Consultation outcome

A public consultation on reclassifying Nuromol from prescription pharmacy (P) to general sale (GSL)

Published 13 May 2021

1. Response number: 1

Organisation/individual: North Tees & Hartlepool NHS Foundation Trust

Agree/ Disagree: Disagree

No definitive view – issues raised: No response

Confidential: No

1.1 Comments

Availability of Nuromol without the supervision of a pharmacist holds a significant safety issue.
Paracetamol and ibuprofen are already readily available to the public. The addition of a combination product increases the risk of overdose of the two medications. Patient may take Nuromol in addition to the separate ingredients of paracetamol and ibuprofen.

Paracetamol and ibuprofen both have significant adverse effects, particularly if taken in larger quantises than are recommended. Ibuprofen should be taken with food to reduce the chances of GI irritation, but paracetamol does not require to be. Thus this restricts times when the medication can be taken, when paracetamol as an individual ingredient does not require to be taken with food.

The addition of Nuromol to the GSL list will be disadvantageous to patients as its licensed dose is actually a sub therapeutic total dose of paracetamol which should be taken up to 1g QDS. Moreover this product is likely to have a greater cost than the separate ingredients, therefore actually being less cost effective as well as less effective with additional safety issues for members of the public.

1.2 Do you have any other comments on the reclassification?

NSAIDs such as ibuprofen should only be used if and when required. The NHS spends significant time and money on dealing with the adverse effects of NSAIDs. These include GI bleeds, acute renal failure and exacerbations of asthma.

If this product became more readily available patients who only have Nuromol available to hand may take this product as a first line treatment instead of paracetamol alone, exposing themselves to the possible adverse effects discussed above unnecessarily.

2. Response number 2

Organisation/individual: Individual

Agree/ Disagree: Agree

No definitive view – issues raised

Confidential: No

2.1 Comments

On a number of occasions I have been advised by GP and Dentist to take paracetamol and ibuprofen together, to benefit from the dual properties at the same time.

As the individual drugs have different dosing frequencies, the ability to take both drugs with clear dosing instructions would be very beneficial when distracted by pain and potentially not paying as close attention as usual.

As both drugs are available on general sale, a combination product would, I my opinion, carry no additional risk of misuse.

3. Response number 3

Organisation/individual: Individual (Pharmacist)

Agree/ Disagree: Disagree

No definitive view – issues raised: No response

Confidential: No

3.1 Comments

It’s confusing for patients, there is a risk it could be taken in addition to both ingredients. I don’t think it can be fully mitigated by labelling.

4. Response number 4

Organisation/individual: Individual (semi-retired pharmacist)

Agree/ Disagree: Agree

No definitive view – issues raised: No response

Confidential: No

4.1 Comments

Previous 10-year P status safety review, as summarized in the consultation. Recommendation for second-line use, which is clearly stated on the package. Proposed 3-days only pack size.

4.2 Do you have any specific comments on the leaflet or label provided at Annexes, 2 & 3?

For a GSL product, the Nuromol Leaflet may be unduly complicated. A simpler leaflet containing only essential points might be better. For example, perhaps show only the text shown in bold font in the proposed leaflet. It is well-known that patients do not read package insert leaflets, even when prompted to by their doctor or pharmacist.

4.3 Do you have any other comments on the reclassification?

In view of the well-known liver toxicity of Paracetamol, perhaps the precaution not to take Nuromol in addition to other products containing Paracetamol should be more strongly emphasized. For example, a warning on the face of the package, together with the second line use directive. Especially of concern because there will usually be no oversight by a pharmacist or doctor.

5. Response number 5

Organisation/individual: Individual (pharmaceutical consultant)

Agree/ Disagree: No definitive view – issues raised

Not sure (There Is insufficient information provided in this public consultation document for safety of this product as it has been marketed in New Zealand).

Confidential: No

5.1 Comments

There Is insufficient information provided in this public consultation document for safety of this product as it has been marketed in New Zealand.

I refer to the below paragraph in the consultation document which does not state the pharmacovigilance data and how many years of marketing has occurred in New Zealand to justify the conclusion drawn.

“Six years of use of Nuromol as a P medicine in the UK did not identify any unknown and significant safety risks and data from New Zealand, where Nuromol has been classified as medicine that can be sold without prescription in non-pharmacy outlets, revealed that the incidence of Adverse Drug Reactions (ADRs) is low.”

6. Response number 6

Organisation/individual: Individual (pharmacist)

Agree/ Disagree: Agree

No definitive view – issues raised: No response

Confidential: No

6.1 Comments

Satisfactory reasoning has been provided to change the classification of the product from Pharmacy Only to GSL.

6.2 Do you have any specific comments on the leaflet or label provided at Annexes, 2 & 3?

Yes, I have specific comments about the SmPC, label and leaflet. Please see separate sheets provided.

Response to Nuromol public consultation (ARM 100)

Comment: In the interest of clarity and ease of understanding, the following changes to the SmPC are proposed.

4.1 Therapeutic indications

For the temporary relief of mild to moderate pain such as migraine, headache, backache, period pain, dental pain, rheumatic and muscular pain, cold and flu symptoms, sore throat and fever which has not been relieved by taking either ibuprofen or paracetamol alone

Comment: In the sentence above, it would suffice to use the word ‘either’ or ‘alone. However, using both words makes the message more emphatic.

Comment: Use of the word ‘alone’ is more appropriate than the word ‘individually’ because it reduces the potential scope for any misunderstanding.

4.2 Posology and method of administration

Posology

For short term-use only.

Question: Shouldn’t short term be clearly defined?

Before taking Nuromol Dual Action is taken, the patient should first try taking either ibuprofen or paracetamol alone for pain relief day one of treatment. If the pain has not been relieved by taking either ibuprofen or paracetamol alone on day one of treatment, then Nuromol Dual Action can be taken instead from day two onwards. The lowest effective dose should be used for the shortest duration necessary to relieve symptoms (see section 4.4). The patient should consult a doctor if the symptoms persist for more than 3 days, or worsen.

Comment : Consider deletion of the phrase ‘in accordance with the product instructions’ as shown above since the text adds little value, but has the potential scope to create confusion. The applicant has already undertaken two user testing studies of the label to demonstrate that participants could differentiate and self-select Nuromol from other products according to the criteria which would need to be taken into account when buying the product in the absence of a pharmacist.

Comment : Even the above proposed amended text for section 4.2 is still quite wordy and has the scope to be simplified much further.

Adults: One tablet to be taken up to three times per day with water. Leave at least six hours between doses.

If necessary the dose may be increased to a maximum of two tablets to be taken up to three times a day. Leave at least six hours between doses.

To minimise side effects, it is recommended that patients take Nuromol Dual Action Pain Relief with food.

Comment: The sentence about food is better placed as shown above, for greater impact.

Comment: The phrase ‘dose does’ is rather confusing and best not used.

Do not take more than six tablets of Nuromol Dual Action Pain Relief (3000mg Paracetamol, 1200mg Ibuprofen) in any 24 hour period.

Comment: Consider using the product name consistently throughout the SmPC. Currently, it is inconsistently used either as Nuromol Dual Action or Nuromol Dual Action Pain Relief (3000mg Paracetamol, 1200mg Ibuprofen).

Elderly: No special dosage modifications are required (see section 4.4).

The elderly are at increased risk of the serious consequences of adverse reactions. If an NSAID is considered necessary, the lowest effective dose should be used for the shortest possible duration. The patient should be monitored regularly for gastrointestinal bleeding during NSAID therapy.

Not for use by anyone under 18 years of age.

4.4 Special warnings and precautions for use

Do not exceed the recommended dose.

Do not use this product unless you have first tried taking either ibuprofen or paracetamol individually alone for pain relief.

If symptoms persist for more than 3 days, or worsen consult your doctor.

Keep out of the sight and reach of children.

Carton front face

For use only after first trying either ibuprofen or paracetamol alone first.

Carton rear face

This product is intended to treat pain that has not been relieved by taking either ibuprofen or paracetamol alone. Read enclosed leaflet before taking this product. Each tablet Contains: Ibuprofen 200 mg and Paracetamol 500 mg.

WHEN TO TAKE THIS PRODUCT:

On day one of treatment, try taking either ibuprofen or paracetamol. If the pain has not been relieved then you can start taking this product instead, from day two onwards.

DOSAGE:

For oral administration and short term use only. Adults aged 18 or over and elderly: take 1 tablet (or 2 if necessary), up to 3 times daily with food. Leave 6 hours between doses. Do not exceed 6 tablets in 24 hours. Do not give to anyone under 18 years of age. If your symptoms persist for more than 3 days or worsen, consult your healthcare professional.

WARNING: Do not take more medicine than the label tells you to. If you do not get better within 3 days or your symptoms worsen, talk to your doctor. Do not use this product if unless you have not first tried taking either ibuprofen or paracetamol alone, for pain relief. Keep out of the sight and reach of children.

Comment: ‘Healthcare professional’ has been used in one of the sections of text shown above and ‘doctor’ in another. The SmPC states ‘doctor’. It is important that the pack and leaflet text is aligned with the SmPC text.

Patient leaflet

All of the changes proposed to the SmPC and label text also apply to the patient leaflet. A small number of examples are provided below.

1. What this medicine is and what it is used for

This medicine contains two active ingredients (which make the medicine work). They are Ibuprofen and Paracetamol.

1. Before you take this medicine

Do not take this medicine if you:

• are already taking any other paracetamol containing product
• are taking any other pain relieving products including ibuprofen, high dose aspirin (above 75mg per day), or other non-steroidal anti inflammatory drugs (NSAIDs) including cyclo-oxygenase-2 (COX-2) specific inhibitors

Comment: Foer the text above, consider stating one example of a COX-2 specific inhibitor

Do not take this medicine unless you have first tried taking either ibuprofen or paracetamol individually alone, for pain relief. See Section 3.

1. How to take this medicine

On day one of treatment, try taking (either ibuprofen or paracetamol) alone. If the pain has not been relieved, you can take Nuromol Dual Action Pain Relief from day two onwards, following the instructions below.

7. Response number 8

Organisation/individual: PAGB

Agree/ Disagree: Agree

No definitive view – issues raised: No response

Confidential: No

7.1 Comments

Nuromol is an analgesic containing both ibuprofen and paracetamol and is indicated for temporary relief of mild to moderate pain, which has not been relieved by ibuprofen or paracetamol individually, such as migraine, headache, backache, period pain, dental pain, rheumatic and muscular pain, cold and flu symptoms, sore throat and fever in adults 18 years and over.

GSL is the correct classification for Nuromol Dual Action Pain Relief 200mg/500mg tablets

This product contains two well known and established active ingredients and was granted a licence in 2010. The consultation has shown that the product meets the GSL criteria as laid down in the HMR 2021, regulation 62(5) i.e. the product can, with reasonable safety, be sold or supplied otherwise than by or under the supervision of a pharmacist, where the term “with reasonable safety” has been defined as: “where the hazard to health, the risk of misuse, or the need to take special precautions in handling is small and where wider sale would be a convenience to the purchaser”.

Fulfilling GSL criteria

As defined in the consultation, the product has been sold in the UK as P product without any significant safety issues for six years and is available in an equivalent GSL setting in New Zealand, with low Adverse Drug Reactions (ADRs). The dosage regimen and quantity of actives in the product mean that if taken correctly the product can be used with minimal incremental risk. As detailed in the consultation, even if the tablets were taken at the “normal” paracetamol dosing regimen, the amount taken of both paracetamol and ibuprofen would not be harmful and is inside maximum daily doses. For those people with body weight lower than 50 kg the reduced amount of paracetamol in the product (compared to the usual solid dose oral paracetamol) is less than that already approved at the GSL classification and the maximum daily dose for paracetamol is 3g, rather than 4g (compared to the usual solid dose oral paracetamol).
As such the proposal shows that Nuromol is not a hazard to health.

The consultation also shows that the risk of misuse is minimal, as it is indicated for well-established GSL indications relating to mild and moderate pain. The maximum duration of use is in line with other GSL painkillers with a maximum pack size of 16 tablets. The warnings on the packs and labelling to show that the product contains both paracetamol and ibuprofen are clear, as demonstrated by two user testing studies that 100% of participants were able to identify the product contained both these actives. As mentioned in the hazard to health section, even if an individual did take the product according to paracetamol dosing, the amount of paracetamol and ibuprofen would still be well within the prescribing limit of the product. As such the risk of misuse is minimal.

The studies performed to determine whether people could correctly identify that this product was for second line treatment showed that people could appropriately purchase the product according to the correct criteria without a pharmacist present.

Wider access to self care products

Having an additional product that can be used for second line treatment when paracetamol or ibuprofen alone have not provided relief will be of great benefit to people experiencing mild to moderate pain. This increased access in a GSL setting provides alternative options, which people can purchase outside of pharmacy hours, when they may require immediate relief from pain. This will enable people to take more control of their self care and health.

Do you have any specific comments on the leaflet or label provided at Annexes, 2 & 3? The label and leaflet are clear. They have been user tested and shown to enable people to correctly identify the product contains ibuprofen and paracetamol, as well as to only take the product if paracetamol or ibuprofen individually doesn’t work as a first line treatment.

8. Response number 9

Organisation/individual: RPS

Agree/ Disagree: Disagree

No definitive view – issues raised: No response

Confidential: No

8.1 Comments

Pharmacy plays a vital role in ensuring individuals have access to medicines. The supply of P medicines provides a touchpoint with patients and enables a direct interaction to take place between the patient and the pharmacist potentially including an intervention around medicines or giving lifestyle advice. It is crucial that these important interactions are not lost and that appropriate opportunity for the patient to be supported with medicines and health advice tailored to their individual needs are maintained.

Regardless of the route of access the RPS believes that medicines supply should be:

1. safe
2. person-centred
3. timely
4. equitable
5. efficient & effective

We have concerns about the safety of making this combination product available as a general sales item. Ibuprofen is contraindicated in several patients, such as patients with previous hypersensitivity reactions, history of gastrointestinal bleeding or perforation (related to previous NSAIDs therapy), severe renal failure, severe hepatic failure and severe heart failure [1].

There are also many times when it should be used with caution, for example in the first and third trimester [2].

We are concerned about the potential for people to confuse the product with paracetamol alone and take the standard paracetamol dose of two tablets four times a day. This has the potential to cause patient harm and is not considered in the consultation.

We also note that annually in the UK, paracetamol overdose results in approximately 100,000 Emergency Department presentations and 50,000 acute hospital admissions, and is the direct cause of death in around 150 people (ECM, HES)

The National Institute for Health and Care Excellence (NICE) clinical guidelines in the UK for the treatment of mild-moderate pain specify a stepwise approach to pain management, with medicines with a combination of paracetamol and ibuprofen a suitable third line choice for people who can take it. It is highlighted on the box that Nuromol is for use only after trying ibuprofen or paracetamol individually first. We believe that people should consult a healthcare professional when initial GSL products have failed, this should be part of identifying any concerns and red flags. Therefore, placing this into a GSL category is not a valid position in the care pathway of any of the conditions listed.

8.2 Do you have any specific comments on the leaflet or label provided at Annexes, 2 & 3?

The outer packaging and patient information leaflet for a GSL product consistently advises patients to seek advice from their doctor or pharmacist. In non-pharmacy outlets where GSL medicines are sold, professional advice is not available. The request for all GSL and P medicine in a Pharmacy setting will be handled by trained health care advisors, with pharmacists on hand to offer further professional advice where needed in order to ensure the safe and appropriate use of medicines.

8.3 Do you have any other comments on the reclassification?

We are supportive of wider access to medicines however this access must be carefully managed balancing the convenience of self-selection with the risk of losing the opportunity for a health intervention or health advice.

Pharmacy sale of medicines offer added safety for patients, as pharmacists and trained healthcare advisors are on hand to counsel the patients on their medicines and we would advocate this added safety measure is needed for a combination medicine.

Our aim as the Royal Pharmaceutical Society is to ensure patients get the most from their medicines. To facilitate this we advocate that patients must be able to self-care with the support of the professional expertise and judgment of a pharmacist, and the P category of medicines help facilitate this interaction. This is especially important when a product contains more than one medicine.

https://www.medicines.org.uk/emc/product/7020/smpc#gref [1] https://www.medicines.org.uk/emc/product/7020/smpc#gref

The National Institute for Health and Care Excellence (NICE) clinical guidelines in the UK for the treatment of mild-moderate pain specify a stepwise approach to pain management, with medicines with a combination of paracetamol and ibuprofen a suitable third line choice for people who can take it. It is highlighted on the box that nuromol is for use only after trying ibuprofen or paracetamol individually first. We believe that this would be the time to consult a healthcare professional when initial GSL products have failed and should be part of identifying any red flags or potential for misdiagnosing. Therefore placing this into a GSL category is not a valid position in the care pathway of any of the conditions.