Black Triangle

Today sees the launch of the National Flu service in the UK. As well as advice on Swine Flu, and the use of a checklist to diagnose cases, the site will also issue vouchers for Tamiflu (from now on referred to by its generic name oseltamivir) which can be redeemed at designated collection points. Only by providing appropriate answers to questions will the voucher be provided. This is analogous to the the sale of over-the-counter medicines within pharmacies. People can, if they wish, provide the answers to questions that they think are expected. If denied a sale at one pharmacy, and armed with the reason for that denial, they can go to another pharmacy and obtain the product. With an internet site, and a condition with well-known symptoms, visitors will have little difficulty in obtaining a supply – with no professional oversight. In the case of a pandemic such a system is sensible, in order to take pressure off general practitioners – even if some unscrupulous individuals abuse the system.

Interestingly, it appears that professional oversight is already influencing the supply of oseltamivir. Last Friday, Newsnight covered swine flu in my local patch, Birmingham, and included the following short segment were a GP at a swine flu centre admitted to holding back oseltamivir because of their experience of adverse effects in patients.

She is not alone. Another GP has also noted that he is reserving oseltamivir for specific groups of patients due to adverse drug reactions:

Peter Holden, the lead expert on swine flu for the British Medical Association and a GP in Matlock, Derbyshire, said: “There is a danger that we will give Tamiflu out too easily.” Tamiflu was associated with side-effects, including diarrhoea, vomiting and hallucinations, “so with just mild symptoms, very few people actually need it.

Sarah Vine has described her reaction to oseltamivir in The Times:

I took my first Tamiflu at around 6pm. After about an hour, I became dimly aware of a strange foreboding in my stomach. I turned over, willing it to subside. Nope, there it was again: unmistakable. I adjusted my pillows, hoping for a reprieve. No, I was going to be sick. Really sick. I barely made it to the bathroom before my body unceremoniously ejected the Tamiflu, along with the only other thing I had swallowed that day, Ribena.

Another patient reports diarrhoea in the Daily Mail.

Simon Jenkins writes in The Guardian about his friends’ anecdotal experiences:

I have family and friends who have had swine flu [...] I do not want to dent the soaring profits of Roche pharmaceuticals, but most I spoke to found the Tamiflu side-effects, of bad dreams, nausea and irritability, far worse than the illness.

[Note: The rest of Simon Jenkins article and advice is not recommended. See Gimpy's blog for further details]

I have previously written on the subject of oseltamivir adverse effects in The Pharmaceutical Journal, and the reports above are in-line with published evidence. Clinical trials of oseltamivir for influenza show nausea, vomiting, bronchitis, insomnia and vertigo to be common. In children, oseltamivir causes similar reactions, with vomiting occurring in 14.8 per cent of children. Despite concerns about neuropsychiatric events (such as hallucinations, suicidality and abnormal behaviour) with the use of oseltamivir, and the inclusion of these in product literature, pharmacoepidemiological studies and case report analysis cast doubt on such an association. However, they are worth bearing in mind if you are caring for an individual with influenza (itself a cause of neuropsychiatric events). Overall, oseltamivir is a safe drug, but some of the adverse effects will influence patient adherence, as some of the media reports above show.

The stocks of oseltamivir obtained by the UK government have been presented as evidence of the UK’s preparedness for an influenza outbreak. Governments want to be seen to be doing things. The public want a “cure”. Even with the caveats that have been given in the media by spokespersons, it may be that the public have a perception of the benefits of oseltamivir which is out of line with the published evidence. Ben Goldacre gave a balanced appraisal in the The Guardian:

I would take these drugs. Things might be different in a pandemic, and the Cochrane review recommends them in such circumstances. If they make my symptoms less severe then I’m guessing I’m less likely to die, and they might reduce the spread of the disease throughout a whole country.

But they’re not a miracle cure, and if this is worrying to you, that just shows how ill-equipped we are to consider the risk.

Given the H1N1 influenza virus is causing only relatively mild symptoms in many people, then annoying adverse effects that can reduce patient adherence become relatively more important. People may put up with additional nausea and insomnia if the disease is killing a large number of individuals. However, if they judge their influenza to be mild, and judge the number of deaths reported in the media to be low, then the decision to stop therapy may be taken.

A GP at Onmedica also expresses some frustration with patient expectations of oseltamivir, which are out of line with the evidence of its efficacy and may paradoxically lead to greater pressure than the influenza pandemic itself.

It’s interesting to speculate that the very act of preparing for a pandemic by stockpiling oseltamivir, and creating a demand for the drug, may be in part responsible for the pressure on health services – which might better be employed in catching the more serious cases with secondary complications. This may be an unforeseen, and perhaps unavoidable, adverse effect of sensible goverment policies on preparedness for a potentially more serious Avian influenza outbreak (assuming some of the worst case scenarios for Swine flu do not develop).

Patients and healthcare professionals should also be aware that if they are taking oseltamivir and experience any adverse effects, they can report their concerns through a dedicated Swine Flu portal at the Medicines and Healthcare products Regulatory Agency.