Amoclav Special Precautions

Hypersensitivity Reactions: Serious and occasionally fatal hypersensitivity reactions (including anaphylactoid and severe cutaneous adverse reactions) have been reported in patients on penicillin therapy. Careful inquiry should be made concerning previous hypersensitivity to penicillins, cephalosporins, or other drugs before initiating therapy with Co-amoxiclav. Serious anaphylactic reactions require immediate emergency treatment with epinephrine. Oxygen, intravenous steroids, and airway management, including intubation, should also be instituted.
Clostridium difficile-associated disease (CDAD): This has been reported with the use of nearly all antibacterial agents, including Co-amoxiclav, and may range in severity from mild diarrhea to fatal colitis. It is important to consider this diagnosis in patients who present with diarrhea, or symptoms of colitis, pseudomembranous colitis, toxic megacolon, or perforation of colon subsequent to the administration of any antibacterial agents. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.
Hepatic Dysfunction: Hepatic dysfunction, including hepatitis and cholestatic jaundice has been associated with the use of Co-amoxiclav. Hepatic toxicity is usually reversible; however, deaths have been reported. Hepatic function should be monitored at regular intervals in patients with hepatic impairment.
In patients with renal impairment, the dose of Co-amoxiclav should be adjusted based on the degree of impairment [see Dosage & Administration].
During administration of high doses of amoxicillin, it is recommended to maintain adequate fluid intake and urinary output in order to reduce the possibility of crystalluria associated with amoxicillin therapy.
Appropriate monitoring should be undertaken when anticoagulants are prescribed concomitantly with Co-amoxiclav since prolongation of prothrombin time has been reported rarely in patients receiving Co-amoxiclav.
Although Co-amoxiclav has a low toxicity profile, the renal, hepatic, and hematopoietic status of patients undergoing prolonged treatment with the drug should be evaluated periodically.
Co-amoxiclav should be avoided if infectious mononucleosis is suspected since the occurrence of a morbilliform rash has been associated with this condition following the use of amoxicillin.
As with other antibacterial drugs, long term or repeated use may result in overgrowth of non-susceptible organisms, including fungi.
Carcinogenesis, Mutagenesis, Impairment of Fertility: The carcinogenic potential of Co-amoxiclav has not been evaluated in long-term animal studies.
The mutagenic potential of the drug has been investigated in vitro using Ames test, a human lymphocyte cytogenic assay, a yeast test and a mouse lymphoma forward mutation assay, and in vivo using mouse micronucleus tests and a dominant lethal test. Results were negative for all tests except for the in vitro mouse lymphoma assay where weak activity was found at very high, cytotoxic concentrations.
Oral doses of Co-amoxiclav up to 1,200 mg/kg/day (5.7 times the maximum human dose) was found to have no effect on fertility and reproductive performance in rats, dosed with a 2:1 ratio formulation of amoxicillin:clavulanic acid.
Effects on Ability to Drive and Use Machines: No studies on the effects on the ability to drive and use machines have been performed. However, undesirable effects may occur (e.g., allergic reactions, dizziness and convulsions), which may influence the ability to drive and use machines.
Renal Impairment: Dosage adjustments are based on the maximum recommended level of amoxicillin. No adjustment in dose is required in patients with creatinine clearance greater than 30 mL/min.
Hepatic Impairment: Dose with caution; monitor hepatic function at regular intervals for both adults and children.
Use in Children: Children weighing over 40 kg should be dosed based on recommended dosing in adult patients. The safety and efficacy of Co-amoxiclav tablets in children weighing less than 40 kg have not been established.
Use in the Elderly: Since elderly patients have increased risk of renal impairment, dose adjustment and renal function monitoring may be necessary.