The short answer
Yes, there is evidence of an interaction. Piperine, the compound that gives pippali (long pepper) and black pepper their bite, raised blood levels of phenytoin in healthy volunteers and in people with epilepsy. In one study a single 20 mg dose of piperine significantly increased phenytoin levels.
Phenytoin is an epilepsy medicine with a narrow therapeutic index, so small changes in blood level can matter. Pippali is an ingredient of common formulations such as Sitopaladi Churna. If you take phenytoin, tell your prescribing doctor before starting any product that contains pippali or piperine.
At a glance
| What was seen | How it may work | Direction | Evidence |
|---|---|---|---|
| Higher phenytoin levels (AUC, Cmax)[1][2][3] | Increased absorption; slower elimination | More phenytoin in the blood | Small clinical study |
No listing is not a clearance. A missing interaction here never means a combination is safe.
The evidence, study by study
Patients with epilepsy, Chandigarh, 2006 Small clinical study
Twenty patients with uncontrolled epilepsy already on phenytoin were given a single 20 mg dose of piperine. Mean phenytoin levels rose at most time points, with significant increases in total exposure (AUC) and peak level (Cmax). The authors suggest piperine increases absorption.[1]
Black pepper in food, AIIMS New Delhi, 2001 Small clinical study
Six healthy volunteers took phenytoin 30 minutes after a soup (rasam) with or without black pepper. With pepper, phenytoin was absorbed faster, total exposure rose and elimination was delayed. Rat data pointed to slower metabolism as well. The authors call phenytoin a drug with a narrow therapeutic index.[2]
Healthy volunteers, Jammu, 1987 Small clinical study
The first human report that piperine changes phenytoin pharmacokinetics. Later studies cite it as showing increased oral bioavailability.[3]
What to tell your prescribing doctor
You can read this out, or show them this page:
“I am taking, or planning to take, a product that contains pippali or piperine (name of product, dose) along with phenytoin. Studies show piperine can raise phenytoin levels. Should my phenytoin level be checked?”
Withheld until review
Related
Sitopaladi Churna
A classical cough powder, about half sugar by weight. It contains pippali, which can raise phenytoin levels.
InteractionTurmeric and blood thinners
One reported case of a raised INR, and lab data on liver enzymes. The evidence is thin, but blood thinners leave little margin.
Sources
- Pattanaik S, Hota D, Prabhakar S, et al. Effect of piperine on the steady-state pharmacokinetics of phenytoin in patients with epilepsy. Phytother Res. 2006;20(8):683-6. PMID 16767797.
- Velpandian T, Jasuja R, Bhardwaj RK, et al. Piperine in food: interference in the pharmacokinetics of phenytoin. Eur J Drug Metab Pharmacokinet. 2001;26(4):241-7. PMID 11808866.
- Bano G, Amla V, Raina RK, et al. The effect of piperine on pharmacokinetics of phenytoin in healthy volunteers. Planta Med. 1987;53(6):568-9. PMID 3444866.
Awaiting review by The Good Vaidya Medical Board. Prepared from the sources below and checked against each one.
Published 4 November 2026 · Last updated 4 November 2026
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