210 Drug Profiles

shortened the duration of fever by 1.27 days (Demicheli 2000). Rimantadine may also be effective in children (Clover 1986, Crawford 1988).

Resistance

Point mutations in the M gene leading to amino acid changes in the M2 protein may lead to high-level resistance to rimantadine. The mutants are as virulent and have been shown to be as transmissible as wild-type virus and to cause a typical influenza illness. Such strains may develop in up to one third of treated patients, although in immunocompromised individuals, the percentage may be even higher (Englund 1998). Drug-resistant influenza A virus (H3N2) can be recovered from rimantadine-treated children and adults as early as 2 days after starting treatment (Hayden 1991).

Transmissibility is an important aspect when using rimantadine. An early study demonstrated failure of prevention of influenza infection due to apparent transmission of drug-resistant viral strains. The study concluded that rimantadine was ineffective in protecting household members from influenza A infection (Hayden 1989).

Avian influenza virus subtype H5N1, which has been associated with the human disease in East Asia between late 2003 and early 2004, is resistant to rimantadine (asparagine residue at position 31 of the M2 protein) (Li 2004).

Over the last decade, drug resistance to amantadine and rimantadine has increased from 0.4 % to 12.3 % (Bright 2005).

Drug Interactions

No clinically substantial interactions between rimantadine and other drugs have been identified. Cimetidine seems to reduce rimantadine clearance by 18 % (Holazo 1989). Acetaminophen reduces the peak concentration and AUC values of rimantadine by 11 %. Aspirin reduces the peak plasma concentrations and the AUC of rimantadine by approximately 10 %.

Recommendations for Use

In the EU, medicinal products containing rimantadine have been approved nationally (for additional information, please check the prescribing information).

In the US, rimantadine is licensed for prophylaxis in adults and children. For treatment, rimantadine is licensed for adults only. Rimantadine (Flumadine®) is available as 100 mg film-coated tablets and as syrup for oral administration.

Adults

In the US, the recommended dose for both prophylaxis and treatment is 100 mg bid.

A dose reduction to 100 mg daily is recommended in patients with

•severe hepatic dysfunction

•renal failure (CrCl ≤ 10 ml/min)

•elderly nursing home patients (Patriarca 1984, Monto 1995).