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Pyrimethamine oral

Updated 2 Feb 2023 | Toxoplasmosis

Presentation

Oral formulations containing pyrimethamine.

Drugs List

  • DARAPRIM 25mg tablets
  • pyrimethamine 25mg tablets
  • Therapeutic Indications

    Uses

    Foetal toxoplasmosis in pregnancy in combination with other drugs
    Toxoplasmosis in the immunocompromised in combination with other drugs
    Toxoplasmosis: treatment

    Pyrimethamine in combination with a sulfonamide is effective in the treatment of the following conditions associated with toxoplasma infection:
    Treatment of toxoplasmosis.
    Toxoplasmic encephalitis and other manifestations in immunodeficient patients (including those with AIDS).
    Proven foetal infection following maternal infection during pregnancy.

    Treatment is not usually required for asymptomatic or mild toxoplasmosis.

    Dosage

    The duration of treatment of the acute infection will depend on the clinical response and tolerability, but pyrimethamine should normally be administered for three to six weeks (not less than six weeks in immunosuppressed patients). If therapy is needed beyond this period, an interval of two weeks should separate each course of therapy.

    The following recommendations are for guidance only. Refer to relevant dose information for drugs used in combination therapy.

    Maintenance therapy is required indefinitely in immunocompromised patients in order to avoid relapses.

    Adults

    Toxoplasmosis, including ocular infections
    Loading dose: 100mg daily for the first one to two days of treatment.
    Maintenance dose: 25mg to 50mg per day.

    Foetal toxoplasmosis during pregnancy
    Loading dose: 50mg every 12 hours for two days.
    Maintenance dose: 50mg per day.

    Children

    Children over 6 years
    (See Dosage; Adult).

    Children 5 to 6 years
    Initial dose: 2mg/kg bodyweight, to a maximum of 50mg.
    Maintenance dose: 1mg/kg bodyweight per day, to a maximum of 25mg.

    Children under 5 years
    Not recommended.

    Additional Dosage Information

    Immunocompromised adults and adolescents

    60kg or more bodyweight
    Loading dose: 200mg.
    Maintenance dose: 75mg per day.

    Less than 60kg bodyweight
    Loading dose: 200mg.
    Maintenance dose: 50mg per day.

    Contraindications

    Breastfeeding
    Galactosaemia

    Precautions and Warnings

    Children under 5 years
    Predisposition to folate deficiency
    Glucose-galactose malabsorption syndrome
    Hepatic impairment
    History of seizures
    Lactose intolerance
    Megaloblastic anaemia secondary to folate deficiency
    Pregnancy
    Renal impairment

    Advise ability to drive/operate machinery may be affected by side effects
    Folate supplementation may be necessary in some patients
    Must be used as part of combination therapy
    Contains lactose
    Continue to monitor full blood count after discontinuation of drug
    Monitor full blood count regularly
    Pregnancy: Monitor folate levels as supplements are recommended
    If folate deficiency occurs, discontinue and treat appropriately

    Folate supplementation (e.g calcium folinate) is advised to reduce the risk of bone marrow depression.

    Full blood counts should be carried out weekly during therapy and for two weeks after cessation of therapy. In immunocompromised patients, full blood counts must be carried out twice weekly.

    In patients with megaloblastic anaemia due to folate deficiency the risks and benefits of pyrimethamine administration must be carefully considered.

    Elderly patients may be more susceptible to folate depression and therefore the daily administration of a folate supplement is advised in this age group.

    Pregnancy and Lactation

    Pregnancy

    Use pyrimethamine with caution in pregnancy. Ensure folate supplementation is given to pregnant women receiving pyrimethamine.

    The manufacturer suggests that pyrimethamine use should be restricted to the second and third trimesters of pregnancy, due to the theoretical risk of foetal abnormality in early pregnancy. The risks and benefits of pyrimethamine use should, however, be balanced against the risk of harm from the infection itself.

    Pyrimethamine crosses the placenta. No adverse foetal effects have been observed during pregnancy, however animal studies have indicated teratogenicity.

    There is a theoretical risk of foetal abnormalities from all folate inhibitors administered during pregnancy.

    The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

    Lactation

    Pyrimethamine is contraindicated in breastfeeding.

    The manufacturer states that breast feeding should be avoided for the duration of treatment with pyrimethamine. The Drugs and Lactation Database (LactMed) and Briggs (2015) suggest that pyrimethamine is acceptable for use in breastfeeding as no adverse reactions have been reported in breastfed infants.

    Pyrimethamine enters human breast milk. It is believed that over a 9 day period, the infant would receive about 45% of the dose ingested by the mother.

    Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
    Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

    Side Effects

    Anaemia
    Buccal ulceration
    Colic
    Convulsions
    Dermatitis
    Diarrhoea
    Dizziness
    Eosinophilic pneumonia
    Fever
    Headache
    Leucopenia
    Nausea
    Pancytopenia
    Rash
    Skin pigmentation changes
    Thrombocytopenia
    Vomiting

    Overdosage

    It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

    The following number will direct the caller to the relevant local centre (0844) 892 0111

    Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

    Further Information

    Last Full review Date: December 2017

    Reference Sources

    Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

    Summary of Product Characteristics for Daraprim tablets. GlaxoSmithKline UK Ltd. June 2017.

    NICE Evidence Services Available at: www.nice.org.uk Last accessed: 29 November 2017

    US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
    Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
    Pyrimethamine Last revised: September 7, 2013.
    Last accessed:29 November 2017

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