CurrentmhnPolicy CP.PHAR.337

Telotristat Ethyl (Xermelo)

Policy governing medical necessity and prior authorization criteria for telotristat ethyl (Xermelo) for treatment of carcinoid syndrome diarrhea and related coverage rules for affected lines of business.

Policy Summary

Payermhn

PolicyTelotristat Ethyl (Xermelo)

Policy CodePolicy CP.PHAR.337

Change TypeStep therapy bypass addedgeneric redirectionPA note for SSA

Effective Date06.01.17

Next Review Date

Key ActionPrior authorization is required and providers must submit documentation demonstrating the member meets all approval criteria (including SSA trial requirements except where IL HIM bypass applies).

SourceLink

POLICY UPDATE CHANGES

Added step therapy bypass for Illinois HIM per IL HB 5395.

Added redirection to generic telotristat for brand Xermelo requests.

Added note that prior authorization may be required for somatostatin analog (SSA) therapy.

250 mg TIDrecommended dosing regimen (carcinoid syndrome diarrhea)

750 mg/daymaximum daily dose

Tablet: 250 mgproduct availability

hypersensitivityexplicit contraindication

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Coverage Criteria

inv-01: Initial Therapy - Carcinoid Syndrome Diarrhea

Covered when ALL of the following are met

Initial Approval - Carcinoid Syndrome Diarrhea: 1. Diagnosis of carcinoid syndrome diarrhea; 2. Failure of a one month trial of a somatostatin analog (SSA) (e.g., octreotide, lanreotide) at up to maximally indicated doses unless clinically significant adverse effects occur or all SSAs are contraindicated; 3. Xermelo (telotristat ethyl) is prescribed in combination with an SSA unless clinically significant adverse effects or contraindications to SSAs exist; 4. Member must use telotristat ethyl (generic if available) unless contraindicated or clinically significant adverse effects occur; 5. Dose does not exceed both: (a) 750 mg per day; and (b) 3 tablets per day.dose <= 750 mg/day AND tablets <= 3/day

Prior authorization may be required for SSA therapy. For Illinois HIM requests, the SSA step therapy requirement does not apply per IL HB 5395 as of 1/1/2026.

inv-02: Continuation Therapy

Covered when ALL of the following are met for continuation

Continuation Therapy - Carcinoid Syndrome Diarrhea: 1. Member meets one of the following: (a) currently receiving medication via the Centene benefit or previously met initial approval criteria; or (b) currently receiving medication and enrolled in a state/product with continuity of care regulations; 2. Member is responding positively to therapy (see Appendix D for examples such as reduction in bowel movement frequency or reduction in urinary 5‑HIAA); 3. Member continues to have diarrhea; 4. Xermelo is prescribed in combination with an SSA unless clinically significant adverse effects or contraindications to SSAs exist; 5. Member must use telotristat ethyl (generic if available) unless contraindicated or clinically significant adverse effects occur; 6. If request is for a dose increase, the new dose does not exceed both: (a) 750 mg per day; and (b) 3 tablets per day.dose <= 750 mg/day AND tablets <= 3/day

See Appendix D for examples of positive response to therapy.

Coverage is not authorized for non‑FDA approved indications that are not specifically addressed in this policy unless the provider supplies sufficient documentation of efficacy and safety in accordance with applicable off‑label use policies: CP.CPA.09 (Commercial), HIM.PA.154 (Health Insurance Marketplace), or CP.PMN.53 (Medicaid), or other evidence of coverage documents.

Use of telotristat ethyl for other symptoms of carcinoid syndrome (for example, flushing or abdominal pain) is considered not authorized in the absence of supporting evidence per the referenced off‑label use policies.

Coding and Dosing

No explicit CPT/HCPCS/NDC codes listedmixed

No codes listed

Maximum daily dose

Maximum daily dose750 mg/day

Equivalent tablet limit3 tablets per day (250 mg each)

Per-dosing regimen250 mg PO TID (recommended regimen)

Provider Actions and Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required for Xermelo (telotristat ethyl). For somatostatin analog (SSA) therapy (e.g., octreotide, lanreotide), prior authorization may also be required.

Affected therapies: Xermelo (telotristat ethyl); SSA therapies (e.g., octreotide, lanreotide)

Step Therapy

SSA Step Therapy Requirement and IL HIM Bypass

A one‑month trial of a somatostatin analog (SSA) at up to maximally indicated doses is required prior to approval of Xermelo, unless clinically significant adverse effects are experienced or all SSAs are contraindicated. For Illinois HIM requests, the SSA step therapy requirement does not apply per IL HB 5395 (effective 1/1/2026).

Step required: 1 month trial of SSA at up to maximally indicated doses
IL HIM bypass: IL HB 5395 — SSA step therapy bypass effective 01/01/2026

Background

Carcinoid syndrome is commonly managed with somatostatin analogs (SSAs). Telotristat ethyl (Xermelo) is indicated as adjunctive therapy for carcinoid syndrome diarrhea inadequately controlled by SSA therapy; requests for use outside those indications are addressed by the policy exclusions above and applicable off‑label policies.

Definitions

somatostatin analog

AbbreviationSSA = somatostatin analog

ExamplesIncludes agents such as octreotide and lanreotide (used in policy step therapy)

Role in therapyStandard of care for carcinoid syndrome and required as combination therapy with Xermelo unless contraindicated

Response to therapy

Clinical response example 1Reduction in bowel movement frequency

Clinical response example 2Reduction in urinary 5‑HIAA levels

Additional detail

Initial Therapy Criteria

inv-14: Initial Therapy

Initial approval criteria

Initial Therapy: Diagnosis of carcinoid syndrome diarrhea; failure of a one month trial of an SSA at up to maximally indicated doses unless clinically significant adverse effects or contraindications; Xermelo prescribed in combination with an SSA unless contraindicated; member must use telotristat ethyl (generic if available) unless contraindicated; dosing limits apply: not to exceed 750 mg per day and 3 tablets per day.

Prior authorization required; SSA prior trial may be bypassed for Illinois HIM requests per IL HB 5395.

Continuation Criteria

inv-15: Continuation Therapy

Continuation criteria for ongoing users

Continuation: Member is currently receiving medication via the Centene benefit or previously met initial approval criteria or is eligible under continuity of care; member is responding positively to therapy (see Appendix D) and continues to have diarrhea; Xermelo used in combination with an SSA unless contraindicated; member must use telotristat ethyl (generic if available) unless contraindicated; dosing limits apply and any requested dose increase must not exceed 750 mg per day and 3 tablets per day.

See Appendix D for examples of positive response.

Step Therapy Requirements

Step	Requirement	Duration / Notes
1	Trial of a somatostatin analog (SSA) at up to maximally indicated doses (e.g., octreotide, lanreotide) is required prior to initiation of telotristat ethyl (Xermelo)	One month trial; prior authorization may be required for SSA therapy.
Bypass for Illinois HIM	Step therapy requirements do not apply for Illinois HIM requests per IL HB 5395	Effective 1/1/2026 (policy change added 06.27.25)
Exceptions	Clinical significant adverse effects to SSAs or contraindications exempt the member from the SSA trial requirement	Documented adverse effects or contraindications required in submitted records

Quantity Limits

telotristat ethyl

Quantity limit (tablets/day)3 per day

Drugtelotristat ethyl (Xermelo)

Per-tablet strengthTablet: 250 mg

Site of Care

Note

Site of care: office

Site of care for administration/management is office.

Brand and Generic Handling

Billing Rule

Redirect to generic telotristat when available

When a request is for brand Xermelo (telotristat ethyl) and a generic telotristat is available, redirect to the generic product unless there is a contraindication or clinically significant adverse effect to the generic.

Provider should indicate contraindication or adverse reaction if claiming medical necessity for brand Xermelo over generic telotristat.