DARAPRIM

Posology Toxoplasmosis (including ocular infections) Daraprim should be given concurrently with sulphadiazine or another appropriate antibiotic. 4). Daraprim treatment should generally be given for 3 to 6 weeks and not less than six weeks in immunosuppressed patients.

If further therapy is indicated, a period of two weeks should elapse between treatments. There have been no dose response studies of pyrimethamine in the treatment of toxoplasmosis. The following recommendations are therefore for guidance only.

Adults A loading dose of Daraprim 100 mg should be given for the first 1 to 2 days, followed by 25 mg to 50 mg daily. This should be given together with 2 g to 4 g of sulphadiazine daily in divided doses. • Foetal toxoplasmosis during pregnancy Daraprim 50 mg every 12 hours for 2 days, followed by 50 mg daily.

6). 5 g orally every 6 hours. Paediatric Population Children over 6 years A loading dose of Daraprim 100 mg should be given for the first 1 to 2 days, followed by 25 mg to 50 mg daily. This should be given together with 2 g to 4 g of sulphadiazine daily in divided doses.

Children aged 5 to 6 years An initial dose of Daraprim 2 mg/kg bodyweight (to a maximum of 50 mg) followed by 1 mg/kg bodyweight/day (to a maximum of 25 mg); combined with sulphadiazine 150 mg/kg bodyweight (maximum 2 g) daily in four divided doses.

Children under 5 years There is insufficient data to provide specific dose recommendations. This formulation is not suitable for children under 5 years. Immune-deficient children Dosage regimens for immune-deficient children are not defined.

Elderly There is no definitive information on the effect of Daraprim on elderly individuals. 2). Patients with renal impairment Daraprim should be given with caution to patients with renal impairment. 4). Patients with hepatic impairment Daraprim should be given with caution to patients with hepatic impairment.

4). Method of administration For oral administration.

Since a concurrent sulphonamide is to be taken with pyrimethamine for the indications listed, the relevant prescribing information for the sulphonamide should be consulted for sulphonamide-associated adverse events. It is important to note that the frequency categories assigned for each adverse event below are only estimates as suitable data for accurately calculating incidence were not available.

Adverse events may vary in their incidence according to the indication and the possible contribution of concomitant sulphonamides to the occurrence of these events is unknown. In addition some events may be related to the underlying disease.

Adverse drug reactions (ADRs) are listed below by MedDRA system organ class and by frequency. Frequencies are defined as: very common ≥1/10, common ≥1/100 and <1/10, uncommon ≥1/1000 and <1/100, rare ≥1/10,000 and <1/1000, very rare <1/10,000.

7) Respiratory, thoracic and mediastinal Disorders Very rare: Pneumonia with cellular and eosinophilic pulmonary infiltration (observed when pyrimethamine was administered once weekly in association with sulfadoxine) Gastrointestinal disorders Very common: Vomiting, nausea, diarrhoea Very rare: Colic, buccal ulceration Skin and subcutaneous tissue disorders Very common: Rash Uncommon: Abnormal skin pigmentation Very rare: Dermatitis General disorders and administrative site conditions Uncommon: Fever Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or by searching for MHRA Yellow Card in the Google Play or Apple App Store.

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.

Daraprim is contraindicated in:

Hypersensitivity to pyrimethamine or to any of the excipients of this medicinal product. 6). Since Daraprim is to be taken in conjunction with another drug for the indications listed, the relevant prescribing information for the synergistic agent should also be considered.

Breast-feeding should be avoided during toxoplasmosis treatment. 6).