Policy responses and statements
- Name of organisation:
- Medicines and Healthcare Products Regulatory Agency (MHRA)
- Name of policy document:
- ARM 48: Request to Reclassify a Product from P to GSL - Galpharm Four in One Flu Relief
- Deadline for response:
- 14 December 2007
Background: The active ingredients per 20ml dose Galpharm Four In One Flu Relief are:
Paracetamol 1000mg
Phenylephrine Hydrochloride 12.18mg
Guaifenesin 200mg
Cetylpyridinium Chloride 3.0mg
Indications: For the short term symptomatic relief of the symptoms of colds and influenza, including aches and pains, headache, nasal congestion, dry tickly sore throat and chesty coughs.
COMMENTS ON
MEDICINES AND HEALTHCARE PRODUCTS REGULATORY AGENCY (MHRA)
ARM 48: REQUEST TO RECLASSIFY A PRODUCT FROM P TO GSL - GALPHARM FOUR IN ONE FLU RELIEF
The Royal College of Physicians of Edinburgh is pleased to respond to the MHRA on consultation ARM 48: Request to Reclassify a Product from P to GSL - Galpharm Four in One Flu Relief.
This product contains four ingredients, the clinical justification for three of which (phenylephrine, guaifenesin and cetylpyridinium) must remain questionable. The efficacy of cetylpiridinium and guaifenesin are not supported by clinical evidence, and although phenylephrine is a vasoconstrictor, there are at least reasonable concerns this compound may be associated with two specific adverse effects, firstly increased risk of cardiac malformations when taken by mothers taking the product (A case control study to examine the pharmacological factors underlying ventricular septal defects in the North of England. Eur J Clin Pharmacol2004; 60: 635-641) and, secondly, potential for adverse cardiovascular effects.
While this product is currently available on pharmacy advice, its move to GSL is more likely to make it more heavily used as it will be promoted by advertising, and hence increase the amount of phenylephrine being used in the community.
The issue of paracetamol, which is the main focus of the consultation, is equally troubling. Paracetamol continues to be a major cause of acute hepatic injury, and currently is thought to result in approximately 20-30 deaths per annum. While the majority of these are the result of intentional drug ingestion, a significant but important minority occur in otherwise healthy adults who by error consume multiple preparations containing paracetamol. There is significant confusion in the public mind about the content of different analgesic preparations, and since this would be a liquid formulation, it seems much more likely that confusion regarding its contents versus those of the tablets that people are normally familiar with, will be likely. In the view of the College, the warnings on the label are not adequate in addressing this danger. The “Important information” section does not contain reference to the dangers of exceeding the dose of paracetamol. This is, in essence, the most important risk for patients using this. Patients with influenza tend not to eat very well, and it is currently thought that acute starvation may be an additional risk factor for paracetamol-induced liver damage. Taking this preparation at full dose, together with additional oral paracetamol tablets, could, in a relatively small adult, result in a potentially lethal dose.
The College remains unconvinced that the benefits of making this product GSL outweigh the potential disadvantages outlined in this response.
The bottom line is, yes, it would be helpful to have an oral solution of paracetamol available GSL, at an appropriate concentration for adult use. The additional ingredients in this product add to the confusion about its indications and efficacy and, in our view, could result in an unacceptably high risk of medication combination resulting in risk of liver failure. Professional experience leads us to believe that patients do not read the labels adequately, and may not appreciate that a liquid preparation may contain the same ingredients as a solid one. We already have deaths from these therapeutic errors; the College would like to stop more occurring and therefore does not endorse this recommendation. If the product is licensed it should carry an appropriately worded warning on the bottle, along the lines of Warning: contains paracetamol. Do not exceed the stated dose. Do not combine with other paracetamol-containing medicines due to risk of serious liver injury or death.
Copies of this response are available from:
Lesley Lockhart,
Royal College of Physicians of Edinburgh,
9 Queen Street,
Edinburgh,
EH2 1JQ.
Tel: 0131 225 7324 ext 608
Fax: 0131 220 3939
[14 December 2007] |
