Immunizations

INDICATIONS
COMVAX is indicated for vaccination against invasive disease caused by Haemophilus influenzae type b and against infection caused by all known subtypes of hepatitis B virus in infants 6 weeks to 15 months of age born of HBsAg negative mothers.

Infants born to HBsAg positive mothers should receive Hepatitis B Immune Globulin and Hepatitis B Vaccine (Recombinant) at birth and should complete the hepatitis B vaccination series given according to a particular schedule (see manufacturer's circular for Hepatitis B Vaccine [Recombinant]).

Infants born to mothers of unknown HBsAg status should receive Hepatitis B Vaccine (Recombinant) at birth and should complete the hepatitis B vaccination series given according to a particular schedule (see manufacturer's circular for Hepatitis B Vaccine [Recombinant]).

Vaccination with COMVAX should ideally begin at approximately 2 months of age or as soon thereafter as possible. In order to complete the three-dose regimen of COMVAX, vaccination should be initiated no later than 10 months of age. Infants in whom vaccination with a PRP-OMPC-containing product (i.e., PedvaxHIB, COMVAX) is not initiated until 11 months of age do not require three doses of PRP-OMPC; however, three doses of an HBsAg-containing product are required for complete vaccination against hepatitis B, regardless of age. For infants and children not vaccinated according to the recommended schedule see DOSAGE AND ADMINISTRATION.

COMVAX will not protect against invasive disease caused by Haemophilus influenzae other than type b or against invasive disease (such as meningitis or sepsis) caused by other microorganisms. COMVAX will not prevent hepatitis caused by other viruses known to infect the liver. Because of the long incubation period for hepatitis B, it is possible for unrecognized infection to be present at the time the vaccine is given. The vaccine may not prevent hepatitis B in such patients.

As with other vaccines, COMVAX may not induce protective antibody levels immediately following vaccination and may not result in a protective antibody response in all individuals given the vaccine.

Use With Other Vaccines
Immunogenicity results from open-labeled studies indicate that COMVAX can be administered concomitantly with DTP, DTaP, OPV, IPV, M-M-R II, and VARIVAX using separate sites and syringes for injectable vaccines

DOSAGE AND ADMINISTRATION
FOR INTRAMUSCULAR ADMINISTRATION

Do not inject intravenously, intradermally, or subcutaneously.

Recommended Schedule
Infants born to HBsAg negative mothers should be vaccinated with three 0.5 mL doses of COMVAX, ideally at 2, 4, and 12-15 months of age. If the recommended schedule cannot be followed, the interval between the first two doses should be at least six weeks and the interval between the second and third dose should be as close as possible to eight to eleven months.

Infants born to HBsAg-positive mothers should receive Hepatitis B Immune Globulin and Hepatitis B Vaccine (Recombinant) at birth and should complete the hepatitis B vaccination series given according to a particular schedule (see manufacturer's circular for Hepatitis B Vaccine [Recombinant]).

Infants born to mothers of unknown HBsAg status should receive Hepatitis B Vaccine (Recombinant) at birth and should complete the hepatitis B vaccination series given according to a particular schedule (see manufacturer's circular for Hepatitis B Vaccine [Recombinant]).

The subsequent administration of COMVAX for completion of the hepatitis B vaccination series in infants who were born to HBsAg positive mothers and received HBIG or infants born to mothers of unknown status has not been studied.

COMVAX should not be administered to any infant before the age of 6 weeks.

Modified Schedules
Children previously vaccinated with one or more doses of either hepatitis B vaccine or Haemophilus b conjugate vaccine
Children who receive one dose of hepatitis B vaccine at or shortly after birth may be administered COMVAX on the schedule of 2, 4, and 12-15 months of age. There are no data to support the use of a three-dose series of COMVAX in infants who have previously received more than one dose of hepatitis B vaccine. However, COMVAX may be administered to children otherwise scheduled to receive concurrent RECOMBIVAX HB and PedvaxHIB.

Children not vaccinated according to recommended schedule for COMVAX
Vaccination schedules for children not vaccinated according to the recommended schedule should be considered on an individual basis. The number of doses of a PRP-OMPC-containing product (i.e., COMVAX, PedvaxHIB) depends on the age that vaccination is begun. An infant 2 to 10 months of age should receive three doses of a product containing PRP-OMPC. An infant 11 to 14 months of age should receive two doses of a product containing PRP-OMPC. A child 15 to 71 months of age should receive one dose of a product containing PRP-OMPC. Infants and children, regardless of age, should receive three doses of an HBsAg-containing product.

COMVAX is for intramuscular injection. The anterolateral thigh is the recommended site for intramuscular injection in infants. Data suggests that injections given in the buttocks frequently are given into fatty tissue instead of into muscle. Such injections have resulted in a lower seroconversion rate (for hepatitis B vaccine) than was expected.

Injection must be accomplished with a needle long enough to ensure intramuscular deposition of the vaccine. The ACIP has recommended that for intramuscular injections, the needle should be of sufficient length to reach the muscle mass itself. In a clinical trial, Antibody Responses to COMVAX in Infants Not Previously Vaccinated with Hib or Hepatitis B Vaccine, Table 1) vaccination was accomplished with a needle length of 5/8 inches in accordance with ACIP recommendations in effect at that time.62 ACIP currently recommends that needles of longer length (7/8 to 1 inch) be used.63

The vaccine should be used as supplied; no reconstitution is necessary.

Shake well before withdrawal and use. Thorough agitation is necessary to maintain suspension of the vaccine.

Parenteral drug products should be inspected visually for extraneous particulate matter and discoloration prior to administration whenever solution and container permit. After thorough agitation, COMVAX is a slightly opaque, white suspension.

It is important to use a separate sterile syringe and needle for each patient to prevent transmission of infectious agents from one person to another.

Interchangeability of COMVAX and Licensed Haemophilus b Conjugate Vaccines or Recombinant Hepatitis B Vaccines
Since 1990, the Advisory Committee on Immunization Practices (ACIP) and the Committee on Infectious Diseases of the American Academy of Pediatrics (AAP) have recommended routine immunization of infants starting at 2 months of age with a polysaccharide-protein conjugate vaccine to prevent invasive Hib disease.32,33

Three Hib vaccines are licensed for infant vaccination: 1) oligosaccharide conjugate Hib vaccine (HbOC) (HibTITER®**), 2) polyribosylribitol phosphate-tetanus toxoid conjugate (PRP-T) (ActHIB®** and OmniHIB®**), and 3) Haemophilus b conjugate vaccine (meningococcal protein conjugate) (PRP-OMPC) (PedvaxHIB®). According to the ACIP, these products are now considered interchangeable for primary as well as booster vaccination.66

Because vaccination recommendations limited to high-risk individuals have failed to substantially lower the overall incidence of hepatitis B infection, both the Advisory Committee on Immunization Practices (ACIP) and the Committee on Infectious Diseases of the American Academy of Pediatrics (AAP) have endorsed universal infant immunization as part of a comprehensive strategy for the control of hepatitis B infection.32,50

HOW SUPPLIED
No. 4898 - COMVAX is supplied as 7.5 mcg PRP polysaccharide conjugated to approximately 125 mcg OMPC and 5 mcg HBsAg in a box of 10 single dose vials.

NDC 0006-4898-00. Storage

Store vaccine at 2-8°C (36-46°F). Storage above or below the recommended temperature may reduce potency.

DO NOT FREEZE since freezing destroys potency.

REFERENCES

32. Centers for Disease Control. MMWR 40(RR-1):1-25, 1991.

33. Committee on Infectious Disease. Update Pediatrics 88(1): 169-172, 1991.

50. Universal Hepatitis B Immunization, Committee on Infectious Diseases. Pediatr 89(4): 795-800, 1992.

66. Centers for Disease Control. MMWR 47(1): 9, 1998.

** HibTITER is a registered trademark of Lederle Laboratories, ActHIB is a registered trademark of Aventis Pasteur Inc. and OmniHIB is a registered trademark of GlaxoSmithKline. Manuf. and Dist. by: MERCK&CO.,INC,Whitehouse Station, NJ 08889, USA. Issued August 2004. FDA Rev date: 8/1/2004

INDICATIONS
Diphtheria and Tetanus Toxoids Adsorbed (For Pediatric Use) (DT) is indicated for active immunization of children up to age 7 years against diphtheria and tetanus. Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine (DTaP) TripediaÒ,or DTP is recommended for primary immunization of infants and persons up to 7 years of age. However, in instances where the pertussis vaccine component is contraindicated, or where the physician decides that pertussis vaccine is not to be administered, DT should be used.2 Immunization should be started at 6 weeks to 2 months of age and be completed before the seventh birthday. Immunization always should be started at once if diphtheria is present in the community.

This vaccine is NOT to be used for the treatment of diphtheria or tetanus infection.

This vaccine should NOT be used for immunizing persons 7 years of age and older. For persons 7 years of age and older, the recommended vaccine is Tetanus and Diphtheria Toxoids Adsorbed for Adult Use (Td).

As with any vaccine, vaccination with DT may not protect 100% of susceptible individuals.

If passive immunization is required, Tetanus Immune Globulin (Human) (TIG) and/or equine Diphtheria Antitoxin are the products of choice for tetanus and diphtheria, respectively (see DRUG INTERACTIONS and DOSAGE AND ADMINISTRATION sections).

DOSAGE AND ADMINISTRATION²

Parenteral drug products should be inspected visually for extraneous particulate matter and/or discoloration prior to administration whenever solution and container permit. If these conditions exist, the vaccine should not be administered.

SHAKE VIAL WELL before withdrawing each dose. Discard vial of vaccine if it cannot be resuspended.

Inject 0.5 mL intramuscularly only. The preferred injection sites are the anterolateral aspect of the thigh and the deltoid muscle of the upper arm. The vaccine should not be injected into the gluteal area or areas where there may be a major nerve trunk. During the course of primary immunizations, injections should not be made more than once at the same site.

The following guidelines are derived from the Advisory Committee on Immunization Practices (ACIP).2

PRIMARY IMMUNIZATION

This vaccine is recommended for children 6 weeks through 6 years (up to the seventh birthday),ideally beginning when the infant is 6 weeks to 2 months of age.

For infants 6 weeks through 12 months, the primary series consists of 4 doses: administer three 0.5 mL doses intramuscularly 4 to 8 weeks apart. A reinforcing dose is given 6 to 12 months after the third injection.

For children 1 year through 6 years (up to the seventh birthday), the primary series consists of 3 doses: administer two 0.5 mL doses intramuscularly 4 to 8 weeks apart. A reinforcing dose is given 6 to 12 months after the second injection. In the event the final immunizing dose would be given after the seventh birthday, use Tetanus and Diphtheria Toxoids Adsorbed for Adult Use.

BOOSTER IMMUNIZATION

For children between 4 and 6 years of age (preferably at time of kindergarten or elementary school entrance), a booster of 0.5 mL should be administered intramuscularly. Those who receive all four primary immunizing doses before their fourth birthday should receive a single dose of DT just before entering kindergarten or elementary school. This booster dose is not necessary if the fourth dose in the primary series was given after the fourth birthday. Thereafter, routine booster immunizations should be with Tetanus and Diphtheria Toxoids Adsorbed for Adult Use, at intervals of 10 years. PERSONS 7 YEARS OF AGE AND OLDER SHOULD NOT BE IMMUNIZED WITH DIPHTHERIA AND TETANUS TOXOIDS ADSORBED (FOR PEDIATRIC USE).

Preterm infants should be vaccinated according to their chronological age from birth.2

Interruption of the recommended schedule with a delay between doses does not interfere with the final immunity achieved with DT. There is no need to start the series over again, regardless of the time elapsed between doses.

The simultaneous administration of DT, oral polio virus vaccine (OPV), and measles-mumps-rubella vaccine (MMR) has resulted in seroconversion rates and rates of side effects similar to those observed when the vaccines are administered separately. Simultaneous vaccination (at separate sites and separate syringes) with DT, MMR, OPV, or inactivated poliovirus vaccine (IPV), and Haemophilus b Conjugate Vaccine (HbCV) is also acceptable. The ACIP recommends the simultaneous administration, at separate sites and separate syringes, of all vaccines appropriate to the age and previous vaccination status of the recipients including the special circumstance of simultaneous administration of DT, OPV, HbCV, and MMR at >/=15 months of age.2

If passive immunization for tetanus is needed, TIG (Human) is the product of choice. It provides longer protection than antitoxin of animal origin and causes few adverse reactions. The currently recommended prophylactic dose of TIG (Human) for wounds of average severity is 250 units intramuscularly. When tetanus toxoid and TIG (Human) are given concurrently, separate syringes and separate sites should be used. The ACIP recommends the use of only adsorbed toxoid in this situation.2

HOW SUPPLIED
Vial,1 Dose (contains NO preservative) (10 per package) Product No.49281-278-10

Vial,10 Dose (5 mL) (contains preservative) Product No.49281-275-10

STORAGE

Store between 2° - 8°C (35° - 46°F).DO NOT FREEZE.

REFERENCES

2. Recommendations of the Advisory Committee on Immunization Practices (ACIP). Diphtheria, Tetanus, and Pertussis: Recommendations for vaccine use and other preventive measures. MMWR 40:No.RR-10,1991

INDICATIONS
HAVRIX is indicated for active immunization of persons >/=12 months of age against disease caused by hepatitis A virus (HAV). Primary immunization should be administered at least 2 weeks prior to expected exposure to HAV. The Advisory Committee on Immunization Practices (ACIP) has issued recommendations for hepatitis A vaccination for persons who are at increased risk for infection and for any person wishing to obtain immunity (www.cdc.gov).6

When passive protection against hepatitis A is required either following exposure to hepatitis A virus or in persons requiring both immediate and long-term protection, HAVRIX may be administered concomitantly with IG with different syringes and at different injection sites.

DOSAGE AND ADMINISTRATION

HAVRIX should be administered by intramuscular injection. Do not inject intravenously, intradermally, or subcutaneously. In adults, the injection should be given in the deltoid region. HAVRIX should not be administered in the gluteal region; such injections may result in suboptimal response.

Children and Adolescents: Primary immunization for children and adolescents (12 months through 18 years of age) consists of a single dose of 720 EL.U. in 0.5 mL and a booster dose (720 EL.U. in 0.5 mL) should be administered anytime between 6 and 12 months later.

Adults: Primary immunization for adults consists of a single dose of 1440 EL.U. in 1 mL and a booster dose (1440 EL.U. in 1 mL) should be administered anytime between 6 and 12 months later.

For all age groups, a booster dose should be administered anytime between 6 and 12 months after the initiation of the primary dose in order to ensure the highest antibody titers.

HAVRIX may be administered concomitantly with IG, although the ultimate antibody titer obtained is likely to be lower than when the vaccine is given alone.

For individuals with clotting factor disorders at risk of hematoma formation following intramuscular injection, the ACIP recommends that when any intramuscular vaccine is indicated for such patients, "... the vaccine should be administered intramuscularly if, in the opinion of a physician familiar with the patient's bleeding risk, the vaccine can be administered with reasonable safety by this route. If the patient receives antihemophilia or other similar therapy, intramuscular vaccinations can be scheduled shortly after such therapy is administered. A fine needle (<23 gauge) should be used for the vaccination and firm pressure applied to the site, without rubbing, for >2 minutes. The patient or family should be instructed concerning the risk for hematoma from the injection.8

When concomitant administration of other vaccines or IG is required, they should be given with different syringes and at different injection sites.

In those with an impaired immune system, adequate anti-HAV response may not be obtained after the primary immunization course. Such patients may therefore require administration of additional doses of vaccine.

Preparation for Administration: Shake vial or syringe well before withdrawal and use. Parenteral drug products should be inspected visually for particulate matter or discoloration prior to administration. With thorough agitation, HAVRIX is a slightly turbid white suspension. Discard if it appears otherwise.

The vaccine should be used as supplied; no dilution or reconstitution is necessary. The full recommended dose of the vaccine should be used. After removal of the appropriate volume from a single-dose vial, any vaccine remaining in the vial should be discarded.

STORAGE

Store refrigerated between 2° and 8°C (36° and 46°F). Do not freeze; discard if product has been frozen. Do not dilute to administer.

HOW SUPPLIED

HAVRIX is supplied as a slightly turbid white suspension in vials and prefilled TIP-LOK® syringes.

720 EL.U./0.5 mL in Single-Dose Vials and Prefilled Syringes NDC 58160-837-01 Package of 1 Single-Dose Vial NDC 58160-837-11 Package of 10 Single-Dose Vials

NDC 58160-837-46 Package of 5 Prefilled Disposable TIP-LOK Syringes (packaged without needles)

NDC 58160-837-50 Package of 25 Prefilled Disposable TIP-LOK Syringes (packaged without needles)

1440 EL.U./mL in Single-Dose Vials and Prefilled Syringes NDC 58160-835-01 Package of 1 Single-Dose Vial

NDC 58160-835-11 Package of 10 Single-Dose Vials

NDC 58160-835-41 Package of 1 Prefilled Disposable TIP-LOK Syringe (packaged without needle)

NDC 58160-835-46 Package of 5 Prefilled Disposable TIP-LOK Syringes (packaged without needles)

REFERENCES

6. Centers for Disease Control and Prevention. Prevention of hepatitis A through active or passive immunization: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 1999;48(RR-12):26-29.

8. Centers for Disease Control and Prevention. General recommendations on immunization: Recommendations of the Advisory Committee on Immunization Practices and the American Academy of Family Physicians. MMWR 2002;51(RR-2):23-24.

Manufactured by GlaxoSmithKline Biologicals, Rixensart, Belgium, US License No. 1617 Distributed by GlaxoSmithKline, Research Triangle Park, NC 27709

OMNIHIB™ [Haemophilus b Conjugate Vaccine (Tetanus Toxoid Conjugate)] is a trademark of GlaxoSmithKline and was manufactured by Pasteur-M©rieux. HAVRIX and TIP-LOK are registered trademarks of GlaxoSmithKline.

©2005, GlaxoSmithKline. All rights reserved.

Indications & Dosage
VAQTA is indicated for active immunization against disease caused by hepatitis A virus in persons 12 months of age and older. Primary immunization should be given at least 2 weeks prior to expected exposure to HAV.

The Advisory Committee on Immunization Practices (ACIP) has issued recommendations for hepatitis A vaccination for persons who are at increased risk for infection and for any person wishing to obtain immunity.7 Please consult the Centers for Disease Control and Prevention for updates to those recommendations (www.cdc.gov).

If passive protection against hepatitis A is required either following exposure to hepatitis A virus or in persons in need of combined immediate and long-term protection, VAQTA may be administered along with immune globulin at a separate site with a separate syringe.

REFERENCES

7. Recommendations of the Advisory Committee on Immunization Practices (ACIP); Prevention of Hepatitis A Through Active or Passive Immunization, MMWR 48(RR 12):1-37, 1999.

DOSAGE AND ADMINISTRATION
Do not inject intravascularly, intradermally, or subcutaneously.

VAQTA is for intramuscular injection. The deltoid muscle is the preferred site for intramuscular injection.

DOSAGE
The vaccination regimen consists of one primary dose and one booster dose for healthy children, adolescents, and adults, as follows:

Children/Adolescents

Individuals 12 months through 18 years of age should receive a single 0.5 mL (~25U) dose of vaccine at elected date and a booster dose of 0.5 mL (~25U) 6 to 18 months later.

Adults

Adults 19 years of age and older should receive a single 1.0 mL (~50U) dose of vaccine at elected date and a booster dose of 1.0 mL (~50U) 6 to 18 months later.

For all age groups, a booster dose is recommended anytime between 6 and 18 months after the administration of the primary dose in order to elicit a high antibody titer.

Interchangeability of the Booster Dose

A booster dose of VAQTA may be given at 6 to 12 months following the initial dose of other inactivated hepatitis A vaccines (e.g., HAVRIX).

Use With Other Vaccines

VAQTA may be given concomitantly with typhoid and yellow fever vaccines. The GMTs for hepatitis A when VAQTA, typhoid and yellow fever vaccines were administered concomitantly were reduced when compared to VAQTA alone. Following receipt of the booster dose of VAQTA, the GMTs for hepatitis A in these two groups were observed to be comparable. VAQTA may be given concomitantly with M-M-R II. Data on concomitant use with other vaccines are limited. Separate injection sites and syringes should be used for concomitant administration of injectable vaccines. (See package insert for CLINICAL PHARMACOLOGY, Use With Other Vaccines.)

Use With Immune Globulin

VAQTA may be administered concomitantly with immune globulin (IG) using separate sites and syringes. The vaccination regimen for VAQTA should be followed as stated above. Consult the manufacturer's product circular for the appropriate dosage of IG. A booster dose of VAQTA should be administered at the appropriate time as outlined above.

ADMINISTRATION

Known or Presumed Exposure to HAV/Travel to Endemic Areas

For individuals requiring either post-exposure prophylaxis or combined immediate and longer term protection (e.g., travelers departing on short notice to endemic areas), VAQTA may be administered concomitantly with IG using separate sites and syringes (see PACKAGE INSERT FOR CLINICAL PHARMACOLOGY).

The following are the ACIP and AAFP recommendations for all intramuscular injections: "For administration of VAQTA for children and adolescents (persons >/= 12 months to 18 years), the deltoid muscle can be used if the muscle mass is adequate. The needle size can range from 22 to 25 gauge and from 7/8 to 1 ¼ inches, on the basis of the size of the muscle. For toddlers, the anterolateral thigh can be used, but the needle should be longer, usually 1 inch.

For adults (persons aged >18 years) the deltoid muscle is recommended for routine intramuscular vaccinations. The anterolateral thigh can be used. The suggested needle size is 1 - 1 ½ inches and 22- 25 gauge."8

The vaccine should be used as supplied; no reconstitution is necessary.

Shake well before withdrawal and use. Thorough agitation is necessary to maintain suspension of the vaccine. Discard if the suspension does not appear homogenous.

Parenteral drug products should be inspected visually for extraneous particulate matter and discoloration prior to administration whenever solution and container permit. After thorough agitation, VAQTA is a slightly opaque, white suspension.

A separate sterile syringe and sterile disposable needle or a sterile disposable unit should be used for each individual patient to prevent transmission of hepatitis or other infectious agents from one person to another. Needles should be disposed of properly and should not be recapped.

REFERENCES

8. Recommendations of the Advisory Committee on Immunization Practices (ACIP); General Recommendations on Immunization, MMWR 51(RR-2): 1-35, 2002.

HOW SUPPLIED
PEDIATRIC/ADOLESCENT FORMULATION

Vials

No. 4831 --- VAQTA for pediatric/adolescent use is supplied as 25U/0.5 mL of hepatitis A virus protein in a 0.5 mL single-dose vial, NDC 0006-4831-00.

No. 4831 --- VAQTA for pediatric/adolescent use is supplied as 25U/0.5 mL of hepatitis A virus protein in a 0.5 mL single-dose vial, in a box of 10 single-dose vials, NDC 0006 4831-41.

Syringes

No. 4845 --- VAQTA for pediatric/adolescent use is supplied as 25U/0.5 mL of hepatitis A virus protein in a 0.5 mL single-dose prefilled syringe, with a 5/8 inch needle, NDC 0006-4845-00.

No. 4845 --- VAQTA for pediatric/adolescent use is supplied as 25U/0.5 mL of hepatitis A virus protein in a 0.5 mL single-dose prefilled syringe, with a 5/8 inch needle, in a box of 5 single-dose prefilled syringes, with 5/8 inch needles, NDC 0006-4845-38.

ADULT FORMULATION

Vials

No. 4841 --- VAQTA for adult use is supplied as 50U/1 mL of hepatitis A virus protein in a 1 mL single-dose vial, NDC 0006-4841-00.

No. 4841 --- VAQTA for adult use is supplied as 50U/1 mL of hepatitis A virus protein in a 1 mL single-dose vial, in a box of 5 single-dose vials, NDC 0006-4841-38.

No. 4841 --- VAQTA for adult use is supplied as 50U/1 mL of hepatitis A virus protein in a 1 mL single-dose vial, in a box of 10 single-dose vials, NDC 0006-4841-41.

Syringes

No. 4844 --- VAQTA for adult use is supplied as 50U/1 mL of hepatitis A virus protein in a 1 mL single-dose prefilled syringe, with a one inch needle, NDC 0006-4844-00.

No. 4844 --- VAQTA for adult use is supplied as 50U/1 mL of hepatitis A virus protein in a 1 mL single-dose prefilled syringe, with a one inch needle, in a box of 5 single-dose, prefilled syringes, with one inch needles, NDC 0006-4844-38.

Storage
Store vaccine at 2-8°C (36-46°F).
DO NOT FREEZE since freezing destroys potency.

Manuf. and Dist. by: Whitehouse Station, NJ 08889 USA
Syringes of VAQTA are also filled by: Evans Vaccines Ltd. Gaskill Road, Speke, Liverpool L24 9GR, England.  Issued August 2005

INDICATIONS
RECOMBIVAX HB is indicated for vaccination against infection caused by all known subtypes of hepatitis B virus. RECOMBIVAX HB Dialysis Formulation is indicated for vaccination of adult predialysis and dialysis patients against infection caused by all known subtypes of hepatitis B virus.

Vaccination with RECOMBIVAX HB is recommended for:

Infants including those born to HBsAg positive mothers (high-risk infants).
Children born after November 21, 1991.30
Adolescents (see package insert for CLINICAL PHARMACOLOGY).
Other persons of all ages in areas of high prevalence or those who are or may be at increased risk of infection with hepatitis B virus, such as:³⁰

• Health Care Personnel
  • Dentists and oral surgeons.
  • Physicians and surgeons.
  • Nurses.
  • Paramedical personnel and custodial staff who may be exposed to the virus via blood or other patient specimens.
  • Dental hygienists and dental nurses.
  • Laboratory personnel handling blood, blood products, and other patient specimens.
  • Dental, medical and nursing students.
• Selected Patients and Patient Contacts
  • Staff in hemodialysis units and hematology/oncology units.
  • Hemodialysis patients and patients with early renal failure before they require hemodialysis.
  • Patients requiring frequent and/or large volume blood transfusions or clotting factor concentrates (e.g., persons with hemophilia, thalassemia).
  • Individuals with hepatitis C virus infection.³⁵
  • Clients (residents) and staff of institutions for the mentally handicapped.
  • Classroom contacts of deinstitutionalized mentally handicapped persons who have persistent hepatitis B surface antigenemia and who show aggressive behavior.
  • Household and other intimate contacts of persons with persistent hepatitis B surface antigenemia.
• Sub-populations with a known high incidence of the disease, such as:
  • Alaskan Natives.
  • Pacific Islanders.
  • Refugees from areas where hepatitis B virus infection is endemic.
  • Adoptees from countries where hepatitis B virus infection is endemic.
• International Travelers
• Military Personnel identified as being at increased risk
• Morticians and Embalmers
• Blood bank and plasma fractionation workers
• Persons at Increased Risk of the Disease Due to Their Sexual Practices, such as:
  • Persons who have heterosexual activity with multiple partners.
  • Persons who repeatedly contract sexually transmitted diseases.
  • Homosexual and bisexual adolescent and adult men.
  • Female prostitutes.
• Prisoners
• Injection drug users

Neither dosage strength will prevent hepatitis caused by other agents, such as hepatitis A virus, hepatitis C virus, hepatitis E virus or other viruses known to infect the liver.

Revaccination
See package insert for CLINICAL PHARMACOLOGY.

Use with Other Vaccines
Results from clinical studies indicate that RECOMBIVAX HB can be administered concomitantly with DTP (Diphtheria, Tetanus and whole cell Pertussis), OPV (oral Poliomyelitis vaccine), M-M-R* II (Measles, Mumps, and Rubella Virus Vaccine Live), Liquid PedvaxHIB* [Haemophilus b Conjugate Vaccine (Meningococcal Protein Conjugate)] or a booster dose of DTaP [Diphtheria, Tetanus, acellular Pertussis], using separate sites and syringes for injectable vaccines. No impairment of immune response to individually tested vaccine antigens was demonstrated.

The type, frequency and severity of adverse experiences observed in these studies with RECOMBIVAX HB were similar to those seen when the other vaccines were given alone.

In addition, an HBsAg-containing product, COMVAX* [Haemophilus b Conjugate (Meningococcal Protein Conjugate) and Hepatitis B (Recombinant) Vaccine], was given concomitantly with Eipv (enhanced inactivated Poliovirus vaccine) or VARIVAX* [Varicella Virus Vaccine Live (Oka/Merck)], using separate sites and syringes for injectable vaccines. No impairment of immune response to these individually tested vaccine antigens was demonstrated. No serious vaccine-related adverse events were reported.

COMVAX has also been administered concomitantly with the primary series of DTaP to a limited number of infants. No serious vaccine-related adverse events were reported.10

Separate sites and syringes should be used for simultaneous administration of injectable vaccines.

DOSAGE AND ADMINISTRATION
Do not inject intravenously or intradermally.

RECOMBIVAX HB Hepatitis B Vaccine (Recombinant) DIALYSIS FORMULATION [(40 mcg/mL) (WITHOUT PRESERVATIVE)] IS INTENDED ONLY FOR ADULT PREDIALYSIS/DIALYSIS PATIENTS.RECOMBIVAX HB Hepatitis B Vaccine (Recombinant) PEDIATRIC/ADOLESCENT (WITHOUT PRESERVATIVE) and ADULT FORMULATIONS (WITHOUT PRESERVATIVE) ARE NOT INTENDED FOR USE IN PREDIALYSIS/DIALYSIS PATIENTS.

Three-Dose Regimen
The vaccination regimen for each population consists of 3 doses of vaccine given according to the following schedule:

First dose: at elected date

Second dose: 1 month later

Third dose: 6 months after the first dose

For infants born of mothers who are HBsAg positive or mothers of unknown HBsAg status, treatment recommendations are described in the subsection titled: Guidelines for Treatment of Infants Born of HBsAg Positive Mothers or Mothers of Unknown HBsAg Status.

Two-Dose Regimen - Adolescents (11 through 15 years of age)
An alternate two-dose regimen is available for routine vaccination of adolescents (11 through 15 years of age). The regimen consists of two doses of vaccine (10 mcg) given according to the following schedule:

First injection: at elected date

Second injection: 4-6 months later

Table 1 summarizes the dose and formulation of RECOMBIVAX HB for specific populations, regardless of the risk of infection with hepatitis B virus.

Table 1

Group	Dose/Regimen	Formulation	Color Code
Infants, Children and Adolescents 0-19 years of age	5 mcg (0.5 mL) 3 x 5 mcg	Pediatric/Adolescent	Yellow
Adolescents 11 through 15 years of age	10 mcg** (1.0 mL) 2 x 10 mcg	Adult	Green
Adults ≥ 20 years of age	10 mcg** (1.0 mL) 3 x 10 mcg	Adult	Green
Predialysis and Dialysis Patients†	40 mcg (1.0 mL) 3 x 40 mcg	Dialysis	Blue
** If the suggested formulation is not available, the appropriate dosage can be achieved from another formulation provided that the total volume of vaccine administered does not exceed 1 mL. However, the Dialysis Formulation may be used only for adult predialysis/dialysis patients. * Adolescents (11 through 15 years of age) may receive either regimen: the 3 x 5 mcg (Pediatric/Adolescent Formulation) or the 2 x 10 mcg (Adult Formulation). † See also recommendations for revaccination of predialysis and dialysis patients in DOSAGE AND ADMINISTRATION, Revaccination.

 

RECOMBIVAX HB is for intramuscular injection. The deltoid muscleis the preferred site for intramuscular injection in adults. Data suggest that injections given in the buttocks frequently are given into fatty tissue instead of into muscle. Such injections have resulted in a lower seroconversion rate than was expected. The anterolateral thighis the recommended site for intramuscular injection in infants and young children.

For persons at risk of hemorrhage following intramuscular injection, RECOMBIVAX HB may be administered subcutaneously. However, when other aluminum-adsorbed vaccines have been administered subcutaneously, an increased incidence of local reactions including subcutaneous nodules has been observed. Therefore, subcutaneous administration should be used only in persons (e.g., hemophiliacs) who are at risk of hemorrhage following intramuscular injections.

The vaccine should be used as supplied; no dilution or reconstitution is necessary. The full recommended dose of the vaccine should be used.

For All Formulations: Since none of the formulations contain a preservative, once the single-dose vial has been penetrated, the withdrawn vaccine should be used promptly, and the vial must be discarded.

Shake well before use. Thorough agitation at the time of administration is necessary to maintain suspension of the vaccine.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. After thorough agitation, the vaccine is a slightly opaque, white suspension.

Withdraw the recommended dose from the vial using a sterile needle and syringe free of preservatives, antiseptics, and detergents.

It is important to use a separate sterile syringe and needle for each individual patient to prevent transmission of hepatitis and other infectious agents from one person to another. Needles should be disposed of properly and should not be recapped.

Injection must be accomplished with a needle long enough to ensure intramuscular deposition of the vaccine.

Guidelines for Treatment of Infants Born of HBsAg Positive Mothers or Mothers of Unknown HbsAg Status
Each infant should receive three 5 mcg doses of RECOMBIVAX HB irrespective of the mother's HBsAg status (see Table 1). The ACIP recommends that if the mother is determined to be HbsAg positive within 7 days of delivery, the infant also should be given a dose of HBIG (0.5 mL) immediately. The first dose of RECOMBIVAX HB may be given at the same time as HBIG, but it should be administered in the opposite anterolateral thigh.7

Revaccination
The duration of the protective effect of RECOMBIVAX HB in healthy vaccinees is unknown at present and the need for booster doses is not yet defined (see package insert for CLINICAL PHARMACOLOGY).

A booster dose or revaccination with RECOMBIVAX HB Dialysis Formulation (blue color code) may be considered in predialysis/dialysis patients if the anti-HBs level is less than 10 mIU/mL 1 to 2 months after the third dose.23 The ACIP recommends that the need for booster doses of vaccine should be assessed by annual antibody testing and a booster dose given when antibody levels decline to < 10 mIU/mL.30

Known or Presumed Exposure to HBsAg
There are no prospective studies directly testing the efficacy of a combination of HBIG and RECOMBIVAX HB in preventing clinical hepatitis B following percutaneous, ocular or mucous membrane exposure to hepatitis B virus. However, since most persons with such exposures (e.g., health-care workers) are candidates for RECOMBIVAX HB and since combined HBIG plus vaccine is more efficacious than HBIG alone in perinatal exposures, the following guidelines are recommended for persons who have been exposed to hepatitis B virus such as through (1) percutaneous (needlestick), ocular, mucous membrane exposure to blood known or presumed to contain HBsAg, (2) human bites by known or presumed HBsAg carriers, that penetrate the skin, or (3) following intimate sexual contact with known or presumed HBsAg carriers.

HBIG (0.06 mL/kg) should be given intramuscularly as soon as possible after exposure and within 24 hours if possible. RECOMBIVAX HB (see dosage recommendation) should be given intramuscularly at a separate site within 7 days of exposure and second and third doses given one and six months, respectively, after the first dose.

HOW SUPPLIED
PEDIATRIC/ADOLESCENT FORMULATION (PRESERVATIVE FREE)
Vials
No. 4980 - RECOMBIVAX HB for use in infants, children, and adolescents is supplied as 5 mcg/0.5 mL of HBsAg in a 0.5 mL single-dose vial, color coded with a yellow cap and stripe on the vial labels and cartons and an orange banner on the vial labels and cartons stating “Preservative Free”, NDC 0006-4980-00.

No. 4981 - RECOMBIVAX HB for use in infants, children, and adolescents is supplied as 5 mcg/0.5 mL of HBsAg in a 0.5 mL single-dose vial, in a box of 10 single-dose vials, color coded with a yellow cap and stripe on the vial labels and cartons and an orange banner on the vial labels and cartons stating “Preservative Free”, NDC 0006-4981-00.

Syringes
No. 4093 - RECOMBIVAX HB for use in infants, children and adolescents is supplied as 5 mcg/0.5 mL of HBsAg in a prefilled single-dose Luer Lock syringe, preassembled with UltraSafe Passive®** delivery system in a box of 6 single-dose, prefilled syringes color coded with a yellow plunger rod and stripe on the peel-off syringe labels and cartons and an orange banner on the cartons stating “Preservative Free.” Six one-inch 23 gauge needles are provided separately in the package. NDC 0006-4093-06.

No. 4093 - RECOMBIVAX HB for use in infants, children and adolescents is supplied as 5 mcg/0.5 mL of HBsAg in a carton of 6 prefilled single-dose Luer Lock syringes with tip caps, color coded with a yellow plunger rod and stripe on the peel-off syringe labels and cartons and an orange banner on the cartons stating “Preservative Free.” NDC 0006-4093-09.

ADULT FORMULATION (PRESERVATIVE FREE)
Vials
No. 4995 - RECOMBIVAX HB for use in adults and adolescents (11 through 15 years of age) is supplied as 10 mcg/mL of HBsAg in a 1 mL single-dose vial, color coded with a green cap and stripe on the vial labels and cartons and an orange banner on the vial labels and cartons stating “Preservative Free”, NDC 0006-4995-00.

No. 4995 - RECOMBIVAX HB for use in adults and adolescents (11 through 15 years of age) is supplied as 10 mcg/mL of HBsAg in a 1 mL single-dose vial, in a box of 10 single-dose vials, color coded with a green cap and stripe on the vial labels and cartons and an orange banner on the vial labels and cartons stating “Preservative Free”, NDC 0006-4995-41.

Syringes
No. 4094 - RECOMBIVAX HB for use in adults and adolescents (11 through 15 years of age) is supplied as 10 mcg/1.0 mL HBsAg in a single-dose prefilled Luer Lock syringe, preassembled with UltraSafe Passive® delivery system, color coded with a green plunger rod and stripe on the peel-off syringe labels and cartons and an orange banner on the cartons stating “Preservative Free.” A one-inch 23 gauge needle is provided separately in the package. NDC 0006-4094-31.

No. 4094 - RECOMBIVAX HB for use in adults and adolescents (11 through 15 years of age) is supplied as 10 mcg/1.0 mL HBsAg in a single-dose prefilled Luer Lock syringe, preassembled with UltraSafe Passive® delivery system in a box of 6 single-dose, prefilled syringes color coded with a green plunger rod and stripe on the peel-off syringe labels and cartons and an orange banner on the cartons stating “Preservative Free.” Six one-inch 23 gauge needles are provided separately in the package. NDC 0006-4094-06.

No. 4094 - RECOMBIVAX HB for use in adults and adolescents (11 through 15 years of age) is supplied as 10 mcg/1.0 mL HBsAg in a carton of 6 single-dose prefilled Luer Lock syringes with tip caps, color coded with a green plunger rod and stripe on the peel-off syringe labels and cartons and an orange banner on the carton stating “Preservative Free.” NDC 0006-4094-09.

DIALYSIS FORMULATION (PRESERVATIVE FREE)
Vials
No. 4992 - RECOMBIVAX HB Dialysis Formulation is supplied as 40 mcg/mL of HBsAg in a 1 mL single-dose vial, color coded with a blue cap and stripe on the vial labels and cartons and an orange banner on the vial labels and cartons stating “Preservative Free”, NDC 0006-4992-00.

Storage
Store vials and syringes at 2-8°C (36-46°F). Storage above or below the recommended temperature may reduce potency.

Do not freeze since freezing destroys potency.

REFERENCES

7. Recommendations of the Immunization Practices Advisory Committee (ACIP): Hepatitis B Virus: A Comprehensive Strategy for Eliminating Transmission in the United States Through Universal Childhood Vaccination, MMWR 40(RR-13): 1-25, November 22, 1991.

10. Data on file at Merck Research Laboratories.

23. Recommendations of the Immunization Practices Advisory Committee (ACIP): Update on Hepatitis B Prevention, MMWR 36(23): 353-366, June 19, 1987.

30. Recommendations of the Advisory Committee on Immunization Practices (ACIP): Hepatitis B Virus Infection: A Comprehensive Strategy to Eliminate Transmission in the United States, 1996 update, MMWR (draft January 13, 1996).

33. WHO Bulletin, Expanded Programme on Immunization, Hepatitis B Vaccine - Making Global Progress. October, 1996.

35. National Institutes of Health, National Institutes of Health Consensus Development Conference Panel Statement: Management of Hepatitis C, Hepatology, 26(Suppl. 1): 2S-10S, 1997.

Issued December 2007. Merck & Co Inc., Whitehouse Station, NJ 08889, USA. FDA rev date: 5/15/2007

TOP

INDICATIONS
FLUARIX is indicated for active immunization of adults (18 years of age and older) against influenza disease caused by influenza virus types A and B contained in the vaccine.

This indication is based on immune response elicited by FLUARIX, and there have been no controlled trials demonstrating a decrease in influenza disease after vaccination with FLUARIX (see CLINICAL PHARMACOLOGY).

The Advisory Committee on Immunization Practices (ACIP) has issued recommendations regarding the use of the inactivated influenza virus vaccine.3

Annual vaccination with the current vaccine is necessary because immunity declines during the year after vaccination. Vaccine prepared for a previous influenza season should not be administered to provide protection for the current season.3

FLUARIX IS NOT INDICATED FOR USE IN CHILDREN.

Concomitant Administration With Other Vaccines: There are insufficient data to assess the concurrent administration of FLUARIX with other vaccines.

DOSAGE AND ADMINISTRATION
Parenteral drug products should be inspected visually for particulate matter and/or discoloration prior to administration whenever solution and container permit. If either of these conditions exist, the vaccine should not be administered.

The prefilled syringe should be shaken well before administration.

Do NOT inject intravenously.

The dose of FLUARIX is a single 0.5 mL injection in adults. Injections of FLUARIX should be administered intramuscularly, preferably in the region of the deltoid muscle. The vaccine should not be injected in the gluteal area or areas where there may be a major nerve trunk. A needle length of >/= 1 inch is preferred because needles <1 inch might be of insufficient length to penetrate muscle tissue in certain adults. Before injection, the skin over the site to be injected should be cleansed with a suitable germicide. After insertion of the needle, aspirate to ensure that the needle has not entered a blood vessel.

STORAGE
Store FLUARIX refrigerated between 2º and 8ºC (36º and 46ºF). Do not freeze. Discard if the vaccine has been frozen. Store in the original package to protect from light.

HOW SUPPLIED
FLUARIX is supplied as a colorless to slightly opalescent suspension in prefilled syringes containing a 0.5-mL single dose.

Single-Dose Prefilled Disposable TIP-LOK® Syringes (packaged without needles) NDC 58160-874-46 (package of 5)

INDICATIONS
Fluzone vaccine is indicated for active immunization against influenza disease caused by influenza virus types A and B contained in the vaccine in subjects from 6 months of age and older.

The optimal time to vaccinate is usually during October-November. ACIP recommends that vaccine providers focus their vaccination efforts in October and earlier primarily on persons aged >/= 50 years, persons aged < 50 years at increased risk for influenza-related complications (including children aged 6-23 months), household contacts of persons at high risk (including out-of-home caregivers and household contacts of children aged 0-23 months), and health-care workers. Vaccination of children aged < 9 years who are receiving vaccine for the first time should also begin in October or earlier because those persons need a booster dose 1 month after the initial dose. Efforts to vaccinate other persons who wish to decrease their risk for influenza infection should begin in November; however, if such persons request vaccination in October, vaccination should not be deferred.1 After November, many persons who should or want to receive influenza vaccine remain unvaccinated. In addition, substantial amounts of vaccine remained unused during the past four influenza seasons. To improve vaccine coverage, influenza vaccine should continue to be offered in December and throughout the influenza season as long as vaccine supplies are available, even after influenza activity has been documented in the community. In the US, seasonal influenza activity can begin to increase as early as October or November, but influenza activity has not reached peak levels in the majority of recent seasons until late December-early March. Therefore, although the timing of influenza activity can vary by region, vaccine administered after November is likely to be beneficial in the majority of influenza seasons. Adults develop peak antibody protection against influenza infection 2 weeks after vaccination.1

To avoid missed opportunities for vaccination of persons at high risk for serious complications, such persons should be offered vaccine beginning in September during routine health-care visits or during hospitalizations, if vaccine is available. In facilities housing older persons (eg, nursing homes), vaccination before October typically should be avoided because antibody levels in such persons can begin to decline within a limited time after vaccination.

Persons planning substantial organized vaccination campaigns should consider scheduling these events after mid-October because the availability of vaccine in any location cannot be ensured consistently in the early fall. Scheduling campaigns after mid-October will minimize the need for cancellations because vaccine is unavailable.1 (For information on vaccination of travelers, see PACKAGE INSERT FOR TRAVELERS subsection.)

Dosage recommendations vary according to age group (TABLE 3). Among previously unvaccinated children aged < 9 years, who are receiving influenza vaccine for the first time, two doses administered >/= 1 month apart are recommended for satisfactory antibody responses. If possible, the second dose should be administered before December. If a child aged < 9 years receiving vaccine for the first time does not receive a second dose of vaccine within the same season, only 1 dose of vaccine should be administered the following season (see TABLE 3). Among adults, studies have indicated limited or no improvement in antibody response when a second dose is administered during the same season. Even when the current influenza vaccine contains >/= 1 antigen administered in previous years, annual vaccination with the current vaccine is necessary because immunity declines during the year after vaccination. Vaccine prepared for a previous influenza season should not be administered to provide protection for the current season.1

The intramuscular route is recommended for influenza vaccine (see DOSAGE AND ADMINISTRATION section). Dosage recommendations for the 2007-2008 season are given in Table 3. Guidelines for the use of vaccine among certain patient populations are given below.1

Influenza vaccine (subvirion) is strongly recommended for any person aged >= 6 months who is at increased risk for complications of influenza. In addition, health-care workers and other persons (including household members) in close contact with persons at high risk should be vaccinated to decrease the risk of transmitting influenza to persons at high risk. Influenza vaccine also can be administered to any person aged >/= 6 months to reduce the chance of becoming infected with influenza.1 (See TARGET GROUPS FOR VACCINATION subsection.)

SAFETY AND EFFECTIVENESS OF FLUZONE VACCINE (SUBVIRION) IN INFANTS BELOW THE AGE OF 6 MONTHS HAVE NOT BEEN ESTABLISHED.

Target Groups For Vaccination
Persons at Increased Risk for Complications
According to ACIP, vaccination is recommended for the following groups of persons who are at increased risk for complications from influenza:1

• persons aged ≥ 65 years;
• residents of nursing homes and other chronic-care facilities that house persons of any age who have chronic medical conditions;
• adults and children who have chronic disorders of the pulmonary or cardiovascular systems, including asthma;
• adults and children who have required regular medical follow-up or hospitalization during the preceding year because of chronic metabolic diseases (including diabetes mellitus), renal dysfunction, hemoglobinopathies, or immunosuppression (including immunosuppression caused by medications or by human immunodeficiency virus [HIV]);
• children and adolescents (aged 6 months-18 years) who are receiving long-term aspirin therapy and, therefore, might be at risk for developing Reye syndrome after influenza infection;
• women who will be pregnant during the influenza season; and
• children aged 6-23 months.

In 2000, approximately 73 million persons in the US were included in one or more of these target groups, including 35 million persons aged >/= 65 years; and 12 million adults aged 50-64 years, 18 million adults aged 18-49 years, and 8 million children aged 6 months-17 years with one or more medical conditions that are associated with an increased risk of influenza-related complications.1

Persons Aged 50 to 64 Years
Vaccination is recommended for persons aged 50-64 years because this group has an increased prevalence of persons with high risk conditions. In 2000, approximately 42 million persons in the US were aged 50-64 years, of whom 12 million (29%) had one or more high-risk medical conditions. Influenza vaccine has been recommended for this entire age group to increase the low vaccination rates among persons in this age group with high-risk conditions. Age-based strategies are more successful in increased vaccine coverage than patient-selection strategies based on medical conditions. Persons aged 50-64 years without high-risk conditions also receive benefit from vaccination in the form of decreased rates of influenza illness, decreased work absenteeism, and decreased need for medical visits and medication, including antibiotics. Further, 50 years is an age when other preventive services begin and when routine assessment of vaccination and other preventive services has been recommended.1

Also, persons who smoke tobacco products are at increased risk for influenza-related complications and therefore should receive influenza vaccine.5-7

Persons Who Can Transmit Influenza to Those at High Risk: 1
Persons who are clinically or subclinically infected can transmit influenza virus to persons at high risk for complications from influenza. Decreasing transmission of influenza from caregivers and household contacts to persons at high risk might reduce influenza-related deaths among persons at high risk. Evidence from two studies indicates that vaccination of health-care personnel is associated with decreased deaths among nursing home patients. Vaccination of health-care personnel and others in close contact with persons at high risk, including household contacts, is recommended. The following groups should be vaccinated:1

• physicians, nurses, and other personnel in both hospital and outpatient-care settings, including medical emergency response workers (eg, paramedics and emergency medical technicians);
• employees of nursing homes and chronic-care facilities who have contact with patients or residents;
• employees of assisted living and other residences for persons in groups at high risk;
• persons who provide home care to persons in groups at high risk; and
• household contacts (including children) of persons in groups at high risk.

In addition, because children aged 0-23 months are at increased risk for influenza-related hospitalization, vaccination is recommended for their household contacts and out-of-home caretakers, particularly for contacts of children aged 0-5 months, because influenza vaccines have not been approved by the US Food and Drug Administration (FDA) for use among children aged < 6 months.1

General Population
Physicians should administer influenza vaccine to any person who wishes to reduce the likelihood of becoming ill with influenza (the vaccine can be administered to children aged =/> 6 months) depending on vaccine availability. Persons who provide essential community services should be considered for vaccination to minimize disruption of essential activities during influenza outbreaks. Students or other persons in institutional settings (eg, those who reside in dormitories) should be encouraged to receive vaccine to minimize the disruption of routine activities during epidemics.1

Healthy Young Children
Studies indicate that rates of hospitalization are higher among young children than older children when influenza viruses are in circulation. The increased rates of hospitalization are comparable with rates for other groups considered at high risk for influenza-related complications. However, the interpretation of these findings has been confounded by co-circulation of respiratory syncytial viruses, which are a cause of serious respiratory viral illness among children and which frequently circulate during the same time as influenza viruses. Two recent studies have attempted to separate the effects of respiratory syncytial viruses and influenza viruses on rates of hospitalization among children who do not have high-risk conditions. Both studies reported that otherwise healthy children aged < 2 years, and possibly children aged 2-4 years, are at increased risk for influenza-related hospitalization compared with older healthy children. Some studies report that trivalent inactivated influenza vaccine decreases the incidence of influenza-associated otitis media among young children by approximately 30%.1

Because children aged 6-23 months are at substantially increased risk for influenza-related hospitalizations, ACIP, the American Academy of Pediatrics, and the American Academy of Family Physicians recommends vaccination of all children in this age group. ACIP continues to recommend influenza vaccination of persons aged >/= 6 months who have high-risk medical conditions.1

[SEE PACKAGE INSERT FOR ADDITIONAL INFO ON OTHER GROUPS]

DOSAGE AND ADMINISTRATION
Parenteral drug products should be inspected visually for particulate matter and/or discoloration prior to administration whenever solution and container permit. If either of these conditions exist, the vaccine should not be administered.

To help avoid HIV (AIDS), HBV, (Hepatitis) and other infectious diseases due to accidental needlesticks, contaminated needles should not be recapped or removed, unless there is no alternative or such action is required by a specific medical procedure.

The vial should be shaken well before withdrawing each dose.

The prefilled syringe should be shaken well before administering each dose. The 0.25 mL prefilled syringe is preferred for use when 0.25 mL is indicated for children.

Do NOT inject intravenously.

Injections of Influenza Virus Vaccine should be administered intramuscularly, preferably in the region of the deltoid muscle, in adults and older children. A needle length of >/= 1 inch is preferred for these age groups because needles < 1 inch might be of insufficient length to penetrate muscle tissue in certain adults and older children. Before injection, the skin over the site to be injected should be cleansed with a suitable germicide.

Infants and young children should be vaccinated in the anterolateral aspect of the thigh. ACIP recommends a needle length of 7/8-1 inch for children < 12 months for intramuscular vaccination into the anterolateral thigh. When injecting into the deltoid muscle among children with adequate deltoid muscle mass, a needle length of 7/8-1-1/4 inches is recommended.1

Influenza vaccine should be offered beginning in September (see INDICATIONS AND USAGE section).

Children < 9 years who have not previously been vaccinated should receive two doses of 
vaccine >/ = 1 month apart to maximize the likelihood of a satisfactory antibody response to all three vaccine antigens. If possible, the second dose should be administered before December.1

Fluzone vaccine (Subvirion) is to be used for persons 6 months of age and older. Fluzone vaccine (Subvirion) is NOT approved for infants under 6 months of age. The dosage is as follows:

TABLE 3 1 Influenza Vaccine Dosage by Age Group 2007-2008 Season

HOW SUPPLIED
Syringe, without needle, 0.25 mL (contains NO preservative) (10 per package) Shake syringe well before administering. - Product No. 49281-006-25

Syringe, without needle, 0.5 mL (contains NO preservative) (10 per package) Shake syringe well before administering. - Product No. 49281-006-50

Vial, 0.5 mL (contains NO preservative) (10 per package) Shake vial well before administering. - Product No. 49281-006-10

Vial, 5 mL (contains preservative) for administration with needle and syringe or sterile disposable unit. Shake vial well before withdrawing each dose. - Product No. 49281-378-15

Storage
Store at 2° to 8°C (35° to 46°F). DO NOT FREEZE.

REFERENCES

1. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2004;53: 1-40.

5. Mulloy E. Ir Med J Vol 89 (6): 202, 204, 1996.

6. Zimmerman RK, et al. Am Fam Physician 51 (4): 859-867, 1995.

7. Rothbarth PH, et al. Am J Respir Crit Care Med 151: 1682-1686, 1995.

8. Honkanen P, et al. Arch Intern Med 156: 205-208, 1996.

9. Grilli G, et al. Eur J Epidemiol 13: 287-291, 1997.

10. DeStefano F, et al. JAMA 247: 2551-2554, 1982.

11. CDC. MMWR 2003;52:1-33.

INDICATIONS
LYMErix is indicated for active immunization against Lyme disease in individuals 15 to 70 years of age.

Individuals most at risk may be those who live or work in B. burgdorferi-infected, tick-infested grassy or wooded areas (e.g., landscaping brush clearing, forestry, and wildlife and parks management), 4,18-21 as well as those who plan travel to or pursue recreational activities (e.g., hiking, camping, fishing and hunting) in such areas. Most cases of Lyme disease in the United States are thought to be acquired in the peri-residential environment, through routine activities of property maintenance, recreation, and/or exercise of pets.19, 22

Previous infection with B. burgdorferi may not confer protective immunity.23 Therefore people with a prior history of Lyme disease may benefit from vaccination with LYMErix.

Safety and efficacy for this vaccine are based on administration of the second and third doses several weeks prior to the onset of the Borrelia transmission season in the local geographic area (see DOSAGE AND ADMINISTRATION).

LYMErix is not a treatment for Lyme disease. As with any vaccine, LYMErix may not protect 100% of individuals. The vaccine should not be administered to persons outside of the indicated age range.

DOSAGE AND ADMINISTRATION
Primary immunization against Lyme disease consists of a 30 mcg/0.5 mL dose of LYMErix given at 0, 1 and 12 months.

Vaccination with all three doses is required to achieve optimal protection.

Safety and efficacy for this vaccine are based on administration of the second and third doses several weeks prior to the onset of the Borrelia transmission season in the local geographic area (see INDICATIONS). For example, in the pivotal efficacy trial performed primarily in the Northeast United States (see CLINICAL PHARMACOLOGY, Clinical Efficacy), individuals were vaccinated between January and April in both years of the trial.

LYMErix [Lyme Disease Vaccine (Recombinant OspA)] should be administered by intramuscular injection in the deltoid region. Do not inject intravenously, intradermally or subcutaneously.

Preparation for Administration: Shake well before withdrawal and use. Parenteral drug products should be inspected visually for particulate matter or discoloration prior to administration. With thorough agitation, LYMErix is a turbid white suspension. Discard if it appears otherwise. Any vaccine remaining in a single-dose vial should be discarded.

The vaccine should be used as supplied; no dilution or reconstitution is necessary. The full recommended dose of the vaccine should be used.

As with other intramuscular injections, LYMErix should not be given to individuals on anticoagulant therapy or with clotting disorders, unless the potential benefit clearly outweighs the risk of administration.

No data are available on the immune response to LYMErix when administered concurrently with other vaccines. When concomitant administration of other vaccines is required, they should be given with different syringes and at different injection sites (see DRUG INTERACTIONS).

HOW SUPPLIED
LYMErix [Lyme Disease Vaccine (Recombinant OspA)] is supplied in Single-Dose (30 mcg/0.5 mL) Vials and Prefilled Syringes

NDC 58160-845-01 Package of 1 Single-Dose Vial

NDC 58160-845-11 Package of 10 Single-Dose Vials

NDC 58160-845-35 Package of 5 Prefilled Disposable Tip-Lokˆ Syringes with 1-inch 23-gauge needles

STORAGE
Store between 2° and 8°C (36° and 46°F). Do not freeze; discard if product has been frozen.

INDICATIONS
PNEUMOVAX 23 is indicated for vaccination against pneumococcal disease caused by those pneumococcal types included in the vaccine. Effectiveness of the vaccine in the prevention of pneumococcal pneumonia and pneumococcal bacteremia has been demonstrated in controlled trials in South Africa, France and in case-control studies.

PNEUMOVAX 23 will not prevent disease caused by capsular types of pneumococcus other than those contained in the vaccine.

If it is known that a person has not received any pneumococcal vaccine or if earlier pneumococcal vaccination status is unknown, then persons in the categories listed below should be administered pneumococcal vaccine; however, if a person has received a primary dose of pneumococcal vaccine, before administering an additional dose of vaccine, please refer to the Revaccination section.

Vaccination with PNEUMOVAX 23 is recommended for selected individuals as follows:

Immunocompetent persons:

routine vaccination for persons 50 years of age or older †
persons aged >/=2 years with chronic cardiovascular disease (including congestive heart failure and cardiomyopathies), chronic pulmonary disease (including chronic obstructive pulmonary disease and emphysema), or diabetes mellitus1
persons aged >/=2 years with alcoholism, chronic liver disease (including cirrhosis) or cerebrospinal fluid leaks1
persons aged >/=2 years with functional or anatomic asplenia (including sickle cell disease and splenectomy) 1
persons aged >/=2 years living in special environments or social settings (including Alaskan Natives and certain American Indian populations) 1

Immunocompromised persons:

persons aged >/=2 years, including those with HIV infection, leukemia, lymphoma, Hodgkin†s disease, multiple myeloma, generalized malignancy, chronic renal failure or nephrotic syndrome; those receiving immunosuppressive chemotherapy (including corticosteroids); and those who have received an organ or bone marrow transplant. 1

Timing of Vaccination

Pneumococcal vaccine should be given at least two weeks before elective splenectomy, if possible.

For planning cancer chemotherapy or other immunosuppressive therapy (e.g., for patients with Hodgkin†s disease or those who undergo organ or bone marrow transplantation), pneumococcal vaccination should be administered at least two weeks prior to the initiation of immunosuppressive therapy. Vaccination during chemotherapy or radiation therapy should be avoided. Based on literature reports, pneumococcal vaccine may be given as early as several months following completion of chemotherapy or radiation therapy for neoplastic disease.34,36 In Hodgkin†s disease, immune response to vaccination may be impaired for two years or longer after intensive chemotherapy (with or without radiation). During the two years following the completion of chemotherapy or other immunosuppressive therapy, antibody responses improve in some patients as the interval between the end of treatment and pneumococcal vaccination increases. 34

Persons with asymptomatic or symptomatic HIV infection should be vaccinated as soon as possible after their diagnosis is confirmed.

Use With Other Vaccines

The ACIP states that pneumococcal vaccine may be administered at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine. 1 In contrast to pneumococcal vaccine, influenza vaccine is recommended annually, for appropriate populations. 31

Revaccination

Early studies have indicated that local reactions (i. e., arthus-type reactions) among adults receiving the second dose of 14-valent vaccine within 2 years after the first dose are more severe than those occurring after initial vaccination. However, subsequent studies have suggested that revaccination after intervals of >/=4 years is not associated with an increased incidence of adverse side effects.1

Routine revaccination of immunocompetent persons previously vaccinated with 23-valent polysaccharide vaccine is not recommended.1 However, revaccination once is recommended for persons >/=2 years of age who are at highest risk of serious pneumococcal infection and those likely to have a rapid decline in pneumococcal antibody levels, provided that at least five years have passed since receipt of a first dose of pneumococcal vaccine. 1

The highest risk group includes persons with functional or anatomic asplenia (e.g., sickle cell disease or splenectomy), HIV infection, leukemia, lymphoma, Hodgkin†s disease, multiple myeloma, generalized malignancy, chronic renal failure, nephrotic syndrome, or other conditions associated with immunosuppression (e.g., organ or bone marrow transplantation), and those receiving immunosuppressive chemotherapy (including long-term systemic corticosteroids).1

For children </=10 years of age at revaccination and at highest risk of severe pneumococcal infection (e.g., children with functional or anatomic asplenia, including sickle cell disease or splenectomy or conditions associated with rapid antibody decline after initial vaccination including nephrotic syndrome, renal failure or renal transplantation), the ACIP recommends that revaccination may be considered three years after the previous dose.1

If prior vaccination status is unknown for patients in the high risk group, patients should be given pneumococcal vaccine.1

All persons >/=65 years of age who have not received vaccine within 5 years (and were < 65 years of age at the time of vaccination) should receive another dose of vaccine.1

Because data are insufficient concerning the safety of pneumococcal vaccine when administered three or more times, revaccination following a second dose is not routinely recommended.1

DOSAGE AND ADMINISTRATION
Do not inject intravenously or intradermally.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. PNEUMOVAX 23 is a clear, colorless solution. The vaccine is used directly as supplied. No dilution or reconstitution is necessary. Phenol 0.25% has been added as a preservative.

It is important to use a separate sterile syringe and needle for each individual patient to prevent transmission of infectious agents from one person to another.

Withdraw 0.5 mL from the vial using a sterile needle and syringe free of preservatives, antiseptics, and detergents.

Administer a single 0.5 mL dose of PNEUMOVAX 23 subcutaneously or intramuscularly (preferably in the deltoid muscle or lateral mid-thigh), with appropriate precautions to avoid intravascular administration.

Store unopened and opened vials at 2-8° C( 36-46° F). The vaccine is used directly as supplied. No dilution or reconstitution is necessary. Phenol 0.25% has been added as a preservative. All vaccine must be discarded after the expiration date.

Use With Other Vaccines

The ACIP states that pneumococcal vaccine may be administered at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine.1 In contrast to pneumococcal vaccine, influenza vaccine is recommended annually, for appropriate populations. 3

HOW SUPPLIED
No. 4739 † PNEUMOVAX 23 is supplied as one 5-dose vial of liquid vaccine, color coded with a purple cap and stripe on the vial labels and cartons, NDC 0006-4739-00.

No. 4739 † PNEUMOVAX 23 is supplied as one 5-dose vial of liquid vaccine, in a box of 10 five-dose vials, color coded with a purple cap and stripe on the vial labels and cartons, NDC 0006-4739-50.

No. 4943 † PNEUMOVAX 23 is supplied as a single-dose vial of liquid vaccine, in a box of 10 singledose vials, color coded with a purple cap and stripe on the vial labels and cartons, NDC 0006-4943-00.

REFERENCES

1. Recommendation of the Advisory Committee on Immunization Practices † Prevention of Pneumococcal Disease, Morbidity and Mortality Weekly Report, 46(RR-8): 1-25, April 4, 1997.

2. Robbins, J. B.; Lee, C. J.; Schiffman, G.; Austrian, R.; Henrichsen, J.; M?¤kel?¤, RH.; Broome, C. V.; Facklam, R. R.; Tiesjema, RH.; Rastogi, S. C.: Considerations for formulating the second-generation pneumococcal capsular polysaccharide vaccine with emphasis on the cross-reactive types within groups, J. Infect. Dis. 148: 1136-1159, 1983.

3. WHO: Vital statistics and causes of death, World Health Statistics Annual, 1, 1976.