Oseltamivir: A New Option for the Management of Influenza in Children

Marcia L. Buck, Pharm.D., FCCP

Pediatr Pharm. 2001;7(2) 

In This Article

Clinical Trials

Oseltamivir has been shown to be effective in the prevention of influenza infection in adolescents and adults if taken within 48 hours of exposure. As part of a combined prophylaxis/treatment trial published in the October 6, 1999 issue of JAMA, Hayden and colleagues evaluated the safety and efficacy of oseltamivir in adults (ages 18-40 years).[9] The prophylaxis arm involved 33 volunteers who were given 100 mg oseltamivir orally, either once or twice daily, or placebo for 5 days. Subjects began therapy 26 hours prior to being innoculated with influenza virus. Eight (67%) of the 12 subjects given placebo became infected after being exposed to the influenza virus, compared with eight (38%) of the 21 given oseltamivir. A third of the placebo recipients developed clinical symptoms of influenza; none of the oseltamivir-treated subjects became ill. Fifty percent of the subjects in the placebo group shed virus, while none of the group given oseltamivir had documented viral shedding.

A larger trial was published later that month in the New England Journal of Medicine. Hayden et al (as the Oseltamivir Study Group) enrolled 1,559 adults in a study of oseltamivir prophylaxis.[10] Subjects received oseltamivir 75 mg, either once or twice daily, or placebo for 6 weeks during peak influenza season. The primary end point of the study was laboratory- confirmed influenza illness (based on the presence of a fever, respiratory and systemic symptoms). The rate of influenza illness was significantly reduced in the oseltamivir group (5.3% versus 10.6% for placebo). The protective efficacy of oseltamivir was found to be 74% overall. Neither the results of this study, nor the one described earlier, showed a significant difference between once and twice daily dosing. In both of these trials, the authors concluded that oseltamivir was safe and effective for the prevention of influenza infection in adults.

In the treatment arm of the initial JAMA paper, Hayden and colleagues reported the results of oseltamivir versus placebo in 69 adult subjects innoculated with influenza virus in a controlled setting.[9] The authors reported that oseltamivir significantly reduced the viral titer area under the curve compared to placebo. Oseltamivir-treated subjects also had a reduction in the duration of viral shedding (58 hours for the combined treatment groups versus 107 hours for placebo). In addition, symptom scores and nasal proinflammatory cytokine levels were lower in the subjects receiving oseltamivir.

In the February 23, 2000 issue of JAMA, many of these same investigators, as the United States Oral Neuraminidase Study Group, published the results of a randomized, placebo-controlled, double-blind treatment study conducted in 60 healthcare centers.[11] A total of 629 adults were enrolled within 36 hours of onset of influenza-like symptoms. Subjects were given oseltamivir, 75 or 150 mg twice daily, or placebo. Three hundred and seventy-four patients became infected and were evaluated for response. Oseltamivir reduced the duration of illness by more than 30% compared to placebo in infected patients. Severity of illness scores were reduced by 38%. Oseltamivir use also significantly reduced the duration of fever (average 71.5 hours for the 75 mg group and 69.9 hours for the 150 mg group, versus 103.3 hours for the placebo group) and allowed subjects to return to usual activities 2-3 days sooner than placebo.

Three months later, Nicholson and colleagues reported the results of a multinational trial of oseltamivir for the treatment of influenza in TheLancet.[12] Seven hundred and twenty-six patients were enrolled throughout Europe, Canada, and China. As in the previous study, subjects were randomized to receive either 75 mg or 150 mg oseltamivir or placebo twice daily for 5 days. Duration of illness was significantly shorter in both treatment groups compared to placebo. The median duration was 87.4 hours for the 75 mg dose, 81.8 hours for the 150 mg dose, and 116.5 hours for placebo, similar to the results seen in the paper from the Oral Neuraminidase Study Group. Oseltamivir use was associated with improved symptom scores, less viral shedding, and subjective improvements in health, activity levels, and sleep quality.

While these studies have established the utility of oseltamivir in adults, data on its use in children have only recently become available. In a double-blind, placebo-controlled trial enrolling children between 1 and 12 years of age, oseltamivir, when started within 48 hours of symptoms, significantly reduced the length of illness. On average, resolution of symptoms occurred 1.5 days sooner in the oseltamivir-treated children than in the placebo group. The oseltamivir dose used in this study, 2 mg/kg given twice daily, became the foundation for the dosage recommendations now provided by the manufacturer.[5]

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