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P T. 2017;42(6): 384-387,393

Cost-Savings From an Antipsychotic Tablet-Splitting Program

Heather Carey PharmD, BCPP
Mark Fondriest RPh

INTRODUCTION

Newer atypical antipsychotics were developed to improve tolerability while enhancing clinical efficacy. Lurasidone (Latuda, Sunovion) and aripiprazole (Abilify, Otsuka) are two newer atypical antipsychotics with novel pharmacodynamic mechanisms that are frequently prescribed for a variety of psychiatric diagnoses due to their favorable safety and efficacy profiles. These agents have a decreased risk of sedation, hyperprolactinemia, extrapyramidal symptoms, and long-term metabolic complications often associated with other atypical antipsychotics.13 The improved safety profile makes these agents additional options for patients who have few or no alternatives due to adverse reactions or inefficacy experienced with other antipsychotic agents. While these agents add to the available armamentarium of atypical antipsychotics, their clinical use is often hampered by higher costs. At University Hospitals Richmond Medical Center, we determined that aripiprazole and lurasidone could be split, which helps reduce costs while ensuring accessibility to clinically appropriate medication options.

Lurasidone and aripiprazole have proven efficacy for a variety of psychiatric diagnoses outside of schizophrenia. At our facility, lurasidone is frequently prescribed for bipolar depression and aripiprazole for augmentation of antidepressant treatment. Lurasidone is approved by the Food and Drug Administration (FDA) for treating bipolar depression, which is important given that there are only two other approved antipsychotics for this indication: quetiapine and olanzapine/fluoxetine.4,5 While no direct, head-to-head studies have compared the efficacy and safety of FDA-approved pharmacological options for bipolar depression, the number needed to treat (NNT) and number needed to harm (NNH) from previous studies help to quantify clinical relevance. The NNT represents how many patients would have to be treated in order for one patient to have a positive outcome of interest (e.g., response, remission).6,7 Similarly, NNH signifies the number of patients that would have to be exposed to treatment in order to result in harm (e.g., adverse effect).8 One previous review of FDA-approved therapies for bipolar depression found similar NNT for lurasidone for response (NNT = 6) and remission (NNT = 7) compared with quetiapine (response, NNT = 6; remission, NNT = 6) and olanzapine/fluoxetine (response, NNT = 4; remission, NNT = 5).9 However, this review indicated that lurasidone may offer improved tolerability over other approved agents for bipolar depression based on an NNH of 14 to 130 for somnolence and an NNH of 29 to 5,550 for weight gain of 7% or more compared to quetiapine (NNH of three for somnolence) and olanzapine/fluoxetine (NNH of six for weight gain of 7% or more).9

Aripiprazole has FDA-approved indications for treating acute manic or mixed episodes of bipolar I disorder, adjunctive treatment of major depressive disorder (MDD), and irritability associated with autistic disorder and Tourette’s syndrome.10 Only two other atypical antipsychotic agents are FDA-approved for adjunctive treatment of MDD: quetiapine XR and brexpiprazole (Rexulti, Otsuka). While aripiprazole has not been directly compared with either of these agents, it has been shown to provide a statistically significant reduction in depressive symptoms compared with placebo.1113

Aripiprazole augmentation for MDD may offer an advantage over quetiapine XR due to improved tolerability. A review by Chen and colleagues reported study withdrawal rates due to an adverse event of 2.2% to 6.2% for aripiprazole versus 1.1% to 1.7% for placebo, compared with 6.6% to 19.5% for quetiapine XR versus 0.7% to 3.7% for placebo.12 This review reported lower rates of sedation, somnolence, hyperglycemia, and dyslipidemia for aripiprazole augmentation over quetiapine but higher rates of akathisia for aripiprazole.

Despite the potential advantages of lurasidone and aripiprazole, the substantial cost associated with these newer agents often hinders their use in clinical practice, which may impact patient care. Many newer psychotropic medications have a similar or identical price structure for each available strength. Thus, splitting individual tablet strengths may dramatically lower costs for health care systems. University Hospitals Richmond Medical Center piloted a tablet-splitting program beginning in August 2015 in which various strengths of aripiprazole and lurasidone were prepackaged as halved tablets (Table 1) in order to reduce cost and drug waste.

It had previously been common practice for nurses at our facility to split certain tablets, including aripiprazole and lurasidone, in half while patients’ medications are being titrated. This is often due to limited shelf space that prevents purchasing of all available tablet strengths. This technique allows for more patient-specific therapy, especially during titrations requiring gradual increases in dose to avoid unwanted side effects. The unused half-tablets were often discarded, creating a significant amount of waste. In addition, the patient was billed for the entire tablet, resulting in more expense. Splitting tablets in the pharmacy prior to patient administration results in a substantial reduction in medication waste and cost while potentially improving the safety and accuracy of tablet splitting.

Beginning in August 2015, our facility began splitting the lurasidone and aripiprazole tablets listed in Table 1 in the pharmacy. We determined that the average cost to split and package each tablet ranges from $0.30 to $0.50 for labor and materials. Tablet splitting is performed by certified pharmacy technicians using the Acu-Life pill splitter, model PS12E. This tablet splitter consists of a vertical razor blade in the upper platform that is perpendicular to a V-shaped stationary section for tablet placement in the lower platform. The V-shaped section of the splitter allows for symmetrical positioning of tablets to ensure an even split down the center. A tablet is split by applying firm pressure to the top platform to bring the razor blade to the bottom platform. Pharmacy technicians use one tablet splitter for each individual medication, thus preventing drug-residue transference that could result from using the same tablet splitter for multiple medications. It takes approximately 30 minutes for a pharmacy technician to split and package 30 tablets. Prior to packaging split lurasidone or aripiprazole tablets, pharmacists tested the ability to split these medications. It was determined that both of these medications split easily without crushing or crumbling.

The pharmacy has a system built into the electronic medical record (EMR) to allow for patients to be billed for half-tablets of aripiprazole and lurasidone. This results in a 50% cost-savings. In addition to our institution, health maintenance organizations, state Medicaid programs, and the Veterans Administration (VA) also report use of tablet splitting.14 Neither aripiprazole nor lurasidone are listed on the Institute for Safe Medication Practices Do Not Crush List.15 While no specific studies have tested content uniformity, stability, or pharmacodynamic or clinical implications of splitting these specific agents, previous literature suggests that many immediate-release tablets that lack certain characteristics (i.e., sublingual, enteric coated, or extended/delayed release mechansims) are safe to split or crush.16,17

Using tablet splitting for antipsychotic medications has several advantages for both the health system and the patient population. The primary advantage is the potential to decrease prescription costs by as much as 50%. One previous review of 12 psychotropic agents determined a potential cost-savings of $1.45 billion annually if all eligible prescription tablets were split.14 Polli and colleagues reported a one-year cost-savings of $565,000 from a tablet-splitting initiative in the VA Maryland Health Care System.18 Drugs included in this tablet-splitting initiative included high-cost agents with release mechanisms unmarred by splitting that were easy to cut in half with a standard pill-splitting device. Another review demonstrated simulated cost-savings for seven antidepressants.19 This review reported that 42% of all antidepressant pills sold in 2000 were at strengths amenable to tablet splitting, which if performed could have saved more than $1.7 billion.

Despite the potential for cost-savings when using the technique, some argue that splitting tablets may alter the effectiveness of the medication. Previous literature suggests varying results regarding the average percentage of weight deviation after tablet splitting. McDevitt and colleagues reported that 41% of tablets split deviated by more than 10% from their ideal weight.20 Rosenberg and colleagues evaluated variability of tablet halves and found that only 5.4% deviated by more than 15% from the ideal weight.21 In addition, a weight-uniformity study by Polli and colleagues performed at the VA Maryland Health Care System found that eight of 12 tested medications passed a weight uniformity test.18 They did not find that scored tablets clearly predicted passing the weight uniformity test. Authors from this study suggest that product hardness and shape may impact the ability to accurately split a particular tablet rather than tablet scoring. Deviation from ideal weight may be critical for certain medications, such as cardiovascular or thyroid agents, but antipsychotic medications are generally unaffected by small deviations. Antipsychotic agents are ideal to split because they do not have a narrow therapeutic index and their clinical effects are dependent on long-term alterations in neurotransmitter function production and receptor sensitivity, suggesting that a slight alteration in tablet dose will not impact overall efficacy.14

Previous literature suggests that appropriate product candidates for tablet splitting should not be sustained release or enteric coated and should not possess other release mechanisms that may be altered by splitting.18,22,23 Neither lurasidone nor aripiprazole are extended-release or sustained-release tablets, and their respective manufactuers do not specify that the tablets should not be split, crushed, or chewed.5,10 Neither product is scored, but they are manufactured in flat, symmetrical shapes, such as round tablets (aripiprazole 20 mg and lurasidone 20 mg and 40 mg) or oblong tablets (aripiprazole 5 mg and 10 mg and lurasidone 60 mg, 80 mg, and 120 mg) that are amenable to splitting.

Despite the potential for cost-savings, pill splitting may have some disadvantages. For example, there is increased pharmacist responsibility and time, questionable length of tablet stability, and patient confusion after discharge. We devised mitigation strategies around these issues to maximize the benefit of tablet splitting. In terms of pharmacist responsibility, the pharmacist only verifies the final product after a certified technician completes the accurate splitting of tablets. Pharmacy technicians use separate pill splitters for individual medications and strengths. The prepack-aged medications are given an expiration date of one year from the date of packaging or the manufacturer expiration date, whichever comes first. Addtionally, during order verification within the EMR, the pharmacist ensures that a medication that is already halved will not be halved a second time. For example, if lurasidone 40 mg is ordered, a half-tablet of 80 mg will be dispensed. If the dose is further decreased to 20 mg, the pharmacist will select a new item of a half 40-mg tablet to be dispensed. Pharmacists and nursing staff have been educated on this process at our facility to prevent medication errors. Patients are counseled by pharmacists and/or nursing staff upon discharge that the tablets they will receive at home are whole tablets and do not need to be split. Thus far, implementation of these strategies has assisted with the practicality and safety of tablet splitting for hospitalized patients.

METHODS

To evaluate the potential cost-savings related to tablet splitting at University Hospitals Richmond Medical Center, a chart review was completed for all patients who were dispensed aripiprazole or lurasidone oral tablets from May 1, 2015, through December 31, 2015. A computer-generated report through the EMR was used to identify patients prescribed these medications. Two-hundred thirty-five charts were reviewed from this eight-month period. Eight months was selected because it was felt that this would provide a reasonable time period and number of charts to appreciate average utilization of specific agents at our facility in order to project potential cost-savings. For each chart reviewed, only doses documented as being given by the nursing staff were counted as one dose. Each strength of each medication received a subtotal representative of the total number of tablets given per strength during the eight-month period. Charts that were excluded from our data collection included formulations of aripiprazole other than the tablet as well as patients who didn’t take a single dose during their stay. Data collection and cost-savings analysis was performed through Excel. Findings were extrapolated to 12 months to represent a potential annual cost-savings from tablet splitting (Table 2).

RESULTS

We evaluated the benefits and drawbacks of tablet splitting and found that our facility would benefit greatly from this practice. We serve a large mental health population that is mostly dependent on Medicare and Medicaid to cover health care costs. By cutting the costs of our patients’ medications, we are benefiting both the patients and the government-funded programs. Also, we selected medications that have at least a 30% to 50% cost-savings. Because these medications have a larger therapeutic window, the efficacy will likely not be altered by very small differences in tablet size. Aripiprazole and lurasidone are two of the most frequently used medications at our facility that meet this criteria. Table 2 displays the potential cost-savings for our patients from tablet splitting over a 12-month period.

DISCUSSION

At University Hospitals Richmond Medical Center, a potential cost-savings exists for splitting both aripiprazole and lurasidone at the specific strengths shown in Table 2. Among inpatients, both the hospital system and the patient have the opportunity to save 50% of the cost with every dose. Generic versions of aripiprazole were approved by the FDA in April 2015, so the current average wholesale price has decreased substantially, now ranging between $1.50 to $2.50 per tablet, meaning that the savings for this item have decreased. Still, with the continuation of the tablet-splitting program, we continue to save 50% on doses as prices fluctuate.

It is important to note that during the inpatient stay, certified technicians and pharmacists are responsible for tablet splitting to ensure proper splitting, eliminating barriers that could lead to inaccuracies. Patients admitted to our facility are not discharged with prescriptions for half-tablets, eliminating concerns for improper splitting. This was decided to avoid discharging patients who may be poor candidates for self-splitting of tablets, such as the elderly, persons with poor hand dexterity, visually impaired patients, patients with cognitive impairment or disorganized thinking, or patients taking multiple medications.14

Although several previous studies highlight weight variation from tablet splitting, no studies have been conducted to compare differences in efficacy outcomes between split versus whole antipsychotic tablets. However, given the mechanism of action of antipsychotic agents along with their larger therapeutic index, it seems unlikely that small weight variations would have clinically relevant effects on efficacy outcome measures.14 There is a paucity of data evaluating the impact of tablet splitting on chemical composition or tablet stability. One previous study of a drug with a narrow therapeutic index, levothyroxine, demonstrated that tablet splitting had no significant impact on chemical stability or content uniformity compared with whole tablets based on chemical assay measurements.24 While the majority of previous studies have focused on weight differences among split tablets, the more relevant question of impact on clinical efficacy has yet to be explored.

There are several limitations to the present study. Data collection was based on a retrospective chart review for a limited period: eight months, which was chosen to provide a reasonable sample representative of prescribing practices for lurasidone and aripiprazole at our hospital. The accuracy of administered doses included in cost data was dependent on the accuracy of nursing documentation within the EMR. This review did not study the average percentage of weight deviation after tablet splitting. Additionally, we did not analyze the impact of antipsychotic tablet splitting on chemical composition or stability. Lastly, this review does not allow for clinical conclusions, as no efficacy measures were assessed.

CONCLUSION

Many of the newer atypical antipsychotic medications are costly and can pose a significant financial burden for both government health care programs and private insurance companies. The practice of tablet splitting is of particular interest in patients with psychiatric conditions as this population has high utilization of the health care system. The Agency for Healthcare Research and Quality has reported data showing that hospitalizations for mental illness increased at a faster rate than any other type of hospitalization (including medical, surgical, injury, or maternal/neonatal) from 2003 to 2011.25 In addition, quality data from 2011 reported that patients with schizophrenia and mood disorders had the highest number of all-cause 30-day hospital readmissions among adult Medicaid patients.25 Our facility includes a large number of psychiatric beds because it houses the primary inpatient psychiatric units for the University Hospitals Healthcare System. Thus, development of cost-saving initiatives for this patient population is prudent both locally and at a system level. In our state, Medicare and Medicaid patients are unable to receive coverage for outpatient tablet splitting, but select patient populations may be eligible for this cost-savings. In the present study, we determined that an inpatient hospital tablet-splitting program for selected antipsychotic agents substantially decreases costs and drug waste while potentially increasing patient access to these valuable treatments.

Tables

Tablet-Splitting Plan Implemented in August 2015

Lurasidone
Currently Supplied Products Cost per Unit (Quantity = 30)* Cost per Dose*
 Lurasidone 40 mg $1,215.72 $40.52
 Lurasidone 80 mg $1,215.72 $40.52
Proposed Splitting
Orderable Dosage Product Supplied Cost per Dose*
 Lurasidone 20 mg One-half lurasidone 40-mg tablet $20.26
 Lurasidone 40 mg One-half lurasidone 80-mg tablet $20.26
 Lurasidone 80 mg Lurasidone 80-mg tablet $40.52
Aripiprazole
Currently Supplied Products Cost per Unit (Quantity = 30)* Cost per Dose
 Aripiprazole 2 mg $1,070.36 $35.68
 Aripiprazole 5 mg $1,070.36 $35.68
 Aripiprazole 10 mg $1,070.36 $35.68
 Aripiprazole 15 mg $1,070.36 $35.68
 Aripiprazole 20 mg $1,513.62 $50.45
Proposed Splitting
Orderable Dosage Product Supplied Cost per Dose
 Aripiprazole 2.5 mg One-half aripiprazole 5-mg tablet $17.84
 Aripiprazole 5 mg One-half aripiprazole 10-mg tablet $17.84
 Aripiprazole 15 mg Aripiprazole 10-mg tablet + 5-mg tablet $35.68
 Aripiprazole 10 mg One-half aripiprazole 20-mg tablet $25.22
 Aripiprazole 20 mg Aripiprazole 20-mg tablet $50.45

*Based on average wholesale price as of October 11, 2016.

Based on average wholesale price as of January 6, 2015.

Estimated Annual Cost-Savings at Time of Implementation*

Medication Number of Doses Original Annual Cost Annual Splitting Cost Annual Savings Annual Savings (%)
Aripiprazole 5-mg tablet 248 $13,273 $6,636 (10-mg tablet cut in half) $6,637 50%
Aripiprazole 10-mg tablet 391 $20,926 $10,463 (20-mg tablet cut in half) $10,463 50%
Lurasidone 20-mg tablet 119 $7,233 $3,616 (40-mg tablet cut in half) $3,617 50%
Lurasidone 40-mg tablet 125 $7,597 $3,798 (80-mg tablet cut in half) $3,799 50%

*Based on average wholesale prices as of October 11, 2016, for lurasidone and January 6, 2015, for aripiprazole.

Number of total doses administered to patients over the course of eight months; this is the basis for the annual estimate.

Author bio: 
Dr. Carey is a Clinical Specialist in Psychiatry at University Hospitals Richmond Medical Center in Richmond Heights, Ohio. Mr. Fondriest is Pharmacy Manager at that institution.

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