NICE technology appraisal guidance
Issued: September 2008
TA158

Oseltamivir, amantadine (review) and zanamivir for the prophylaxis of influenza

This is an extract from the guidance. The complete guidance is available at guidance.nice.org.uk/ta158

3 The technologies

Oseltamivir

3.1 Oseltamivir (Tamiflu, Roche) is a neuraminidase inhibitor that is active against influenza A and B viruses. It prevents viral release from infected cells and subsequent infection of adjacent cells. It has a marketing authorisation for post-exposure prophylaxis in people 1 year of age or older following contact with a clinically diagnosed influenza case when influenza virus is circulating in the community. The appropriate use of oseltamivir for prevention of influenza should be determined on a case-by-case basis by the circumstances and the population requiring protection. In exceptional situations (for example in the case of a mismatch between the circulating and vaccine virus strains, and a pandemic situation) seasonal prevention can be considered in people 1 year of age or older. For post-exposure prophylaxis, oseltamivir should be started within 48 hours of contact with an index case of influenza-like illness and continued for 10 days. For seasonal prophylaxis, oseltamivir is given for up to 6 weeks. Oseltamivir is administered orally.

3.2 Adverse effects associated with oseltamivir include gastrointestinal symptoms, bronchitis and cough, dizziness and fatigue and neurological symptoms such as headache, insomnia and vertigo. Skin rashes and allergic reactions and, rarely, hepatobiliary system disorders have been reported. Convulsions and psychiatric events, mainly in children and adolescents, have also been reported but a causal link has not been established. For full details of adverse effects and contraindications, see the summary of product characteristics (SPC).

3.3 Oseltamivir costs £16.36 for a 10-day course for an adult (excluding VAT; 'British national formulary' [BNF] edition 54). Costs may vary in different settings because of negotiated procurement discounts.

Amantadine

3.4 Amantadine (Lysovir, Symmetrel, Alliance Pharmaceuticals) acts against influenza A virus by blocking viral replication. The marketing authorisation recommends amantadine prophylactically in people particularly at risk. This can include those with chronic respiratory disease or debilitating conditions, the elderly and those living in crowded conditions. It can also be used for members of families in which influenza has already been diagnosed, for control of institutional outbreaks or for those in essential services who are unvaccinated or when vaccination is unavailable or contraindicated. It is also recommended as post-exposure prophylaxis in conjunction with inactivated vaccine during an outbreak until protective antibodies develop, or in people who are not expected to have a substantial antibody response (because of immunosuppression). Amantadine is licensed for use in people aged 10 years or older. The SPC states that treatment is recommended for as long as protection from infection is required and that in most instances this is expected to be for 6 weeks. In clinical practice this corresponds to its use as seasonal prophylaxis. For post-exposure prophylaxis, amantadine is usually given for 4–5 days. Amantadine is administered orally.

3.5 The adverse effects associated with amantadine are often mild and transient. The most commonly reported effects are gastrointestinal disturbances such as anorexia and nausea, and central nervous system effects such as loss of concentration, dizziness, agitation, nervousness, depression, insomnia, fatigue, weakness and myalgia. Central nervous system effects are most common in older people. For full details of adverse effects and contraindications, see the SPC.

3.6 Amantadine costs £2.40 for five capsules (100 mg each), £4.80 for 14 capsules and £5.55 for 150 ml syrup (50 mg/5 ml) (excluding VAT; BNF edition 54). Costs may vary in different settings because of negotiated procurement discounts.

Zanamivir

3.7 Zanamivir (Relenza, GlaxoSmithKline) is a neuraminidase inhibitor that is active against influenza A and B viruses. It prevents viral release from infected cells and subsequent infection of adjacent cells. It has a marketing authorisation for post-exposure prophylaxis of influenza A and B in adults and children (5 years and older) following contact with a clinically diagnosed case in a household. In exceptional circumstances, zanamivir may be considered for seasonal prophylaxis of influenza A and B (for example, during a community outbreak in the case of a mismatch between circulating and vaccine strains, and in a pandemic situation). For post-exposure prophylaxis zanamivir should be initiated within 36 hours of contact with an index case of influenza-like illness and continued for 10 days. For seasonal prophylaxis, zanamivir is given for up to 28 days. Zanamivir is administered by oral inhalation using an inhaler device.

3.8 Adverse effects associated with zanamivir are rare. They include bronchospasm and allergic phenomena. For full details of adverse effects and contraindications, see the SPC.

3.9 The price of zanamivir was reduced during the course of the appraisal to £16.36 for a 10-day course. The price of zanamivir currently listed in the BNF is £24.55 for a 10-day course (excluding VAT; BNF edition 54). Costs may vary in different settings because of negotiated procurement discounts.