216 Drug Profiles

Efficacy

Inhaled zanamivir reduces the median time to alleviation of major influenza symptoms by up to 2.5 days if taken within 48 h of symptom onset. These benefits appear to be particularly marked in severely ill patients and in individuals ≥ 50 years of age, who have underlying illnesses, or who are considered high risk. Patients with a lower temperature or less severe symptoms appear to derive less benefit from treatment with zanamivir.

When used for prophylaxis, zanamivir significantly reduces the number of families with new cases of influenza compared with placebo, and prevented new cases of influenza in long-term care facilities.

Treatment

The first clinical experience with zanamivir included patients from separate randomised, double-blind studies in 38 centres in North America and 32 centres in Europe in 1994-1995. These studies demonstrated approximately a one-day reduction in the time to alleviation of symptoms in treated patients (4 vs. 5 days) (Hayden 1997). An even larger treatment benefit (3 days) was seen in patients who had severe symptoms at entry (Monto 1999). A 3 day treatment benefit was also observed in patients aged > 50 years, compared with 1 day in patients aged < 50 years. In “high-risk” patients there was a treatment benefit of 2.5 days (Monto 1999). In addition, zanamivir has been shown to be effective in patients at risk of developing influenza-related complications such as age ≥ 65 years and the presence of underlying chronic disease including asthma, chronic obstructive pulmonary disease, cardiovascular disease, diabetes mellitus, and immunocompromise (Lalezari 2001).

Influenza infections may lead to respiratory tract complications that result in antibiotic treatment. A meta-analysis of 7 clinical trials reported that 17 % of placebo recipients developed a respiratory event leading to antibiotic use, mainly for acute bronchitis or acute sinusitis, whereas among zanamivir-treated patients the incidence of respiratory events leading to the use of antimicrobials was 11 % (Kaiser 2000b). However, these finding have not remained unquestioned. In the setting of a large managed care plan (> 2,300 patients treated), the patterns of influenza complications were found to be similar in zanamivir-treated and untreated patients (Cole 2002).

Prophylaxis

A series of randomised trials have proven the efficacy of zanamivir in the prevention of influenza. In a study involving healthy adults, 10 mg once a day or placebo was administered by oral inhalation at the start of the influenza outbreak. Prophylaxis continued for a 4-week period. Zanamivir was 67 % efficacious in preventing clinical influenza (6 % [34/554] clinical influenza in the placebo group vs. 2 % [11/553] in the zanamivir group) and 84 % efficacious in preventing illnesses with fever (Monto 1999b).

Another clinical trial enrolled families with two to five members and at least one child who was five years of age or older. As soon as an influenza-like illness developed in one family member, the family received either zanamivir (10 mg zanamivir inhaled once daily for 10 days) or placebo. In the zanamivir families, 4 % of families had at least one new influenza case, compared with 19 % in the placebo fami-