Introduction
1. We are writing to consult you on the continued availability of diclofenac as a Pharmacy (P) medicine and in particular on risk minimisation measures advised by the Commission on Human Medicines.
Application to England, Wales, Scotland and Northern Ireland:
2. This consultation is being made available in England, Wales, Scotland and Northern Ireland. The proposed changes would apply throughout the United Kingdom.
Background:
3. As a result of an EU-wide review of the cardiovascular (CV) risks of the non-steroidal analgesic diclofenac, the European Medicines Agency’s Pharmacovigilance Risk Assessment Committee (PRAC) has recently recommended new contraindications, warnings and precautions to all marketing authorisation for diclofenac.
4. Diclofenac is a non-selective non-steroidal anti-inflammatory (NSAID) available in a variety of indications, forms, dosages and pack size quantities for relieving pain and inflammation. It is available as injections; tablets and capsules for oral use; and as gels and creams for topical use. A summary of UK products containing diclofenac appears in Appendix 1.
5. Studies have consistently shown that when given systemically (by means such as capsules, tablets or injections) there is an increased risk with diclofenac of cardiovascular side effects, such as heart attack or stroke compared to other similar painkillers, such as ibuprofen and naproxen. The risks are similar to those of selective COX -2 inhibitors, another group of painkillers.
6. The evidence of additional risk is clear when diclofenac is used at a high dose (150mg) daily and for long term treatment. The findings could not rule out the possibility that this increased risk could be associated with the low doses and short lengths of treatment of non- prescription products.
7. The new advice is that people who have serious underlying heart or circulatory conditions, such as heart failure, heart disease, circulatory problems or a previous heart attack or stroke, should not use diclofenac. Patients with certain cardiovascular risk factors (such as high blood pressure, raised blood cholesterol, diabetes or smoking) should only use diclofenac after careful risk assessment. Healthcare professionals have also been advised to periodically re-assess the need for patients to continue taking the medicine. The product information recommends that NSAIDs be used at the lowest effective dose for the shortest period of time necessary to control pain symptoms.
8. The new advice does not apply to topical (ie, gel or cream) formulations of diclofenac.
Availability of diclofenac without prescription
9. Diclofenac is available in the UK without prescription in tablet form as a P medicine, supplied from pharmacies by or under the supervision of a pharmacist, under the following circumstances:
Indication: For the short term relief of headache, dental pain, period pain, rheumatic and muscular pain, backache and the symptoms of colds and flu, including fever, in adults and children aged 14 years and over.
Maximum strength: 25mg
Maximum dose: 25mg
Maximum daily dose: 75mg
Maximum duration of treatment: 3 days
Maximum pack size: 225mg of product (9 x 25mg tablets)
Recommendations of the Commission on Human Medicines (CHM)
11. In June 2013 the CHM considered the implications of the PRAC recommendations for the current circumstances for non-prescription classification in the UK of medicinal products containing diclofenac in oral dosage forms.
12. The CHM noted that it was difficult to identify people with high cardiovascular risk although the risk would be higher with age. The CHM also considered that the wide availability of other NSAIDs without prescription – as P and GSL medicines – presented a risk that the products could be used together and that indications for OTC diclofenac were wide ranging, and included colds, flu and fever.
13. The CHM advised that a number of measures should be taken to strengthen the risk minimisation of oral diclofenac as a P medicine, including:
- Removing from the indications, ‘the symptoms of colds and flu, including fever’,
- Strengthening the warnings on the pack about use by those with cardiovascular disease or with significant risk factors for cardiovascular events
- Strengthening warnings on the pack and about not taking diclofenac with other NSAIDs.
- Engaging with the pharmacy profession to support the implementation of further measures to minimise the risk of OTC diclofenac
- Requesting that the Marketing Authorisation Holders prepare a Risk Management Plan to strengthen the risk minimisation of oral diclofenac as a P medicine.
Options for risk minimisation
14. The MHRA wishes to take into account all stakeholders views when reaching a final position on regulatory action, and therefore seeks views on the following options for risk minimisation.
Option 1
14.1 No new risk minimisation measures
Option 2
14.2 Implement all the measures identified by CHM:
- Remove from the indications, ‘the symptoms of colds and flu, including fever’,
- Strengthen the warnings on the pack about use by those with cardiovascular disease or with significant risk factors for cardiovascular events
- Strengthen warnings on the pack and about not taking diclofenac with other NSAIDs.
- Engage with the pharmacy profession to support the implementation of further measures to minimise the risk of OTC diclofenac
- Request that the Marketing Authorisation holders prepare a Risk Management Plan to strengthen the risk minimisation of oral diclofenac as a P medicine.
Option 3
14.3 Amend the current conditions for supply of diclofenac as a P medicine so that preparations for oral use can no longer be supplied without prescription. This would result in diclofenac tablets currently authorised as P medicines being required to be reclassified from P to POM (Prescription Only). Topical formulations would continue to be available without prescription.
Comments on Medicines and Healthcare Products Regulatory Agency (MHRA)
MLX 382 - Consultation on Availability of Diclofenac as a Pharmacy Medicine
The Royal College of Physicians of Edinburgh is pleased to respond to the MHRA on Consultation MLX 382 on the Availability of Diclofenac as a Pharmacy Medicine.
The College is very aware of the on-going concerns regarding NSAIDs (including Cox 2 antagonists) generally and diclofenac oral preparations specifically and agrees that the availability of oral preparations of diclofenac, under the supervision of a pharmacist, should be reviewed and the risk management assessed and the warnings strengthened. That said, the College does not think this warrants moving diclofenac oral preparations from pharmacist only (P) to Prescription only Medicine (POM) at this present time and with the current relative risk evidence provided. Diclofenac likely poses a significantly increased cardiovascular risk (CV) to certain cohorts of high CV risk patients relative to marginally safer other NSAIDs. However, the evidence is not strong enough to deny the patient population as a whole the use of oral diclofenac unless a doctor provides a prescription.
As part of the warning strengthening process, it would be of value to have a standardised step at the start of the Pharmacist-Patient discussion, during which the pharmacist assesses if an alternative (lower CV risk) NSAID preparation would be suitable on a case by case basis. There are very few indications for diclofenac oral preparations that cannot be met by the safer alternatives such as naproxen or ibuprofen. The current 3 day limit to the diclofenac supplied should also minimise the CV risk posed to an individual patient.
The College supports option 2 to implement the recommendations of the Commission on Human Medicines.