Friday August 21 2009
A report on side effects of Tamiflu and Relenza has been published by the Medicines and Healthcare products Regulatory Agency (MHRA). This is the first weekly report, and is based on information gathered between April 1 and August 13 2009.
The MHRA has stressed that the report on suspected adverse reactions to Tamiflu and Relenza involves only suspected reactions to the antivirals, and the actual causes could be due to other illnesses or could be purely coincidental rather than being caused by the drugs themselves. It also says the list cannot be used to determine how often these side effects occur or to make direct comparisons between the safety of Tamiflu and Relenza. Information about known side effects of Tamiflu and Relenza is available in the product information (see http://emc.medicines.org.uk/) or at www.mhra.gov.uk/swineflu.
The information is submitted by healthcare professionals and members of the public via a special website for reporting adverse drug reactions (ADRs) and the Yellow Card Scheme. It also includes reports submitted by the manufacturers of the drugs.
- No new safety concerns have been identified for either Tamiflu or Relenza, and there is no change to the product information. Patients should continue to take the drugs as advised by their healthcare provider.
- The balance of risks and benefits for Tamiflu and Relenza remains positive.
- As of August 13 2009, the MHRA had received 533 reports about Tamiflu, mentioning 895 suspected adverse reactions (reports can list more than one suspected adverse reaction).
- For the same period there were 12 reports for Relenza (with 19 suspected adverse reactions).
- For both antivirals most of the reported suspected adverse reactions resemble already known mild side effects of the drugs and are listed as such. Many can also be caused by flu-like illness, so it is unclear whether they were caused by the drugs or by the illness.
- The MHRA will continue to monitor the situation.
There have been a total of 533 reports (together reporting 895 suspected adverse reactions) in association with Tamiflu. The most common fall within recognised side effects of Tamiflu and include mild allergic reactions, gastrointestinal problems, and headache and dizziness. The MHRA reports that these can also be caused by flu-like illness. No new safety issues have been identified.
Possible drug interaction between Tamiflu and warfarin
There have been several reports suggesting a possible interaction between Tamiflu and warfarin leading to a prolonged blood clotting time. Available evidence is currently insufficient to establish whether such cases are a true drug interaction between the two or whether blood-clotting control in these patients may have been affected by underlying infection and associated illness.
Therefore, at present there is no change to the product information for Tamiflu and patients should continue to take Tamiflu and warfarin as advised by their healthcare provider. All reports of a possible interaction with warfarin remain under close review by the MHRA.
Suspected adverse drug reactions with a fatal outcome
There have been two reports of patients dying following treatment with Tamiflu: one case of unexplained death and one case of acute hepatic failure. Both cases have been fully evaluated and in neither case is there evidence to confirm that Tamiflu was the direct cause of death, which was possibly due to underlying infection and illness.
Neuropsychiatric adverse events
Neuropsychiatric adverse effects, including convulsions and delirium (with symptoms such as confusion, abnormal behaviour, hallucinations, agitation, anxiety and nightmares) are listed as possible side effects in the Tamiflu product information.
However, flu itself can be associated with a variety of neurologic and behavioural symptoms, sometimes without obvious signs of a severe infection. Some studies have found that these types of events are no more frequent in flu patients on Tamiflu compared with those who have not taken the drug. It therefore remains unclear whether these neuropsychiatric events may be a true side effect of Tamiflu or whether they are due to underlying infection (or a combination of both).
Reported cases will remain under close review by MHRA, but those reported so far do not raise any new safety concerns. Nonetheless, patients should remain vigilant to the possibility of such events and discuss any serious concerns with their healthcare provider.
Serious skin reactions
Some patients treated with Tamiflu have reported serious skin disorders such as Toxic Epidermal Necrolysis (TEN), Stevens-Johnson Syndrome (SJS) and erythema multiforme (blistering conditions of the skin). They are listed as possible side effects of Tamiflu in the product information.
However, such conditions may also be caused by various infections including influenza. It is therefore unclear whether cases of severe skin disorders in influenza patients are due to Tamiflu or to the underlying infection and illness. The MHRA will continue to keep such reports under close review.
A total of 12 reports (including 19 suspected adverse reactions) have been reported in association with Relenza. Most resemble known side effects of Relenza such as allergic reactions and bronchospasm. Most other reported events such as diarrhoea, nausea, vomiting, fatigue, headache and dizziness can also be caused by flu-like illness. No new safety issues have been identified.
Relenza in pregnancy
There has been one reported case of miscarriage in early pregnancy. Cases of miscarriage are not uncommon in early pregnancy and some may inevitably occur by coincidence following Relenza therapy without the drug playing any role in the event. There is no evidence to indicate that Relenza carries any risks in pregnancy, to either the foetus or expecting mother.
This is supported by a recent review of available evidence by European regulatory authorities. Indeed, this review led to a recommendation that, due to the potentially serious risks of H1N1 swine influenza in pregnancy, the benefits of using Relenza (and Tamiflu) in treating influenza in pregnant or breastfeeding women outweigh any known risks.