Cystoisosporiasis (formerly Isosporiasis) in patients with HIV (alternative agent) (off-label use):
Note: For patients unable to use sulfa agents (Ref).
Acute infection, treatment: Oral: 50 to 75 mg once daily in combination with leucovorin calcium (Ref).
Chronic maintenance therapy (secondary prophylaxis): Oral: 25 mg once daily in combination with leucovorin calcium (Ref).
Pneumocystis pneumonia in patients with HIV (alternative agent) (off-label use):
Prophylaxis, primary or secondary: Oral: 50 or 75 mg once weekly in combination with dapsone and leucovorin calcium. Continue until CD4 count ≥200 cells/mm3 for ≥3 months in response to antiretroviral therapy (ART); may consider discontinuation of prophylaxis in patients with CD4 counts between 100 and 200 cells/mm3 who are receiving ART and have had an undetectable viral load for ≥3 to 6 months (Ref).
Toxoplasmosis:
Patients with HIV:
Primary prophylaxis (alternative agent) (off-label use): Oral: 50 or 75 mg once weekly in combination with dapsone and leucovorin calcium; or 25 mg once daily in combination with atovaquone and leucovorin calcium. Continue until CD4 count >200 cells/mm3 for >3 months in response to ART and viral load is undetectable; some experts discontinue prophylaxis in patients with CD4 counts between 100 and 200 cells/mm3 who are receiving ART and have had an undetectable viral load for ≥3 to 6 months (Ref).
Encephalitis, treatment: Oral: 200 mg as a single dose, followed by 50 mg once daily (patient weight ≤60 kg) or 75 mg once daily (patient weight >60 kg), in combination with leucovorin calcium and other appropriate agents (eg, atovaquone, clindamycin, or sulfadiazine [preferred]). Duration is for ≥6 weeks (longer if extensive disease or incomplete response) followed by chronic maintenance therapy. Note: If pyrimethamine is unavailable or there is a procurement delay, trimethoprim-sulfamethoxazole should be used in place of pyrimethamine-containing regimens until pyrimethamine is available (Ref).
Chronic maintenance therapy (secondary prophylaxis) (off-label use): Oral: 25 to 50 mg once daily in combination with sulfadiazine and leucovorin calcium; or 25 to 50 mg once daily in combination with clindamycin and leucovorin calcium (alternative regimen); or 25 mg once daily in combination with atovaquone and leucovorin calcium (alternative regimen). May discontinue in patients who remain asymptomatic of signs/symptoms of Toxoplasma gondii encephalitis, and have a CD4 count >200 cells/mm3 for >6 months in response to ART (Ref).
Patients without HIV:
Primary prophylaxis in solid organ transplant recipients (alternative agent) (off-label use): Oral: 50 mg once weekly in combination with dapsone and leucovorin calcium. Primary prophylaxis is often lifelong for donor-seropositive/recipient-seronegative (D+/R-) cardiac recipients, although discontinuation of prophylaxis may be considered with close clinical and laboratory monitoring; prophylaxis may be considered for D+/R- noncardiac recipients with duration dependent on patient-specific factors and/or institutional protocols (Ref).
Treatment: Oral: 50 to 75 mg once daily in combination with a sulfonamide and leucovorin calcium for 1 to 3 weeks depending on patient's tolerance and response, then may reduce dose by 50% and continue for 4 to 5 weeks (Ref).
Solid organ transplant recipients: Oral: 200 mg as a single dose, followed by 50 mg once daily (patient weight <60 kg) or 75 mg once daily (patient weight ≥60 kg), in combination with leucovorin calcium and other appropriate agents (eg, atovaquone, clindamycin, or sulfadiazine [preferred]). Duration is ≥6 weeks, followed by lifelong suppression (Ref).
Chronic suppressive therapy in solid organ transplant recipients (off-label use): Oral: 25 mg (patient weight <60 kg) or 50 mg (patient weight ≥60 kg) once daily in combination with leucovorin calcium and other appropriate agents (eg, atovaquone, clindamycin, sulfadiazine [preferred]) (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer’s labeling. Use with caution.
There are no dosage adjustments provided in the manufacturer’s labeling. Use with caution.
Refer to adult dosing.
(For additional information see "Pyrimethamine: Pediatric drug information")
Note: Oral leucovorin should be administered throughout the entire course to prevent hematologic toxicity (Ref).
Cystoisosporiasis (formerly isosporiasis), HIV-exposed/-infected: Alternative therapy to sulfamethoxazole/trimethoprim.
Treatment :
Infants and Children: Oral: 1 mg/kg/day once daily in combination with leucovorin for 14 days; maximum daily dose: 25 mg/day (Ref).
Adolescents: Oral: 50 to 75 mg once daily in combination with leucovorin (Ref).
Chronic maintenance (secondary prophylaxis):
Infants and Children: Oral: 1 mg/kg/day once daily in combination with leucovorin; maximum daily dose: 25 mg/day (Ref).
Adolescents: Oral: 25 mg once daily in combination with leucovorin (Ref).
Pneumocystis jirovecii pneumonia (PCP), HIV-exposed/-infected; primary prophylaxis or chronic maintenance (secondary prophylaxis): Alternative therapy (Ref):
Adolescents: Oral:
In combination with dapsone and leucovorin: 50 to 75 mg once weekly (dose depends on dapsone dose).
In combination with atovaquone and leucovorin: 25 mg once daily.
Toxoplasmosis, acquired infection (including encephalitis); treatment:
HIV-exposed/-infected:
Infants and Children: Oral: 2 mg/kg/day (maximum dose: 50 mg/dose) once daily for 3 days followed by 1 mg/kg/day once daily (maximum dose: 25 mg/dose) in combination with leucovorin and either sulfadiazine or clindamycin; treat for at least 6 weeks; consider longer duration if clinical or radiologic disease is extensive or incomplete response; follow with chronic suppressive therapy in patients experiencing encephalitis (Ref).
Adolescents: Oral: Encephalitis: 200 mg once as a single dose, followed by weight-based daily dosing; treat for at least 6 weeks (Ref):
Weight <60 kg: 50 mg once daily.
Weight ≥60 kg: 75 mg once daily.
Non-HIV-exposed/-infected (Ref):
Note: Use in combination with leucovorin and either sulfadiazine or clindamycin.
Infants, Children, and Adolescents:
<60 kg: Oral: Initial: 2 mg/kg/day in divided doses twice daily for 2 days (maximum dose: Chorioretinitis: 25 mg/dose; severe or CNS disease: 50 mg/dose); followed by 1 mg/kg/day once daily (maximum dose: Chorioretinitis: 25 mg/dose; severe or CNS disease: 50 mg/dose). Continue therapy for 1 to 2 weeks after symptom resolution, for a total therapy of 4 to 6 weeks.
≥60 kg: Oral: Initial: 2 mg/kg/day in divided doses twice daily for 2 days (maximum dose: Chorioretinitis: 25 mg/dose; severe or CNS disease: 50 mg/dose); followed by 1 mg/kg/day once daily (maximum dose: Chorioretinitis: 25 mg/dose; severe or CNS disease: 75 mg/dose). Continue therapy for 1 to 2 weeks after symptom resolution, for a total therapy of 4 to 6 weeks.
Toxoplasmosis, congenital infection (independent of HIV status); treatment: In combination with sulfadiazine and leucovorin:
Infants: Oral: Initial: 2 mg/kg/day once daily or in 2 divided doses for 2 days, then 1 mg/kg/day once daily for 2 to 6 months, then 1 mg/kg/dose 3 times weekly (eg, Monday, Wednesday, Friday); maximum dose: 25 mg/dose; total treatment duration: 12 months (Ref).
Toxoplasmosis, prophylaxis, in hematopoietic cell transplantation recipients (Ref):
Infants and Children: Oral: 1 mg/kg/day once daily with clindamycin and leucovorin; maximum dose: 75 mg/dose. Start after engraftment and administer as long as the patient remains on immunosuppressive therapy.
Adolescents: Oral: 25 to 75 mg once daily with clindamycin and leucovorin. Start after engraftment and administer as long as the patient remains on immunosuppressive therapy.
Toxoplasmosis, prophylaxis, in HIV-exposed/-infected patients:
Primary prophylaxis: Alternative therapy to sulfamethoxazole/trimethoprim:
Infants and Children (Ref): Oral:
In combination with dapsone and oral leucovorin: 1 mg/kg/day once daily; maximum dose: 25 mg/dose.
In combination with atovaquone and oral leucovorin: Infants and Children 4 to 24 months: 1 mg/kg/day or 15 mg/m2/day once daily; maximum dose: 25 mg/dose.
Adolescents (Ref): Oral:
In combination with dapsone and oral leucovorin: 50 mg or 75 mg once weekly.
In combination with atovaquone and oral leucovorin: 25 mg once daily.
Secondary prophylaxis/suppressive therapy:
Infants and Children: Oral: 1 mg/kg/day or 15 mg/m2/day once daily (maximum dose: 25 mg/dose) with leucovorin and sulfadiazine, clindamycin, or atovaquone (Ref).
Adolescents (Ref): Oral:
In combination with sulfadiazine or clindamycin: 25 to 50 mg once daily plus leucovorin.
In combination with atovaquone: 25 mg once daily plus leucovorin.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling; use with caution.
There are no dosage adjustments provided in the manufacturer's labeling; use with caution.
The following adverse drug reactions are derived from product labeling unless otherwise specified. Reported adverse reactions include combination therapy.
Frequency not defined:
Cardiovascular: Cardiac arrhythmia
Dermatologic: Erythema multiforme
Gastrointestinal: Anorexia, glossitis (atrophic), vomiting
Genitourinary: Hematuria
Hematologic & oncologic: Hematologic abnormality (hyperphenylalaninemia), megaloblastic anemia, neutropenia, pancytopenia
Postmarketing:
Dermatologic: Stevens-Johnson syndrome (Phillips-Howard 1990), toxic epidermal necrolysis (Phillips-Howard 1990)
Hematologic & oncologic: Agranulocytosis (Booth 1984), granulocytopenia (Phillips-Howard 1990), leukopenia (Phillips-Howard 1990), thrombocytopenia (Phillips-Howard 1990)
Hepatic: Hepatic impairment (including hepatitis) (Phillips-Howard 1990)
Hypersensitivity: Drug reaction with eosinophilia and systemic symptoms (Sousa 2016), hypersensitivity reaction (including anaphylaxis, angioedema) (Phillips-Howard 1990)
Nervous system: Seizure (Phillips-Howard 1990)
Ophthalmic: Iritis (Phillips-Howard 1990), toxic amblyopia (Phillips-Howard 1990)
Respiratory: Eosinophilic pneumonitis (Davidson 1988)
Hypersensitivity to pyrimethamine or any component of the formulation; megaloblastic anemia secondary to folate deficiency
Concerns related to adverse effects:
• Hematologic: Megaloblastic anemia, leukopenia, thrombocytopenia, neutropenia, and pancytopenia have been reported; most commonly with high doses.
Disease-related concerns:
• Folate deficiency: Use caution in patients with possible folate deficiency (eg, malabsorption syndrome, alcoholism).
• G6PD deficiency: Use with caution in patients with possible G6PD deficiency.
• Hepatic impairment: Use with caution in patients with hepatic impairment.
• Renal impairment: Use with caution in patients with renal impairment.
• Seizure disorders: Use with caution in patients with a history of seizure disorders.
Other warnings/precautions:
• Leucovorin: Administer leucovorin to prevent hematologic complications due to pyrimethamine-induced folic acid deficiency state; continue leucovorin during therapy and for 1 week after therapy is discontinued (to account for long half-life of pyrimethamine) (HHS [OI pediatric 2019])
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Tablet, Oral:
Daraprim: 25 mg [DSC] [scored]
Daraprim: 25 mg [scored; contains corn starch]
Generic: 25 mg
Yes
Tablets (Daraprim Oral)
25 mg (per each): $900.00
Tablets (Pyrimethamine Oral)
25 mg (per each): $796.88 - $855.00
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Oral: Administer with meals to minimize GI distress.
Oral: Administer with meals to minimize loss of appetite and/or vomiting.
Toxoplasmosis: Treatment of toxoplasmosis when used in combination with a sulfonamide.
Cystoisosporiasis (formerly Isosporiasis) in patients with HIV; Pneumocystis pneumonia in patients with HIV, prophylaxis; Toxoplasma gondii encephalitis, prophylaxis
Daraprim may be confused with Dantrium, Daranide
Inhibits MATE1/2-K, OCT1, OCT2;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Artemether and Lumefantrine: Antimalarial Agents may increase adverse/toxic effects of Artemether and Lumefantrine. Management: Artemether/lumefantrine (combination product) should not be used with other antimalarials unless there is no other treatment option. If combined, monitor patients for increased toxicities of both agents, including QTc interval prolongation. Risk D: Consider Therapy Modification
ChlorproMAZINE: Antimalarial Agents may increase serum concentration of ChlorproMAZINE. Risk C: Monitor
Clofarabine: OCT2 Inhibitors may increase serum concentration of Clofarabine. Risk C: Monitor
CYP3A4 Inducers (Strong): May decrease serum concentration of Pyrimethamine. Risk C: Monitor
Dalfampridine: OCT2 Inhibitors may increase serum concentration of Dalfampridine. Management: Consider alternatives to this combination. Carefully weigh the risk of seizures against the benefit of combining OCT2 inhibitors with dalfampridine. Risk D: Consider Therapy Modification
Dapsone (Systemic): Antimalarial Agents may increase adverse/toxic effects of Dapsone (Systemic). Specifically, concomitant use of antimalarial agents with dapsone may increase the risk of hemolytic reactions. Dapsone (Systemic) may increase adverse/toxic effects of Antimalarial Agents. Specifically, concomitant use of dapsone with antimalarial agents may increase the risk for hemolytic reactions. Management: Closely monitor patients for signs/symptoms of hemolytic reactions with concomitant use of dapsone and antimalarial agents, particularly in patients deficient in glucose-6-phosphate dehydrogenase (G6PD), methemoglobin reductase, or with hemoglobin M. Risk D: Consider Therapy Modification
Dapsone (Topical): Antimalarial Agents may increase adverse/toxic effects of Dapsone (Topical). Specifically, the risk of hemolytic reactions may be increased. Management: Consider avoidance of this combination when possible. If combined, closely monitor for signs/symptoms of hemolytic reactions. Patients with glucose-6-phosphate dehydrogenase deficiency may be at particularly high risk for adverse hematologic effects. Risk D: Consider Therapy Modification
Dofetilide: MATE1/2-K Inhibitors may increase serum concentration of Dofetilide. Risk X: Avoid
Folic Acid: May decrease therapeutic effects of Pyrimethamine. Management: Folic acid doses greater than 2.5 mg per day should be avoided due to the potential for sulfadoxine/pyrimethamine treatment failure. Consider limiting folic acid use to no more than 0.4 mg per day for women of child-bearing age. Risk D: Consider Therapy Modification
LORazepam: May increase hepatotoxic effects of Pyrimethamine. Risk C: Monitor
MetFORMIN: MATE1/2-K Inhibitors may increase serum concentration of MetFORMIN. Risk C: Monitor
Methotrexate: Pyrimethamine may increase adverse/toxic effects of Methotrexate. Risk C: Monitor
PEMEtrexed: Pyrimethamine may increase adverse/toxic effects of PEMEtrexed. Risk C: Monitor
Phenobarbital-Primidone: May decrease serum concentration of Pyrimethamine. Risk C: Monitor
PRALAtrexate: Pyrimethamine may increase adverse/toxic effects of PRALAtrexate. Risk C: Monitor
Proguanil: Pyrimethamine may increase adverse/toxic effects of Proguanil. Risk C: Monitor
Raltitrexed: Pyrimethamine may increase adverse/toxic effects of Raltitrexed. Risk C: Monitor
Sulfonamide Antibiotics: Pyrimethamine may increase adverse/toxic effects of Sulfonamide Antibiotics. Risk C: Monitor
Trimethoprim: Pyrimethamine may increase adverse/toxic effects of Trimethoprim. Risk C: Monitor
Pregnancy should be avoided during therapy.
Pyrimethamine crosses the placenta (Peytavin 2000).
Pyrimethamine should be used with caution in patients with possible folate deficiency, including pregnant patients. If administered during pregnancy (ie, for toxoplasmosis), supplementation of folate is strongly recommended. Avoid use during the first trimester for indications other than toxoplasmosis due to adverse events observed in animal reproduction studies.
Pyrimethamine is recommended for treatment of T. gondii encephalitis in pregnant patients with HIV. Dosing is the same as in nonpregnant patients. Maternal use of pyrimethamine is also recommended for the treatment of fetal toxoplasmosis infection. Agents other than pyrimethamine are recommended for the management of Pneumocystis pneumonia during pregnancy (HHS [OI adult 2024]).
Pyrimethamine is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, the manufacturer recommends a decision be made to discontinue breastfeeding or to discontinue the drug, considering the importance of treatment to the mother.
Take with meals.
CBC, including platelet counts twice weekly with high-dose therapy (eg, when used for toxoplasmosis treatment; frequency not defined for lower doses); hepatic and renal function
Inhibits parasitic dihydrofolate reductase, resulting in inhibition of vital tetrahydrofolic acid synthesis
Absorption: Well absorbed
Distribution: Vd: Adults: 2.9 L/kg; distributed to the kidneys, lung, liver, and spleen
Protein binding: 87%
Half-life elimination: 80 to 95 hours (White 1985)
Time to peak, serum: 2 to 6 hours
Excretion: Urine (16% to 32%)