Drug/Laboratory Test Interactions
Oral administration of AUGMENTIN XR will result in high urine concentrations of amoxicillin. High urine concentrations of ampicillin may result in false-positive reactions when testing for the presence of glucose in urine using CLINITEST®, Benedict’s Solution, or Fehling’s Solution. Since this effect may also occur with amoxicillin and therefore AUGMENTIN XR, it is recommended that glucose tests based on enzymatic glucose oxidase reactions (such as CLINISTIX®) be used.
Following administration of ampicillin to pregnant women, a transient decrease in plasma concentration of total conjugated estriol, estriol-glucuronide, conjugated estrone, and estradiol has been noted. This effect may also occur with amoxicillin, and therefore, AUGMENTIN XR.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term studies in animals have not been performed to evaluate carcinogenic potential. The mutagenic potential of AUGMENTIN was investigated in vitro with an Ames test, a human lymphocyte cytogenetic assay, a yeast test, and a mouse lymphoma forward mutation assay, and in vivo with mouse micronucleus tests and a dominant lethal test. All were negative apart from the in vitro mouse lymphoma assay, where weak activity was found at very high, cytotoxic concentrations. AUGMENTIN at oral doses of up to 1,200 mg/kg/day (1.9 times the maximum human dose of amoxicillin and 15 times the maximum human dose of clavulanate based on body surface area) was found to have no effect on fertility and reproductive performance in rats dosed with a 2:1 ratio formulation of amoxicillin:clavulanate.
Pregnancy Category B. Reproduction studies performed in pregnant rats and mice given AUGMENTIN at oral doses up to 1,200 mg/kg/day revealed no evidence of harm to the fetus due to AUGMENTIN. In terms of body surface area, the doses in rats were 1.6 times the maximum human oral dose of amoxicillin and 13 times the maximum human dose for clavulanate. For mice, these doses were 0.9 and 7.4 times the maximum human oral dose of amoxicillin and clavulanate, respectively. 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.
Following overdosage, patients have experienced primarily gastrointestinal symptoms including stomach and abdominal pain, vomiting, and diarrhea. Rash, hyperactivity, or drowsiness have also been observed in a small number of patients.
In the case of overdosage, discontinue AUGMENTIN XR, treat symptomatically, and institute supportive measures as required. If the overdosage is very recent and there is no contraindication, an attempt at emesis or other means of removal of drug from the stomach may be performed. A prospective study of 51 pediatric patients at a poison control center suggested that overdosages of less than 250 mg/kg of amoxicillin are not associated with significant clinical symptoms and do not require gastric emptying.5
Interstitial nephritis resulting in oliguric renal failure has been reported in a small number of patients after overdosage with amoxicillin.
Crystalluria, in some cases leading to renal failure, has also been reported after amoxicillin overdosage in adult and pediatric patients. In case of overdosage, adequate fluid intake and diuresis should be maintained to reduce the risk of amoxicillin crystalluria.
Renal impairment appears to be reversible with cessation of drug administration. High blood levels may occur more readily in patients with impaired renal function because of decreased renal clearance of both amoxicillin and clavulanate. Both amoxicillin and clavulanate are removed from the circulation by hemodialysis (see DOSAGE AND ADMINISTRATION).
AUGMENTIN XR is contraindicated in patients with a history of allergic reactions to any penicillin. It is also contraindicated in patients with a previous history of cholestatic jaundice/hepatic dysfunction associated with treatment with amoxicillin/clavulanate potassium.
AUGMENTIN XR is contraindicated in patients with severe renal impairment (creatinine clearance <30 mL/min.) and in hemodialysis patients.
- Clinical and Laboratory Standards Institute (CLSI) (formerly the National Committee for Clinical Laboratory Standards). Performance Standards for Antimicrobial Susceptibility Testing − Fifteenth Informational Supplement. CSLI Document M100-S15. CLSI, Wayne, PA, 2005.
- Clinical and Laboratory Standards Institute (CLSI) (formerly the National Committee for Clinical Laboratory Standards). Methods for Antimicrobial Susceptibility Testing of Anaerobic Bacteria − Sixth Edition. Approved Standard CSLI Document M11-A6, Vol. 24, No. 2. CLSI, Wayne, PA, 2004.
- Clinical and Laboratory Standards Institute (CLSI) (formerly the National Committee for Clinical Laboratory Standards). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically − Sixth Edition. Approved Standard CLSI Document M7-A6, Vol. 23, No. 2. CLSI, Wayne, PA, 2003.
- Clinical and Laboratory Standards Institute (CLSI) (formerly the National Committee for Clinical Laboratory Standards). Performance Standards for Antimicrobial Disk Susceptibility Tests − Eighth Edition. Approved Standard CLSI Document M2-A8, Vol. 23, No. 1. CLSI, Wayne, PA, 2003.
- Swanson-Biearman B, Dean BS, Lopez G, Krenzelok EP. The effects of penicillin and cephalosporin ingestions in children less than six years of age. Vet Hum Toxicol 1988;30:66-67.
AUGMENTIN XR and AUGMENTIN are registered trademarks of GlaxoSmithKline.
MAALOX is a registered trademark of Novartis Consumer Health, Inc.
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©2006, GlaxoSmithKline. All rights reserved.
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