UTAH MEDICAID DUR REPORT JANUARY 2021 LONG-ACTING INJECTABLE & ORALLY DISINTEGRATING SECOND GENERATION ANTIPSYCHOTICS Report Finalized in December 2020 Report Presented in January 2021 Drug Regimen Review Center Valerie Gonzales, Pharm.D., Clinical Pharmacist Lauren Heath, Pharm.D., MS, BCACP, Assistant Professor Vicki Frydrych, B.Pharm., Pharm.D., Clinical Pharmacist Joanne LaFleur, PharmD, MSPH, Associate Professor University of Utah College of Pharmacy Copyright © 2021 by University of Utah College of Pharmacy Salt Lake City, Utah. All rights reserved 1 | Page Contents Introduction ............................................................................................................................................................ 4 Table 1. Long-Acting Injectable SGAs, FDA Indicated Disorders ........................................... 4 Table 2. ODT Antipsychotics, FDA Indicated Disorders ............................................................ 5 Methods .................................................................................................................................................................... 5 A. Long-Acting, Injectable Second-Generation Antipsychotics ........................................................ 6 Diagram 1. Administration Frequency for LAI Products .......................................................... 7 Administration of early doses ................................................................................................................. 8 A.1. Concomitant Use of LAI and Oral Antipsychotics ........................................................................ 8 When initiating LAI antipsychotics ....................................................................................................... 8 If a missed dose occurs .............................................................................................................................. 9 When metabolism modifiers are prescribed ..................................................................................... 9 Management of Breakthrough Psychosis ........................................................................................ 10 A.2. Additional Tables and Considerations for LAI Products ....................................................... 11 Switching from Other LAIs .................................................................................................................... 11 Table 3. Product Prescribing Information Regarding Switching Therapies .................. 11 Unique Safety Warnings for SGA LAIs ............................................................................................... 12 Table 4. Second Generation, LAI Antipsychotics and Labeled Dosing ............................. 13 Table 5. Pharmacokinetics for LAI SGAs ...................................................................................... 15 A.3. Place in Therapy .................................................................................................................................... 17 Overview of Potential Advantages and Disadvantages of LAI Antipsychotics .................. 17 Place in Therapy per Clinical Guidelines .......................................................................................... 18 For Schizophrenia ................................................................................................................................. 18 For Bipolar I Disorder ......................................................................................................................... 19 Pediatric Use ............................................................................................................................................... 19 B. ODT Products .............................................................................................................................................. 20 B.1. ODT Product Description ................................................................................................................... 20 Table 6. ODT Second Generation Antipsychotics, Approved Indications ...................... 20 Table 7. ODT Product Pharmacokinetic Information ............................................................. 21 B.2. Place in Therapy for ODT Products ................................................................................................ 22 Adherence or Compliance ...................................................................................................................... 22 2 | Page Further Information Regarding Rapid Mitigation of Acute Agitation/Aggression Associated with Various Psychiatric Disorders ............................................................................. 23 Prior Authorization (PA) Considerations ................................................................................................. 25 Summary ............................................................................................................................................................... 27 References ............................................................................................................................................................ 28 Appendix A: Literature Searches ................................................................................................................. 32 Appendix B: Treatment Guidelines Addressing Rapid Mitigation of Acute Agitation/Aggression ....................................................................................................................................... 33 3 | Page Introduction This document compliments the December 2020 DUR report, Newer Oral Antipsychotics, that reviewed second generation antipsychotics (SGAs*) and their place in therapy, with focus on 3 newer drug moieties. This report describes considerations regarding the SGA long-acting injectable (LAI) and orally disintegrating tablet (ODT) formulations, their place in therapy according to guideline recommendations, potential advantages, and unique features or directions for use. LAI antipsychotics offer the potential for improved adherence with less frequent dosing intervals compared to daily oral regimens. These agents must be administered directly by a healthcare provider. The 8 available LAI SGA products are shown in Table 1; all are intramuscular (IM) injections except the subcutaneous product, Perseris. Each LAI SGA is approved for use in schizophrenia. Additionally, Invega Sustenna is approved for schizoaffective disorder; and Abilify Maintena and Risperdal Consta are approved for bipolar I disorder.1-8 None are FDA labeled for use in the pediatric population. Labeling recommendations for initiation of LAI therapy vary. Invega Trinza is indicated for patients who have received at least 4 months of Invega Sustenna therapy. For other LAIs, patients should have tolerated the corresponding oral antipsychotic prior to initiation (or risperidone for Invega Sustenna). Supplementation with an oral antipsychotic is required during the initiation of Abilify Maintena, Aristada, and Risperdal Consta. Aristada Initio is used as a single loading dose for initiation of Aristada, or as a single supplementation dose following a missed Aristada dose. Table 1. Long-Acting Injectable SGAs, FDA Indicated Disorders 1-8, a LAI Product (administration interval) Aripiprazole Aripiprazole Olanzapine Paliperidone palmitate Risperidone lauroxil pamoate Abilify Aristada Zyprexa Invega Invega Risperdal Perseris Maintena (monthly – Relprevv Sustenna Trinzac Consta (monthly) (monthly) 2 months) (2-4 weeks) (monthly) (3 months) (2 weeks) Aristada Initiob Bipolar I disorder X X Schizophrenia X X X X Xd X X Schizoaffective X disorder a Per labeling, Abilify Maintena has not been studied in patients 18 years or younger, and the other LAIs have not been established in patients less than 18 years of age. b Aristada Initio is only to be used as a single dose, as part of the loading dose phase for initiation of Aristada or as a single supplementation dose in the event of a missed dose of Aristada. c Invega Trinza is for patients who stabilized onto at least 4 months of Invega Sustenna. d Prescribing information recommends against use in the pediatric population. Four ODT antipsychotics are available as shown in Table 2. These formulations were developed to increase usability in patients with difficulty swallowing tablets. Experts note that the ODT formulation may also help circumvent discreet non-compliance (“cheeking”).9 The ODT antipsychotics have the same indications as their conventional-tablet counterpart but are quickly dissolved once placed on the * For this report, we will use the terminology of SGA, with third generation antipsychotics included among SGAs. 4 | Page tongue— usually dissolved within 1 minute—and the dissolution contents can be more easily swallowed without liquid. Aside from other solid dosage forms, 3 of these ODT drug moieties are also available as oral solutions (aripiprazole generic solution, clozapine as a brand product [Versacloz], and risperidone generic solution), while olanzapine is unavailable as an oral solution. Table 2. ODT Antipsychotics, FDA Indicated Disorders10-15 Aripiprazole Clozapine Olanzapine Risperidone ODT ODT ODT ODT Zyprexa Zydis Generic Generic Generic and Generic Bipolar I disorder (acute X X (also for X treatment for manic/mixed maintenance episodes) treatment) Schizophrenia X X (for treatment resistant X X (and Schizoaffective disorder for disease,