Brief Summary
This 2-arm study will investigate the safety and tolerability of oseltamivir for the treatment of influenza in immunocompromised participants and characterize the effects of oseltamivir in immunocompromised participants on the development of resistant influenza virus. Eligible immunocompromised participants with laboratory-confirmed influenza will be randomized to receive either conventional dose (30 milligrams \[mg\] to 75 mg twice daily orally \[po\], depending on age and weight) or double dose (60 mg-150 mg twice daily po depending on age and weight) olseltamivir for 10 days. Nasal and throat swabs will be taken, and safety evaluations made, at intervals during the study. The anticipated time on study medication is 10 days and the anticipated time on study is 40 days.
Brief Title
A Study of Oseltamivir (Tamiflu) for Treatment of Influenza in Immunocompromised Participants.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Influenza, Human
Eligibility Criteria
Inclusion Criteria:
* Rapid diagnostic test, PCR, or viral culture positive for influenza in the 96 hours prior to first dose
* Immunocompromised participants with primary or secondary immunodeficiency
* Symptoms suggestive of influenza-like illness
* Use of an effective contraceptive, as specified by protocol; women of childbearing potential cannot be pregnant or breastfeeding
Exclusion Criteria:
* Influenza vaccination with live attenuated vaccine in the 2 weeks prior to randomization
* Antiviral treatment for influenza in 2 weeks prior to randomization
* Severe hepatic impairment
* Any current renal replacement therapy
* Any gastrointestinal disorders which may interfere with the absorption of oseltamivir
* Participation in a study with an investigational drug from 4 weeks prior to study start until study end
* Rapid diagnostic test, PCR, or viral culture positive for influenza in the 96 hours prior to first dose
* Immunocompromised participants with primary or secondary immunodeficiency
* Symptoms suggestive of influenza-like illness
* Use of an effective contraceptive, as specified by protocol; women of childbearing potential cannot be pregnant or breastfeeding
Exclusion Criteria:
* Influenza vaccination with live attenuated vaccine in the 2 weeks prior to randomization
* Antiviral treatment for influenza in 2 weeks prior to randomization
* Severe hepatic impairment
* Any current renal replacement therapy
* Any gastrointestinal disorders which may interfere with the absorption of oseltamivir
* Participation in a study with an investigational drug from 4 weeks prior to study start until study end
Inclusion Criteria
Inclusion Criteria:
* Rapid diagnostic test, PCR, or viral culture positive for influenza in the 96 hours prior to first dose
* Immunocompromised participants with primary or secondary immunodeficiency
* Symptoms suggestive of influenza-like illness
* Use of an effective contraceptive, as specified by protocol; women of childbearing potential cannot be pregnant or breastfeeding
* Rapid diagnostic test, PCR, or viral culture positive for influenza in the 96 hours prior to first dose
* Immunocompromised participants with primary or secondary immunodeficiency
* Symptoms suggestive of influenza-like illness
* Use of an effective contraceptive, as specified by protocol; women of childbearing potential cannot be pregnant or breastfeeding
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
1 Year
NCT Id
NCT00545532
Org Class
Industry
Org Full Name
Hoffmann-La Roche
Org Study Id
NV20234
Overall Status
Completed
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Double-Blind, Randomized, Stratified Multi-Center Trial Evaluating Conventional and Double Dose Oseltamivir in the Treatment of Immunocompromised Patients With Influenza
Primary Outcomes
Outcome Description
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Outcome Measure
Percentage of Participants With Adverse Events
Outcome Time Frame
Baseline up to Day 40
Outcome Description
Resistance was defined as the presence of oseltamivir resistance mutations in viruses isolated from nasopharyngeal swab samples, identified by sequencing of the neuraminidase (NA) and hemagglutinin (HA) genes (genotypic resistance) and/or determination of the oseltamivir concentration at which the response is reduced by half (IC50) in an NA inhibition assay (phenotypic resistance). Reported are post-baseline phenotypic and genotypic resistance in adults \>/= 18 years and children and adolescents \<18 years in the modified Intent-to-Treat infected (mITTi) population.
Outcome Measure
Percentage of Participants Who Developed Viral Resistance to Oseltamivir
Outcome Time Frame
Baseline up to Day 40
Outcome Description
The percentage of transplant patients in the safety population who experienced tissue rejection and/or GvHD is reported.
Outcome Measure
Percentage of Participants With Tissue Rejection or Graft Versus Host Disease (GVHD)
Outcome Time Frame
Baseline up to Day 40
Secondary Ids
Secondary Id
2006-002468-24
Secondary Outcomes
Outcome Description
TTR of all clinical influenza symptoms was defined as the time from treatment initiation to the start of the 24-hour period in which all 7 influenza symptoms had scores \</= 1 (mild) and remained \</=1 for at least 21.5 hours. . Reported are TTRs in adults \>/= 18 years, adults and adolescents \>/= 13 years and children \<13 years in the mITTi population.
Outcome Time Frame
Baseline up to Day 40
Outcome Measure
Time to Resolution (TTR) of All Clinical Influenza Symptoms
Outcome Description
The overall extent and severity of illness was quantified by the AUE of the total symptom scores over the duration of illness, i.e., from the start of treatment to the time symptoms first alleviated. Total symptom scores were calculated from the sum of seven individual symptom scores with each individual symptom scored from 0 (healthy) to 3 (worst sickness) and a maximum total symptom score of 21. The AUE of these average scores was then calculated for each participant using the trapezoidal rule (the trapezoidal rule calculates the area under any curve by adding up all trapezoids under such a curve). A larger area indicates more severe disease. In this study participants were treated for 10 days. If a participant had scored 21 on every visit then AUE would have been 21 score x 10 days x 24 hours/day =5040 score x hours units, which is the highest possible score. The lowest possible score is 0. Reported are results for adults \>/= 18 years in the mITTi population.
Outcome Time Frame
Baseline up to Day 40
Outcome Measure
Total Symptom Score Area Under the Efficacy Curve (AUE)
Outcome Description
Fever was defined as temperature \>/= 37.8 degrees Celsius at any time point during the study. TTR of fever was determined in Adults \>/= 18 years, Adults and adolescents \>/= 13 years and Children \< 13 years of the mITTi population.
Outcome Time Frame
Baseline up to Day 40
Outcome Measure
Time to Resolution of Fever
Outcome Description
Nasopharyngeal swab samples were cultured in Madin-Darby Canine Kidney cells. Culture supernatants were harvested after 2 weeks, or after a full-blown cytopathic effect was observed. Presence of infectious viruses in the cell culture supernatants (viral titer), expressed as log10 50% Tissue Culture Infectious Dose/milliliter (TCID50/mL), was determined by hemagglutination assay using turkey erythrocytes for H1 and B viruses or by detection of the virus nucleoprotein (NP) using ELISA for H3 viruses. A value of \< 0.5 log10 TCID50/mL was interpreted as negative. Data are reported for adults \>/= 18 years and adolescents and children \< 18 years.
Outcome Time Frame
Baseline (Day 1), Day 2/3, Day 6, Day 8, Day 11 end of treatment (EOT), follow-up (FU) Day 15 and FU Day 40.
Outcome Measure
Change From Baseline in Viral Load Assessed by Culture
Outcome Description
Viral shedding was determined through measurement of the viral titer after viral culture in Madin-Darby Canine Kidney cells by hemagglutination assay (for Flu A/H1N1 and Flu B) and NP-ELISA (for Flu A/H3N2) and expressed in log10 TCID50/mL. Reported is the percentage of participants with viral shedding over time in adults \>/= 18 years and adolescents and children \< 18 years.
Outcome Time Frame
Baseline (Day 1), Day 2/3, Day 6, Day 8, Day 11 end of treatment (EOT), follow-up (FU) Day 15 and FU Day 40.
Outcome Measure
Percentage of Participants With Viral Shedding Assessed by Culture Over Time
Outcome Description
Viral shedding was determined through measurement of the viral titer after viral culture in Madin-Darby Canine Kidney cells by hemagglutination assay (for Flu A/H1N1 and Flu B) and NP-ELISA (for Flu A/H3N2) and expressed in log10 TCID50/mL. Reported is the time to cessation of viral shedding over time in adults \>/= 18 years and adolescents and children \< 18 years.
Outcome Time Frame
Baseline up to Day 40
Outcome Measure
Time to Cessation of Viral Shedding by Cell Culture
Outcome Description
Nasopharyngeal swab samples were tested for influenza A and B RNA using semi-quantitative RT-PCR specific for influenza A and B matrix gene, respectively, after viral RNA isolation. Cycle threshold (Ct) value was determined for each sample. Conversion of Ct values into viral load, expressed as log10 virus particles/mL (vp/mL), was obtained using external standard curves ran in parallel in all RT-PCR experiments. A value of \< 2.6 log10 vp/mL for Flu A strains and \< 3.0 log10 vp/mL for Flu B strains was interpreted as a negative result. Data are reported for adults \>/= 18 years and adolescents and children \< 18 years.
Outcome Time Frame
Baseline (Day 1), Day 2/3, Day 6, Day 8, Day 11 end of treatment (EOT), follow-up (FU) Day 15 and FU Day 40.
Outcome Measure
Change From Baseline in Viral Load Assessed by Reverse Transcription Polymerase Chain Reaction (RT-PCR)
Outcome Description
Viral shedding was determined by direct viral load measurement from nasopharyngeal swabs by RT-PCR assay and expressed in log10 vp/mL. Reported is the percentage of subjects with viral shedding over time in adults \>/= 18 years and adolescents and children \< 18 years.
Outcome Time Frame
Baseline (Day 1), Day 2/3, Day 6, Day 8, Day 11 end of treatment (EOT), follow-up (FU) Day 15 and FU Day 40.
Outcome Measure
Percentage of Participants With Viral Shedding Assessed by RT-PCR Over Time
Outcome Description
Viral shedding was determined by direct viral load measurement from nasopharyngeal swabs by RT-PCR assay and expressed in log10 vp/mL. Reported is the time to cessation of viral shedding over time in adults \>/= 18 years and adolescents and children \< 18 years.
Outcome Time Frame
Baseline up to Day 40
Outcome Measure
Time to Cessation of Viral Shedding by RT-PCR
Outcome Description
Persistent shedding was defined as a viral load reduction \<1 log10 vp/mL at end of treatment compared with baseline. Reported is the percentage of participants with persistent viral shedding at end of treatment in adults \>/= 18 years and adolescents and children \< 18 years.
Outcome Time Frame
Baseline to Day 11 (EOT)
Outcome Measure
Percentage of Participants With Persistent Viral Shedding
Outcome Description
Secondary illness included bronchitis, pneumonia, acute sinusitis, sinusitis, lower respiratory infection or otitis media. Reported is the percentage of participants with at least one event in adults \>/= 18 years and adolescents and children \< 18 years.
Outcome Time Frame
Baseline up to Day 40
Outcome Measure
Percentage of Participants Who Developed Secondary Illness
Outcome Description
Secondary illness included bronchitis, pneumonia, acute sinusitis, sinusitis, lower respiratory infection or otitis media. Reported is the percentage of participants with secondary illness, who initiated antibiotic treatment, in adults \>/= 18 years and adolescents and children \< 18 years.
Outcome Time Frame
Baseline up to Day 40
Outcome Measure
Percentage of Participants Who Initiated Antibiotic Treatment
Outcome Description
Reported is the percentage of participants, who required hospitalization at any time between treatment initiation and the end of the study period, in adults \>/= 18 years and adolescents and children \< 18 years.
Outcome Time Frame
Baseline up to Day 40
Outcome Measure
Percentage of Participants Hospitalized
Outcome Description
Reported is the duration of hospitalization at any time between treatment initiation and the end of the study period, in adults \>/= 18 years and adolescents and children \< 18 years.
Outcome Time Frame
Baseline up to Day 40
Outcome Measure
Duration of Hospitalization
Outcome Description
Reported here are oseltamivir Cmax data for adults \>/= 18 years.
Outcome Time Frame
Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose
Outcome Measure
Pharmacokinetics: Maximum Plasma Concentration (Cmax) of Oseltamivir in Adults
Outcome Description
Reported here are oseltamivir Ctrough data for adults \>/= 18 years.
Outcome Time Frame
Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose
Outcome Measure
Pharmacokinetics: Trough Plasma Concentration (Ctrough) of Oseltamivir in Adults
Outcome Description
AUC0-12 was reported at steady state as nanograms per hour per milliliter. (ng\*hr/mL). Reported here are oseltamivir AUC0-12 data for adults \>/= 18 years.
Outcome Time Frame
Pre-dose (30 minutes), 1.5, 4, 8 hours on Day 6 or any day after the 11th dose
Outcome Measure
Pharmacokinetics : Area Under the Concentration-Time Curve From 0 to 12 Hours (AUC0-12) at Steady State of Oseltamivir in Adults
Outcome Description
Reported here are oseltamivir tmax data for adults \>/= 18 years.
Outcome Time Frame
Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose
Outcome Measure
Pharmacokinetics: Time to Maximum Concentration (Tmax) of Oseltamivir in Adults
Outcome Description
Reported here are oseltamivir ke data for adults \>/= 18 years.
Outcome Time Frame
Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose
Outcome Measure
Pharmacokinetics: Elimination Constant (ke) of Oseltamivir in Adults
Outcome Description
Reported here are oseltamivir CL/F data for adults \>/= 18 years.
Outcome Time Frame
Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose
Outcome Measure
Pharmacokinetics: Apparent Clearance (CL/F) of Oseltamivir in Adults
Outcome Description
Reported here are oseltamivir Vc/F data for adults \>/= 18 years.
Outcome Time Frame
Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose
Outcome Measure
Pharmacokinetics: Apparent Volume of Distribution (Vc/F) of Oseltamivir in Adults
Outcome Description
Reported here are oseltamivir carboxylate Cmax data for adults \>/= 18 years.
Outcome Time Frame
Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose
Outcome Measure
Pharmacokinetics: Cmax of Oseltamivir Carboxylate in Adults
Outcome Description
Reported here are oseltamivir carboxylate Ctrough data for adults \>/= 18 years.
Outcome Time Frame
Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose
Outcome Measure
Pharmacokinetics: Ctrough of Oseltamivir Carboxylate in Adults
Outcome Description
Reported here are oseltamivir carboxylate AUC0-12 data for adults \>/= 18 years.
Outcome Time Frame
Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose
Outcome Measure
Pharmacokinetics : AUC0-12 at Steady State of Oseltamivir Carboxylate in Adults
Outcome Description
Reported here are oseltamivir carboxylate tmax data for adults \>/= 18 years.
Outcome Time Frame
Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose
Outcome Measure
Pharmacokinetics: Tmax of Oseltamivir Carboxylate in Adults
Outcome Description
Reported here are oxeltamivir carboxylate ke data for adults \>/= 18 years.
Outcome Time Frame
Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose
Outcome Measure
Pharmacokinetics: Elimination Constant (ke) of Oseltamivir Carboxylate in Adults
Outcome Description
Reported here are oseltamivir carboxylate CL/F data for adults \>/= 18 years.
Outcome Time Frame
Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose
Outcome Measure
Pharmacokinetics: Apparent Clearance (CL/F) of Oseltamivir Carboxylate in Adults
Outcome Description
Reported here are oseltamivir carboxylate Vc/F data for adults \>/= 18 years.
Outcome Time Frame
Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose
Outcome Measure
Pharmacokinetics: Apparent Volume of Distribution (Vc/F) of Oseltamivir Carboxylate in Adults
Outcome Description
Reported here are oseltamivir Cmax data for adolescents and children \< 18 years. Individual data are provided as participants received different drug doses. Drug dose is indicated in the row title for each participant.
Outcome Time Frame
Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose
Outcome Measure
Pharmacokinetics: Cmax of Oseltamivir in Adolescents and Children
Outcome Description
Reported here are oseltamivir Ctrough data for adolescents and children \< 18 years. Individual data are provided as participants received different drug doses. Drug dose is indicated in the row title for each participant.
Outcome Time Frame
Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose
Outcome Measure
Pharmacokinetics: Ctrough of Oseltamivir in Adolescents and Children
Outcome Description
AUC0-12 will be reported at steady state as ng\*hr/mL. Reported here are oseltamivir AUC0-12 data for adolescents and children \< 18 years. Individual data are provided as participants received different drug doses. Drug dose is indicated in the row title for each participant.
Outcome Time Frame
Pre-dose (30 minutes), 1.5, 4, 8 hours on Day 6 or any day after the 11th dose
Outcome Measure
Pharmacokinetics: AUC0-12 at Steady State of Oseltamivir in Adolescents and Children
Outcome Description
Reported here are oseltamivir data for adolescents and children \< 18 years. Individual data are provided as participants received different drug doses. Drug dose is indicated in the row title for each participant.
Outcome Time Frame
Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose
Outcome Measure
Pharmacokinetics: Tmax of Oseltamivir in Adolescents and Children
Outcome Description
Reported here are oseltamivir carboxylate Cmax data for adolescents and children \< 18 years. Individual data are provided as participants received different drug doses. Drug dose is indicated in the row title for each participant.
Outcome Time Frame
Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose
Outcome Measure
Pharmacokinetics: Cmax of Oseltamivir Carboxylate in Adolescents and Children
Outcome Description
Reported here are oseltamivir carboxylate Ctrough data for adolescents and children \< 18 years. Individual data are provided as participants received different drug doses. Drug dose is indicated in the row title for each participant.
Outcome Time Frame
Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose
Outcome Measure
Pharmacokinetics: Ctrough of Oseltamivir Carboxylate in Adolescents and Children
Outcome Description
AUC0-12 will be reported at steady state as ng\*hr/mL. Reported here are oseltamivir carboxylate AUC0-12 data for adolescents and children \< 18 years. Individual data are provided as participants received different drug doses. Drug dose is indicated in the row title for each participant.
Outcome Time Frame
Pre-dose (30 minutes), 1.5, 4, 8 hours on Day 6 or any day after the 11th dose
Outcome Measure
Pharmacokinetics: AUC0-12 at Steady State of Oseltamivir Carboxylate in Adolescents and Children
Outcome Description
Reported here are oseltamivir carboxylate tmax data for adolescents and children \< 18 years. Individual data are provided as participants received different drug doses. Drug dose is indicated in the row title for each participant.
Outcome Time Frame
Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose
Outcome Measure
Pharmacokinetics: Tmax of Oseltamivir Carboxylate in Adolescents and Children
Outcome Description
Reported here are oseltamivir ke data for adolescents and children \< 18 years. Individual data are provided as participants received different drug doses. Drug dose is indicated in the row title for each participant.
Outcome Time Frame
Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose
Outcome Measure
Pharmacokinetics: Elimination Constant (ke) of Oseltamivir in Adolescents and Children
Outcome Description
Reported here are oseltamivir CL/F data for adolescents and children \< 18 years. Individual data are provided as participants received different drug doses. Drug dose is indicated in the row title for each participant.
Outcome Time Frame
Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose
Outcome Measure
Pharmacokinetics: Apparent Clearance (CL/F) of Oseltamivir in Adolescents and Children
Outcome Description
Reported here are oseltamivir Vc/F data for adolescents and children \< 18 years. Individual data are provided as participants received different drug doses. Drug dose is indicated in the row title for each participant.
Outcome Time Frame
Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose
Outcome Measure
Pharmacokinetics: Apparent Volume of Distribution (Vc/F) of Oseltamivir in Adolescents and Children
Outcome Description
Reported here are oseltamivir carboxylate ke data for adolescents and children \< 18 years. Individual data are provided as participants received different drug doses. Drug dose is indicated in the row title for each participant.
Outcome Time Frame
Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose
Outcome Measure
Pharmacokinetics: Elimination Constant (ke) of Oseltamivir Carboxylate in Adolescents and Children
Outcome Description
Reported here are oseltamivir carboxylate CL/F data for adolescents and children \< 18 years. Individual data are provided as participants received different drug doses. Drug dose is indicated in the row title for each participant.
Outcome Time Frame
Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose
Outcome Measure
Pharmacokinetics: Apparent Clearance (CL/F), of Oseltamivir Carboxylate in Adolescents and Children
Outcome Description
Reported here are oseltamivir carboxylate Vc/F data for adolescents and children \< 18 years. Individual data are provided as participants received different drug doses. Drug dose is indicated in the row title for each participant.
Outcome Time Frame
Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose
Outcome Measure
Pharmacokinetics: Apparent Volume of Distribution (Vc/F) of Oseltamivir Carboxylate in Adolescents and Children
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Child
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
1
Investigators
Investigator Type
Principal Investigator
Investigator Name
Tsoline kojaoghlanian
Investigator Email
Investigator Phone
Categories Mesh Debug
COVID-19 --- RESPIRATORY TRACT INFECTIONS
Lung --- RESPIRATORY TRACT INFECTIONS
COVID-19 --- INFECTIONS
Infectious Disease --- INFECTIONS
COVID-19 --- RNA VIRUS INFECTIONS
Infectious Disease --- RNA VIRUS INFECTIONS
COVID-19 --- VIRUS DISEASES
Hepatitis --- VIRUS DISEASES
Infectious Disease --- VIRUS DISEASES
Asthma and Other Respiratory Diseases --- RESPIRATORY TRACT DISEASES
Lung & Chest Cancers --- RESPIRATORY TRACT DISEASES
COVID-19 --- RESPIRATORY TRACT DISEASES
Lung --- RESPIRATORY TRACT DISEASES
MeSH Terms
INFLUENZA, HUMAN
RESPIRATORY TRACT INFECTIONS
INFECTIONS
ORTHOMYXOVIRIDAE INFECTIONS
RNA VIRUS INFECTIONS
VIRUS DISEASES
RESPIRATORY TRACT DISEASES
OSELTAMIVIR
COUNTERFEIT DRUGS
ACETAMIDES
AMIDES
ORGANIC CHEMICALS
CYCLOHEXENES
CYCLOHEXANES
CYCLOPARAFFINS
HYDROCARBONS, ALICYCLIC
HYDROCARBONS, CYCLIC
HYDROCARBONS
SUBSTANDARD DRUGS
PHARMACEUTICAL PREPARATIONS