CurrentCignaPolicy IP0348

Pyrimethamine

Cigna drug coverage policy for pyrimethamine tablets (Daraprim and generic) outlining medical necessity criteria for treatment and prophylaxis of toxoplasmosis, cystoisosporiasis, and Pneumocystis pneumonia, preferred product requirements, employer/individual plan brand-generic exceptions, and non-covered indications.

Policy Summary

PayerCigna

PolicyPyrimethamine

Policy CodePolicy IP0348

Change TypeCriteria revisions and combination therapy clarifications

Effective DateMar 15, 2025

Next Review Date

Key ActionPrior authorization required for listed indications with approvals for 1 year and pyrimethamine must be prescribed with leucovorin and by or in consultation with an infectious diseases or HIV specialist.

POLICY UPDATE CHANGES

Added requirement that medication is prescribed in combination with leucovorin for all indications and relocated brand/generic step-through to preferred product tables.

Changed various prior language about 'failure, contraindication, or intolerance' to 'patient has tried at least one other therapy' with examples moved to Notes.

Added requirement that certain indications must be prescribed in combination with systemic dapsone OR atovaquone (or systemic clindamycin/atovaquone where specified).

7Covered Indications (listed)

1Not Covered Example (malaria)

Approval Duration (years)

Coverage Summary

Cigna covers pyrimethamine tablets (Daraprim and generic) with criteria for treatment and prophylaxis of toxoplasmosis, cystoisosporiasis (formerly isosporiasis), and Pneumocystis pneumonia when medical necessity criteria are met (including specialist involvement, preferred product requirements, and combination therapy requirements). Approvals are generally for 1 year per the policy.

Policy metadata

Policy numberIP0348

Effective date2025-03-15

Last review2024-06-15

StatusCURRENT

SubjectPyrimethamine (Daraprim) tablets

Medical Necessity Criteria

Medical Necessity Criteria - General

Pyrimethamine tablets (Daraprim, generic) are medically necessary when ONE of the following is met:

ANY of the following

FDA-Approved Indication: Toxoplasmosis - Treatment
- Approve for 1 year
  Authorization duration
- Combination with sulfonamide or alternatives
  - Medication is prescribed in combination with sulfadiazine
  - ALL of the following
    Medication is prescribed in combination with systemic clindamycin

Provider Actions & Billing Rules

Actionable provider callouts

Other provider-impact notes & definitions

Applicable Codes

Drug (NDC) / ProductNDC

No codes listed

Note

Background and Clinical Evidence

Pyrimethamine is a folic acid antagonist indicated primarily for the treatment of toxoplasmosis when used conjointly with a sulfonamide; it is considered the most effective drug against toxoplasmosis. Leucovorin (a folinic acid) is required concomitantly to protect bone marrow from pyrimethamine toxicity. Clinical guidelines recommend pyrimethamine for treatment and chronic maintenance (secondary prophylaxis) of Toxoplasma gondii encephalitis and as an option for primary prophylaxis of Toxoplasma gondii encephalitis and for primary/secondary prophylaxis and treatment of Pneumocystis pneumonia and cystoisosporiasis.

Evidence

Guideline sourceGuidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV (last updated September 2023)

Prescribing informationDaraprim prescribing information, Vyera, August 2017

Unproven / Exclusions

Uses not listed in the policy are considered experimental, investigational, or unproven and are not covered. Specifically, malaria chemoprophylaxis or treatment is not covered. Brand Daraprim is covered for employer and individual plans only when the patient has tried the bioequivalent generic and cannot take the generic due to a formulation difference in inactive ingredients that would, per the prescriber, cause a significant allergy or serious adverse reaction.

Revision History

6/15/2024revised

Added 'medication is prescribed in combination with leucovorin' for all indications; relocated requirement to step through generic pyrimethamine to preferred product tables and updated language. Changed prior 'failure, contraindication, or intolerance to ONE of the following' phrasing to 'patient has tried at least one other therapy' with examples moved to a Note for cystoisosporiasis, Pneumocystis pneumonia, and Toxoplasma gondii prophylaxis/treatment; added combination requirements with systemic dapsone OR atovaquone for certain prophylaxis indications. Detail: Multiple indications had language changed from 'failure, contraindication, or intolerance to ONE of the following' to 'patient has tried at least one other therapy' with examples moved to Notes; added combination requirements with systemic dapsone or atovaquone for some prophylaxis indications.

3/15/2025revisedLatest

Policy effective date 3/15/2025 with continued inclusion that pyrimethamine must be prescribed in combination with leucovorin and clarification of prior-language changes to 'patient has tried at least one other therapy' and combination requirements for certain indications. Detail: Added requirement that medication is prescribed in combination with leucovorin for all indications and relocated brand/generic step-through to preferred product tables.

Policy Summary

PayerCigna

PolicyPyrimethamine

Policy CodePolicy IP0348

Change TypeCriteria revisions and combination therapy clarifications

Effective DateMar 15, 2025

Next Review Date

On This Page

Medication is prescribed in combination with atovaquone

Medication is prescribed by or in consultation with an infectious diseases specialist or a physician specializing in HIV infection

Preferred product criteria is met for the product(s) as listed in the below table(s)

Cystoisosporiasis - Secondary Prophylaxis (Chronic Maintenance Treatment)

Approve for 1 year
Patient has tried at least one other therapy for this condition
Examples include trimethoprim-sulfamethoxazole and systemic ciprofloxacin
Medication is prescribed in combination with leucovorin
Medication is prescribed by or in consultation with an infectious diseases specialist or a physician specializing in HIV infection
Preferred product criteria is met for the product(s) as listed in the below table(s)

Cystoisosporiasis - Treatment

Approve for 1 year
Patient has tried at least one other therapy for this condition
Examples include trimethoprim-sulfamethoxazole and systemic ciprofloxacin
Medication is prescribed in combination with leucovorin
Medication is prescribed by or in consultation with an infectious diseases specialist or a physician specializing in HIV infection
Preferred product criteria is met for the product(s) as listed in the below table(s)

Pneumocystis Pneumonia - Primary Prophylaxis

Approve for 1 year
Patient has tried at least one other therapy for this condition
Examples include trimethoprim-sulfamethoxazole, systemic dapsone, aerosolized pentamidine (via Respigard II nebulizer), and atovaquone
Medication is prescribed in combination with leucovorin
ANY of the following
- Medication is prescribed in combination with systemic dapsone
- Medication is prescribed in combination with atovaquone
Medication is prescribed by or in consultation with an infectious diseases specialist or a physician specializing in HIV infection
Preferred product criteria is met for the product(s) as listed in the below table(s)

Pneumocystis Pneumonia - Secondary Prophylaxis (Chronic Maintenance Therapy)

Approve for 1 year
Patient has tried at least one other therapy for this condition
Examples include trimethoprim-sulfamethoxazole, systemic dapsone, aerosolized pentamidine (via Respigard II nebulizer), and atovaquone
Medication is prescribed in combination with leucovorin
ANY of the following
- Medication is prescribed in combination with systemic dapsone
- Medication is prescribed in combination with atovaquone
Medication is prescribed by or in consultation with an infectious diseases specialist or a physician specializing in HIV infection
Preferred product criteria is met for the product(s) as listed in the below table(s)

Toxoplasma gondii Encephalitis - Primary Prophylaxis

Approve for 1 year
Patient has tried at least one other therapy for this condition
Examples include trimethoprim-sulfamethoxazole and atovaquone
Medication is prescribed in combination with leucovorin
ANY of the following
- Medication is prescribed in combination with systemic dapsone
- Medication is prescribed in combination with atovaquone
Medication is prescribed by or in consultation with an infectious diseases specialist or a physician specializing in HIV infection
Preferred product criteria is met for the product(s) as listed in the below table(s)

Toxoplasma gondii Encephalitis - Secondary Prophylaxis (Chronic Maintenance Therapy)

Approve for 1 year
Medication is prescribed in combination with leucovorin
ANY of the following
- Medication is prescribed in combination with sulfadiazine
- ALL of the following
  - Medication is prescribed in combination with systemic clindamycin
  - Medication is prescribed in combination with atovaquone
Medication is prescribed by or in consultation with an infectious diseases specialist or a physician specializing in HIV infection
Preferred product criteria is met for the product(s) as listed in the below table(s)

3/15/2025clarifiedLatest

Clarified that certain indications require pyrimethamine to be prescribed in combination with systemic dapsone OR atovaquone (and where specified, systemic clindamycin/atovaquone alternatives). Detail: Specifically added combination requirements for Pneumocystis Pneumonia and Toxoplasma primary/secondary prophylaxis and others as noted.

This policy has a material change. Key material updates include: a requirement that pyrimethamine be prescribed in combination with leucovorin for all indications; changed language from 'failure, contraindication, or intolerance to ONE of the following' to the less prescriptive 'patient has tried at least one other therapy' with examples moved to Notes; and added specific combination requirements (for example, needing concomitant systemic dapsone OR atovaquone, or other specified combinations) for certain prophylaxis indications.