ABSTRAL, Fentanyl Citrate SUBSYS, Fentanyl LAZANDA, Fentanyl Citrate FENTORA, Fentanyl Citrate ACTIQ, Fentanyl Citrate Form

The following are potent opioid agonist products requiring prior authorization: oral transmucosal fentanyl citrate lozenge (Actiq®), fentanyl buccal tablet (Fentora®), fentanyl nasal spray (Lazanda®), fentanyl sublingual spray (Subsys®).
____ *For Health Insurance Marketplace (HIM), if request is through pharmacy benefit, Fentora and Lazanda are non- formulary and should not be approved using these criteria; refer to the formulary exception policy, HIM.PA.103.
FDA Approved Indication(s) Transmucosal immediate release fentanyl products are indicated for the management of breakthrough pain in cancer patients (≥ 16 years old for Actiq and ≥ 18 years old for Fentora, Lazanda, and Subsys) who are already receiving and who are tolerant to around-the-clock opioid therapy for their underlying persistent cancer pain. Patients considered opioid tolerant are those who are taking, for one week or longer, around-the- clock medicine consisting of at least 60 mg of oral morphine per day, at least 25 mcg of transdermal fentanyl per hour, at least 30 mg of oral oxycodone per day, at least 8 mg of oral hydromorphone per day, at least 25 mg oral oxymorphone per day, at least 60 mg oral hydrocodone per day, or an equianalgesic dose of another opioid daily for a week or longer. Patients must remain on around-the-clock opioids while taking Actiq, Fentora, Lazanda, or Subsys. Limitation(s) of use: • Not for use in opioid non-tolerant patients. • Not for use in the management of acute or postoperative pain, including headache/migraine, dental pain, or in the emergency room. • As a part of the Transmucosal Immediate Release Fentanyl Risk Evaluation and Mitigation Strategy (TIRF REMS) Access program, potent opioid agonist products may be dispensed only to outpatients enrolled in the program. For inpatient administration (e.g., hospitals, hospices, and long-term care facilities that prescribe for inpatient use), patient and prescriber enrollment is not required. 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.
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CLINICAL POLICY Transmucosal Immediate-release Fentanyl It is the policy of health plans affiliated with Centene Corporation® that Actiq, Fentora, Lazanda, and Subsys are medically necessary when the following criteria are met:
I. Initial Approval Criteria
Please note: for HIM-Arkansas – if a member's covered prescription pain medication requires a prior authorization, then the prior authorization shall not be denied if the member has a terminal illness. A. Cancer Pain (must meet all):

1. Diagnosis of cancer pain;
2. Prescribed for the management of breakthrough pain;
3. Member is on fentanyl transdermal patches;
4. For Actiq requests, age ≥ 16 years;
5. For Fentora, Lazanda, or Subsys requests, age ≥ 18 years;

6. Failure of a trial of two formulary short-acting opioid analgesics, unless clinically significant adverse effects are experienced or all are contraindicated;

   7. For brand Actiq, Fentora, Lazanda and Subsys requests: Member must use generic fentanyl citrate oral transmucosal lozenge (Actiq), unless contraindicated or clinically significant adverse effects are experienced;
   8. A treatment plan is required, including: a. Pain intensity (scales or ratings); b. Functional status (physical and psychosocial); c. Patient`s goal of therapy (level of pain acceptable and/or functional status); d. Current analgesic (opioid and adjuvant) regimen; e. Current non-pharmacological treatment; f. Opioid-related side effects; g. Indications of medical misuse; h. Action plan if analgesic failure occurs;
   9. For Actiq requests on the HIM plan: Dose does not exceed 4 lozenges per day. Approval duration:
      Medicaid/Commercial – 6 months HIM – 6 months (refer to HIM.PA.103 for Fentora and Lazanda) B. Other diagnoses/indications (must meet 1 or 2):
   10. 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 9

   CLINICAL POLICY Transmucosal Immediate-release Fentanyl

   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.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
      II. Continued Therapy Please note: for HIM-Arkansas – if a member's covered prescription pain medication requires a prior authorization, then the prior authorization shall not be denied if the member has a terminal illness. A. Cancer Pain (must meet all):
   3. 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);
   4. Member is responding positively to therapy as evidenced by reduction in breakthrough pain without significant toxicity
   5. For Actiq requests on the HIM plan: Dose does not exceed 4 lozenges per day.
      Approval duration:
      Medicaid/Commercial – 12 months HIM – 12 months (refer to HIM.PA.103 for Fentora and Lazanda) B. Other diagnoses/indications (must meet 1 or 2):
   6. 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
   7. 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 – Page 3 of 9

   CLINICAL POLICY Transmucosal Immediate-release Fentanyl 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 FDA: Food and Drug Administration REMS: Risk Evaluation and Mitigation Strategy TIRF: transmucosal immediate-release fentanyl Dose Limit/ Maximum Dose Varies
   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 formulary agents for all relevant lines of business and may require prior authorization.
   Drug Name Dosing Regimen Varies morphine sulfate
   immediate-release 10 mg – 30 mg PO Q 4 H PRN
   Individualize dosage based on extent of pre- existing opioid tolerance
   5 mg - 15 mg PO Q 4 to 6 H PRN
   Individualize dosage based on extent of pre- existing opioid tolerance
   2 mg – 4 mg PO Q 3 to 4 H PRN
   Individualize dosage based on extent of pre- existing opioid tolerance
   5 mg – 20 mg PO Q 4 to 6 H PRN
   Individualize dosage based on extent of pre- existing opioid tolerance
   Apply one patch topically every 72 hours oxycodone immediate-release (Roxicodone®)
   hydromorphone immediate-release (Dilaudid®)
   oxymorphone immediate-release (Opana®)
   fentanyl transdermal patches (Duragesic®) 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. Varies
   Varies
   Varies Appendix C: Contraindications/Boxed Warnings • Contraindication(s): opioid non-tolerant patients; management of acute or postoperative pain including headache/migraines dental pain or use in the emergency department; significant respiratory depression; acute or severe bronchial asthma in an unmonitored setting or in absence of resuscitative equipment; gastrointestinal obstruction, including paralytic ileus; hypersensitivity to fentanyl or components of the fentanyl product. • Boxed Warning(s): life-threatening respiratory depression; accidental ingestion; cytochrome P450 3A4 interactions; risk of medication errors; risks from concomitant use with benzodiazepines or other CNS depressants; addiction, abuse, and misuse; REMS access program; neonatal opioid withdrawal syndrome. Appendix D: General Information • Because of the potential risk for misuse, abuse, and overdose, the fentanyl sublingual and transmucosal products listed below are only available through restricted distribution Page 4 of 9

   CLINICAL POLICY Transmucosal Immediate-release Fentanyl programs. Under the TIRF REMS program, only prescribers, pharmacies, and patients registered with TIRF REMS are able to prescribe, dispense, and receive these products. Additional information is available at: www.tirfremsaccess.com/TirfUISplashWeb/index.html or by calling 1-866-822-1483. • These products are not interchangeable and must not be used in opioid non-tolerant patients because life-threatening hypoventilation could occur at any dose in patients not taking chronic opiates. Substantial differences exist in the pharmacokinetic profiles of these drugs that result in clinically important differences in the extent of absorption of fentanyl. As a result of these differences, the substitution of these products may result in fatal overdose. Patients considered opioid tolerant are those who are taking around the clock medicine consisting of at least 60 mg morphine/day, at least 25 mcg transdermal fentanyl/hour, at least 30 mg of oxycodone daily, at least 8 mg oral hydromorphone daily, or an equianalgesic dose of another opioid for a week or longer. • Fentanyl absorption with different formulations of transmucosal delivery systems can be substantially different. Patients should not be converted on a mcg per mcg basis between any transmucosal fentanyl products. • The initial dose of Fentora and Subsys is always 100 mcg with the only exception being patients already using Actiq. Patients switching from Actiq to Fentora or Subsys should be initiated as shown:
   Actiq dose (mcg) Fentora dose (mcg) Subsys dose (mcg)
   100 100 200 200 400 400 200 400 600 800 1200 1600 100 100 200 200 400 400 V. Dosage and Administration
   Drug Name Dosing Regimen Oral transmucosal fentanyl citrate (Actiq)
   Initiate dosing with 200 mcg PO and if breakthrough episode is not relieved in 30 minutes, patients may take only 1 additional dose using the same strength and must wait at least 4 hours before taking another dose. Individually titrate to a dose that provides adequate analgesia using single dosage unit per breakthrough cancer pain episode and minimizes side effects. Initial prescription recommendation for maximum of 6 units; Once a successful dose has been found, use no more than 4 doses per day; separate by at least 4 hours.
   Initiate dosing with 100 mcg PO and if breakthrough episode is not relieved in 30 minutes, patients may take only 1 additional dose using the same strength and must wait Maximum Dose Varies
   If more than 4 episodes of breakthrough pain are experienced per day, the dose of the long-acting opioid used for persistent underlying cancer pain should be re-evaluated Varies
   If more than 4 episodes of breakthrough pain are Oral transmucosal fentanyl Page 5 of 9

   CLINICAL POLICY Transmucosal Immediate-release Fentanyl Drug Name Dosing Regimen citrate (Fentora)
   at least 4 hours before taking another dose. Maximum: 4 tablets simultaneously
   Fentanyl nasal spray (Lazanda)
   Fentanyl sublingual spray (Subsys)
   Initial dose of Lazanda for all patients is 100 mcg (one spray) into one nostril. Individually titrate to an effective dose, from 100 mcg to 200 mcg to 400 mcg, and up to a maximum of 800 mcg, that provides adequate analgesia with tolerable side effects. Dose is a single spray into one nostril or a single spray into each nostril (2 sprays), three single sprays (alternating nostrils), or two sprays into each nostril (4 sprays). Maximum dose is a single spray into one nostril or single spray into each nostril per episode; no more than four doses per 24 hours. Wait at least 2 hours before treating another episode of breakthrough pain with Lazanda.
   Initial dose of Subsys: 100 mcg SL except patients already using Actiq. Individually titrate to a tolerable dose that provides adequate analgesia using a single Subsys dose per breakthrough cancer pain episode. No more than two doses can be taken per breakthrough pain episode. Wait at least 4 hours before treating another episode of breakthrough pain with Subsys. Limit consumption to four or fewer doses per day once successful dose is found.
   Maximum Dose experienced per day, the dose of the long-acting opioid used for persistent underlying cancer pain should be re-evaluated Varies
   If more than 4 episodes of breakthrough pain are experienced per day, the dose of the long-acting opioid used for persistent underlying cancer pain should be re-evaluated Varies
   If more than 4 episodes of breakthrough pain are experienced per day, the dose of the long-acting opioid used for persistent underlying cancer pain should be re-evaluated VI. Product Availability
   Drug Name Oral transmucosal fentanyl citrate (Actiq)
   Oral transmucosal fentanyl citrate (Fentora)
   Fentanyl nasal spray (Lazanda)
   Fentanyl sublingual spray (Subsys)
   Availability Lozenges: 200 mcg, 400 mcg, 600 mcg, 800 mcg, 1200 mcg, 1600 mcg (30 lozenges per package)
   Buccal tablet: 100 mcg, 200 mcg, 400 mcg, 600 mcg, 800 mcg (Package of 7 blister cards containing 4 tablets in each card) Metered dose nasal spray: 100 mcg, 300 mcg, 400 mcg per spray (Each 5 mL bottle contains 8 sprays)
   Single spray units: 100 mcg, 200 mcg, 400 mcg, 600 mcg, 800 mcg, 1200 mcg, 1600 mcg per spray
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   CLINICAL POLICY Transmucosal Immediate-release Fentanyl VII.