Pyrimethamine & Nutrient Depletion
Also searched as Daraprim. What the clinical evidence reports, what it may mean, and what to discuss with your pharmacist.
Pyrimethamine has been associated with depletion of FOLIC ACID, ACETYL-L-CARNITINE, L-CARNITINE and PROPIONYL-L-CARNITINE. This does not mean a deficiency will occur — it means these are worth knowing about and, if you take Pyrimethamine long-term, worth raising with your pharmacist or healthcare provider.
Take more than one medication? Open the checker with Pyrimethamine pre-loaded and add the rest to see overlapping nutrient signals.
Reported nutrient depletions with Pyrimethamine
Each record below is shown as published in our licensed clinical database, with its evidence rating and citations. Expand a section for food sources and talking points.
FOLIC ACID
Moderate DepletionPYRIMETHAMINE (Daraprim)
Pyrimethamine is a folate antagonist that prevents conversion of folic acid to its active form. At high doses, 50-75 mg daily, megaloblastic anemia may occur due to deficiency of active folate, and it's recommended that all patients receive folinic acid (leucovorin calcium, an active form of folic acid). Folinic acid doesn't antagonize the therapeutic effect of pyrimethamine because Toxoplasma does not have a membrane transport system for exogenous folinic acid. Advise patients to avoid other forms of folic acid since they can antagonize the therapeutic effect of pyrimethamine against Toxoplasma and Pneumocystis carinii. Advise patients taking lower doses of pyrimethamine for prolonged periods to maintain the recommended dietary folate intake. Monitor for folate deficiency. For information on foods that are rich in folate, see our chart.
Pyrimethamine works specifically by blocking the step your body uses to convert folic acid, the vitamin that supports healthy red blood cells and cell repair, into its usable form. Because of that block, the drug can deplete active folate in your system over time, and at higher doses this raises a real risk of megaloblastic anemia. This is a moderate, well-documented concern, so your doctor will typically prescribe folinic acid (leucovorin) alongside pyrimethamine to protect you. Importantly, regular folic acid supplements are actually off-limits during this treatment because they can interfere with how the drug works, so please check with your doctor or pharmacist before taking anything on your own.
What Folic acid (folate) does & food sources
Folate is needed for cell division, red blood cell formation, and healthy fetal development.
Common food sources:
- Leafy green vegetables
- Beans, lentils, and peas
- Fortified grains and cereals
- Citrus fruits
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
What to discuss with your clinician
Ask your provider whether folate monitoring or supplementation is appropriate for you — this matters most before and during pregnancy, and with long-term use of certain seizure or arthritis medications.
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
Supplement considerations
Folate needs are individual. With some medications (for example, methotrexate), folic acid is often prescribed deliberately on a specific schedule — follow your prescriber's instructions rather than adding your own.
Do not start or stop medications or supplements without professional guidance — supplements can interact with prescription medications.
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
Caution: High-dose folic acid can mask vitamin B12 deficiency, so the two are often evaluated together.
Learn more about this nutrient: Folic Acid — uses, safety & interactions
References (3)
- Garabedian-Ruffalo SM, Ruffalo RL. Drug and nutrient interactions. Am Fam Physician 1986;33:165-74.
- Glaxo-Wellcome, Inc. Daraprim package insert. Research Triangle Park, NC; August 1996.
- Van Delden C, Hirschel B. Folinic acid supplements to pyrimethamine-sulfadiazine for Toxoplasma encephalitis are associated with better outcome (letter). J Infect Dis 1996;173:1294-5. PubMed
ACETYL-L-CARNITINE
Insufficient EvidencePYRIMETHAMINE (Daraprim)
A single case report describes symptomatic L-carnitine deficiency in a patient treated with pyrimethamine plus sulfadiazine, which reversed when both drugs were stopped. The mechanism of this effect is not known and further data is needed before L-carnitine or acetyl-L-carnitine depletion can be linked to these drugs.
Acetyl-L-carnitine is a compound your body uses for energy production and nerve function, particularly in the brain. There is one old case report suggesting pyrimethamine might somehow interfere with carnitine in the body, but the mechanism is unknown and that single report involved a second drug as well. With an 'insufficient evidence' rating, this is more of a theoretical curiosity than a practical concern right now. If you have questions about carnitine while taking pyrimethamine, it is worth bringing up with your doctor or pharmacist.
Learn more about this nutrient: Acetyl-l-carnitine — uses, safety & interactions
References (1)
- Sekas G, Paul HS. Hyperammonemia and carnitine deficiency in a patient receiving sulfadiazine and pyrimethamine. Am J Med 1993;95:112-3. PubMed
L-CARNITINE
Insufficient EvidencePYRIMETHAMINE (Daraprim)
A single case report describes symptomatic L-carnitine deficiency in a patient treated with pyrimethamine plus sulfadiazine which reversed when both drugs were stopped. The mechanism of this effect is not known and further data is needed before L-carnitine depletion can be linked to these drugs.
L-carnitine is a compound your body uses to turn fat into usable energy, particularly for your muscles and heart. There is one old case report of a patient on pyrimethamine plus a second antibiotic developing a deficiency, but the mechanism is simply not understood, and the evidence is far too thin to draw firm conclusions. For most people taking pyrimethamine, this is not something to lose sleep over. If you have concerns, a quick conversation with your pharmacist or doctor is the right place to start.
What Carnitine does & food sources
Carnitine shuttles fatty acids into cells' mitochondria so they can be burned for energy.
Common food sources:
- Red meat (the richest source)
- Poultry and fish
- Dairy products
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
What to discuss with your clinician
Carnitine questions come up with specific medications (for example, valproic acid) and specific situations — this is a conversation for your prescriber, who can weigh testing or supplementation.
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
Supplement considerations
Carnitine supplements are usually reserved for clinician-identified situations rather than general use.
Do not start or stop medications or supplements without professional guidance — supplements can interact with prescription medications.
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
Learn more about this nutrient: L-carnitine — uses, safety & interactions
References (1)
- Sekas G, Paul HS. Hyperammonemia and carnitine deficiency in a patient receiving sulfadiazine and pyrimethamine. Am J Med 1993;95:112-3. PubMed
PROPIONYL-L-CARNITINE
Insufficient EvidencePYRIMETHAMINE (Daraprim)
A single case report describes symptomatic L-carnitine deficiency in a patient treated with pyrimethamine plus sulfadiazine which reversed when both drugs were stopped. The mechanism of this effect is not known and further data is needed before L-carnitine or propionyl-L-carnitine depletion can be linked to these drugs.
Propionyl-L-carnitine is a compound your body uses to help convert fat into energy, particularly in muscle tissue. There is one old case report suggesting that pyrimethamine, possibly in combination with another antibiotic, may have played a role in lowering carnitine levels, though how or why that might happen is genuinely not understood. The evidence here is quite thin, so this is more of an open question than an established concern. If you are on long-term pyrimethamine and are curious about this, it is worth a quick conversation with your pharmacist or doctor.
Learn more about this nutrient: Propionyl-l-carnitine — uses, safety & interactions
References (1)
- Sekas G, Paul HS. Hyperammonemia and carnitine deficiency in a patient receiving sulfadiazine and pyrimethamine. Am J Med 1993;95:112-3. PubMed
This tool is educational and is not a substitute for professional medical advice. An association is not a diagnosis and does not mean a deficiency will occur. Always talk to your pharmacist or healthcare provider before starting, stopping, or changing any medication or supplement.
Disclaimer: This checker finds which nutrients might be depleted by prescription or over-the-counter medications. Each nutrient depletion issue is rated based on clinical significance. Use your own professional judgment prior to making clinical decisions.© 2026 Therapeutic Research Center Licensed records refresh weekly · last updated July 3, 2026.
More about Pyrimethamine
What drug-induced nutrient depletion means
Some medications can, over time, lower the levels of certain vitamins, minerals, or other nutrients — through reduced absorption, increased loss, or changes in how the body uses them.
Association is not deficiency
An entry here means a depletion has been reported or studied — not that it happens to everyone, or that you are deficient. Dose, duration, diet, and your own health all matter.
Evidence varies by pair
Some drug–nutrient links (like metformin and vitamin B12) are well studied; others rest on limited or preliminary research. Each entry shows the evidence rating from our licensed clinical database.
When to ask about labs
If you take an associated medication long-term, ask your healthcare provider whether monitoring is appropriate for you. Not everyone needs testing — your provider can weigh your dose, duration, and symptoms.
Don't self-supplement blindly
Supplements are not risk-free: some can interact with medications, and some (like potassium or magnesium) can be risky with kidney disease. Talk to your pharmacist before adding anything.
Never stop a medication over this
These medications are prescribed for good reasons, and the benefit usually far outweighs a manageable nutrient consideration. Any change belongs in a conversation with your prescriber.
Food first, usually
For many nutrients, a varied diet covers the gap. Each entry lists common food sources; a supplement is a decision to make with your pharmacist or provider, not a default.
Pyrimethamine & nutrients: FAQs
Does Pyrimethamine deplete FOLIC ACID?
Should I take a supplement because I take Pyrimethamine?
Should I stop taking Pyrimethamine?
Where does this information come from?
Questions about Pyrimethamine and your nutrition?
Ask a licensed pharmacist — free, no appointment needed.
Sources & How We Checked
Nutrient depletion records for Pyrimethamine are evidence-graded and sourced from the Natural Medicines database, and are displayed as published with their citations.
- Natural Medicines (Therapeutic Research Center) — Evidence-graded clinical reference for drug-induced nutrient depletions, supplements, and interactions — the basis for this page.
- MedlinePlus, U.S. National Library of Medicine — NIH consumer drug information, used for medication overviews across the site.
Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.