What happens when you take phenytoin with ginkgo?
Phenytoin (Dilantin, Phenytek) is a narrow-therapeutic-index anticonvulsant. Even small changes in how fast your body clears it can move its blood level a lot, because phenytoin follows saturable, non-linear pharmacokinetics. Ginkgo biloba, one of the best-selling herbal supplements for memory and circulation, can speed up an enzyme that helps clear phenytoin. Here is the sequence of what can happen:
- You start taking ginkgo while already on phenytoin.
- Over a couple of weeks, ginkgo induces the liver enzyme CYP2C19, one of the enzymes that helps metabolize phenytoin.
- With faster clearance, phenytoin blood levels can drift down toward the subtherapeutic range.
- Lower drug exposure can allow a breakthrough seizure in someone whose epilepsy was previously controlled.
- Separately, ginkgo itself carries a seizure-related signal (discussed below), so the two effects can point the same direction.
A human pharmacokinetic study (Yin and colleagues, 2004) showed that ginkgo induces CYP2C19 and changes the metabolism of a CYP2C19 substrate. Because phenytoin shares this pathway, reduced phenytoin exposure with chronic ginkgo use is the predicted effect. A separate fatal case report (Kupiec and Raj, 2005) described a man on phenytoin and valproate who died of a breakthrough seizure and was found at autopsy to have subtherapeutic levels of both drugs while self-administering ginkgo and other supplements. This is associational, not proof of cause, but the mechanism and the outcome line up.
There is a second, independent concern. Ginkgo seeds contain ginkgotoxin (4'-O-methylpyridoxine), a neurotoxin that can provoke seizures. Standardized leaf extracts contain far less than seeds, but batch-to-batch variability and adulteration have been documented, and seizures have occasionally been reported with ginkgo use even in people without epilepsy.
Why is this important?
For someone with epilepsy on phenytoin, both arms of this interaction point the same way: potentially lower drug exposure plus an independent seizure signal from the supplement itself, which together can raise seizure risk.
The overlap of people at risk is large. Ginkgo is marketed for the exact memory and cognition concerns many people with epilepsy have, whether from seizures, from anticonvulsants, or from ordinary aging. Many users consider ginkgo "natural" and do not list it on medication forms, so prescribers may never learn it is on board.
The interaction is also asymmetric in time. Starting ginkgo can lower phenytoin levels over a couple of weeks. Stopping ginkgo lets enzyme activity regress, which can let phenytoin levels rebound. If a prescriber raised the phenytoin dose to compensate during ginkgo use, abruptly stopping the herb can push phenytoin toward the toxic range, with signs such as side-to-side eye flickering (nystagmus), unsteadiness, slurred speech, double vision, and confusion.
What should you do?
The single most useful step is to keep phenytoin and ginkgo out of the same regimen, and to make any change with your prescriber rather than on your own.
Before any change: If you already take both, tell your prescriber or pharmacist before you stop the ginkgo. Ask whether a phenytoin level (free and total) should be checked first, and agree on a plan rather than stopping the herb cold.
Every day, while both are still on board: Take phenytoin exactly as prescribed and do not adjust it yourself. Watch for early signs of phenytoin toxicity (nystagmus, unsteadiness, slurred speech, double vision, drowsiness, confusion) and report any new or breakthrough seizure.
After a change: If ginkgo is stopped, ask whether a follow-up phenytoin level is warranted a few weeks later to catch any rebound. If you have a breakthrough seizure on the combination, treat it as a safety event: do not drive, get evaluated, and stop ginkgo only under medical supervision.
If you are looking for help with memory, mental clarity, or fatigue, raise it with your neurologist. Anticonvulsants themselves can cause cognitive side effects that may respond to a dose adjustment or a different drug, and treatable contributors like depression, poor sleep, anemia, and thyroid problems are worth ruling out before reaching for a supplement.
Which specific products are affected?
On the medication side, this applies to phenytoin in all its forms:
- Dilantin (capsules, chewable tablets, oral suspension)
- Phenytek (extended-release capsules)
- Generic phenytoin sodium
- Fosphenytoin (Cerebyx), the IV prodrug used in hospital, follows the same metabolic pathway
On the supplement side, all forms of ginkgo biloba are relevant:
- Standardized ginkgo leaf extract capsules and tablets (often labeled EGb 761)
- Ginkgo teas and tinctures
- Combination "memory" or "brain" supplements that include ginkgo
- Raw ginkgo seeds, which carry the highest ginkgotoxin content
There is no clearly safe ginkgo product to pair with phenytoin. Treat the combination as one to avoid rather than to dose around.
The science behind it
The evidence base for this pairing is small and largely associational, so it is worth being honest about its limits.
- Kupiec T, Raj V. Fatal seizures due to potential herb-drug interactions with Ginkgo biloba. J Anal Toxicol. 2005;29(7):755-758. (PMID 16419414) A postmortem case report of a man on phenytoin and valproate who died of a breakthrough seizure with subtherapeutic levels of both drugs while self-administering ginkgo. A single fatal case, hypothesis-generating rather than confirmatory.
- Yin OQ, Tomlinson B, et al. Pharmacogenetics and herb-drug interactions: experience with Ginkgo biloba and omeprazole. Pharmacogenetics. 2004;14(12):841-850. (PMID 15608563) A human pharmacokinetic study showing ginkgo induces CYP2C19 and alters the metabolism of a CYP2C19 substrate, supplying the plausible mechanism.
Together these give a documented enzyme-induction mechanism plus one fatal case linked to it. That is enough for major drug-information resources to flag the combination, but it is not large-trial evidence, and the case report does not prove ginkgo caused the death.
Frequently Asked Questions
Can I take ginkgo with phenytoin if I keep the amount small?
There is no clearly safe amount to recommend. Even shorter-term ginkgo use can begin to induce CYP2C19, and the supplement carries its own seizure signal, so the safest approach is to avoid the pairing and discuss alternatives with your doctor.
I have been taking both for a while. Can I just stop the ginkgo today?
Do not stop it abruptly on your own. If your phenytoin dose was raised while you were on ginkgo, stopping the herb suddenly can let phenytoin levels rebound toward the toxic range. Tell your prescriber first and agree on a monitoring plan.
What are the warning signs of phenytoin getting too high?
Side-to-side eye flickering (nystagmus), unsteadiness, slurred speech, double vision, drowsiness, and confusion. Report these to your prescriber promptly.
What are the warning signs that phenytoin is too low?
The main concern is a breakthrough seizure or an increase in seizure frequency in someone who was previously well controlled. Any new seizure on this combination should be evaluated.
I want a supplement for memory. What should I do instead?
Raise the concern with your neurologist. Some cognitive complaints come from the anticonvulsants themselves and may respond to a dose change, and conditions like depression, poor sleep, anemia, and thyroid problems are worth checking before adding any supplement.
Does this apply to fosphenytoin too?
Fosphenytoin (Cerebyx) is converted to phenytoin in the body and follows the same metabolic pathway, so the same interaction concern applies.
Key takeaways
- Ginkgo can induce CYP2C19 and may lower phenytoin levels, which can raise seizure risk in someone whose epilepsy was controlled.
- A published fatal case report linked subtherapeutic phenytoin and valproate to ginkgo self-administration; the evidence is associational, not proof of cause.
- If you take phenytoin, avoid ginkgo, and never start or stop the herb without telling your prescriber.
- Stopping ginkgo abruptly can let phenytoin rebound toward toxicity, so arrange level monitoring around any change.
- Take memory and cognition concerns to your neurologist rather than the supplement aisle.