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Therapeutics

Postexposure prophylaxis with inhaled zanamivir was efficacious for household contacts of persons with influenza

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ACP J Club. 2001 Sep-Oct;135:42. doi:10.7326/ACPJC-2001-135-2-042

Related Content in this Issue
• Companion Abstract and Commentary: Oseltamivir reduced new cases of influenza in household contacts of persons with clinical or confirmed influenza


Source Citation

Hayden FG, Gubareva LV, Monto AS, et al., for the Zanamivir Family Study Group. Inhaled zanamivir for the prevention of influenza in families. N Engl J Med. 2000 Nov 2;343:1282-9. [PubMed ID: 11058672] (All 2001 articles were reviewed for relevancy, and abstracts were last revised in 2007.)


Abstract

Question

In household contacts of persons with influenza, what is the efficacy of postexposure prophylaxis with inhaled zanamivir?

Design

Randomized {allocation concealed*}†, blinded {patients, clinicians, outcome assessors, and statisticians}†* controlled trial with follow-up to 28 days.

Setting

15 centers in the United States, Canada, the United Kingdom, and Finland.

Participants

337 families with 2 to 5 members, including ≥ 1 adult and ≥ 1 child who was 5 to 17 years of age. Family members who were hypersensitive to zanamivir, immunocompromised, pregnant, breast-feeding, or using an anti-influenza agent were not assigned to a study drug. All families were included in the intention-to-treat analysis, and 1147 of 1158 (99%) participants completed the study.

Intervention

Within 36 hours after 1 family member contracted an influenza-like illness (index case), eligible family members began to take the study drug. Influenza-like illness was defined as ≥ 2 of temperature ≥ 37.8° C, feverishness, cough, headache, sore throat, and myalgia. The 321 index-case patients (mean age 19 y, 58% women) were allocated to inhaled zanamivir (n = 163), 10 mg, or placebo (n = 158) twice a day for 5 days. The 837 other healthy family members (mean age 26 y, 55% women) received the same drug as did the index-case patient (414 received zanamivir, 10 mg once daily for 10 d, and 423 received placebo).

Main outcome measure

Proportion of families with ≥ 1 initially healthy family member who developed symptomatic, laboratory-confirmed influenza (≥ 3 consecutive diary-card entries listing ≥ 2 of temperature ≥ 37.8° C, feverishness, cough, headache, sore throat, and myalgia).

Main results

Intention-to-treat analysis showed that fewer families in the zanamivir group had ≥ 1 household contact in whom symptomatic laboratory-confirmed influenza developed than did families in the placebo group (Table). No resistant variants to zanamivir were detected. Median duration of symptoms in ill index-case patients was shorter in the zanamivir group than in the placebo group (5.0 vs 7.5 d, P = 0.01).

Conclusion

Postexposure inhaled zanamivir prevented development of influenza in household contacts of family members with influenza-like illness who were also treated with inhaled zanamivir.

*See Glossary.

†Information provided by author.

Source of funding: Glaxo Wellcome.

For correspondence: Dr. F.G. Hayden, University of Virginia, Health Sciences Center, Box 800473, Charlottesville, VA 22908, USA.


Table. Postexposure zanamivir vs placebo for prevention of influenza in household contacts of persons with influenza-like illness‡

Outcome at 28 d Zanamivir Placebo RRR (95% CI) NNT (CI)
Families with laboratory-confirmed influenza in ≥ 1 contact 4% 19% 78% (53 to 90) 7 (5 to 12)

‡Abbreviations defined in Glossary; RRR, NNT, and CI calculated from data in article.


Commentary

Although inactivated influenza vaccines remain the cornerstone of prevention for both influenza A and B, a new class of antiviral agents, the neuraminidase inhibitors, now have a role in both the treatment and prevention of influenza.

Two neuraminidase inhibitors are licensed in the United States. Zanamivir (administered by inhalation) is approved for treatment of influenza A and B. Oseltamivir phosphate (administered orally) is approved for both treatment and chemoprophylaxis of influenza A and B. For both treatment of ill persons and chemoprophylaxis of household contacts, the efficacy of the 2 drugs appears similar; although zanamivir has fewer side effects overall than does oseltamivir, it does have the side effect of bronchospasm.

Neuraminidase inhibitors offer advantages over the current drugs, amantadine and rimantadine, in that they are effective against both influenza A and B and have fewer bothersome side effects. Their usefulness, however, is limited by cost; currently, the wholesale cost of neuraminidase inhibitors is about $50 per 5-day course of treatment.

The side effects of neuraminidase inhibitors vary by route of administration. Treatment with zanamivir may exacerbate underlying airway disease. Other reported side effects include nausea, dizziness, diarrhea, nasal symptoms, and other symptoms; none occurred in more than 5% of patients. About 10% of persons treated with oseltamivir had nausea or vomiting. About 10% to 30% of persons taking amantadine had central nervous system side effects (anxiety, nervousness, lightheadedness, and difficulty concentrating) compared with < 10% of those taking rimantadine.

These 2 studies indicate that neuraminidase inhibitors have a role in prevention, if only to provide a brief period for persons to become immunized after the start of an influenza epidemic. Published recommendations for the preventive use of these drugs incorporate 2 main strategies: temporarily protecting high-risk persons who may not be immune after vaccination and institutional outbreak control (1, 2).

For treatment, the duration of therapy for either drug is 5 days, provided that the drug is started within 2 days of symptom onset. The duration of administration of the drug for chemoprophylaxis varies. If used as described in these studies for prevention of influenza in healthy persons, the duration of administration is 7 to 10 days. To prevent influenza among persons with compromised immune systems who will not respond adequately to influenza vaccine, the drug should be administered for the duration of influenza activity in the community.

The choice of antiviral drug depends on the strain of virus circulating, the known efficacy of the drug, expected side effects, and cost. To prevent influenza in persons for whom immunization may not be effective, an antiviral drug should be taken for an extended period. In these patients, the cost of neuraminidase inhibitors, which is higher than that of amantadine and rimantadine, may limit their acceptability.

Neuraminidase inhibitors can prevent the less serious complications of influenza, such as otitis and sinusitis. The information is insufficient to ascertain the degree to which these drugs reduce the most serious complications of influenza—pneumonia and death.

Charles E. Haley, MD, MS
TrailBlazer Health Enterprises, LLC
Dallas, Texas, USA


References

1. Couch RB. Prevention and treatment of influenza. N Engl J Med. 2000;343:1778-87. [PubMed ID: 11114318]

2. Bridges CB, Fukuda K, Cox JN, Singleton JA; Advisory Committee on Immunization Practices. Prevention and control of influenza. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Wkly Rep. 2001;50(RR-4):1-44. [PubMed ID: 11334444]