Summary

• RISPERDAL Tablets are not scored and are not intended to be split. Splitting unscored RISPERDAL Tablets is not recommended due to the inability to ensure the intended dosage in each fragment. No evaluations have been performed to assure the safety and efficacy when using broken, divided, or otherwise altered tablets.
• RISPERDAL Tablets contain a film coating to protect the active medication from degradation when exposed to air and light. RISPERDAL Tablets are not intended to be crushed. The film coating does not crush as well as the core tablet.

PUBLISHED LITERATURE

Weissman et al (2007)¹ conducted a retrospective analysis of administrative claims data from the New York/New Jersey region of the Veterans Health Administration to determine whether risperidone tablet splitting is associated with changes in medication adherence, resource utilization, or clinical outcomes. The analysis included patients (N=1878) with schizophrenia or schizoaffective disorder, engaged in outpatient treatment who: (1) had at least one prescription for risperidone outside of hospital discharge from January 2001-March 2003; (2) were active in outpatient treatment for ≥90 days (demonstrated by patients receiving an outpatient service or receipt of an antipsychotic outpatient prescription); and (3) attended at least one scheduled mental health appointment. The patients' mean age was 51.6 years and most (95%) patients were male.

MPR (medication possession ratio) was calculated (number of days supply dispensed/number of days patient expected to take medication), with an MPR of 1.0 representing on-time refill rates. An MPR <1 indicates that the patient refilled their medication less frequently than as prescribed. To determine resource utilization, the proportion of kept, scheduled appointments was determined. In addition, the ratio of unscheduled (walk-in) appointments to kept, scheduled appointments was calculated. Furthermore, psychiatric and non-psychiatric admission rates were calculated (number of admissions per patient-year), as indicators of relapse or adverse medical outcomes, respectively.

Patients were classified into two groups: whole-tablet and splitters. Splitters received at least one prescription with a >7-day supply with instructions to split tablets. The age and sex of both groups were similar. Prior to initiating splitting, the MPR, rate of kept appointments, proportion of kept appointments, and psychiatric or non-psychiatric admission rates in the whole-tablet group and the splitter group were similar. However, the whole tablet group: (1) received higher doses of risperidone (4.11 vs. 3.30 mg/day; P<0.001); (2) had higher rates of unscheduled appointments (0.19 vs. 0.09 per person per month; P<0.001); and (3) a higher ratio of unscheduled to scheduled, kept appointments (0.25 vs. 0.10; P<0.001) than splitters prior to initiating splitting. After initiating splitting, the MPR of the splitter group increased significantly, from 0.83 to 0.90 (n=442; P<0.001). After initiating splitting, increases in both the number of monthly unscheduled appointments (0.08/person to 0.32/person; P<0.001; n=442) and the ratio of unscheduled appointments to scheduled, kept appointments (0.08 to 0.54; P<0.001; n=371) were found. However, no significant differences were found in: (1) the number of scheduled, kept appointments; (2) the ratio of scheduled, kept appointments to scheduled appointments; and (3) the psychiatric or non-psychiatric admission rate.

During the first 60 days of splitting, the kept appointment rate and unscheduled appointment rate of the splitter group increased, but the rate of kept appointments returned to baseline during the next 60 days, and the unscheduled appointment rate decreased.

However, the authors caution the MPR increase likely stems from tablet loss (by destruction during splitting) or patients misunderstanding instructions and taking a whole tablet, both of which would increase the apparent MPR. Weissman et al. studied risperidone “because tablets are scored and relatively easy to split.” However, since the introduction of 0.25 mg and 0.5 mg tablets, scored Risperdal tablets are no longer available.

Nolly et al (2005)² evaluated the weight variation of half-tablets obtained from splitting scored and unscored tablets of psychotropic medications that were split using a tablet-splitting device. Paroxetine 20 mg and 40 mg, risperidone 2 mg and 4 mg, and sertraline 100 mg were the psychotropic drugs selected to assess half-tablet dosage accuracy. Paroxetine 20 mg and sertraline 100 mg are scored on one side of the tablet whereas paroxetine 40 mg, risperidone 2 mg, and risperidone 4 mg are unscored. Fifteen whole tablets of each strength were assessed for whole tablet weight variability and divided into three groups of 5 tablets each for splitting.

Whole tablets were split using a tablet-splitting device. The tablets were weighed as whole and half-sized with the use of a digital electronic balance. The USP method was utilized and adapted to assess the weight variation of half-tablets. The criteria indicated that the weight per 10 half-tablets should be within a range of 85% to 115% of theoretical weight. Relative standard deviation (RSD) was established as less than or equal to 6%. The criteria were also validated if the weight of no more than one half-tablet for 30 half-tablets was outside of the 85% to 115%, no half-tablet was outside the theoretical weight range of 75% to 125%, and the RSD of 30 half-tablets did not exceed 7.8%.

The weights for the whole tablets of all three drugs were within 85% to 115% with an RSD less than 6%. All 3 sets of paroxetine 20 mg and 40 mg, sertraline 100 mg, and risperidone 2 mg half-tablet sets of 10 were within 85% to 115% of theoretical weight with an RSD less than 6%. Two out of three sets of risperidone 4 mg met the weight variation criteria. But one set of half-tablets of risperidone 4 mg had an RSD of over 6%. Although one set of risperidone 4 mg half-tablets fell outside of the RSD range, risperidone 4 mg as a group met the weight variation criteria as the 30 half-tablet set containing that set had no tablet outside the theoretical weight range of 75% to 125%.

SELECTED ADDITIONAL REFERENCES

Several citations, with respect to the pharmacoeconomics of splitting risperidone tablets, are listed in the bibliography.^3-5 An article⁶ and a cited reference^,7 from the Institute of Safe Medication Practices regarding tablet splitting are also referenced for your review.

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT Drug File (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 04 April 2024.