Dtsch Arztebl Int 113(47): 799-807

PMC: PMC5240024

PMID: 28043323

Antiviral Medications in Seasonal and Pandemic Influenza

^{Federal Institute for Drugs and Medical Devices, Bonn}

^{Center for Infectious Diseases and Infection Control, Jena University Hospital}

^{Robert Koch Institute, Berlin}

^{Agaplesion Diakoniekrankenhaus Rotenburg (Wümme)}

*Federal Institute for Drugs and Medical Devices Kurt-Georg-Kiesinger Allee 3 53175 Bonn, Germany ed.mrafb@trenheL.enigeR

Received 2016 Jan 24; Accepted 2016 Sep 29.

Abstract

Background

Amantadine, oseltamivir, and zanamivir are currently available in Germany for the prevention and treatment of influenza. We review their efficacy and side-effect profiles.

Methods

This review is based on pertinent randomized and controlled trials (RCTs) and systematic reviews retrieved by a systematic literature search, and on other relevant literature.

Results

The efficacy of antiviral drugs for the prevention of symptomatic influenza ranges from 60% to 90% (number needed to treat [NNT], 8–89) depending on the population and type of drug in question. Antiviral drugs shorten the duration of illness by 0.5–1.5 days when given within 48 hours of the onset of symptoms. Neuraminidase inhibitors do not significantly lower the incidence of bronchitis in adults, or of otitis media in children; they do have a positive effect against reported, but not necessarily diagnostically confirmed pneumonia in adults (NNT, 89 [50–232]). The RCTs yielded no information about possible effects on severe cases of influenza, or on mortality, as they included only mildly or moderately ill patients, but observational studies have yielded some evidence of benefit. The most common side effects of oseltamivir (>10%) are headache, nausea, and vomiting; of zanamivir (>1%), a skin rash; and of amantadine (>1%), loss of appetite, nausea, and central nervous effects.

Conclusion

The benefits of antiviral drugs, particularly neuraminidase inhibitors, outweigh their risks. In deciding whether to use them, physicians should consider the properties of the currently circulating viruses and the patient’s individual risk constellation, as directed in clinical treatment recommendations.

Abstract

In Germany, the drugs available for influenza prophylaxis and therapy are amantadine and the neuraminidase inhibitors (NIs) oseltamivir and zanamivir. Unlike neuraminidase inhibitors, amantadine, as an M2 membrane channel blocker, is only effective against influenza A viruses. The use of amantadine is no longer recommended, principally due to rapid development of resistance during its use and high resistance rates in circulating influenza viruses, as well as poor tolerability (1, 2).

Most randomized controlled trials (RCTs)—the gold standard for proving efficacy—for amantadine, zanamivir, and oseltamivir are more than 15 years old. Since they were conducted, these trials have been summarized in many systematic reviews and meta-analyses. This review came about as part of Germany’s national pandemic plan and was performed by a working group of the Robert Koch Institute (RKI) Expert Advisory Board on Influenza. It brings together the most important information from the chapter Medicines relevant in a pandemic of the scientific part of the German Influenza Pandemic Preparedness Plan. This provides comprehensive details on the amount of underlying data and the epidemiology of influenza (3). Regarding questions on political implications and data transparency, see earlier articles in Deutches Ärzteblatt (4, 5).

Public health institutions and specialist societies have published treatment recommendations on the use of antiviral drugs for influenza (box). The biased nature of some public debate on the issue makes an objective representation of the available evidence on antiviral drugs particularly important.

BOX

Clinical recommendations

Summary of the most important current recommendations on the use of antiviral drugs for influenza made by the World Health Organization (WHO), the European Centre for Disease Prevention and Control (ECDC), the US Centers for Disease Control (CDCs), and Public Health England (PHE) (6– 9)

Who should be treated?

Therapy is recommended for patients with confirmed or suspected influenza who meet the following criteria:

Hospitalized
Severe, complicated, or progressive disease
High risk of influenza-related complications*

There is an increased risk of influenza-related complications in:

Children aged under 2 years (PHE: under 6 months)
Adults aged over 65 years
Patients with chronic diseases such as chronic obstructive pulmonary disease (COPD), heart failure, diabetes mellitus, severe underlying neurological diseases, or morbid obesity (body mass index [BMI] =40)
Immunosuppressed patients (e.g. iatrogenic or HIV infection)
Pregnant or postpartum (<2 weeks) women
Patients aged over 19 years receiving long-term aspirin treatment (risk of Reye’s syndrome)
Residents of nursing homes and other chronic-care facilities

Which drugs are recommended?

Primarily, the authorized neuraminidase inhibitors. Oral oseltamivir is recommended as first-line treatment unless there is known resistance among circulating viruses or enteral resorption disorder in the patient.

When should treatment begin?

Treatment should be started as soon as possible, i.e. on clinical suspicion even without laboratory confirmation. This is because the greatest benefit from antiviral treatment can be expected if it begins within 48 hours of onset of typical influenza symptoms. For patients with severe, complicated, or progressive disease and for hospitalized patients, all the institutions stated above also recommend a later initiation of treatment, as there is evidence of a benefit if treatment begins up to 5 days after symptom onset.

What doses should be used?

See eBox 1

How long should treatment last?

Optimum treatment duration for severe, complicated, or progressive disease and for immunosuppressed patients is unknown. Individual clinical assessment is considered particularly important when deciding whether to prolong treatment after 5 days.

Who should receive prophylactic treatment?

Widespread use of antiviral drugs for post-exposure and pre-exposure chemoprophylaxis is not recommended. It may be indicated on an individual basis for the risk groups stated above.

How should adult patients with community-acquired pneumonia be treated?

In the German S3 guideline, the specialized societies mentioned therein recommend calculated, early administration of oseltamivir for hospitalized patients with moderate or severe pneumonia in the event of an influenza pandemic or high seasonal influenza activity.

This treatment should be concomitant to antibacterial therapy. No maximum time interval between symptom onset and beginning of treatment is given. If the initial influenza PCR test remains negative, antiviral treatment should be discontinued. The S3 guideline rates the evidence for this recommendation as weak (recommendation grade C) (10).

*For treatment indication, the importance of individual clinical assessment of the patient is emphasized. PCR: Polymerase chain reaction

Below, we provide a brief description of the evidence on the efficacy and safety of the antiviral drugs available for influenza in Germany. This takes the form of answers to questions that are of particular clinical importance for the potential use of these drugs.

BOX

Search of the literature

Key Messages

Dosage recommendations for neuraminidase inhibitors

Acknowledgments

Acknowledgement

We would like to thank the members of the Expert Advisory Board on Influenza of the Robert Koch Institute (RKI) for their valuable contributions to the content of this article: Dr. Bernhard Bornhofen, PD Dr. Roswitha Bruns, Prof. Dr. Petra Gastmeier, Prof. Dr. Timm Harder, Prof. Dr. Ulrich Hartenauer, Prof. Dr. Eberhard Hildt, Prof. Dr. Hanna Kaduszkiewicz, Peter Lang, Prof. Dr. Thomas Mertens, Prof. Dr. Georg Peters, and Prof. Dr. Horst Schroten.

We would also like to thank the following guests of the Expert Advisory Board on Influenza for their advice during sessions: the Consortium of the Upper Federal State Authorities (AOLG, Arbeitsgemeinschaft der oberen Landesbehörden), the Working Group on Protection Against Infection of the AOLG, the German Federal Office of Civil Protection and Disaster Assistance (BBK, Bundesamt für Bevölkerungsschutz und Katastrophenhilfe), the German Medical Association (Bundesärztekammer), the German Federal Ministry of Labour and Social Affairs, the German Federal Ministry of Health, the German Federal Ministry of Defence, the German Federal Ministry of the Interior, the Federal Union of German Associations of Pharmacists (ABDA, Bundesvereinigung Deutscher Apothekerverbände), the German Hospital Federation (Deutsche Krankenhausgesellschaft), the Federal Joint Committee (G-BA, Gemeinsamer Bundesausschuss), the National Association of Statutory Health Insurance Physicians (KBV, Kassenärztliche Bundesvereinigung), the Umbrella Organization of Health Insurers (Spitzenverband Bund der Krankenkassen), and the German Standing Vaccination Committee (STIKO, Ständige Impfkommission) of the Robert Koch Institute.

In addition, our thanks go to Prof. Dr. med. Walter Haas for his helpful specialist comments and to Yvonne Bichel for performing the literature search.

Acknowledgments

Footnotes

Conflict of interest statement

The authors declare that no conflict of interest exists.

Translated from the original German by Caroline Shimakawa-Devitt, M.A.

Footnotes

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