SMZ-TMP - Bactrim - Septra - Septrin: UK parliament debates side-effects risks

House of Commons, March 22 1995

1.59 pm

Ms Margaret Hodge (Barking): I have called this debate on the drug known as Septrin, or Bactrim, as I am horrified by what I have learnt about the possible side effects of this commonly prescribed antibiotic.

The significance of the drug goes beyond the horrendous suffering that it has caused a considerable number of those who have taken it, to wider questions about the effectiveness of our regulatory system for drugs and medicines. I have called the debate for two reasons: first, to ask the Minister urgently and thoroughly to review the licence of the drug; and, secondly, to draw the attention of the House to my concerns about the framework for licensing drugs, and the need for change.

I first became aware of the issue of septrin, the generic name of which is co-trimoxazole, in January this year. My constituent, Kate Reid, a young woman in her 30s, came to my advice surgery. She told me that, eight years ago, she visited her general practitioner, as she had a sore throat. She was prescribed Septrin. After two days of taking the medicine, she collapsed, her tongue having swollen so badly that she could hardly breathe. She was rushed to hospital. Six weeks followed, during which she continued to suffer because of her allergic reaction to the drug. The skin over her whole body blistered horribly and completely fell away. Her vagina closed up. Her finger and toe nails fell out, and she was unable to walk or talk. She was very lucky to have survived at all. Her suffering has, of course, continued and she will never regain her good health. The physical scars will never disappear, nor will the mental scars.

Not only has Kate Reid had to endure numerous skin grafts and surgery, but she is left unable to walk properly because of the pain in her feet left by the blistering. Her tongue remains black and blistered. He body has stopped producing saliva or tears. Her finger and toe nails have never grown back. She has lost her job and lives on benefit. Her relationship with her boyfriend fell apart and she has had to have psychotherapy to come to terms with the trauma. As one can imagine, when she told me all this, I was horrified at the suffering that this woman had endured as a result of a drug prescribed for a sore throat. At least, I thought, it must be a one- off. Surely such an horrendous reaction must be almost unique. Tragically, that is not the case. As I have discovered, more and more people are coming forward following recent publicity about Septrin. As many as 700 people who have suffered, or whose relatives have suffered similar reactions to those experienced by Kate, after being prescribed Septrin for minor ailments such as sore threats or cystitis, have contacted either journalists or one of the Septrin action groups. Most of those people are women, as women more commonly get urinary tract infections.

No one knows precisely how many people have died as a result of having taken Septrin. A recent report to the Committee on Safety of Medicines in England says that deaths linked to the sulphonamide component of septrin have so far reached 137. The same committee's research, however, shows that 10 times as many cases go unreported. As Septrin has been one of the most popular antibiotics since the 1970s, the total figure may well be much higher, and, of course, there are thousands of people like Kate who suffer in varying degrees because of its side effects.

What I have tried to do, as a layperson, is to see whether there is a case for reviewing the drug's licence. I submit to the House that the Department of Health cannot continue to ignore the evidence of totally unnecessary human suffering resulting from the inappropriate prescription of Septrin. The Department is failing in its duty if it does not call for an immediate and thorough review. More people's lives will be destroyed and more families may lose loved ones in the future.

Septrin was first marketed in 1969 and has been a highly successful commercial product for the Wellcome Foundation. Worldwide sales are said to be worth up to $5 billion. Since it was first licensed, however, extensive medical research has shown that only one of its ingredients, the sulphonamide component, causes those horrific side effects. Furthermore, in most cases, that ingredient is not necessary. Giving patients the other ingredient, trimethoprim, on its own, would be just as effective and much safer.

I am aware that Septrin may have a very important role to play in certain circumstances, for example in the treatment of people with acquired immune deficiency syndrome--AIDS--where trimethoprim has not been shown to be as effective as Septrin. However, all the major studies have shown that, in most circumstances, trimethoprim alone is just as effective as Septrin and much safer. What I cannot understand, therefore, is why the data sheet, which licenses the use of septrin, has not been changed to limit its use to the few circumstances where no other treatment will do.

The case of septrin shows up the failure of our drugs regulation system. The evidence against the wider use of Septrin has been around for 20 years, but it has not resulted in a change in the drug's data sheet or licence. Why not? What is in our regulatory framework that can lead to an appalling failure to protect people? First, the system is governed by secrecy. Section 118 of the Medicines Act 1968 basically gags the experts involved in regulation from revealing information on drugs beyond that specifically contained in the data sheet; so the experts cannot tell us, the public, or even the doctors, that Septrin should be prescribed only in certain circumstances. That is particularly dangerous because the Medicines Control Agency, which regulates drugs, is totally funded by the pharmaceutical industry. Its members mostly have an interest in the products on which they advise. Indeed, almost all research in this field is funded by the drugs industry itself. One is left wondering whether the financial interests of the industry have too great an influence at the expense of safety of the patients.

Which? magazine recently undertook a telling piece of research. It sent duplicate requests for information about Septrin to the US Food and Drugs Administration and the United Kingdom Medicines Control Agency. The FDA sent the equivalent of 300 pages of detailed data on the drug, including its side effects. The MCA, our agency, took longer to reply and could send a mere 22 pages. The Government's refusal to repeal section 118 is, in my view, misguided and seems to put the interests of industry profit above those of patient safety. My second point is that patients need better access to authority to complain about the side effects of drugs. At present, they can speak only to their doctor, who may not want to hear that their prescription is responsible for the side effects that the patient has suffered. My constituent, for example, was so persistent that the GP finally removed her from his register--perhaps that is another story. Again, precisely because there is no channel for complaints, the GP will be unaware of similar cases and may presume that it is a one- off, not to be taken as a reflection on the drug as a whole. We need a proper system to monitor openly all cases of side effects. The Committee on Safety of Medicines is a watchdog that never barks. At the very least, there should be patient representatives on it to beef it up so that cases like Septrin are taken seriously and are not swept under the carpet. We also need a system under which patients can seek redress for the harm done to them. We seem to have learnt nothing from the thalidomide tragedy. Incredibly, the success rate of legal claims against drug companies in Britain is zero. I hope that the Select Committee on Health will examine the position.

A third change to the regulatory system would have prevented much of the suffering related to Septrin had it been introduced 20 years ago. We need a proper, stringent and thorough review of drug licences when they are renewed. The Medicines Act requires the renewal of licences every five years, but I understand that the reviews are generally conducted by administrative staff at the Department of Health rather than by experts, and tend to go through almost on the nod. We can only presume that that happened with the renewal of the licence for Septrin; how else can the licence have been renewed time after time with no change in the rules governing its use? In its report last summer, the Select Committee on Health made precisely that point to the Government. It recommended a national prescribing list of medicines for the NHS, with drugs being reviewed stringently every five years for inclusion in the list. In a vast and ever-changing market, it is essential that the Government accept the Committee's recommendations: regular reviews of drug licences are essential to determining which drug is the most appropriate, in terms of both effectiveness and cost.

The final change that I consider crucial to the safeguarding of patients is for the Department of Health to take responsibility for informing doctors when a drug's licence has changed. At present, even if the information were getting through to the Medicines Control Agency and drug licences changed when they should, GPs would be unlikely to be aware of the change. That is borne out by evidence that most hospitals have largely abandoned the use of Septrin, other than for the treatment of people with AIDS. GPs have not followed suit. There are so many products on the market that GPs tend to use those that they have heard of--those that drug companies have promoted heavily, or tried and tested products that they are used to. Just one example is griseofulvin, an anti-fungal medicine. Last year, the data sheet for griseofulvin was changed, stating that it should not be prescribed for men who expect to father a child in the next six months. There was no announcement of the change to GPs. How many have continued to prescribe griseofulvin in exactly the same way as they always have, unaware of any change in the data sheet? If the Government made the changes that I have recommended to tighten drug regulation, tragedies such as those that have befallen my constituent and countless others might be avoided in the future. The onus is on the Government to reassure the British people that their concern lies with the health of the patient, not the health of the drug industry. The evidence on septrin itself overwhelmingly suggests that the sulphonamide component increases both the danger and the cost of the product. I call on the Government to change the licence for the drug with the utmost urgency, before any more people suffer as Kate Reid has suffered.

2.13 pm

Mr. Doug Hoyle (Warrington, North): I thank my hon. Friend the Member for Barking (Ms Hodge) for allowing me to speak, and for the detailed way in which she put her case.

My interest in Septrin began when a constituent, Mr. Beddows, came to see me in November last year. He had been prescribed the drug for bronchitis, but when he took it his skin peeled off and he blew up like a huge balloon. He was in a dangerous condition, and had to go to hospital. Moreover, he could cite other cases among his small circle of friends. A child had lost skin off both legs; an adult had suffered from internal bleeding; another had experienced low blood pressure. According to Mr. Beddows, an action group had established that as many as 25 per cent. of users of Septrin were suffering from adverse effects.

Having heard all that, I wrote to the Secretary of State for Health and received a reply from the Under-Secretary of State, Baroness Cumberlege. I thought it rather complacent: although she admitted that there were adverse side effects, she suggested that they were a matter for GPs, who knew their patients. I wrote to Mr. Beddows, who came to see me again, bringing with him the case against septrin that had been prepared by Professor Richard Lacey--an extremely detailed case.

I wrote again to the Minister, whose reply went a little further this time. She repeated her view that, although dangers existed, they were a matter for GPs; but she also took up Professor Lacey's suggestion that trimethoprim, taken on its own, was the answer. She claimed that that, too, had side effects, but admitted that clinical practice was changing in relation to the prescribing of antibiotics, and that "in some situations"-- I believe that in this regard she was following Professor Lacey to some extent--clinical practice "favours the use of single rather than combination antibiotic therapy."

She added:

"The Medicines Control Agency is reviewing whether the licence for Septrin should reflect this."

I wrote to the Minister again on 2 March, and am still awaiting a reply. In my letter, I asked what evidence there was that serious side effects from co-trimoxazole -- Septrin --were rare, and what evidence there was that trimethoprim also had side effects. According to Professor Lacey, those side effects are minor in comparison, and trimethoprim would be much safer to use. I hope that the Minister will mention that when he replies.

More and more people are joining the new action group, saying that they, too, have experienced adverse effects. It is time for a complete review of the drug, and if it is found to have serious side effects, I hope that it will be withdrawn from the market without hesitation.

2.17 pm

The Parliamentary Under-Secretary of State for Health (Mr. Tom Sackville): The safety of medicines is an enormously important topic. Many medicines have serious side effects, and many people suffer without knowing that their suffering results from an adverse reaction.

The story of Kate Reid, related to us by the hon. Member for Barking (Ms Hodge), is very harrowing. I have visited hospitals and seen people who have been badly affected by drugs, including antibiotics. It goes without saying that there is an element of risk in all medicinal compounds, however many efforts are made to test them and avoid side effects; a balance must always be struck. As the hon. Lady said, co-trimoxazole has been sold as Septrin by Wellcome and as Bactrim by Roche Products Ltd. Some 100 generic licences for the production of the compound have now been issued. Since 1969, 85 million prescriptions for co-trimoxazole, under its different names, have been issued in this country. Some 3,500 adverse reactions have been reported to the Medicines Control Agency, and 137 deaths have been linked to the use of co-trimoxazole. However, before coming to any conclusions on that, we must assess whether those adverse reactions and the tragic deaths were attributable to co-trimoxazole or to one of its constituent parts. It has been alleged in the press recently--and, I think, implied by the hon. Member for Barking--that sulphamethoxazole, the other constituent, has mainly been responsible for the adverse reactions. I, too, speak as a layman and I am informed by the Medicines Control Agency that no difference exists between the pattern of adverse reactions to co-trimoxazole and the pattern of adverse reactions to trimethoprim alone.

It has been fairly widely alleged that it would be safer to use trimethoprim. I understand that not only is the pattern of adverse reactions to the compound and to the substance similar but a comparable pattern of adverse reactions exists across the range of widely used antibiotics. That takes the debate much wider into the question of the use of antibiotics and how widely they are used, but we are talking specifically about whether a case exists for a review or, as the hon. Member for Warrington, North (Mr. Hoyle) said, for withdrawing co-trimoxazole from the market. I understand that such a case does not exist because, as I said, the pattern of reactions is comparable across the range of antibiotics.

A body of expert literature exists about this subject. It confirms the Medicines Control Agency's advice, which it arrives at through its yellow card system of adverse drug reactions reporting, that no special degree of risk is associated with co-trimoxazole. As I think the hon. Gentleman knows, a study has been carried out recently by Dr. Hershel Jick at Boston university, who is a much-renowned expert on drug reactions. It has considered the prescribing data on tens of thousands of people and compared the adverse reactions of co-trimoxazole with those of alternative antibiotics. That work, which I suspect will be published soon, has been made available to researchers and professionals in advance of publication. It confirms that the risk of severe adverse reaction from co-trimoxazole is not only low but comparable with that from other widely used antibiotics.

It has also been said during the debate that a lack of information about medicines exists for patients and doctors. Recently, the Medicines Control Agency was asked for the information about co-trimoxazole and it gave 22 pages of the precisely relevant data. I am not aware that anyone has made a case that anything is missing from that data. The equivalent body in America produced 300 pages simply because it handed over the entire file on the product. One cannot measure relevance or efficacy of information by the weight of paper. As far as I know, all the relevant data were made available on that occasion.

The British National Formulary , which is supplied free to all doctors, clearly states the side effects of co-trimoxazole. There is an alarming list, as there often is on antibiotics and many other drugs. It starts with nausea, vomiting, diarrhoea, glossitis, rashes and gives a list of Latin names which I shall not go through. No one is in any doubt that there are adverse reactions to the antibiotic, as there are to most others. A large number of adverse reactions, and indeed deaths, are associated with the range of penicillins, but, if one considers the pattern, it is broadly similar. Clearly, therefore, no simple answer exists, except by raising the question of the use of antibiotics.

Co-trimoxazole still has a place. It is less widely used than it was, and trimethoprim is more commonly prescribed than co-trimoxazole.

Ms Hodge: If it is true that co-trimoxazole is less well used than before, will the Minister please just listen to the speeches that my hon. Friend the Member for Warrington, North (Mr. Hoyle) and I made today? Instead of coming here with a prepared speech, will the Minister go away and really do a thorough review? The reason that it is used less often is that a safer alternative drug is available which can deal with many of the common ailments. He should consider limiting the licence under which septrin is marketed so that it is used only where it is absolutely necessary.

Mr. Sackville:I have not used a prepared speech. I have some notes that I made during the hon. Lady's speech, but I happen to have spent some time with the Medicines Control Agency to try to find out the detail of the argument. A reason still exists for co-trimoxazole to be in the British National Formulary. The hon. Lady referred to drug resistance. It is well known, and a great body of evidence exists on this, that trimethoprim, given alone, leads to greater resistance to antibiotics. There is a great deal of data to suggest that, in some parts of the country --I have a letter from a leading paediatrician to prove this--there is up to 30 per cent. resistance to trimethoprim given alone. There are cases, and she cited one of them--pneumocystis carinii pneumonia, or PCP, among AIDS victims--where it is clear that trimethoprim given alone leads to too much resistance and quickly becomes ineffective. Other practitioners will tell us that much larger doses of trimethoprim must be given if it is given alone, and that it is possible to give a much smaller dose if it is accompanied by the other constituent of co-trimoxazole.

Clearly, antibiotics have been one of the great advances of modern medicine. Thousands, if not millions of lives, have been saved by them, but, like many other medicines, they have an attendant risk. What we have to be clear about--this is germane to the debate--is whether co-trimoxazole has a higher level of risk than antibiotics generally. The evidence that has been given to me is that that is not the case. The hon. Lady mentioned that there should be a five-yearly review. She will forgive me if I say that the Select Committee was talking about the efficacy and value of drugs rather than safety. Safety is reviewed all the time. There is a yellow card system of adverse reactions reporting in this country which, I hesitate to say, is the envy of the world because it is such a comprehensive system. The Medicines Control Agency advises the Secretary of State about drug safety. That body is also widely respected as probably the agency with the greatest professionalism and probity of any in the world. I challenge the hon. Lady to find another country with a more efficient system.

I can assure all those who are concerned about co-trimoxazole that that drug and all others like it are constantly under review. Drug leaflets will be issued with all drugs in future. Since last year there has been a rolling programme for all medicines to have a drug information leaflet and one has already been approved for co-trimoxazole. We have a high-grade system for the monitoring and licensing of medicines and I can assure the hon. Lady that drug safety will continue to be of the highest priority.

It being half-past Two o'clock, the motion for the Adjournment of the House lapsed, pursuant to Order [19 December].