Drug & supplement interaction

K2/spice + Fosphenytoin

Fosphenytoin brand name: Cerebyx.

Moderate Interaction
The bottom line Moderate

Fosphenytoin falls into 2 drug categories that K2/spice can interact with; the most serious is rated moderate. Theoretically, K2/spice might have an additive effect with drugs that prolong the QT interval and increase the risk of ventricular arrhythmias.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

K2/spice and Fosphenytoin

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

K2/spice interacts with whole categories of medication. Fosphenytoin falls into 2 of those categories, so it can interact with K2/spice in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

QT INTERVAL-PROLONGING DRUGS

1 of 2

Why this applies to Fosphenytoin

Fosphenytoin falls under QT INTERVAL-PROLONGING DRUGS — the group K2/spice interacts with.

Theoretically, K2/spice might have an additive effect with drugs that prolong the QT interval and increase the risk of ventricular arrhythmias.
There have been numerous cases of increased QT and corrected QT intervals in patients using K2/spice.
Severity Moderate Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

First things first: K2/Spice isn't a real supplement. It's plant material sprayed with lab-made cannabinoid chemicals, and it has been linked to seizures, heart trouble, and even deaths. Since you're taking fosphenytoin (Cerebyx) specifically to control seizures, using something that can trigger seizures works directly against your treatment.

The interaction on file here is about the heart's rhythm. Fosphenytoin can affect the QT interval (the heart's electrical timing), and there have been reports of K2/Spice doing the same. Together, they could in theory add up and raise the risk of a dangerous, irregular heartbeat. This is based on anecdotal reports, so it's not proven, but it's a real concern worth taking seriously. Please talk with your doctor or pharmacist before mixing anything with your seizure medicine.

References
  1. Ahmed T, Khan A, See VY, Robinson S. Cardiac arrest associated with synthetic cannabinoid use and acquired prolonged QTc interval: A case report and review of literature. HeartRhythm Case Rep. 2020;6(5):283-286. PubMed
  2. Yildiz SS, Sutasir MN, Sigirci S, et al. Acute effects of synthetic cannabinoids on ventricular repolarization parameters. Turk Kardiyol Dern Ars. 2019;47(5):384-390.
Moderate

ANTICONVULSANTS

2 of 2

Fosphenytoin also falls under ANTICONVULSANTS.

Theoretically, K2/spice might increase or decrease the effectiveness of anticonvulsant drugs.
Some animal research suggests that certain types of synthetic cannabinoids found in some K2/spice products can potentiate the effects of anticonvulsants. However, seizures have also been reported with inhalation of K2/spice.
Severity Moderate Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

First things first: I really don't want you mixing K2/spice with anything, let alone a seizure medicine. These products are synthetic chemicals sprayed on plant material, and they're wildly unpredictable. One of the documented dangers is that K2/spice itself can trigger seizures, which directly works against what fosphenytoin is trying to do for you.

Fosphenytoin turns into phenytoin in your body, and phenytoin has a very narrow safety window, meaning small shifts in its level can tip you toward either breakthrough seizures or toxicity (think slurred speech, unsteady walking, double vision, severe drowsiness). The interaction here is theoretical, based mostly on animal research, so the exact direction isn't certain. Honestly though, the bigger issue is that K2/spice is simply unsafe. Please talk with your doctor or pharmacist before using anything alongside your seizure treatment.

References
  1. Davidson C, Opacka-Juffry J, Arevalo-Martin A, Garcia-Ovejero D, Molina-Holgado E, Molina-Holgado F. Spicing up pharmacology: a review of synthetic cannabinoids from structure to adverse events. Adv Pharmacol 2017;80:135-68. PubMed
  2. Tait RJ, Caldicott D, Mountain D, Hill SL, Lenton S. A systematic review of adverse events arising from the use of synthetic cannabinoids and their associated treatment. Clin Toxicol (Phila) 2016;54(1):1-13. PubMed

What These Ratings Mean

Every interaction above is graded three ways — here’s the key to each label.

Severity how clinically significant the interaction is
Major

Clinically significant. Avoid the combination, or use only under close professional supervision.

Moderate

Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.

Minor

Generally not serious. Be aware of it and mention it to your pharmacist.

Likelihood how strong the evidence is that the interaction actually happens in people
  • LikelyWell-controlled human studies have demonstrated the likely existence of this interaction.
  • ProbableInteraction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
  • PossibleInteraction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.
  • UnlikelyInteraction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
Evidence the quality of the studies behind the rating (graded A–D)
  • AHigh-quality meta-analysis (quantitative systematic review).
  • BCase-control study.
  • CConsensus.
  • DAnecdotal evidence.

These ratings are for information only. Never start, stop, or otherwise change your therapy before speaking with your provider.

Keep it in perspective

K2/spice Also Interacts With Other Medications

K2/spice has 207 moderate known drug interactions in our database — the Fosphenytoin one above is among them. If you take anything else, check it against the full list below.

Taking anything else?

Check Another of Your Medications Against K2/spice

Covers the 2,830 medications we’ve checked against K2/spice. Pick one to open its full report.

Everything else you take

See Every Supplement That Interacts With Fosphenytoin

This page covers K2/spice only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Fosphenytoin page lists 205 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: 1,4-butanediol (major), American Hellebore (major), Arsenic (major), Beer (major) and Cesium (major).

By severity: 14 major · 172 moderate · 19 minor.

From our pharmacist’s overview on the Fosphenytoin page

“St. John's wort is the entry I would flag first with fosphenytoin (Cerebyx).”

Reviewed by 2 · Jul 18, 2026

Open the Fosphenytoin interaction page

How much people look this up

Where K2/spice and Fosphenytoin Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement K2/spice
Steady interest

#810 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Fosphenytoin
Top half

#1,114 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Supplement

About K2/spice

What is K2/spice?

  • Recreational drug ('legal high')
  • Marijuana substitute
  • Mood or perception changes
  • Sometimes used to avoid drug testing

K2/Spice is NOT a herbal supplement — it is plant material sprayed with man-made synthetic cannabinoid chemicals. It is dangerous, unpredictable, and has caused seizures, heart problems, psychosis, and deaths, so it should not be used.

Read the full K2/spice monograph & all interactions
Medication

About Fosphenytoin Injection

What Is Fosphenytoin Injection Used For?

Brand name: Cerebyx

Fosphenytoin injection is used to treat generalized tonic-clonic status epilepticus (a prolonged, life-threatening seizure emergency) and to prevent or treat seizures that occur during or after brain surgery. It is given by intravenous (IV) or intramuscular (IM) injection in a hospital or clinical setting.

It can also be used short-term as a substitute for oral phenytoin when a patient cannot take medicine by mouth. This use is temporary — as soon as oral phenytoin is possible again, it should replace the injection.

See full Fosphenytoin Injection drug information
Keep checking

Other Drugs & K2/spice

Browse every other medication we’ve checked against K2/spice — both the ones with a known interaction and the ones without. Select any drug for the full detail.

0Major
207Moderate
0Minor
2,622No known interaction
Moderate

207 interactions

Showing 60 of 207 moderate interactions — see all 207 on the K2/spice page.

No interaction 2,622 drugs checked — show the list
Sources

Sources & How We Checked

Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.

Parts of this content are provided by the Therapeutic Research Center, LLC.

DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

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Pharmacist Counseling Corner

Taking K2/spice and Fosphenytoin Together: Common Questions

Can you take K2/spice with Fosphenytoin?
There is a moderate interaction, so it may be acceptable with monitoring or timing changes — but check with your pharmacist first. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 2 interactions listed for K2/spice and Fosphenytoin?
Fosphenytoin belongs to more than one drug category, and K2/spice interacts with each of those categories a little differently. We list every one so nothing is missed — your overall risk is driven by the most serious of them.
How serious is the K2/spice and Fosphenytoin interaction?
We rate it Moderate. This combination may require monitoring, a dose adjustment, or separating the times you take each one. Consult your pharmacist before using them together.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

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This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.