Efficacy and Safety of Enzymatic Formulation of Amoxicillin/Clavulanic Acid Compared to Conventional Amoxicillin/Clavulanic Acid in the Treatment of Upper Respiratory Tract Infections in Children: A Post Marketing Surveillance Study

Background: Conventional amoxicillin produced on industrial scale is made using a chemical process with use of solvents. These solvents are present in the final formulation of amoxicillin and may lead to increased chance of side effects, namely diarrhea and abdominal pain. On the other hand, enzymatic amoxicillin, is made with the help of enzymes instead of the chemical solvents, and this results in purer amoxicillin, which may have lesser chances of side effects.

Objective: The purpose of this study was to explore the safety and efficacy of 'enzymatic formulation' of amoxicillin and Clavulanic acid (400 mg/57 mg) suspension compared to 'conventional formulation' of amoxicillin and Clavulanic acid (400 mg/57 mg) for 7 days in treatment of upper respiratory tract infections in pediatric patients.

Methods: This was an open-label prospective study comparing 'enzymatic formulation' of amoxicillin/Clavulanic acid (enzymatic formulation group) with 'conventional formulation' of amoxicillin/Clavulanic acid (conventional formulation group) in a 1:1 ratio in pediatric patients with upper respiratory tract infections. The treatment duration was for 7 days, and the patient was followed up on Day 3 (Visit 2) and at end of the treatment (Visit 3). Efficacy was assessed based on Physicians assessment of Clinical response at Visit 2 and Visit 3 defined as 'Cure': Disappearance of clinical signs and symptoms within the treatment period, 'Improved': Subsiding of clinical signs and symptoms but with incomplete resolution and 'Treatment Failure': Unchanged or worsening of baseline clinical signs and symptoms. Tolerability was evaluated based on Investigators' assessment on patient response, and classified as: 'Good tolerability': Side effects mild or not observed, 'Moderate tolerability': Side effects of moderate intensity, 'Poor tolerability': Side effects severe or discontinuation because of side effects. Safety was assessed for occurrence of any adverse events namely diarrhea and abdominal pain.

Results: In all 100 pediatric patients with upper respiratory tract infections like acute otitis media, Tonsilitis and sinusitis, were equally randomized to enzymatic formulation group (n = 50) and conventional formulation group (n = 50). Treatment duration was for 7 days and the average age was 4 years of which 28 were females and 68 were males. The primary efficacy end point of 'Physicians overall assessment' of 'Improved' and 'Cure' though not statistically significant was better in patients receiving enzymatic formulation at Visit 2 and Visit 3, respectively, was 100% (50) with enzymatic formulation group as compared to 96% (48) in the conventional group. 'Moderate tolerability' was seen in only 2% (1) in enzymatic formulation group as compared to 6% (3) of patients in conventional formulation group at visit 2; On visit 3 'Moderate tolerability' was seen in 6% (3) of patients in conventional formulation only. 'Poor tolerability' was seen in 4% (2) of patients in conventional formulation group only on visit 2. Overall adverse events reported in the enzymatic formulation group and conventional group was 4% (2) and 20% (10) respectively. Incidence of adverse event namely diarrhea and abdominal pain on Visit 2, was seen in 2% (1) patients on enzymatic formulation group as compared to 14% (7) in the conventional group; and on Visit 3, was seen in 2% (1) of patients on enzymatic formulation group as compared to 6% (3) in the conventional group. Treatment failure was noted in 2 patients in the conventional formulation group. The difference in the tolerability parameters was not statistically significant. Conventional formulation was discontinued on visit 2 in one patient due to poor tolerability and diarrhea.

Conclusion: 'Enzymatic formulation' of amoxicillin-clavulanic acid provided similar clinical response of 'Improvement' and 'Cure' with good tolerability and lesser incidence of diarrhea and abdominal pain, as compared to the 'conventional formulation' of amoxicillin-clavulanic acid.