CurrentCentenePolicy CP PMN.222

Pretomanid (for drug-resistant pulmonary tuberculosis)

Defines Centene clinical policy for medical necessity, initial and continuation approval criteria, dosing, limitations, contraindications, and administrative requirements for pretomanid as part of the BPaL regimen (bedaquiline, pretomanid, linezolid) for treatment of specified drug-resistant pulmonary tuberculosis across Commercial, HIM, and Medicaid lines of business.

Policy Summary

PayerCentene

PolicyPretomanid (for drug-resistant pulmonary tuberculosis)

Policy CodePolicy CP PMN.222

Change TypeRevised / Clarified (annual reviews)

Effective Date03.01.20

Next Review Date

Key ActionProvider must submit documentation (chart notes, lab results, culture and susceptibility testing) showing the member meets all approval criteria, including resistance patterns or treatment intolerance/nonresponse.

POLICY UPDATE CHANGES

Lowered age requirement from 17 to 15 years per updated WHO 2022 guidance and clarified approval duration as 26 weeks.

Updated linezolid dosing from 1,200 mg to 600 mg per updated CDC recommendations.

Clarified expert in treatment of tuberculosis to include public health departments, CDC-designated Centers of Excellence specialists, and ID specialists managing TB clinics.

Updated approved indication language to align with prescribing information and removed references to multidrug-resistant and extensively drug-resistant TB terminology.

1Approved Combination Regimen (BPaL)

26 weeksStandard Approval Duration

>=15

200 mg/dayMaximum Pretomanid Dose

Coverage Summary

Coverage stance: covered_with_criteria for pretomanid when used as part of the BPaL combination regimen (bedaquiline, pretomanid, linezolid). Scope: defines Centene clinical policy for medical necessity, initial and continuation approval criteria, dosing, limitations, contraindications, and administrative requirements for pretomanid as part of the BPaL regimen for treatment of specified drug-resistant pulmonary tuberculosis across Commercial, HIM, and Medicaid lines of business. Approved combination regimen requirement: BPaL (bedaquiline + pretomanid + linezolid) is required for approval; prior authorization may be required for bedaquiline and linezolid. Status: CURRENT. Effective date: 2020-03-01. Last review date: 2025-02-25.

Key Coverage Thresholds

Minimum age>= 15 years

Maximum pretomanid dose200 mg/day

Initial approval duration26 weeks

Maximum treatment duration with delayed culture conversionUp to 9 months (39 weeks)

Initial Therapy Criteria

Initial Approval Criteria

Pretomanid is medically necessary when ALL of the following are met:

Diagnosis of pulmonary TB
Resistant Tuberculosis; documentation of one of the following (a or b):
- a: Resistance to isoniazid and rifampin, AND member is treatment-intolerant or nonresponsive to standard therapy
  see Appendix D
- b: Resistance to isoniazid, rifamycins, a fluoroquinolone, and a second-line injectable antibacterial (e.g., amikacin, capreomycin, kanamycin)

Approval Duration

Initial approval duration: 26 weeks26 weeks

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Continuation Therapy Criteria

Continued Therapy (Criteria for Renewal/Continuation)

Member must meet ALL of the following for continued therapy:

Continuation eligibility: Member is currently receiving medication via Centene benefit or has previously met initial approval criteria
Response: Member is responding positively to therapy
Concurrent bedaquiline/linezolid
- option a: Member continues to receive bedaquiline and linezolid in combination with pretomanid

Unproven / Exclusions

Diagnoses/Indications Not Authorized

Off-label not authorized without documentation: Non-FDA approved indications not addressed in this policy are not authorized unless sufficient documentation per off-label use policies is provided
See off-label policies CP.CPA.09, HIM.PA.154, CP.PMN.53
Not for drug-sensitive TB: Pretomanid is not indicated for drug-sensitive TB
Not for latent TB: Pretomanid tablets are not indicated for latent Mycobacterium tuberculosis infection
Not for extra-pulmonary TB:

Applicable Codes

Product NDC / HCPCS (not specified in policy)NDC|HCPCS

No codes listed

Associated drugs referenced (therapeutic alternatives and combination regimen)mixed

bedaquiline	Sirturo - combination required with pretomanid
linezolid	Part of BPaL regimen
moxifloxacin	Off-label combination option if fluoroquinolone resistance not documented

Provider Actions

Documentation Required

Documentation for medical necessity

Submit chart notes, laboratory results, and culture and susceptibility testing that demonstrate the member meets all approval criteria, including documentation of resistance patterns or treatment intolerance/nonresponse.

Chart notes
Laboratory results
Culture and susceptibility testing

Prior Authorization

Combination therapy requirement

Prior authorization requires pretomanid to be prescribed in combination with bedaquiline (Sirturo) and linezolid. Note that prior authorization may also be required separately for bedaquiline and for linezolid.

Clinical Evidence

Phase 3 study NCT02333799Key trial(s) referenced in policy and FDA materials

FDA/WHO/CDC guidanceGuidance sources cited (Prescribing Information, WHO, CDC)

Evidence: Key clinical evidence referenced includes the Phase 3 study NCT02333799 assessing bedaquiline + pretomanid (PA-824) + linezolid for resistant pulmonary tuberculosis. Approval is noted to be based on limited clinical safety and efficacy data, and regulatory guidance and practice guidance sources (FDA prescribing information, WHO, CDC) are cited. The policy specifies that pretomanid’s use is restricted to the BPaL combination (bedaquiline and linezolid). The policy record documents updates to dosing and guidance: WHO 2022 guidance supported lowering the minimum age to 15 years, and 1Q2024 updates aligned linezolid dosing to 600 mg per day per updated CDC recommendations.

Background

Background: Pretomanid is a nitroimidazooxazine antimycobacterial that is FDA-approved only as part of the BPaL regimen for a limited population of adults with pulmonary tuberculosis meeting specified drug-resistance criteria (resistant to isoniazid, rifamycins, a fluoroquinolone and a second-line injectable, or resistant to isoniazid and rifampin with treatment-intolerance or nonresponse to standard therapy). The FDA approval and policy emphasize that approval is based on limited clinical safety and efficacy data and that pretomanid’s safety and effectiveness have not been established outside use in combination with bedaquiline and linezolid.

Definitions

Scope & Policy Identifiers

Revision History

02.231Q 2023 annual review noted this change; P&T Approval Date = 02.23.

Lowered age requirement from 17 to 15 years per updated WHO 2022 guidance and clarified approval duration as 26 weeks.

02.241Q 2024 annual review; P&T Approval Date = 02.24.

Updated linezolid dosing from 1,200 mg to 600 mg per updated CDC recommendations.

05.21P&T Approval Date = 05.21 (clarification date earlier noted).

Clarified expert in treatment of tuberculosis to include public health departments, CDC-designated Centers of Excellence specialists, and ID specialists managing TB clinics.

Policy Summary

PayerCentene

PolicyPretomanid (for drug-resistant pulmonary tuberculosis)

Policy CodePolicy CP PMN.222

Change TypeRevised / Clarified (annual reviews)

Effective Date03.01.20

Next Review Date

On This Page

Prescriber: Prescribed by or in consultation with an expert in the treatment of tuberculosis (e.g., state or county public health department, specialists affiliated with TB Centers of Excellence as designated by the CDC, infectious disease specialists managing TB clinics)

Combination therapy: Prescribed in combination with Sirturo (bedaquiline) and linezolid

Prior authorization may be required for Sirturo and linezolid

Age ≥ 15 years>= 15 years

Off-label moxifloxacin option

option a: Prescribed in combination with moxifloxacin (off-label)
option b: Documented resistance to fluoroquinolones, unless contraindicated or clinically significant adverse effects are experienced

title": "Initial Approval Criteria"}

option b: Member continues to receive bedaquiline and has completed at least 4 weeks of linezolid therapy

Extended treatment attestation: If request is for treatment beyond 26 weeks, provider attestation of delayed treatment response within the first 8 weeks as assessed by time to culture conversion, persistent culture positivity, clinical response to treatment, and other underlying clinical factors

Dose increase limit: If request is for a dose increase, new dose does not exceed 200 mg (tablet strength) per day<= 200 mg/day

Pretomanid is not indicated for extra-pulmonary Mycobacterium tuberculosis infection

Not when resistance to BPaL component: Not indicated when there is TB with known resistance to any component of the BPaL combination

Not established with other drugs: Safety and effectiveness of pretomanid in combination with drugs other than bedaquiline and linezolid has not been established

Documentation Required

Specialist prescribing or consultation

Prescription must be by or in consultation with an expert in the treatment of tuberculosis, such as a state or county public health department clinician, a specialist affiliated with a CDC-designated TB Centers of Excellence, or an infectious disease specialist who manages TB clinics.

Documentation Required

Attestation for extended therapy

When requesting treatment beyond 26 weeks, the provider must attest that there is a delayed treatment response within the first 8 weeks, assessed by time to culture conversion, persistent culture positivity, clinical response to treatment, and other relevant clinical factors.

Billing Rule

Dose limit for approval

Any requested pretomanid dose increase for approval must not exceed 200 mg (tablet strength) per day.

References reviewed and updated per latest prescribing information.Latest

Updated approved indication language to align with prescribing information and removed references to multidrug-resistant and extensively drug-resistant TB terminology.