Amoxicillin is a beta-lactam antibiotic that inhibits bacterial cell wall synthesis by binding to and inactivating penicillin-binding proteins (PBPs). Enzymes that facilitate peptidoglycan cross-linkage, PBPs play an integral role in the formation of bacterial cell walls. As a resistance mechanism, certain bacteria began producing beta-lactamase, an enzyme that destroys the beta-lactam ring in antibiotics such as amoxicillin, rendering them ineffective. Clavulanic acid (also known as clavulanate) is a beta-lactamase inhibitor that binds to bacterial beta-lactamase, allowing amoxicillin to have an expanded spectrum of activity.
“In general, combination products are interchangeable only if they have the same ratio of amoxicillin to clavulanic acid.”
CHOOSING THE APPROPRIATE PRODUCT
The various formulations of amoxicillin/clavulanate contain different strengths of each component. Although amoxicillin/clavulanate is dosed based on the amoxicillin component, PAs should take into consideration the amount of clavulanate when choosing a combination product. Underdosing clavulanate may promote resistance and reduce the spectrum of activity of the combination. Conversely, excessive clavulanate often results in diarrhea. Indeed, the incidence of diarrhea is higher with amoxicillin/clavulanate than with amoxicillin alone.1
Extra-strength amoxicillin/clavulanate, which contains 600 mg of amoxicillin, is a powder for suspension and perhaps the most commonly misunderstood and incorrectly prescribed product. This product should be used only in children who weigh less than 40 kg and at doses of 80 to 100 mg/kg per day. When used in adults or in children at lower doses, the amount of clavulanic acid may be insufficient for this product to be effective against strains of bacteria that are beta-lactamase-positive. The extrastrength formulation is indicated in children for the treatment of sinusitis or otitis media in cases that are severe or recurrent or have failed prior antibiotic therapy. This formulation may also be used off-label in children for community-acquired pneumonia (again, at doses of 80 to 100 mg/kg per day). When prescribing lower doses of amoxicillin (20 to 40 mg/kg per day), do not use the extra-strength formulation.
In general, children younger than 3 months should not be prescribed amoxicillin in doses greater than 30 mg/kg per day and therefore should not receive the extra-strength formulation. The preferred product for infants younger than 3 months is the 125-mg/5-mL suspension. This is not interchangeable with the 200-mg suspension or the chewable tablet because they contain different amounts of clavulanate. In general, combination products are interchangeable only if they have the same ratio of amoxicillin to clavulanic acid (see Table 1, available online). Additionally, the extended-release product, which contains 1,000 mg amoxicillin is not interchangeable with any other product and should be used only in adults.
Prescribing amoxicillin/clavulanic acid products can clearly be confusing, particularly in children. In addition to containing different amounts of amoxicillin and clavulanic acid, each product contains inactive ingredients that must be taken into consideration. Some products contain phenylalanine and should be avoided in patients with phenylketonuria. Furthermore, some products should be avoided in patients with kidney disease. When prescribing amoxicillin/ clavulanate, begin by determining the appropriate individual dose of amoxicillin, and consult a reliable source as an aid for choosing the correct product.2
Symbol ONLINE EXTRAS AT www.jaapa.com
• Table 1: Summary of products containing amoxicillin and clavulanic acid
1. Salvo F, Polimeni G, Moretti U, et al. Adverse drug reactions related to amoxicillin alone and in association with clavulanic acid: data from spontaneous reporting in Italy. J Antimicrob Chemother.
2. Lacy CF, Armstrong LL, Goldman MP, Lance LL. Drug Information Handbook.
20th ed. Hudson, Ohio: Lexi-Comp, Inc; 2011:101-104.