While co-amoxiclav 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 developed 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 co-amoxiclav 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.
Information for Patients: Patients should be counseled that antibacterial drugs including co-amoxiclav, should only be used to treat bacterial infections. They do not treat viral infections (eg, the common cold). When co-amoxiclav 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 co-amoxiclav or other antibacterial drugs in the future.
Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as ≥2 months after having taken the last dose of the antibiotic.
Carcinogenicity, Mutagenicity and Impairment of Fertility: Long-term carcinogenicity studies in animals have not been performed to evaluate carcinogenic potential.
The mutagenic potential of co-amoxiclav was investigated in vitro with an Ames test, a human lymphocyte cytogenic assay, a yeast test and a mouse lymphoma forward mutation assay and in vitro with mouse micronucleus tests and a dominant lethal test. All were negative apart from in vitro mouse lymphoma assay where weak activity was found at very high, cytotoxic concentrations.
Co-amoxiclav at oral doses of up to 1200 mg/kg/day (5.7 times the maximum human dose, 1480 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 co-amoxiclav.
Use in pregnancy: Teratogenic Effects: Reproduction studies performed in pregnant rats and mice given with co-amoxiclav administered orally and parenterally with dosages up to 1200 mg/kg/day, equivalent to 7200 and 4080 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 co-amoxiclav.
There are however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, co-amoxiclav 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 IV 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 co-amoxiclav 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 preterm, premature rupture of the fetal membrane (pPROM), it was reported that prophylactic treatment with co-amoxiclav may be associated with an increase risk of necrotizing enterocolitis in neonates. As with all medicines, use should be avoided in pregnancy especially during the 1st trimester, unless considered essential by the physician.
Use in lactation: Ampicillin class antibiotics are excreted in the milk; therefore, caution should be exercised when co-amoxiclav is administered to a nursing woman.
Co-amoxiclav may be administered during the period of lactation. With the exception of the risk of sensitization, associated with the excretion of trace quantities in breast milk, there are no known detrimental effects for the breastfed infant.
Use in children: Pediatric patients weighing ≥40 kg should be dosed according to the adult recommendations (see Pediatric Patients under Dosage & Administration). Safety and effectiveness of co-amoxiclav tablets in pediatric patients weighing <40 kg have not been established. (See also Dosage & Administration.)
Use in elderly: An analysis of clinical studies of co-amoxiclav was conducted to determine whether subjects ≥65 years respond differently from younger subjects. Of the 3119 patients in this analysis, 68% were <65 years, 32% were ≥65 years and 14% were ≥75 years.
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.
Co-amoxiclav 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.