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  1. Aliyu B, Raji YE, Chee HY, Wong MY, Sekawi ZB
    PLoS One, 2022;17(12):e0277206.
    PMID: 36454880 DOI: 10.1371/journal.pone.0277206
    Efforts are ongoing by researchers globally to develop new drugs or repurpose existing ones for treating COVID-19. Thus, this led to the use of oseltamivir, an antiviral drug used for treating influenza A and B viruses, as a trial drug for COVID-19. However, available evidence from clinical studies has shown conflicting results on the effectiveness of oseltamivir in COVID-19 treatment. Therefore, this systematic review and meta-analysis was performed to assess the clinical safety and efficacy of oseltamivir for treating COVID-19. The study was conducted according to the PRISMA guidelines, and the priori protocol was registered in PROSPERO (CRD42021270821). Five databases were searched, the identified records were screened, and followed by the extraction of relevant data. Eight observational studies from four Asian countries were included. A random-effects model was used to pool odds ratios (ORs), mean differences (MD), and their 95% confidence intervals (CI) for the study analysis. Survival was not significantly different between all categories of oseltamivir and the comparison groups analysed. The duration of hospitalisation was significantly shorter in the oseltamivir group following sensitivity analysis (MD -5.95, 95% CI -9.91--1.99 p = 0.003, heterogeneity I2 0%, p = 0.37). The virological, laboratory and radiological response rates were all not in favour of oseltamivir. However, the electrocardiographic safety parameters were found to be better in the oseltamivir group. However, more studies are needed to establish robust evidence on the effectiveness or otherwise of oseltamivir usage for treating COVID-19.
    Matched MeSH terms: Oseltamivir/adverse effects
  2. Kamal MA, Smith PF, Chaiyakunapruk N, Wu DBC, Pratoomsoot C, Lee KKC, et al.
    Br J Clin Pharmacol, 2017 07;83(7):1580-1594.
    PMID: 28176362 DOI: 10.1111/bcp.13229
    AIMS: A modular interdisciplinary platform was developed to investigate the economic impact of oseltamivir treatment by dosage regimen under simulated influenza pandemic scenarios.

    METHODS: The pharmacology module consisted of a pharmacokinetic distribution of oseltamivir carboxylate daily area under the concentration-time curve at steady state (simulated for 75 mg and 150 mg twice daily regimens for 5 days) and a pharmacodynamic distribution of viral shedding duration obtained from phase II influenza inoculation data. The epidemiological module comprised a susceptible, exposed, infected, recovered (SEIR) model to which drug effect on the basic reproductive number (R0 ), a measure of transmissibility, was linked by reduction of viral shedding duration. The number of infected patients per population of 100 000 susceptible individuals was simulated for a series of pandemic scenarios, varying oseltamivir dose, R0 (1.9 vs. 2.7), and drug uptake (25%, 50%, and 80%). The number of infected patients for each scenario was entered into the health economics module, a decision analytic model populated with branch probabilities, disease utility, costs of hospitalized patients developing complications, and case-fatality rates. Change in quality-adjusted life years was determined relative to base case.

    RESULTS: Oseltamivir 75 mg relative to no treatment reduced the median number of infected patients, increased change in quality-adjusted life years by deaths averted, and was cost-saving under all scenarios; 150 mg relative to 75 mg was not cost effective in low transmissibility scenarios but was cost saving in high transmissibility scenarios.

    CONCLUSION: This methodological study demonstrates proof of concept that the disciplines of pharmacology, disease epidemiology and health economics can be linked in a single quantitative framework.

    Matched MeSH terms: Oseltamivir/economics; Oseltamivir/pharmacology; Oseltamivir/therapeutic use*
  3. Ishaqui AA, Khan AH, Syed Sulaiman SA, Alsultan MT, Khan I, Al Nami H
    Pak J Pharm Sci, 2019 May;32(3 (Supplementary)):1225-1233.
    PMID: 31326884
    The aim of the study is to assess and compare the impact of antiviral drug alone and in combination with antibiotic for prevention of Influenza-A H1N1 induced acute kidney injury (AKI) in hospitalized patients. Hospitalized admitted patients with confirmed diagnosis of Influenza-A H1N1 infection were divided into two groups: group 1, which received antiviral (oseltamivir) drug alone and group 2, which received antiviral (oseltamivir) in combination with empirically prescribed antibiotic. Patients of both groups were assessed for incidences of AKI by two criteria i.e Acute Kidney Injury Network (AKIN) and RIFLE. A total of 329 patients (176 for group 1 and 153 for group 2) were enrolled. According to RIFLE criteria, 23(13%) of group 1 and 9(6%) patients of groups 2 were suffered from AKI with statistically significant difference (P<0.05). Also as per AKIN criteria, the incidence of AKI is statistically significantly difference (P<0.05) between both groups with 18(10%) patients and 6(4%) patients of group 1 and 2 respectively. Length of hospitalization was statistically less (P<0.05) in group 2 patients. The incidences of AKI in Influenza-A H1N1 treated with antiviral and antibiotic combination was statistically less as compared to patients who were given antiviral alone for treatment of influenza infection.
    Matched MeSH terms: Oseltamivir
  4. Yusuf M, Mohamed N, Mohamad S, Janezic D, Damodaran KV, Wahab HA
    J Chem Inf Model, 2016 Jan 25;56(1):82-100.
    PMID: 26703840 DOI: 10.1021/acs.jcim.5b00331
    Increased reports of oseltamivir (OTV)-resistant strains of the influenza virus, such as the H274Y mutation on its neuraminidase (NA), have created some cause for concern. Many studies have been conducted in the attempt to uncover the mechanism of OTV resistance in H274Y NA. However, most of the reported studies on H274Y focused only on the drug-bound system, so the direct effects of the mutation on NA itself prior to drug binding still remain unclear. Therefore, molecular dynamics simulations of NA in apo form, followed by principal component analysis and interaction energy calculations, were performed to investigate the structural changes of the NA binding site as a result of the H274Y mutation. It was observed that the disruption of the NA binding site due to the H274Y mutation was initiated by the repulsive effect of Y274 on the 250-loop, which in turn altered the hydrogen-bonding network around residue 274. The rotated W295 side chain caused the upward movement of the 340-loop. Consequently, sliding box docking results suggested that the binding pathway of OTV was compromised because of the disruption of this binding site. This study also highlighted the importance of the functional group at C6 of the sialic acid mimicry. It is hoped that these results will improve the understanding of OTV resistance and shed some light on the design of a novel anti-influenza drug.
    Matched MeSH terms: Oseltamivir/metabolism*; Oseltamivir/pharmacology*
  5. Wu DBC, Chaiyakunapruk N, Pratoomsoot C, Lee KKC, Chong HY, Nelson RE, et al.
    Epidemiol Infect, 2018 03;146(4):496-507.
    PMID: 29446343 DOI: 10.1017/S0950268818000158
    Simulation models are used widely in pharmacology, epidemiology and health economics (HEs). However, there have been no attempts to incorporate models from these disciplines into a single integrated model. Accordingly, we explored this linkage to evaluate the epidemiological and economic impact of oseltamivir dose optimisation in supporting pandemic influenza planning in the USA. An HE decision analytic model was linked to a pharmacokinetic/pharmacodynamics (PK/PD) - dynamic transmission model simulating the impact of pandemic influenza with low virulence and low transmissibility and, high virulence and high transmissibility. The cost-utility analysis was from the payer and societal perspectives, comparing oseltamivir 75 and 150 mg twice daily (BID) to no treatment over a 1-year time horizon. Model parameters were derived from published studies. Outcomes were measured as cost per quality-adjusted life year (QALY) gained. Sensitivity analyses were performed to examine the integrated model's robustness. Under both pandemic scenarios, compared to no treatment, the use of oseltamivir 75 or 150 mg BID led to a significant reduction of influenza episodes and influenza-related deaths, translating to substantial savings of QALYs. Overall drug costs were offset by the reduction of both direct and indirect costs, making these two interventions cost-saving from both perspectives. The results were sensitive to the proportion of inpatient presentation at the emergency visit and patients' quality of life. Integrating PK/PD-EPI/HE models is achievable. Whilst further refinement of this novel linkage model to more closely mimic the reality is needed, the current study has generated useful insights to support influenza pandemic planning.
    Matched MeSH terms: Oseltamivir/economics*; Oseltamivir/therapeutic use*
  6. Ishaqui AA, Khan AH, Sulaiman SAS, Alsultan MT, Khan I, Naqvi AA
    Expert Rev Respir Med, 2020 05;14(5):533-541.
    PMID: 32053044 DOI: 10.1080/17476348.2020.1730180
    Objectives: This study aimed to assess the efficacy of oseltamivir-Azithromycin combination therapy for prevention of Influenza-A (H1N1)pdm09 infection associated complications and early relief of influenza symptoms.Methods: In a retrospective observational cohort study, Influenza-A (H1N1)pdm09 infection hospitalized patients were identified and divided into two groups based on the initial therapy. Group-AV patients were initiated on Oseltamivir without any antibiotic in treatment regimen while Group-AV+AZ patients were initiated on Oseltamivir and Azithromycin combination therapy for at least 3-5 days. Patients were evaluated for different clinical outcomes.Results: A total of 227 and 102 patients were identified for Group-AV and Group-AV+AZ respectively. Multivariate regression analysis showed that incidences of secondary bacterial infections were significantly less frequent (23.4% vs 10.4%; P-value = 0.019) in Group-AV+AZ patients. Group-AV+AZ patients were associated with shorter length of hospitalization (6.58 vs 5.09 days; P-value = <0.0001) and less frequent incidences of respiratory support (38.3% vs 17.6%; P-value = 0.016). Overall influenza symptom severity score was statistically significant less for Group-AV+AZ patients on Day-5 (10.68 ± 2.09; P-value = 0.001) of hospitalization.Conclusion: Oseltamivir-Azithromycin combination therapy was found to be more efficacious as compared to oseltamivir alone in rapid recovery and prevention of Influenza associated complications especially in high risk patients.
    Matched MeSH terms: Oseltamivir
  7. Suppiah J, Yusof MA, Othman KA, Saraswathy TS, Thayan R, Kasim FM, et al.
    PMID: 21323171
    The 2009 pandemic influenza A(H1N1) infection in Malaysia was first reported in May 2009 and oseltamivir was advocated for confirmed cases in postexposure prophylaxis. However, there are cases of oseltamivir-resistance reported among H1N1-positive patients in other countries. Resistance is due to substitution of histidine by tyrosine at residue 275 (H275Y) of neuraminidase (NA). In this study, we have employed Sanger sequencing method to investigate the occurrence of mutations in NA segments of 67 pandemic 2009 A(H1N1) viral isolates from Malaysian patients that could lead to probable oseltamivir resistance. The sequencing analysis did not yield mutation at residue 275 for all 67 isolates indicating that our viral isolates belong to the wild type and do not confer resistance to oseltamivir.
    Matched MeSH terms: Oseltamivir/therapeutic use
  8. Hurt AC, Selleck P, Komadina N, Shaw R, Brown L, Barr IG
    Antiviral Res, 2007 Mar;73(3):228-31.
    PMID: 17112602
    Since 2003, highly pathogenic A(H5N1) influenza viruses have been the cause of large-scale death in poultry and the subsequent infection and death of over 140 humans. A group of 55 influenza A(H5N1) viruses isolated from various regions of South East Asia between 2004 and 2006 were tested for their susceptibility to the anti-influenza drugs the neuraminidase inhibitors and adamantanes. The majority of strains were found to be fully sensitive to the neuraminidase inhibitors oseltamivir carboxylate, zanamivir and peramivir; however two strains demonstrated increased IC50 values. Sequence analysis of these strains revealed mutations in the normally highly conserved residues 116 and 117 of the N1 neuraminidase. Sequence analysis of the M2 gene showed that all of the A(H5N1) viruses from Vietnam, Malaysia and Cambodia contained mutations (L26I and S31N) associated with resistance to the adamantane drugs (rimantadine and amantadine), while strains from Indonesia were found to be a mix of both adamantane resistant (S31N) and sensitive viruses. None of the A(H5N1) viruses from Myanmar contained mutations known to confer adamantane resistance. These results support the use of neuraminidase inhibitors as the most appropriate class of antiviral drug to prevent or treat human A(H5N1) virus infections.
    Matched MeSH terms: Oseltamivir/pharmacology
  9. Premila Devi J, Noraini W, Norhayati R, Chee Kheong C, Badrul AS, Zainah S, et al.
    Euro Surveill, 2014 May 08;19(18).
    PMID: 24832116
    On 14 April 2014, the first laboratory-confirmed case of Middle East respiratory syndrome coronavirus (MERS-CoV) infection was reported in Malaysia in a man in his mid-fifties, who developed pneumonia with respiratory distress, after returning from a pilgrimage to Saudi Arabia. The case succumbed to his illness three days after admission at a local hospital. The follow-up of 199 close contacts identified through contact tracing and vigilant surveillance did not result in detecting any other confirmed cases of MERS-CoV infection.
    Matched MeSH terms: Oseltamivir/therapeutic use
  10. Ishaqui AA, Khan AH, Sulaiman SA, Alsultan M, Khan I
    Saudi Med J, 2020 Sep;41(9):1015-1021.
    PMID: 32893285 DOI: 10.15537/smj.2020.9.25249
    OBJECTIVES: To assess the comparative efficacy of oseltamivir alone and oseltamivir-antibiotic therapy for early relief of symptoms associated with severe influenza-A (non-H1N1) and influenza-B infection hospitalized patients.

    METHODS: In this retrospective multicenter study conducted from 2016-2019, enrolled patients were divided into 2 treatment groups. Group 1 patients were started on Antiviral drug (oseltamivir) alone therapy. Group 2 patients were initiated on Antiviral drug (oseltamivir) in combination with Antibiotic therapy. Using acute respiratory illness scoring, symptom severity score was assessed daily for 8 symptoms namely, fever, fatigue, headache, cough, sore throat, wheezing, muscle ache and nasal congestion. For each symptom the severity was scored from scale 0-3. Results: Overall mean ARI severity score was statistically significantly lower (p less than 0.05) on day 2 (14.65-vs-13.68), day 3 (12.95-vs-11.67) and day 4 (10.31-vs-9.12 ) for influenza-A (non-H1N1) while day 3 (12.52-vs-11.87) and day 4 (11.21-vs-10.18) for influenza-B patients for patients who were initiated on oseltamivir-antibiotic combination therapy. Fever, cough and nasal congestion showed statistically significant improvement within 4 days of initiation of combination treatment. Fatigue, sore throat and muscle ache improvement pattern was same for both treatment protocols.

    CONCLUSION: Oseltamivir-antibiotic combination treatment showed early resolution of some symptoms with cumulatively reduced mean symptom severity score in severe influenza infection hospitalized patients.

    Matched MeSH terms: Oseltamivir/administration & dosage*
  11. Ishaqui AA, Khan AH, Syed Sulaiman SA, Alsultan MT, Khan I, Al Nami H
    Pak J Pharm Sci, 2019 May;32(3 (Supplementary)):1225-1233.
    PMID: 31303595
    The aim of the study is to assess and compare the impact of antiviral drug alone and in combination with antibiotic for prevention of Influenza-A H1N1 induced acute kidney injury (AKI) in hospitalized patients. Hospitalized admitted patients with confirmed diagnosis of Influenza-A H1N1 infection were divided into two groups: group 1, which received antiviral (oseltamivir) drug alone and group 2, which received antiviral (oseltamivir) in combination with empirically prescribed antibiotic. Patients of both groups were assessed for incidences of AKI by two criteria i.e Acute Kidney Injury Network (AKIN) and RIFLE. A total of 329 patients (176 for group 1 and 153 for group 2) were enrolled. According to RIFLE criteria, 23(13%) of group 1 and 9(6%) patients of groups 2 were suffered from AKI with statistically significant difference (P<0.05). Also as per AKIN criteria, the incidence of AKI is statistically significantly difference (P<0.05) between both groups with 18(10%) patients and 6(4%) patients of group 1 and 2 respectively. Length of hospitalization was statistically less (P<0.05) in group 2 patients. The incidences of AKI in Influenza-A H1N1 treated with antiviral and antibiotic combination was statistically less as compared to patients who were given antiviral alone for treatment of influenza infection.
    Matched MeSH terms: Oseltamivir/therapeutic use*
  12. Tan KX, Jacob SA, Chan KG, Lee LH
    Front Microbiol, 2015;6:140.
    PMID: 25798131 DOI: 10.3389/fmicb.2015.00140
    The novel avian influenza A H7N9 virus which caused the first human infection in Shanghai, China; was reported on the 31st of March 2013 before spreading rapidly to other Chinese provinces and municipal cities. This is the first time the low pathogenic avian influenza A virus has caused human infections and deaths; with cases of severe respiratory disease with pneumonia being reported. There were 440 confirmed cases with 122 fatalities by 16 May 2014; with a fatality risk of ∼28%. The median age of patients was 61 years with a male-to-female ratio of 2.4:1. The main source of infection was identified as exposure to poultry and there is so far no definitive evidence of sustained person-to-person transmission. The neuraminidase inhibitors, namely oseltamivir, zanamivir, and peramivir; have shown good efficacy in the management of the novel H7N9 virus. Treatment is recommended for all hospitalized patients, and for confirmed and probable outpatient cases; and should ideally be initiated within 48 h of the onset of illness for the best outcome. Phylogenetic analysis found that the novel H7N9 virus is avian in origin and evolved from multiple reassortments of at least four origins. Indeed the novel H7N9 virus acquired human adaptation via mutations in its eight RNA gene segments. Enhanced surveillance and effective global control are essential to prevent pandemic outbreaks of the novel H7N9 virus.
    Matched MeSH terms: Oseltamivir
  13. Ishaqui AA, Khan AH, Syed Sulaiman SA, Alsultan M, Khan I
    Pak J Pharm Sci, 2020 Jul;33(4(Supplementary)):1763-1770.
    PMID: 33612459
    Secondary bacterial infection is considered as a major complication associated with severe Influenza-A (H1N1)pdm09 infection responsible for the mortalities and morbidities worldwide. Use of antibiotics in viral Influenza infection is still debatable. All the confirmed diagnosed hospitalized Influenza-A (H1N1)pdm09 infection patients fulfilling inclusion/exclusion criteria during the study period were divided into two groups based on drug therapy for initial 72 hours. Group-1 included those patients who received oral oseltamivir alone while Group-2 included patients who were initiated on oseltamivir in combination with empiric cephalosporin antibiotic within 6-8 hours after hospitalization. The patients of both groups were assessed for incidences of various complication associated with Influenza-A (H1N1)pdm09 infection. A total of 227 and 116 patients were enrolled for Group-1 and Group-2 respectively. The incidences of secondary bacterial infections were significantly less (P<0.05). Moreover, length of stay in hospitalization, need of ICU admission, multiple organ failure and need of respiratory support were also significantly less (P<0.05) for Group-2 patients. Majority of patients that suffered complications were unvaccinated and aged more than 50 years with multiple comorbidities. Among cephalosporins, cefuroxime was found to be least effective in prevention of Influenza associated complications. Early initiation of empiric antibiotic therapy in combination with oseltamivir can prevent complications associated with Influenza-A (H1N1)pdm09 infection especially in elderly and unvaccinated high risk patients. Different combinations of antibiotics and antiviral medications need to be analysed for the prevention of severe Influenza infection complications.
    Matched MeSH terms: Oseltamivir
  14. Mohd R, Nesam T, Kamaruzaman L, Cader RA, Mustafar R, Kong WY
    Respir Med Case Rep, 2018;24:147-149.
    PMID: 29977783 DOI: 10.1016/j.rmcr.2018.05.019
    Acinetobacter baumannii is an aerobic Gram-negative coccobacillus that is associated with hospital acquired pneumonia. There is increased reporting of emergent cases of community acquired multidrug resistance (MDR) acinetobacter associated with a higher mortality due to antibiotic resistance. Community acquired MDR acinetobacter pneumonia has not been reported in Malaysia. Here we report a case of a 19-year-old army officer who presented with fever and respiratory symptoms for 5 days. He had no known medical illness before and no history of hospitalization. Upon arrival, he was in septicaemic shock, requiring invasive ventilator support and renal replacement therapy in intensive care unit. Chest radiograph showed bilateral lung consolidations and bronchoscopy revealed haemoserous and greenish bronchiole secretion. He was treated with broad spectrum antibiotics and oseltamivir. Unfortunately he died on day 3 of hospital admission. His bronchial lavage culture came back positive for MDR Acinetobacter baumannii. This case illustrates that clinicians need to be aware that MDR Acinetobacter baumannii can cause severe community acquired pneumonia. We may need to consider this diagnosis in patients who do not respond to standard therapy.
    Matched MeSH terms: Oseltamivir
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