Pyrimethamine

Pyrimethamine should not be used during the first trimester of pregnancy unless the benefits outweigh the risk. Pyrimethamine has been shown to be teratogenic in animal studies. The risks associated with the administration of pyrimethamine must be balanced against the dangers of abortion or foetal malformation due to the infection.

Treatment with pyrimethamine and sulfadiazine during pregnancy is indicated in the presence of confirmed placental or foetal infection or when the mother is at risk of serious sequelae. However, in view of the theoretical risk of foetal abnormality arising from the use of pyrimethamine in early pregnancy, its use in combination therapy should be restricted to the second and third trimesters.

Pregnant women receiving pyrimethamine must be given a concurrent folinic acid supplement.

Pyrimethamine enters human breast milk. It has been estimated that over a 9-day period an average weight infant would receive about 45% of the dose ingested by the mother. In view of the high doses of pyrimethamine and concurrent sulphonamides needed in toxoplasmosis treatment, breast feeding should be avoided for the duration of treatment.

Fertility

There are no relevant data available.

No studies on the effects on the ability to drive and use machines have been performed. Some patients may experience dizziness or convulsions, therefore, caution is recommended.

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.

Blood and lymphatic system disorders

Very common: Anaemia

Common: Leucopenia, thromboctopenia

Very rare: Pancytopenia

Nervous system disorders

Very common: Headache

Common: Dizziness

Very rare: Convulsions

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