Ингибиторы нейраминидазы: доказанная эффективность в лечении гриппа

Леонова М.В. Ингибиторы нейраминидазы: доказанная эффективность в лечении гриппа. Справочник поликлинического врача. 2018; 4: 18-22

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Leonova M.V. Neuraminidase inhibitors: proven effectiveness in the treatment of influenza. Handbook for Practitioners Doctors. 2018; 4: 18-22

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Аннотация

Представлен научный обзор результатов клинических, эпидемиологических исследований и метаанализов по оценке эффективности ингибиторов нейраминидазы (занамивира и осельтамивира) в лечении и профилактике гриппа. Наибольшая доказательная база представлена для осельтамивира. Так, применение препарата для лечения гриппа сокращает время до облегчения симптомов гриппа на 16,8 ч у взрослых и на 29 ч – у детей; значимо снижается риск развития осложнений респираторного тракта (пневмонии, бронхита, среднего отита) – на 44% и частоты госпитализаций, риск повторных сердечно-сосудистых исходов – на 42% у пациентов с кардиоваскулярными заболеваниями, а также риск смертности – на 19%. Эффективность ингибиторов нейраминидазы показана также и у госпитализированных пациентов. Осельтамивир включен в список основных лекарственных средств для лечения гриппа, рекомендованных Всемирной организацией здравоохранения, а также в Российские рекомендации по диагностике и лечению гриппа.

Ключевые слова: ингибиторы нейраминидазы, занамивир, осельтамивир, грипп, осложнения, смертность.

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A scientific review of the results of clinical, epidemiological studies and meta-analyzes on the efficacy of neuraminidase inhibitors (zanamivir and oseltamivir) in the treatment and prevention of influenza is presented. The largest evidence base is for oseltamivir. Thus, the use of the drug to treat influenza reduces the time to relief of flu symptoms by 16.8 hours in adults and 29 hours in children; significantly reduces the risk of complications of the respiratory tract (pneumonia, bronchitis, otitis media) – by 44% and hospitalization rates, the risk of repeated cardiovascular outcomes – by 42% in patients with cardiovascular diseases, as well as the risk of mortality – by 19%. The efficacy of neuraminidase inhibitors is also shown in hospitalized patients. Oseltamivir is included in the list of essential medicines for influenza treatment recommended by The World Health Organization, as well as in the list of the Russian practitioners' recommendations on the diagnosis and treatment of influenza.

Key words: neuraminidase inhibitors, zanamivir, oseltamivir, influenza, complications, mortality.

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Список литературы

1. Fiore AE, Shay DK, Broder K et al. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2008. MMWR Recomm Rep 2008; 57: 1–60.
2. Cass LMR, Efthymiopoulos C, Bye A. Pharmacokinetics of zanamivir after intravenous, oral, inhaled or intranasal administration to healthy volunteers. Clin Pharmacokinet 1999; 36 (Suppl. 1): 1–11.
3. Kaiser L, Keene ON, Hammond JMJ et al. Impact of zanamivir on antibiotic use for respiratory events following acute influenza in adolescents and adults. Arch Intern Med 2000; 160: 3234–40.
4. He G, Massarella J, Ward P. Clinical pharmacokinetics of the prodrug oseltamivir and its active metabolite Ro 64-0802. Clin Pharmacokinet 1999; 37 (6): 471–84.
5. Oo C, Barrett J, Hill G et al. Pharmacokinetics and dosage recommendations for an oseltamivir oral suspension for the treatment of influenza in children. Paediatr Drugs 2001; 3 (3): 229–36.
6. Nicholson KG, Aoki FY, Osterhaus AD et al. Efficacy and safety of oseltamivir in treatment of acute influenza: a randomised controlled trial. Neuraminidase Inhibitor Flu Treatment Investigator Group. Lancet 2000; 355: 1845–50.
7. Treanor JJ, Hayden FG, Vrooman PS et al. Efficacy and safety of the oral neuraminidase inhibitor oseltamivir in treating acute influenza: a randomized controlled trial. US Oral Neuraminidase Study Group. JAMA 2000; 283: 1016–24.
8. Aoki FY, Macleod MD, Paggiaro P et al. Early administration of oral oseltamivir increases the benefits of influenza treatment. J Antimicrob Chemother 2003; 51: 123–9.
9. Kaiser L, Wat C, Mills T et al. Impact of oseltamivir treatment on influenza-related lower respiratory tract complications and hospitalizations. Arch Intern Med 2003; 163: 1667–72.
10. Whitley RJ, Hayden FG, Reisinger KS et al. Oral oseltamivir treatment of influenza in children. Pediatr Infect Dis J 2001; 20: 127–33.
11. Johnston SL, Ferrero F, Garcia ML et al. Oral oseltamivir improves pulmonary function and reduces exacerbation frequency for influenza-infected children with asthma. Pediatr Infect Dis J 2005; 24: 225–32.
12. Tamura D, Miura T, Kikuchi Y. Oseltamivir phosphate in infants under 1 year of age with influenza infection. Pediatr Int 2005; 47: 484.
13. Singh S, Barghoorn J, Bagdonas A et al. Clinical benefits with oseltamivir in treating influenza in adult populations: results of a pooled and subgroup analysis. Clin Drug Invest 2003; 23: 561–9.
14. McGeer A, Green KA, Plevneshi A et al. Antiviral therapy and outcomes of influenza requiring hospitalization in Ontario, Canada. Clin Infect Dis 2007; 45: 1568–75.
15. Lee N, Choi K, Chan P et al. Outcomes of adults hospitalized with influenza. Thorax 2010; 65: 510–5.
16. Dutkowski R. Oseltamivir in seasonal influenza: cumulative experience in low- and high-risk patients. J Antimicrob Chemother 2010; 65 (Suppl. 2): ii11–24.
17. Majid M, Curkendall S, Blumentals WA. The influence of oseltamivir on the risk of stroke after influenza infection. Cardiology 2009; 113: 98–107.
18. Casscells SW, Granger E, Kress AM et al. Use of oseltamivir after influenza infection is associated with reduced incidence of recurrent adverse cardiovascular outcomes among military health system beneficiaries with prior cardiovascular disease. Circ Cardiovasc Qual Outcomes 2009; 2: 108–15.
19. Jefferson T, Jones MA, Doshi P et al. Neuraminidase inhibitors for preventing and treating influenza in healthy adults and children. Cochrane Database Syst Rev 2014; (4): CD008965.
20. Dobson J, Whitley RJ, Pocock S, Monto AS. Oseltamivir treatment for influenza in adults: a meta-analysis of randomised controlled trials. Lancet 2015; 385 (9979): 1729–37.
21. Hsu J, Santesso N, Mustafa R et al. Antivirals for treatment of influenza: a systematic review and meta-analysis of observational studies. Ann Intern Med 2012; 156: 512–24.
22. Muthuri SG, Venkatesan S, Myles PR et al. Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data. Lancet Respirator Med 2014; 2 (5): 395–404.
23. Wang K, Shun-Shin M, Gill P et al. Neuraminidase inhibitors for preventing and treating influenza in children (published trials only). Cochrane Database Syst Rev 2012; 4: CD002744.
24. Jackson RJ, Cooper KL, Tappenden P et al. Oseltamivir, zanamivir and amantadine in the prevention of influenza: а systematic review. J Infect 2011; 62: 14–25.
25. WHO Guidelines for Pharmacological Management of Pandemic Influenza A (H1N1) 2009 and other Influenza Viruses. Geneva: World Health Organization, 2010.
26. Методические рекомендации по диагностике и лечению гриппа. МЗ РФ, 2016. / Metodicheskie rekomendacii po diagnostike i lecheniyu grippa. MZ RF, 2016. [in Russian]

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1. Fiore AE, Shay DK, Broder K et al. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2008. MMWR Recomm Rep 2008; 57: 1–60.
2. Cass LMR, Efthymiopoulos C, Bye A. Pharmacokinetics of zanamivir after intravenous, oral, inhaled or intranasal administration to healthy volunteers. Clin Pharmacokinet 1999; 36 (Suppl. 1): 1–11.
3. Kaiser L, Keene ON, Hammond JMJ et al. Impact of zanamivir on antibiotic use for respiratory events following acute influenza in adolescents and adults. Arch Intern Med 2000; 160: 3234–40.
4. He G, Massarella J, Ward P. Clinical pharmacokinetics of the prodrug oseltamivir and its active metabolite Ro 64-0802. Clin Pharmacokinet 1999; 37 (6): 471–84.
5. Oo C, Barrett J, Hill G et al. Pharmacokinetics and dosage recommendations for an oseltamivir oral suspension for the treatment of influenza in children. Paediatr Drugs 2001; 3 (3): 229–36.
6. Nicholson KG, Aoki FY, Osterhaus AD et al. Efficacy and safety of oseltamivir in treatment of acute influenza: a randomised controlled trial. Neuraminidase Inhibitor Flu Treatment Investigator Group. Lancet 2000; 355: 1845–50.
7. Treanor JJ, Hayden FG, Vrooman PS et al. Efficacy and safety of the oral neuraminidase inhibitor oseltamivir in treating acute influenza: a randomized controlled trial. US Oral Neuraminidase Study Group. JAMA 2000; 283: 1016–24.
8. Aoki FY, Macleod MD, Paggiaro P et al. Early administration of oral oseltamivir increases the benefits of influenza treatment. J Antimicrob Chemother 2003; 51: 123–9.
9. Kaiser L, Wat C, Mills T et al. Impact of oseltamivir treatment on influenza-related lower respiratory tract complications and hospitalizations. Arch Intern Med 2003; 163: 1667–72.
10. Whitley RJ, Hayden FG, Reisinger KS et al. Oral oseltamivir treatment of influenza in children. Pediatr Infect Dis J 2001; 20: 127–33.
11. Johnston SL, Ferrero F, Garcia ML et al. Oral oseltamivir improves pulmonary function and reduces exacerbation frequency for influenza-infected children with asthma. Pediatr Infect Dis J 2005; 24: 225–32.
12. Tamura D, Miura T, Kikuchi Y. Oseltamivir phosphate in infants under 1 year of age with influenza infection. Pediatr Int 2005; 47: 484.
13. Singh S, Barghoorn J, Bagdonas A et al. Clinical benefits with oseltamivir in treating influenza in adult populations: results of a pooled and subgroup analysis. Clin Drug Invest 2003; 23: 561–9.
14. McGeer A, Green KA, Plevneshi A et al. Antiviral therapy and outcomes of influenza requiring hospitalization in Ontario, Canada. Clin Infect Dis 2007; 45: 1568–75.
15. Lee N, Choi K, Chan P et al. Outcomes of adults hospitalized with influenza. Thorax 2010; 65: 510–5.
16. Dutkowski R. Oseltamivir in seasonal influenza: cumulative experience in low- and high-risk patients. J Antimicrob Chemother 2010; 65 (Suppl. 2): ii11–24.
17. Majid M, Curkendall S, Blumentals WA. The influence of oseltamivir on the risk of stroke after influenza infection. Cardiology 2009; 113: 98–107.
18. Casscells SW, Granger E, Kress AM et al. Use of oseltamivir after influenza infection is associated with reduced incidence of recurrent adverse cardiovascular outcomes among military health system beneficiaries with prior cardiovascular disease. Circ Cardiovasc Qual Outcomes 2009; 2: 108–15.
19. Jefferson T, Jones MA, Doshi P et al. Neuraminidase inhibitors for preventing and treating influenza in healthy adults and children. Cochrane Database Syst Rev 2014; (4): CD008965.
20. Dobson J, Whitley RJ, Pocock S, Monto AS. Oseltamivir treatment for influenza in adults: a meta-analysis of randomised controlled trials. Lancet 2015; 385 (9979): 1729–37.
21. Hsu J, Santesso N, Mustafa R et al. Antivirals for treatment of influenza: a systematic review and meta-analysis of observational studies. Ann Intern Med 2012; 156: 512–24.
22. Muthuri SG, Venkatesan S, Myles PR et al. Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data. Lancet Respirator Med 2014; 2 (5): 395–404.
23. Wang K, Shun-Shin M, Gill P et al. Neuraminidase inhibitors for preventing and treating influenza in children (published trials only). Cochrane Database Syst Rev 2012; 4: CD002744.
24. Jackson RJ, Cooper KL, Tappenden P et al. Oseltamivir, zanamivir and amantadine in the prevention of influenza: а systematic review. J Infect 2011; 62: 14–25.
25. WHO Guidelines for Pharmacological Management of Pandemic Influenza A (H1N1) 2009 and other Influenza Viruses. Geneva: World Health Organization, 2010.
26. Metodicheskie rekomendacii po diagnostike i lecheniyu grippa. MZ RF, 2016. [in Russian]

Авторы

М.В.Леонова

Межрегиональная общественная организация «Ассоциация клинических фармакологов России»
anti23@mail.ru

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M.V.Leonova
anti23@mail.ru

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