P&T News: Fall/Winter 2003

Influenza Virus Vaccines

Joan M. Murhammer, R.Ph.
Peer Review Status: Internally Peer Reviewed by Loreen A. Herwaldt, M.D., Professor, Department of Internal Medicine


Influenza illness is characterized by the abrupt onset of fever, myalgia, headache, severe malaise, nonproductive cough, sore throat, and rhinitis. The risk for complications, hospitalizations, and deaths from influenza are higher among persons aged 65 years of age and older, young children, and persons of any age with certain underlying health conditions than among healthy older children and younger adults. Influenza can exacerbate underlying medical conditions (e.g., pulmonary or cardiac disease), lead to secondary bacterial pneumonia or primary influenza viral pneumonia, or occur as part of a coinfection with other viral or bacterial pathogens in high-risk patients. Influenza was responsible for an average of 36,000 deaths per year during 1990 to 1999.1

Vaccines
Influenza vaccination is the primary method for preventing influenza and its severe complications.1 Previously, only injectable trivalent, inactivated influenza vaccine (TIV) (Fluzone®, Fluvirin®) was available. TIV is approved for persons 6 months of age and older with or without chronic medical conditions.2,3 In June 2003, the Food and Drug Administration approved a live, attenuated intranasal influenza vaccine (LAIV) (FluMist®-- MedImmune/Wyeth).4 It is approved for the active immunization of healthy children and adults, 5 to 49 years of age, for prevention of influenza A and B disease.4,5 This article will provide a comparison of the place in therapy of these formulations.

The 2003-2004 vaccine formulation for TIV and LAIV contains the influenza strains recommended by the US Public Health Service for this year: A/New Caledonia/20/99-like (H1N1), A/Panama/2007/99-like (H3N2), and B/Hong Kong/330/2001-like viruses.1-5 The virus strains for this year's vaccine are the same as the 2002-2003 vaccine formulation.6 Annual vaccination with the current vaccine is necessary because immunity declines during the year after vaccination.1

Clinical Efficacy of LAIV
LAIV was evaluated in 4,561 participants in a placebo-controlled trial of healthy adults 18 to 64 years of age. The overall incidence of febrile illness during the peak outbreak periods did not differ between vaccinated and placebo groups (13.2 % compared to 14.6% respectively, p=0.19). The incidence of severe febrile illnesses was reduced 18.8% (p=0.002) and the incidence of febrile upper respiratory tract illnesses was reduced 23.6% (p<0.001) in vaccine recipients during peak outbreak periods. Vaccine recipients did experience fewer days of work missed because of illness, the use of antibiotics was reduced 42.9% (p<0.001), and the use of over-the-counter medications was reduced 23.3% (p<0.001) in vaccine recipients compared to placebo during the peak outbreak periods. Culture-confirmed influenza was not evaluated.7

LAIV was evaluated in a two-year, placebo-controlled study in children 15 to 71 months of age. Overall vaccine efficacy was 93% (95% CI 88% to 96%) in the first year and 87% (95% CI 78% to 93%) in the second year. Overall during the two years of the study, LAIV was 92% (95% CI 88% to 94%) effective at preventing culture-confirmed influenza.8,9

Person-to-Person Transmission of LAIV

LAIV contains live-attenuated influenza viruses that replicate in the nasopharynx and are shed in respiratory secretions.4,5
One unpublished prospective, randomized, double-blind, placebo-controlled trial in a daycare setting in children assessed the viral transmission of the LAIV viruses to unvaccinated contacts. The probability of acquiring a transmitted vaccine virus was estimated to be 2.4 % (95% CI: 0.13, 4.6) with the documented transmission in one unvaccinated subject and possible transmission in four unvaccinated subjects.10

Immunocompromised persons should avoid contact with LAIV recipients for three weeks following immunization. Therefore, the use of TIV is preferred for vaccination of household members, health-care workers, and others who have close contact with immunocompromised persons.4,5

Recommendations for Influenza Vaccination
Influenza virus vaccine is strongly recommended for any person 6 months of age or older who is at an increased risk from complications from influenza because of age or presence of certain medical conditions (see Table 1). In addition, healthcare workers and other persons (including house-hold contacts) in close contact with persons at high-risk should be vaccinated to decrease the risk for transmitting influenza to high-risk persons (see Table 2).1 Vaccination is also recommended for those with close contact to infants up to 6 months of age. Vaccination of children 6 to 23 months and their close contacts and caregivers is also encouraged.1,11

Table 1: Patients at Increased Risk for Complications Due to Influenza1
  • Persons > 65 years old
  • Residents of nursing home and other chronic-care facilities that house persons of any age who have a chronic medical condition
  • Adults and children who have chronic disorders of the pulmonary or cardiovascular systems, including asthma
  • Adults and children who have required medical follow-up or hospitalization during the preceding year because of chronic metabolic disease (including diabetes mellitus), renal dysfunction, hemoglobinopathies, or immunosuppression (including immunosuppression caused by medications or by human immunodeficiency virus [HIV])
  • Children and adolescents (6 months to 18 years old) who are receiving long-term aspirin therapy and, therefore, might be at risk for experiencing Reye syndrome after influenza infections
  • Women who will be in the second or third trimester of pregnancy during the influenza season

Table 2: Additional Persons Who Are Recommended for Influenza Vaccination1
  • Persons aged 50 to 64 years because this group has an increased prevalence of persons with high-risk conditions. Vaccination is recommended for this entire age group to increase the low vaccination rates among persons in this age group with high-risk conditions.
  • Persons who can transmit influenza to those at high risk, including:
    • Health-care workers including physicians, nurses, and other personnel in both hospital and outpatient-care settings
    • Employees of nursing homes and chronic-care facilities who have contact with patients or residents
    • Employees of assisted living and other residencies for persons in groups at high risk
    • Persons who provide home care to persons in groups at high-risk
    • Household contact (including children) of persons in groups at high-risk
  • Children 6 to 23 months old
  • Household contacts of children < 6 months old

Dosage

Inactivated influenza vaccine (TIV):

Table 3 outlines the dosing regimens for TIV. The preferred site for infants and young children is the anterolateral aspect of the thigh using a 7/8 to 1 inch needle. For adults and older children, the recommended site for vaccination is the deltoid muscle using a > 1 inch needle. A preservative-free inactivated influenza vaccine 0.25 ml syringe (Fluzone®) is available for children 6 to 35 months of age. It contains only a trace amount of thimerosal which is considered insignificant by the CDC.1-3

Table 3: Inactivated Influenza Vaccine (TIV) Dosage Recommendations1-3
Age Group
Dose
Number of Doses
Route
6 to 35 months
0.25 ml
1 or 2*
IM
3 to 8 years
0.5 ml
1 or 2*
IM
> 9 years
0.5 ml
1
IM

* 2 doses one month apart if patient (< 9 years) is receiving vaccine for the first time

Live, attenuated intranasal influenza vaccine (LAIV):

Table 4 outlines the dosing regimen for LAIV. The dose is given as 0.25 ml into each nostril while the patient is in an upright position for a total dose of 0.5 ml. The vaccine is stored frozen at -15°C and must be thawed prior to administration. The dose should not be re-frozen. Once administered, the used sprayer should be disposed as biohazard waste. 5

Table 4: Live, Attenuated Influenza Vaccine (LAIV) Dosage Recommendations4,5
Age Group
Dose
Number of Doses
Route
5 to 8 years
0.5 ml
1 or 2*
Intranasal
> 9 years
0.5 ml
1
Intranasal

* 2 doses 6 to 10 weeks apart if patient (< 9 years) is receiving vaccine for the first time

Timing of Vaccination

The optimal time to vaccinate is generally October and November. Patients, especially elderly patients, should not be vaccinated before this time because antibody levels can begin to decline before the end of the influenza season. Vaccination can continue throughout the influenza season. Children less than 9 years old, who receive influenza vaccine for the first time, should begin immunization in October because a second dose is required (> 4 weeks for TIV and > 6 weeks for LAIV). If possible, the second dose should be administered before December.1,4

Summary

While the administration of LAIV is relatively easy and painless, it is not approved by the FDA for use in the usual main target groups for influenza vaccination, particularly people older than 50 years of age and any person with a chronic medical condition that puts them at high risk for complications from influenza infection. Protection from influenza in these groups should continue to be accomplished by using the TIV. LAIV is also substantially more expensive. In addition, because LAIV is a live-virus vaccine and has the potential for viral shedding, TIV is the recommended vaccine for health-care workers and for family members and other close contacts of immunocompromised patients. Table 5 summarizes the similarities and differences between the two influenza vaccines.

Table 5: Comparison of LAIV and TIV1-5

Inactivated Influenza Vaccine (TIV)
Live, Attenuated Influenza Vaccine (LAIV)

Type of vaccine

Killed virus
Live, attenuated

Number of included virus strains

Trivalent (2 influenza A, 1 influenza B)
Trivalent (2 influenza A, 1 influenza B)

Route

Intramuscular injection
Intranasal spray

Frequency of administration

Annual
Annual

Can be administered to children less than 6 months of age

No
No

Can be administered to children 6 to 59 months of age

Yes
No

Can be administered to persons 5 to 49 years of age

Yes
Yes

Can be administered to adults > 49 years of age.

Yes
No

Can be administered to persons at high risk for complications resulting from influenza (see Table 1)

Yes
No

Can be administered to family members or close contacts of persons at high risk of complications from influenza but who are immunocompromised

Yes
No

Can be administered to family members or close contacts of persons at high risk for complications from influenza but who are immunocompetent

Yes
Yes

Can be administered to immunocompromised patients

Yes
No

Can be administered to patients with asthma or reactive airway disease

Yes
No

Can be administered to patients with a history of severe hypersensitivity to eggs

No
No

Can be administered to children or adolescent (5-17 years old) receiving aspirin or other salicylates

Yes
No

Can be administered simultaneously with other vaccines

Yes
Yes

If not administered simultaneously, can be administered within 4 weeks of a live vaccine

Yes
No

Can be administered concurrently with influenza antiviral agents (e.g., oseltamivir, zanamivir, amantadine).

Yes

No - LAIV should not be administered until 48 hours after cessation of influenza antiviral therapy. Influenza antiviral medications should not be administered for 2 weeks after receipt of LAIV.

Can be administered to pregnant patients

Yes
No

Stocked/Formulary at UIHC

Yes
No

References

  1. MMWR 2003;52(RR-08):1-36.
  2. Fluzone current prescribing information. Swiftwater, PA: Aventis Pasteur: 2003 July.
  3. Fluvirin current prescribing information. Speke, Liverpool, UK: Evans Vaccines Limited. 2003 May.
  4. MMWR 2003; 52(RR-13):1-8.
  5. FluMist current prescribing information. Philadelphia, PA: MedImmune, Inc.: 2003 June.
  6. MMWR 2002; 51(RR-03):1-31.
  7. JAMA. 1999; 282:137-44.
  8. N Engl J Med. 1998; 338: 1405-12.
  9. J Pediatr. 2000;136:168-75.
  10. Vesikari T, et al. Presented at the 41st Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), Chicago, IL, 2001. Abstract G-450.
  11. Pediatrics. 2002; 110: 1-18.
  12. MMWR 2003; 52:796-8.

 


Do You Have an Adverse Drug Reaction to Report?

Use the Computerized Incident Reporting (CIR) System to Report These Occurrences.
Look for "Adverse Drug Reaction" under IPR's Incident Reporting Tab.

Beginning in November 2003, the UIHC Adverse Drug Reaction (ADR) Reporting Program will begin receiving ADR reports via the hospital's Computerized Incident Reporting System which is currently utilized by staff to report and document other types of patient adverse incidents. The Adverse Drug Reaction Reporting Program (administered under the auspices of the Pharmacy and Therapeutics Subcommittee and coordinated by the Department of Pharmaceutical Care) monitors adverse drug reactions that affect our patients. The World Health Organization has defined an adverse drug reaction as "a response to a drug which is noxious and unintended, and which occurs at doses normally used in man for the prophylaxis, diagnosis, or therapy of disease, or for the modification of physiological function." (Please note that adverse drug reactions are distinct from medication errors.)

ADR reports involve a wide variety of medications, including agents that are new to the market as well as older, well-established products. All health care professionals must perform vigilant post-marketing surveillance in order to continue necessary monitoring after new agents reach the market. New data are used to update the prescribing information of recently approved agents and, in some cases, drug entities that have been marketed for years. The data may also lead to the market withdrawal of products associated with adverse reactions that were previously unrecognized or occur frequently with widespread use. We have all heard or seen information about adverse drug reactions that have occurred in the course of patient care within the hospital; unfortunately, many of these occurrences are never documented or reported by staff who are most familiar with the patient and the adverse event.

Whenever you become aware of an adverse drug reaction (whether in the inpatient or ambulatory care environments), please complete and submit an adverse drug reaction incident report using CIR. The yellow adverse drug reaction reporting cards formerly located on patient care units and ambulatory care clinics will no longer be available.

Thank you for your support of this important patient safety program.


List of Dangerous Medical Abbreviations Updated

Abbreviations are frequently used by health care providers to reduce the time it takes to communicate vital patient information. But in the course of patient care, several medical and drug name abbreviations have been mistaken or misinterpreted by other care providers, leading to errors that have caused significant patient harm. This problem has been extensively reviewed by several national safety organizations, including the Institute for Safe Medication Practices (ISMP), the National Coordinating Council for Medication Error Reporting and Prevention (NCCMERP), and the Joint Commission on the Accreditation of Healthcare Organizations (JCAHO).1,2,3 These organizations and others have identified several abbreviations that have been associated with medical errors and should not be used in patient care.

To avoid a compromise in patient safety at the UIHC, the Pharmacy and Therapeutics Subcommittee and the Health Information Management Subcommittee last year approved a list of dangerous medical abbreviations that may not be used. This list of dangerous abbreviations has recently been updated and expanded to include additional designations that have been associated with errors. The following medical abbreviations, designated as dangerous and not approved for use in written or printed communications associated with patient care, may not be used at UIHC:

Dangerous Medical Abbreviations
Abbreviation
Common Error
Appropriate Action
IU

Mistaken as "IV" (intravenous) or 10 (ten).

Write international unit(s)
MgSO4

Misinterpreted as morphine sulfate, resulting in the wrong medication being administered

Write magnesium sulfate
MS / MSO4 / MSO4

Misinterpreted as magnesium sulfate, resulting in the wrong medication being administered.

Write morphine
Q.D. / QD / q.d. / qd

Mistaken for Q.O.D./ qod, resulting in an appropriate dosing schedule

Write daily
Q.O.D. / QOD / q.o.d. / qod

Mistaken for Q.D./qd, resulting in an inappropriate dosing schedule

Write every other day
T I W

Misinterpreted as "three times a day" or "twice a week."

Specify days of the week
U / u

Mistaken as a zero or a four (4), resulting in overdose. Also mistaken for "cc" (cubic centimeters) when poorly written.

Write unit(s)
µg

Mistaken for "mg" (milligrams) when written, resulting in an overdose.

Write microgram(s) or mcg

Similarly, chemotherapy drug name abbreviations are never permitted to be used. The following abbreviations are particularly prone to misinterpretation if used in printed communications and must always be avoided:

Dangerous Chemotherapy Abbreviations

Abbreviation

Complete Drug Name To Be Written/Printed Out

2-CDA

Cladribine

5-FU

Fluorouracil

6-MP

Mercaptopurine

CPT-11

Irinotecan

IL-2

Aldesleukin

VP-16

Etoposide

CDDP

Cisplatin

MTX

Methotrexate

Prescribers will be notified to rewrite any orders using these dangerous abbreviations. Verbal orders will not be accepted to correct improperly written orders.

Please note that the list of dangerous medical abbreviations is continuously under review and may be revised at any time. The list of dangerous medical abbreviations is typically posted in those areas of the hospital where medication and treatment orders are written. In addition, the current lists of approved and dangerous medical abbreviations may be viewed at http://www.vh.org/formulary/Form/16ApprovedDrug.html and http://www.vh.org/formulary/Form/dangerousmedicalabbrev.html.

1 "Medication Errors Related to Potentially Dangerous Abbreviations," JCAHO Sentinel Event Alert, Issue 23, September 2001, at www.jcaho.org .

2 ISMP Medication Safety Alert!, May 2, 2001, www.ismp.org.

3 "Recommendations to Correct Error-Prone Aspects of Prescription Writing," NCCMERP Council Recommendation, adopted Sept. 4, 1996, at www.nccmerp.org (under Council Recommendations).

 

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