Expert Review of Anti-infective Therapy
ISSN: 1478-7210 (Print) 1744-8336 (Online) Journal homepage: http://www.tandfonline.com/loi/ierz20
Antiviral therapy in seasonal influenza and 2009 H1N1 pandemic influenza: Korean experiences and perspectives Joon Young Song, Ji Yun Noh, Won Suk Choi, Hee Jin Cheong & Woo Joo Kim To cite this article: Joon Young Song, Ji Yun Noh, Won Suk Choi, Hee Jin Cheong & Woo Joo Kim (2015): Antiviral therapy in seasonal influenza and 2009 H1N1 pandemic influenza: Korean experiences and perspectives, Expert Review of Anti-infective Therapy, DOI: 10.1586/14787210.2015.1076334 To link to this article: http://dx.doi.org/10.1586/14787210.2015.1076334
Published online: 09 Aug 2015.
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Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ierz20 Download by: [University of Otago]
Date: 27 September 2015, At: 03:45
Review
Antiviral therapy in seasonal influenza and 2009 H1N1 pandemic influenza: Korean experiences and perspectives Downloaded by [University of Otago] at 03:45 27 September 2015
Expert Rev. Anti Infect. Ther. Early online, 1–12 (2015)
Joon Young Song1,2, Ji Yun Noh1,2, Won Suk Choi1,2, Hee Jin Cheong1,2 and Woo Joo Kim*1,2 1 Division of Infectious Diseases, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea 2 Transgovernmental Enterprise for Pandemic Influenza in Korea (TEPIK), Seoul, Republic of Korea *Author for correspondence: Tel.: +82 2 2626 3051 Fax: +82 2 2626 1105 [email protected]
Influenza is a major cause of substantial morbidity and mortality in humans every year. Vaccination is the main strategy to prevent influenza infection, but antiviral agents also play an important role in the control of both seasonal and pandemic influenza. During the influenza A/H1N1 pandemic in 2009, early prompt antiviral therapy may have reduced the severity of the influenza outcomes including pneumonia, hospitalization and mortality in the Republic of Korea. Since the 2009 H1N1 pandemic, there have been increasing usages of antiviral agents for the treatment of patients with seasonal influenza. Although currently rare, antiviral resistance among influenza viruses may emerge and increase with increased use of neuraminidase inhibitors. New agents with different modes of action are under investigation, including favipiravir, DAS181, nitazoxanide and broad-spectrum neutralizing monoclonal antibodies. Data are limited with respect to high-dose and combination antiviral therapies. So, clinical trials are warranted to evaluate diverse antiviral combinations that may be synergistic and less likely to induce breakthrough resistance. KEYWORDS: antiviral agents . drug resistance . epidemics . influenza . Republic of Korea
Influenza causes significant morbidity in children, healthy adults and elderly people, irrespective of age [1]. In children, fatal cases are rare, but influenza attack rate is the highest compared to any age group and is responsible for the community spread of influenza viruses [1]. Among healthy adults aged 19 through 49 years, influenza is an important cause of outpatient medical visits and worker absenteeism [1]. Although most persons who become infected with influenza viruses will recover without sequelae, influenza can cause serious illness and death, particularly among persons aged ‡65 years and those with chronic medical conditions. Annual influenza epidemics typically occur throughout the winter and spring seasons in temperate regions, including the Republic of Korea (ROK), but influenza viruses circulate all year round in tropical regions [2]. Annually, 10–20% of the general population is known to be affected by seasonal influenza [1]. Influenza is responsible for approximately 3–5
informahealthcare.com
10.1586/14787210.2015.1076334
million severe cases and 250,000– 500,000 deaths worldwide in epidemic years [1,3,4]. Historically, influenza pandemics have repeated every 10–40 years; four pandemics (1918, 1957, 1968 and 2009) have occurred in the last 100 years. In the Spanish influenza pandemic of 1918–1919, the overall influenza case fatality rate was estimated to be about 4% [1]. In the ROK, an excess of 306,353 hospitalizations and 7109 deaths were associated with influenza infection during three interpandemic seasons (2005–2006, 2006–2007 and 2007–2008) using the Thompson model, reaching about 1.0% of the total mortality rate [2009 REPORT OF THE NATIONAL EVIDENCEBASED HEALTHCARE COLLABORATING AGENCY, UNPUBLISHED DATA] [5] Most fatal cases (80.8%) were aged over 65 years, and mortality was related to pneumonia and acute exacerbation of cardiopulmonary diseases. During the 2009 influenza pandemic, inpatient and outpatient visits increased 15–20-fold and
2015 Informa UK Ltd
ISSN 1478-7210
1
Review
Song, Noh, Choi, Cheong & Kim
10-fold, respectively, compared with the two previous seasons [6]. Accordingly, the total medical costs of inpatient visits also increased 20-fold and those of outpatient visits increased 50-fold [6].
Downloaded by [University of Otago] at 03:45 27 September 2015
Influenza surveillance in Korea
Public influenza surveillance systems are important for early detection and rapid response to epidemics as well as pandemics. In the ROK, two separate surveillance systems are in operation. The first, Korean Influenza and Respiratory Viruses Surveillance Scheme, is an outpatient influenza-like illness (ILI) surveillance network organized by Korea Centers for Disease Control and Prevention [7,8]. Korean Influenza and Respiratory Viruses Surveillance Scheme is composed of 200 local clinics reporting ILI cases, and 36 out of 200 ILI sentinel sites are included in the laboratory surveillance network. The second, hospital-based influenza surveillance system (Hospital-based Influenza Morbidity and Mortality [HIMM]), was established by the Trans-government Enterprise of Pandemic Influenza in Korea in 2011 after the 2009 H1N1 pandemic [2,8]. HIMM consists of emergency roombased ILI and hospitalized influenza surveillance to monitor severe acute respiratory infections, influenza-related complications and mortality. In the ROK, three influenza subtypes (A/H1N1, A/H3N2 and B) have been co-circulating with characteristic bi-modal epidemic peaks during influenza seasons [2,7]. Influenza A viral infection is usually predominant in the winter from December to February, typically followed by influenza B in early spring from March to April. The 2012– 2013 and 2013–2014 influenza seasons were unusual in that single peak epidemics were observed (FIGURE 1A); influenza A/ H3N2 strains were predominantly isolated. In addition to monitoring epidemics, both surveillance systems estimated vaccine effectiveness and antiviral resistance for each season. During the 2008–2009 season right before the 2009 H1N1 pandemic, most circulating influenza viruses were identified as the A/H1N1 strains, almost all of which were resistant to oseltamivir (Tamiflu, 99.6%) by the H275Y mutation, but susceptible to zanamivir (Relenza) [9]. Oseltamivir-resistant influenza viruses with the H275Y mutation in neuraminidase may also be resistant to peramivir (Peramiflu), because the hydrophobic side chains of peramivir are similar to those of oseltamivir [3]. Fortunately, oseltamivir-susceptible A/H1N1 strains replaced the resistant strains after the 2009 H1N1 pandemic [10]. On the other hand, resistance to zanamivir has rarely been reported in the ROK [10]. The rare zanamivir resistance is related to its higher structural homology to the natural neuraminidase substrate and its lower market consumption compared to that of oseltamivir (FIGURE 1B & TABLE 1) [3]. After licensure in the ROK in 2010, use of peramivir has gradually increased (TABLE 1, data given by sales volume collected by the pharmaceutical company). During the 2013–2014 influenza season, antiviral consumption markedly increased, reflecting a larger epidemic than in the previous seasons (FIGURE 1B). doi: 10.1586/14787210.2015.1076334
Antiviral treatment during 2009 influenza A/ H1N1 pandemic
Before the 2009 H1N1 pandemic, antivirals were rarely prescribed to patients with influenza in the ROK; most antivirals were stockpiled and managed by the government to be used for the response against the 2009 H1N1 pandemic. During the 2009 H1N1 pandemic, early antiviral therapy might have contributed to the mitigation of pandemic damage among people in the ROK [11]. According to the policy of the public health department, free antiviral agents such as oseltamivir or zanamivir were provided to patients with ILI based on the individual clinician’s decision without diagnostic confirmation during the full-blown pandemic period. To enhance accessibility to the antiviral agents, they were widely distributed to local pharmacies also [12]. During the early period of pandemic until the midOctober 2009, 1500–2000 treatment courses (two doses per day of oral oseltamivir or inhaled zanamivir for 5 days) were prescribed each day (FIGURE 2A) [11]. As the number of cases increased, the antiviral consumption also increased, leading to more than 100,000 course prescriptions per day around the peak of the pandemic in early November 2009. In the following months, the occurrence of pandemic influenza cases declined gradually and the antiviral requirements also decreased proportionately (FIGURE 2B) [11]. According to the report from the Antiviral Drug Surveillance System, approximately 6% of the total Korean population received antiviral drugs between September 1 and December 31, 2009 [13]. Among them, 95.9% (2,709,611 subjects) were outpatients, 4.1% (114,840 subjects) were hospitalized and 0.05% (1370 subjects) were admitted to the intensive care unit. The overall mortality rate was estimated to be 0.33/100,000 population, with the highest mortality reported in the elderly aged over 60 years (1.31/100,000 population). Another study reported that a total of 740,835 patients were diagnosed with laboratory-confirmed H1N1 pandemic influenza and 225 died in Korea during the 2009 H1N1 pandemic until January 31, 2010 [14]. The incidence was calculated as 1492 per 100,000 population and the case fatality rate was 30 per 100,000 cases [14]. Contrary to some countries with high mortality rates (e.g., Mexico and Argentina) [15], case fatality was low in the ROK, although a large number of cases occurred. Thus, large-scale intervention with early antiviral therapy could reduce person-to-person transmission and disease severity, thereby decreasing pandemic influenza-related morbidity and mortality, as suggested in the PRIDE study [16]. Although the data are not sufficient regarding high-dose antiviral treatment, a double dose of oseltamivir (150 mg twotimes a day [b.i.d.] for adults) was used in some patients with severe influenza infection, particularly in those complicated with pneumonia (TABLE 2) [17–20]. Standard-dose oseltamivir was used for the pediatric patients, whereas either high-dose oseltamivir or a combination regimen was applied for adult patients with severe H1N1 influenza virus infections [17–23]. However, there are no data supporting high-dose oseltamivir therapy. Actually, blood trough concentrations after the administration of standard-dose oseltamivir (b.i.d. at 75 mg) are about Expert Rev. Anti Infect. Ther.
Review
Antiviral therapy in seasonal influenza & 2009 H1N1 pandemic influenza
A ILI index (ILI patients per 1000 ER visit)
240 2011-12 season
200
2012-13 season 160
2013-14 season
120 80 40
34 week
32 week
30 week
28 week
26 week
24 week
22 week
20 week
18 week
16 week
14 week
12 week
8 week
10 week
6 week
4 week
2 week
52 week
50 week
48 week
46 week
44 week
42 week
40 week
38 week
36 week
Downloaded by [University of Otago] at 03:45 27 September 2015
0
B (No.†) 1,200,000 1,000,000 800,000 600,000 400,000 Oseltamivir Zanamivir
200,000
Peramivir 0 2010-2011
95.2%
2011-2012
98.5%
2012-2013
2013-2014
98.2%
98.2%
(Years)
Figure 1. (A) Trends of influenza activity based on the surveillance in 2011–2012, 2012–2013 and 2013–2014 seasons by Hospital-based Influenza Morbidity and Mortality. (B) Annual (September–August) consumption of antiviral agents for the treatment of influenza (data given by sales volume collected by the pharmaceutical company). † Consumed numbers of defined treatment courses (e.g., oseltamivir 75 mg twice a day for 5 days in adults). ILI: Influenza-like illness.
8–18-times higher than the 90% inhibitory concentration [24]. Although a triple-combination antiviral regimen (oseltamivir, amantadine and ribavirin) showed lower 30-day mortality compared to oseltamivir alone (17 vs 35%) among critically ill informahealthcare.com
patients with laboratory-confirmed H1N1 pandemic influenza in a retrospective study, the difference was not statistically significant (p = 0.08) [25]. Antiviral combinations are usually not recommended. Although the combination of oseltamivir and doi: 10.1586/14787210.2015.1076334
Review
Song, Noh, Choi, Cheong & Kim
Table 1. Antiviral use for the treatment of influenza in the Republic of Korea (data given by sales volume collected by the pharmaceutical company). Season
Annual consumption of antiviral agents in Korea (no. of treatment courses for each antiviral agent)
Downloaded by [University of Otago] at 03:45 27 September 2015
Oseltamivir†
Zanamivir
Peramivir
2010–2011
177,127
8310
550
2011–2012
381,090
605
4900
2012–2013
369,378
1784
4800
2013–2014
1,065,515
5026
13,850
A treatment course was defined for each antiviral agent: oseltamivir (30/45/ 75 mg b.i.d., 5 days), zanamivir (10 mg b.i.d., 5 days) and peramivir (300 mg, single dose). † Recommended dosage for children by body weight: weight £15 kg, 30 mg b.i.d.; 15 kg
ISSN: 1478-7210 (Print) 1744-8336 (Online) Journal homepage: http://www.tandfonline.com/loi/ierz20
Antiviral therapy in seasonal influenza and 2009 H1N1 pandemic influenza: Korean experiences and perspectives Joon Young Song, Ji Yun Noh, Won Suk Choi, Hee Jin Cheong & Woo Joo Kim To cite this article: Joon Young Song, Ji Yun Noh, Won Suk Choi, Hee Jin Cheong & Woo Joo Kim (2015): Antiviral therapy in seasonal influenza and 2009 H1N1 pandemic influenza: Korean experiences and perspectives, Expert Review of Anti-infective Therapy, DOI: 10.1586/14787210.2015.1076334 To link to this article: http://dx.doi.org/10.1586/14787210.2015.1076334
Published online: 09 Aug 2015.
Submit your article to this journal
Article views: 16
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ierz20 Download by: [University of Otago]
Date: 27 September 2015, At: 03:45
Review
Antiviral therapy in seasonal influenza and 2009 H1N1 pandemic influenza: Korean experiences and perspectives Downloaded by [University of Otago] at 03:45 27 September 2015
Expert Rev. Anti Infect. Ther. Early online, 1–12 (2015)
Joon Young Song1,2, Ji Yun Noh1,2, Won Suk Choi1,2, Hee Jin Cheong1,2 and Woo Joo Kim*1,2 1 Division of Infectious Diseases, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea 2 Transgovernmental Enterprise for Pandemic Influenza in Korea (TEPIK), Seoul, Republic of Korea *Author for correspondence: Tel.: +82 2 2626 3051 Fax: +82 2 2626 1105 [email protected]
Influenza is a major cause of substantial morbidity and mortality in humans every year. Vaccination is the main strategy to prevent influenza infection, but antiviral agents also play an important role in the control of both seasonal and pandemic influenza. During the influenza A/H1N1 pandemic in 2009, early prompt antiviral therapy may have reduced the severity of the influenza outcomes including pneumonia, hospitalization and mortality in the Republic of Korea. Since the 2009 H1N1 pandemic, there have been increasing usages of antiviral agents for the treatment of patients with seasonal influenza. Although currently rare, antiviral resistance among influenza viruses may emerge and increase with increased use of neuraminidase inhibitors. New agents with different modes of action are under investigation, including favipiravir, DAS181, nitazoxanide and broad-spectrum neutralizing monoclonal antibodies. Data are limited with respect to high-dose and combination antiviral therapies. So, clinical trials are warranted to evaluate diverse antiviral combinations that may be synergistic and less likely to induce breakthrough resistance. KEYWORDS: antiviral agents . drug resistance . epidemics . influenza . Republic of Korea
Influenza causes significant morbidity in children, healthy adults and elderly people, irrespective of age [1]. In children, fatal cases are rare, but influenza attack rate is the highest compared to any age group and is responsible for the community spread of influenza viruses [1]. Among healthy adults aged 19 through 49 years, influenza is an important cause of outpatient medical visits and worker absenteeism [1]. Although most persons who become infected with influenza viruses will recover without sequelae, influenza can cause serious illness and death, particularly among persons aged ‡65 years and those with chronic medical conditions. Annual influenza epidemics typically occur throughout the winter and spring seasons in temperate regions, including the Republic of Korea (ROK), but influenza viruses circulate all year round in tropical regions [2]. Annually, 10–20% of the general population is known to be affected by seasonal influenza [1]. Influenza is responsible for approximately 3–5
informahealthcare.com
10.1586/14787210.2015.1076334
million severe cases and 250,000– 500,000 deaths worldwide in epidemic years [1,3,4]. Historically, influenza pandemics have repeated every 10–40 years; four pandemics (1918, 1957, 1968 and 2009) have occurred in the last 100 years. In the Spanish influenza pandemic of 1918–1919, the overall influenza case fatality rate was estimated to be about 4% [1]. In the ROK, an excess of 306,353 hospitalizations and 7109 deaths were associated with influenza infection during three interpandemic seasons (2005–2006, 2006–2007 and 2007–2008) using the Thompson model, reaching about 1.0% of the total mortality rate [2009 REPORT OF THE NATIONAL EVIDENCEBASED HEALTHCARE COLLABORATING AGENCY, UNPUBLISHED DATA] [5] Most fatal cases (80.8%) were aged over 65 years, and mortality was related to pneumonia and acute exacerbation of cardiopulmonary diseases. During the 2009 influenza pandemic, inpatient and outpatient visits increased 15–20-fold and
2015 Informa UK Ltd
ISSN 1478-7210
1
Review
Song, Noh, Choi, Cheong & Kim
10-fold, respectively, compared with the two previous seasons [6]. Accordingly, the total medical costs of inpatient visits also increased 20-fold and those of outpatient visits increased 50-fold [6].
Downloaded by [University of Otago] at 03:45 27 September 2015
Influenza surveillance in Korea
Public influenza surveillance systems are important for early detection and rapid response to epidemics as well as pandemics. In the ROK, two separate surveillance systems are in operation. The first, Korean Influenza and Respiratory Viruses Surveillance Scheme, is an outpatient influenza-like illness (ILI) surveillance network organized by Korea Centers for Disease Control and Prevention [7,8]. Korean Influenza and Respiratory Viruses Surveillance Scheme is composed of 200 local clinics reporting ILI cases, and 36 out of 200 ILI sentinel sites are included in the laboratory surveillance network. The second, hospital-based influenza surveillance system (Hospital-based Influenza Morbidity and Mortality [HIMM]), was established by the Trans-government Enterprise of Pandemic Influenza in Korea in 2011 after the 2009 H1N1 pandemic [2,8]. HIMM consists of emergency roombased ILI and hospitalized influenza surveillance to monitor severe acute respiratory infections, influenza-related complications and mortality. In the ROK, three influenza subtypes (A/H1N1, A/H3N2 and B) have been co-circulating with characteristic bi-modal epidemic peaks during influenza seasons [2,7]. Influenza A viral infection is usually predominant in the winter from December to February, typically followed by influenza B in early spring from March to April. The 2012– 2013 and 2013–2014 influenza seasons were unusual in that single peak epidemics were observed (FIGURE 1A); influenza A/ H3N2 strains were predominantly isolated. In addition to monitoring epidemics, both surveillance systems estimated vaccine effectiveness and antiviral resistance for each season. During the 2008–2009 season right before the 2009 H1N1 pandemic, most circulating influenza viruses were identified as the A/H1N1 strains, almost all of which were resistant to oseltamivir (Tamiflu, 99.6%) by the H275Y mutation, but susceptible to zanamivir (Relenza) [9]. Oseltamivir-resistant influenza viruses with the H275Y mutation in neuraminidase may also be resistant to peramivir (Peramiflu), because the hydrophobic side chains of peramivir are similar to those of oseltamivir [3]. Fortunately, oseltamivir-susceptible A/H1N1 strains replaced the resistant strains after the 2009 H1N1 pandemic [10]. On the other hand, resistance to zanamivir has rarely been reported in the ROK [10]. The rare zanamivir resistance is related to its higher structural homology to the natural neuraminidase substrate and its lower market consumption compared to that of oseltamivir (FIGURE 1B & TABLE 1) [3]. After licensure in the ROK in 2010, use of peramivir has gradually increased (TABLE 1, data given by sales volume collected by the pharmaceutical company). During the 2013–2014 influenza season, antiviral consumption markedly increased, reflecting a larger epidemic than in the previous seasons (FIGURE 1B). doi: 10.1586/14787210.2015.1076334
Antiviral treatment during 2009 influenza A/ H1N1 pandemic
Before the 2009 H1N1 pandemic, antivirals were rarely prescribed to patients with influenza in the ROK; most antivirals were stockpiled and managed by the government to be used for the response against the 2009 H1N1 pandemic. During the 2009 H1N1 pandemic, early antiviral therapy might have contributed to the mitigation of pandemic damage among people in the ROK [11]. According to the policy of the public health department, free antiviral agents such as oseltamivir or zanamivir were provided to patients with ILI based on the individual clinician’s decision without diagnostic confirmation during the full-blown pandemic period. To enhance accessibility to the antiviral agents, they were widely distributed to local pharmacies also [12]. During the early period of pandemic until the midOctober 2009, 1500–2000 treatment courses (two doses per day of oral oseltamivir or inhaled zanamivir for 5 days) were prescribed each day (FIGURE 2A) [11]. As the number of cases increased, the antiviral consumption also increased, leading to more than 100,000 course prescriptions per day around the peak of the pandemic in early November 2009. In the following months, the occurrence of pandemic influenza cases declined gradually and the antiviral requirements also decreased proportionately (FIGURE 2B) [11]. According to the report from the Antiviral Drug Surveillance System, approximately 6% of the total Korean population received antiviral drugs between September 1 and December 31, 2009 [13]. Among them, 95.9% (2,709,611 subjects) were outpatients, 4.1% (114,840 subjects) were hospitalized and 0.05% (1370 subjects) were admitted to the intensive care unit. The overall mortality rate was estimated to be 0.33/100,000 population, with the highest mortality reported in the elderly aged over 60 years (1.31/100,000 population). Another study reported that a total of 740,835 patients were diagnosed with laboratory-confirmed H1N1 pandemic influenza and 225 died in Korea during the 2009 H1N1 pandemic until January 31, 2010 [14]. The incidence was calculated as 1492 per 100,000 population and the case fatality rate was 30 per 100,000 cases [14]. Contrary to some countries with high mortality rates (e.g., Mexico and Argentina) [15], case fatality was low in the ROK, although a large number of cases occurred. Thus, large-scale intervention with early antiviral therapy could reduce person-to-person transmission and disease severity, thereby decreasing pandemic influenza-related morbidity and mortality, as suggested in the PRIDE study [16]. Although the data are not sufficient regarding high-dose antiviral treatment, a double dose of oseltamivir (150 mg twotimes a day [b.i.d.] for adults) was used in some patients with severe influenza infection, particularly in those complicated with pneumonia (TABLE 2) [17–20]. Standard-dose oseltamivir was used for the pediatric patients, whereas either high-dose oseltamivir or a combination regimen was applied for adult patients with severe H1N1 influenza virus infections [17–23]. However, there are no data supporting high-dose oseltamivir therapy. Actually, blood trough concentrations after the administration of standard-dose oseltamivir (b.i.d. at 75 mg) are about Expert Rev. Anti Infect. Ther.
Review
Antiviral therapy in seasonal influenza & 2009 H1N1 pandemic influenza
A ILI index (ILI patients per 1000 ER visit)
240 2011-12 season
200
2012-13 season 160
2013-14 season
120 80 40
34 week
32 week
30 week
28 week
26 week
24 week
22 week
20 week
18 week
16 week
14 week
12 week
8 week
10 week
6 week
4 week
2 week
52 week
50 week
48 week
46 week
44 week
42 week
40 week
38 week
36 week
Downloaded by [University of Otago] at 03:45 27 September 2015
0
B (No.†) 1,200,000 1,000,000 800,000 600,000 400,000 Oseltamivir Zanamivir
200,000
Peramivir 0 2010-2011
95.2%
2011-2012
98.5%
2012-2013
2013-2014
98.2%
98.2%
(Years)
Figure 1. (A) Trends of influenza activity based on the surveillance in 2011–2012, 2012–2013 and 2013–2014 seasons by Hospital-based Influenza Morbidity and Mortality. (B) Annual (September–August) consumption of antiviral agents for the treatment of influenza (data given by sales volume collected by the pharmaceutical company). † Consumed numbers of defined treatment courses (e.g., oseltamivir 75 mg twice a day for 5 days in adults). ILI: Influenza-like illness.
8–18-times higher than the 90% inhibitory concentration [24]. Although a triple-combination antiviral regimen (oseltamivir, amantadine and ribavirin) showed lower 30-day mortality compared to oseltamivir alone (17 vs 35%) among critically ill informahealthcare.com
patients with laboratory-confirmed H1N1 pandemic influenza in a retrospective study, the difference was not statistically significant (p = 0.08) [25]. Antiviral combinations are usually not recommended. Although the combination of oseltamivir and doi: 10.1586/14787210.2015.1076334
Review
Song, Noh, Choi, Cheong & Kim
Table 1. Antiviral use for the treatment of influenza in the Republic of Korea (data given by sales volume collected by the pharmaceutical company). Season
Annual consumption of antiviral agents in Korea (no. of treatment courses for each antiviral agent)
Downloaded by [University of Otago] at 03:45 27 September 2015
Oseltamivir†
Zanamivir
Peramivir
2010–2011
177,127
8310
550
2011–2012
381,090
605
4900
2012–2013
369,378
1784
4800
2013–2014
1,065,515
5026
13,850
A treatment course was defined for each antiviral agent: oseltamivir (30/45/ 75 mg b.i.d., 5 days), zanamivir (10 mg b.i.d., 5 days) and peramivir (300 mg, single dose). † Recommended dosage for children by body weight: weight £15 kg, 30 mg b.i.d.; 15 kg
