Overview
CLINICAL PHARMACOLOGY Pyrimethamine is well absorbed with peak levels occurring between 2 to 6 hours following administration. It is eliminated slowly and has a plasma half-life of approximately 96 hours. Pyrimethamine is 87% bound to human plasma proteins. Microbiology : Pyrimethamine is a folic acid antagonist and the rationale for its therapeutic action is based on the differential requirement...
Mechanism of Action
CLINICAL PHARMACOLOGY Pyrimethamine is well absorbed with peak levels occurring between 2 to 6 hours following administration. It is eliminated slowly and has a plasma half-life of approximately 96 hours. Pyrimethamine is 87% bound to human plasma proteins. Microbiology : Pyrimethamine is a folic acid antagonist and the rationale for its therapeutic action is based on the differential requirement between host and parasite for nucleic acid precursors involved in growth. This activity is highly selective against Toxoplasma gondii . The action of pyrimethamine against Toxoplasma gondii is greatly enhanced when used in conjunction with sulfonamides. This was demonstrated by Eyles and Coleman 1 in the treatment of experimental toxoplasmosis in the mouse.
Indications
- INDICATIONS AND USAGE Treatment of Toxoplasmosis : Pyrimethamine tablets are indicated for the treatment of toxoplasmosis when used conjointly with a sulfonamide, since synergism exists with this combination.
Common Doses
- 75 mg
- 4 g
- 1 mg
Dosage
DOSAGE AND ADMINISTRATION For Treatment of Toxoplasmosis : The dosage of pyrimethamine tablets for the treatment of toxoplasmosis must be carefully adjusted so as to provide maximum therapeutic effect and a minimum of side effects. At the dosage required, there is a marked variation in the tolerance to the drug. Young patients may tolerate higher doses than older individuals. Concurrent administration of folinic acid is strongly recommended in all patients. The adult starting dose is 50 to 75 mg of the drug daily, together with 1 to 4 g daily of a sulfonamide of the sulfapyrimidine type, e.g.
Contraindications
- CONTRAINDICATIONS Use of pyrimethamine tablets are contraindicated in patients with known hypersensitivity to pyrimethamine or to any component of the formulation. Use of the drug is also contraindicated in patients with documented megaloblastic anemia due to folate deficiency.
Side Effects
- 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 complete prescribing information for the relevant sulfonamide for sulfonamide-associated adverse events. With doses of pyrimethamine used for the treatment of toxoplasmosis, anorexia and vomiting may occur.
Interactions
- Drug Interactions Pyrimethamine may be used with sulfonamides, quinine and other antimalarials, and with other antibiotics. However, the concomitant use of other antifolic drugs or agents associated with myelosuppression including sulfonamides or trimethoprim-sulfamethoxazole combinations, proguanil, zidovudine, or cytostatic agents (e.g., methotrexate), while the patient is receiving pyrimethamine, may increase the risk of bone marrow suppression. If signs of folate deficiency develop, pyrimethamine should be discontinued.