Information for the Patient
Ceftin
Pharmacology
Cefuroxime axetil is an orally active prodrug of cefuroxime. After oral administration, cefuroxime axetil, as CEFTIN, is absorbed from the gastrointestinal tract and rapidly hydrolyzed by nonspecific esterases in the intestinal mucosa and blood to release cefuroxime into the blood stream. Conversion to cefuroxime, the microbiologically active form, occurs rapidly. The inherent properties of cefuroxime are unaltered after its administration as cefuroxime axetil. Cefuroxime exerts its bactericidal effect by binding to an enzyme or enzymes referred to as penicillin-binding proteins (PBPs) involved in bacterial cell wall synthesis.
This binding results in inhibition of bacterial cell wall synthesis and subsequent cell death. Specifically, cefuroxime shows high affinity for PBP 3, a primary target for cefuroxime in gram-negative organisms such as E. coli.
Indications
CEFTIN (cefuroxime axetil) is indicated for the treatment of patients with mild to moderately severe infections caused by susceptible strains of the designated organisms in the following diseases:
Upper Respiratory Tract Infections: Pharyngitis and tonsillitis caused by S. pyogenes. Otitis Media caused by S. pneumoniae, S. pyogenes (group A beta-hemolytic streptococci), H. influenzae (beta-lactamase negative and beta-lactamase positive strains) or M. catarrhalis. Sinusitis caused by M. catarrhalis, S. pneumoniae or H. influenzae (including ampicillin-resistant strains).
Lower Respiratory Tract Infections: Pneumonia or bronchitis caused by S. pneumoniae, H. influenzae (including ampicillin-resistant strains), H. parainfluenzae, K. pneumoniae or M. catarrhalis.
Skin Structure Infections: Skin structure infections caused by S. aureus, S. pyogenes or S. agalactiae.
Gonorrhea: Acute uncomplicated urethritis and cervicitis caused by N. gonorrheae.
Bacteriologic studies to determine the causative organism and its susceptibility to cefuroxime should be performed. Once these results become available, antibiotic treatment should be adjusted if required.
Precautions
Drugs which reduce gastric acidity may result in a lower bioavailability of CEFTIN compared with that of the fasting state and tend to cancel the effect of post-prandial absorption.
In common with other antibiotics, cefuroxime axetil may affect the gut flora, leading to lower estrogen reabsorption and reduced efficacy of combined oral contraceptives.
Ability to Perform Tasks That Require Judgement, Motor or Cognitive Skills: As this medicine may cause dizziness, patients should be warned to be cautious when driving or operating machinery.
Since cefuroxime is excreted in human milk, consideration should be given to discontinuing nursing temporarily during treatment with CEFTIN.
Broad-spectrum antibiotics including CEFTIN (cefuroxime axetil) should be administered with caution to individuals with a history of gastrointestinal disease, particularly colitis.
The concomitant administration of aminoglycosides and some cephalosporins has caused nephrotoxicity. There is no evidence that CEFTIN, when administered alone, is nephrotoxic, although transient elevations of BUN and serum creatinine have been observed in clinical studies. However, the effect of administering CEFTIN concomitantly with aminoglycosides is not known.
Studies suggest that the concomitant use of potent diuretics, such as furosemide and ethacrynic acid, may increase the risk of renal toxicity with cephalosporins.
As with other antibiotics, use of CEFTIN may result in the overgrowth of Candida. Prolonged use may also result in the overgrowth of other non-susceptible organisms (e.g. enterococci and C. difficile), which may require interruption of treatment. Repeated evaluation of the patient's condition is essential. If superinfection occurs during therapy, appropriate measures should be taken. Should an organism become resistant during antibiotic therapy, CEFTIN should be discontinued and another appropriate antibiotic should be substituted.
The sucrose content of CEFTIN suspension (see Supplied) should be taken into account when treating diabetic patients.
A false-positive reaction for glucose in the urine may occur with copper reduction tests (Benedict's or Fehling's solution or with Clinitest Tablets) but not with enzyme-based tests for glycosuria (e.g., Clinistix, Tes-Tape). As a false-negative result may occur in the ferricyanide test, it is recommended that either the glucose oxidase or hexokinase method be used to determine blood plasma glucose levels in patients receiving CEFTIN.
Cefuroxime does not interfere with the assay of serum and urine creatinine by the alkaline picrate method.
Cephalosporins as a class tend to be absorbed onto the surface of red cell membranes and react with antibodies directed against the drug to produce a positive Coombs' test (which can interfere with cross-matching of blood) and, very rarely, hemolytic anemia.
The safety of CEFTIN in pregnancy has not been established. The use of CEFTIN in pregnant women requires that the likely benefit from the drug be weighed against the possible risk to the mother and fetus. Animal studies following parenteral administration have shown cefuroxime to affect bone calcification in the fetus and to cause maternal toxicity in the rabbit. Reproduction studies that have been performed in mice and rats at oral doses of up to 50 to 160 times the human dose have revealed no evidence of impaired fertility or harm to the fetus due to cefuroxime axetil. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Supplied
Each white to off-white, film-coated, capsule-shaped, biconvex tablet, engraved with “GXEG2” on one side, contains: cefuroxime 500 mg (as cefuroxime axetil). Nonmedicinal ingredients: colloidal silicon dioxide, croscarmellose sodium, hydrogenated vegetable oil, hydroxypropyl methylcellulose, methylparaben, microcrystalline cellulose, propylene glycol, propylparaben, sodium benzoate, sodium lauryl sulfate and titanium dioxide. Bottles of 60. Store between 15 and 30°C.
Each white to off-white, film-coated, capsule-shaped, biconvex tablet, engraved with “GXES7” on one side, contains: cefuroxime 250 mg (as cefuroxime axetil). Nonmedicinal ingredients: colloidal silicon dioxide, croscarmellose sodium, hydrogenated vegetable oil, hydroxypropyl methylcellulose, methylparaben, microcrystalline cellulose, propylene glycol, propylparaben, sodium benzoate, sodium lauryl sulfate and titanium dioxide. Bottles of 60. Store between 15 and 30°C.
Dry, white to pale yellow, tutti-frutti-flavored granules. After reconstitution, each 5 mL contains: cefuroxime 125 mg (as cefuroxime axetil). Nonmedicinal ingredients: acesulfame potassium, aspartame, polyvinyl pyrrolidone, stearic acid, sucrose (about 3 g/5 mL), tutti frutti flavoring and xanthan gum. Bottles of 70 and 100 mL, containing 1.75 g and 2.5 g cefuroxime (as cefuroxime axetil), respectively. Store granules between 2 and 30°C. The reconstituted suspension must be stored immediately between 2 and 8°C in a refrigerator, and discarded after 10 days.
Contraindications
CEFTIN (cefuroxime axetil) is contraindicated for patients who have shown Type 1 hypersensitivity to cefuroxime, to any of its components, or to any of the cephalosporin group of antibiotics.
Warnings
Before therapy with CEFTIN (cefuroxime axetil) is instituted, careful inquiry should be made to determine whether the patient has had previous hypersensitivity reactions to cefuroxime, cephalosporins, penicillin, or other drugs. CEFTIN should be administered with caution to any patient who has demonstrated some form of allergy, particularly to drugs. There is some clinical and laboratory evidence of partial cross-allergenicity of the cephalosporins and penicillin. Special care is indicated in patients who have experienced anaphylactic reaction to penicillins or other beta-lactams. If an allergic reaction to CEFTIN occurs, treatment should be discontinued and standard agents (e.g. epinephrine, antihistamines, corticosteroids) administered as necessary.
Pseudomembranous colitis has been reported to be associated with the use of CEFTIN and other broad-spectrum antibiotics. Therefore, it is important to consider its diagnosis in patients administered CEFTIN who develop diarrhea. Treatment with broad spectrum antibiotics, including CEFTIN, alters the normal flora of the colon and may permit overgrowth of Clostridia. Studies indicate that a toxin produced by C. difficile is one primary cause of antibiotic associated colitis. Mild cases of colitis may respond to drug discontinuance alone. Moderate to severe cases should be managed with fluid, electrolyte, and protein supplementation as indicated. When the colitis is severe or not relieved by discontinuance of CEFTIN administration, consideration should be given to the administration of oral vancomycin or other suitable therapy. Other possible causes of colitis should also be considered.
CEFTIN suspension contains aspartame, which is a source of phenylalanine and so should be avoided in patients with phenylketonuria.
Adverse Effects
pseudomembranous colitis (see Warnings).
thrombocytopenia, and leucopenia (sometimes profound).
The following hypersensitivity reactions have been reported: anaphylaxis, angioedema, pruritus, rash, serum sickness-like reaction, urticaria.
In addition to adverse events reported during clinical trials, the following events have been identified during clinical practice in patients treated with CEFTIN Tablets or with CEFTIN for Oral Suspension and were reported spontaneously. Data are generally insufficient to allow an estimate of incidence or to establish causation.
rashes (0.6%), pruritus (0.3%), urticaria (0.2%), shortness of breath and rare reports of bronchospasm. Hypersensitivity reactions to CEFTIN may occur in patients who report delayed hypersensitivity to penicillins (see Warnings). As with other cephalosporins, there have been rare reports of drug fever.
erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis.
transient increases of hepatic enzyme levels (ALT, AST, LDH).
The following adverse reactions have been observed to occur, although infrequently, in association with parenteral cefuroxime sodium and may be potential adverse effects of oral cefuroxime axetil: drowsiness, vaginitis, positive direct Coombs test, and transient increases in serum bilirubin, creatinine, alkaline phosphatase and urea nitrogen (BUN). In addition, the incidence of diaper rash (1.4%) has been associated with CEFTIN suspension in children.
diarrhea (5.6%), nausea (2.4%), vomiting (2%), loose stools (1.3%). Reports of abdominal pain have occurred.
Jaundice (predominantly cholestatic) and hepatitis have been reported very rarely.
Overdose
Other than general supportive treatment, no specific antidote is known. Excessive serum levels of cefuroxime can be reduced by dialysis. For treatment of hypersensitivity reactions, see Warnings.
Dosage
CEFTIN (cefuroxime axetil) may be given orally without regard to meals. Absorption is enhanced when CEFTIN is administered with food. In comparative bioavailability studies in healthy adults, CEFTIN suspension was not bioequivalent to CEFTIN tablets. The area under the curve for the suspension averaged 91% of that for the tablet, while the Cmax for the suspension averaged 71% of the Cmax of the tablets.
CEFTIN suspension contains aspartame, which is a source of phenylalanine and so should be avoided in patients with phenylketonuria. (See Warnings.)
Tablets: Adults and Children (12 Years of Age and Older): The usual recommended dosage is 250 mg twice a day. However, dosage may be modified according to the type of infection present, as indicated in Table 1.
Table 1: CEFTIN TabletsDosage According to the Type of Infection | Type of Infection | Dosage |
| Pharyngitis, tonsillitis, sinusitis, bronchitis, skin structure infections | 250 mg twice daily |
| More severe infections e.g., pneumonia | 500 mg twice daily |
| Uncomplicated gonorrhea | 1000 mg single dose |
There are presently no data available on the effects of CEFTIN in patients with renal impairment. However, in patients where there is significant impairment, a reduction in CEFTIN dosage may be required.
Infants and Children Less Than 12 Years of Age: CEFTIN tablets are not recommended for children less than 12 years of age.
Oral Suspension: Infants and Children 3 Months to 12 Years of Age: There is no experience in infants under the age of 3 months.
There is no clinical trial experience with the use of CEFTIN suspension in the treatment of lower respiratory tract infections.
The recommended dosage of CEFTIN suspension for various types of infections is indicated in Table 2, Table 3 and Table 4.
Table 2: CEFTIN SuspensionRecommended Dosage for Various Infections | Type of Infection | Dosage |
| Otitis media, skin structure infections | 15 mg/kg twice daily
Maximum dose 1 g/day |
| Pharyngitis, tonsillitis | 10 mg/kg twice daily
Maximum dose 500 mg/day |
Table 3: CEFTIN SuspensionRecommended Dosage for Pharyngitis and Tonsillitis Infections Weight
(kg) | mg/day | Doses/day | Dosage |
| Multidose Bottle mL/dose |
| 6 | 125 | 2 | 2.5 |
| 13 | 250 | 2 | 5.0 |
| 19 | 375 | 2 | 7.5 |
| 25 | 500 | 2 | 10.0 |
| >25 | 500 | 2 | 10.0 |
Table 4: CEFTIN SuspensionRecommended Dosage for Otitis Media and Skin Structure Infections Weight
(kg) | mg/day | Doses/day | Dosage |
| Multidose Bottle mL/dose |
| 4 | 125 | 2 | 2.5 |
| 8 | 250 | 2 | 5.0 |
| 13 | 375 | 2 | 7.5 |
| 17 | 500 | 2 | 10.0 |
| 21 | 625 | 2 | 12.5 |
| 25 | 750 | 2 | 15.0 |
| 29 | 875 | 2 | 17.5 |
| 33 | 1000 | 2 | 20.0 |
| >33 | 1000 | 2 | 20.0 |
The usual duration of treatment for CEFTIN tablets and CEFTIN for oral suspension is 7 to 10 days. For β-hemolytic streptococcal infections, therapy should be continued for at least 10 days.
Directions for Reconstituting Suspension in Bottles: Prepare a suspension at time of dispensing, as follows: 1) Shake the bottle to loosen the granules, and remove the cap. 2) Add the total amount of water for reconstitution all at once (see Table 5) and replace cap. 3)Invert the bottle and rock the bottle vigorously until the sound of the granules against the container disappears. 4) Turn the bottle into an upright position and shake vigorously. Each 5 mL provides 125 mg cefuroxime. 5) Refrigerate immediately at between 2 and 8°C.
Note: Shake the bottle vigorously until the suspension can be heard moving in the bottle before each use. Replace cap securely after each opening. If desired, the dose of the reconstituted suspension may be added to one of the following cold beverages immediately prior to administration: milk (i.e. skim, 2% or homogenized), fruit juice (i.e. apple, orange, or grape) or lemonade.
Note: CEFTIN granules should not be reconstituted in hot beverages.
