d. |
10 |
| Acute bacterial maxillary sinusitis |
250 mg b.i.d. |
10 |
| Acute bacterial exacerbations of chronic bronchitis |
250 or 500 mg b.i.d. |
10* |
| Secondary bacterial infections of acute bronchitis |
250 or 500 mg b.i.d. |
5-10 |
| Uncomplicated skin and skin structure infections |
250 or 500 mg b.i.d. |
10 |
| Uncomplicated urinary tract 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)
|
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| Acute otitis media |
250 mg b.i.d. |
10 |
| Acute bacterial maxillary sinusitis |
250 mg b.i.d. |
10 |
Patients with Renal Failure:
HOW SUPPLIED
Cefuroxime Axetil Tablets, USP:
Store at 20° to 25°C (68° to 77°F). [See USP controlled room temperature]. Replace cap securely after each opening.
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 betalactamase inhibitor. An intent-to-treat analysis of the submitted clinical data yielded the following results:
| U.S. Patients* | South American Patients† | |||
|---|---|---|---|---|
| CefuroximeAxetil (n = 49) |
Control (n = 43) |
Cefuroxime Axetil (n = 87) |
Control (n = 89) |
|
|
*95% Confidence interval around the success difference [-0.08, +0.32]. †95% Confidence interval around the success difference [-0.10, +0.16]. |
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| Clinical success (cure + improvement) |
65% |
53% |
77% |
74% |
| Clinical cure |
53% |
44% |
72% |
64% |
| Clinical improvement |
12% |
9% |
5% |
10% |
In this trial and in a supporting maxillary puncture trial, 15 evaluable patients had non-beta-lactamase–producing Haemophilus influenzae as the identified pathogen. Ten (10) of these 15 patients (67%) had their pathogen (non-beta-lactamase–producing Haemophilus influenzae) eradicated. Eighteen (18) evaluable patients had Streptococcus pneumoniae as the identified pathogen. Fifteen (15) of these 18 patients (83%) had their pathogen (Streptococcus pneumoniae) eradicated.
Safety: The incidence of drug-related gastrointestinal adverse events was statistically significantly higher in the control arm (an oral antimicrobial agent that contained a specific beta-lactamase inhibitor) versus the cefuroxime axetil arm (12% versus 1%, respectively; P<.001), particularly drug-related diarrhea (8% versus 1%, respectively; P = .001).
Early Lyme Disease: Two adequate and well-controlled studies were performed in patients with early Lyme disease. In these studies all patients had to present with physician-documented erythema migrans, with or without systemic manifestations of infection. Patients were randomized in a 1:1 ratio to a 20-day course of treatment with cefuroxime axetil 500 mg twice daily or doxycycline 100 mg 3 times daily. Patients were assessed at 1 month posttreatment for success in treating early Lyme disease (Part I) and at 1 year posttreatment for success in preventing the progression to the sequelae of late Lyme disease (Part II).
A total of 355 adult patients (181 treated with cefuroxime axetil and 174 treated with doxycycline) were enrolled in the 2 studies. In order to objectively validate the clinical diagnosis of early Lyme disease in these patients, 2 approaches were used: 1) blinded expert reading of photographs, when available, of the pretreatment erythema migrans skin lesion; and 2) serologic confirmation (using enzyme-linked immunosorbent assay [ELISA] and immunoblot assay [“Western” blot]) of the presence of antibodies specific to Borrelia burgdorferi, the etiologic agent of Lyme disease. By these procedures, it was possible to confirm the physician diagnosis of early Lyme disease in 281 (79%) of the 355 study patients. The efficacy data summarized below are specific to this “validated” patient subset, while the safety data summarized below reflect the entire patient population for the 2 studies.
Analysis of the submitted clinical data for evaluable patients in the “validated” patient subset yielded the following results:
| Part I | Part II | |||
|---|---|---|---|---|
| (1 Month Posttreatment)* | (1 Year Posttreatment)† | |||
| Cefuroxime Axetil (n = 125) |
Doxycycline (n = 108) |
Cefuroxime Axetil (n = 105‡) |
Doxycycline (n = 83‡) |
|
|
* 95% confidence interval around the satisfactory difference for Part I (-0.08, +0.05). † 95% confidence interval around the satisfactory difference for Part II (-0.13, +0.07). ‡ n’s include patients assessed as unsatisfactory clinical outcomes (failure + recurrence) in Part I (Cefuroxime Axetil- 11 [5 failure, 6 recurrence]; doxycycline - 8 [6 failure, 2 recurrence]). §Satisfactory clinical outcome includes cure + improvement (Part I) and success + improvement (Part II). |
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| Satisfactory clinical outcome§ |
91% |
93% |
84% |
87% |
| Clinical cure/success |
72% |
73% |
73% |
73% |
| Clinical improvement |
19% |
19% |
10% |
13% |
Safety: Drug-related adverse events affecting the skin were reported significantly more frequently by patients treated with doxycycline than by patients treated with cefuroxime axetil (12% versus 3%, respectively; P = .002), primarily reflecting the statistically significantly higher incidence of drug-related photosensitivity reactions in the doxycycline arm versus the cefuroxime axetil arm (9% versus 0%, respectively; P<.001). While the incidence of drug-related gastrointestinal adverse events was similar in the 2 treatment groups (cefuroxime axetil - 13%; doxycycline - 11%), the incidence of drug-related diarrhea was statistically significantly higher in the cefuroxime axetil arm versus the doxycycline arm (11% versus 3%, respectively; P = .005).
Secondary Bacterial Infections of Acute Bronchitis: Four randomized, controlled clinical studies were performed comparing 5 days versus 10 days of cefuroxime axetil for the treatment of patients with secondary bacterial infections of acute bronchitis. These studies enrolled a total of 1,253 patients (CAE-516 n = 360; CAE-517 n = 177; CAEA4001 n = 362; CAEA4002 n = 354). The protocols for CAE-516 and CAE-517 were identical and compared cefuroxime axetil 250 mg twice daily for 5 days, cefuroxime axetil 250 mg twice daily for 10 days, and AUGMENTIN® 500 mg 3 times daily for 10 days. These 2 studies were conducted simultaneously. CAEA4001 and CAEA4002 compared cefuroxime axetil 250 mg twice daily for 5 days, cefuroxime axetil 250 mg twice daily for 10 days, and CECLOR® 250 mg 3 times daily for 10 days. They were otherwise identical to CAE-516 and CAE-517 and were conducted over the following 2 years. Patients were required to have polymorphonuclear cells present on the Gram stain of their screening sputum specimen, but isolation of a bacterial pathogen from the sputum culture was not required for inclusion. The following table demonstrates the results of the clinical outcome analysis of the pooled studies CAE-516/CAE-517 and CAEA4001/CAEA4002, respectively:
| CAE-516 and CAE-517* | CAEA4001 and CAEA4002† |
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|---|---|---|---|---|
| 5 Day (n = 127) |
10 Day (n = 139) |
5 Day (n = 173) |
10 Day (n = 192) |
|
|
*95% Confidence interval around the success difference [-0.164, +0.029]. †95% Confidence interval around the success difference [-0.061, +0.103]. |
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| Clinical success (cure + improvement) |
80% |
87% |
84% |
82% |
| Clinical cure |
61% |
70% |
73% |
72% |
| Clinical improvement |
19% |
17% |
11% |
10% |
Safety:
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.
Alkem Laboratories Limited
ALKEM HOUSE,
Lower Parel,Mumbai – 400 013, INDIA
Principal Display Panel - Cefuroxime Axetil Tablets USP 250 mg
CEFUROXIME
AXETIL TABLETS, USP
250 mg
Rx only
20 Tablets
Principal Display Panel - Cefuroxime Axetil Tablets USP 500 mg
CEFUROXIME
AXETIL TABLETS, USP
500 mg
Rx only
60 Tablets
Cefuroxime axetilCefuroxime axetil TABLET, FILM COATED
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Cefuroxime axetilCefuroxime axetil TABLET, FILM COATED
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