Am Fam Physician. 2003;67(4):763-766
Family physicians should be familiar with the various drugs available for treating and preventing viral infections. Part II of this two-part article focuses on agents used to manage influenza and respiratory syncytial virus. Rimantadine and amantadine traditionally have been used to prevent and treat influenza type A infections. The neuraminidase inhibitors zanamivir and oseltamivir have a broadened spectrum of activity in the treatment and prevention of influenza types A and B. Ribavirin has been used in some high-risk infants to treat respiratory syncytial virus infections, and palivizumab can be used for prophylaxis.
RNA viruses generally are benign in the early stage of infection, but they have the potential to induce acute respiratory distress syndrome if they spread to the lower respiratory tract or progress to pneumonia. Antiviral drugs can be used to treat and prevent these infections, although they are not a substitute for vaccine. Part II of this article focuses on antiviral agents used in the management of influenza and respiratory syncytial virus (RSV).
Influenza Viruses
Antiviral drugs that prevent and treat influenza should be considered adjuncts to vaccine—not substitutes. Traditionally, amantadine (Symmetrel) and, to a lesser extent, rimantadine (Flumadine) have been used for preventing and treating influenza type A (Table 1).1–4 However, in 1999, two drugs that effectively treat and prevent influenza types A and B were introduced. These drugs, zanamivir (Relenza) and oseltamivir (Tamiflu), provide more complete coverage when the type of influenza is unknown (Table 2).1–4
| Drug factors | Amantadine (Symmetrel) | Rimantadine (Flumadine) | ||
|---|---|---|---|---|
| Generic availability | Yes | Yes | ||
| Dosage forms | Liquid and tablet | Liquid and tablet | ||
| Treatment and prevention of influenza type A in adults | Yes | Yes | ||
| Treatment of influenza type A in children | Yes | Not approved | ||
| Prevention of influenza type A in children | Yes | Yes | ||
| Dosages for treatment of influenza type A | Adults* and children 12 years of age: 200 mg daily until 24 to 48 hours after symptoms have disappeared | Adults* and children 10 years of age: 100 mg twice daily for seven days | ||
| or | Not approved for children < 10 years of age | |||
| 100 mg twice daily† until 24 to 48 hours after symptoms have disappeared | ||||
| Children one to nine years of age: 5 mg per kg daily (up to 150 mg daily) until 24 to 48 hours after symptoms have disappeared | ||||
| Children 10 to 11 years of age: 100 mg twice daily until 24 to 48 hours after symptoms have disappeared | ||||
| Dosages for prevention of influenza A‡ | Adults* and children 12 years of age: 200 mg daily for at least seven days | Adults* and children 10 years of age: 100 mg twice daily for at least seven days | ||
| or | ||||
| 100 mg twice daily for at least seven days | Children < 10 years of age: 5 mg per kg daily (up to 150 mg daily) for at least seven days | |||
| Children one to nine years of age: 5 mg per kg daily (up to 150 mg daily) for at least seven days | ||||
| Children 10 to 11 years of age: 100 mg twice daily for at least seven days | ||||
| Prevention and treatment of influenza B | No | No | ||
| Dosage reduction in renal impairment | Yes (creatinine clearance 50 mL per minute [0.83 mL per second]) | Yes (creatinine clearance 10 mL per min [0.17 mL per second]) | ||
| Side effects | CNS and GI | Primarily GI | ||
| Cost (generic)§ | ||||
| Five-day treatment (adult dosage) | $18 ($4 to $5) | $29 ($26) | ||
| 42-day treatment (adult dosage in community outbreaks) | $106 ($28 to $31) | $171 ($154) | ||
| Drug factors | Oseltamivir (Tamiflu) | Zanamivir (Relenza) | ||
|---|---|---|---|---|
| Generic availability | No | No | ||
| Dosage forms | Liquid and capsule | Powder for oral inhalation | ||
| Treatment of influenza types A and B in adults | Yes | Yes | ||
| Treatment of influenza types A and B in children | Yes, in children > one year of age | Yes, in children seven years of age | ||
| Prevention of influenza types A and B in adults | Yes | FDA approval pending | ||
| Prevention of influenza types A and B in children | Yes, in children 13 years of age | FDA approval pending | ||
| Dosage for treatment of influenza types A and B* | Adults and children 13 years: 75 mg twice daily for five days | Two inhalations (10 mg) twice daily for five days | ||
| Children one to 12 years (following doses are given twice daily for five days): | ||||
| 15 kg (33 lb) or less: 30 mg | ||||
| 15 kg to 23 kg (51 lb): 45 mg | ||||
| 23 kg to 40 kg (88 lb): 60 mg | ||||
| > 40 kg: 75 mg | ||||
| Dosage for prevention of influenza types A and B | Adults and children 13 years: 75 mg once daily for at least seven days† | Approval pending. Two inhalations (10 mg) once daily for at least seven days† | ||
| Dosage reduction in renal impairment | Yes (creatinine clearance 30 mL per minute [0.5 mL per second]) | No | ||
| Side effects | GI | Minimal | ||
| Cost‡ | ||||
| Five-day treatment (adult dosage) | $63 | $50 | ||
| 42-day treatment (adult dosage in community outbreaks) | $265 | $212 (approval pending) | ||
| Precautions | Take with food to improve tolerance | Not recommended in patients with asthma or COPD | ||
| Suspension should be shaken before each use and is stable at room temperature for 10 days | ||||
| May cause bronchospasm | ||||
INFLUENZA TYPE A
Amantadine and Rimantadine
Amantadine was the first drug approved for prophylaxis of influenza type A (in 1966), and in 1976, it was approved for treatment and prophylaxis in adults and children older than one year. Rimantadine became available in 1993 for treatment and prophylaxis of influenza type A in adults and for prophylaxis in children. Neither of these drugs is effective against influenza type B.
Treatment usually is continued for three to five days or discontinued 24 to 48 hours following resolution of symptoms. The efficacy of both drugs is similar, and the average duration of illness is shortened by approximately one day.5
These drugs can be used for prophylaxis in high-risk patients (Table 3)6 and for influenza-related complications if an outbreak of influenza occurs within two weeks following vaccination.4 In a recent review, the average effectiveness of amantadine and rimantadine for the prevention of influenza was 61 and 72 percent, respectively.7
Although amantadine is considerably less expensive than rimantadine, it crosses the blood-brain barrier and appears to cause more central nervous system side effects, including dizziness, ataxia, hallucinations, agitation, and confusion. This is especially true in elderly patients and may be associated with higher serum concentrations. A split dosage may help minimize adverse events.
| Creatinine clearance, mL per minute (mL per second) | Suggested maintenance regimen |
|---|---|
| 30 to 50 (0.5 to 0.83) | 100 mg daily* |
| 15 to 29 (0.25 to 0.48) | 100 mg every other day* |
| < 15 (0.25) | 200 mg every seven days |
Rimantadine's adverse drug-reaction profile is similar to that of amantadine with respect to gastrointestinal side effects such as nausea, vomiting, and dyspepsia, but rimantadine appears to cause fewer central nervous system side effects.9
Oseltamivir and Zanamivir
Zanamivir is inhaled and requires the use of an inhalation device, which may be difficult for elderly patients to use. Because of its potential to induce bronchospasm and reduce lung function, use of zanamivir generally should be avoided in patients with asthma and chronic obstructive pulmonary disease.
INFLUENZA TYPE B
Oseltamivir and zanamivir are first-line choices for prevention and treatment of infection during outbreaks of influenza type B.
Respiratory Syncytial Virus (RSV)
RSV is a frequent cause of bronchiolitis in children. Treatment consists primarily of supportive care with fluids, oxygen, and aerosolized bronchodilators.
Ribavirin
In a select group of high-risk infants (premature infants younger than 36 weeks and infants with bronchopulmonary dysplasia, congenital heart disease, or immunodeficiency) with severe infections, aerosolized ribavirin (Virazole) has been used.15 The use of this drug requires special equipment and expert respiratory monitoring. It is expensive, with a cost exceeding $1,000 per day.
RSV Immune Globulin and Palivizumab
In high-risk patients, prophylaxis against RSV should be considered. During the winter months, monthly administration of intravenous RSV immune globulin (RespiGam) or intramuscular palivizumab (Synagis) may decrease the number of RSV episodes. Because of increased morbidity, RSV immune globulin should not be given to patients with congenital heart disease.