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Expert Opinion on Drug Safety May 2009Influenza infection is a global problem affecting millions of people worldwide, despite efficacious vaccines. Treatment and prophylaxis against influenza have been... (Review)
Review
BACKGROUND
Influenza infection is a global problem affecting millions of people worldwide, despite efficacious vaccines. Treatment and prophylaxis against influenza have been successful using antiviral medications such as adamantanes and neuraminidase inhibitors.
OBJECTIVE
To review the antiviral agents and specifically the neuraminidase inhibitor, oseltamivir, for use in treatment and prophylaxis of influenza infection.
METHODS
This review focuses on published literature regarding the clinical use of oseltamivir, as well as discussing emerging threats such as avian influenza, antiviral resistance, and strategies such as combination antiviral treatment to mitigate these threats.
RESULTS
Oseltamivir is effective in reducing symptom burden in those with influenza A or B infection, and is preventative against developing infection after exposure. Emergence of naturally occurring or post-treatment oseltamivir-resistant influenza as well as an avian influenza pandemic may limit its future use as a monotherapeutic antiviral treatment agent.
Topics: Animals; Antiviral Agents; Humans; Influenza, Human; Orthomyxoviridae Infections; Oseltamivir
PubMed: 19355841
DOI: 10.1517/14740330902840519 -
Lancet (London, England) Jan 2016
Topics: Antiviral Agents; Humans; Influenza, Human; Oseltamivir; Randomized Controlled Trials as Topic
PubMed: 26841993
DOI: 10.1016/S0140-6736(15)01282-9 -
Clinical Pharmacokinetics Nov 2010Oseltamivir is the ester-type prodrug of the neuraminidase inhibitor oseltamivir carboxylate. It has been shown to be an effective treatment for both seasonal influenza... (Review)
Review
Oseltamivir is the ester-type prodrug of the neuraminidase inhibitor oseltamivir carboxylate. It has been shown to be an effective treatment for both seasonal influenza and the recent pandemic 2009 A/H1N1 influenza, reducing both the duration and severity of the illness. It is also effective when used preventively. This review aims to describe the current knowledge of the pharmacokinetic and pharmacodynamic characteristics of this agent, and to address the issue of possible therapeutic drug monitoring. According to the currently available literature, the pharmacokinetics of oseltamivir carboxylate after oral administration of oseltamivir are characterized by mean ± SD bioavailability of 79 ± 12%, apparent clearance of 25.3 ± 7.0 L/h, an elimination half-life of 7.4 ± 2.5 hours and an apparent terminal volume of distribution of 267 ± 122 L. A maximum plasma concentration of 342 ± 83 μg/L, a time to reach the maximum plasma concentration of 4.2 ± 1.1 hours, a trough plasma concentration of 168 ± 32 μg/L and an area under the plasma concentration-time curve from 0 to 24 hours of 6110 ± 1330 μg · h/L for a 75 mg twice-daily regimen were derived from literature data. The apparent clearance is highly correlated with renal function, hence the dosage needs to be adjusted in proportion to the glomerular filtration rate. Interpatient variability is moderate (28% in apparent clearance and 46% in the apparent central volume of distribution); there is no indication of significant erratic or limited absorption in given patient subgroups. The in vitro pharmacodynamics of oseltamivir carboxylate reveal wide variation in the concentration producing 50% inhibition of influenza A and B strains (range 0.17-44 μg/L). A formal correlation between systemic exposure to oseltamivir carboxylate and clinical antiviral activity or tolerance in influenza patients has not yet been demonstrated; thus no formal therapeutic or toxic range can be proposed. The pharmacokinetic parameters of oseltamivir carboxylate after oseltamivir administration (bioavailability, apparent clearance and the volume of distribution) are fairly predictable in healthy subjects, with little interpatient variability outside the effect of renal function in all patients and bodyweight in children. Thus oseltamivir carboxylate exposure can probably be controlled with sufficient accuracy by thorough dosage adjustment according to patient characteristics. However, there is a lack of clinical study data on naturally infected patients. In addition, the therapeutic margin of oseltamivir carboxylate is poorly defined. The usefulness of systematic therapeutic drug monitoring in patients therefore appears to be questionable; however, studies are still needed to extend the knowledge to particular subgroups of patients or dosage regimens.
Topics: Antiviral Agents; Area Under Curve; Disease Outbreaks; Dose-Response Relationship, Drug; Drug Monitoring; Humans; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H5N1 Subtype; Influenza Vaccines; Influenza, Human; Oseltamivir; Pandemics; Prodrugs; United States
PubMed: 20923248
DOI: 10.2165/11534730-000000000-00000 -
American Journal of Health-system... Jan 2015Published evidence regarding the use of the antiinfluenza agent oseltamivir outside of the standard dosing recommendations is reviewed. (Review)
Review
PURPOSE
Published evidence regarding the use of the antiinfluenza agent oseltamivir outside of the standard dosing recommendations is reviewed.
SUMMARY
Oseltamivir is a neuraminidase inhibitor indicated for the treatment of uncomplicated influenza in patients two weeks of age or older who have been symptomatic for no more than two days; the recommended dosage is 75 mg twice daily by mouth for five days. A literature search identified six studies evaluating the effects of administering oseltamivir 48 hours or more after the onset of influenza symptoms, administering the drug at double the standard dose, or continuing therapy for more than five days. Two randomized controlled trials found that double-dose oseltamivir therapy conferred no significant survival benefit. The results of one retrospective study of intensive care unit (ICU) patients infected with the influenza H1N1 strain suggested improved survival among those who received oseltamivir no later than five days after symptom onset.
CONCLUSION
Oseltamivir may increase survival when used within five days of symptom onset in influenza H1N1-infected patients who require ICU admission. There appears to be no benefit in starting treatment more than 48 hours after symptom onset in hospitalized general medicine patients or outpatients infected with either H1N1 or other influenza strains or in doubling the dose of oseltamivir in hospitalized patients or outpatients. There are scant data supporting the use of oseltamivir for longer than five days in any patient population, with the possible exception of critically ill H1N1-infected ICU patients, who may benefit from extended treatment in some cases.
Topics: Animals; Humans; Influenza A Virus, H1N1 Subtype; Influenza, Human; Off-Label Use; Oseltamivir; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 25550133
DOI: 10.2146/ajhp140390 -
European Journal of Medicinal Chemistry Dec 2022Influenza with a tendency to cause pandemic and epidemic is an infectious disease with a high of morbidity and mortality. Neuraminidase (NA) inhibitors are proved to... (Review)
Review
Influenza with a tendency to cause pandemic and epidemic is an infectious disease with a high of morbidity and mortality. Neuraminidase (NA) inhibitors are proved to prevent and treat influenza. Among the four Neuraminidase inhibitors (NAIs) licensed, oseltamivir is most commonly used. With the extensive usage, several variants containing mutant NAs especially H274Y point mutation exhibit reduced susceptibility. In this review, we covered the current drugs available for influenza, the analysis of active site of NA, the mutant types of NAs and the molecular mechanism of drug resistance brought by H274Y mutant NAs. For recovering the susceptibility to oseltamivir, many series of oseltamivir analogues were designed. We present the details of the strategies of strengthening the interactions with S2 via introducing strong basic fragment, targeting additional subpockets and making full use of Zone X by modifying 3-pentyl of OC. PROTAC targeting NA and combination therapies are also introduced. Further, the advantages and disadvantages of these methods are also discussed.
Topics: Humans; Oseltamivir; Neuraminidase; Influenza, Human; Zanamivir; Mutation; Antiviral Agents; Enzyme Inhibitors; Guanidines; Glycoside Hydrolases; Drug Resistance, Viral
PubMed: 36055001
DOI: 10.1016/j.ejmech.2022.114711 -
Lancet (London, England) Sep 2015
Topics: Antiviral Agents; Humans; Influenza, Human; Oseltamivir; Randomized Controlled Trials as Topic
PubMed: 26461901
DOI: 10.1016/S0140-6736(15)00203-2 -
Lancet (London, England) Sep 2015
Topics: Antiviral Agents; Humans; Influenza, Human; Oseltamivir; Randomized Controlled Trials as Topic
PubMed: 26461899
DOI: 10.1016/S0140-6736(15)00202-0 -
Lancet (London, England) Sep 2015
Topics: Antiviral Agents; Humans; Influenza, Human; Oseltamivir; Randomized Controlled Trials as Topic
PubMed: 26461897
DOI: 10.1016/S0140-6736(15)00200-7 -
Lancet (London, England) Sep 2015
Topics: Antiviral Agents; Humans; Influenza, Human; Oseltamivir; Randomized Controlled Trials as Topic
PubMed: 26461900
DOI: 10.1016/S0140-6736(15)00201-9 -
Emergency Medicine Journal : EMJ Jan 2019A short cut review was carried out to establish whether Oseltamivir leads to faster alleviation of symptoms, fewer hospital admissions and lower mortality in adult... (Review)
Review
A short cut review was carried out to establish whether Oseltamivir leads to faster alleviation of symptoms, fewer hospital admissions and lower mortality in adult patients with confirmed influenza B presenting to the Emergency Department. Two studies were directly relevant to the question using the described search methodology on Ovid Medline and Embase. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. The clinical bottom line: there is no good evidence that oseltamivir results in quicker alleviation of symptoms, fewer hospital admissions or lower mortality in adult patients with influenza B.
Topics: Antiviral Agents; Cough; Emergency Service, Hospital; Evidence-Based Emergency Medicine; Fatigue; Humans; Influenza B virus; Influenza, Human; Male; Middle Aged; Oseltamivir
PubMed: 30635346
DOI: 10.1136/emermed-2018-208381.1