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