October 12, 2017 by Casey Carr
Brian K. Lindner, PharmD, PGY1 Pharmacy Practice Resident
Every winter emergency departments (EDs) incur an influx of patients presenting with symptoms related to the influenza virus. There are three neuraminidase inhibitors (NIs) available in the U.S., oseltamivir (Tamiflu©), zanamivir (Relenza©), and peramivir (Rapivab©). Oseltamivir is the most widely used due to its availability as an oral formulation.
Treatment of influenza:
Underlying conditions, disease severity, and time since symptom onset are important factors to consider before initiating antiviral therapy for influenza. In a previously healthy, symptomatic outpatient with confirmed influenza, treatment is only indicated within 48 hours of symptom onset. Considerations for treatment outside of this 48 hour window or for empiric treatment without respiratory virus testing are listed in Table 1. When the decision to initiate treatment is made, dosing recommendations and monitoring can be found in Table 2.
Table 1. Guidance on Treatment of Patients with Symptoms for Longer than 48 hours and Empiric Treatment
|Patients who qualify for treatment past 48 hours of symptom onset:
· Hospitalized patients with influenza
· Children <2 years
· Adults > 65
· Immunosuppressed patients
· Women who are pregnant or are less than 2 weeks postpartum
|Empiric treatment can be considered in the following patients:
· Fever plus influenza symptoms
· Unexplained interstitial pneumonia
· New respiratory failure without an obvious non-influenza cause
Table 2. Adult Dosing and Monitoring for Oseltamivir Treatment
|Medication||Dosing||Side effects||Renal dose adjustments|
|Oseltamivir (Tamiflu)||Adult Treatment: 75 mg BID x 5 days*
|Common: nausea, vomiting
Severe: hypersensitivity, neuropsychiatric effects
|CrCl >60: 75mg q12h
CrCl 30-60: 75mg q24h
CrCl 10-29: 30mg q24h
<10 or iHD: 30mg every HD session
*Solid organ transplant, hematologic malignancy, or bone marrow transplant patients may be treated for 10 days
Before prescribing antiviral treatment, a clinician should thoughtfully consider both the likelihood of viral infection and the likelihood of therapy completion. While it may seem giving an empiric one time dose of oseltamivir is benign, acquired resistance to antivirals has been demonstrated. Adamantine antivirals have become almost obsolete as a treatment strategy for influenza, in part due to their ineffectiveness against influenza B, but also due to significant resistance of influenza A. Furthermore, the influenza virus has already demonstrated resistance to NIs in the 2007 and 2009 seasons. The prevention of NI resistance is crucial from a public health and public safety perspective.
In conclusion, oseltamivir should be given to patients within 48 hours of symptom onset, or in patients who are high risk for complications from a severe lung infection. Proper dosing in terms of strength and duration is crucial in limiting adverse effects and in the prevention of resistance to current antiviral therapies.
- Peters T, Suerken C, Snively B, et al. Influenza Testing, Diagnosis, and Treatment in the Emergency Department in 2009-2010 and 2010-2011. Acad Emerg Med. Aug 2013;20(8):786-794.
- Centers for Disease Control and Prevention. [Antiviral Agents for the Treatment and Chemoprophylaxis of Influenza]. MMWR 2011;60(1):1-18.
- Lexicomp Online®, AHFS Essentials®, Hudson, Ohio: Lexi-Comp, Inc.; September 19, 2017.
- Cosgrove S, Avdic E, Dzintars K, et al. The Johns Hopkins Antibiotic Guidelines 2016-2017.p95.
- Li T, Chan M, Lee N. Clinical Implications of Antiviral Resistance in Influenza. Viruses. 2015;7:4929-4944.