Acute malaria, Malaria prophylaxis, Toxoplasmosis Hypersensitivity, resistant malaria, megaloblastic anaemia secondary to folate deficiency. Pregnancy and lactation.

Administration: Should be taken with food. Adult Dose: Oral Acute malaria Adult: As a single dose, in combination with a sulfonamide: 75 mg pyrimethamine with 1.5 g sulfadoxine. Prophylaxis of malaria Adult: Pyrimethamine 25 mg as single dose once wkly. 1st dose should be taken 1-2 days before arrival in the endemic area, continue admin during stay and for 4-6 wk after leaving the area. Toxoplasmosis Adult: 50-75 mg pyrimethamine daily with 1-4 g sulfadiazine daily. Continue at this dosage for 1-3 wk, depending on the patient's response and tolerance, then half the dosage and continue for another 4-5 wk. Child Dose: Oral Acute malaria Child: 7-13 yr: 50 mg pyrimethamine with 1 g sulfadoxine; 1-6 yr: 25 mg pyrimethamine with 500 mg sulfadoxine; 5-11 mth: 12.5 mg pyrimethamine and 250 mg sulfadoxine. To be taken as a single dose, in combination with a sulfonamide. Prophylaxis of malaria Child: <4 yr: 6.25 mg once wkly; 4-10 yr: 12.5 mg once wkly; >10 yr: 25 mg once wkly. 1st dose should be taken 1-2 days before arrival in the endemic area, continue admin during stay and for 4-6 wk after leaving the area. Congenital Toxoplasmosis >2 Months Old Loading dose: 2 mg/kg/day divided q12hr PO for 2 days Maintenance.: First 2-6 months old: 1 mg/kg PO qD for 2-6 months old; THEN remainder of 12 months old; 1 mg/kg PO 3 times/week Toxoplasmosis Loading dose: 2 mg/kg/d divided q12hr PO for 3 days Maintenance: 1 mg/kg PO qD for 4 weeks < 2 months old: Safety and efficacy not established

Lorazepam may induce hepatotoxicity. Increased risk of bone marrow suppression when used with agents that have myelosuppressive properties e.g. proguanil, sulfonamides, zidovudine and cytostatic agents. Increased risk of serious pancytopenia and megaloblastic anaemia when used with co-trimoxazole or other sulfonamides.

Hypersensitivity, resistant malaria, megaloblastic anaemia secondary to folate deficiency. Pregnancy and lactation.

Rashes, macrocytic anaemia (high dose), leucopenia, thrombocytopenia, megaloblastic anaemia, pancytopenia, abdominal pain, vomiting, atrophic glossitis. Depression, Fever, Insomnia, Lightheadedness, Malaise, Seizures, Dermatitis, Erythema multiforme Potentially Fatal: Cutaneous reactions e.g. erythema multiforme and Stevens-Johnson syndrome and toxic epidermal necrolysis with sulfadoxine at large doses.

Precaution: Renal or hepatic impairment; folate deficiency; monitor blood and platelet counts every 2 wk with prolonged treatment and large doses. Discontinue use if skin reactions, sore throats or shortness of breath occurs. Lactation: enters breast milk, do not nurse

Anti-malarial drugs

Pyrimethamine is a folic acid antagonist structurally similar to trimethoprim. It inhibits parasitic dihydrofolate reductase, thus inhibiting vital tetrahydrofolic acid synthesis. It is active against pre-erythrocytic forms and is also a slow-acting schizontocide.

Pregnancy Category C. Pyrimethamine has been shown to be teratogenic in rats when given in oral doses 7 times the human dose for chemoprophylaxis of malaria or 2.5 times the human dose for treatment of toxoplasmosis. At these doses in rats, there was a significant increase in abnormalities such as cleft palate, brachygnathia, oligodactyly, and microphthalmia. Pyrimethamine has also been shown to produce terata such as meningocele in hamsters and cleft palate in miniature pigs when given in oral doses 170 and 5 times the human dose, respectively, for chemoprophylaxis of malaria or for treatment of toxoplasmosis.There are no adequate and well-controlled studies in pregnant women. Pyrimethamine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.Concurrent administration of folinic acid is strongly recommended when used for the treatment of toxoplasmosis during pregnancy.Nursing Mothers: Pyrimethamine is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from pyrimethamine and from concurrent use of a sulfonamide with Pyrimethamine for treatment of some patients with toxoplasmosis, 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