Amoxicillin/Clavulanic Acid for the Treatment of Odontogenic Infections: A Randomised Study Comparing Efficacy and Tolerability versus Clindamycin

Abstract

Background. Treatment of odontogenic infections includes surgical drainage and adjunctive antibiotics. This study was designed to generate efficacy and safety data to support twice daily dosing of amoxicillin/clavulanic acid compared to clindamycin in odontogenic infections. Methods. This was a phase IV, randomised, observer blind study; 472 subjects were randomised to receive amoxicillin/clavulanic acid (875 mg/125 mg BID, n = 235) or clindamycin (150 mg QID, n = 237) for 5 or 7 days based on clinical response. The primary endpoint was percentage of subjects achieving clinical success (composite measure of pain, swelling, fever, and additional antimicrobial therapy required) at the end of treatment. Results. The upper limit of two-sided 95% confidence interval for the treatment difference between the study arms (7.7%) was within protocol specified noninferiority margin of 10%, thus demonstrating noninferiority of amoxicillin/clavulanic acid to clindamycin. Secondary efficacy results showed a higher clinical success rate at Day 5 in the amoxicillin/clavulanic acid arm. Most adverse events (raised liver enzymes, diarrhoea, and headache) were similar across both arms and were of mild to moderate intensity. Conclusion. Amoxicillin/clavulanic acid was comparable to clindamycin in achieving clinical success (88.2% versus 89.7%) in acute odontogenic infections and the safety profile was consistent with the known side effects of both drugs. Trial Registration. This trial is registered with Clinicaltrials.gov identifier: NCT02141217.

Is the demonstration of bioequivalence for clavulanic acid required in amoxicillin–clavulanic acid orally administered immediate-release products?

“…Further, Tancawan et al . did not notice any clinically relevant shifts in liver function indicators ALT and AST values …”

“…Tancawan et al . too reported good safety profile of Co‐amoxiclav in phase IV clinical study in which 236 patients received the product . Only mild to transient gastrointestinal adverse effects were recorded.…”

“…Clavulanic acid is also free of serious side effects. Over 3 decades of successful use bears the testimony to the Co‐amoxiclav combination's exceptional tolerability . The majority of the adult and paediatric patients have received the combination well and only minority group of patients has reported mild adverse effects related to gastrointestinal disturbance such as diarrhoea, nausea and vomiting (SPC, Co‐amoxiclav 1000 mg/200 mg).…”

“…Increased LFT (liver function test) was the predominant ongoing adverse effect seen in 46 subjects receiving Co‐amoxiclav and in 40 subjects receiving clindamycin. As no subjects showed a shift in ALT and AST from normal values, these were not considered of clinical concern …”

“…[28,29] Tancawan et al too reported good safety profile of Co-amoxiclav in phase IV clinical study in which 236 patients received the product. [30] Only mild to transient gastrointestinal adverse effects were recorded. The incidence of adverse effects was similar to clindamycin which was tested in the same study on 235 patients.…”