Policy governing prior authorization and medical necessity criteria for immediate-release transmucosal fentanyl products (Actiq, Fentora, Lazanda, Subsys) for Centene lines of business including Commercial, HIM, and Medicaid; affects prescribers and pharmacies requesting coverage.
Key ActionSubmit prior authorization with documentation of opioid tolerance and REMS enrollment status for current users; initiation for new patients is not permitted.
TIRF REMS program is no longer accepting enrollments for new patients, prescribers, or pharmacies due to product discontinuation of all TIRF products on September 30, 2024.
Initiation of TIRF products is not permitted due to discontinuation of all TIRF products; current users may be continued under specified continued therapy criteria.
Initial approval criteria for cancer were removed due to discontinuation of all TIRF products by manufacturers.
Appendix E added to document discontinuation details and guidance for transitioning patients off TIRF products.
TIRF REMS is no longer accepting new enrollments for new patients, prescribers, or pharmacies due to product discontinuation on September 30, 2024.
Dosing conversion guidance for switching between Actiq and other TIRF products (Fentora, Subsys) provided with explicit mapped initial doses.
4Named products
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3Lines of business
Sep 30, 2024REMS/enrollment cutoff
12 monthsTypical approval duration
4Max doses/day
Coverage and Medical Necessity Criteria
inv-01: Initial Approval
Covered only under very limited circumstances — initiation prohibited; continuation allowed for current users meeting criteria.
Initial Approval: Member may not initiate therapy with a TIRF product due to manufacturer discontinuation of all TIRF products; initiation is not permitted.
See Appendix E for information on product discontinuation and continuation options for current users.
inv-02: Continuation Therapy
Continued therapy for cancer pain — all criteria must be met for continuation.
Continued Therapy - Cancer Pain: Member is currently receiving the TIRF medication via the Centene benefit or has previously met initial approval criteria; member is responding positively to therapy as evidenced by reduction in breakthrough pain without significant toxicity.Approval duration: Medicaid/Commercial 12 months; HIM 12 months (Actiq HIM dose limit applies)
Continuity of care provisions may apply in certain states/products; refer to state addendums.
inv-03: Other Indications / Referral Policies
Other diagnoses/indications and exclusions
Other Indications / Referral: For uses not specifically listed or for drugs on/off formulary, follow the relevant no-coverage, non-formulary, or off‑label use policy for the member's line of business (see referenced policies).
Dosing and conversion guidance for transmucosal fentanyl products
General conversion guidance: Patients should not be converted mcg-for-mcg between different transmucosal fentanyl products due to substantial differences in absorption and pharmacokinetics.
Conversion mappings and exceptions provided below.
Fentora and Subsys initial dosing (general rule): Initial dose of Fentora and Subsys is 100 mcg for patients not switching from Actiq.
See Actiq-to-Fentora/Subsys mapping for patients switching from Actiq.
Actiq-to-Fentora/Subsys mapping: When switching from Actiq, use the mapped initial doses: Actiq 200 or 400 mcg → Fentora/Subsys 100 mcg; Actiq 600 or 800 mcg → Fentora/Subsys 200 mcg; Actiq 1200 or 1600 mcg → Fentora/Subsys 400 mcg.
Exact mapping listed in policy Appendix/tables.
These transmucosal immediate‑release fentanyl products are not indicated for the management of acute or postoperative pain (including headache/migraine, dental pain, or use in the emergency department). The policy excludes coverage for non‑FDA approved indications unless adequate documentation of efficacy and safety is provided per the referenced off‑label use policies. Additionally, outpatient dispensing historically required enrollment in the TIRF REMS access program; inpatient administration (hospitals, hospices, long‑term care) does not require patient/prescriber REMS enrollment.
Use of transmucosal immediate‑release fentanyl in opioid non‑tolerant patients is explicitly contraindicated and will not be authorized. Similarly, these agents are not appropriate for acute or postoperative pain contexts (including headache/migraine, dental pain, or emergency department use) due to risks such as life‑threatening respiratory depression described in boxed warnings.
Initiation of any TIRF product for new patients is not permitted because manufacturers have discontinued all TIRF products. Requests for new starts will be denied; non‑FDA approved uses remain excluded unless supported by the applicable off‑label use policies and documentation.
Treatment of patients who are not opioid tolerant with transmucosal fentanyl is considered not medically necessary because of the high risk of severe or life‑threatening respiratory depression and other boxed‑warning risks. Contraindications that will prompt denial include opioid non‑tolerance, significant respiratory depression, severe bronchial asthma in unmonitored settings, gastrointestinal obstruction (including paralytic ileus), and hypersensitivity to fentanyl or product components.
Initial Therapy
inv-22: Initial Therapy
Initiation rules
Initiation prohibition: Initiation of any TIRF product is not permitted due to manufacturer discontinuation; new patients cannot be started on TIRF products and new enrollments in TIRF REMS are not accepted.
Existing users should be managed per continuation criteria and Appendix E guidance.
inv-23: Initial Therapy
Initial dosing recommendations and conversion when switching between TIRF products
Fentora/Subsys default initial dose: The default initial dose for Fentora and Subsys is 100 mcg for patients not switching from Actiq.
Exceptions and specific mappings apply for patients switching from Actiq (see mapping).
Continuation and Transition Guidance
inv-24: Continuation for Current Users
Criteria for continuing therapy in current users
Continued therapy requirements: Member currently receiving TIRF medication via the Centene benefit or who previously met initial approval criteria; member demonstrates clinical benefit with reduction in breakthrough pain and without significant toxicity.Approval duration: Medicaid/Commercial 12 months; HIM 12 months (Actiq HIM dose limit applies)
Providers must submit documentation (e.g., chart notes) supporting continued benefit; continuity of care rules may apply per state.
inv-25: Continuation Therapy after Discontinuation
Guidance for patients currently receiving TIRF products following discontinuation announcement
Continuation while supply exists: Patients currently on a TIRF medicine may continue treatment under the REMS while supply remains available; prescribers should work to transition patients to non‑TIRF alternatives as supply allows.
Provider Responsibilities and Authorization
Prior Authorization
Prior Authorization Required
Prior authorization is required for listed transmucosal immediate‑release fentanyl (TIRF) products (Actiq, Fentora, Lazanda, Subsys). Provider must submit supporting documentation (e.g., office chart notes, lab results, other clinical information) demonstrating the member meets all approval criteria.
Prior authorization required for Actiq, Fentora, Lazanda, Subsys
Requests to initiate TIRF products are not permitted because manufacturers have discontinued all TIRF products and the TIRF REMS is no longer accepting new enrollments for patients, prescribers, or pharmacies. Members currently receiving a TIRF product may continue while supply remains available; prescribers should transition patients to non‑TIRF alternatives as appropriate.
Definitions and Coding Thresholds
Opioid tolerance threshold
Opioid tolerance thresholdAt least 60 mg oral morphine/day OR at least 25 mcg transdermal fentanyl/hour OR at least 30 mg oral oxycodone/day OR at least 8 mg oral hydromorphone/day (for ≥1 week)
Duration for tolerance assessmentTaken for one week or longer while on around-the-clock opioid therapy
PurposeDefines opioid-tolerant patients eligible for TIRF products (continuation only)
Actiq daily lozenge limit (HIM plan)
Actiq HIM daily lozenge limitDose does not exceed 4 lozenges per day (HIM plan)
Approval duration for HIMHIM continuation approval: 12 months (refer to HIM.PA.103 for Fentora and Lazanda)
Step Therapy and Therapeutic Alternatives
Step
Requirement / Preferred alternative
Notes
1
Immediate‑release oral opioids (e.g., morphine sulfate IR, oxycodone IR, hydromorphone IR, oxymorphone IR)
Listed as therapeutic alternatives in Appendix B; may require prior authorization and may not be on all formularies.
1
Transdermal fentanyl (Duragesic)
Included in Appendix B as an alternative; dosing individualized based on pre‑existing opioid tolerance.
Policy version / date
Historical step requirement
Change noted in history
2Q 2021 annual review
Revised trial requirement for generic Actiq to 'must' language; Abstral, Fentora, and Lazanda noted as non‑formulary (NF) on HIM
Trial requirement language was tightened and HIM formulary status for several agents was explicitly documented.
2Q 2022 annual review
No significant changes to step edits recorded; template and continued therapy sections updated
Template changes applied to other diagnoses/indications and continued therapy sections; references reviewed and updated.
Quantity Limits and Dispensing Constraints
Actiq (HIM plan)
Actiq HIM daily lozenge limitDose does not exceed 4 lozenges per day (HIM plan)
Inpatient vs outpatient REMS enrollment requirements
Inpatient administration (hospitals, hospices, long‑term care) does not require patient or prescriber enrollment in TIRF REMS; outpatient dispensing requires REMS enrollment when the REMS program is active, though new enrollments are closed following product discontinuation.
For outpatients, confirm REMS enrollment status historically and consider REMS enrollment closure when adjudicating PA requests.
Note
Avoid unmonitored settings for patients at high respiratory risk
Do not use TIRF products in unmonitored settings for patients with severe respiratory compromise; avoid use where resuscitative equipment and monitoring are not available (e.g., some office or home settings).
Settings without resuscitative equipment or monitoring (unmonitored home use, certain office settings) increase risk and are contraindicated for patients with severe respiratory compromise.
Background and Indications
Transmucosal immediate‑release fentanyl (TIRF) products are indicated only for management of breakthrough pain in opioid‑tolerant cancer patients. Opioid tolerance is defined as patients taking, for one week or longer, around‑the‑clock opioid therapy equivalent to at least 60 mg oral morphine daily, 25 mcg/hour transdermal fentanyl, 30 mg oral oxycodone daily, 8 mg oral hydromorphone daily, or an equianalgesic dose of another opioid. The REMS access program historically limited outpatient dispensing to enrolled patients, prescribers, and pharmacies; note that REMS enrollment and product availability have been affected by manufacturer discontinuation.
Key ActionSubmit prior authorization with documentation of opioid tolerance and REMS enrollment status for current users; initiation for new patients is not permitted.
Initiate Actiq at 200 mcg PO; if breakthrough episode not relieved in 30 minutes, one additional dose of the same strength may be taken; wait at least 4 hours before treating another episode. Individually titrate to effective dose. Initial prescription recommended maximum 6 units; once a successful dose is found, limit to no more than 4 doses per 24 hours.
Initial Rx max 6 units; then max 4 doses/24 hrs
If >4 breakthrough episodes/day, re-evaluate baseline long-acting opioid therapy.
Fentora dosing: For Fentora, if the breakthrough episode is not relieved within the specified time, patients may take one additional dose of the same strength and must wait at least 4 hours before treating another episode. Maximum of 4 tablets per episode as specified; once a successful dose is established, limit to no more than 4 doses per 24 hours.Max 4 doses/24 hrs
If >4 breakthrough episodes/day, reassess baseline therapy.
Lazanda dosing: Initial Lazanda dose is 100 mcg; titrate through 100 → 200 → 400 up to 800 mcg as needed. Dose configurations vary (single spray or multiple sprays per episode). No more than four doses per 24 hours; wait at least 2 hours before treating another episode with Lazanda.Max 4 doses/24 hrs
Individually titrate to effective dose with tolerable side effects.
Subsys dosing: Initial Subsys dose is 100 mcg SL for patients not switching from Actiq; patients already using Actiq follow mapped dosing. Individually titrate; no more than two doses per breakthrough episode and wait at least 4 hours before treating another episode. Once successful dose identified, limit to four or fewer doses per 24 hours.Max 4 doses/24 hrs
Do not convert products on mcg-per-mcg basis.
Actiq initiation and titration:
Initiate Actiq at 200 mcg PO; if not relieved in 30 minutes, one additional dose of same strength may be taken; wait at least 4 hours before treating another episode. Titrate individually; initial prescription recommended maximum of 6 units.
Initial Rx max 6 units; then max 4 doses/24 hrs
Once effective dose identified, limit to no more than 4 doses per 24 hours.
Actiq-to-Fentora/Subsys conversion mapping: When converting patients from Actiq to Fentora/Subsys use the specified mappings (e.g., Actiq 200 or 400 mcg → Fentora/Subsys 100 mcg; Actiq 600 or 800 mcg → 200 mcg; Actiq 1200 or 1600 mcg → 400 mcg).
Do not perform mcg-for-mcg conversions between products.
TIRF REMS is no longer accepting new enrollments as of manufacturers' discontinuation; see Appendix E for transition guidance.
New patient, prescriber, and pharmacy enrollments into TIRF REMS are halted
Initiation of TIRF therapy is not allowed
Documentation Required
Prior Authorization and REMS Enrollment — Documentation Required
Because TIRF products were distributed under the TIRF REMS, prior authorization must account for REMS distribution constraints and product discontinuation. Documentation should explicitly state the member's REMS enrollment status and, if continuing therapy, a transition plan given limited/ending product supply.
Document REMS enrollment status for patient, prescriber, and dispensing pharmacy
If member currently on TIRF, include plan to transition to non‑TIRF therapy when supply is exhausted
Denial Risk
Contraindications That Trigger Denial
Use of TIRF products in certain situations is a contraindication and will trigger denial. Do not approve when used in opioid non‑tolerant patients, for acute or postoperative pain (including headache/migraine, dental, or emergency department use), in significant respiratory depression or acute severe bronchial asthma in an unmonitored setting, with gastrointestinal obstruction (including paralytic ileus), or in patients with hypersensitivity to fentanyl or product components. Boxed warnings (respiratory depression, accidental ingestion, CYP3A4 interactions, concomitant CNS depressant risks, abuse/misuse) should be considered when assessing requests.
Contraindicated in opioid non‑tolerant patients
Contraindicated for acute/postoperative pain (including headache/migraine, dental, ED use)
Contraindicated in significant respiratory depression or acute severe bronchial asthma without resuscitative equipment
Contraindicated with gastrointestinal obstruction (including paralytic ileus)
Hypersensitivity to fentanyl or product components
Step Therapy
Therapeutic Alternatives / Step
Therapeutic alternatives and step therapy expectations should be considered prior to approval. Preferred alternatives include immediate‑release oral opioids (e.g., morphine, oxycodone, hydromorphone, oxymorphone) and transdermal fentanyl patches, individualized to the member's opioid tolerance and dosing needs. These alternatives may require prior authorization under their respective benefit rules.
Immediate‑release oral opioids (morphine, oxycodone, hydromorphone, oxymorphone) as alternatives
Transdermal fentanyl patches (Duragesic) as an alternative
Alternatives may require prior authorization and must be individualized to opioid tolerance
Step Therapy
Step Therapy Notes
Earlier versions of the policy included specific step requirements (for example, trial of generic Actiq). Policy history reflects revisions to step language and removals related to discontinuation; current practice is to consider non‑TIRF alternatives and document any prior trials of alternatives where clinically applicable.
Policy history revised trial/step requirements (e.g., generic Actiq language updated)
When applicable, document prior trials of non‑TIRF alternatives
Documentation noteProvider must document continued positive response and lack of significant toxicity
Episode spacing
Wait at least 4 hours between breakthrough episodes for most TIRF products (Lazanda: at least 2 hours between episodes)
Actiq (initial prescription)
Initial Actiq prescription limitMaximum of 6 units for initial prescription
Initial dosing regimenInitiate Actiq at 200 mcg PO; may take one additional dose after 30 minutes if not relieved; wait at least 4 hours before next episode
Titration guidanceIndividually titrate to effective dose using single dosage unit per breakthrough episode