Sunflower Health Plan AUSTEDO, Deutetrabenazine Form

Deutetrabenazine (Austedo®, Austedo® XR) is a vesicular monoamine transporter 2 (VMAT2) inhibitor. FDA Approved Indication(s) Austedo and Austedo XR are indicated in adults for the treatment of: • Chorea associated with Huntington’s disease • Tardive dyskinesia (TD) in adults Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria. It is the policy of health plans affiliated with Centene Corporation® that Austedo or Austedo XR is medically necessary when the following criteria are met: I. Initial Approval Criteria A. Chorea Associated with Huntington Disease (must meet all): 1. Diagnosis of chorea associated with Huntington disease; 2. Prescribed by or in consultation with a neurologist; 3. Age ≥ 18 years; 4. Targeted mutation analysis demonstrates a cytosine-adenine-guanine (CAG) trinucleotide expansion of ≥ 36 repeats in the huntingtin (HTT) gene; 5. Evidence of chorea is supported by a Unified Huntington Disease Rating Scale (UHDRS) score ranging from 1 to 4 on any one of chorea items 1 through 7 (see Appendix D); 6. Failure of tetrabenazine (e.g., no improvement on any one of UHDRS chorea items 1 through 7) at up to 100 mg per day, unless contraindicated or clinically significant adverse effects are experienced; 7. Austedo/Austedo XR is not prescribed concurrently with tetrabenazine or Ingrezza®; 8. Dose does not exceed 48 mg per day. Approval duration: 6 months B. Tardive Dyskinesia (must meet all): 1. Diagnosis of TD secondary to treatment with a centrally acting dopamine receptor blocking agent (DRBA) (see Appendix G); 2. Prescribed by or in consultation with a psychiatrist or neurologist; Page 1 of 10 CLINICAL POLICY Deutetrabenazine 3. Age ≥ 18 years; 4. Evidence of moderate to severe TD is supported by an Abnormal Involuntary Movement Scale (AIMS) score of 3 or 4 on any one of items 1 through 9 (see Appendix H); 5. Failure of tetrabenazine (e.g., no improvement on any one of AIMS items 1 through 9) at up to 200 mg per day, unless contraindicated or clinically significant adverse effects are experienced; 6. Austedo/Austedo XR is not prescribed concurrently with tetrabenazine or Ingrezza; 7. Dose does not exceed 48 mg per day. Approval duration: 6 months C. Other diagnoses/indications (must meet 1 or 2): 1. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.PMN.16 for Medicaid; or 2. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.PMN.53 for Medicaid. II. Continued Therapy A. All Indications in Section I (must meet all): 1. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B); 2. Member meets one of the following (a or b): a. For Huntington disease: Member is responding positively to therapy as evidenced by a reduction since baseline in any one of UHDRS chorea items 1 through 7 (see Appendix D); b. For TD: Member is responding positively to therapy as evidenced by a reduction since baseline in any one of AIMS items 1 through 9 (see Appendix H); 3. Austedo/Austedo XR is not prescribed concurrently with tetrabenazine or Ingrezza; 4. If request is for a dose increase, new dose does not exceed 48 mg per day. Approval duration: 12 months Page 2 of 10 CLINICAL POLICY Deutetrabenazine B. Other diagnoses/indications (must meet 1 or 2): 1. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.PMN.16 for Medicaid; or 2. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.PMN.53 for Medicaid. III. Diagnoses/Indications for which coverage is NOT authorized: A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policies – CP.PMN.53 for Medicaid or evidence of coverage documents. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key AAN: American Academy of Neurology AIMS: Abnormal Involuntary Movement Scale APA: American Psychiatry Association DRBA: dopamine receptor blocking agent DSM V: Diagnostic and Statistical Manual, Version 5 FDA: Food and Drug Administration HTT: huntingtin MAOI: monoamine oxidase inhibitor TD: tardive dyskinesia UHDRS: Unified Huntington Disease Rating Scale VMAT: vesicular monoamine transporter Appendix B: Therapeutic Alternatives This table provides a listing of preferred alternative therapy recommended in the approval criteria. The drugs listed here may not be a formulary agent for all relevant lines of business and may require prior authorization. Drug Name Dosing Regimen Dose Limit/ Maximum Dose 25 mg/dose and 50 mg/day (37.5 mg/dose and 100 mg/day for CYP2D6 intermediate or extensive metabolizers) 200 mg/day in divided doses tetrabenazine (Xenazine) Huntington’s Chorea 12.5 mg PO QD for 1 week, then 12.5 mg BID, then titrated by 12.5 mg weekly to a tolerated dose up to maximum of 50 mg/day (100 mg/day for CYP2D6 intermediate or extensive metabolizers) TD (off-label) Typical dosing range (mg/day): 25-75 Comments: Give in divided doses: increase from initial dose of 25-50 mg/day by 12.5 mg/week to Page 3 of 10 CLINICAL POLICY Deutetrabenazine Drug Name Dosing Regimen Dose Limit/ Maximum Dose maximum of 150-200 mg/day. Retitrate dose for treatment interruptions of more than 5 days. Test for CYP2D6 metabolizer status before giving doses > 50 mg/day. Do not exceed 50 mg/day in poor metabolizers or in patients treated with a strong inhibitor of CYP2D6. The American Psychiatric Association practice guideline for the treatment of patients with schizophrenia. 2020. Third Ed. Therapeutic alternatives are listed as Brand name® (generic) when the drug is available by brand name only and generic (Brand name®) when the drug is available by both brand and generic. Appendix C: Contraindications/Boxed Warnings • Contraindication(s): o Suicidal or untreated/inadequately treated depression in patients with Huntington’s disease o Hepatic impairment o Taking reserpine, MAOIs, tetrabenazine or valbenazine • Boxed warning(s): depression and suicidality in patients with Huntington’s disease Appendix D: Chorea and the Unified Huntington Disease Rating Scale (UHDRS) • The UHDRS encompasses motor, behavioral, cognitive, and functional components for use in evaluating patients with Huntington disease and is commonly used in both research and clinical practice. • The American Academy of Neurology (AAN) guidelines evaluating pharmacologic therapies for chorea associated with Huntington disease describe the chorea subscore of the UHDRS motor component as a rating of 7 body regions (facial, bucco-oral-lingual, trunk, extremities) on a five-point scale from 0 to 4 with 0 representing no chorea. • See Huntington Study Group 1996 and Mestre et al. 2018 for additional information about the UHDRS. (AAN Guidelines 2012, Huntington Study Group 1996, Mestre 2018) Appendix E: Tardive Dyskinesia General Information • The 2020 American Psychiatric Association (APA) Practice Guideline for the Treatment of Patients With Schizophrenia recommends that patients who have moderate to severe or disabling TD be treated with a reversible VMAT2 inhibitor (i.e., deutetrabenazine, tetrabenazine, and valbenazine); the guideline notes that the AIMS tool can be instrumental in such decision-making. • Medication-induced movement disorders, including tardive dyskinesia, are organized in the DSM V as follows: neuroleptic-induced parkinsonism/other medication-induced parkinsonism, neuroleptic malignant syndrome, medication-induced acute dystonia, medication-induced acute akathisia, tardive dyskinesia, tardive dystonia/tardive akathisia, medication-induced postural tremor, other medication-induced movement disorder, antidepressant discontinuation syndrome, and other adverse effects of medication. Page 4 of 10 CLINICAL POLICY Deutetrabenazine • Tardive dyskinesia is a type of movement disorder that occurs secondary to therapy with centrally acting DRBAs (see Appendix F). (DSM V) • Typical therapeutic drug classes containing DRBAs include first- and second-generation antipsychotics, antiemetics, and tri-cyclic antidepressants (see Appendix G). (DSM V) • Other therapeutic drug classes containing agents that have been variously associated with movement disorders are listed below: (Waln 2013, Meyer 2014, Lerner 2015) o Antiarrhythmics o Antibiotics o Anticholinergics o Antidepressants o Antiepileptics o Antihistamines o Antimanics o Bronchodilators o Calcium channel blockers o Central nervous system stimulants o Dopamine agonists o Dopamine depleting agents o Dopaminergics o Glucocorticoids o Immunosuppressants o Mood stabilizers o Muscle relaxants o Oral contraceptives Appendix F: Tardive Dyskinesia: DSM-V Definition Tardive Dyskinesia (ICD-9 333.85/ICD-10 G24.01) • Involuntary athetoid or choreiform movements (lasting at least a few weeks) generally of the tongue, lower face and jaw, and extremities (but sometimes involving the pharyngeal, diaphragmatic, or trunk muscles) developing in association with the use of a neuroleptic medication for at least a few months. • Symptoms may develop after a shorter period of medication use in older persons. In some patients, movements of this type may appear after discontinuation, or after change or reduction in dosage, of neuroleptic medications, in which case the condition is called neuroleptic withdrawal emergent dyskinesia. Because withdrawal emergent dyskinesia is usually time limited, lasting less than 4-8 weeks, dyskinesia that persists beyond this window is considered to be tardive dyskinesia. Appendix G: Tardive Dyskinesia: Centrally Acting Dopamine Receptor Blocking Agents (Neuroleptics) Pharmacologic Class Tri-cyclic antidepressants Amoxapine† First-generation (typical) antipsychotics Chlorpromazine Fluphenazine Perphenazine Thioridazine Thiothixene Trifluoperazine Haloperidol Phenothiazine Butryophenone Substituted benzamide Dibenzazepine Loxapine Therapeutic Class Antiemetic agents Chlorpromazine Perphenazine Prochlorperazine Promethazine* Thiethylperazine Droperidol Haloperidol** Metoclopramide Trimethobenzamide Page 5 of 10 CLINICAL POLICY Deutetrabenazine Pharmacologic Class First-generation (typical) antipsychotics Therapeutic Class Antiemetic agents Tri-cyclic antidepressants Second-generation (atypical) antipsychotics Diphenylbutylpiperidine Pimozide Pharmacologic Class Quinolone Dibenzazepine Piperazine Dibenzodiazephine Benzisoxazole Benzisothiazole Thienobenzodiazepine Pyrimidinone (DSM V, Meyer 2014, Smith 2010, Clinical Pharmacology, Lexicomp) *First generation H1 antagonist **Off-label use †A dibenzoxapine that shares properties with phenothiazines Aripiprazole, brexpiprazole Asenapine Cariprazine Clozapine, quetiapine Iloperidone Lurasidone, ziprasidone Olanzapine Paliperidone, risperidone Appendix H: The Abnormal Involuntary Movement Scale (AIMS) • The AIMS is a clinician-rated 12-item assessment tool developed by the National Institute of Mental Health to evaluate severity of involuntary movements in multiple movement disorders including TD. The AIMS is commonly used in both research and clinical practice. • AIMS items 1-10 are rated on a 5-point scale (0 - none; 1 - minimal; 2 - mild; 3 - moderate; 4 - severe). Items 1-7 assess dyskinesia severity by body region (items 1-4 orofacial; items 5-7 extremity and trunk). Items 8-10 assess overall severity, incapacitation, and patient awareness respectively - item 8 uses the highest score of any one of items 1-7. Items 11 (dental) and 12 (dentures) are yes/no questions which help characterize lip, jaw, and tongue movements. • See Munetz 1988 for additional information about the AIMS. V. Dosage and Administration Indication Huntington’s chorea TD Dosing Regimen When not switching from tetrabenazine: Recommended starting dose • Austedo XR: 12 mg PO QD • Austedo: 6 mg PO BID Titrate at weekly intervals by 6 mg/day based on reduction of chorea or tardive dyskinesia, and tolerability, up to a maximum recommended daily dosage of 48 mg. When switching between Austedo and Austedo XR, switch to the same total daily dosage. Maximum Dose 48 mg/day (36 mg/day in poor CYP2D6 metabolizers or with strong CYP2D6 metabolizers) Page 6 of 10 CLINICAL POLICY Deutetrabenazine Indication Dosing Regimen When switching from tetrabenazine: see Prescribing Information dosage chart Maximum Dose VI. Product Availability Drug Name Austedo Austedo XR Availability Immediate-release tablets: 6 mg, 9 mg, 12 mg Extended-release tablets: 6 mg, 12 mg, 24 mg VII.