Drug Safety Update

Volume 3, Issue 1 August 2009

Latest advice for medicines users

Safety information on oseltamivir (Tamiflu) and zanamivir (Relenza) for pandemic swine influenza A/H1N1

Article date: August 2009

Tamiflu and Relenza are both neuraminidase enzyme inhibitors. They act by inhibiting entry of influenza virus into uninfected cells and preventing the release of recently formed virus particles from infected cells. Tamiflu is given orally (capsules and solution) and Relenza is given by inhalation (Diskhaler system).

Both have substantial experience of use and favourable benefit-risk profiles.

Further information about these medicines, including a list of known side effects, can be found in the Summary of Product Characteristics and Patient Information Leaflet (external link).

Tamiflu

Side effect profile
The most common side effects of Tamiflu are nausea, vomiting, diarrhoea, abdominal pain, and headache. These may usually occur after the first dose and will usually stop as treatment continues. The frequency of these effects is reduced if Tamiflu is taken with food. More-serious side effects are very rare (see Summary of Product Characteristics for further information).

The product information for Tamiflu lists neuropsychiatric disorders (reports of convulsions and delirium) in the side-effects section. These events were added to the product information as a precautionary measure—a causal association between Tamiflu and the reported events is uncertain.

Drug interactions
Clinically important drug interactions with Tamiflu are unlikely, including those involving competition for renal tubular secretion. However, care should be taken when prescribing Tamiflu for patients who are taking co-excreted medicines with a narrow therapeutic margin (eg, chlorpropamide or methotrexate).

No dose adjustment is required when coadministering with probenecid in patients with normal renal function. Coadministration of probenecid, a potent inhibitor of the anionic pathway of renal tubular secretion, results in an approximate two-fold increase in exposure to the active metabolite of oseltamivir.

Renal impairment
Dose adjustment is recommended for adults with severe renal insufficiency (ie, ≤30 mL/min). Tamiflu is not recommended for patients with a creatinine clearance of ≤10 mL/min or in those undergoing dialysis.

The National Pandemic Flu Service is directing anyone with a kidney disorder to their healthcare professional; Relenza has been procured for these individuals (see below).

Shelf-life
Packs of Tamiflu capsules manufactured since June 2009 have a shelf-life of 7 years. Packs manufactured before then, including most in UK stockpiles, have a shelf-life of 5 years. Although the longer shelf-life cannot be retrospectively applied to the licence for the older packs, the European Medicines Agency (EMEA) has issued guidance that Tamiflu capsules already on the market may be used for up to 2 more years after their current 5-year expiry date during the swine flu pandemic.

Press release: European Medicines Agency recommendations on extension of shelf life for Tamiflu (external link)

Relenza

Relenza is delivered by inhalation using a Diskhaler. The recommended doses are provided in the product information.

The National Pandemic Flu Service is directing anyone with a kidney disorder or who may be pregnant to their healthcare professional; Relenza has been procured for these individuals.

Side effects
Recognised side effects to Relenza are very rare, but may include allergic-type reactions such as swelling of the face, mouth, or throat; skin rash; or hives. Acute bronchospasm or serious decline in respiratory function (or both) have been seen in patients with a history of asthma or chronic obstructive pulmonary disease (COPD), and in those without a history of respiratory disease (see below).

The product information for Relenza also lists neuropsychiatric disorders as a possible side effect of the medicine. As with Tamiflu, these events were added to the product information as a precautionary measure and a causal association with Relenza is uncertain.

Drug interactions
Clinically significant drug interactions with Relenza are unlikely.

Patients with asthma or COPD
Patients with severe asthma should not receive Relenza unless close medical monitoring and appropriate clinical facilities are available, in case of bronchoconstriction. In patients with persistent asthma or severe COPD, management of the underlying disease should be optimised during Relenza treatment.

If Relenza is considered appropriate for any patient with asthma or COPD, the patient should be informed of the potential risk of bronchospasm and should have a fast-acting bronchodilator available. Patients on maintenance inhaled bronchodilating therapy should be advised to use their bronchodilators before taking Relenza.

How to report suspected adverse reactions to Tamiflu and Relenza

We have a special web-based system for reporting suspected adverse drug reactions (ADRs) to Tamiflu and Relenza, called the Swine Flu ADR Portal. This is available now and will continue to operate for the duration of the pandemic:

Please report all suspected ADRs to Tamiflu and Relenza via the Swine Flu ADR Portal.

Please remember to include the following important information in your report:

  • patient age
  • indication (prophylaxis or treatment)
  • outcome of the ADR
  • information on any underlying risk factors for the ADR or for influenzacomplications; or state if there are no known risk factors
  • any other information about the patient or additional clinical details that will help us in our assessment of the case.

When swine influenza A/H1N1 vaccines become available, the Swine Flu ADR Portal should also be used to report suspected ADRs to these vaccines.

The existing Yellow Card Scheme will remain in operation during this time for reporting suspected ADRs to all other medicines.

Before this swine flu outbreak, use of these medicines in the UK was limited—UK public health policy for prevention of seasonal influenza infection focused on yearly seasonal influenza vaccination. It is possible that the wider prescribing of these medicines in a pandemic situation may reveal rare effects that have not previously been seen. Therefore, it is vitally important that suspected ADRs to Tamiflu and Relenza are reported to us. If you suspect that a patient has experienced an adverse reaction to these antivirals, please report as outlined above.

Given the novel mechanisms that will be in place for provision of antivirals during the pandemic, we particularly welcome reports from patients of suspected side effects to their antiviral medication. Please remind patients that they can report such suspected side effects through the Swine Flu ADR Portal.

Mechanisms in place for diagnosis of swine flu and supply of antivirals

As the swine flu pandemic progresses in the UK, special mechanisms are being put in place by the NHS to ensure that patients are quickly diagnosed with flu and can rapidly access antiviral medication. In England, the National Pandemic Flu Service is now operating. Mechanisms for supply of antivirals may vary between regions depending on local circumstances. Please keep up to date on such mechanisms via the information links below.

Further information

MHRA information is available at www.mhra.gov.uk/swineflu
Northern Ireland - nidirect (external link)
Scotland - NHS24 (external link)
Wales - National Public Health Service for Wales (external link)
England - NHS Direct (external link)

 

Article citation: Drug Safety Update Aug 2009, vol 3 issue 1: 2.

References

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Page last modified: 06 September 2010