NUEDEXTA, Dextromethorphan HBr-Quinidine Sulfate Form

Dextromethorphan and quinidine (Nuedexta®) is a fixed-dose combination of dextromethorphan hydrobromide, an N-methyl-D-aspartate (NMDA) receptor antagonist and sigma-1 agonist, and quinidine sulfate, a CYP450 2D6 inhibitor. FDA Approved Indication(s) Nuedexta is indicated for the treatment of pseudobulbar affect (PBA). Policy/Criteria Provider must submit documentation (including 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 Nuedexta is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Pseudobulbar Affect (must meet all):

1. Diagnosis of PBA secondary to multiple sclerosis or amyotrophic lateral sclerosis;
   2. Prescribed by or in consultation with a neurologist, neuropsychologist, or psychiatrist;
   3. Age ≥ 18 years;
   4. Baseline Center for Neurologic Study-Lability Scale (CNS-LS) score > 13 (see Appendix C);
2. Dose does not exceed 40 mg dextromethorphan and 20 mg quinidine (2 capsules) per day. Approval duration: 12 weeks
   B. Other diagnoses/indications (must meet 1 or 2):

3. 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.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and 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: Page 1 of 6

   CLINICAL POLICY Dextromethorphan-Quinidine CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or

4. 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.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
   II. Continued Therapy A. Pseudobulbar Affect (must meet all):
5. 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);
6. Member is responding positively to therapy as evidenced by, including but not limited to, a decreased frequency of PBA episodes or a decrease in the CNS-LS score of ≥ 3 points from baseline (see Appendix C);
7. If request is for a dose increase, new dose does not exceed 40 mg dextromethorphan and 20 mg quinidine (2 capsules) per day.
   Approval duration: 12 months B. Other diagnoses/indications (must meet 1 or 2):
8. 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.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and 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.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or

9. 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.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and 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.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid, or evidence of coverage documents.
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   CLINICAL POLICY Dextromethorphan-Quinidine IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key ALS: amyotrophic lateral sclerosis FDA: Food and Drug Administration MS: multiple sclerosis
   Appendix B: Therapeutic Alternatives
   Not applicable NMDA: N-methyl-D-aspartate PBA: pseudobulbar affect Appendix C: Contraindications/Boxed Warnings • Contraindication(s): concomitant use with quinidine, quinine, or mefloquine; history of quinidine, quinine or mefloquine-induced thrombocytopenia, hepatitis, or other hypersensitivity reactions; known hypersensitivity to dextromethorphan; use with an MAOI or within 14 days of stopping an MAOI; prolonged QT interval, congenital long QT syndrome, history suggestive of Torsade’s de Pointes, or heart failure; complete atrioventricular (AV) block without implanted pacemaker, or patients at high risk of complete AV block; concomitant use with drugs that both prolong QT interval and are metabolized by CYP2D6 (e.g., thioridazine or pimozide). • Boxed warning(s): none reported. Appendix C: General Information
   • Nuedexta was studied in 367 patients with PBA secondary to dementia, stroke, or traumatic brain injury. Although use of Nuedexta resulted in statistically significant improvement from baseline in CNS-LS scores, applicability of this data in clinical practice is limited as the study was open-label and not compared to placebo.
   • There is one randomized, double-blind, placebo-controlled phase 2 trial evaluating the use of Nuedexta in 220 patients with aggression or agitation secondary to Alzheimer’s disease over 10 weeks. Nuedexta showed that the treatment difference in Neuropsychiatric Inventory (NPI) Agitation/Aggressive scores was -1.8 (95% CI, -2.8 to -0.7, p = 0.003) compared to placebo. Although this outcome was statistically significant, it did not meet the prespecified difference of 2.5 points. Also, unlike the total NPI score, use of the single NPI domain of agitation/aggression is not well validated as an endpoint. Additional long-term data is needed to confirm evidence of benefit and safety.
   • The CNS-LS is a short (seven-item), self-administered questionnaire, designed to be completed by the patient, that provides a quantitative measure of the perceived frequency of PBA episodes. Each question is scored from 1 (applies never) to 5 (applies most of the time). A CNS-LS score of 13 or higher may suggest PBA. A complete list of included questions is available at: https://www.nuedextahcp.com/documents/CNS-LS-English.pdf V. Dosage and Administration
   Indication PBA Dosing Regimen 1 capsule PO QD for the initial 7 days, then 1 capsule PO BID for maintenance Maximum Dose Dextromethorphan 40 mg/quinidine 20 mg/day Page 3 of 6

   CLINICAL POLICY Dextromethorphan-Quinidine VI. Product Availability
   Capsules: dextromethorphan hydrobromide 20 mg combined with quinidine sulfate 10 mg VII.