Usage
- Medical Conditions: Pyrimethamine + Sulphadoxine is prescribed for the treatment and prevention of malaria. It is also used for the prophylaxis of Pneumocystis jirovecii pneumonia (PCP) when other options are unavailable. It is specifically indicated for intermittent preventive treatment of malaria in pregnancy (IPTp) starting in the second trimester.
- Pharmacological Classification: Antimalarial, Antiparasitic, Antifolate.
- Mechanism of Action: This combination drug inhibits two different steps in the folic acid synthesis pathway essential for the survival and reproduction of the malaria parasite (Plasmodium falciparum). Pyrimethamine inhibits dihydrofolate reductase, while sulfadoxine inhibits dihydropteroate synthase. The synergistic action of these two components provides enhanced antimalarial activity.
Alternate Names
- Fansidar (brand name)
- S-Pyrimac (brand name)
- Swidar (brand name)
- MA163 (WHO code)
- SP (abbreviation)
- Sulfadoxine-pyrimethamine
- Pyrimethamine/sulfadoxine
- MALAKANT DISPERSIBLE JUNIOR (brand name for dispersible pediatric formulation)
How It Works
- Pharmacodynamics: Pyrimethamine and sulfadoxine disrupt the folic acid synthesis pathway, essential for the synthesis of purines and pyrimidines required for DNA and RNA synthesis in the malaria parasite. This ultimately inhibits parasite growth and reproduction.
- Pharmacokinetics:
- Absorption: Both drugs are well-absorbed orally. Absorption is improved with food intake.
- Metabolism: Sulfadoxine is partially metabolized in the liver by acetylation and glucuronidation. Pyrimethamine is metabolized to several unidentified metabolites.
- Elimination: Both drugs are primarily excreted in the urine. Pyrimethamine has a longer half-life than sulfadoxine.
- Mode of Action: Inhibition of folic acid synthesis within the parasite.
- Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: Pyrimethamine inhibits dihydrofolate reductase, while sulfadoxine inhibits dihydropteroate synthase.
- Elimination Pathways: Renal excretion (primarily), hepatic metabolism (sulfadoxine).
Dosage
Standard Dosage
Adults:
- Malaria Treatment: 3 tablets (75 mg pyrimethamine / 1500 mg sulfadoxine) as a single dose, preferably after a 3-7 day course of quinine.
- Malaria Prophylaxis: 1 tablet weekly or 2 tablets every two weeks, starting 1-2 days before travel to an endemic area and continuing for 4-6 weeks after returning.
- PCP Prophylaxis: 1 tablet once or twice weekly (generally not recommended unless other options are unavailable).
Children:
- Dosing is weight-based. Consult pediatric dosage charts and guidelines available in the WHO and national malaria control program recommendations.
- Malaria Treatment: See sources like WHO guidelines for detailed, weight-based dosing recommendations.
- Malaria Prophylaxis: See sources like WHO guidelines for detailed, weight-based dosing recommendations.
- Pediatric Safety Considerations: Contraindicated in infants less than 2 months of age. Careful monitoring for adverse reactions is essential.
Special Cases:
- Elderly Patients: Dose adjustments may be necessary due to potential age-related decline in renal and hepatic function.
- Patients with Renal Impairment: Dosage reduction may be required depending on the degree of impairment.
- Patients with Hepatic Dysfunction: Dosage adjustments might be necessary, especially for sulfadoxine.
- Patients with Comorbid Conditions: Caution is advised in patients with G6PD deficiency, blood dyscrasias, or pre-existing folate deficiency.
Clinical Use Cases
- Intubation, Surgical Procedures, Mechanical Ventilation, ICU Use, and Emergency Situations: Pyrimethamine + Sulphadoxine does not have a specific role in these clinical settings. Its primary indication is for malaria treatment and prevention, and PCP prophylaxis in specific circumstances.
Dosage Adjustments:
- Adjust dosage based on renal and hepatic function.
Side Effects
Common Side Effects:
- Nausea, vomiting, diarrhea
- Headache, dizziness
- Anorexia, abdominal pain
- Skin rash, itching
- Hair loss
Rare but Serious Side Effects:
- Severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis)
- Blood dyscrasias (agranulocytosis, aplastic anemia, thrombocytopenia, leukopenia, hemolytic anemia)
- Hepatotoxicity
- Seizures
- Hallucinations
Long-Term Effects:
- Folate deficiency with prolonged use
Adverse Drug Reactions (ADR):
- Any signs of severe skin reactions require immediate discontinuation of the drug.
- Blood dyscrasias should be promptly investigated and managed.
Contraindications
- Hypersensitivity to pyrimethamine, sulfadoxine, or other sulfonamides.
- Megaloblastic anemia due to folate deficiency.
- Severe renal or hepatic impairment.
- Infants younger than 2 months of age.
- Late pregnancy (near term) and breastfeeding.
Drug Interactions
- Folic Acid: High doses of folic acid (>5 mg/day) can antagonize the antimalarial effects of pyrimethamine+sulfadoxine.
- Other Sulfonamides/Trimethoprim: Concurrent use can increase the risk of hematological and cutaneous adverse reactions.
- Drugs affecting folate metabolism (e.g., phenytoin, trimethoprim): Increased risk of folate deficiency.
- Drugs affecting blood counts (e.g., proguanil, zidovudine, methotrexate): Increased risk of myelosuppression.
- CYP450 interactions: Pyrimethamine+sulfadoxine may inhibit certain CYP enzymes, potentially affecting the metabolism of co-administered drugs.
- Other potential interactions: Lorazepam, penicillamine, dofetilide.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C (FDA). Contraindicated in the first trimester and near term. Can be used for IPTp during the second and third trimesters in areas with moderate to high malaria transmission, where it remains effective.
- Fetal Risks: Teratogenic effects observed in animal studies. Folate antagonism can lead to neural tube defects.
- Breastfeeding: Both pyrimethamine and sulfadoxine are excreted in breast milk. Contraindicated during breastfeeding due to the risk of kernicterus and other adverse effects in the infant.
Drug Profile Summary
- Mechanism of Action: Inhibits folic acid synthesis in the malaria parasite.
- Side Effects: Nausea, vomiting, rash, headache, serious skin reactions (rare), blood disorders (rare).
- Contraindications: Hypersensitivity to sulfonamides, folate deficiency, severe renal/hepatic disease, infants <2 months, late pregnancy/breastfeeding.
- Drug Interactions: Folic acid, other sulfonamides, trimethoprim. See above for a comprehensive list.
- Pregnancy & Breastfeeding: Contraindicated in the first trimester, at term, and during breastfeeding. Can be used for IPTp during the second and third trimesters.
- Dosage: See section above for detailed dosages.
- Monitoring Parameters: Complete blood counts, liver function tests (especially with prolonged use).
Popular Combinations
- Artesunate + Sulfadoxine/Pyrimethamine (AS+SP): Recommended by the WHO for the treatment of uncomplicated P. falciparum malaria in certain regions.
Precautions
- Monitor for skin rash and blood disorders.
- Adequate fluid intake is essential to prevent crystalluria and kidney stones.
- Folate supplementation may be necessary with prolonged use.
- Avoid in G6PD deficiency.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Pyrimethamine + Sulphadoxine for malaria treatment in adults?
A: 3 tablets (75 mg pyrimethamine / 1500 mg sulfadoxine) as a single dose.
Q2: Can Pyrimethamine + Sulphadoxine be used during pregnancy?
A: It is contraindicated in the first trimester and near term. It can be used for IPTp during the second and third trimesters in areas with moderate to high malaria transmission, as recommended by the WHO.
Q3: What are the most serious side effects of Pyrimethamine + Sulphadoxine?
A: Severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis) and blood disorders (e.g., agranulocytosis, aplastic anemia).
Q4: What are the contraindications for Pyrimethamine + Sulphadoxine?
A: Hypersensitivity to sulfonamides, folate deficiency, severe renal/hepatic disease, infants <2 months, late pregnancy/breastfeeding.
Q5: Can Pyrimethamine + Sulphadoxine be used for malaria prophylaxis?
A: Yes, 1 tablet weekly or 2 tablets every two weeks. Start 1-2 days before traveling to an endemic area and continue for 4-6 weeks after returning.
Q6: How does Pyrimethamine + Sulphadoxine work?
A: It inhibits folic acid synthesis, which is essential for the survival and reproduction of the malaria parasite.
Q7: What should be done if a patient develops a skin rash while taking Pyrimethamine + Sulphadoxine?
A: The drug should be discontinued immediately, and the patient should be evaluated for severe cutaneous reactions.
Q8: What are some common drug interactions with Pyrimethamine + Sulphadoxine?
A: Interactions can occur with high doses of folic acid, other sulfonamides, and drugs that affect folate metabolism or blood counts.
Q9: How is Pyrimethamine + Sulphadoxine administered?
A: Orally, preferably with food. Tablets should be swallowed whole and not crushed or chewed. The dispersible pediatric formulation is available for infants and children. Follow the instructions for preparation as advised by the healthcare provider.
Q10: What is the role of Pyrimethamine + Sulphadoxine in the treatment of Pneumocystis jirovecii pneumonia (PCP)?
A: It can be used for PCP prophylaxis but is generally not recommended unless other options, such as trimethoprim-sulfamethoxazole, are unavailable.
