Amoxicillin and Clavulanic Acid Precautions 

General

While AUGMENTIN possesses the characteristic low toxicity of the penicillin group of antibiotics, periodic assessment of organ system functions, including renal, hepatic, and hematopoietic function, is advisable during prolonged therapy. 

A high percentage of patients with mononucleosis who receive ampicillin develop an erythematous skin rash. Thus, ampicillin-class antibiotics should not be administered to patients with mononucleosis. 

The possibility of superinfections with mycotic or bacterial pathogens should be kept in mind during therapy. If superinfections occur (usually involving Pseudomonas or Candida), the drug should be discontinued and/or appropriate therapy instituted. 

Prescribing AUGMENTIN in the absence of a proven  or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. 

Drug Interactions 

Probenecid decreases the renal tubular secretion of amoxicillin. Concurrent use with AUGMENTIN may result in increased  and prolonged blood levels of amoxicillin. Coadministration of probenecid cannot be recommended. 
The concurrent administration of allopurinol  and ampicillin increases substantially the incidence of rashes in patients receiving both drugs as compared  to patients receiving ampicillin alone. It is not known whether this potentiation  of ampicillin rashes is due to  allopurinol or the hyperuricemia present in these patients. There are no data with AUGMENTIN  and allopurinol administered concurrently. 

In common with other broad-spectrum antibiotics, AUGMENTIN  may reduce  the efficacy of oral contraceptives. 

Drug/Laboratory Test Interactions 

Oral administration of AUGMENTIN 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, 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. 

Information for Patients 

Patients  should be counseled  that antibacterial drugs including AUGMENTIN, should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When AUGMENTIN is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may: (1)  decrease the effectiveness of the immediate treatment, and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by AUGMENTIN or other antibacterial drugs in the future. 

Carcinogenesis, Mutagenesis, Impairment of Fertility 

Long-term studies in animals have not been performed  to evaluate carcinogenic potential. 

Mutagenesis  

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. 

Impairment of Fertility 

AUGMENTIN at oral doses of up to 1,200 mg/kg/day (5.7 times the maximum human dose, 1,480 mg/m2/day, 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. 

Teratogenic effects 

Pregnancy (Category B). Reproduction studies performed in pregnant rats and mice given AUGMENTIN at oral dosages up to 1,200 mg/kg/day, equivalent to 7,200 and 4,080 mg/m2/day, respectively (4.9 and 2.8 times the maximum human oral dose based on body surface area), revealed no evidence of harm to the fetus due to AUGMENTIN. 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. 

Labor and Delivery 

Oral ampicillin-class antibiotics are generally poorly absorbed during labor. Studies in guinea pigs have shown that intravenous administration of ampicillin decreased the uterine tone, frequency of contractions, height of contractions, and duration of contractions; however, it is not known whether the use of AUGMENTIN in humans during labor or delivery has immediate or delayed adverse effects on the fetus, prolongs the duration of labor, or increases the likelihood that forceps delivery or other obstetrical intervention or resuscitation of the newborn will be necessary. In a single study in women with premature rupture of fetal membranes, it was reported that prophylactic treatment with AUGMENTIN may be associated with an increased risk of necrotizing enterocolitis in neonates. 

Nursing Mothers 

Ampicillin-class antibiotics are excreted in the milk; therefore, caution should be exercised when AUGMENTIN is administered to a nursing woman. 

Pediatric Use 

Pediatric patients weighing 40kg or more  should be dosed according to the adult recommendations (see DOSAGE AND ADMINISTRATION: Pediatric Patients). Safety and effectiveness of AUGMENTIN Tablets in pediatric patients weighing less than 40 kg have not been established. (See prescribing information for AUGMENTIN Powder for Oral Suspension and Chewable Tablets.) 

Geriatric Use 

An analysis of clinical studies of AUGMENTIN was conducted to determine whether subjects aged 65 and over respond differently from younger subjects. Of  the 3,119 patients in this analysis, 68% were <65 years old, 32% were ≥65 years old and 14% were ≥75 years old.This analysis and other reported clinical experience have not identified differences in responses between the elderly and younger patients, but a greater sensitivity of some older individuals cannot be ruled out. 

This drug  is known to be substantially excreted by  the kidney, and  the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in  dose selection, and it may be useful  to monitor renal function.