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Daraprim (Pyrimethamine) Information

Daraprim (pyrimethamine) is an orally administered antiparasitic compound that acts as a potent folic acid antagonist. It is a cornerstone medication, typically used in combination with a sulfonamide (such as sulfadiazine) and often with folinic acid (leucovorin), for the treatment of specific protozoal infections. Daraprim is primarily indicated for the acute and chronic treatment of toxoplasmosis, including ocular infections and congenital toxoplasmosis, particularly in immunodeficient patients such as those with HIV/AIDS. It is also an FDA-approved antimalarial agent for treating chloroquine-resistant P. falciparum malaria when used with another agent, and for certain forms of prophylaxis. However, it is not recommended for malaria prophylaxis for travellers in any region due to global widespread parasite resistance. The dosage required for toxoplasmosis treatment is substantially higher (10 to 20 times) than the dose used for malaria prophylaxis, which places it close to its toxic level, necessitating highly cautious and carefully monitored administration. The co-administration of leucovorin is vital to serve as a rescue agent that protects human bone marrow cells from pyrimethamine's toxic effects.

The mechanism of action for pyrimethamine centers on its role as a selective dihydrofolate reductase (DHFR) inhibitor. It competitively inhibits the DHFR enzyme, which is necessary for the regeneration of tetrahydrofolic acid from dihydrofolate. Tetrahydrofolic acid is an essential cofactor for the synthesis of nucleic acids (DNA and RNA) and proteins. The rationale for its therapeutic action is based on the differential requirement between the human host and the parasite (Toxoplasma gondii or Plasmodium species) for these precursors. Pyrimethamine exhibits a far greater affinity for the protozoal DHFR enzyme than for the human enzyme. This effectively starves the parasite of the folic acid derivatives necessary for growth and reproduction, thereby halting the infection. Pyrimethamine is well absorbed following oral administration and is eliminated slowly, with a half-life of approximately 80 to 95 hours.

Daraprim Side Effects

Pyrimethamine is associated with a narrow therapeutic window, and most side effects, particularly hematologic ones, are dose-related. Common side effects often associated with the high doses used in toxoplasmosis treatment include gastrointestinal disturbances such as anorexia, nausea, and vomiting, which may be minimized by taking the drug with meals or with the administration of folinic acid (leucovorin). Other non-serious effects include headache, lightheadedness, and dry mouth.

However, more serious side effects can occur, primarily stemming from its mechanism as a folic acid antagonist. These severe effects are often preventable or reversible with prompt discontinuation of the drug and the administration of folinic acid. If any of the following symptoms are experienced, the patient should stop taking the medication and seek immediate medical attention:

• Acute Central Nervous System (CNS) Toxicity / Seizures (Overdose): High doses or overdose can lead to severe CNS excitement, including tremors and generalized seizures. Pyrimethamine should be used with caution in patients with a history of seizure disorders.

• Cardiac Arrhythmias: Abnormal heart rhythms have been reported with high doses, which can occasionally lead to fainting or more serious cardiac events.

• Hepatic Failure: Rare reports of severe liver injury or impairment, requiring caution in patients with pre-existing hepatic disease.

• Hypersensitivity Reactions / Severe Cutaneous Adverse Reactions (SCARs): Hypersensitivity reactions, sometimes severe, can occur, particularly when pyrimethamine is used with a sulfonamide. These include widespread skin rashes, Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN), Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome, and erythema multiforme.

• Pulmonary Eosinophilia: A rare but severe lung reaction characterized by an increase in eosinophils, leading to breathing problems.

• Severe Blood Dyscrasias: The most common serious toxicity, resulting from interference with human folic acid metabolism. This includes severe, potentially fatal megaloblastic anemia, leukopenia (low white blood cells), thrombocytopenia (low platelets), and pancytopenia (a reduction in all major blood cell types). Close monitoring of complete blood and platelet counts (at least weekly) is mandatory, especially with high-dose therapy.

Daraprim Precautions

A detailed discussion of medical history is crucial before initiating pyrimethamine therapy. Pyrimethamine is contraindicated in patients with known hypersensitivity to the drug and in those with documented megaloblastic anemia due to folate deficiency. Caution is warranted in patients with pre-existing impaired renal or hepatic function, seizure disorders, or conditions that predispose to folate deficiency, such as alcoholism or malabsorption syndromes. Due to the high risk of severe blood dyscrasias, folinic acid (leucovorin) should be administered concurrently with pyrimethamine, especially at the high doses required for toxoplasmosis, and should continue during therapy and for at least one week after drug discontinuation to allow for sufficient bone marrow recovery. Use during pregnancy requires a careful assessment of the potential benefit versus the possible risk, as animal studies have shown teratogenic effects; concurrent folinic acid is strongly recommended if used in a pregnant patient. Pyrimethamine is excreted in breast milk, and caution should be exercised when administering to nursing mothers. Furthermore, pyrimethamine has numerous clinically significant drug interactions, and concomitant use with other folate antagonists or agents that suppress the bone marrow (e.g., methotrexate, trimethoprim-sulfamethoxazole, zidovudine) is likely to increase the risk of severe hematological toxicity significantly and should be avoided or intensely monitored.

Do I need a prescription to order Daraprim?

Yes, a prescription is required from your physician to order Daraprim.