SIDE EFFECTS
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 the recommended dosages of cefuroxime axetil
(125 to 500 mg twice a day). 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 1000, 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).
Multiple-Dose Dosing Regimens¾Clinical
Trials: Incidence ³1%: Diarrhea/loose stools
(3.7%), nausea/vomiting (3.0%), transient elevation in
AST (2.0%), transient elevation in ALT (1.6%), eosinophilia
(1.1%), transient elevation in LDH (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 STUDIES):
In clinical trials using cefuroxime axetil in a dose of
250 mg bid in the treatment of secondary bacterial infections
of acute bronchitis, 399 patients were treated for 5 days
and 402 pateints were treated for 10 days. No difference
in the occurrence of adverse events was found between
the two 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's 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, 1061 patients were treated with the recommended
dosage of cefuroxime axetil (1000 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 1000-mg single-dose clinical trials
of cefuroxime axetil tablets in the treatment of uncomplicated
gonorrhea conducted in the U.S.
1-g Single-Dose Regimen for Uncomplicated Gonorrhea¾Clinical
Trials: Incidence ³1%: 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.
Cefuroxime Axetil Powder for Oral Suspension
in Clinical Trials
In clinical trials using multiple doses of cefuroxime
axetil powder for oral suspension, pediatric patients
(96.7% of whom were younger than 12 years of age) were
treated with the recommended dosages of cefuroxime axetil
(20 to 30 mg/kg per day divided twice a day up to a maximum
dose of 500 or 1000 mg per day, respectively). There were
no deaths or permanent disabilities in any of the patients
in these studies. Eleven U.S. patients (1.2%) discontinued
medication due to adverse events thought by the investigators
to be possibly, probably, or almost certainly related
to drug toxicity. The discontinuations were primarily
for gastrointestinal disturbances, usually diarrhea or
vomiting. During clinical trials, discontinuation of therapy
due to the taste and/or problems with administering this
drug occurred in 13 (1.4%) pediatric patients enrolled
at centers in the U.S.
The following adverse events were thought by the investigators
to be possibly, probably, or almost certainly related
to cefuroxime axetil for oral suspension in multiple-dose
clinical trials (n=931 cefuroxime axetil-treated US patients).
Multiple-Dose Dosing Regimens-Clinical Trials:
Incidence ³1%: Diarrhea/loose stools (8.6%), dislike
of taste (5.0%), diaper rash (3.4%), nausea/vomiting (2.6%).
Incidence <1% but >0.1%: Abdominal pain, flatulence,
gastrointestinal infection, candidiasis, vaginal irritation,
rash, hyperactivity, irritable behavior, eosinophilia,
positive direct Coombs' test, elevated liver enzymes,
viral illness, upper respiratory infection, sinusitis,
cough, urinary tract infection, joint swelling, arthralgia,
fever, ptyalism.
Postmarketing experience with ceftin products
In addition to the 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.
General: The following hypersensitivity
reactions have been reported: Anaphylaxis, angioedema,
pruritus, rash, serum sickness-like reaction, and urticaria.
Gastrointestinal: Pseudomembranous colitis
(see WARNINGS).
Hematologic: Hemolytic anemia, leukopenia,
pancytopenia, and thrombocytopenia and increased prothrombin
time.
Hepatic: Hepatic impairment including
hepatitis and cholestasis, jaundice.
Neuroligic: Seizure.
Skin: Erythemia multiforme, Stevens-Johnson
syndrome, and 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 ADMINISTRATION
and OVERDOSAGE). If seizures associated with drug therapy
occur, the drug should be discontinued. Anticonvulsant
therapy can be given if clinically indicated.
DRUG INTERACTIONS
Concomitant administration of probenecid with cefuroxime
axetil tablets increases the area under the serum concentration
versus time curve by 50%. The peak serum cefuroxime concentration
after a 1.5-g single dose is greater when taken with 1
g of probenecid (mean=14.8 mcg/ml) than without probenecid
(mean=12.2 mcg/ml).
Drugs that reduce gastric acidity may result in a lower
bioavailability of cefuroxime axetil compared with that
of fasting state and tend to cancel the effect of postprandial
absorption.
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