FOI release

Freedom of Information request on adverse reactions following co-administration of opioid and benzodiazepine (FOI 21/743)

Published 29 December 2021

27th July 2021

FOI 21/743

Dear

Thank you for your email dated 30th June 2021, where you asked for information on the following:

1. Number and types of Adverse Side effects reported, due to co-administration of Opioid and Benzodiazepine, for each year from 2019 through till 2021.
2. Number of deaths reported, due to and/or including co-administration of Opioid and Benzodiazepine, for each year from 2019 through till 2021.

When considering the attached spontaneous data, it is important to be aware of the following points:

• The fact that symptoms occur after use of a vaccine or medicine, and are reported via the Yellow Card scheme, does not in itself mean that they are proven to have been caused by it. Underlying or concurrent illnesses may be responsible and such events can also be coincidental.
• It is also important to note that the number of reports received via the Yellow Card scheme does not directly equate to the number of people who suffer adverse reactions and therefore cannot be used to determine the incidence of a reaction or compare the safety profile of different vaccines. ADR reporting rates are influenced by the seriousness of ADRs, their ease of recognition, the extent of use of a particular medicine, and may be stimulated by promotion and publicity about a drug. Reporting tends to be highest for newly introduced medicines during the first one to two years on the market and then falls over time.

Further to your request please find attached the relevant Drug Analysis Prints (DAPs). The prints contain information on all the UK spontaneous Adverse Drug Reaction (ADR) reports received where an opioid and benzodiazepine have been reported as suspect medications received since the start of the Yellow Card scheme, 01/07/1963 until 13/07/2021.

As these data do not necessarily refer to proven side effects, you should refer to the product information which can be found here: https://products.mhra.gov.uk/ for details on the possible side effects of each product.

The following benzodiazepine substances were included in the database search: Alprazolam, bromazepam, brotizolam, chlordiazepoxide, clobazam, clonazepam, clonazolam, clotiazepam, delorazepam, diazepam, diclazepam, estazolam, etizolam, flualprazolam, flubromazepam, flubromazolam, flunitrazepam, flurazepam, halazepam, ketazolam, loprazolam, lorazepam, lormetazepam, medazepam, metizolam, midazolam,nitrazepam, nordazepam, oxazepam, phenazepam, prazepam, quazepam, remimazolam, temazepam, tetrazepam, triazolam. The following opioid substances were also included in the database search: alfentanil, buprenorphine, carfentanil, codeine, codeine sulphate, diamorphine, dihydrocodeine, fentanyl, furanylfentanyl, morphine, norbuprenorphine, norfentanyl, oxycodone, remifentanil, sufentanil, tapentadol, tramadol.

With regards to point 2 please see below table outlining the number of UK spontaneous ADR reports received since the start of the Yellow Card scheme, 01/07/1963 until 13/07/2021 with a fatal outcome where an opioid

Year	Number of fatal reports
2019	20
2020	18
2021 (up to and including 13/07/2021)	53

I hope the information provided is helpful, but 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