Pyrimethamine with Trimethoprim Interaction Details
Brand Names Associated with Trimethoprim
- Primsol®
- Proloprim®
- Trimethoprim
- Trimpex®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 20, 2023
Interaction Effect
An increased risk of megaloblastic anemia and pancytopenia
Interaction Summary
Coadministration of pyrimethamine with cotrimoxazole, an antifolic drug, may increase the risk of bone marrow suppression. Coadministered cotrimoxazole and pyrimethamine may result in megaloblastic anemia or pancytopenia . The extent to which sulfamethoxazole and trimethoprim individually contribute to this interaction is unknown.
Severity
Major
Onset
Delayed
Evidence
Probable
How To Manage Interaction
Avoid giving cotrimoxazole (sulfamethoxazole/trimethoprim), an antifolic agent, and pyrimethamine concomitantly. Should it become clinically necessary to coadminister these agents, aggressively monitor complete blood counts and observe the patient for bruising and excessive bleeding. Consider adding leucovorin (folinic acid) to therapy.
Mechanism Of Interaction
Additive dihydrofolate reductase inhibition
Literature Reports
A) A 27-year-old female patient was receiving pyrimethamine 25 mg weekly plus cotrimoxazole for malaria prophylaxis. The patient developed megaloblastic anemia which resolved with oral iron therapy and discontinuation of both drugs. The reaction was thought to be due to the additive inhibition by both drugs of dihydrofolate reductase .
B) A 43-year-old female was taking pyrimethamine 50 mg weekly for malaria prophylaxis. After signs of a urinary tract infection developed, she self-treated with cotrimoxazole (trimethoprim 320 mg/sulfamethoxazole 800 mg per day) for ten days prior to admission. On admission, the patient was found to have diffuse petechial hemorrhages and widespread bruising. Her hemoglobin level was 9.4 g/dl, hematocrit 30%, platelets 28,000/mm(3), and white blood cell count 3100/mm(3); red blood cells exhibited anisocytosis, some poikilocytosis, occasional multilobed polymorphs, and no macrocytes. Bone marrow aspiration showed grossly megaloblastic erythropoiesis, numerous giant metamyelocytes, and scanty megakaryocytes. All medications were stopped except for chloroquine for malaria prophylaxis. She responded rapidly to treatment with hydroxocobalamin and folic acid .
C) An in vitro study using bone marrow was undertaken to determine the mechanism of pyrimethamine-induced megaloblastosis . Pyrimethamine was found to cause defective deoxyuridine conversion to thymidylate, thereby interfering with effective DNA synthesis.
Trimethoprim Overview
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Trimethoprim eliminates bacteria that cause urinary tract infections. It is used in combination with other drugs to treat certain types of pneumonia. It also is used to treat traveler's diarrhea. Antibiotics will not work for colds, flu, or other viral infections.
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This medication is sometimes prescribed for other uses; ask your doctor or pharmacist for more information.
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Definitions
Severity Categories
Contraindicated
These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.
Major
This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.
Moderate
This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.
Minor
While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.
Onset
Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.
Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.
Evidence
Level of documentation of the interaction.
Established: The interaction is documented and substantiated in peer-reviewed medical literature.
Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.
How To Manage The Interaction
Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.
It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.
Mechanism Of Interaction
The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.
Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.
Where Does Our Information Come From?
Information for our drug interactions is compiled from several drug compendia, including:
The prescribing information for each drug, as published on DailyMED, is also used.
Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.
The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.