Levodopa Inhalation Powder (Inbrija) Form

Levodopa inhalation powder (Inbrija®) is an aromatic amino acid. FDA Approved Indication(s) Inbrija is indicated for the intermittent treatment of OFF episodes in patients with Parkinson’s disease (PD) treated with carbidopa/levodopa. 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 Inbrija is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Parkinson’s Disease (must meet all):

1. Diagnosis of PD;
   2. Prescribed by or in consultation with neurologist;
   3. Age ≥ 18 years;
   4. Inbrija will be used as intermittent treatment for OFF episodes;
   5. Prescribed concurrently with carbidopa/levodopa at a dose not exceeding 1,600 mg levodopa per day;
2. Member is experiencing motor fluctuations with a minimum of 2 hours of average daily "off" time per waking day (excluding early morning "off" time) while on carbidopa/levodopa therapy (see Appendix D);

3. Failure of at least two anti-Parkinson agents from different therapeutic classes, unless clinically significant adverse effects are experienced or all are contraindicated:
   a. MAO-B inhibitor: rasagiline; b. COMT inhibitor: entacapone (Comtan®/Stalevo®), tolcapone; c. Dopamine agonist: ropinirole/ropinirole ER, pramipexole/pramipexole ER; Prior authorization may be required for the above agents

   8. Dose does not exceed both of the following (a and b):
      a. 84 mg (two capsules) per inhalation;
      b. Five inhalations (420 mg) per day. Approval duration: 12 months Page 1 of 6

   CLINICAL POLICY Levodopa Inhalation Powder B. Other diagnoses/indications (must meet 1 or 2):

4. 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
5. 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. Parkinson’s Disease (must meet all):
6. 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 is responding positively to therapy;
   3. Member continues to receive concurrent treatment with carbidopa/levodopa;
   4. If request is for a dose increase, new dose does not exceed both of the following (a and b):
      a. 84 mg (two capsules) per inhalation;
      b. Five inhalations (420 mg) per day. Approval duration: 12 months B. Other diagnoses/indications (must meet 1 or 2):

7. 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 Page 2 of 6

   CLINICAL POLICY Levodopa Inhalation Powder

8. 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. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key COMT: catechol-O-methyl transferase FDA: Food and Drug Administration MAO-B: monoamine oxidase type B
   PD: Parkinson’s disease 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 entacapone (Comtan) tolcapone (Tasmar®) PO: 100 mg 3 times daily, as adjunct to COMT Inhibitors carbadopa/levodopa/ entacapone (Stalevo) MAO-B Inhibitors rasagiline (Azilect) Dopamine Agonists pramipexole (Mirapex) PO: Dose should be individualized based on therapeutic response; doses may be adjusted by changing strength or adjusting interval. Fractionated doses are not recommended and only 1 tablet should be given at each dosing interval. PO: 200 mg with each dose of levodopa/carbidopa levodopa/carbidopa PO: Monotherapy or adjunctive therapy (not including levodopa): 1 mg once daily. Adjunctive therapy with levodopa: Initial: 0.5 mg once daily; may increase to 1 mg once daily based on response and tolerability.
   1,200 mg levodopa/day
   1,600 mg/day
   300 mg/day 1 mg/day PO: Initial dose: 0.125 mg 3 times daily, increase gradually every 5 to 7 days; maintenance (usual): 0.5 to 1.5 mg 3 times daily 4.5 mg/day
   Page 3 of 6

   CLINICAL POLICY Levodopa Inhalation Powder Drug Name Dosing Regimen pramipexole ER (Mirapex ER) ropinirole (Requip) ropinirole ER (Requip ER) PO: Initial dose: 0.375 mg once daily; increase gradually not more frequently than every 5 to 7 days to 0.75 mg once daily and then, if necessary, by 0.75 mg per dose PO: Recommended starting dose: 0.25 mg 3 times/day. Based on individual patient response, the dosage should be titrated with weekly increments: Week 1: 0.25 mg 3 times/day; total daily dose: 0.75 mg; week 2: 0.5 mg 3 times/day; total daily dose: 1.5 mg; week 3: 0.75 mg 3 times/day; total daily dose: 2.25 mg; week 4: 1 mg 3 times/day; total daily dose: 3 mg. After week 4, if necessary, daily dosage may be increased by 1.5 mg/day on a weekly basis up to a dose of 9 mg/day, and then by up to 3 mg/day weekly to a total of 24 mg/day.
   PO: Initial dose: 2 mg once daily for 1 to 2 weeks, followed by increases of 2 mg/day at weekly or longer intervals based on therapeutic response and tolerability Dose Limit/ Maximum Dose 4.5 mg/day 24 mg/day
   24 mg/day 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): concomitant use of nonselective monoamine oxidase (MAO) inhibitor (e.g., phenelzine, tranylcypromine) or have recently (within 2 weeks) taken a nonselective MAO inhibitor • Boxed warning(s): none reported
   Appendix D: General Information • Off time/episodes represent a return of Parkinson’s disease symptoms (bradykinesia, rest tremor or rigidity) when the L-dopa treatment effect wears off after each dosing interval. • Parkinson’s disease symptoms, resulting from too little levodopa (L-dopa), are in contrast with dyskinesia which typically results from too much L-dopa. The alterations between “on” time (the time when Parkinson’s disease symptoms are successfully suppressed by L-dopa) and “off” time is known as “motor fluctuations”. • The addition of carbidopa to L-dopa prevents conversion of L-dopa to dopamine in the systemic circulation and liver. V. Dosage and Administration
   Indication PD
   Dosing Regimen Inhale the contents of two capsules (84 mg) as needed for OFF symptoms, up to 5 times daily Maximum Dose 84 mg/dose, 420 mg/day Page 4 of 6

   CLINICAL POLICY Levodopa Inhalation Powder VI. Product Availability
   Inhalation powder: one capsule contains 42 mg levodopa; carton containing 4 capsules, 12 capsules, 60 capsules or 92 capsules VII.