Depression of haematopoesis Daily therapeutic doses of Daraprim have been shown to depress haematopoesis in 25% to 50% of patients. The likelihood of inducing leucopenia, anaemia or thrombocytopenia is reduced by concurrent administration of calcium folinate.
Pancytopenia, responsive to folate, has been reported in patients with probable pre- existing folate deficiency. Fatalities have occurred in the absence of folate treatment. Prevention of haematological toxicity During pregnancy and in other conditions predisposing to folate deficiency, a folate supplement should be given.
2). Full blood counts should be carried out weekly during therapy and for a further two weeks after treatment is stopped. In immunosuppressed patients, full blood counts should be carried out twice weekly. Should signs of folate deficiency develop, treatment must be discontinued and high doses of calcium folinate administered.
Calcium folinate should be used because folic acid does not correct folate deficiency due to dihydrofolate reductase inhibitors. Daraprim may exacerbate folate deficiency in subjects predisposed to this condition through disease or malnutrition.
Accordingly, a calcium folinate supplement should be given to such individuals. In patients with megaloblastic anaemia due to folate deficiency the risks versus benefits of administering Daraprim require careful consideration. 8). Risk of crystalluria When a sulphonamide is given an adequate fluid intake should be ensured to minimise the risk of crystalluria.
Precautions applicable to sulphonamides Since Daraprim is administered with a sulphonamide for the conditions indicated the general precautions applicable to sulphonamides should be observed. Renal impairment The kidney is not the major route of excretion of pyrimethamine and excretion is not significantly altered in patients with renal failure.
There are, however, no substantial data on the use of Daraprim in patients with renal impairment, therefore Daraprim should be given with caution. Since Daraprim is co-administered with a sulphonamide, care should be taken to avoid accumulation of the sulphonamide in renally impaired patients.
Hepatic impairment The liver is the main route for metabolism of pyrimethamine. Data on the use of Daraprim in patients with liver disease are limited. Daraprim should be given with caution to patients with hepatic impairment. There are no general recommendations for dosage reductions for liver-impaired states but consideration should be given to dose adjustment for individual cases.
Lactose This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine. Sodium This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.