CurrentCentenePolicy CP.PMN.125

Milnacipran (Savella) Coverage and Prior Authorization Criteria

Defines medical necessity, prior authorization, and coverage criteria for milnacipran (Savella) for fibromyalgia (FDA-approved) and off-label depression across Centene lines of business.

Policy Summary

PayerCentene

PolicyMilnacipran (Savella) Coverage and Prior Authorization Criteria

Policy CodePolicy CP.PMN.125

Change TypeNo material changes

Effective DateAug 1, 2012

Next Review DateN/A

Key ActionProvider must submit documentation (office notes, labs, or other clinical information) demonstrating the member meets all approval criteria for prior authorization.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

≥18minimum age for coverage

200 mgmaximum daily dose

12 mostandard approval duration

FibromyalgiaFDA-approved indication

4 strengthstablet strengths

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Initial Therapy - Fibromyalgia

Covered when ALL of the following are met for Initial Approval – Fibromyalgia:

Fibromyalgia initial approval

Diagnosis of fibromyalgia
Age >= 18 years
Prior therapy requirement
- a: Failure of a 30-day trial of duloxetine at up to maximally indicated doses in the last 180 days30 days within 180 days
- b
  - i (age <65): For age <65 years: any tricyclic antidepressant (TCA) or cyclobenzaprine at up to maximally indicated doses
  - ii: Gabapentin at >= 1,800 mg/day>=1800 mg/day
Dose limits: Dose does not exceed both: 200 mg/day AND 2 tablets/day200 mg/day and 2 tablets/day

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Initial Therapy - Depression (off-label)

Covered when ALL of the following are met for Off-label Depression:

Depression initial approval

Diagnosis of depression
Age >= 18 years
Step/therapy requirements
- a: Request is for treatment of a member in a State with limitations on step therapy in certain mental health settings (see Appendix E)
- b
  - i: Failure of a >=4-week trial of one SSRI at up to maximally indicated doses unless contraindicated or clinically significant adverse effects are experienced

Continuation Therapy

Continuation/renewal criteria (applies to all indications in Section I):

Continuation

Current therapy: Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Savella for a covered indication and has received this medication for at least 30 days>=30 days
Clinical response: Member is responding positively to therapy
Dose limit for increases: If request is for a dose increase, new dose does not exceed both 200 mg/day and 2 tablets/day200 mg/day and 2 tablets/day

Non–FDA approved indications not specifically addressed in this policy are not authorized for coverage unless the provider submits sufficient documentation of efficacy and safety in accordance with the referenced off‑label use policies (CP.CPA.09 for commercial lines, HIM.PA.154 for Health Insurance Marketplace, and CP.PMN.53 for Medicaid) or applicable evidence of coverage documents.

Concomitant use of milnacipran (Savella) with a monoamine oxidase inhibitor (MAOI) is contraindicated due to the risk of serious, potentially fatal interactions including symptoms consistent with serotonin syndrome. Providers must document adherence to recommended MAOI washout intervals: allow at least 14 days after stopping an MAOI before starting Savella, and allow at least 5 days after stopping Savella before starting an MAOI.

Requests for milnacipran to treat non‑FDA‑approved conditions must be supported by adequate clinical documentation per the referenced off‑label use policies. Use for an off‑label indication without submission of sufficient supporting evidence as described in CP.CPA.09, HIM.PA.154, or CP.PMN.53 will be considered not authorized.

Initial Therapy

Initial therapy coverage criteria for fibromyalgia and off‑label depression (top-level):

Initial therapy (top-level)

Fibromyalgia branch: See Fibromyalgia initial approval criteria
Includes diagnosis, age >=18, prior trial requirements including duloxetine failure or alternatives, and dose limits
Depression branch: See Off‑label Depression initial approval criteria
Includes diagnosis, age >=18, state step-therapy redirection exceptions or failure of specified antidepressant trials, and dose limits

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Initial dosing

Initial dosing and titration schedules for initiation:

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Continuation Therapy

Continuation therapy requirements (applies to all indications in Section I):

Continuation requirements

Prior use documentation: Currently receiving medication via Centene benefit, or documentation supports current use and member has received Savella for at least 30 days>=30 days
Provider must submit supporting documentation (e.g., office notes)
Positive clinical response: Member is responding positively to therapy
Clinical notes should document symptom improvement or functional benefit
Dose cap on increases: If request is for a dose increase, new dose does not exceed both 200 mg/day and 2 tablets/day200 mg/day and 2 tablets/day

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Continued therapy updates

Updates and notes relevant to continued therapy:

Continuity allowance: Revised continued therapy criteria to allow continuity of care in antidepressants for all indications
Effective 06.07.24 (see policy history)
Approval durations: Medicaid/HIM 12 months; Commercial 12 months or duration of request, whichever is less12 months

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Step Therapy Requirements

Prior trial or exception	Required trial duration / timing	Notes
Failure of a 30-day trial of duloxetine at up to maximally indicated doses	30 days within the last 180 days	Applies to initial approval for fibromyalgia; member must have failed duloxetine unless contraindicated or intolerant
If contraindication or intolerance to duloxetine: failure of a 30-day trial of one of the following in the last 180 days	30 days within the last 180 days	Options include (i) for age <65 years: any TCA or cyclobenzaprine at up to maximally indicated doses, or (ii) gabapentin at ≥1,800 mg/day
Documented contraindication or intolerance to required prior agents	N/A	If contraindicated or clinically significant adverse effects occur, trials of those agents are not required; documentation must be provided

Requirement	Trial duration	State-specific exceptions / notes
Failure of one SSRI at up to maximally indicated doses unless contraindicated or intolerant	≥4 weeks	Trial durations for antidepressants shortened from 8 to 4 weeks per 2Q2023 update
Failure of two SNRIs at up to maximally indicated doses unless contraindicated or intolerant	Each used ≥4 weeks	Applies to depression off‑label initial approval when not eligible for state redirection bypass
Failure of one other generic antidepressant (e.g., bupropion, TCA, mirtazapine) at up to maximally indicated doses unless contraindicated or intolerant	≥4 weeks	State redirection bypass: requests for members in states with limitations on step therapy in certain mental health settings follow Appendix E (e.g., Texas HIM requests allow single‑drug redirection rules)
State redirection / bypass for mental health settings	See state-specific requirements	Appendix E lists states with limitations; Texas noted for HIM requests where single‑drug redirection applies

Provider Actions & Documentation

Prior Authorization

Prior Authorization Required

Prior authorization is required. Provider must submit documentation (such as office chart notes, lab results, medication trial history, or other clinical information) demonstrating the member meets all approval criteria. Requests missing supporting documentation that show required trials, contraindications, intolerances, or washout periods may be denied.

Prior authorization required for Savella (CP.PMN.125).
Acceptable documentation: office chart notes, lab results, medication histories, prior authorization forms, and consult notes.

Step Therapy

Step Therapy / Redirection Impact

Step therapy and redirection rules apply and can affect approval. For fibromyalgia, a 30-day trial of duloxetine (unless contraindicated/intolerant) is required prior to Savella except where state redirection/step therapy prohibitions apply (e.g., Illinois HIM per IL HB 5395 effective 01/01/2026). For depression (off‑label) step therapy requirements vary by state; some mental‑health settings allow redirection bypass — see Appendix E.

Fibromyalgia: 30-day duloxetine trial within last 180 days required unless contraindication/intolerance.
Depression: 4‑week trials of specified antidepressants required for most states; state‑specific redirection/shortened trials (see Appendix E).
Illinois HIM: step therapy requirements do not apply as of 01/01/2026.

Step Therapy

Step Therapy and Exceptions

Step therapy requirements and documented exceptions must be met. For fibromyalgia, the patient must have failed a 30‑day trial of duloxetine at up to maximally indicated doses within the last 180 days OR have a documented contraindication/intolerance to duloxetine and failure of a 30‑day trial of an alternative (age <65: TCA or cyclobenzaprine; or gabapentin ≥1,800 mg/day). For depression (off‑label), unless the request qualifies for a state redirection bypass, the member must meet failure criteria of specified antidepressant trials (SSRI ≥4 weeks, two SNRIs each ≥4 weeks, and another generic antidepressant ≥4 weeks) unless contraindicated or intolerant.

Fibromyalgia exceptions: documented contraindication/intolerance to duloxetine allows alternative step of TCA/cyclobenzaprine or gabapentin per age and dosing criteria.
Depression exceptions: requests from states with limitations on step therapy (see Appendix E) may follow redirection bypass rules; otherwise required SSRI/SNRI/other antidepressant trials apply.
Trial durations for antidepressants shortened from 8 to 4 weeks per 2Q 2023 annual review.

Denial Risk

Off‑Label Use Requires Supporting Evidence

Off‑label requests (e.g., Savella for depression) require sufficient supporting evidence per applicable off‑label use policies. Non‑FDA indications that lack adequate documentation of efficacy and safety in the medical record or per off‑label policy citations (CP.CPA.09, HIM.PA.154, CP.PMN.53) may be denied.

Provide literature, specialty consult notes, prior treatment response, and rationale supporting off‑label use.
If off‑label efficacy/safety documentation is not included, the request is at risk for denial.

Denial Risk

MAOI Contraindication / Required Washout Documentation

MAOI contraindication and washout periods must be documented. Concomitant use of MAOIs with Savella is contraindicated. Allow at least 14 days after stopping an MAOI before starting Savella and at least 5 days after stopping Savella before starting an MAOI. Lack of documentation of medication reconciliation or washout intervals may result in denial.

Document current and prior use of MAOIs and dates of discontinuation to confirm required washout intervals.
Monitor and document for serotonin syndrome risks and concomitant serotonergic drugs; include plan for management if needed.

Documentation Required

Supporting Documentation and References

Provide supporting clinical references when available. Include Savella prescribing information and relevant literature (e.g., guideline or review citations) to support coverage decisions for off‑label or complex cases.

Include Savella Prescribing Information (Allergan) and relevant peer‑reviewed literature or guideline citations in the documentation package.
Cite clinical rationale when deviating from standard step therapy due to contraindication or intolerance.

Definitions

inv-21: SNRI

DefinitionSelective serotonin and norepinephrine reuptake inhibitor (SNRI)

MechanismInhibits reuptake of serotonin and norepinephrine

Example agentMilnacipran (Savella) is an SNRI indicated for fibromyalgia

inv-22: MAOI

DefinitionMonoamine oxidase inhibitor (MAOI)

Interaction riskConcomitant use with serotonergic agents (e.g., Savella) is contraindicated due to potentially serious, sometimes fatal interactions

Washout intervalsAllow at least 14 days after stopping an MAOI before starting Savella; allow at least 5 days after stopping Savella before starting an MAOI

inv-23: Serotonin syndrome

DefinitionSerotonin syndrome is an adverse drug reaction associated with serotonergic agents

Key symptomsTremor, myoclonus, diaphoresis, nausea, vomiting, flushing, dizziness, hyperthermia, rigidity, autonomic instability, seizures, and mental status changes

SeverityCan progress to delirium and coma; concomitant use of serotonergic drugs increases risk

OpenPayer

Milnacipran (Savella) Coverage and Prior Authorization Criteria

Coverage Criteria

Initial Therapy

Continuation Therapy

Step Therapy Requirements

Coding & Limits

Quantity Limits

Provider Actions & Documentation

Definitions

Background