Upper Respiratory Infections: The Lowdown

About 25 million Americans see a physician for an upper respiratory infection (URI) every year.¹ There are more than 1 billion colds in the United States every year,² as well, and 3 to 5 million individuals worldwide catch the flu, with more than 250,000 individuals dying from it each year.^2,3

Vaccination, the best preventive measure for the flu, which can be mild to severe,^3,4 is very strongly encouraged for pregnant women and patients at high risk of complications due to other diseases, including asthma, diabetes, heart disease, and immunosuppression.^3,4 The American Academy of Pediatrics even recommends universal use of trivalent or quadrivalent flu shots, with no preference given to either.³

There are 3 types of flu: A, B, and C.⁴ Influenza A is subdivided by hemagglutinin (H protein) and neuraminidase (N protein), such as H1N1.⁴ Influenza B is named for where it was first identified (Victoria or Yamagata lineage).⁴ Influenza C causes milder illness and occurs less often, so it is not included in the seasonal flu shots.⁴

Appropriate Use of Antivirals

Effective management of URIs depends on detection and differentiation within 48 hours of symptom onset—for efficacy, antivirals need to be started within these 48 hours5,6 (Online Table^10-12,14,15). Roche’s new Liat PCR System is a pointof- care test that distinguishes between influenzas A and B, using a nasal swab specimen, in about 20 minutes.^{5, 6} The test is 94% accurate, as well as extremely sensitive (it has a low limit of detection).^5,7 However, it cannot detect influenza C.⁷

Table: Antivirals

Oseltamivir

Zanamivir

Peramivir

Amantadine

Rimantadine

Influenza A treatment

Yes

Yes

Yes

Yes, for H1N1, H2N2, or H2N3

Yes, for H1N1, H2N2, or H2N3

Influenza B treatment

Yes

Yes

Yes

No

No

Influenza prophylaxis

Yes

Yes

Yes

Yes, for influenza A only

Yes, for influenza A only

Use concurrently with flu shot

No

No

No

Yes

Yes

^{Adapted from references 10-12, 14, 15.}

Antivirals are not a substitute for immunization, but can be used for treatment or prophylaxis.³ It is expected that this year’s flu viruses (ie, the 2015-2016 flu season) will be susceptible to all of the neuraminidase inhibitors.³ Therefore, consider early, empiric treatment of hospitalized and other high-risk patients with neuraminidase inhibitors.⁸ Amantadine and rimantadine are not recommended due to high resistance in the currently circulating flu virus.³

For specific recommendations for your pediatric patients, check the American Academy of Pediatrics website (www.aapredbook.org/flu) for updated information when the flu season officially starts.³ Current pediatric guidelines recommend neuraminidase inhibitor antivirals (oseltamivir or zanamivir) for severe or progressive confirmed/highly suspected H1N1 infections.⁹ For H3N2, oseltamivir or zanamivir are recommended, while adamantanes (amantadine, rimantadine) are not recommended.9 For H5N1, oseltamivir and zanamivir are first-line treatment, with amantadine reserved for when neuraminidase inhibitors are not available.⁹

Antivirals are not recommended for influenza-like syndrome: resistance to antivirals is emerging, and they do not seem to affect outcomes much.⁹ About 2% of flu samples (from the 2013 to 2014 flu season) were resistant to neuraminidase inhibitors, primarily oseltamivir.8 Neuraminidase inhibitors also should not be used in close timing with the flu shot, as they could decrease the vaccination’s effectiveness.^10-12

Using oseltamivir for the flu decreases the risk of lower respiratory tract complications and the need for antibiotics by 28%.¹³ Oseltamivir is recommended for postexposure prophylaxis in nonvaccinated, institutionalized people,⁹ as well as for uncomplicated influenza A and B.10 It can be used in renally impaired patients, including those on dialysis.¹⁰ Nausea and vomiting are the most common adverse effects (AEs).¹⁰ Therefore, oseltamivir should be taken with food to decrease stomach upset.¹⁰ Oseltamivir reduces flu symptoms by 1.5 days for pediatric patients, 1 day for geriatric patients, and 1.3 days for adolescents and adults.¹⁰ When used prophylactically, only 1% of patients got an influenza infection.¹⁰

Zanamivir is inhaled, so it is not recommended for patients with airway diseases, as serious bronchospasm has occurred.¹¹ It is given twice daily for 10 or 28 days (treatment and prophylaxis, respectively) and can be used to treat or prevent influenza A or B in patients, but is not proven effective in nursing home patients.¹¹ AEs are similar to placebo in frequency.¹¹ Using zanamivir for postexposure prophylaxis reduced the incidence of flu from 19% to 4.1% in infected households and from 6.1% to 2% in community outbreaks.¹¹ Although zanamivir reduces flu symptoms by 1 to 1.5 days, patients with lower temperatures (100.94°F [38.3°C] or lower) and less severe symptoms benefit less.¹¹

Peramivir is a single-dose intravenous infusion neuraminidase inhibitor approved for flu treatment¹² in adults; however, it did not help patients whose flu was so severe that they were hospitalized.¹² Peramivir reduced flu symptoms by 21 hours.¹²

Amantadine and rimantadine are used for both the treatment and prevention of influenza A (H1N1, H2N2, and H3N2), but have little to no effect on influenza B.^14,15 Although amantadine is approved for the treatment and prevention of influenza A in adults and pediatric patients, rimantadine is approved just to treat influenza A in adults (but can be used for prophylaxis in both adults and children).^14,15 When used for prophylaxis, either drug can be given with a flu shot while immunity develops.^14,15 Common AEs of both drugs include nausea, dizziness, and insomnia.¹⁴ These drugs may be a less desirable treatment, as there are influenza A variants that are resistant to them.¹⁴ Amantadine is dosed orally once a day, but the dose can be divided if there are central nervous system effects.¹⁴ Rimantadine is dosed orally twice daily.¹⁵

Patient Counseling

Treatment focuses on symptoms and time.¹ Therefore, encourage patients to get plenty of rest and drink lots of fluids.² Educate them that although OTC cough and cold medications help with symptoms, they will not affect the course of the cold.² Also inform patients that decongestants help with nasal congestion¹; vitamin and herbal remedies are unproven, but may help¹; and probiotics or yogurt with active cultures may help prevent colds, as well.² Discourage the use of antibiotics, as they are not useful for URIs,^1,2 and emphasize avoidance of infections. Promote frequent hand washing or use of sanitizer, cleaning frequently touched surfaces with a disinfectant, and getting enough sleep.² If symptoms last more than a week, recommend the patient get checked for allergies, sinus infection, or other health problems.²

Debra Freiheit has been a practicing pharmacist and human services professional for over 25 years. Specializing in medical information, Debra has compiled a broad spectrum of experience obtained through research for companies including Cerner and PPD Inc. With an emphasis on clear and concise information transfer, Debra has built a career communicating data with medical professionals and patients. Education and knowledge have been her motivation for a rich career of caregiving through research. Debra’s current project involves the creation of a multinational database of drug information.

References

• Weiss JR, Tessema B, Brown SM. Complementary and integrative treatments: upper respiratory infection. Otolaryngol Clin North Am. 2013;46(3):335-344. doi: 10.1016/j.otc.2012.12.007.
• Common cold. Medline Plus website. www.nlm.nih.gov/medlineplus/ency/article/000678.htm. Updated November 2, 2014. Accessed September 16, 2015.
• Committee on Infectious Diseases. Recommendations for prevention and control of influenza in children, 2015-2016. Pediatrics. 2015;136(4):792-808. doi: 10.1542/peds.2015-2920. http://pediatrics.aappublications.org/content/early/2015/09/01/peds.2015-2920.full.pdf.
• World Health Organization fact sheet: influenza virus infections in humans (February 2014). WHO website. www.who.int/influenza/human_animal_interface/virology_laboratories_and_vaccines/influenza_virus_infections_humans_feb14.pdf?ua=1. Accessed September 29, 2015.
• Roche receives FDA CLIA waiver for flu A/B test for use on its cobas Liat PCR System [media release]. Basel, Switzerland: Roche; September 22, 2015. www.roche.com/media/store/releases/med-cor-2015-09-22.htm. Accessed September 24, 2015.
• Brooks M. FDA clears first real-time PCR test for influenza A/B. Medscape website. www.medscape.com/viewarticle/851413?src=wnl_edit_newsal&uac=201120MY&impID=835981&faf=1. Published September 23, 2015. Accessed September 23, 2015.
• cobas Liat PCR System. Roche Diagnostics USA website. https://usdiagnostics.roche.com/en/instrument/cobas-liat.html#assay-menu-with-a-broad-menu-o/influenza-a-b. Accessed September 27, 2015.
• World Health Organization weekly epidemiological record. WHO website. www.who.int/wer/2015/wer9033.pdf?ua=1. Published August14, 2015. Accessed August 14, 2015.
• Zeng L, Zang L, Hu Z, et al. Systematic review of evidence-based guidelines on medication therapy for upper respiratory tract infection in children with AGREE instrument. PLoS One. 2014;9(2):e877111. doi: 10.1371/journal.pone.0087711.
• Tamiflu [package insert]. South San Francisco, CA: Genentech, Inc; 2014. www.accessdata.fda.gov/drugsatfda_docs/label/2014/021087s060,021246s043lbl.pdf.
• Relenza [package insert]. Research Triangle Park, NC: GlaxoSmithKline; 2011. www.accessdata.fda.gov/drugsatfda_docs/label/2011/021036s027lbl.pdf.
• Rapivab [package insert]. Durham, NC: BioCryst Pharmaceuticals, Inc; 2014. www.accessdata.fda.gov/drugsatfda_docs/label/2014/206426lbl.pdf.
• Hernán MA, Lipsitch M. Oseltamivir and risk of lower respiratory tract complications in patients with flu symptoms: a meta-analysis of eleven randomized clinical trials. Clin Infect Dis. 2011;53(3):277-279. doi: 10.1093/cid/cir400.
• Amantadine hydrochloride capsules, USP [package insert]. Minneapolis, MN: Upsher-Smith Laboratories, Inc; 2011.
• Flumadine [package insert]. St. Louis, MO: Forest Pharmaceuticals, Inc; 2010.