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Amoxicillin/Clavulanate (ClavulinŽ)

 

Carlo Marra, Pharm.D., Luciana Frighetto, B.Sc. (Pharm).
February 1999 Drug & Therapeutics Newsletter
(C) 1999, CSU-Pharmaceutical Sceinces
Vancouver Hospital & Health Sciences Centre

Amoxicillin/clavulanate is a combination product containing amoxicillin, a semi-synthetic penicillin, and the B-lactamase inhibitor, clavulanate potassium. Clavulanate enhances the antibacterial spectrum of amoxicillin by acting as an irreversible "suicide" inhibitor of intracellular and extracellular B-lactamases and, thus protecting deactivation of amoxicillin.1,2 With the continued increase in resistance mediated by the bacterial production of $-lactamases, the addition of amoxicillin/clavulanate to the VHHSC drug formulary appears warranted. Addition of amoxicillin/clavulanate was proposed by the Antibiotic Utilization Subcommittee in October 1998, and approved by the D&T and MAAC in November 1998 and January 1999, respectively.

Spectrum of Activity

Amoxicillin/clavulanate provides additional coverage over amoxicillin of Staphylococcal aureus, Hemophilus influenzae, Escherichia coli, Moraxella catarrhalis, Klebsiella pneumoniae, Bacteroides fragilis and Proteus species.1,2 Consequently, this agent can be used as an alternative to 2nd and 3rd generation oral cephalosporins and/or cotrimoxazole for skin and soft tissue infections including bite wounds, lower respiratory tract infections, and urinary tract infections. In a recent meta-analysis that pooled three decades of trial results from more than four hundred publications and 38,500 patients, amoxicillin/clavulanate was equal or superior to other antibiotics for the treatment of upper and lower respiratory infections, skin structure infections, dental infections, head and neck infections, and selected urinary tract infections. In addition, when the results of these trials were grouped by annual and triennial publication dates, the efficacy of amoxicillin/clavulanate did not appear to have changed over time indicating its continued usefulness.

Dosage

The established adult oral dosing regimen for amoxicillin/clavulanate is 500/125 mg given every eight hours; however, some recent adult trials have indicated that the administration of a new 875/125 mg oral preparation twice daily is as effective as the three times daily regimen for lower respiratory tract infections4 and acute bacterial maxillary sinusitis.5 Table 2 compares the dosage and cost of amoxicillin/clavulanate to amoxicillin alone.

Drug Dose Daily Cost(a)
Amoxicillin/Clavulanate 500/125mg tid
875/125mg bid
$4.00
$4.63
Amoxicillin 500mg tid $0.27
Cefuroxime axetil 500 mg tid $11.88
Cefixime 400 mg daily $4.47
Cotrimoxazole 1 DS tablet bid $0.22

(a) based on VHHSC acquisition costs

Table. Cost comparison of ClavulinŽ to other oral formulary alternatives

Adverse Effects

The incidence and spectrum of adverse effects with amoxicillin/clavulanate is similar to amoxicillin alone. Adverse effects are typically gastrointestinal in nature and include diarrhea, nausea, vomiting and indigestion. The 875/125 mg bid dosing schedule has resulted in a lower rate of gastrointestinal complications than the 500/125mg tid dosing regimen.4,5 There have been rare reports of hepatic dysfunction associated with the use of this agent, mainly in elderly patients receiving prolonged or repeated treatment courses.2

References

1. Todd PA et al. Amoxicillin/clavulanic acid. An update of its antibacterial activity, pharmacokinetic properties and therapeutic use. Drugs 1990;39:264-307.

2. Ball P et al. Amoxycillin clavulanate: an assessment after 15 years of clinical application. J Chemother 1997;9:167-98.

3. Neu HC, Wilson APR, Gruneberg RN. Amoxycillin/clavulanic acid: A review of its efficacy in over 38,500 patients from 1979 to 1992. J Chemother 1993;5:67-93.

4. Calver AD et al. Dosing of amoxicillin/clavulanate given every 12 hours is as effective as dosing every 8 hours for treatment of lower respiratory tract infections. Clin Infect Dis 1997;24:570-4.

5. Seggev JS et al. A combination of amoxicillin and clavulante every 12 hours vs. every 8 hours for treatment of acute bacterial maxillary sinusitis. Arch Otolaryngol Head Neck Surg 1998c; 124(8):921-5.