Note: Oral leucovorin should be administered throughout the entire course to prevent hematologic toxicity (AAP [Red Book 2018]; HHS [OI pediatric 2019]).
Congenital toxoplasmosis (independent of HIV status); treatment: In combination with sulfadiazine and leucovorin: 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); total treatment duration: 12 months (AAP [Red Book 2018]; HHS [OI pediatric 2019]).
Note: Oral leucovorin should be administered throughout the entire course to prevent hematologic toxicity (AAP [Red Book 2018]; HHS [OI pediatric 2019]).
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 (HHS [OI pediatric 2019]).
Adolescents: Oral: 50 to 75 mg once daily in combination with leucovorin (HHS [OI adult 2019]).
Chronic maintenance (secondary prophylaxis):
Infants and Children: Oral: 1 mg/kg/day once daily in combination with leucovorin; maximum daily dose: 25 mg/day (HHS [OI pediatric 2019]).
Adolescents: Oral: 25 mg once daily in combination with leucovorin (HHS [OI adult 2019]).
Pneumocystis jirovecii pneumonia (PCP), HIV-exposed/-infected; primary prophylaxis or chronic maintenance (secondary prophylaxis): Alternative therapy (HHS [OI adult 2019]):
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 (HHS [OI pediatric 2019]).
Adolescents: Oral: Encephalitis: 200 mg once as a single dose, followed by weight-based daily dosing; treat for at least 6 weeks (HHS [OI adult 2019]):
Weight <60 kg: 50 mg once daily.
Weight ≥60 kg: 75 mg once daily.
Non-HIV-exposed/-infected (Red Book [AAP 2018]):
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 (AAP [Red Book 2018]; HHS [OI pediatric 2019]).
Toxoplasmosis, prophylaxis, in hematopoietic cell transplantation recipients (Tomblyn 2009):
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 (HHS [OI pediatric 2019]): 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 (HHS [OI adult 2019]): 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 (HHS [OI pediatric 2019]).
Adolescents (HHS [OI adult 2019]): 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.
(For additional information see "Pyrimethamine: Drug information")
Cystoisosporiasis (formerly Isosporiasis) in patients with HIV (alternative agent) (off-label use):
Note: For patients unable to use sulfa agents (HHS [OI adult 2022]).
Acute infection, treatment: Oral: 50 to 75 mg once daily in combination with leucovorin calcium (HHS [OI adult 2022]).
Chronic maintenance therapy (secondary prophylaxis): Oral: 25 mg once daily in combination with leucovorin calcium (HHS [OI adult 2022]).
Pneumocystis pneumonia in patients with HIV (alternative agent) (off-label use):
Primary prophylaxis: 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 (HHS [OI adult 2022]).
Chronic maintenance therapy (secondary prophylaxis): Oral: 50 to 75 mg once weekly in combination with dapsone and leucovorin calcium; or 25 mg once daily in combination with atovaquone and leucovorin calcium (HHS [OI adult 2022]).
Duration of therapy: Continue until CD4 count >200 cells/mm3 for >3 months in response to antiretroviral therapy (ART); 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. If Pneumocystis pneumonia occurs at a CD4 count >200 cells/mm3 in a patient who is not on ART, consider discontinuing secondary prophylaxis once viral load is undetectable for ≥3 to 6 months; if Pneumocystis pneumonia occurs at a CD4 count >200 cells/mm3 while a patient is on ART, secondary prophylaxis is lifelong (HHS [OI adult 2022]).
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; 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 (HHS [OI adult 2022]).
Encephalitis, treatment (off-label): 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 sulfadiazine and leucovorin calcium for at least 6 weeks; or 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 plus clindamycin or atovaquone (alternative regimens). 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 (HHS [OI adult 2022]).
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 successfully complete initial treatment regimen, remain asymptomatic of signs/symptoms of Toxoplasma gondii encephalitis, and have a CD4 count >200 cells/mm3 for >6 months in response to ART (HHS [OI adult 2022]).
Patients without HIV:
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.
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.
2 mg/mL oral suspension
A 2 mg/mL oral suspension may be made with tablets and a 1:1 mixture of Simple Syrup, NF and methylcellulose 1%. Crush forty 25 mg tablets in a mortar and reduce to a fine powder. Add small portions of vehicle and mix to a uniform paste; mix while adding vehicle in incremental proportions to almost 500 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 500 mL. Label "shake well" and "refrigerate". Stable for 91 days.
Oral: Administer with meals to minimize loss of appetite and/or vomiting.
Oral: Administer with meals to minimize GI distress.
Store at 15°C to 25°C (59°F to 77°F). Protect from light.
Used in combination with a sulfonamide for treatment of toxoplasmosis (FDA approved in pediatric patients [age not specified] and adults); has also been used in combination with dapsone as primary or secondary prophylaxis for Pneumocystis jirovecii in HIV-infected patients.
Daraprim may be confused with Dantrium, Daranide
Inhibits 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.
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
Artemether and Lumefantrine: Antimalarial Agents may enhance the adverse/toxic effect 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 the serum concentration of ChlorproMAZINE. Risk C: Monitor therapy
Clofarabine: OCT2 Inhibitors may increase the serum concentration of Clofarabine. Risk C: Monitor therapy
Dalfampridine: OCT2 Inhibitors may increase the 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 enhance the adverse/toxic effect of Dapsone (Systemic). Specifically, concomitant use of antimalarial agents with dapsone may increase the risk of hemolytic reactions. Dapsone (Systemic) may enhance the adverse/toxic effect 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 enhance the adverse/toxic effect 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 the serum concentration of Dofetilide. Risk X: Avoid combination
Folic Acid: May diminish the therapeutic effect 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 enhance the hepatotoxic effect of Pyrimethamine. Risk C: Monitor therapy
MetFORMIN: MATE1/2-K Inhibitors may increase the serum concentration of MetFORMIN. Risk C: Monitor therapy
Methotrexate: Pyrimethamine may enhance the adverse/toxic effect of Methotrexate. Risk C: Monitor therapy
Methylfolate: May diminish the therapeutic effect of Pyrimethamine. Risk C: Monitor therapy
PEMEtrexed: Pyrimethamine may enhance the adverse/toxic effect of PEMEtrexed. Risk C: Monitor therapy
PRALAtrexate: Pyrimethamine may enhance the adverse/toxic effect of PRALAtrexate. Risk C: Monitor therapy
Proguanil: Pyrimethamine may enhance the adverse/toxic effect of Proguanil. Risk C: Monitor therapy
Raltitrexed: Pyrimethamine may enhance the adverse/toxic effect of Raltitrexed. Risk C: Monitor therapy
Sulfonamide Antibiotics: Pyrimethamine may enhance the adverse/toxic effect of Sulfonamide Antibiotics. Risk C: Monitor therapy
Trimethoprim: Pyrimethamine may enhance the adverse/toxic effect of Trimethoprim. Risk C: Monitor therapy
Take with meals.
Pregnancy should be avoided during therapy.
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.
Pyrimethamine is recommended for treatment of T. gondii in pregnant patients with HIV, including those with a strong suspicion of fetal infection. Pyrimethamine should not be used in the first trimester (HHS [OI adult 2022]).
CBC, including platelet counts twice weekly with high-dose therapy (eg, when used for toxoplasmosis treatment; frequency not defined for lower doses); liver 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%)
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