Kava Fact of the Day FDA adverse event reports involving kava and how to view them.

[The Kap'n]

FAERS - Federal Adverse Events Reporting System

Hello kava lovers! It’s been a while, but life is starting to let up a bit, the shadows are getting longer, and the daytime temps are starting to fall. That means more time for more kava research!

Today’s information is going to come from the FDA’s adverse event reporting system known as FAERS (Formerly AERS). FAERS stands for “Federal Adverse Event Reporting System”. This system was formally started in 1969 with a major revision in 1997. Currently FAERS is the largest repository for spontaneously reported adverse events in the world with over 4 million public reports [1]. The FAERS database is very useful for analyzing associations with drug and herbal interactions; however some shortcomings should be acknowledged.

1. Duplicates and incomplete reports exist in the system. You’ll see this clearly if you scroll down the events list, as many of them have the same source document, indicating they’re from the same instance, just listed several times.
2. Just because these reports exist, they don’t establish causation.
3. Information in these reports is not independently verified.
4. Rates of occurrence of these instances cannot be established with reports [2].

You can follow along with today’s fact of the day as all of this information is publicly available by default.


Launch the FAERS Public Dashboard using these steps:

1. https://www.fda.gov/drugs/questions...event-reporting-system-faers-public-dashboard
2. Click The blue button titled “FAERS Public Dashboard”
3. Some black circles appear as the page loads, and you’re met with a disclaimer. Click “I have read” and click “Accept”.
4. On the top left next to “Home” click “Search”
5. Type “Kava” in the search bar, and then click “Go”
6. Click “listing of cases” on the top blue bar.

If you’ve followed the directions above you’re now met with the FAERS reports for kava. The reports marked with Ropinirole and Haloperidol have several duplicates in this data set, so keep that in mind. The most recent report from March of 2020 we saw unfold almost in real time. On reddit we had a user who reported not being able to walk after visiting the kava bar and checked themselves into a hospital. All the data matches up to the person in question in the report. We’re pretty sure this coincides with report number 17538320.

To get some reference on how harmful some things can be, try searching “Acetaminophen”. It’s quite sobering. Acetaminophen (APAP, Panadol, Tylenol) currently has 8,351 adverse events for the year of 2021 with almost 13,000 for 2020.

There we go. You now know exactly how to see adverse events reports related to herbs and drugs in regards to the public and the FDA.





[1] Sakaeda, Toshiyuki, Akiko Tamon, Kaori Kadoyama, and Yasushi Okuno. 2013. “Data Mining of the Public Version of the FDA Adverse Event Reporting System.” International Journal of Medical Sciences 10 (7): 796–803. https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3689877/

[2] Center for Drug Evaluation, and Research. 2021. “FDA Adverse Event Reporting System (FAERS) Public Dashboard.” April 3, 2021. https://www.fda.gov/drugs/questions...event-reporting-system-faers-public-dashboard

 

[Skinskava]

Id be interested to hear a response to the university of michigans page surrounding kava tons of misinformation. Also, why do we hear little going foward regarding the minnesota study that showed so much promise in mice regarding lung cancer

 

[Skinskava]

Kava | University of Michigan Health

Top of the pageKavaTreatment OverviewKava—or kava kava—is a root found on islands in the western Pacific Ocean. Traditionally prepared as a tea, kava root is also available in other forms. These include dietary supplements and liquid or powder extracts. Why It Is UsedKava is used by some people...

www.uofmhealth.org

 

[Skinskava]

My hair hasnt turned yellow yet… hmm

 

[The Kap'n]

My hair hasnt turned yellow yet… hmm

For real. I was hoping to go super saiyan, but no dice.

I'll look over that University's sources to see where they're pulling from. You can write a research paper to say whatever you want it to say at this point there are so many different data points available for kava. You really have to be careful when pulling from sources around the start of the millennium. Quite a bit of research has been officially refuted.

Edit: Nice, they pull from textbooks which keeps me from being able to see what the real sources of that info are.

 

[Skinskava]

For real. I was hoping to go super saiyan, but no dice.

I'll look over that University's sources to see where they're pulling from. You can write a research paper to say whatever you want it to say at this point there are so many different data points available for kava. You really have to be careful when pulling from sources around the start of the millennium. Quite a bit of research has been officially refuted.

Edit: Nice, they pull from textbooks which keeps me from being able to see what the real sources of that info are.

Thank you for finding your way through the treacherous seas of misinformation on the internet and deliver the facts. Always appreciate your time and effort

 

[Skinskava]

“Kava also can prevent convulsions and relax muscles. Although kava is not habit-forming, its effect may decrease with use”. This really is a head shaker. When i drink kava once a week 65 grams feels like 35 grams or so when i am having kava several days in a row. The effects seem to increase maybe the user is just more accustomed to the effects of the root

 

[The Kap'n]

Here's one source:

Sci-Hub | Kava in generalized anxiety disorder: three placebo-controlled trials. International Clinical Psychopharmacology, 21(5), 249–253 | 10.1097/00004850-200609000-00001

One Textbook it seems there's a chapter about Kava in:

Review of Natural Products

The foremost source of current natural product information for health care professionals.

www.wolterskluwer.com

The Second textbook they gather info from:

Textbook of Natural Medicine - 4th Edition

Purchase Textbook of Natural Medicine - 4th Edition. Print Book & E-Book. ISBN 9781437723335, 9781455740147

www.elsevier.com

Also, check this out. Looks awfully familiar. Maybe they hired the same people to write the article:

Kava

Briefly discusses kava (also known as kava kava), a dietary supplement used to relieve anxiety, restlessness, insomnia, and stress-related symptoms. Covers safety issues and side effects, including liver damage in some when used for long periods.

www.stlukesonline.org

 

[The Kap'n]

“Kava also can prevent convulsions and relax muscles. Although kava is not habit-forming, its effect may decrease with use”. This really is a head shaker. When i drink kava once a week 65 grams feels like 35 grams or so when i am having kava several days in a row. The effects seem to increase maybe the user is just more accustomed to the effects of the root

It's just wrong. Wrapping their minds around a compound that might have a reverse tolerance effect just isn't something they think of as possible. Still to this day people argue over the existence of reverse tolerance (not to be confused with initial tolerance, which we have no evidence for) when we have actual research that shows these time delayed effects of kava such as MAO, Acetylcholine, Glutamate and Noradrenalin. These systems require time to develop their effect and as such may lend to an increasing of kava's physiological effects over time, but to a point. Some people think "reverse tolerance" is just a infinite cycle, but kava's reverse tolerance does have a stopping point.

 

[The Kap'n]

The whole "Shortness of breath" makes me wonder if the people who gravitate towards kava may also bring with them their panic disorders which cause this, but honestly never have I ever found myself short of breath after kava.

They're getting that from this source:
Mathews, J. D., M. D. Riley, L. Fejo, E. Munoz, N. R. Milns, I. D. Gardner, J. R. Powers, E. Ganygulpa, and B. J. Gununuwawuy. 1988. “Effects of the Heavy Usage of Kava on Physical Health: Summary of a Pilot Survey in an Aboriginal Community.” The Medical Journal of Australia 148 (11): 548–55. https://sci-hub.se/10.5694/j.1326-5377.1988.tb93809.x

I highly suggest Alan Clough's work on the Aborigines of Northern Territory. I find it to leave me scratching my head far less than the research done by Mathews.

Currie, Bart J., and Alan R. Clough. 2003. “Kava Hepatotoxicity with Western Herbal Products: Does It Occur with Traditional Kava Use?” The Medical Journal of Australia. mja.com.au. https://sci-hub.se/10.5694/j.1326-5377.2003.tb05279.x

 

[The Kap'n]

I randomly selected one report based on the search term "Jaundice" in regards to kava and came up with this case.

Case ID

Suspect Product Names

Suspect Product Active Ingredients

Reason for Use

Reactions

Serious

Outcomes

Sex

Event Date

Latest FDA Received Date

Case Priority

Patient Age

Patient Weight

Initial FDA Received Date

7336169​

Kava

Piper Methysticum Root;Phenytoin Sodium

Seizure

Headache, Diarrhea, Rash, Coagulopathy, Jaundice, Mental Status Changes, Malaise, Abdominal Pain

Serious

Hospitalized

Female

15-APR-2001

16-MAR-2010

Direct

35 YR

83 KG

16-MAR- 2010

Here we have Kava (Piper Methysticum) combined with Phenytoin Sodium.

Here's a little bit about Phenytoin from Drugbank.ca

The experience of phenytoin toxicity is not limited to situations of acute ingestion, but may also occur due to drug interactions or due to physiological circumstances that impact serum albumin (ie. kidney disease) or drug metabolism. Other changes that may result in phenytoin toxicity include pregnancy, malnutrition and malignancy.

Phenytoin toxicity most often affects the cardiovascular and nervous systems. The most common presentation of toxicity depends on the route of administration.3 Cardiovascular adverse effects are most commonly linked to intravenous phenytoin administration, whereas neurological adverse effects are more common with oral phenytoin administration.

Neurotoxicity is usually dependent on serum concentrations. When concentrations range from 10-20 mg/L, mild nystagmus and lateral gaze may occur, while more significant nystagmus is associated with concentrations ranging from 20-30 mg/L. At concentrations of 30-40 mg/L, slurred speech, tremor, nausea, vomiting and ataxia have been reported. In more serious cases where serum levels range from 40-50 mg/L patients are at risk of lethargy, confusion and hyperactivity, and at levels beyond 50 mg/L, coma and seizures may occur.

Phenytoin is classified as an antiarrhythmic and can cause SA and AV nodal blocks as well as dysrhythmias due to its effect on voltage-gated sodium channels. Further, since phenytoin is poorly soluble, the parenteral form is administered with propylene glycol, which is a cardiac depressant. The infusion rate of parenteral phenytoin should not exceed 50 mg per minute due to the risk of hypotension, bradycardia, and asystole.

Treatment for phenytoin toxicity is non-specific and centres around supportive care. One dose of activated charcoal may be used to prevent phenytoin absorption in cases of acute ingestion.

Although hemodialysis is moderately effective at removing phenytoin, it is not normally recommended due to the risks associated with the procedure, and the general effectiveness of supportive care.

Phenytoin: Uses, Interactions, Mechanism of Action | DrugBank Online

Phenytoin is an anticonvulsant drug used in the prophylaxis and control of various types of seizures.

go.drugbank.com

As we can see, this drug is itself the culprit of the liver toxicity, however to be fair kava may have reduced the person's tolerance to Phenytoin via the CYP enzyme inhibition at CYP2C9 which kava has been shown to inhibit. I should say take that with a grain of salt though, as this CYP inhibitory profile also comes from the same study that said Kava inhibited CYP2D6. Human drug CYP targets have not confirmed this, and it only seems to present itself in vitro.

 

[Alia]

I randomly selected one report based on the search term "Jaundice" in regards to kava and came up with this case.

Case ID

Suspect Product Names

Suspect Product Active Ingredients

Reason for Use

Reactions

Serious

Outcomes

Sex

Event Date

Latest FDA Received Date

Case Priority

Patient Age

Patient Weight

Initial FDA Received Date

7336169​

Kava

Piper Methysticum Root;Phenytoin Sodium

Seizure

Headache, Diarrhea, Rash, Coagulopathy, Jaundice, Mental Status Changes, Malaise, Abdominal Pain

Serious

Hospitalized

Female

15-APR-2001

16-MAR-2010

Direct

35 YR

83 KG

16-MAR- 2010

Here we have Kava (Piper Methysticum) combined with Phenytoin Sodium.

Here's a little bit about Phenytoin from Drugbank.ca



As we can see, this drug is itself the culprit of the liver toxicity, however to be fair kava may have reduced the person's tolerance to Phenytoin via the CYP enzyme inhibition at CYP2C9 which kava has been shown to inhibit. I should say take that with a grain of salt though, as this CYP inhibitory profile also comes from the same study that said Kava inhibited CYP2D6. Human drug CYP targets have not confirmed this, and it only seems to present itself in vitro.

As far as I can read this FDA report, it does not specifically say what form the kava is in that she took.
True-- it says "Piper Methysticum Root" but that does not necessarily equate to aqueous beverage.
Or did I miss something?

 

[The Kap'n]

As far as I can read this FDA report, it does not specifically say what form the kava is in that she took.
True-- it says "Piper Methysticum Root" but that does not necessarily equate to aqueous beverage.
Or did I miss something?

You're right. They don't say. I fully suspect that Phenytoin was the culprit of their issues seeing as every one of those "reactions" falls right in line with Phenytoin, not to mention it has a very narrow band of therapeutic efficacy. The only one I know for sure that's aqueous is the one from 2020.

 

[KavaBobo]

Of course being reported by the FDA…you know it has to be true and accurate/sarc

 

[Groggy]

At what point does a person reasonably make up their minds and do their own research in order to determine what is good for them?

The FDA used to be fully funded by taxpayer dollars up until 1992 at which point manufactures began paying 'user fees' in order to fund the FDA and expedite drug approval. these "fees" must be re-authorized every 5 years by congress. How much faith do you have in a government agency where 65% of the budget come from the very drug companies seeking FDA approval?

The FDA has a place but the consumer has to have the common sense to weed through the minefield of bullshit that is US regulatory agencies.