Summary
The high-risk medicines audits were conducted for lithium, methotrexate, amiodarone and phenobarbital as part of the 2019-2020 Pharmacy Quality Scheme (PQS). This was part of the medicines safety audits complementing General Practice (GP) Quality and Outcomes Framework (QOF) Quality Improvement (QI) module domain.
A total of 40,419 patients were audited as part of this PQS scheme by 10,673 pharmacy contractors.
For any question where the patients/representatives answered no or don’t know, pharmacy contractors provided additional counselling and advice a total of 23,957 times.
All high-risk drug audits were based on current safety guidance and were intended in part to support community pharmacists’ awareness and adherence to relevant guidance.
Recommendations
For community pharmacists
- Patients who report being overdue blood monitoring should be referred to their GP practice.
- Pharmacy teams should be proactive in counselling on the signs and symptoms of toxicity of high-risk medicines and advise how to reduce adverse reactions.
- It is good practice to record details such as the date and time of blood monitoring results and therapeutic drug levels on the patient medication record (PMR).
- Pharmacy teams should routinely discuss how to maintain a healthy lifestyle with patients at the point of handing out these medicines.
- Community pharmacy teams should ensure all patients have access to information and advice so they can fully understand how to take the medication. Not all patients have equal awareness, understanding and access to primary care and pharmacy teams have an important role in ensuring the individually tailored advice is provided. Pharmacy teams should be mindful of communication preferences for patients with disabilities or when English is not their first language as outlined in the accessible information standard.
For the NHS
- Although testing and monitoring levels were high, some patients were identified who were not routinely receiving appropriate monitoring for high-risk medicines. Systems should be improved to ensure monitoring is in place for all patients taking these high-risk medicines.
- Further development and testing of data collection tools would increase the utility of the results for future improvement work at both national and local level. Allowing some free text entries would also be valuable to better understand issues considered important or poorly understood by patients and/or pharmacy teams.
About this report
Audience
- NHS leaders responsible for patient safety, medicines optimisation and primary care contracts.
- Pharmaceutical Services Negotiating Committee and other national pharmacy bodies.
- Community pharmacists, primary care pharmacists and all others responsible for prescribing, dispensing, or optimising medicines for patients.
Purpose
- To report the key findings of the high-risk medicines audit included in the 2019/20 PQS.
- To make recommendations to support safety improvement and re-audit in a future PQS.
Background
In 2017, the World Health Organization (WHO) launched a global patient safety challenge relating to medication safety. The challenge focuses on improving medication safety by strengthening systems to reduce medication errors. Its over-arching aim is to reduce the level of severe avoidable harm related to medications by 50% over five years, globally.
With over one billion prescription items being dispensed each year, medicines safety is an important quality improvement focus for community pharmacy. By complementing the prescribing safety audits introduced in the new GP contract, there will be an opportunity for community pharmacies and general practices across England to work together to reduce the risk of patient harm.
‘Investment and evolution: A five-year framework for GP contract reform to implement The NHS Long Term Plan’ published in January 2019 introduced the creation of two quality improvement modules within a new quality improvement domain.
The module on prescribing safety highlighted the nationally backed roll out of the pharmacist-led information technology intervention for medical errors (such as PINCER (pharmacist-led information technology intervention for medication errors)). Pharmacies completing these audits were asked to collaboratively engage with their local GP practices for the benefit of patients. This also provided an opportunity for a coordinated approach to reducing patient harm in primary care, which may lead to more collaborative working in this area in the future.
Lithium, methotrexate, amiodarone, and phenobarbital are high-risk medications. High-risk medications have a heightened risk of causing significant patient harm when they are used in error, where the consequences of any errors are clearly more devastating to patients.
Lithium is the standard drug used to treat bipolar disorder. Most of its adverse effects are dose-dependent, and there is only a small margin between therapeutic and toxic blood concentrations. A review of 567 reports by the UK National Patient Safety Agency (NPSA) showed that the adverse effects of lithium were mainly due to dosing errors, irregular blood lithium assay, poor monitoring of renal or thyroid function, and inadequate patient information. In practice, regular lithium assay, regular renal and thyroid monitoring, and provision of verbal and written information to patients and their families are essential in preventing adverse effects and significant patient harm.
Methotrexate is a high-alert drug, and extra safeguards are needed whenever it is prescribed, dispensed, and administered, regardless of the setting, dose, or indication for use. While severe harm and fatalities have occurred during hospitalisation, many of the adverse outcomes have occurred after discharge. Effective proactive strategies must be implemented so patients can get the benefits of the therapy safely and harm is prevented.
Amiodarone, a versatile class III antiarrhythmic drug, is considered one of the most effective agents in counteracting supraventricular and ventricular tachyarrhythmia. The drug, however, has a high toxicity profile involving diverse organs.
Adverse amiodarone reactions involve organs, including the lung, thyroid, eye, and liver.
These reactions can be life-threatening and pose challenges when amiodarone is used to prevent ventricular arrhythmias and there are no alternative options. Amiodarone is often prescribed for atrial fibrillation for the elderly, who are at higher risk for adverse drug reactions. The choice of introducing amiodarone in the elderly population should, therefore, be cautiously evaluated considering long and short-term side effects, interaction with other drugs, and patient compliance. Patients taking amiodarone should be strictly monitored to intercept any potential insurgent side effects.
Phenobarbital is a drug used to treat epilepsy and falls into Category 1 of the Medicines and Healthcare products Regulatory Agency (MHRA) guidance, for which specific measures are required to ensure consistent supply of a particular product. This means that individuals should not be switched between brands of these anti-epileptic drugs (AEDs) but should always be kept on the same brand.
Aim
The aim of the audits was to reduce harm caused by the four high-risk medicines whilst providing effective treatment to patients prescribed these medicines.
Methodology
The audits were part of the 2019/20 PQS. Pharmacies intending to complete the audits to receive the incentive payments were asked to discuss this with their local GP practices to enable collaborative working for the benefit of patients. To ensure that the contractor was able to meet the requirements of this quality criterion, they were required to verify whether they had any ongoing patients to whom they had dispensed lithium in the preceding three months prior to choosing the consecutive three-month period for the audit. If the pharmacy had no patients who have had lithium dispensed from the pharmacy in the previous three months, the contractor was required to complete a safety audit of patients prescribed one of the following medicines instead, in the following order of preference: methotrexate, amiodarone or phenobarbital. The audit was completed during a consecutive three-month period between September 2019 and February 2020. The pharmacies submitted audit data via the Manage Your Service (MYS) portal based on the total numbers of patients taking lithium (or methotrexate, amiodarone, or phenobarbital) and their answers in accordance with the data collection template.
No patient identifiable data was submitted via the MYS portal. Following the end of the audit period, the data was cleansed and analysed using Microsoft Excel.
Overall results
A total of 40,419 patients were audited as part of this PQS criteria from 10,673 contractors. A further 163 contractors participated in the audit but reported having dispensed zero prescriptions for lithium, methotrexate, amiodarone, or phenobarbital throughout the three-month audit period.
Lithium audit
A total of 27,507 patients were audited as part of the lithium audit. After cleansing the data, a total of 22,117 patients were included in the data analysis of which 21,883 (99%) consented to participate in the audit and discuss their lithium therapy whilst 234 declined. See appendix 1: PQS lithium audit data tables.
Findings and recommendations for contractors
- 95% of patients reported having had their lithium levels monitored as per NICE guidelines. Contractors should refer patients who have not had the appropriate blood monitoring to their GP practice to ensure the safe use of this medicine.
- A significant proportion of patients did not use or bring their lithium book to the pharmacy when their medication was being dispensed. The audit did not ask specifically about lithium alert cards.
- Community pharmacy could help with the weight management of patients taking lithium as 19% of audited patients reported not having their weight measured in the last 6 months. Measuring Body Mass Index (BMI) and referral to appropriate weight management services such as the NHS Digital Weight Management Programme or Tier 2 local authority commissioned weight management has been incentivised as part of the PQS since 2021. Pharmacy teams could complete this intervention at the point of dispensing.
- A key area for improvement is counselling, particularly the need to increase counselling on the signs of toxicity and what to do if experienced. 34% of audited patients did not know the signs of toxicity and 29% did not know how to prevent them.
- As all pharmacies are now healthy living pharmacies, pharmacy teams are well placed to provide further healthy living advice with respect to alcohol, diet, exercise, smoking, prescribed medicines and herbal remedies/supplements.
- In addition, counselling patients that they should first seek advice from a pharmacist or doctor when purchasing non-prescribed medicines including herbal remedies or supplements.
Methotrexate audit
A total of 12,690 patients were audited as part of the methotrexate audit. After cleansing the data, 11,607 patients were included in the analysis where a total of 10,211 (88%) consented to participate in the audit and discuss their methotrexate therapy whilst 1,396 (12%) declined. See appendix 2: PQS methotrexate audit data tables.
Findings and recommendations for contractors
- 97% of patients reported having had blood tests in the last 3 months. Contractors should ensure that all patients are referred to their GP practice for a blood test if they have not had one in the past 3 months when taking methotrexate to ensure safe use of this medicine.
- 79% of patients reported having a copy of the hand-held methotrexate information booklet or local equivalent.
- 11% of patients taking methotrexate showed a lack of awareness of the signs of toxicity. Pharmacy teams should provide advice and ask questions like those in the audit to check understanding and seek to optimise the safe use of methotrexate and minimise harm from this high-risk medicine.
- It is good practice to update the patient’s PMR with blood tests results and/or the date of the blood test where this information is available, as well as when methotrexate books have been provided. Patients who have not had a blood test in the past 3 months should be counselled regarding the reasons this is important and referred as appropriate.
- Areas of improvement include counselling on smoking as research indicates that cigarette smokers have a diminished chance of responding well to first- and second-line agents of choice in early rheumatoid arthritis treatment.
- Suitable patients could be offered smoking cessation support from community pharmacies.
Amiodarone audit
A total of 146 patients were audited as part of the amiodarone audit – all of which were included in the data analysis. A total of 142 (97%) consented to participate in the audit and discuss their amiodarone therapy, whilst 2 (2%) declined participation. See appendix 3: PQS amiodarone audit data tables.
Findings and recommendations for contractors
- Community pharmacy teams should ensure patients receive all the necessary information during dispensing. 16% of patients reported not knowing why they were taking amiodarone, while 24% didn’t know what to do if they missed a dose.
- 30% of audited patients reported not being aware of the side effects of amiodarone. A key area for improvement is counselling particularly on the:
- appropriate actions to reduce the risk of phototoxic reactions
- appropriate actions if the patient develops a cough or, new or progressive shortness of breath.
- In addition, pharmacy teams should provide counselling on:
- non-prescribed medicines including herbal remedies or supplements
- how to maintain a healthy lifestyle with regards to alcohol, diet, exercise and smoking.
Phenobarbital audit
A total of 66 patients were audited as part of the phenobarbital audit – all of which were included in the data analysis. A total of 52 (79%) consented to participate in the audit and discuss their Phenobarbital therapy, whilst 14 (21%) declined participation. See appendix 4: PQS phenobarbital audit data tables.
Findings and recommendations for contractors
- 10% of patients reported not knowing what to do if they missed a dose. Pharmacy teams can play a key role in educating patients and ensuring they get the most out of their medicines.
- A key area for improvement is counselling on how to maintain a healthy lifestyle in relation to diet, exercise and smoking. 29% of audited patients reported not knowing how to maintain a healthy lifestyle in relation to smoking.
- Contractors should also ensure they record (after confirming) the usual preparation for each patient as there can be variation in absorption of the same medicine produced by different manufacturers.
Discussion
90% of community pharmacies in England participated in this audit, providing valuable insight into the provision of care and patient understanding of taking high- risk medicines including lithium, methotrexate, amiodarone, and phenobarbital.
In 2010, an audit of 436 clinical teams recovered follow-up data on 2,976 patients treated with lithium for a year or more to benchmark monitoring against recommended standards. It showed that versus NICE standards, the monitoring of lithium serum levels was only met 30% of the time. In contrast, this pharmacy audit showed that 95% of patients had received blood monitoring as per NICE guidelines. In addition, a higher number of patients were audited as part of the PQS. As part of the actions of the 2009 National Patient Safety Alert (NPSA) Safety Alert, prescribers and pharmacists are required to check that blood tests are monitored regularly and that it is safe to dispense the repeat prescription. Pharmacists are reminded of this requirement and the need to refer patients back to the prescriber to ensure the safe use of this medicine.
There was a sizeable minority of patients across all four high risk medicines audited who were not aware of the signs and symptoms of toxicity of the medicines they were taking. Pharmacists are important health educators and play a vital role in ensuring that all patients receive accurate, understandable information about their medicine including how to take it safely and the signs of toxicity, as well as be provided with the opportunity to ask questions. The MHRA has produced Drug safety updates for both methotrexate and amiodarone in the last two years to remind both prescribers and dispensers of their responsibilities when using these high-risk medicines, emphasising the importance of highlighting the symptoms of toxicity to patients.
Around 1 in 5 patients audited were unable to explain how to maintain a healthy lifestyle regarding smoking. Research has shown that patients treated for rheumatoid arthritis who are also smokers are less likely to respond to methotrexate than those who have never smoked. Pharmacy teams have been recognised as playing a pivotal role in prevention and public health as one of the most visited health care settings in England. Pharmacy teams can provide patients with support by routinely discussing stopping smoking when they present with prescriptions and offer smoking cessation services to those who require them.
Lithium specifically also requires the monitoring of a patient’s weight or BMI every 6 months. Pharmacies are well equipped to do this as this is currently a requirement of the PQS weight management criterion, contribute to the safe use of this medicine in partnership with the prescriber. Pharmacists can also refer patients who would like support with their weight to programmes such as the NHS Digital Weight Management Programme, which is also incentivised as part of the PQS 2022/23.
Conclusion
This audit indicates that the pharmacist and the extended pharmacy team have a very important role to play in ensuring that these highly toxic medicines are understood and used appropriately to reduce harm. The majority of patients confirmed that they received the appropriate blood monitoring, but there was a concerning minority who had not, all of whom should be referred to their GP practice. There are also a concerning proportion of patients not aware of the signs of toxicity and how to respond to them.
Recommendations for community pharmacists and the NHS can be found in the Summary of this report. All pharmacy professionals should consider these recommendations in the context of General Pharmaceutical Council professional standards and document referrals for these patients on the PMR or another appropriate record.
Appendix 1: PQS lithium audit data
Audit questions: |
Yes |
No |
Don’t know |
|
1. |
Has the patient agreed to have a discussion about their lithium? (Patients representative if lack of capacity) |
21,883 (99%) |
234 (1%) |
– |
2. |
Does the patient have a copy of their Lithium Record Book? (If the patient states they have a Lithium Record Book at home answer ‘yes’ for this question) |
12,489 (57%) |
8,134 (37%) |
1,260 (6%) |
3. |
Does the patient report that they have had their lithium level monitored in the last 3 or 6 months? (As per NICE guidance) |
20,722 (95%) |
674 (3%) |
487 (2%) |
4. |
Does the patient report that they have had all the appropriate blood tests in the last 6 months? (Kidney and thyroid function and calcium levels) |
20,140 (92%) |
788 (4%) |
955 (4%) |
5. |
Does the patient report that they have had their weight measured (by a health care professional in relation to their lithium) in the last 6 months? (Body mass index (BMI)) |
16,226 (74%) |
4,089 (19%) |
1,568 (7%) |
6. |
Can the patient describe the signs of lithium toxicity? (e.g. upset stomach) |
14,499 (66%) |
7,384 (34%) |
– |
7. |
Can the patient describe how to prevent lithium toxicity? (e.g. adequate fluid intake especially if exercising heavily) |
15,429 (71%) |
6,454 (29%) |
– |
8. |
Can the patient describe appropriate action to take if they miss one or more doses? |
17,850 (82%) |
4,033 (18%) |
– |
9a. |
Does the patient know how to maintain a healthy lifestyle in relation to: Alcohol (advice on alcohol consumption is essential) |
19,318 (88%) |
2,565 (12%) |
– |
9b. |
Diet (advice is essential with particular attention to hydration) |
19,624 (90%) |
2,259 (10%) |
– |
9c |
Exercise (advice is essential with particular attention to hydration) |
19,248 (88%) |
2,635 (12%) |
– |
9d. |
Smoking |
17,594 (80%) |
4,289 (20%) |
– |
10. |
Is the patient aware that they should not take non-prescribed medicines, including herbal remedies or supplements, without first seeking advice from a pharmacist or doctor? |
19,429 (89%) |
2,454 (11%) |
– |
11 |
Did you refer the patient to their GP or specialist? |
3,905 (19%) |
17,978 (81%) |
– |
12. |
For any question where the patient has answered no or Don’t know was the appropriate advice provided? (Appropriate advice must be provided in all cases as part of this audit) |
17,393 |
Not collected |
– |
13. |
Have the answers to questions 3, 4 and 5, been recorded on the PMR or appropriate patient record? |
20,157 (92%) |
1,726 (8%) |
– |
Total: 22,117
Appendix 2: PQS methotrexate audit data
Audit questions: |
Yes |
No |
Don’t know |
|
1. |
Has the patient agreed to have a discussion about their methotrexate? (Patients representative if lack of capacity) |
10,211 (88%) |
1,396 (12%) |
– |
2. |
Does the patient have a copy of the hand-held methotrexate information booklet or local equivalent? (If the patient states they have an information booklet at home answer ‘yes’ for this question) |
8,017 (79%) |
1,646 (16%) |
548 (5%) |
3. |
Does the patient report they have had blood tests in the last 3 months? (Full Blood Count, kidney and liver function tests in an appropriate timeframe as per NICE guidance) |
9,908 (97%) |
166 (2%) |
137 (1%) |
4. |
Does the patient know it is essential to take methotrexate once weekly as a single dose? (Note: there are very rare exceptions to this) |
10,101 (99%) |
110 (1%) |
– |
5. |
Can the patient describe appropriate action to take if they miss one or more doses? |
8,834 (87%) |
1,377 (13%) |
– |
6. |
Does the patient know to report immediately the onset of any features of blood disorders, liver toxicity and respiratory effects? (Blood disorders, eg, sore throat, bruising, and mouth ulcers, liver toxicity, eg, nausea, vomiting, abdominal discomfort and dark urine, respiratory effects, eg, shortness of breath, stomatitis) |
9,083 (89%) |
1,128 (11%) |
– |
7a. |
Does the patient know how to maintain a healthy lifestyle in relation to: Alcohol (Advice on alcohol consumption is essential) |
9,230 (90%) |
981 (10%) |
– |
7b. |
Diet |
9,143 (90%) |
1,068 (10%) |
– |
7c. |
Exercise |
9,031 (88%) |
1,180 (12%) |
– |
7d. |
Smoking |
8,251 (81%) |
1,960 (19%) |
– |
8. |
Does the patient know they should not take non-prescribed medicines including herbal remedies or supplements without first seeking advice from a pharmacist or doctor? |
9,422 (92%) |
789 (8%) |
– |
9 |
Did you refer the patient to their GP or specialist? |
628 (6%) |
9,583 (94%) |
– |
10. |
For any question where the patient has answered NO or DON’T KNOW was the appropriate advice provided?(Appropriate advice must be provided in all cases as part of this audit) |
6,423 |
Not collected |
– |
11. |
Have the answers to questions 3 been recorded on the PMR, or appropriate form/patient records? |
8,916 (87%) |
1,295 (13%) |
– |
Total: 11,607
Appendix 3: PQS amiodarone audit data
Audit questions: |
Yes |
No |
Don’t know |
|
1. |
Has the patient agreed to have a discussion about their amiodarone? (Patients representative if lack of capacity) |
142 (97%) |
4 (3%) |
– |
2. |
Does the patient report that they have had blood tests in the last 6 months? * (Thyroid function tests (TFTs), liver function tests, serum electrolyte, urea measurement) |
121 (85%) |
5 (4%) |
16 (11%) |
3. |
Does the patient report that they have had an electrocardiogram (ECG) in the last 12 months? * |
107 (75%) |
12 (8%) |
23 (16%) |
4. |
Is the patient prescribed a dose which is 200mg (or less) daily? |
140 (99%) |
2 (1%) |
– |
5. |
Can the patient describe the reason, dose and frequency for taking amiodarone? |
119 (84%) |
23 (16%) |
– |
6. |
Can the patient describe appropriate action to take if they miss one or more doses? |
108 (76%) |
34 (24%) |
– |
7a. |
Can the patient describe symptoms that may indicate side-effects? (Phototoxicity, vision and cough / new progressive SOB) |
99 (70%) |
43 (30%) |
– |
8b. |
Can the patient describe appropriate actions that they would take if they noticed any changes in vision? (Contact their GP for an appointment) |
113 (80%) |
29 (20%) |
– |
8c. |
Can the patient describe appropriate actions to reduce the risk of phototoxic reactions? |
91 (64%) |
51 (36%) |
– |
8d. |
Can the patient describe appropriate actions that they would take if they developed a cough or, new or progressive shortness of breath? (Eg, seek advice from their pharmacist, see their GP or go to A&E depending on severity) |
114 (80%) |
28 (20%) |
– |
9a. |
Does the patient know how to maintain a healthy lifestyle in relation to: Alcohol (Advice on alcohol consumption is essential) |
115 (81%) |
27 (19%) |
– |
9b. |
Diet |
120 (85%) |
22 (15%) |
– |
9c. |
Exercise |
108 (76%) |
34 (24%) |
– |
9d. |
Smoking |
100 (70%) |
42 (30%) |
– |
10. |
Does the patient know they should not take non-prescribed medicines including herbal remedies or supplements without first seeking advice from a pharmacist or doctor? |
120 (85%) |
22 (15%) |
– |
11. |
Did you refer the patient to their GP or specialist? |
19 (13%) |
123 (87%) |
– |
12. |
For any question where the patient has answered NO or DON’T KNOW was the appropriate advice provided? (Appropriate advice must be provided in all cases as part of this audit) |
112 |
Not collected |
– |
Total: 146
Appendix 4: PQS phenobarbital audit data
Audit questions: |
Yes |
No |
|
1. |
Has the patient agreed to have a discussion about their phenobarbital? (Patients representative if lack of capacity) |
51 (78%) |
14 (22%) |
2. |
Does the patient report they have had any recent change in seizure frequency? |
2 (4%) |
49 (96%) |
3. |
Can the patient describe appropriate action to take if they miss one or more doses? |
46 (90%) |
5 (10%) |
4a. |
Does the patient know the importance of safe alcohol consumption while taking phenobarbital? (advice on alcohol consumption is essential) |
50 (98%) |
1 (2%) |
4b. |
Does the patient know how to maintain a healthy lifestyle in relation to: Diet |
49 (96%) |
2 (4%) |
4c. |
Exercise |
46 (90%) |
5 (10%) |
4d. |
Smoking |
36 (71%) |
15 (29%) |
5. |
Is the patient aware that they should not take non-prescribed medicines, including herbal remedies or supplements, without first seeking advice from a pharmacist or doctor? |
45 (88%) |
6 (12%) |
6a. |
Did you refer the patient to their GP or specialist? (patients should be referred if they have any recent change in seizure frequency) |
1 (2%) |
Not collected |
7. |
For any question where the patient has answered NO was the appropriate advice provided? (Appropriate advice must be provided in all cases as part of this audit) |
29 |
Not collected |
Total: 65
Publishing reference: B2021