Pyrimethamine


Generic Medicine Info
Indications and Dosage
Oral
Toxoplasmosis
Adult: In combination with a sulfonamide or another appropriate antibacterial: Initially, 100 mg for 1-2 days then 25-50 mg daily. Alternatively, 50-75 mg daily in combination with a sulfonamide and leucovorin calcium, for 1-3 weeks depending on patient response and tolerability. Dose may be reduced by 50% and continued for 4-5 weeks.
Child: In combination with a sulfonamide or another appropriate antibacterial: 5-6 years Initially, 2mg/kg (Max: 50 mg), then 1mg/kg (Max: 25 mg) daily; >6 years Same as adult dose.
Administration
Should be taken with food.
Contraindications
Hypersensitivity. Megaloblastic anaemia secondary to folate deficiency. 1st trimester of pregnancy. Lactation.
Special Precautions
Patient with seizure disorders, G6PD deficiency, folate deficiency (e.g. malabsorption syndrome, alcoholism). Renal and hepatic impairment. Children. Pregnancy (2nd and 3rd trimester).
Adverse Reactions
Significant: Megaloblastic anaemia, leucopenia, thrombocytopenia, pancytopenia; crystalluria (with sulfonamides).
Cardiac disorders: Cardiac arrhythmia.
Gastrointestinal disorders: Nausea, vomiting, diarrhoea, glossitis.
General disorders and administration site conditions: Fever.
Immune system disorders: Anaphylaxis.
Metabolism and nutrition disorders: Anorexia.
Nervous system disorders: Headache, dizziness.
Skin and subcutaneous tissue disorders: Rash, abnormal skin pigmentation, dermatitis.
Monitoring Parameters
Monitor CBC and platelets twice weekly in high dose therapy; hepatic and renal function.
Overdosage
Symptoms: Severe and repeated vomiting, nausea, abdominal pain, convulsions, ataxia, tremor, and respiratory depression. Management: Symptomatic and supportive treatment. Maintain the airways and perform gastric lavage. May administer diazepam to control convulsions; calcium folinate for possible folinate deficiency.
Drug Interactions
May cause convulsion with methotrexate in patient with CNS leukaemia, and seizures with antimalarial drugs. Further depression of folate metabolism with co-trimoxazole, proguanil, zidovudine, or cytostatic agents (e.g. methotrexate). Decreased absorption with antacids and kaolin. Increased risk of hepatotoxicity with lorazepam.
Potentially Fatal: May cause bone marrow aplasia with daunorubicin, cytosine arabinoside in patient with acute myeloid leukaemia.
Action
Description: Pyrimethamine is an antiparasitic agent. It impairs the protein synthesis and nuclear division of susceptible parasites through the inhibition of the dihydrofolate reductase enzyme.
Pharmacokinetics:
Absorption: Almost completely absorbed from the gastrointestinal tract. Time to peak plasma concentration: 2-6 hours.
Distribution: Mainly distributed in the kidneys, lungs, liver, and spleen. Crosses placenta and enters breast milk. Volume of distribution: 2.9 L/kg. Plasma protein binding: Approx 80-90%.
Metabolism: Metabolised in the liver.
Excretion: Via urine (16-32%). Elimination half-life: Approx 96 hours.
Chemical Structure

Chemical Structure Image
Pyrimethamine

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 4993, Pyrimethamine. https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimethamine. Accessed Oct. 27, 2020.

Storage
Store below 30°C. Protect from light.
MIMS Class
ATC Classification
P01BD01 - pyrimethamine ; Belongs to the class of diaminopyrimidine antimalarials.
References
Anon. Pyrimethamine. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 16/10/2020.

Buckingham R (ed). Pyrimethamine. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 16/10/2020.

Daraprim 25 mg Tablets (The Wellcome Foundation Ltd). MHRA. https://products.mhra.gov.uk/. Accessed 16/10/2020.

Joint Formulary Committee. Pyrimethamine. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 16/10/2020.

Pyrimethamine Tablet (Dr. Reddys Laboratories INC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 16/10/2020.

Disclaimer: This information is independently developed by MIMS based on Pyrimethamine from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2021 MIMS. All rights reserved. Powered by MIMS.com
Register or sign in to continue
Asia's one-stop resource for medical news, clinical reference and education
Sign up for free
Already a member? Sign in