DARAPRIM Tablet Ref.[9301] Active ingredients: Pyrimethamine

Posology

Toxoplasmosis (including ocular infections)

Daraprim should be given concurrently with sulphadiazine or another appropriate antibiotic.

In the treatment of toxoplasmosis, all patients receiving Daraprim should be given a folinic acid supplement (calcium folinate) to reduce the risk of bone marrow depression (see section 4.4).

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. This should be given together with an initial dose of sulfadiazine 75 mg/kg, followed by 50 mg/kg every 12 hours (to a maximum of 4 g daily) (see section 4.4 and section 4.6).

Immune-deficient adults and adolescents

Guidelines for the treatment of opportunistic infections in HIV-infected adults and adolescents consider pyrimethamine plus sulfadiazine to be the initial therapy of choice for Toxoplasma gondii encephalitis and recommend the following doses, based on body-weight, be given for at least 6 weeks:

• less than 60 kg – pyrimethamine 200 mg orally, followed by 50 mg daily plus sulfadiazine 1 g orally every 6 hours
• 60 kg or more – pyrimethamine 200 mg orally, followed by 75 mg daily plus sulfadiazine 1.5 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.

Immune-deficient children: Dosage regimens for immune-deficient children are not defined.

Children under 5 years: There is insufficient data to provide specific dose recommendations in children. This formulation is not suitable for children under 5 years.

Elderly

There is no definitive information on the effect of Daraprim on elderly individuals. It is theoretically possible that elderly patients might be more susceptible to folate depression associated with the daily administration of Daraprim in the treatment of toxoplasmosis, and supplementation of folinic acid is therefore essential (see section 4.2).

Patients with renal impairment

Daraprim should be given with caution to patients with renal impairment. Since Daraprim is co-administered with a sulphonamide care should be taken to avoid accumulation of the sulphonamide in patients with renal impairment (see section 4.4).

Patients with hepatic impairment

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 adjustments for individual cases (see section 4.4).

Method of administration

For oral administration.

Symptoms

Vomiting and convulsions occur in cases of severe, acute overdoses. Ataxia, tremor and respiratory depression can also occur. There have been isolated cases with fatal outcomes following acute overdose of pyrimethamine.

Chronic excess doses can result in bone marrow depression (e.g. megaloblastic anaemia, leucopenia, thrombocytopenia) resulting from folic acid deficiency.

Management

Routine supportive treatment, including maintenance of a clear airway and control of convulsions.

Adequate fluids should be given to ensure optimal diuresis.

To counteract possible folate deficiency, calcium folinate should be given until signs of toxicity have subsided. There may a delay of 7 to 10 days before the full leucopenic side effects become evident, therefore calcium folinate therapy should be continued for the period at risk.

Further management should be as clinically indicated or as recommended by the national poisons centre, where available.

Shelf life: 5 years.

Store below 30°C.

Store in the original container.

PVC/PVdC/aluminium foil blister pack or PVC/PVdC/child-resistant aluminium foil blister pack.

Pack size: 30 tablets.

Not applicable.