Practice Guidelines

ACIP Releases 2003 Guidelines on the Prevention and Control of Influenza



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Am Fam Physician. 2003 Oct 1;68(7):1426-1433.

The Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) has issued recommendations on the prevention and control of influenza for the 2003–2004 influenza season. This report updates the 2002 recommendations by the ACIP for the use of influenza vaccine and antiviral agents.

The 2003 recommendations include new or updated information about the timing of influenza vaccination, the 2003–2004 trivalent inactivated vaccine virus strains (A/Moscow/10/99 [H3N2]-like, A/New Caledonia/20/99 [H1N1]-like, and B/Hong Kong/330/2001-like), availability of certain influenza vaccine doses with reduced thimerosal content, including single 0.25-mL dose syringes, and manufacturers of influenza vaccine for the U.S. market.

The recommendations appear in the April 25, 2003 recommendations and reports series of Morbidity and Mortality Weekly Report and an update released August 22, 2003.

Epidemics of influenza usually occur during the winter months and are responsible for approximately 36,000 deaths per year in the United States. According to ACIP, rates of infection are highest among children, but rates of serious illness and death are highest among persons 65 years and older and persons of any age who have medical conditions that place them at increased risk for complications from influenza. Vaccination is the primary method for preventing influenza and its complications. The target groups for vaccination should be (1) persons who are at increased risk for influenza-related complications; (2) persons 50 to 64 years of age, because they have an elevated prevalence of certain chronic medical conditions; and (3) persons who live with or care for anyone in the high-risk category.

Recommendations for Using Influenza Vaccine

TARGET GROUPS

Groups at high risk for complications from influenza include persons 65 years and older; residents of nursing homes and other chronic care facilities who have chronic medical conditions; persons who have chronic pulmonary or cardiovascular system disorders; persons who have required regular medical follow-up or hospitalization during the past year because of metabolic diseases, renal dysfunction, hemoglobinopathies, or immunosuppression; persons six months to 18 years of age who are receiving long-term aspirin therapy and might be susceptible to Reye's syndrome; and women who will be in the second or third trimester of pregnancy during the influenza season.

SPECIFIC POPULATIONS

ACIP recommends that women who will be beyond the first trimester of pregnancy during the influenza season be vaccinated to decrease the risk of influenza-related complications. Women with medical conditions that increase the risk of complications should be vaccinated regardless of the stage of pregnancy. The vaccine does not affect the safety of women who are breastfeeding or their infants.

Persons infected with human immunodeficiency virus, including pregnant women, will benefit from vaccination because it decreases the risk of serious illness and can result in the production of protective antibody titers.

ACIP recommends that persons at high risk for influenza-related complications who were not vaccinated during the past fall or winter should receive the vaccine before traveling if they plan to go to the tropics, travel with an organized tour group any time of year, or travel to the southern hemisphere during April through September.

PERSONS WHO SHOULD NOT BE VACCINATED

Persons known to have anaphylactic hypersensitivity to eggs or other components of the influenza vaccine should not be vaccinated without consulting a physician first. Persons with acute febrile illness should not be vaccinated until the symptoms have abated. Minor illnesses with or without fever such as mild upper respiratory tract infection or allergic rhinitis, particularly in children, are not a contraindication to vaccination.

TIMING OF VACCINATION

The optimal time to be vaccinated is October and November. In an update on August 11, 2003, the CDC projected that production and distribution schedules will allow for sufficient supply of the vaccine. Vaccination should proceed for all high-risk and healthy persons as soon as vaccine is available.

DOSAGE

Dosage recommendations vary according to age (Table 1). For children younger than nine years who have not been vaccinated, ACIP recommends two doses administered at least a month apart. The second dose should be administered before December if possible.

SIDE EFFECTS AND ADVERSE REACTIONS

Physicians should remind patients that the vaccine contains noninfectious killed viruses and cannot cause influenza, and coincidental respiratory disease unrelated to the vaccine can occur after vaccination. In adults, the most frequent side effect is soreness at the vaccination site, which usually lasts less than two days. Fever, malaise, myalgia, and other systemic symptoms can occur after vaccination and most often affect persons who have not been exposed to the influenza virus antigens in the vaccine. Immediate allergic reactions (e.g., hives, angioedema, allergic asthma, and systemic anaphylaxis) rarely occur after vaccination.

INFLUENZA VACCINE SUPPLY

For 2003, only two companies (Aventis Pasteur, Inc., and Evans Vaccines, Ltd.) will be producing influenza vaccine for the U.S. market. The CDC has determined that vaccine production of this season is proceeding satisfactorily. No delays are expected.

Recommendations for Using Antiviral Agents for Influenza

Antiviral drugs are an adjunct to vaccination and should not be considered a substitute. Amantadine, rimantadine, zanamivir, and oseltamivir are the licensed agents available in the United States. Amantadine is approved for chemoprophylaxis of influenza A in adults and children one year or older. Rimantadine is approved for treatment and chemoprophylaxis of influenza A in adults and prophylaxis in children.

Zanamivir and oseltamivir have activity against influenza A and B viruses. Zanamivir is approved for treating persons A and B viruses. Zanamivir is approved for treating persons seven years or older, and oseltamivir is approved for use in persons one year and older. Oseltamivir also is approved for chemoprophylaxis in persons 13 years and older.

TABLE 1

Influenza Vaccine* Dosage, by Age Group—United States, 2003–2004 Season

Age group Dose Number of doses Route

Six to 35 months

0.25 mL

One or two§

Intramuscular

Three to eight years

0.50 mL

One or two§

Intramuscular

Nine years and older

0.50 mL

One

Intramuscular


*—Contains 15 mg each of A/Moscow/10/99 (H3N2)-like, A/New Caledonia/20/99 (H1N1)-like, and B/Hong Kong/330/2001-like antigens. For the A/Moscow/10/99 (H3N2)-like antigen, manufacturers will use the antigenically equivalent A/Panama/2007/99 (H3N2) virus. For the B/Hong Kong/330/2001-like antigen, manufacturers will use either B/Hong Kong/330/2001 or the antigenically equivalent B/Hong Kong/1434/2002. Manufacturers include Aventis Pasteur, Inc. (Fluzone split); Evans Vaccines, Ltd. (Fluvirin purified surface antigen vaccine). Fluzone is Food and Drug Administration-approved for use among persons six months and older. Fluvirin is approved for use among persons four years and older. For further product information, call Aventis Pasteur, Inc. at 800–822–2463; Evans Vaccine, Ltd. at 800–200–4278.

†—Because of their decreased potential for causing febrile reactions, only split-virus vaccines should be used for children younger than 13 years. Split-virus vaccine might be labeled as split, subvirion, or purified-surface-antigen vaccine. Immunogenicity and side effects of split- and whole-virus vaccines are similar among adults when vaccines are administered at the recommended dosage. Whole-virus vaccine is not available in the United States.

‡—For adults and older children, the recommended site of vaccination is the deltoid muscle. The preferred site for infants and young children is the anterolateral aspect of the thigh.

§—Two doses administered one month or more apart are recommended for children younger than nine years who are receiving influenza vaccine for the first time.

Reprinted from MMWR Morb Mortal Wkly Rep April 25, 2003;52(RR-8):12.

TABLE 1   Influenza Vaccine* Dosage, by Age Group—United States, 2003–2004 Season

View Table

TABLE 1

Influenza Vaccine* Dosage, by Age Group—United States, 2003–2004 Season

Age group Dose Number of doses Route

Six to 35 months

0.25 mL

One or two§

Intramuscular

Three to eight years

0.50 mL

One or two§

Intramuscular

Nine years and older

0.50 mL

One

Intramuscular


*—Contains 15 mg each of A/Moscow/10/99 (H3N2)-like, A/New Caledonia/20/99 (H1N1)-like, and B/Hong Kong/330/2001-like antigens. For the A/Moscow/10/99 (H3N2)-like antigen, manufacturers will use the antigenically equivalent A/Panama/2007/99 (H3N2) virus. For the B/Hong Kong/330/2001-like antigen, manufacturers will use either B/Hong Kong/330/2001 or the antigenically equivalent B/Hong Kong/1434/2002. Manufacturers include Aventis Pasteur, Inc. (Fluzone split); Evans Vaccines, Ltd. (Fluvirin purified surface antigen vaccine). Fluzone is Food and Drug Administration-approved for use among persons six months and older. Fluvirin is approved for use among persons four years and older. For further product information, call Aventis Pasteur, Inc. at 800–822–2463; Evans Vaccine, Ltd. at 800–200–4278.

†—Because of their decreased potential for causing febrile reactions, only split-virus vaccines should be used for children younger than 13 years. Split-virus vaccine might be labeled as split, subvirion, or purified-surface-antigen vaccine. Immunogenicity and side effects of split- and whole-virus vaccines are similar among adults when vaccines are administered at the recommended dosage. Whole-virus vaccine is not available in the United States.

‡—For adults and older children, the recommended site of vaccination is the deltoid muscle. The preferred site for infants and young children is the anterolateral aspect of the thigh.

§—Two doses administered one month or more apart are recommended for children younger than nine years who are receiving influenza vaccine for the first time.

Reprinted from MMWR Morb Mortal Wkly Rep April 25, 2003;52(RR-8):12.

DIAGNOSIS

Early diagnosis of influenza can reduce the inappropriate use of antibiotics and provide the option of using antiviral therapy. Tests for diagnosing influenza include viral culture, serology, rapid antigen testing, polymerase chain reaction, and immunofluorescence. Rapid tests can detect the virus within 30 minutes, but because of the lower sensitivity, physicians should confirm negative tests with a viral culture or other means.

TREATMENT

In otherwise healthy adults, amantadine and rimantadine can reduce the duration of uncomplicated influenza A illness when administered within two days of illness onset. Zanamivir and oseltamivir can reduce the duration of uncomplicated influenza A and B illness by approximately one day compared with placebo. None of these agents has been demonstrated to be effective in preventing serious influenza-related complications (e.g., bacterial or viral pneumonia or exacerbation of chronic diseases). Amantadine or rimantadine therapy should be discontinued after three to five days of treatment or within 24 to 48 hours after the disappearance of signs and symptoms. The recommended duration of treatment with zanamivir or oseltamivir is five days.

PROPHYLAXIS

Amantadine and rimantadine are about 70 to 90 percent effective in preventing illness from influenza A infection. When used as a prophylaxis, these antiviral agents can prevent illness while permitting subclinical infection and development of protective antibody against circulating influenza viruses. Zanamivir and oseltamivir are similarly effective in preventing febrile, laboratory-confirmed influenza illness, but only oseltamivir has been approved for prophylaxis. To be most effective, the antiviral agent must be taken each day for the duration of influenza activity in the community. A more cost-effective approach would be to take the agent only during the period of peak activity.

DOSING

Dosing recommendations vary by age and medical conditions (Table 2). The report includes guidelines for children, persons 65 years and older, and persons with impaired renal function, liver disease, and seizure disorders.

Children

In children younger than one year, amantadine has not been adequately evaluated. In children one to nine years of age, the U.S. Food and Drug Administration has approved 4.4 to 8.8 mg per kg per day, not to exceed 150 mg per day, for treatment and prophylaxis. To reduce the risk of toxicity, it is recommended that physicians only prescribe 5 mg per kg per day. For children 10 years or older, weighing at least 40 kg (88 lb), the approved dosage is 200 mg per day (100 mg twice a day).

Rimantadine is approved for prophylaxis in children one year or older and for treatment and prophylaxis in adults. It should be administered in one or two divided doses at 5 mg per kg per day, not to exceed 150 mg per day for children one to nine years of age. For children 10 years and older, the approved dosage is 200 mg per day (100 mg twice a day). If the child weighs less than 40 kg, the physicians should prescribe 5 mg per kg per day regardless of age.

Zanamivir is approved for treatment in children seven years and older. The recommended dosage is two inhalations (one 5-mg blister per inhalation for a total dose of 10 mg) twice daily approximately 12 hours apart.

Oseltamivir is approved for treatment in persons one year and older and for prophylaxis in persons 13 years and older. Recommended dosages for children vary by the weight of the child: less than 15 kg (33 lb) is 30 mg twice a day; more than 15 to 23 kg (50.6 lb) is 45 mg twice a day; more than 23 to 40 kg is 60 mg twice a day; more than 40 kg is 75 mg twice a day. For persons 13 years and older, the dosage is 75 mg twice a day. For prophylaxis, the dosage is 75 mg once a day for persons 13 years and older.

Persons 65 Years and Older

The daily dosage of amantadine for persons 65 years and older should not exceed 100 mg for prophylaxis or treatment because renal function declines with age.

For rimantadine, the recommended dosage is 100 mg per day for prophylaxis. For treatment, the dosage is 200 mg per day, which should be reduced to 100 mg per day if the patient experiences side effects.

There is no recommended reduction in dosage for zanamivir and oseltamivir on the basis of age alone.

SIDE EFFECTS AND ADVERSE REACTIONS

Physicians must consider the patient's age, weight, and renal function; presence of other medical conditions; indications for use; and the potential for interaction with other medications when considering using influenza antiviral medications.

Amantadine and rimantadine can cause central nervous system and gastrointestinal side effects when administered to young, healthy adults at dosages of 200 mg per day, but incidence of nervousness, anxiety, insomnia, difficulty concentrating, and lightheadedness is higher in persons taking amantadine than in those taking rimantadine. Side effects are usually mild and stop shortly after discontinuing the drug.

Zanamivir is not recommended for treatment in patients with underlying airway disease because of the risk patients with underlying airway disease because of the risk of serious adverse events and because the efficacy has not been demonstrated in this population. Patients with asthma or chronic obstructive pulmonary disease are advised to have a fast-acting bronchodilator available when inhaling zanamivir and to stop using the drug and contact their physician if they have difficulty breathing.

TABLE 2

Recommended Daily Dosage of Influenza Antiviral Medications for Treatment and Prophylaxis

Age groups
Antiviral agent One to six years Seven to nine years 10 to 12 years 13 to 64 years 65 years and older

Amantadine*

Treatment, influenza A

5 mg per kg per day up to 150 mg in two divided doses†

5 mg per kg per day up to 150 mg in two divided doses†

100 mg twice daily‡

100 mg twice daily‡

100 mg or less per day

Prophylaxis, influenza A

5 mg per kg per day up to 150 mg in two divided doses†

5 mg per kg per day up to 150 mg in two divided doses†

100 mg twice daily‡

100 mg twice daily‡

100 mg or less per day

Rimantadine§

Treatment∥, influenza A

NA

NA

NA

100 mg twice daily‡¶

100 mg per day#

Prophylaxis, influenza A

5 mg per kg per day up to 150 mg in two divided doses†

5 mg per kg per day up to 150 mg in two divided doses†

100 mg twice daily‡

100 mg twice daily‡

100 mg per day#

Zanamivir**††

Treatment, influenza A and B

NA

10 mg twice daily

10 mg twice daily

10 mg twice daily

10 mg twice daily

Oseltamivir

Treatment‡‡, influenza A and B

Dose varies by child's weight§§

Dose varies by child's weight§§

Dose varies by child's weight§§

75 mg twice daily

75 mg twice daily

Prophylaxis, influenza A and B

NA

NA

NA

75 mg per day

75 mg per day


NA = not applicable; FDA = U.S. Food and Drug Administration.

*—The drug package insert should be consulted for dosage recommendations for administering amantadine to persons with creatinine clearance of 50 mL or less per minute per 1.73 m2.

†—5 mg per kg of amantadine or rimantadine syrup = 1 teaspoon per 22 lb.

‡—Children 10 years or older who weigh less than 40 kg (88 lb) should be administered amantadine or rimantadine at a dosage of 5 mg per kg per day.

§—A reduction in dosage to 100 mg per day of rimantadine is recommended for persons who have severe hepatic dysfunction or those with creatinine clearance of 10 mL or less per minute. Other persons with less severe hepatic or renal dysfunction taking 100 mg per day of rimantadine should be observed closely, and the dosage should be reduced or the drug discontinued, if necessary.

∥—Only approved by the FDA for treatment in adults.

¶—Rimantadine is approved by the FDA for treatment in adults. However, certain specialists in the management of influenza consider rimantadine appropriate for treatment in children.

#—Elderly residents of nursing homes should be administered only 100 mg per day of rimantadine. A reduction in dosage of 100 mg per day should be considered for all persons 65 years or older if they experience side effects when taking 200 mg per day.

**—Zanamivir is administered via inhalation by using a plastic device included in the medication package. Patients will benefit from instruction and demonstration of correct use of the device.

††—Zanamivir is not approved for prophylaxis.

‡‡—A reduction in the dose of oseltamivir is recommended for persons with creatinine clearance of less than 30 mL per minute.

§§—The dosage recommendation for children who weigh 15 kg (33 lb) or less is 30 mg twice a day; for children weighing >15 to 23 kg (50.6 lb), the dosage is 45 mg twice a day; for children weighing >23 to 40 kg, the dosage is 60 mg twice a day; and for children weighing more than 40 kg, the dosage is 75 mg twice a day.

Reprinted from MMWR Morb Mortal Wkly Rep April 25, 2003;52(RR-8):20.

TABLE 2   Recommended Daily Dosage of Influenza Antiviral Medications for Treatment and Prophylaxis

View Table

TABLE 2

Recommended Daily Dosage of Influenza Antiviral Medications for Treatment and Prophylaxis

Age groups
Antiviral agent One to six years Seven to nine years 10 to 12 years 13 to 64 years 65 years and older

Amantadine*

Treatment, influenza A

5 mg per kg per day up to 150 mg in two divided doses†

5 mg per kg per day up to 150 mg in two divided doses†

100 mg twice daily‡

100 mg twice daily‡

100 mg or less per day

Prophylaxis, influenza A

5 mg per kg per day up to 150 mg in two divided doses†

5 mg per kg per day up to 150 mg in two divided doses†

100 mg twice daily‡

100 mg twice daily‡

100 mg or less per day

Rimantadine§

Treatment∥, influenza A

NA

NA

NA

100 mg twice daily‡¶

100 mg per day#

Prophylaxis, influenza A

5 mg per kg per day up to 150 mg in two divided doses†

5 mg per kg per day up to 150 mg in two divided doses†

100 mg twice daily‡

100 mg twice daily‡

100 mg per day#

Zanamivir**††

Treatment, influenza A and B

NA

10 mg twice daily

10 mg twice daily

10 mg twice daily

10 mg twice daily

Oseltamivir

Treatment‡‡, influenza A and B

Dose varies by child's weight§§

Dose varies by child's weight§§

Dose varies by child's weight§§

75 mg twice daily

75 mg twice daily

Prophylaxis, influenza A and B

NA

NA

NA

75 mg per day

75 mg per day


NA = not applicable; FDA = U.S. Food and Drug Administration.

*—The drug package insert should be consulted for dosage recommendations for administering amantadine to persons with creatinine clearance of 50 mL or less per minute per 1.73 m2.

†—5 mg per kg of amantadine or rimantadine syrup = 1 teaspoon per 22 lb.

‡—Children 10 years or older who weigh less than 40 kg (88 lb) should be administered amantadine or rimantadine at a dosage of 5 mg per kg per day.

§—A reduction in dosage to 100 mg per day of rimantadine is recommended for persons who have severe hepatic dysfunction or those with creatinine clearance of 10 mL or less per minute. Other persons with less severe hepatic or renal dysfunction taking 100 mg per day of rimantadine should be observed closely, and the dosage should be reduced or the drug discontinued, if necessary.

∥—Only approved by the FDA for treatment in adults.

¶—Rimantadine is approved by the FDA for treatment in adults. However, certain specialists in the management of influenza consider rimantadine appropriate for treatment in children.

#—Elderly residents of nursing homes should be administered only 100 mg per day of rimantadine. A reduction in dosage of 100 mg per day should be considered for all persons 65 years or older if they experience side effects when taking 200 mg per day.

**—Zanamivir is administered via inhalation by using a plastic device included in the medication package. Patients will benefit from instruction and demonstration of correct use of the device.

††—Zanamivir is not approved for prophylaxis.

‡‡—A reduction in the dose of oseltamivir is recommended for persons with creatinine clearance of less than 30 mL per minute.

§§—The dosage recommendation for children who weigh 15 kg (33 lb) or less is 30 mg twice a day; for children weighing >15 to 23 kg (50.6 lb), the dosage is 45 mg twice a day; for children weighing >23 to 40 kg, the dosage is 60 mg twice a day; and for children weighing more than 40 kg, the dosage is 75 mg twice a day.

Reprinted from MMWR Morb Mortal Wkly Rep April 25, 2003;52(RR-8):20.

In adults receiving treatment with oseltamivir, nausea and vomiting were reported more frequently than in persons receiving placebo. These symptoms may be less severe if the drug is taken with food.

These antivirals should be used during pregnancy only if the potential benefit outweighs the potential risk to the embryo or fetus.



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