What is the aim of the Yellow Card Scheme?
The YCS allows the MHRA to monitor the safety of all medicines and medical devices on the market continuously over the entire product life.
The YCS primarily serves as an early warning of possible hazards associated with medicines and provides valuable information on recognised ADRs, allowing the MHRA to identify and refine the understanding of risk factors that may affect the clinical management of patients.
Since its inception over 50 years ago, the YCS has helped to identify numerous important safety issues, many of which were not previously recognised as being related to a particular medicine until the MHRA received information from Yellow Card reports.
The YCS is widely replicated by many medicines regulators internationally.
Infographic - Reporting suspected side effects to medicines.
Infographic reproduced by permission from the MHRA
Who can submit a Yellow Card report and how do you submit a report?
Anyone can report a Yellow Card, including any healthcare professional (HCP) or member of the public.
You can report a suspected ADR to the YCS in many ways:
Please note: There is a different way to report a problem with a medical device in Wales, Scotland or Northern Ireland and details can be found on the Government website.
Are all medicines and medical devices covered by the Yellow Card Scheme?
All medicines, both prescribed and those available without a prescription, are covered by the YCS including vaccines, blood factors and immunoglobulins, radiographic contrast media, herbal medicines and homeopathic remedies. For biologicals (including biosimilar medicines and vaccines) ADR reports should clearly state the brand name and the batch number of the suspected medicine. Suspected ADRs that are associated with misuse, overdose, medication errors, unlicensed and off-label medicines use, defective medicines and suspected fake medicines are also included. From May 2016, safety concerns associated with e-cigarette products and their refills are reportable. The YCS also covers medical devices used in healthcare for diagnosis, prevention, monitoring or treatment of illness or disability. Examples of medical devices include contact lenses; heart valves; blood glucose monitors; surgical instruments; wheelchairs.
What are the responsibilities for healthcare professionals, including pharmacists, around submitting Yellow Card reports?
Although the reporting of suspected ADRs is voluntary for HCPs and the public, it is vital to improve the national and global understanding of the benefit:risk profile of medicines, to ensure the safe use of medicines, and to protect patients from unwanted harm. Reporting is therefore supported within the codes of practice of all HCPs, by their associations and their regulators.1 The Royal Pharmaceutical Society encourages, as a matter of best practice, the reporting of suspected ADRs to the YCS.2 HCPs should be vigilant to actively detect suspected ADRs and promptly report them. Reporting helps improve medicines information to further educate HCPs and the public on the safe use of medicines, and to prevent future harm to patients.
How can pharmacists help improve reporting to the Yellow Card Scheme?
Under-reporting is a common problem for all spontaneous ADR reporting systems worldwide, like the YCS in the UK, both for adults3 and for children4. Pharmacists are in a unique position to identify and report suspected ADRs to the YCS.5 They also play a key role in promoting patient safety by informing the public about the potential ADRs of medicines and medical devices.
Pharmacist reporting to the YCS adds value to patient safety through contributing to the safety profile of medicines and medical devices, and helping to build the benefit:risk profile of such products. Pharmacists are also well placed to inform patients about the YCS and can encourage patients to report all possible ADRs that they may have experienced with medicines (including minor reactions and reactions that may not be included in the Patient Information Leaflet). Such opportunities can arise when providing dispensed medicines to patients and when conducting consultations with patients. Pharmacists have a professional responsibility to advise patients, carers and the public on the reporting of any suspected ADRs associated with their medicines, including medicines available without a prescription, herbal medicines and complementary remedies.
In 2017, pharmacists submitted approximately 29% of all suspected ADR reports received directly from all HCPs to the YCS. As a key reporter source, the MHRA values the contribution that pharmacists make to the YCS and is keen to encourage more reporting from pharmacists.
Pharmacists and their teams can help raise awareness about the importance of reporting and show their support on social media by sharing Yellow Card animation and supporting infographics which summarise how the YCS works, linking to www.mhra.gov.uk/yellowcard, and using the hashtag #patientsafety. More information on ways to help promote the YCS can be obtained by contacting the MHRA.
Yellow Card reports have helped identify numerous important safety issues, many of which were not known about until the information was received via the YCS. The MHRA has described case studies that highlight the contribution of Yellow Card reports in identifying safety issues6 some of which are outlined below. Pharmacists have submitted Yellow Card reports that have resulted in reviews being carried out by the MHRA and it is interesting to note that a very small number of reports may be required to trigger action by the MHRA; in some cases, less than five Yellow Card reports, taken together with reports from other sources, can be sufficient to initiate an MHRA review. This highlights the importance of all HCPs, including pharmacists, and patients submitting Yellow Card reports as even a single report can help identify a safety issue with a medicine.
Phenytoin and Purple Glove Syndrome
A female patient taking phenytoin injections for a serious epileptic condition developed redness and swelling in her right arm after 15 to 20 injections were administered at different sites. This condition was later diagnosed as purple glove syndrome, a rare condition that causes discolouration, swelling, and blister formation on the hand which can lead to localised tissue death and may lead to disability. The patient spoke to her local pharmacist who referred the patient for urgent medical treatment. The pharmacist also reported this ADR to the pharmaceutical company that manufactured the medicine who sent the report to the MHRA because they were legally obliged to do so.
Through routine assessment of the case alongside three other UK reports from the medical literature and seventeen reports from other countries, the MHRA requested a worldwide safety review from the pharmaceutical company. This analysis resulted in the addition of purple glove syndrome and warnings under possible ADRs of the phenytoin product information.
Posaconazole tablets and oral suspension are not interchangeable
Posaconazole, an antifungal, is available as an oral suspension and as tablets which are not to be used interchangeably due to the differences between these two formulations in terms of frequency of dosing, administration with food and plasma drug concentration achieved.
A hospital patient was prescribed posaconazole oral suspension but was instead given tablets which resulted in the patient receiving an overdose of posaconazole, developing kidney problems and a headache. On discovering this issue the hospital pharmacist contacted the pharmaceutical company that makes the medicine who subsequently reported the suspected ADR to the MHRA.
Similarly, other Yellow Card reports were sent in by hospital pharmacists across the country about instances where the posaconazole tablets and oral suspension were directly substituted, resulting in patients not receiving enough posaconazole and developing infections.
All available global safety data, Yellow Card reports and other safety information were gathered and after a UK and European review, a letter from the pharmaceutical company was sent to HCPs to increase awareness of this issue and to prevent patients receiving incorrect dosages of posaconazole. In addition, the labelling of posaconazole products was strengthened to state clearly that the oral suspension cannot be directly substituted for the tablet, or vice versa, at the same dose, and the outer packaging of the oral suspension and tablets was also changed to prevent confusion between them.
Natalizumab ▼: importance of early detection of progressive multifocal leukoencephalopathy
Natalizumab is a disease-modifying therapy for adults with multiple sclerosis who have high disease activity or who have rapidly evolving severe relapsing-remitting disease. Natalizumab is associated with a risk of progressive multifocal leukoencephalopathy (PML), a rare, progressive disease that damages nerves in the brain and can lead to severe disability or death. PML is caused by activation of John Cunningham virus (JCV), which usually remains latent and typically causes PML in immunocompromised patients only.
Up to 30 March 2016, the MHRA received 36 Yellow Card reports of PML in patients receiving natalizumab, three directly via the YCS and 33 indirectly from the pharmaceutical company. Evidence from these reports and other studies indicated that PML can be diagnosed by MRI scans and positive JCV DNA in the cerebrospinal fluid before noticeable symptoms of PML become evident. This led to new clinical advice on screening being issued to clinicians to support risk stratification, aid early detection of PML, and minimise potential risk to patients.
Drug interaction between dexamethasone and ritonavir, increased risk of systemic adrenal effects
A hospital pharmacist submitted a Yellow Card report raising his concerns over the lack of knowledge and warnings relating to the interaction between ritonavir and corticosteroids, particularly during the use of topical corticosteroids. The report related to a young male on long-term anti-retroviral therapy with a boosted protease inhibitor regimen (darunavir 800 mg/ritonavir 100 mg once a day). He developed keratoconjunctivitis, an inflammation of the cornea and conjunctiva, and was prescribed dexamethasone eye drops to be taken every two hours. Within a short period, he was completely adrenally suppressed with Cushing’s syndrome, symptoms of which include facial swelling/puffiness and weight gain. The hospital pharmacist felt warnings about interactions may need to be clearer, particularly for dexamethasone because there are limited alternative treatment options for keratoconjunctivitis and HIV medications may need to be changed. The MHRA also received a further UK case report of an interaction between topical dexamethasone and ritonavir that described Cushingoid reactions.
As a result of a routine EU review of all available safety information, the MHRA agreed with the pharmacist’s concerns in their Yellow Card report and took regulatory action to ensure the product information was strengthened. Information was added about potential ADRs, including the interaction between ophthalmic dexamethasone and ritonavir, to highlight that Cushing’s syndrome and/or adrenal suppression may occur after intensive or long-term therapy in predisposed patients, including children. It was advised that treatment should be progressively reduced, not discontinued abruptly. The MHRA also published a Drug Safety Update article to communicate advice from the product information and raise awareness among HCPs.
What is the minimum information that should be included in a Yellow Card report?
As much information as possible should be supplied on the Yellow Card report to enable a full assessment by the MHRA, but HCPs and the public should not be put off sending in a Yellow Card report if all the information is not available at the time of reporting. However, as a minimum, a Yellow Card report must include:
- Details about the patient
- Details about the drug(s)/vaccine(s) they were taking, including self-medication and complementary remedies
- Details of the ADR they experienced
- Details of the individual completing the report i.e. their contact details
Following the submission of a report, the MHRA may contact the individual completing the report for further details to support the analysis of the report.
What types of suspected adverse drug reactions should be reported?
The MHRA strongly encourages pharmacists, other HCPs and the public to report all suspected ADRs that are:
- associated with newer drugs and vaccines that are under additional monitoring – these display a black triangle (▼) in their Patient Information Leaflet (PIL) and Summary of Product Characteristics (SmPC). An up-to-date list of black triangle medicines is available.
- serious, medically significant or result in harm (for established medicines, even if the ADR is well recognised). Serious events are fatal, life-threatening, a congenital abnormality, disabling or incapacitating, or resulting in hospitalisation.
Only a suspicion is needed to complete a Yellow Card. If there is any doubt about whether to report a suspected ADR, a Yellow Card should be completed; examples of ADRs that should be reported to the YCS have been proposed.
Although the MHRA monitors suspected ADRs associated with all medicines on the market, suspected ADRs in the following areas are of particular interest:
- Children, young people, and those over 65
- Drug misuse, abuse and medication errors
- Rare, long term reactions and delayed drug effects
- Biological medicines (such as biosimilar medicines, blood products, antibodies, advanced therapies such as gene and tissue therapy, and vaccines) - for these medicines, the brand name and the batch number of the suspected medicine should be clearly stated in the Yellow Card report
- Interactions with other medicines and food substances
- Reactions not mentioned in the PIL or SmPC
- Complementary products e.g. herbal and homeopathic remedies
In England and Wales, where harm occurs to a patient as a result of a medication error, this should be reported through local risk management systems into the National Reporting and Learning System (NRLS). The NRLS collects reports of patient safety incidents, including medication errors, primarily to enable learning from these incidents and to reduce their recurrence. The NRLS shares incident reports and data with various national bodies, including the MHRA, to support improved patient safety. If a local risk management system that links to the NRLS is not available, an eForm should be used (https://improvement.nhs.uk/resources/report-patient-safety-incident/#healthcare). Where harm occurs as a result of an ADR then this should be reported through the YCS.
In Scotland each NHS Board operates its own patient safety reporting system, while the Scottish Patient Safety Programme is a unique national programme that aims to improve the safety and reliability of healthcare and reduce harm.
What happens to my Yellow Card report?
Any information provided to the YCS is kept safe, secure and confidential. No details that could identify the reporter or patient are passed on without permission.
Anyone submitting a Yellow Card report will receive a confirmation of receipt of the report and may be contacted for additional information to help with the assessment of the report. The report will be entered into the MHRA’s safety database. An anonymous version without any identifiable patient or reporter information may be shared with the European Medicines Agency or World Health Organization for wider patient safety learning.
Yellow Card reports are analysed by the MHRA alongside reports collected by the pharmaceutical company together with additional sources of information such as clinical and epidemiological studies, worldwide medical literature, data from other international medicines regulators, and other databases. Where appropriate, the MHRA takes action and communicates any safety issues, when necessary, to minimise risk and maximise benefit to patients. Information on how the safety of medicines is monitored can be found on the MHRA website and examples of regulatory action include:
- Changes or warnings in the product information or on the package label
- Changing the information on how the medicine should be used
- Changes in the specified dose of the medicine
- Restricting the indications for use of a medicine, for example advising that it should not be used by particular groups of patients
- Changing the legal status of a medicine, for example, from over-the-counter to prescription only
- In rare circumstances, removal of the medicine from the market, if the risks of a medicine are found to outweigh the benefits
Information provided to HCPs and the public on the nature of benefit and risk enables informed choices to be made about treatment options and in the management of ADRs should they occur. Sometimes this information or training may come from pharmaceutical companies directly to HCPs, patients or carers.
Where can I access information about suspected adverse drug reactions?
There are many sources of information on suspected ADRs. The MHRA provides transparent information about the suspected ADRs received via the YCS that is freely accessible through interactive Drug Analysis Profiles (iDAPs). These can be accessed directly from the YCS reporting website.
As reports of suspicions of ADRs are received through the YCS, the iDAPs are not a full list of recognised ADRs. Recognised effects can be found within the product information produced by pharmaceutical companies. Product information includes the SmPC aimed at HCPs and the PIL supplied within a medicines packaging. These can be requested from the pharmaceutical company and are available online on the electronic Medicines Compendium (eMC) and the MHRA website.
The MHRA produces a monthly bulletin called Drug Safety Update which includes the latest emerging news about medicines, including suspected ADRs. You can also use the Yellow Card app to select medicines of interest to your ‘watch list’ to receive tailored news.
Are there any online learning modules available for healthcare professionals?
The MHRA has made available an e-learning package for HCPs focused on ADR reporting and the importance of monitoring the safety of medicines, developed through the Strengthening Collaboration for Operating Pharmacovigilance in Europe (SCOPE) Joint Action project. Other e-learning modules on the YCS and ADRs can be found on the websites of the Centre for Pharmacy Postgraduate Education (CPPE), NHS Education for Scotland (NES) through Turas Learn and Wales Centre for Pharmacy Professional Education (WCPPE).
1Royal Pharmaceutical Society. Professional Standards for Public Health Practice for Pharmacy, 2014: Standard 5.0 health protection.
2 Royal Pharmaceutical Society. Medicines Ethics and Practice – The professional guide for pharmacists, edition 42. 2018; 111.
3 Hazell L, Shakir SAW. Under-reporting of adverse drug reactions A systematic review. Drug Safety 2006; 29(5): 385-396.
4 Hawcut DB, et al. Spontaneous adverse drug reaction reports for neonates and infants in the UK 2001–2010: content and utility analysis. British Journal of Clinical Pharmacology 2016; 82(6): 1601-1612.
5 Cheema E, et al. Barriers to reporting of adverse drugs reactions: a cross sectional study among community pharmacists in United Kingdom. Pharm Pract (Granada) 2017; 15(3): 931. doi: 10.18549/PharmPract.2017.03.948
6 Contribution of Yellow Cards to identifying safety issues. Medicines and Healthcare products Regulatory Agency, London 2018. (Accessed 7 August 2018).