Rimantadine 209

Rarely, seizures may develop in patients with a history of seizures, who are not receiving anticonvulsant medication. In these cases, rimantadine should be discontinued.

Generally, symptoms resolve rapidly after discontinuation of treatment.

The safety and pharmacokinetics of rimantadine in renal and hepatic insufficiency have only been evaluated after single-dose administration. Because of the potential for accumulation of rimantadine and its metabolites in plasma, caution should be exercised when treating patients with renal or hepatic insufficiency.

No well-controlled studies have been done in pregnant women to evaluate the safety of amantadine. We thus recommend that rimantadine is not prescribed for pregnant women. Likewise, rimantadine should not be administered to nursing mothers because of the adverse effects noted in the offspring of rats treated with rimantadine during the nursing period.

Comparative studies indicate that rimantadine is better tolerated than amantadine at equivalent doses (Jefferson 2004). In a direct comparison of prophylactic use of amantadine and rimantadine, more patients on amantadine (13 %) than recipients of rimantadine (6 %) withdrew from the study because of central nervous system side effects (Dolin 1982).

Efficacy

Rimantadine is not active against the avian flu subtype H5N1 strains that have recently caused disease in humans (Li 2004). Rimantadine may be effective for both the prevention and treatment of influenza A infection in “classic” human strains (H1N1, H2N2 and H3N2). The efficacy of rimantadine is comparable to amantadine. In a Cochrane review of 3 placebo-controlled trials on the prophylactic effect of rimantadine, however, rimantadine had only moderate effects on influenza cases and influenza-like illnesses (Jefferson 2006). In treatment, rimantadine significantly shortened the duration of fever but had no or at best moderate effect on nasal shedding of influenza A viruses. The low efficacy of rimantadine together with the relatively high rate of adverse events led the authors to conclude that the use of both M2 ion channel-blocking drugs, rimantadine and amantadine, should be discouraged in seasonal and pandemic influenza (Jefferson 2006) (see also the CDC recommendation in the Introduction).

Treatment

In early trials involving patients with uncomplicated influenza A H3N2 subtype virus infection, rimantadine treatment (200 mg/day for 5 days) was associated with significant reductions in nasal secretion viral titres, maximum temperature, time until defervescence (mean, 37 h shorter), and systemic symptoms compared with placebo (Hayden 1986). Rimantadine seems to be relatively safe even among vaccinated elderly individuals living in nursing homes (Monto 1995). In this population, a dosage reduction to 100 mg/day is recommended. In experimentally infected adults, rimantadine had no effect on nasal patency, mucociliary clearance, nasal signs, or on symptoms and signs of otologic complications (Doyle 1998).

Prophylaxis

Efficacy rates reported from prophylaxis trials vary widely. A review of clinical studies found that rimantadine was 64 % efficacious in prevention, and significantly