INDICATIONS

DARAPRIM® (pyrimethamine) is indicated for the treatment of toxoplasmosis when used conjointly with a sulfonamide.

IMPORTANT SAFETY INFORMATION

DARAPRIM is contraindicated in patients with known hypersensitivity to pyrimethamine or to any component of the formulation and in patients with documented megaloblastic anemia due to folate deficiency.

Potential for folate deficiency: Dosage required for toxoplasmosis treatment approaches the toxic level. If signs of folate deficiency develop, reduce the dosage or discontinue the drug according to patient response. Administer folinic acid (leucovorin) at 5-15 mg per day until normal hematopoiesis is restored.

Carcinogenic potential: Data indicates that pyrimethamine may be carcinogenic.

Adverse reactions:

• Hypersensitivity reactions, occasionally severe (such as Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, and anaphylaxis), and hyperphenylalaninemia, can occur particularly when pyrimethamine is administered concomitantly with a sulfonamide. Consult the full prescribing information for relevant sulfonamide-associated adverse events.
• Megaloblastic anemia, leukopenia, thrombocytopenia, pancytopenia, neutropenia, atrophic glossitis, hematuria, cardiac rhythm disorders, anorexia and vomiting may occur with doses used for toxoplasmosis treatment. Hematologic effects may also occur at low doses in certain individuals.
• Pulmonary eosinophilia has been reported rarely.

Pregnancy Category C:

• There are no adequate and well-controlled studies in pregnant women. DARAPRIM should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Women of childbearing potential should be warned against becoming pregnant during treatment with DARAPRIM.

Pyrimethamine is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from pyrimethamine, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Keep out of the reach of infants and children: Deaths in pediatric patients have been reported after accidental ingestion.

Drug Interactions:

• The concomitant use of pyrimethamine with other antifolic drugs or agents associated with myelosuppression including sulfonamides or trimethoprim-sulfamethoxazole combination, proguanil, zidovudine, or cytostatic agents (e.g., methotrexate), may increase the risk of bone marrow suppression. If signs of folate deficiency develop, pyrimethamine should be discontinued and folinic acid should be given until hematopoiesis is restored (see above).
• Use DARAPRIM with caution in patients receiving therapy, such as phenytoin, that affect folate levels.
• Mild hepatotoxicity can occur when lorazepam and pyrimethamine are administered concomitantly.

Dosing Information:

• For specific dosing instructions see the Full Prescribing Information.
• Do not exceed the recommended dosage.
• Start with a small dose for toxoplasmosis in patients with convulsive disorders to avoid the potential nervous system toxicity of pyrimethamine (see Overdosage).
• Use with caution in patients with impaired renal or hepatic function; in patients with possible folate deficiency such as individuals with malabsorption syndrome, alcoholism, or who are pregnant; and in the elderly due to the potential for decreased hepatic, renal, or cardiac function, and concomitant disease or other drug therapy in this population.
• Concurrent administration of folinic acid is strongly recommended when used for the treatment of toxoplasmosis in ALL patients.
• In patients receiving a high dosage, semiweekly blood counts, including platelet counts should be performed.
• Taking DARAPRIM with meals may minimize associated anorexia and vomiting.

Overdosage:

• Following the ingestion of 300 mg or more of pyrimethamine, gastrointestinal and/or central nervous system signs may be present, including convulsions and death.
• There is no specific antidote to acute pyrimethamine poisoning. Symptomatic and supportive measures should be employed. Gastric lavage is recommended and is effective if carried out very soon after drug ingestion. Parenteral diazepam may be used to control convulsions. Folinic acid should be administered within 2 hours of drug ingestion to be most effective in counteracting the effects on the hematopoietic system. Daily monitoring of peripheral blood counts is recommended for up to several weeks until normal hematologic values are restored.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088. To report SUSPECTED ADVERSE REACTIONS contact Tilde Sciences LLC at 1-877-258-2033, press 1.

Please See Full Prescribing Information