FOI release

Freedom of Information request on how many times have yohimbe/yohimbine, synephrine and ephedrine been reported to the Yellow Card Scheme since 2011 (FOI 21-779)

Published 27 April 2022

5th August 2021 FOI 21/779

Dear

Thank you for your Freedom of Information request dated 6th July 2021, where you asked for information on the following: • Please confirm many times have yohimbe/yohimbine (please search both spellings), synephrine and ephedrine been reported to the Yellow Card Scheme since 2011?

• For each of these instances please provide the year as well as details of the side effects reported and any information about the product, where it was purchased and how/why was it taken (i.e. purchased as a weight loss pill).

• For each of these instances please also provide any action taken by the MHRA or responsible regulator.

Since 01/01/2011, the MHRA has received a total of 6 UK spontaneous suspected Adverse Drug Reaction (ADR) reports associated with Yohimbe/Yohimbine, 2 ADR reports associated with synephrine and 34 ADR reports associated with ephedrine. This includes a total of 41 unique reports. Please note that the sum of reports in each of the attached tables may not be equal to the number of unique reports as one report may contain more than one suspect drug and a product may contain more than one active substance. Yellow Card data is releasable to members of the public provided that patient and reporter confidentiality is maintained. Under the Freedom of Information Act (FOIA) 2000, the data for this request has been provided as category Ib. For this FOI, the line listings contain the fields below. Please note, any blank cells within the table are fields which have not been provided to us by the reporter. Case number Patient Age Category (35-44, 45-54, 55-64, 65-74, 75-84, >85 years) Patient Gender Suspect drug(s) Suspect drug indication(s) Suspect drug route(s) Treatment duration (days) Suspected Adverse Drug Reaction(s) Reaction onset first dose (days) Reaction outcome(s) Medical History Please see attached tables for a breakdown of the requested ADR reports of Yohimbine/Yohimbe (Table 1) and ephedrine (Table 2). The information is presented in a line listing (Table a), and aggregated patient age and sex (Table b and c). The MHRA will not release any data subset in which there are five or fewer cases. As we have only received 2 reports associated with synephrine, we have provided a written case summary below. The second case is contained within the Yohimbe/Yohimbine data set (case 6) as the reported product, Katana contains multiple active substances including both yohimbine and synephrine. Synephrine - Case 1 of 2: Female patient taking ciprofloxacin, Melanotan and T500 Fury presented with right upper quadrant pain (outcome unknown), hepatotoxicity (outcome recovered). Please be aware that it is not mandatory to provide the suspect drug indication when submitting a Yellow Card report to the MHRA. The Yellow Card Scheme does not ask the reporter for information on where the product was purchased, so we are unable to provide this information. The MHRA continuously monitors the safety of medicinal products and vaccines through a variety of pharmacovigilance processes including the Yellow Card scheme. As part of our signal detection processes all adverse reaction reports received by the Yellow Card scheme are individually assessed and cumulative information reviewed at regular intervals. Using specialised software, Yellow Card data are subjected to statistical analysis of all drug-reaction combinations on the database. This identifies ‘signals’—drug-reaction combinations that occur more frequently than would be expected when compared to the background frequency of other drug-reaction combinations in the database. Signals that meet defined criteria are evaluated further by a team of safety experts to assess the likelihood of causal relationship between the drugs and reported reactions. Examples of regulatory action include restrictions on use, refinement of dose instructions or the introduction of specific warnings of side-effects in product information, which allow medicines to be used more safely and effectively. As you may be aware, products containing these substances would normally be subject to controls as Prescription Only Medicines. The majority of products marketed as weight loss/slimming products or nutritional supplements are unlicenced medicines or are regulated as foods and therefore fall outside of the MHRA’s remit. However, on investigation the MHRA determined Katana, OxyElite Pro, Shredabull and T500 Fury as medicinal products. As the products do not have a marketing authorisation, in these cases Medicines Borderline issued Urgent Notices in accordance with Regulation 165, Part 9 of the Human Medicines Regulations 2012 (SI 2012/1916). This Notice was issued to the company placing the product on the market to inform that they must cease to sell, supply or advertise the product in the UK. The Notices were issued to different companies that had been brought to our attention as sellers of the products. You may also be interested to read about some of the work the MHRA has done in the areas of slimming and sports nutrition, which are available at the following links:

https://www.gov.uk/government/news/dodgy-diet-pills-dying-to-lose-weight

https://www.gov.uk/government/news/new-research-shows-desperate-dieters-in-danger-the-secret-world-of-online-slimming-pills

https://www.gov.uk/government/news/mhra-review-shows-sports-supplement-industry-improvement

It is important to note that due to the nature of the Yellow Card Scheme, neither the incidence nor the prevalence of a reaction can be derived from these data, as neither the total number of reactions occurring, nor the number of patients using the drug is included in this data. Many factors influence the number of reports received. Reporting rates are influenced by the seriousness of the adverse drug reactions, their ease of recognition, the extent of use of a product, and may also be stimulated by promotion and publicity about a product. Furthermore, it is also important to note that a report of a reaction does not necessarily mean that it has been caused by the drug in question. We encourage reporters to report suspected ADRs i.e. the reporter does not have to be sure of a causal association between the drug and the reactions – a mere suspicion will suffice. Therefore, reports submitted to MHRA may be true side-effects or they may be due to concurrent diagnosed or undiagnosed illness, other medicines, or they may be purely co-incidental events that would have occurred anyway in the absence of therapy. I hope the information provided is helpful. The MHRA encourages the use of Yellow Card data however wishes to ensure that the data is studied and applied appropriately, and any conclusions/interpretations take into account the above information. For this reason, if you wish to use this information for a publication, we request that you engage with the MHRA during this process and provide a copy of the report. If you are dissatisfied with the handling of your request, you have the right to ask for an internal review. Internal review requests should be submitted within two months of the date of this response; and can be addressed to this email address. Yours sincerely, FOI Team, Vigilance and Risk Management of Medicines Division