218 Drug Profiles

Drug Interactions

Zanamivir is administered via inhalation and the low level of absorption of the drug results in low serum concentrations and modest systemic exposure to zanamivir after inhalation. Zanamivir is not metabolised, and the potential for clinically relevant drug-drug interactions is low (Cass 1999b). Zanamivir is not a substrate nor does it affect cytochrome P450 (CYP) isoenzymes (CYP1A1/2, 2A6, 2C9, 2C18, 2D6, 2E1, and 3A4) in human liver microsomes (Relenza 2003). There is no theoretical basis for expecting metabolic interactions between zanamivir and other coadministered compounds (Daniel 1999).

Recommendations for Use

•Zanamivir is indicated for the treatment of uncomplicated acute illness due to

influenza A and B viruses in adults and paediatric patients (EU: 12 years or older; US: 7 years and older) who have been symptomatic for no more than

2 days.

•Zanamivir is not recommended for the treatment of patients with underlying airways disease (such as asthma or chronic obstructive pulmonary disease).

Zanamivir (Relenza®) is delivered by inhalation because of its low oral bioavailability. Each Relenza® Rotadisk contains 4 double-foil blisters and each blister contains 5 mg of zanamivir (plus 20 mg of lactose which contains milk proteins). The contents of each blister are inhaled using a plastic device called a “Diskhaler”. Here, a blister is pierced and zanamivir is dispersed into the air stream when the patient inhales through the mouthpiece. The amount of drug delivered to the respiratory tract depends on patient factors such as inspiratory flow.

Patients should be instructed in the use of the delivery system, and instructions should include a demonstration – which may be difficult in daily medical practice. When prescribed for children, zanamivir should only be used under adult supervision and instruction.

There has been concern over the ability of elderly people to use the inhaling device for zanamivir. A study of 73 patients (aged 71 to 99 years) from wards providing acute elderly care in a large general hospital found that most elderly people could not use the inhaler device and that zanamivir treatment for elderly people with influenza was unlikely to be effective (Diggory 2001).

Dosage

The recommended dose of zanamivir for the treatment of influenza in adults and paediatric patients aged 7 years and older is 10 mg bid (= twice daily 2 consecutive inhalations of one 5-mg blister) for 5 days.

On the first day of treatment, two doses should be taken at least 2 hours apart. On the following days, doses should be taken about 12 hours apart.

No dosage adjustment is required in patients with renal impairment (Cass 1999a).

Patients with pulmonary dysfunction should always have a fast-acting bronchodilator available and discontinue zanamivir if respiratory difficulty develops.