ModifiedCentenePolicy CP PMN.44

Pyrimethamine (Daraprim) coverage

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

Policy Summary

PayerCentene

PolicyPyrimethamine (Daraprim) coverage

Policy CodePolicy CP PMN.44

Change TypeStep therapy bypassprophylaxis clarificationextended continued therapy

Effective Date11.01.15

Next Review Date

Key ActionSubmit prior authorization with documentation showing diagnosis of toxoplasmosis and specialist consultation as specified.

SourceLink

POLICY UPDATE CHANGES

For initial therapy for toxoplasmosis active disease, added step therapy bypass for Illinois HIM per IL HB 5395.

For toxoplasmosis prophylaxis, clarified member must use TMP-SMX unless contraindicated or clinically significant adverse effects are experienced.

In continued therapy for chronic maintenance following initial therapy for active disease, increased duration of approval to 12 months.

In Appendix B, clarified dosing regimen per guideline and updated Section V per guidelines; references reviewed and updated.

25 mgtablet strength available

75 mg/weekmax primary prophylaxis dose

12 monthscontinued therapy approval

08.25last review

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Coverage Criteria for Pyrimethamine (Daraprim)

Initial Therapy

Initial approval — Covered when ALL of the following are met

Initial Therapy for Toxoplasmosis: 1. Diagnosis of toxoplasmosis; 2. Prescribed by or in consultation with an infectious disease or HIV specialist; 3. Pyrimethamine prescribed concurrently with sulfadiazine or clindamycin, and leucovorin; 4. For Daraprim requests, member must use pyrimethamine unless contraindicated or clinically significant adverse effects are experienced; 5. Dosing limits per immunocompromised/immunocompetent status as specified in policy: immunocompromised — initial loading dose up to 200 mg followed by ≤75 mg/day; immunocompetent — initial loading dose up to 100 mg followed by ≤50 mg/day; 6. Step therapy: member must have used trimethoprim-sulfamethoxazole (TMP-SMX) at maximum indicated doses for ≥10 days or have radiologic deterioration within 7 days unless TMP-SMX is contraindicated or causes clinically significant adverse effects (note: for Illinois HIM requests, step therapy requirements do not apply as of 1/1/2026 per IL HB 5395).See dosing nodes

Provider must submit supporting documentation

Primary Prophylaxis

Primary prophylaxis (off-label) — Covered when ALL of the following are met

Primary Prophylaxis for Toxoplasmosis: 1. Diagnosis of HIV infection; 2. Prescribed by or in consultation with an infectious disease or HIV specialist; 3. Request is for prevention of toxoplasmosis; 4. Seropositive for Toxoplasma gondii IgG; 5. Pyrimethamine prescribed with leucovorin and dapsone; 6. Member must use TMP-SMX unless contraindicated or clinically significant adverse effects are experienced; 7. For Daraprim requests, member must use pyrimethamine unless contraindicated or clinically significant adverse effects are experienced; 8. Dose does not exceed 75 mg per week; 9. Age/CD4 criteria apply (e.g., age ≥26 years: CD4 count <100 cells/mm3; age ≥6 years: CD4 percentage <15%).Dose <=75 mg/week

Continued Therapy

Continued therapy / Chronic maintenance — Covered when ALL of the following are met

Chronic Maintenance Following Initial Therapy: 1. Currently receiving medication via Centene benefit or previously met initial approval criteria; 2. Member is HIV-infected with qualifying CD4 criteria (e.g., CD4 <200 cells/mm3) or CD4 percentage rise of ≥15% from baseline within the previous 6 months as specified in policy; 3. Demonstrated adherence to antiretroviral therapy (evidenced by pharmacy claims or office notes); 4. For Daraprim requests, member must use pyrimethamine unless contraindicated or clinically significant adverse effects are experienced; 5. Dose does not exceed 50 mg/day unless supported by practice guidelines or peer-reviewed literature (prescriber must submit supporting evidence).Dose <=50 mg/day unless supported

Dosing and regimen

Policy-level coverage points and dosing considerations referenced in this section include:

Dosing for acute and maintenance toxoplasmosis: Recommended treatment regimens include pyrimethamine combined with leucovorin and sulfadiazine or alternatives; examples in policy and guidelines include: pyrimethamine 50–75 mg PO daily (adult treatment) with sulfadiazine 2,000–4,000 mg PO daily plus leucovorin 10–25 mg PO daily; HHS/CDC guidance lists initial loading doses (e.g., 200 mg loading then 50 mg/day in some HIV-infected patients; 100 mg loading then 25–50 mg/day for ocular disease); primary prophylaxis regimens include pyrimethamine 50–75 mg/week PO with dapsone and leucovorin; chronic maintenance dosing is 25–50 mg/day PO in combination with leucovorin and sulfadiazine, clindamycin, or atovaquone.

Exact regimens and appendix dosing per referenced guidelines and Appendix B.

Authorization duration and step therapy

Authorization durations and step therapy provisions:

Approval durations and step therapy: 1. Continued therapy (chronic maintenance) approval duration: 12 months; 2. Initial approval duration for congenital toxoplasmosis in newborns was previously set to 12 months per CDC guidance; 3. Step therapy requirement: members must use TMP-SMX prior to pyrimethamine for initial active toxoplasmosis unless contraindicated; 4. Illinois HIM bypass: step therapy bypass for IL HIM per IL HB 5395 applies as indicated (effective 1/1/2026) for initial active disease requests; 5. Providers must follow state-specific bypass provisions and document contraindications or adverse effects to TMP-SMX when requesting exception.

Providers should document use of TMP-SMX when required and follow state-specific exceptions.

Coverage for pyrimethamine for the indication of malaria is not authorized. The policy explicitly lists malaria among diagnoses/indications for which coverage is not authorized, and the FDA labeling was updated to remove malaria treatment and chemoprophylaxis. Additionally, CDC guidance discourages use of pyrimethamine for malaria because of widespread global resistance.

For Medicaid members, state Medicaid coverage provisions take precedence where they conflict with this clinical policy. Providers should consult the applicable state Medicaid manual for any state‑specific coverage rules related to this policy.

Requests for non‑FDA approved (off‑label) indications that are not addressed in this policy are not covered unless the provider supplies sufficient documentation of efficacy and safety in accordance with the applicable off‑label use policies (e.g., CP CPA.09 for commercial, HIM.PA.154 for marketplace, CP.PMN.53 for Medicaid) or other evidence of coverage documents.

No explicit statement declaring any particular use as 'not medically necessary' appears in the extracted portion of the document provided. The policy materials emphasize that coverage determinations were developed by clinical experts based on current standards, guidelines, and evidence, but an explicit 'not medically necessary' line is not present in the sections shown.

Dosing and Coding Summary

Primary prophylaxis dose

Primary prophylaxis dose50-75 mg per week PO (in combination with dapsone and leucovorin)

Maximum primary prophylaxis dose75 mg per week

Typical prophylaxis regimensExamples: pyrimethamine 50 mg/week + dapsone 50 mg daily + leucovorin 25 mg/week; or pyrimethamine 75 mg/week + dapsone 200 mg/week + leucovorin 25 mg/week

Chronic maintenance dose

Chronic maintenance dose25-50 mg per day PO (secondary prophylaxis) in combination with leucovorin and sulfadiazine, clindamycin, or atovaquone

Recommended maintenance regimen examplePyrimethamine 25-50 mg PO daily + sulfadiazine 2,000–4,000 mg PO daily (divided) + leucovorin 10–25 mg PO daily

Provider Requirements and Authorization Steps

Prior Authorization

Prior Authorization Required

Prior authorization is required. Requests must include clinical documentation demonstrating the member meets all approval criteria (diagnosis of toxoplasmosis or indicated use, specialist involvement when required, dosing and concurrent therapies). Prior auth must show the prescriber is or consulted with an infectious disease or HIV specialist when specified in the criteria.

A complete submission should include office notes, relevant labs, imaging reports, and medication history.
Authorization duration notes (see policy history) may apply for certain indications (e.g., congenital toxoplasmosis).

Documentation Required

Documentation Required for Review

Provider must submit supporting clinical documentation (office chart notes, laboratory results, radiology reports, medication lists) that clearly demonstrates the member meets the policy criteria. Incomplete documentation may result in denial or delay.

Background and Drug Information

Pyrimethamine (Daraprim) is a folic acid antagonist indicated by the FDA for treatment of toxoplasmosis when used in combination with a sulfonamide. It is used for initial therapy, chronic maintenance, and select prophylactic situations and must be coadministered with leucovorin to reduce hematologic toxicity. FDA labeling revisions removed malaria indications, and higher doses may be required for severe or sequestered infections per clinical guidance.

Definitions

Daraprim (pyrimethamine)

Generic and brandPyrimethamine (Daraprim)

Pharmacologic classFolic acid antagonist

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

AdministrationOral formulation; used in combination with a sulfonamide (e.g., sulfadiazine) plus leucovorin to mitigate hematologic toxicity

Chronic maintenance therapy

DefinitionChronic maintenance therapy (secondary prophylaxis): ongoing lower‑dose pyrimethamine following initial treatment of active toxoplasmosis to prevent relapse