Is splitting propranolol tablet safe for pediatric use? Results from an experimental test

Objectives. Recent studies have shown that propranolol is widely used in the treatment of infantile hemangiomas. The recommended dose regimen of a starting dose of 0.5 mg/kg/day followed by a slow increase up to 2 mg/kg/day is not reproducible with the actual dose strength of the available propranolol marketed product (40 mg tablets unit dose), particularly in younger subject. For this reason, it is necessary breaking of tablets to obtain the correct starting 10 mg dose. This study evaluated the weight and dose uniformity in split quarters of propranolol tablets. Study design. Twenty pharmacy students split 70 propranolol tablets by using a kitchen knife to obtain 280 quarters, which were evaluated for their integrity and adequacy for administration. Intact tablets and quarters were weighed. The content of propranolol in tablet quarters was determined by using high performance liquid chromatography. Results. Overall, 265 parts (94.6% of total) were integral and 213 (76.1%) were considered as adequate for administration. The mean (± standard deviation) weight of quarters judged as suitable and non suitable for administration was 49.56 ± 5.27 mg and 46.24 ± 7.53 mg, respectively. Splitting caused a mean loss of weight from the entire tablet equal to 2.97 ± 2.91 mg (median 2.06 mg). The percentage of quarters with weight lower than theoretical was 55.88%, and the remaining weighted more than expected. The mean propranolol content in quarters was 9.52 ± 0.96 mg (median 9.42 mg, range 7.36-12.23 mg) and 42% of quarters (95% CI: 35.07 – 49.17%) were not in within the ± 10% acceptance range. Conclusions. The manual splitting of propranolol 40 mg tablets produced a significant proportion of quarters not suitable for the administration in children or with a weight outside of the required range ± 10%. The availability of a pediatric oral solution of propranolol will reduce the risk of inappropriate dosing and will reduce the related risk of inefficacy or of safety concerns in case of administration of inappropriate doses.