SAN FRANCISCO — The antiviral drug oseltamivir was well tolerated by healthy adults in doses up to 450 mg twice daily, results from a randomized, multicenter, double-blind trial showed.
Oseltamivir (Tamiflu) is Food and Drug Administration–approved for use in adults at a treatment of 75 mg twice daily for 5 days, but “there are some questions about whether or not you might need a higher dose if you a have higher viral load or a more virulent virus,” Regina Dutkowski, Ph.D., said in an interview during a poster session at the annual meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy.
Dr. Dutkowski, medical director in virology at Hoffmann-LaRoche Inc., Nutley, N.J., and her associates studied 391 healthy adult volunteers aged 18-65 years from nine medical centers and randomized them to the following twice-daily dosing regimens of oseltamivir for 5 days: placebo (100), 75 mg (95), 225 mg (97), and 450 mg (99). The volunteers were required to be in good general health with normal vital signs, laboratory tests, and electrocardiograms; and have a body mass index within 40% of accepted normal values. Women were required to comprise at least 40% of the study population. The mean age of patients was 34 years, 53% were female, and 81% were white.
All doses of oseltamivir were well tolerated. Headache was the most common adverse event and occurred in 20% of the placebo group, 17% of the 75-mg group, 24% of the 225-mg group, and 23% of the 450-mg group.
Gastrointestinal events, dizziness, and sensations of heat or hot flushes also were observed and appeared to be dose related. For example, nausea occurred in 8% of the placebo group, 8% of the 75- mg group, 26% of the 225-mg group, and 31% of the 450-mg group; vomiting occurred in 2% of the placebo group, 3% of the 75-mg group, 7% of the 225-mg group, and 16% of the 450-mg group, while feelings of heat or hot flushes occurred in 0% of the placebo group, 2% of the 75-mg group, 3% of the 225-mg group, and 5% of the 450-mg group.
“The safety data from this study are reassuring because they support the known profile that indicates that GI events are associated with the drug,” Dr. Dutkowski said. “What we see here are increases in GI events, but they're not limiting.”
Only four patients withdrew from the trial because of adverse events: two in the placebo group (one case of dermatitis and one mistaken case of QT prolongation) and two in the 225-mg group (one case of urticaria and one case of pruritus).
No apparent effects on cardiac or laboratory parameters were observed.
Hoffmann-La Roche Inc. sponsored the study.