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PubMed2005

Lack of effect of moderate hepatic impairment on the pharmacokinetics of oral oseltamivir and its metabolite oseltamivir carboxylate.

AIMS: To compare the pharmacokinetics of oseltamivir and oseltamivir carboxylate in hepatically impaired patients and healthy subjects. METHODS: Hepatically impaired patients (n = 11) and healthy subjects (n = 11) were individually paired on the basis of gender, age (+/-10 years) and body weight (+/-20%) and administered a single dose of oseltamivir (75 mg). RESULTS: Oseltamivir and oseltamivir carboxylate C(max) were < or =6% and < or =19% lower, and their AUC(0,infinity) 33% higher and < or =19% lower, respectively, in hepatically impaired patients compared with healthy subjects. These changes are within the safety limits for the drug. CONCLUSIONS: The metabolism of oseltamivir is not compromised [corrected] in hepatically impaired patients. No dose adjustment is required in these patients when receiving oseltamivir.

Acetamides↗
PubMed2002

Lack of pharmacokinetic interaction between the oral anti-influenza neuraminidase inhibitor prodrug oseltamivir and antacids.

AIMS: Oseltamivir is an oral ester prodrug of its active metabolite Ro 64-0802, a potent and selective neuraminidase inhibitor of the influenza virus. The object of this study was to evaluate whether the oral absorption of oseltamivir was reduced in the presence of two main classes of antacid, Maalox(R) suspension (containing magnesium hydroxide and aluminium hydroxide) and Titralac(R) tablets (containing calcium carbonate). METHODS: Twelve healthy volunteers completed a randomized, single dose, three-period crossover study. Each volunteer received in a fasted state, 150 mg oseltamivir alone (Treatment A), 150 mg oseltamivir with a 20 ml Maalox suspension (Treatment B), and 150 mg oseltamivir with four Titralac tablets (Treatment C), with 7-10 days washout in between treatments. Plasma and urine concentrations of oseltamivir and Ro 64-0802 were measured using a validated h.p.l.c./MS/MS assay. Pharmacokinetic parameters were calculated for oseltamivir and Ro 64-0802. Since antacids are locally acting drugs and generally not expected to be absorbed substantially into the systemic system, no plasma or urine concentrations of antacids were measured. RESULTS: Bioequivalence was achieved for the primary pharmacokinetic parameters Cmax and AUC(0, infinity ) of Ro 64-0802 following administration of oseltamivir with either Maalox suspension or Titralac(R) tablets vs administration of oseltamivir alone. The bioavailability (90% confidence intervals) of Ro 64-0802 following administration of oseltamivir together with Maalox suspension vs administration of oseltamivir alone, was 90% (83.6, 96.9%) for C(max) and 94.1% (91.4, 96.9%) for AUC(0, infinity); similarly, for Titralac tablets, the equivalent values were 95.1% (88.3, 102%) for C(max) and 94.7% (91.9, 97.5%) for AUC(0, infinity). CONCLUSIONS: The coadministration of either Maalox suspension or Titralac tablets with oseltamivir has no effect on the pharmacokinetics of either oseltamivir or Ro 64-0802, and conversely, there is no evidence that coadministration with oseltamivir has an effect on the safety and tolerability of either Maalox suspension or Titralac tablets. There was no pharmacokinetic interaction between oseltamivir with either antacid, demonstrating that the oral absorption of oseltamivir was not impaired in the presence of antacids containing magnesium, aluminium or calcium.

Acetamides↗
PubMed2003

Safety and pharmacology of oseltamivir in clinical use.

Oseltamivir is a novel agent approved for the treatment and prevention of influenza infection and illnesses in adults and children. Assessment of data from the clinical trial programme, a US health insurance database study and postmarketing surveillance allowed a comprehensive review of the safety of oseltamivir in clinical use in subjects >1 year of age. Oseltamivir has been studied over the course of a 5-year development programme in >11000 subjects from North America, Europe and the Southern Hemisphere, including otherwise healthy adults, approximately 500 elderly/high-risk subjects, and children (>1000) aged 1-12 years. Safety evaluations included treatment-emergent adverse events, hospitalisations and deaths, as well as haematological and biochemical laboratory safety tests. The data reveals that oseltamivir has simple, uncomplicated pharmacology and lacks potential for drug-drug interactions. Electrocardiogram parameters, including corrected QT interval, were unaffected by oseltamivir even at high doses. Postmarketing studies confirmed that transient gastrointestinal disturbance is the major adverse effect of oseltamivir and that this can be reduced by taking oseltamivir after a light snack. On treatment serious adverse events were reported in 1.3% of oseltamivir 75mg twice daily, 0.7% of oseltamivir 150 mg twice daily and 1.2% of placebo recipients, respectively, in the clinical trial programme. Postmarketing, it is estimated that, to date, over 4 million oseltamivir prescriptions have been dispensed worldwide. Approximately 2300 spontaneous reports were received by the manufacturer over the three winter seasons of use. As these events are reported infrequently and from an unknown number of users, it is not possible to definitively assess causality or frequency of reported events. Most reports were of gastrointestinal and skin reactions. However, a clear association between the skin reactions and oseltamivir has not been established. A large study of insurance records, which permitted the assessment of the relative risk of medical events treated in the month following prescription of oseltamivir in general use, showed no evidence of increased risk of cardiac, neuropsychiatric or respiratory events for those receiving oseltamivir compared with those who did not. To conclude, no important safety concerns have evolved which might limit the suitability of oseltamivir for the treatment and prevention of influenza in all patient populations.

Acetamides↗
PubMed2000

Efficacy and safety of the oral neuraminidase inhibitor oseltamivir in treating acute influenza: a randomized controlled trial. US Oral Neuraminidase Study Group.

CONTEXT: Previous studies have shown oseltamivir, a neuraminidase inhibitor, to be effective in preventing influenza and treating experimental influenza. OBJECTIVE: To evaluate the efficacy and safety of oseltamivir in the treatment of naturally acquired influenza infection. DESIGN: Randomized, placebo-controlled, double-blind study conducted January through March 1998. SETTING: Sixty primary care and university health centers throughout the United States. PARTICIPANTS: A total of 629 healthy nonimmunized adults aged 18 to 65 years with febrile respiratory illness of no more than 36 hours' duration with temperature of 38 degrees C or more plus at least 1 respiratory symptom and 1 constitutional symptom. INTERVENTIONS: Individuals were randomized to 1 of 3 treatment groups with identical appearing pills: oral oseltamivir phosphate, 75 mg twice daily (n = 211) or 150 mg (n = 209) twice daily, or placebo (n = 209). MAIN OUTCOME MEASURES: Duration and severity of illness in individuals infected with influenza. RESULTS: Two individuals withdrew before receiving medication and were excluded from further analyses. A total of 374 individuals (59.6%) were infected with influenza. Their duration of illness was reduced by more than 30% with both oseltamivir, 75 mg twice daily (median, 71.5 hours; P < .001), and oseltamivir, 150 mg twice daily (median, 69.9 hours; P = .006), compared with placebo (median, 103.3 hours). Severity of illness was reduced by 38% (median score, 597 score-hours; P < .001) with oseltamivir, 75 mg twice daily, and by 35% (median score, 626 score-hours; P < .001) with oseltamivir, 150 mg twice daily, vs placebo (median score, 963 score-hours). Oseltamivir treatment reduced the duration of fever and oseltamivir recipients returned to usual activities 2 to 3 days earlier than placebo recipients (P < or = .05). Secondary complications such as bronchitis and sinusitis occurred in 15% of placebo recipients compared with 7% of combined oseltamivir recipients (P = .03). Among all 629 subjects, oseltamivir reduced illness duration (76.3 hours and 74.3 hours for 75 mg and 150 mg, respectively, vs 97.0 hours for placebo; P = .004 for both comparisons) and illness severity (686 score-hours and 629 score-hours for 75 mg and 150 mg, respectively, vs 887 score-hours for placebo; P < .001 for both comparisons). Nausea and vomiting occurred more frequently in both oseltamivir groups (combined, 18.0% and 14.1%, respectively; P = .002) than in the placebo group (7.4% and 3.4%; P < .001). CONCLUSIONS: Our data suggest that oral oseltamivir treatment reduces the duration and severity of acute influenza in healthy adults and may decrease the incidence of secondary complications.

Acetamides↗
PubMed2001

[A multicenter study of efficacy and safety of oseltamivir in treatment of naturally acquired influenza].

OBJECTIVE: To evaluate the efficacy and safety of oseltamivir in the treatment of naturally acquired influenza in China. METHODS: A randomized, double-blinded, placebo controlled trial of oseltamivir was conducted in China. Individuals of 18 to 65 years were enrolled presenting within 36 hours of influenzal symptoms and elevated temperature of 37.8 or higher. They should have at least two of the following symptoms: nasal congestion, sore throat, cough, myalgia, fatigue, headache, chill and sweating) during an influenza outbreak in the community. Individuals were randomized either to oseltamivir group (75 mg twice daily for 5 days) or placebo group. RESULTS: A total of 478 individuals were recruited, 16(3.35%) failed to follow up or refused to continue the trial, 3 (0.6%) were excluded immediately before taking medication because they did not meet the entry criteria and 8 (1.7%) individuals were excluded in the blinding review meeting because of protocol violation. Altogether 451 individuals were analyzed for efficacy as intent-to-treat population (ITT) (216 oseltamivir, 235 placebo) and 273 individuals were identified as influenza-infected through laboratory test; they were defined as intent-to-treat infected population (ITTI) (134 oseltamivir, 139 placebo). For safety analysis, 459 individuals were included. In ITTI population, the cumulative alleviation proportion in oseltamivir group was significantly higher than that of placebo group (P = 0.046 6). The median duration of illness was 91.6 hours [95% confident interval (CI) 80.2 - 101.3 hours] in oseltamivir group and 95.0 hours (95% CI 84.5 - 105.3 hours) in placebo group. The median area under the curve (AUC) of decreased total score was significantly higher in oseltamivir group than in placebo group, being 1 382.9 and 1 236.7 score-hours respectively (P = 0.019 6). The median duration of fever and myalgia were 27.9 and 35.5 hours in oseltamivir group, being significantly shorter than that of 51.5 and 36.0 hours in placebo group (P = 0.000 1 and 0.036 1). The median AUC of decreased score for fever and nasal symptom was 337.9 and 108.5 in oseltamivir group, being significantly higher than that of 311.3 and 43.3 in placebo group (P = 0.011 8 and 0.040 3). The proportion of subjects reporting fever in oseltamivir group were significantly lower than that in placebo group at 36, 60, 72, 96, 120 and 132 hours after the initiation of treatment (P = 0.049, 0.001, 0.001, 0.007, 0.007 and 0.030). The amount of paracetamol taken, incidence of secondary complications and antibiotics usage associated with secondary complications were similar in the two groups (P = 0.085 1, 0.944, 1.000). For ITT population, similar results were seen. Adverse events reported were similar in oseltamivir and placebo group. The main adverse events were gastrointestinal symptoms, headache, vertigo, and rashes. CONCLUSION: Oseltamivir was effective and well tolerated in the treatment of early naturally acquired influenza.

Acetamides↗
PubMed2001

Long-term use of oseltamivir for the prophylaxis of influenza in a vaccinated frail older population.

OBJECTIVES: To investigate the efficacy of once-daily oral oseltamivir for 6 weeks (Tamiflu) in prophylaxis against laboratory-confirmed clinical influenza in frail older subjects living in homes for seniors and to determine the safety and tolerability of long-term oseltamivir. DESIGN: Double-blind, placebo-controlled, parallel-group, randomized, multicenter study. SETTING: Thirty-one residential homes for seniors across United States and Europe. PARTICIPANTS: Five hundred forty-eight frail older occupants (mean age 81 years, >80% vaccinated). INTERVENTION: Prophylaxis with oseltamivir 75 mg or placebo once daily for 6 weeks, beginning when influenza was detected locally. MEASUREMENTS: The primary efficacy endpoint was laboratory-confirmed clinical influenza. RESULTS: Oseltamivir administration resulted in a 92% reduction in the incidence of laboratory-confirmed clinical influenza compared with placebo (placebo 12/272 (4.4%), oseltamivir 1/276 (0.4%); P = .002). Of subjects vaccinated against influenza, oseltamivir was 91% effective in preventing laboratory-confirmed clinical influenza (placebo 11/218 (5.0%), oseltamivir 1/222 (0.5%); P = .003). Oseltamivir use was associated with a significant reduction in the incidence of secondary complications (placebo 7/272 (2.6%), oseltamivir 1/276 (0.4%); P = .037). Although nearly all subjects were taking concomitant medication both before and during the study, oseltamivir was well tolerated. A similar incidence of adverse events, including gastrointestinal effects, occurred in both groups. There was no suppression of antibody response in oseltamivir recipients. CONCLUSION: Oral oseltamivir 75 mg once daily for 6 weeks effectively prevented clinical influenza in vaccinated frail older subjects using significant concomitant medications in a residential care setting. The treatment was well tolerated and provided additional protection to that afforded by vaccination.

Acetamides↗
PubMed2006

Lower clinical effectiveness of oseltamivir against influenza B contrasted with influenza A infection in children.

BACKGROUND: Recently, many Japanese physicians have claimed that oseltamivir is less effective in children with influenza B virus infection. This study assesses the effectiveness of oseltamivir against influenza A (H3N2) and influenza B in children on the basis of the duration of febrile illness. METHODS: We used oseltamivir to treat 127 children with influenza A (H3N2; mean age, 6.97 years [range, 1-15 years]) and 362 children with influenza B (mean age, 5.16 years [range, 1-15 years]) in outpatient clinics. The duration of fever after the start of oseltamivir therapy was compared in the influenza A group and the influenza B group. RESULTS: The mean duration of fever after the start of oseltamivir therapy was significantly greater in the influenza B group than in the influenza A (H3N2) group (2.18 days vs. 1.31 days, respectively; P<.001). The difference was marked in young children (1-5 years old; 2.37 days for the influenza B group vs. 1.42 days for the influenza A group) but was not significant among older children (11-15 years old). The 50% inhibitory concentration of oseltamivir against influenza B virus was 75.4+/-41.7 nmol/L and was substantially higher than that for type A (H3N2) virus (0.3+/-0.1 nmol/L). Only 3 (1.6%) of 192 influenza B viruses were resistant to oseltamivir. CONCLUSIONS: Oseltamivir is much less effective against influenza B virus infection in young children, probably because of the low sensitivity of influenza B viruses to oseltamivir. The effectiveness of oseltamivir against influenza B is influenced by age and host immunity. A few oseltamivir-resistant influenza B strains were isolated before the start of oseltamivir therapy.

Adolescent↗
PubMed2001

Oseltamivir: a review of its use in influenza.

UNLABELLED: Oseltamivir is a prodrug of oseltamivir carboxylate (Ro 64-0802, GS4071), a potent and selective inhibitor of the neuraminidase glycoprotein essential for replication of influenza A and B viruses. Studies in volunteers with experimental human influenza A or B showed that administration of oral oseltamivir 20 to 200 mg twice daily for 5 days reduced both the quantity and duration of viral shedding compared with placebo. Subsequent assessment of the drug at a dosage of 75 mg twice daily for 5 days in otherwise healthy adults with naturally acquired febrile influenza showed that oseltamivir reduced the duration of the disease by up to 1.5 days and the severity of illness by up to 38% compared with placebo when initiated within 36 hours of symptom onset (earlier initiation of therapy was associated with faster resolution). The incidence of secondary complications and the use of antibacterials were also reduced significantly in oseltamivir recipients. A liquid formulation of oseltamivir (2 mg/kg twice daily for 5 days) has been shown to be effective in the treatment of children with influenza, and data presented in abstracts suggest that the drug may also be of use in high-risk populations such as the elderly or those with chronic cardiac or respiratory disease. In addition to treatment efficacy, the drug has demonstrated efficacy when used for seasonal or household prophylaxis. Oral oseltamivir (75 mg once or twice daily for 6 weeks) during a period of local influenza activity significantly prevented the development of naturally acquired influenza by >70% compared with placebo in unvaccinated otherwise healthy adults. The drug also demonstrated efficacy when used adjunctively in previously vaccinated high-risk elderly patients (92% protective efficacy). Short term administration of oseltamivir (75 mg once daily for 7 days) may significantly reduce the risk of illness in household contacts of infected persons when administered within 48 hours of symptom onset in the infected person. Oseltamivir 75 mg twice daily for 5 days was well tolerated in clinical trials in healthy adults and high-risk patients, with nausea and vomiting being the most commonly reported events. Gastrointestinal events were mild and transient and both nausea and vomiting were less likely when oseltamivir was taken with food. CONCLUSIONS: Oseltamivir is a well tolerated orally active neuraminidase inhibitor which significantly reduces the duration of symptomatic illness and hastens the return to normal levels of activity when initiated promptly in patients with naturally acquired influenza. It therefore represents a useful therapeutic alternative to zanamivir (especially in patients who prefer oral administration or who have an underlying respiratory disorder) and the M2 inhibitors amantadine and rimantadine (because of its broader spectrum of anti-influenza activity and lower likelihood of resistance) in patients with influenza. In addition, although annual vaccination remains the best means of influenza prevention, there may be a place for oseltamivir in providing household prophylaxis or adjunctive prophylaxis in high-risk vaccinated patients during an outbreak of the disease or for use in patients in whom vaccination is unsuitable or ineffective.

Acetamides↗
PubMedDate not supplied

Resistant influenza A viruses in children treated with oseltamivir: descriptive study.

BACKGROUND: Oseltamivir is an effective inhibitor of influenza virus neuraminidase. Although viruses resistant to oseltamivir emerge less frequently than those resistant to amantadine or rimantadine, information on oseltamivir-resistant viruses arising during clinical use of the drug in children is limited. Our aim was to investigate oseltamivir resistance in a group of children treated for influenza. METHODS: We analysed influenza A viruses (H3N2) collected from 50 children before and during treatment with oseltamivir. We sequenced the genes for neuraminidase and haemagglutinin and studied the mutant neuraminidases for their sensitivity to oseltamivir carboxylate. FINDINGS: We found neuraminidase mutations in viruses from nine patients (18%), six of whom had mutations at position 292 (Arg292Lys) and two at position 119 (Glu119Val), which are known to confer resistance to neuraminidase inhibitors. We also identified another mutation (Asn294Ser) in one patient. Sensitivity testing to oseltamivir carboxylate revealed that the neuraminidases of viruses that have an Arg292Lys, Glu119Val, or Asn294Ser mutation were about 10(4)-10(5)-fold, 500-fold, or 300-fold more resistant than their pretreatment neuraminidases, respectively. Oseltamivir-resistant viruses were first detected at day 4 of treatment and on each successive day of the study. More than 10(3) infectious units per mL of virus were detected in some of the patients who did not shed drug-resistant viruses, even after 5 days of treatment. INTERPRETATION: Oseltamivir-resistant mutants in children being treated for influenza with oseltamivir arise more frequently than previously reported. Furthermore, children can be a source of viral transmission, even after 5 days of treatment with oseltamivir.

Acetamides↗
PubMed2001

Oral oseltamivir treatment of influenza in children.

BACKGROUND: Oral oseltamivir administration is effective treatment for influenza in adults. This study was conducted to determine the efficacy, safety and tolerability of oseltamivir in children with influenza. METHODS: In this randomized, double blind, placebo-controlled study, children 1 through 12 years with fever [> or =100 degrees F (> or =38 degrees C)] and a history of cough or coryza <48 h duration received oseltamivir 2 mg/kg/dose or placebo twice daily for 5 days. The primary efficacy endpoint was the time to resolution of illness including mild/absent cough and coryza mild/absent, return to normal activity and euthermia. RESULTS: Of 695 enrolled children 452 (65%) had influenza (placebo, n = 235; oseltamivir, n = 217). Among infected children the median duration of illness was reduced by 36 h (26%) in oseltamivir compared with placebo recipients (101 h; 95% confidence interval, 89 to 118 vs. 137 h; 95% confidence interval, 125 to 150; P < 0.0001). Oseltamivir treatment also reduced cough, coryza and duration of fever. New diagnoses of otitis media were reduced by 44% (12% vs. 21%). The incidence of physician-prescribed antibiotics was significantly lower in influenza-infected oseltamivir (68 of 217, 31%) than placebo (97 of 235, 41%; P = 0.03) recipients. Oseltamivir therapy was generally well-tolerated, although associated with an excess frequency of emesis (5.8%). Discontinuation because of adverse events was low in both groups (1.8% with oseltamivir vs. 1.1% with placebo). Oseltamivir treatment did not affect the influenza-specific antibody response. CONCLUSIONS: Oral oseltamivir administration is an efficacious and well-tolerated therapy for influenza in children when given within 48 h of onset of illness.

Acetamides↗
PubMed2006

Pharmacokinetics of oseltamivir in young and very elderly subjects.

BACKGROUND: Pharmacokinetic studies of oseltamivir in very elderly patients (> or = 80 y) have not previously been performed. OBJECTIVE: To compare the pharmacokinetics of oseltamivir and the active carboxylate metabolite in healthy young and very elderly Japanese subjects. METHODS: Young (20-35 y, fasting, n = 7) and very elderly subjects (> or = 80 y, fed, n = 5) were enrolled in single-center studies and received a single oral dose of oseltamivir 75 mg. Plasma and urine samples were collected (24 h) for pharmacokinetic analysis, and safety was assessed. RESULTS: The time to maximum plasma concentration (tmax) for oseltamivir was delayed in the very elderly compared with the young subjects (2.30 vs 0.71 h, respectively). Furthermore, oseltamivir maximum plasma concentration (Cmax) and AUC(inf) were 52% and 80% higher, respectively, in the very elderly compared with the young subjects. Oral clearance was 45% lower in elderly patients, possibly due to the effects of administration of oseltamivir with a meal. For the active metabolite, oseltamivir carboxylate, Cmax and AUC(inf) values were, respectively, 22% and 91% higher in the very elderly subjects than in the young subjects, while oral clearance was 50% lower in the elderly population. The increased exposure of the active metabolite is likely to correlate with an age-related decline in renal function. For both oseltamivir and the active metabolite, there was large interpatient variability in the Cmax values. The data reported here indicate that oseltamivir would be effective in both of these populations, as trough concentrations for the active metabolite at 12 and 24 hours exceeded the 50% inhibitory concentration against the neuraminidase of influenza A and B isolates by more than 50-fold. Oseltamivir was well tolerated in both groups. CONCLUSIONS: Exposures (AUC(inf)) to both the parent drug and active metabolite were increased by more than 80% in the small number of very elderly subjects presented here. However, oseltamivir was well tolerated by these subjects.

Adult↗
PubMed2004

Skin reactions in patients with influenza treated with oseltamivir: a retrospective cohort study.

Oseltamivir phosphate is an FDA-approved treatment for influenza that has been available for prescription use in the USA since 1999. The present report describes findings from a post-marketing safety study of skin reactions associated with oseltamivir use. All patients in the claims-derived Ingenix Research Database with a physician diagnosis of influenza and/or a dispensing of oseltamivir between 1 December 1999 and 31 March 2002 were identified. Cohort eligibility criteria included minimum baseline enrolment duration of 3 months, age of at least 1 year and no influenza vaccination on the date of influenza diagnosis or oseltamivir dispensing. Patients were classified into two primary cohorts, influenza diagnosis and oseltamivir dispensing on the same day, and influenza diagnosis but no oseltamivir at any time, and a cohort included for secondary analyses comprising patients who received an oseltamivir dispensing without an influenza diagnosis on the same day. Outcomes included general skin reactions and several specific skin reactions. Events occurring during the 30 days following the date of influenza diagnosis or oseltamivir dispensing were examined using Cox proportional hazards models. Model covariates included age, use of another influenza drug, month and year of index date, and use of antitussives. Adjusted rate ratios for the general class of skin reactions among the primary cohort of oseltamivir users versus non-users were 1.05 (95% CI: 0.88-1.24) for incident cases and 0.98 (95% CI: 0.77-1.24) among patients with a history of a skin reaction. Similar results were seen for the other skin reaction categories, and secondary analyses investigating the oseltamivir users without influenza revealed no elevation in risk. It is concluded that oseltamivir use does not appear to be associated with an increased risk of skin reactions.

Acetamides↗
PubMed1999

Use of the selective oral neuraminidase inhibitor oseltamivir to prevent influenza.

BACKGROUND: Safe and effective antiviral agents are needed to prevent infection with influenza A and B virus. Oseltamivir (GS4104), which can be administered orally, is the prodrug of GS4071, a potent and selective inhibitor of influenzavirus neuraminidases. We studied the use of oseltamivir for long-term prophylaxis against influenza in two placebo-controlled, double-blind trials at different U.S. sites during the winter of 1997-1998. METHODS: We randomly assigned 1559 healthy, nonimmunized adults 18 to 65 years old to receive either oral oseltamivir (75 mg given once or twice daily, for a total daily dose of 75 or 150 mg) or placebo for six weeks during a peak period of local influenzavirus activity. The primary end point with respect to efficacy was laboratory-confirmed influenza-like illness (defined as a temperature of at least 37.2 degrees C accompanied by at least one respiratory and at least one systemic symptom). RESULTS: In the two studies combined, the risk of influenza among subjects assigned to either once-daily or twice-daily oseltamivir (1.2 percent and 1.3 percent, respectively) was lower than that among subjects assigned to placebo (4.8 percent; P<0.001 and P=0.001 for the comparison with once-daily and twice-daily oseltamivir, respectively). The protective efficacy of oseltamivir in the two active-treatment groups combined was 74 percent (95 percent confidence interval, 53 to 88 percent) at all the sites combined and 82 percent (95 percent confidence interval, 60 to 93 percent) at sites in Virginia, where the rate of influenza infection was higher than the overall rate. For culture-proved influenza, the rate of protective efficacy in the two oseltamivir groups combined was 87 percent (95 percent confidence interval, 65 to 96 percent). The rate of laboratory-confirmed influenza infection was lower with oseltamivir than with placebo (5.3 percent vs. 10.6 percent, P<0.001). Oseltamivir was well tolerated but was associated with a greater frequency of nausea (12.1 percent and 14.6 percent in the once-daily and twice-daily groups, respectively) and vomiting (2.5 percent and 2.7 percent, respectively) than was placebo (nausea, 7.1 percent; vomiting, 0.8 percent). However, the frequency of premature discontinuation of drug or placebo was similar among the three groups (3.1 to 4.0 percent). CONCLUSIONS: Oseltamivir administered daily for six weeks by the oral route is safe and effective for the prevention of influenza.

Administration, Oral↗
PubMed2003

A double-blind, randomized, placebo-controlled multicenter study of oseltamivir phosphate for treatment of influenza infection in China.

OBJECTIVE: To evaluate the efficacy and safety of oseltamivir phosphate as treatment for naturally acquired influenza infection. METHODS: This study was conducted as a double-blind, randomized, placebo-controlled, multicenter trial during the influenza epidemic season from January to April 2001 at 7 centers in China. A total of 478 adults without other medical history, aged 18 to 65 years, were enrolled into the study. All subjects demonstrated febrile respiratory illness of no more than 36 hours' duration with a temperature of 37.8 degrees C or more plus at least two of the following symptoms: coryza/nasal congestion, sore throat, cough, myalgia/muscles aches and pain, fatigue, headache or chills/sweats. Individuals were randomized into either the oseltamivir phosphate or placebo group with identical-looking capsules. Either oral oseltamivir phosphate, 75 mg twice daily, or placebo was administered to the subjects for 5 days. RESULTS: A total of 451 individuals were analyzed for efficacy as the intent-to-treat population (ITT) (216 oseltamivir and 235 placebo) and 273 individuals were identified as influenza-infected through laboratory test, who were then defined as the intent-to-treat infected population (ITTI) (134 oseltamivir and 139 placebo). Four hundred and fifty nine individuals were included in the safety analysis. In the ITTI population, the cumulative alleviation proportion of oseltamivir group was significantly higher than that of the placebo group (P = 0.0466)). The median duration of illness was 91.6 h [95% confidence interval (CI) = 80.2 - 101.3 h] in the oseltamivir group and 95 h (95% CI = 84.5 - 105.3 h) in the placebo group. The median area under the curve of decreased total score was significantly higher in the oseltamivir group than in the placebo group, 1382.9 and 1236.7 score-hours, respectively (P = 0.0196). For the ITT population, similar results were observed. Adverse events (AE) were similarly reported in both the oseltamivir group and the placebo group. The main adverse events following test drug were gastrointestinal symptoms, neurological symptoms and rashes. CONCLUSION: Oseltamivir was effective and well tolerated as treatment of early naturally acquired influenza.

Acetamides↗
PubMed2004

[A multicenter randomized controlled study of the efficacy and safety of oseltamivir in the treatment of influenza in a high risk population].

OBJECTIVE: To evaluate the efficacy and safety of oseltamivir in the treatment of influenza in a high risk population. METHODS: A randomized, open, control trial was conducted from Nov. 2002 to Feb. 2003. Patients with chronic respiratory disease, such as chronic bronchitis, obstructive emphysema, bronchial asthma, bronchiectasis or chronic cardiac disease, and with symptoms of influenza were enrolled. They should satisfy the following criteria: Fever > or = 37.8 degrees C plus at least two of the following influenza symptoms: coryza/nasal congestion, sore throat, cough, myalgia/muscle aches and pain, fatigue, headache and chills/sweats. Within 48 h after the onset of the symptoms, the patients were randomly assigned to oseltamivir group (oseltamivir 75 mg, twice daily for 5 days) or control group (symptom relief medicine only). RESULTS: Fifty-six of the 108 recruited patients were identified as influenza-infected through laboratory test. They were defined as intent-to-treat infected population (ITTI) (27 oseltamivir, 29 control). The duration of influenza symptom was 64 h shorter (36.7%) and AUC score of the influenza symptom was decreased by 618 (43.1%) in the oseltamivir group as compared with those in the control group. The fever duration was 46.8 h (45.0%) less in the oseltamivir group than that in the control group. It took 6 d for the oseltamivir group and 11 days for the control group to recover to the basic health status. Secondary complications such as bronchitis, sinusitis and pneumonia occurred 11% (3/27) in the oseltamivir group and 45% (13/29) in the control group. The treatment expense for influenza and its complication was 587.4 RMB in the oseltamivir group and 786.5 RMB in the control group, which showed no significant difference (P = 0.246). CONCLUSIONS: It is suggested that oseltamivir is effective and well tolerated in patients with chronic respiratory or cardiac diseases. It can reduce the fever duration and severity of influenza symptom, and decrease the incidence of secondary complications and antibiotic use, while does not increase the total medical cost.

Acetamides↗
PubMed2001

Effectiveness of oseltamivir in preventing influenza in household contacts: a randomized controlled trial.

CONTEXT: Influenza virus is easily spread among the household contacts of an infected person, and prevention of influenza in household contacts can control spread of influenza in the community. OBJECTIVE: To investigate the efficacy of oseltamivir in preventing spread of influenza to household contacts of influenza-infected index cases (ICs). DESIGN AND SETTING: Randomized, double-blind, placebo-controlled study conducted at 76 centers in North America and Europe during the winter of 1998-1999. PARTICIPANTS: Three hundred seventy-seven ICs, 163 (43%) of whom had laboratory-confirmed influenza infection, and 955 household contacts (aged >/=12 years) of all ICs (415 contacts of influenza-positive ICs). INTERVENTIONS: Household contacts were randomly assigned by household cluster to take 75 mg of oseltamivir (n = 493) or placebo (n = 462) once daily for 7 days within 48 hours of symptom onset in the IC. The ICs did not receive antiviral treatment. MAIN OUTCOME MEASURE: Clinical influenza in contacts of influenza-positive ICs, confirmed in a laboratory by detection of virus shedding in nose and throat swabs or a 4-fold or greater increase in influenza-specific serum antibody titer between baseline and convalescent serum samples. RESULTS: In contacts of an influenza-positive IC, the overall protective efficacy of oseltamivir against clinical influenza was 89% for individuals (95% confidence interval [CI], 67%-97%; P<.001) and 84% for households (95% CI, 49%-95%; P<.001). In contacts of all ICs, oseltamivir also significantly reduced incidence of clinical influenza, with 89% protective efficacy (95% CI, 71%-96%; P<.001). Viral shedding was inhibited in contacts taking oseltamivir, with 84% protective efficacy (95% CI, 57%-95%; P<.001). All virus isolates from oseltamivir recipients retained sensitivity to the active metabolite. Oseltamivir was well tolerated; gastrointestinal tract effects were reported with similar frequency in oseltamivir (9.3%) and placebo (7.2%) recipients. CONCLUSION: In our sample, postexposure prophylaxis with oseltamivir, 75 mg once daily for 7 days, protected close contacts of influenza-infected persons against influenza illness, prevented outbreaks within households, and was well tolerated.

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