Transcript New advice for users of St. John’s Wort

Risk:benefit analysis of Kava-kava
Update as at 12 Feb 2002
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Update on worldwide situation
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Germany
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France
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Have not yet finalised their assessment.
Expert group has recommended that it becomes a
Prescription Only Medicine.
Have suspended products from sale (includes
homeopathics down to a 1/500 dilution)
Ireland
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Have voluntarily removed from sale all licensed and
unlicensed Kava containing products
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Worldwide update cont.
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Portugal
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USA
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Have suspended all kava containing products including
homeopathics for 1 year.
Distributed a “Dear Doctor” letter requesting doctors to
review all cases of hepatotoxicity to identify whether patients
were taking Kava.
Consumers have been recommended not to take products
containing Kava.
Canada
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Distributed information recommending that consumers
should not use Kava containing products until the risks have
been assessed.
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Worldwide update cont.
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Australia
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Investigating the safety of Kava.
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Consumers have been recommended not to take
Kava containing products.
New Zealand
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3 cases of hepatitis possibly associated with Kava.
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Initiating a toxicology review.
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Kava products are still on sale.
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Scientific Analysis
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Additional useful data
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List of products on the UK market.
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Any further efficacy data.
Efficacy data already available
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Meta-Analysis by Pittler and Ernst.
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Review of risk:benefit profile of herbals by Ernst
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Published studies
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Analysis of case reports by herbal
interest groups
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The majority of submissions included an analysis of
the cases reports.
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The conclusions often differed between submissions.
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No consistent criteria for causality were used.
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Criteria of causality - example of
method used by MCA
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Certain
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A clinical event, including a laboratory test abnormality,
that occurs in a plausible time relation to drug
administration, and which cannot be explained by
coincidental or concurrent disease or other drugs or
chemicals.
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The response to withdrawal of the drug (dechallenge)
should be clinically plausible e.g. the patient recovers.
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The event must be definitive pharmacologically or
phenomenologically, using a satisfactory rechallenge
procedure if necessary.
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Probable
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A clinical event, including a laboratory test
abnormality, with a reasonable time relation to
administration of the drug.
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unlikely to be attributed to concurrent disease or to
other drugs or chemicals.
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which follows a clinically reasonable response on
withdrawal (dechallenge).
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Rechallenge information is not required to fulfil this
definition.
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Possible
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A clinical event, including a laboratory test abnormality,
with a reasonable time relation to administration of the
drug.
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which could also be explained by concurrent disease or
other drugs or chemicals.
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Information on drug withdrawal may be lacking or
unclear.
Unlikely
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A clinical event, including a laboratory test abnormality,
with a temporal relation to administration of the drug.
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which makes a causal relation improbable, and in which
other drugs, chemicals, or underlying disease provide
plausible explanations.
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Unassessable
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A report suggesting an adverse reaction that cannot be
judged, because information is insufficient or
contradictory and cannot be supplemented or verified.
Note: these are possible criteria for causality assessment of
suspected adverse drug reactions derived from a paper published
in the Lancet 2000; 356:1255-1259
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Case number 10 - example of “probable” case
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39 year old female
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Taking a standard extract product (unspecified)
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Experienced hepatitis and confluent necrosis
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ADR confirmed by laboratory tests
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Past medical history
stable on hormone ovulation inhibitor for 6 years (hepatic
reactions associated with this medicine but not in this patient)
also taking paroxetine and St John’s wort PRN
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The consumer took the kava product and experienced the ADR, then
recovered when all medication was stopped
Positive dechallenge
Some months later the consumer restarted the Kava and experience
hepatic ADRs 14 days later
Positive rechallenge
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Case number 17 - example of “possible” case
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60 year old female
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Taking a standard acetone-extract product at the recommended
dose 3x70mg per day
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3 weeks after starting the kava preparation the patient experienced
hepatic ADRs
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ADRs confirmed by laboratory tests
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Good temporal relationship
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Other drugs
Celecoxib taken PRN (hepatic reactions associated with this
medicine)
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The consumer stopped the Kava preparation and recovered within
2 weeks
Positive dechallenge
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Some provisional pointers
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The mechanism of toxicity has not been determined
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The onset of hepatic reactions appears unpredictable
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No data has been put forward to identify what might
be a “safe dose”
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There is insufficient data to support general efficacy
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Some of the cases suggest a “possible/probably”
association between hepatic reactions and Kava
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Possible regulatory options where
there is a herbal safety issue
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Prohibition
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Prescription Only Medicine
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Prohibit the ingredient in unlicensed medicines (e.g. as
was done with Aristolochia).
Make the ingredient a prescription only medicine
(POM).
Restrict usage
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e.g. set a maximum dosage.
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Possible regulatory options (contd)
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Add warnings (e.g. regarding rare hepatic adverse
reactions)
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Initiate variations for the 3 licensed products.
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Obtain voluntary agreement with manufacturers of
unlicensed products to include warning information
Take no regulatory action at this time
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Example of possible labelling
(based on suggestions from the herbal sector)
Do not take this product if you have a history of liver
problems or in combination with alcohol or medication,
unless under the guidance of your doctor.
This product may rarely cause liver problems with
symptoms such as jaundice, brown urine, nausea,
vomiting and unusual tiredness. If you experience an
adverse effect while taking this product please consult
your doctor.
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