mhn fentanyl IR Coverage Update

Coverage Criteria

II.A Continued Therapy - Cancer Pain

Covered when ALL of the following are met for cancer pain continued therapy (initial initiation not permitted):

Continued therapy for cancer pain: 1) Member is currently receiving the medication via Centene benefit or previously met initial approval criteria, OR member is currently receiving medication and is enrolled in a state and product with continuity of care regulations; 2) Member is responding positively to therapy as evidenced by reduction in breakthrough pain without significant toxicity; 3) For Actiq requests on the HIM plan: dose does not exceed 4 lozenges per day; 4) Approval duration per line of business: Medicaid/Commercial 12 months; HIM 12 months (refer to HIM.PA.103 for product-specific HIM guidance).

Initiation of TIRF products is not permitted due to manufacturer discontinuation; continuation criteria apply only to existing users or continuity of care situations.

I.A Initial Therapy - Cancer Pain

Initial approval for cancer pain:

Initial - Cancer Pain: Authorization for initiation is not permitted due to discontinuation of all TIRF products by manufacturers; member may not initiate therapy with a TIRF product.

See continued therapy section for existing users (Appendix E).

I.B / II.B Other Diagnoses

Other diagnoses/indications:

Other Diagnoses/Indications: 1) If this drug has recently (within the last 6 months) undergone a label change not yet reflected in this policy, follow the appropriate formulary or non-formulary/no-coverage policy for the relevant line of business (see policy references); OR 2) If the requested use is not specifically listed under Diagnoses/Indications excluded in section III and criterion 1 does not apply, refer to the off-label use policy for the relevant line of business.

Cross-reference applicable policies: CP.CPA.190, HIM.PA.33, CP.PMN.255, HIM.PA.103, CP.PMN.16, CP.CPA.09, HIM.PA.154, CP.PMN.53 as appropriate.

inv-04: Appropriate use and dosing constraints

Covered when ALL of the following dosing and use conditions are met

Opioid tolerance: Patient is opioid tolerant as defined in policy (taking around-the-clock opioids at or above the opioid-tolerant thresholds for ≥1 week).see definitions (eg ≥60 mg oral morphine/day or equivalent)

Opioid tolerance is required to avoid life‑threatening hypoventilation.

Indication: Use is for documented breakthrough cancer pain per product labeling.N/A

Initial approval criteria were removed due to product discontinuation; dosing constraints still apply for existing users.

Product-specific initial dosing: Fentora and Subsys: initial dose for new users is 100 mcg (exceptions apply for patients switching from Actiq per conversion table). Actiq: initiate at 200 mcg with titration guidance per labeling. Lazanda initial dose 100 mcg and titrate up to 800 mcg as needed.

These transmucosal immediate‑release fentanyl (TIRF) products are not for use in opioid non‑tolerant patients and are not for the management of acute or postoperative pain (examples include headache/migraine, dental pain, or use in the emergency department). Outpatient dispensing is restricted under the TIRF REMS Access program and requires enrollment of prescriber, pharmacy, and patient; inpatient administration does not require REMS enrollment.

Use in patients who are not opioid tolerant is a listed contraindication because of the risk of life‑threatening respiratory depression (hypoventilation). Only patients meeting the policy definition of opioid tolerant (see definitions) should be considered for TIRF therapy; do not initiate in non‑tolerant individuals.

Outpatient prescribing and dispensing of TIRF products requires enrollment in the TIRF REMS Access program. Note the REMS program is no longer accepting enrollments for new patients, prescribers, or pharmacies following manufacturer discontinuation of all TIRF products; prescriptions may be denied if REMS enrollment is not documented for applicable dispenses.

Authorization for initiation of TIRF products is not permitted because manufacturers announced discontinuation of all TIRF products effective September 30, 2024. Existing patients may be considered under continuation criteria where applicable, but new starts are not authorized.

Different transmucosal fentanyl formulations have important pharmacokinetic differences and are not interchangeable. Substituting one TIRF product for another on a microgram‑per‑microgram basis is not medically appropriate and may lead to fatal overdose; exercise caution and do not perform mcg‑for‑mcg substitutions.

Coding / Definitions

Opioid tolerance threshold

Opioid tolerance thresholdAt least 60 mg oral morphine/day (or equivalent) — see full list of equivalent opioid doses in policy.

ReferenceFull list of equivalent opioid dosing thresholds provided in policy definitions and Appendix D/clinical context.

PurposeDefines opioid-tolerant status required before prescribing TIRF products to avoid life‑threatening hypoventilation.

Provider Actions & Prior Authorization

Prior Authorization

Prior Authorization Required

Prior authorization is required for transmucosal immediate‑release fentanyl (TIRF) products (Actiq, Fentora, Lazanda, Subsys) when approval criteria are met. Note: For Health Insurance Marketplace (HIM) pharmacy benefit requests, Fentora and Lazanda are non‑formulary and should not be approved under these criteria; refer to HIM.PA.103 for formulary exception process.

Affected products: Actiq, Fentora, Lazanda, Subsys
HIM pharmacy benefit: Fentora and Lazanda are non‑formulary — follow HIM.PA.103

Denial Risk

Initiation Prohibited — TIRF Discontinuation

Initial authorization for initiating TIRF therapy is not permitted due to manufacturer discontinuation of all TIRF products. Members may not start a TIRF product; requests for new starts should be denied. If a member is currently using a TIRF product, review continuation criteria in the policy and Appendix E (TIRF Product Discontinuation).

Background

Transmucosal immediate‑release fentanyl (TIRF) products are potent opioid agonists indicated for the management of breakthrough cancer pain in opioid‑tolerant patients. These agents require enrollment in the TIRF REMS Access program for outpatient dispensing and are intended only for patients who meet established opioid tolerance thresholds to reduce the risk of life‑threatening respiratory depression.

Definitions

Opioid tolerant — definition

Definition (opioid tolerant)Patients taking, for one week or longer, around‑the‑clock opioids equivalent to at least 60 mg oral morphine/day, 25 mcg transdermal fentanyl/hour, 30 mg oral oxycodone/day, 8 mg oral hydromorphone/day, 25 mg oral oxymorphone/day, 60 mg oral hydrocodone/day, or an equianalgesic dose of another opioid.

Duration requirementMust have been on the listed around‑the‑clock opioid regimen for ≥1 week before TIRF use.

Concurrent therapyPatients must remain on around‑the‑clock opioids while taking Actiq, Fentora, Lazanda, or Subsys.

TIRF REMS requirement

REMS enrollment requirementUnder the TIRF REMS Access program, outpatient prescribers, pharmacies, and patients must be enrolled to prescribe, dispense, and receive TIRF products.

Inpatient exception

Initial Therapy Criteria

inv-24: Initial therapy

Initial therapy:

Initial therapy prohibition: Authorization for initiation is not permitted due to manufacturer discontinuation of all TIRF products; members may not initiate therapy with a TIRF product.

Appendix E describes discontinuation effective September 30, 2024; prescribers should transition patients to non‑TIRF treatments when supply diminishes.

inv-25: Initial therapy dosing

Initial dosing and titration recommendations by product:

Fentora/Subsys initial dosing: Initial dose of Fentora and Subsys is 100 mcg for new users; patients switching from Actiq should follow the conversion table (e.g., Actiq 200 or 400 mcg → Fentora/Subsys 100 mcg; higher Actiq doses map to higher Fentora/Subsys starting doses as specified).100 mcg initial

Conversion table in policy provides mapped starting doses for switchers from Actiq.

Continuation Criteria

inv-26: Continuation criteria

Continued therapy for cancer pain (existing users):

Continuation criteria: 1) Member is currently receiving the medication via Centene benefit or previously met initial approval criteria, OR is in a continuity of care situation; 2) Member is responding positively to therapy as evidenced by reduction in breakthrough pain without significant toxicity; 3) For Actiq on HIM plan: dose ≤ 4 lozenges per day; 4) Approval duration: 12 months for Medicaid/Commercial/HIM (refer to HIM.PA.103 for product-specific HIM notes).

Refer to continuity of care addendums where applicable.

inv-27: Continuation during discontinuation

Continuation limited by product availability and REMS status:

Continue only if supply and REMS enrollment exist: Patients currently on TIRF medicines may continue treatment while supply remains available and while REMS allows dispensing; prescribers should plan transition to non‑TIRF alternatives as supplies dwindle.supply dependent

Step Therapy / Therapeutic Alternatives

Preferred alternative	Typical immediate‑release dosing / notes
Morphine sulfate (immediate‑release)
10–30 mg PO every 4 hours PRN; individualize based on pre‑existing opioid tolerance
Oxycodone (immediate‑release, Roxicodone)
5–15 mg PO every 4–6 hours PRN; individualize based on pre‑existing opioid tolerance
Hydromorphone (immediate‑release, Dilaudid)
2–4 mg PO every 3–4 hours PRN; individualize based on pre‑existing opioid tolerance
Oxymorphone (immediate‑release, Opana)
5–20 mg PO every 4–6 hours PRN; individualize based on pre‑existing opioid tolerance
Fentanyl transdermal (Duragesic patch)
Apply one patch topically every 72 hours (transdermal formulation as an alternative for baseline opioid therapy)

Exception	Applicability / note
Step therapy redirection exception for oncology settings
Policy added by‑passing of redirection (step therapy) when state regulations prohibit step therapy in certain oncology settings; see policy history and Appendix E for details and subsequent removal/updates following TIRF product discontinuation.

Quantity Limits

Actiq (on HIM plan)

Actiq (HIM) daily limitActiq lozenge limit on HIM plan: maximum 4 lozenges per day.

ContextApplied as part of continued therapy criteria for Actiq on the HIM plan.

Approval durationContinued therapy approvals generally provided up to 12 months per line of business.

All listed TIRF products

Maximum dosing frequencyOnce a successful dose is established, no more than 4 doses per 24 hours for all listed TIRF products.

If >4 episodes/dayRe‑evaluate the dose of the long‑acting opioid used for persistent underlying cancer pain.

Product titration

Site of Care

Billing Rule

REMS enrollment required for outpatient dispensing; not required for inpatient use

Outpatient dispensing of TIRF products requires enrollment in the TIRF REMS Access program for the prescriber, pharmacy, and patient; inpatient administration (e.g., hospitals, hospices, long‑term care inpatient use) does not require REMS enrollment.

Outpatient prescribing/dispensing: REMS enrollment required
Inpatient administration: REMS enrollment not required

Note

No other site‑of‑care restrictions documented; REMS still required

No additional site‑of‑care restrictions beyond REMS requirements are documented in the policy chunks provided; while REMS is active, prescribing and dispensing require enrollment.

Policy contains no other site‑of‑care limitations in provided sections

OpenPayer

Clinical Policy: Fentanyl IR (Actiq, Fentora, Lazanda, Subsys)