Is the Tablet Scoring as Indication of Narrow Therapeutic Index (NTI) Drugs? Clinical Pharmacologist Views

As a clinical pharmacist and clinical pharmacologist for about 25 years at the Food and Drugs Administration (FDA), I have always wondered about the question of splitting the tablet, and especially for tablets for the drugs with Narrow Therapeutic Index (NTI). For these drugs, any small increase in the amount ingested to a severe patient has risky consequences, especially in the elderly. I worked on this NTI project during my tenured year at the FDA. I reviewed over 200 commonly prescribed drugs, from the efficacy and safety perspective. My focus was identifying the Maximum Toxic Concentration (MTC), the Minimum Effective Concentration (MEC), Maximum Dose (Max D), and Minimum Dose (Min D). The therapeutic index (TI) was measured from the following equation: TI =MTC/MEC for all drugs. Also, I identified the various strengths available for each drug product and the scoring (if any). The analysis shows that the mean and standard deviation (SD) for all 64 scored tablets was 5.030 (± 2.79 units) and that all unscored drugs was 9.520 (± 14.22 units). As noted, there was more variability in the unscored tablets. This provided evidence that the drugs tending to be NTI were scored to titrate. However, patients, especially elderly, appear to be confused and having difficulty in accurately breaking the tablet scores. However, it is important to note that acetaminophen represents wide TI, maximum daily dose of 4,000 mg/day, and it is no-scored. However, levothyroxine which represents drug with NTI has 12 strengths and all are scored.