Primidone & Nutrient Depletion
Also searched as Mysoline. What the clinical evidence reports, what it may mean, and what to discuss with your pharmacist.
Primidone has been associated with depletion of VITAMIN K, BIOTIN and FOLIC ACID. This does not mean a deficiency will occur — it means these are worth knowing about and, if you take Primidone long-term, worth raising with your pharmacist or healthcare provider.
Take more than one medication? Open the checker with Primidone pre-loaded and add the rest to see overlapping nutrient signals.
Reported nutrient depletions with Primidone
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.
VITAMIN K
Insignificant DepletionANTICONVULSANTS
When taken during pregnancy, anticonvulsants that induce hepatic enzymes (e.g., phenobarbital, phenytoin, carbamazepine) can reduce vitamin K levels in the fetus and increase the risk of intracranial hemorrhage soon after birth. It's thought that liver enzyme induction by these drugs increases vitamin K metabolism. This has a significant effect on vitamin K levels in infants, who haven't built up stores of the vitamin. When anticonvulsants are needed during pregnancy, vitamin K 10-20 mg daily should be taken orally for the last month of pregnancy, and the baby should receive vitamin K immediately after delivery. There is also limited evidence that chronic carbamazepine or phenytoin therapy can cause subclinical reductions in vitamin K activity in adults. There are rare reports of prolonged clotting times and bleeding in people with additional risk factors for vitamin K deficiency, such as poor nutritional intake. These anticonvulsants don't significantly affect vitamin K and clotting parameters in most children and adults. For information on foods that are rich in vitamin K, see our chart.
Primidone is closely related to phenobarbital, and both drugs can ramp up liver enzymes that break down vitamin K faster than usual, which may nudge levels down over time. Vitamin K is the nutrient your blood needs to clot properly. That said, the evidence for this interaction is rated insignificant, meaning most adults taking primidone do not need to worry about or do anything about their vitamin K levels. The main situation where this becomes a real concern is pregnancy, so if that applies to you, please bring it up with your doctor or pharmacist right away.
What Vitamin K does & food sources
Vitamin K is required for normal blood clotting and contributes to bone health.
Common food sources:
- Leafy green vegetables (spinach, kale, broccoli)
- Vegetable oils
- Fermented foods like natto
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
What to discuss with your clinician
If you take warfarin, vitamin K intake is a central part of your therapy — consistency matters more than avoidance. Discuss any planned change in vitamin K intake (diet or supplements) with the clinic that manages your INR.
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
Supplement considerations
Never start or stop a vitamin K supplement on your own if you take warfarin — it directly changes how the medication works.
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: Vitamin K interacts with warfarin: keep intake consistent and involve your anticoagulation clinic in any change.
Learn more about this nutrient: Vitamin K — uses, safety & interactions
References (8)
- Cornelissen M, Steegers-Theunissen R, Kollee L, et al. Increased incidence of neonatal vitamin K deficiency resulting from maternal anticonvulsant therapy. Am J Obstet Gynecol 1993;168:923-8. PubMed
- Cornelissen M, Steegers-Theunissen R, Kollee L, et al. Supplementation of vitamin K in pregnant women receiving anticonvulsant therapy prevents neonatal vitamin K deficiency. Am J Obstet Gynecol 1993;168:884-8. PubMed
- Renzulli P, Tuchschmid P, Eich G, et al. Early vitamin K deficiency bleeding after maternal phenobarbital intake: management of massive intracranial haemorrhage by minimal surgical intervention. Eur J Pediatr 1998;157:663-5. PubMed
- Bleyer WA, Skinner AL. Fatal neonatal hemorrhage after maternal anticonvulsant therapy. JAMA 1976;235:626-7. DOI
- Thorp JA, Gaston L, Caspers DR, Pal ML. Current concepts and controversies in the use of vitamin K. Drugs 1995;49:376-87. PubMed
- Davies VA, Rothberg AD, Argent AC, Atkinson PM, Staub H, Pienaar NL. Precursor prothrombin status in patients receiving anticonvulsant drugs. Lancet 1985;1:126-8. PubMed
- Keith DA, Gundberg CM, Japour A, et al. Vitamin K-dependent proteins and anticonvulsant medication. Clin Pharmacol Ther 1983;34:529-32. PubMed
- Tam DA Jr, Myer EC. Vitamin K-dependent coagulopathy in a child receiving anticonvulsant therapy. J Child Neurol 1996;11:244-6. PubMed
BIOTIN
Moderate DepletionPRIMIDONE (Mysoline)
Reduced plasma biotin levels can occur in people taking primidone. In one study, plasma levels were 50% lower in people taking primidone or various other anticonvulsants than in controls. There may also be increased urinary excretion of organic acids, which is an indicator of reduced biotin-dependent enzyme activity. Suggested mechanisms include competitive inhibition of biotin transport in the intestine, increased catabolism of biotin, and decreased renal tubular reabsorption of biotin. Primidone contains a carbamide group, which is also present in biotin, and may lead to competition for intestinal and renal tubular absorption sites. The clinical significance of these effects on biotin isn't clear, although it's suggested it may contribute to both anticonvulsant effects and side effects.
Biotin is a B vitamin your body uses to run several key enzymes, including ones involved in energy and fat metabolism. Primidone appears to interfere with biotin in a few ways: its chemical structure is similar enough to biotin that the two may compete for the same absorption spots in the gut and kidneys, and the drug may also speed up how quickly the body breaks biotin down. Studies have found blood biotin levels noticeably lower in people taking primidone long-term, so this is worth paying attention to rather than brushing aside. If you have been on primidone for a while, it is reasonable to ask your pharmacist or doctor whether monitoring or a supplement makes sense for you.
Learn more about this nutrient: Biotin — uses, safety & interactions
References (7)
- Said HM, Redha R, Nylander W. Biotin transport in the human intestine: inhibition by anticonvulsant drugs. Am J Clin Nutr 1989;49:127-31. PubMed
- Krause KH, Bonjour JP, Berlit P, Kochen W. Biotin status of epileptics. Ann N Y Acad Sci 1985;447:297-313.
- Krause KH, Kochen W, Berlit P, Bonjour JP. Excretion of organic acids associated with biotin deficiency in chronic anticonvulsant therapy. Int J Vitam Nutr Res 1984;54:217-22.
- Krause KH, Berlit P, Bonjour JP. Vitamin status in patients on chronic anticonvulsant therapy. Int J Vitam Nutr Res 1982;52:375-85.
- Rathman SC, Eisenschenk S, McMahon RJ. The abundance and function of biotin-dependent enzymes are reduced in rats chronically administered carbamazepine. J Nutr 2002;132:3405-10. PubMed
- Mock DM, Dyken ME. Biotin deficiency results from long-term therapy with anticonvulsants (abstract). Gastroenterology 1995;108:A740. DOI
- Mock DM, Dyken ME. Biotin catabolism is accelerated in adults receiving long-term therapy with anticonvulsants. Neurology 1997;49:1444-7. PubMed
FOLIC ACID
Moderate DepletionPRIMIDONE (Mysoline)
In people with low dietary folate intake, primidone might further decrease serum folate levels and might lead to megaloblastic anemia, possibly contributing to neurological side effects, mental changes, and cerebral atrophy. Possible mechanisms include reduced folic acid absorption, increased metabolism, or increased demand for folic acid as a coenzyme for induced hepatic enzymes. Pregnant individual taking primidone may be especially at risk for reduced folate levels, as low folate levels during pregnancy may contribute to birth defects and pregnancy loss. Folic acid therapy seems to reverse these neurological effects. However, folic acid can worsen seizure control. Advise patients taking primidone to consult their physician before taking folic acid supplements. For information on foods that are rich in folate, see our chart.
Folate is a B vitamin your body uses to build healthy red blood cells and support nerve function. Primidone, which is partly converted to phenobarbital in the body, appears to lower folate levels by speeding up how the liver processes it and possibly reducing how well the gut absorbs it, leaving less available in the bloodstream. This is a well-documented concern, especially for people who already eat a folate-poor diet or who are pregnant, so it is worth bringing up with your doctor or pharmacist. One important catch: folic acid supplements can sometimes affect seizure control, so please do not start them 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 (10)
- Froscher W, Maier V, Laage M, et al. Folate deficiency, anticonvulsant drugs, and psychiatric morbidity. Clin Neuropharmacol 1995;18:165-82. PubMed
- Taliani U, Camellini A, Bernardi P, et al. A clinical case of severe megaloblastic anemia during treatment with primidone. Acta Biomed Ateneo Parmense 1989;60:245-8.
- Lambie DG, Johnson RH. Drugs and folate metabolism. Drugs 1985;30:145-55. PubMed
- Botez MI, Peyronnard J, Berube L, Labrecque R. Relapsing neuropathy, cerebral atrophy and folate deficiency. Appl Neurophysiol 1979;42:171-83.. DOI
- Reynolds EH. Neurological aspects of folate and vitamin B12 metabolism. Clin Haematol 1976;5:661-96. DOI
- Reynolds EH. Folate metabolism and anticonvulsant therapy. Proc R Soc Med 1974;67:68.
- Reynolds EH, Trimble MR. Adverse neuropsychiatric effects of anticonvulsant drugs. Drugs 1985;29:570-81. PubMed
- Hiilesmaa VK, Teramo K, Granstrom ML, Bardy AH. Serum folate concentrations during pregnancy in women with epilepsy: relation to antiepileptic drug concentrations, number of seizures, and fetal outcome. Br Med J 1983;287:577-9. DOI
- Dansky LV, Rosenblatt DS, Andermann E. Mechanisms of teratogenesis: folic acid and antiepileptic therapy. Neurology 1992;42:32-42.
- Lewis DP, Van Dyke DC, Stumbo PJ, Berg MJ. Drug and environmental factors associated with adverse pregnancy outcomes. Part I: antiepileptic drugs, contraceptives, smoking, and folate. Ann Pharmacother 1998;32:802-17. 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 Primidone
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.
Primidone & nutrients: FAQs
Does Primidone deplete VITAMIN K?
Should I take a supplement because I take Primidone?
Should I stop taking Primidone?
Where does this information come from?
Questions about Primidone and your nutrition?
Ask a licensed pharmacist — free, no appointment needed.
Sources & How We Checked
Nutrient depletion records for Primidone 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.