CurrentmhnPolicy CP.PMN.44

Pyrimethamine (Daraprim) Coverage

Defines medical necessity criteria, dosing limits, and prior authorization requirements for pyrimethamine (Daraprim) for treatment and prophylaxis of toxoplasmosis for Centene-affiliated health plans.

Policy Summary

Payermhn

PolicyPyrimethamine (Daraprim) Coverage

Policy CodePolicy CP.PMN.44

Change TypeNo material change

Effective DateNov 1, 2015

Next Review Date

Key ActionSubmit prior authorization with documentation showing the member meets clinical criteria, including diagnosis, specialist consult, prior TMP‑SMX trial when required, and dosing information.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

≤75 mg/dayMax treatment dose (immunocompromised)

50-75 mg/weekPrimary prophylaxis limit

12 monthsApproval duration (congenital)

25 mgTablet strength

CP.PMN.44Document ID

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

Continuation/Chronic Maintenance and HIV-specific continuation

Covered continuation/maintenance criteria (must meet all):

ALL of the following

- ANY of the following
  - Currently receiving medication via Centene benefit or member has previously met initial approval criteria
  - Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B)
- ANY of the following
  - Age ≥ 6 years: CD4 count ≤ 200 cells/mm³ at any time in the previous 6 months
  - Age < 6 years: CD4 percentage has risen < 15% from baseline at any time in the previous 6 months
Adherence to antiretroviral therapy as evidenced by pharmacy claims history or office notes
For Daraprim requests, member must use pyrimethamine, unless contraindicated or clinically significant adverse effects are experienced
- ANY of the following
  - Dose does not exceed 50 mg per day
  - Dose is supported by practice guidelines or peer-reviewed literature for the relevant use (prescriber must submit supporting evidence)
Approval duration: 12 months

Other Indications / Off-label pathways

Other/Off-label uses not enumerated (must meet 1 or 2):

ANY of the following

- ANY of the following
  - For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid
  - For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid
If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid

Referenced criteria and historical changes

Referenced criteria and historical changes:

ALL of the following

3Q 2021 annual review: added initial approval duration of 12 months for treatment of congenital toxoplasmosis in newborns per CDC guidelines; revised 'medical justification' to 'must use' language; added requirement for use of generic to continued criteria; references to HIM.PHAR.21 revised to HIM.PA.154; references reviewed and updated., Date = 03.18.21. P&T Approval Date = 08.21.
For primary prophylaxis initial criteria and for all indications continued therapy criteria, added CD4 percentage requirements for members aged < 6 years per HHS guidelines., Date = 09.22.21. P&T Approval Date = 02.22.
3Q 2022 annual review: no significant changes; references reviewed and updated., Date = 03.29.22. P&T Approval Date = .
3Q 2023 annual review: no significant changes; references reviewed and updated., Date = 04.13.23. P&T Approval Date = 08.23.

Provider Actions, Prior Authorization, and Documentation

Prior Authorization

Prior Authorization Required

Prior authorization required — Prior authorization is required. Provider must submit documentation that the member meets the specified clinical criteria (diagnosis, specialist prescriber/consult/ordered concurrent medications and dosing limits) for approval.

Applicable to initial therapy, prophylaxis, and continued therapy requests
For Daraprim requests, member must use pyrimethamine unless contraindicated or significant adverse effects occur

Documentation Required

Documentation Requirement

Documentation requirement — Requests must include clinical documentation demonstrating medical necessity. Failure to submit supporting documentation (office chart notes, lab results, imaging, consult notes, or other clinical information) that the member meets all approval criteria may result in denial or request processing delays.

Include diagnostic evidence of toxoplasmosis or indication for prophylaxis (e.g., Toxoplasma IgG, HIV diagnosis, CD4 counts/percentages where applicable)
If using guideline-supported dosing outside standard limits, submit peer-reviewed literature or guideline references

Documentation Required

Required Supporting Documentation

Required supporting documentation — Provider must submit documentation such as office chart notes, laboratory results (e.g., Toxoplasma IgG, CD4 count or percentage), radiology reports when applicable, consultation notes from infectious disease or HIV specialists, and medication history showing trial and failure or intolerance of TMP-SMX when required by step therapy.

Evidence of specialist prescriber or documented specialist consultation
For step therapy, documentation that member failed ≥10 days (or radiologic deterioration within 7 days) of TMP-SMX at maximum indicated doses, unless contraindicated or significant adverse effects occurred
For prophylaxis, documentation of TMP-SMX use unless contraindicated

Documentation Required

Medical Necessity and Documentation

Medical necessity and documentation — Providers should document medical necessity per Health Plan terms. Coverage decisions are subject to all benefit plan limitations, exclusions, and state/federal requirements. Providers are expected to exercise professional judgment and retain documentation to support that the criteria for pyrimethamine therapy are met.

Coverage is subject to plan contract terms and applicable state Medicaid precedence
Clinical rationale and supporting records should be available upon request

Step Therapy

Step Therapy and TMP‑SMX Requirement

Step therapy and TMP‑SMX requirement — A step therapy requirement applies for initial therapy of active toxoplasmosis in adults: member must have failed ≥10 days of TMP‑SMX at maximum indicated doses (or experienced radiologic deterioration within 7 days), unless TMP‑SMX is contraindicated or causes clinically significant adverse effects. For primary prophylaxis, member must use TMP‑SMX unless contraindicated or clinically significant adverse effects are experienced.

For members <18 years the step therapy requirement does not apply (age <18 is an exception)
Illinois HIM members: step therapy bypass applies per IL HB 5395 effective 1/1/2026 for initial therapy requests
When TMP‑SMX is contraindicated or not tolerated, document the contraindication or adverse reaction

Definitions and Guideline Sources

Daraprim (pyrimethamine) — key definition

Generic / BrandPyrimethamine (Daraprim)

MechanismFolic acid antagonist

FDA indicationIndicated for treatment of toxoplasmosis when used conjointly with a sulfonamide

Dosage form/strength notedTablet available; dosing guidance varies by indication (see dosing section)

Primary prophylaxis (off-label) — pyrimethamine with dapsone + leucovorin

RegimenPyrimethamine prescribed with dapsone and leucovorin for primary prophylaxis in HIV-infected patients (off-label)

TMP‑SMX requirementMember must use TMP‑SMX for prophylaxis unless contraindicated (step therapy requirement)

Dose limitDose does not exceed 75 mg per week for primary prophylaxis

Age/CD4 criteriaAge ≥6 years: CD4 <100 cells/mm3; Age <6 years: CD4% <15%

Guideline sources cited

Key guideline sourcesHHS/IDSA opportunistic infection guidelines (adult & pediatric), CDC clinical guidance, and Daraprim prescribing information

HHS/IDSA (adult)Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents (Toxoplasma gondii encephalitis)

HHS/IDSA (pediatric)Guidelines for prevention and treatment of opportunistic infections in HIV-exposed and HIV-infected children (Toxoplasmosis)

CDC guidanceCDC clinical guidance referenced for related infectious disease management (e.g., malaria guidance cited in references)

OpenPayer

Pyrimethamine (Daraprim) Coverage

Coverage Criteria for Pyrimethamine (Daraprim)

Coding and Clinical Thresholds

Provider Actions, Prior Authorization, and Documentation

Background

Definitions and Guideline Sources