2.1 Vaccination Schedule

VAXELIS is to be administered as a 3-dose series at 2, 4, and 6 months of age. The first dose may be given as early as 6 weeks of age. Three doses of VAXELIS constitute a primary immunization course against diphtheria, tetanus, H. influenzae type b invasive disease and poliomyelitis.

VAXELIS may be used to complete the hepatitis B immunization series.

A 3-dose series of VAXELIS does not constitute a primary immunization series against pertussis; an additional dose of pertussis-containing vaccine is needed to complete the primary series. [See Pertussis Vaccination Following VAXELIS.]

2.2 Administration

Just before use, shake the vial or syringe until a uniform, white, cloudy suspension results.

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

Administer a single 0.5 mL dose of VAXELIS intramuscularly.

In infants younger than 1 year, the anterolateral aspect of the thigh is the preferred site of injection. The vaccine should not be injected into the gluteal area.

VAXELIS should not be combined through reconstitution or mixed with any other vaccine. Discard unused portion.

4.1 Hypersensitivity

Do not administer VAXELIS to anyone with a history of a severe allergic reaction (e.g., anaphylaxis) to a previous dose of VAXELIS, any ingredient of VAXELIS, or any other diphtheria toxoid, tetanus toxoid, pertussis-containing vaccine, inactivated poliovirus vaccine, hepatitis B vaccine, or H. influenzae type b vaccine [See DESCRIPTION (11).]

4.2 Encephalopathy

Do not administer VAXELIS to anyone with a history of encephalopathy (e.g., coma, decreased level of consciousness, prolonged seizures) within 7 days of a previous dose of a pertussis-containing vaccine, that is not attributable to another identifiable cause.

4.3 Progressive Neurologic Disorder

Do not administer VAXELIS to anyone with a history of progressive neurologic disorder, including infantile spasms, uncontrolled epilepsy, or progressive encephalopathy until a treatment regimen has been established and the condition has stabilized.

5.1 Management of Acute Allergic Reactions

Epinephrine hydrochloride solution (1:1,000) and other appropriate agents and equipment must be available for immediate use in case an anaphylactic or acute hypersensitivity reaction occurs.

5.2 Adverse Reactions Following Prior Pertussis Vaccination

If any of the following events occur after administration of a pertussis vaccine, the decision to administer VAXELIS should be based on careful consideration of potential benefits and possible risks.

• Temperature of ≥40.5°C (≥105°F) within 48 hours, not attributable to another identifiable cause.
• Collapse or shock-like state (hypotonic-hyporesponsive episode [HHE]) within 48 hours.
• Persistent, inconsolable crying lasting ≥3 hours within 48 hours.
• Seizures with or without fever within 3 days.

5.3 Guillain-Barré Syndrome and Brachial Neuritis

A review by the Institute of Medicine (IOM) found evidence for a causal relation between tetanus toxoid and both brachial neuritis and Guillain-Barré syndrome. If Guillain-Barré syndrome occurred within 6 weeks of receipt of a prior vaccine containing tetanus toxoid, the risk for Guillain-Barré syndrome may be increased following VAXELIS. (1)

5.4 Altered Immunocompetence

If VAXELIS is administered to immunocompromised persons, including persons receiving immunosuppressive therapy, the expected immune response may not be obtained.

5.5 Apnea in Premature Infants

Apnea following intramuscular vaccination has been observed in some infants born prematurely. The decision about when to administer an intramuscular vaccine, including VAXELIS, to an infant born prematurely should be based on consideration of the infant's medical status and the potential benefits and possible risks of vaccination.

5.6 Limitations of Vaccine Effectiveness

Vaccination with VAXELIS may not protect all individuals.

5.7 Interference with Laboratory Tests

Urine antigen detection may not have definitive diagnostic value in suspected H. influenzae type b disease following vaccination with VAXELIS. [See DRUG INTERACTIONS (7.1).]

6.1 Clinical Trials Experience

Because clinical trials are conducted under varying conditions, adverse reaction rates observed in the clinical trials of a vaccine cannot be directly compared to rates in the clinical trials of another vaccine and may not reflect the rates observed in practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to vaccine use and for approximating rates of those events.

The safety of VAXELIS was evaluated in 6 clinical studies, in which a total of 5,251 infants 43 to 99 days of age at enrollment received at least 1 dose of VAXELIS. Two of these (study 005 and 006) were controlled clinical studies conducted in the US, in which a total of 3,380 infants 46 to 89 days of age at enrollment received at least 1 dose of VAXELIS. The vaccination schedules of VAXELIS, Control vaccines, and concomitantly administered vaccines used in these studies are provided in Table 1. At 15 months of age, participants in Study 005 received a dose of DAPTACEL and a H. influenzae type b conjugate vaccine, whereas participants in Study 006 received a dose of Pentacel. In a non-US study, 294 children received a dose of VAXELIS at 15 months of age.

Across the 2 studies conducted in the US, among all randomized participants (3,392 in the VAXELIS group and 889 in the Control group), 52.6% were male and 47.4% were female. The race distribution was as follows: 71.7% were White, 11.0% were Black, 4.5% were American Indian or Alaska Native, 3.5% were Asian, and 9.3% were of other racial groups. Most participants (81.8%) were of non-Hispanic or Latino ethnicity. The racial/ethnic distribution of participants who received VAXELIS and Control vaccines was similar.

6.2 Postmarketing Experience

The following adverse events have been reported during post-marketing use of VAXELIS or other vaccines containing the antigens of VAXELIS. These adverse events are included based on a suspected causal connection to VAXELIS or the components of DAPTACEL® (Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed), IPOL® (Poliovirus Vaccine Inactivated), COMVAX® [Haemophilus b Conjugate (Meningococcal Protein Conjugate) and Hepatitis B (Recombinant) Vaccine]. (COMVAX is no longer licensed in the US.)

Because these events are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to vaccination.

• Immune System Disorders
  Hypersensitivity (such as rash, urticaria, dyspnea, erythema multiforme), anaphylactic reaction (such as urticaria, angioedema, edema, face edema, shock).
• General Disorders and Administration Site Conditions
  Extensive swelling of injected limb (including swelling that involves adjacent joints).
• Nervous System
  Seizure, febrile seizure, hypotonic-hyporesponsive episode (HHE).

7.1 Interference with Laboratory Tests

Sensitive tests (e.g., Latex Agglutination kits) have detected vaccine-derived polyribosylribitol phosphate (PRP) in the urine of vaccinees for at least 30 days following vaccination with PedvaxHIB [Haemophilus b Conjugate Vaccine (Meningococcal Protein Conjugate)]. (2) Therefore, urine antigen detection may not have definite diagnostic value in suspected H. influenzae type b disease following vaccination with VAXELIS. [See WARNINGS AND PRECAUTIONS (5.7).]

8.1 Pregnancy

VAXELIS is not approved for use in individuals 5 years of age and older. No human or animal data are available to assess vaccine-associated risks in pregnancy.

8.2 Lactation

VAXELIS is not approved for use in individuals 5 years of age and older. No human or animal data are available to assess the impact of VAXELIS on milk production, its presence in breast milk, or its effects on the breastfed infant.

8.4 Pediatric Use

The safety of VAXELIS has been established in the age group 6 weeks through 15 months, and the effectiveness of VAXELIS was established in the age group 6 weeks through 6 months on the basis of clinical studies. [See ADVERSE REACTIONS (6.1) AND CLINICAL STUDIES (14).]

The safety and effectiveness of VAXELIS in older children through 4 years of age are supported by evidence in younger children. The safety and effectiveness of VAXELIS in infants less than 6 weeks of age and in children and adolescents 5 through 17 years of age have not been established.

12.1 Mechanism of Action

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

VAXELIS has not been evaluated for carcinogenic or mutagenic potential or impairment of fertility.

14.1 Effectiveness of VAXELIS

The effectiveness of VAXELIS is based on the immunogenicity of the individual antigens compared to US licensed vaccines. Serological correlates of protection exist for diphtheria, tetanus, hepatitis B, poliomyelitis, and invasive disease due to H. influenzae type b. The effectiveness against pertussis is based upon the pertussis immune responses following 3 doses of VAXELIS compared to 3 doses of Pentacel, as well as the pertussis immune responses following a subsequent dose of DAPTACEL in the same 2 groups of children. VAXELIS, Pentacel and DAPTACEL contain the same pertussis antigens, manufactured by the same processes.

14.2 Immunogenicity

In the US Study 005 (Table 1), infants were randomized to receive 3 doses of VAXELIS at 2, 4, and 6 months of age and DAPTACEL and PedvaxHIB at 15 months of age, or Control group vaccines (3 doses of Pentacel vaccine at 2, 4, and 6 months of age + RECOMBIVAX HB at 2 and 6 months of age and DAPTACEL and ActHIB at 15 months of age). All subjects received concomitant vaccines: RotaTeq at 2, 4 and 6 months and Prevnar 13 at 2, 4, 6, and 15 months of age. [See ADVERSE REACTIONS (6.1).] All infants had received a dose of hepatitis B vaccine prior to study initiation, prior to or at one month of age. Among all randomized participants, 53.0% were male and 47.0% were female. Most (79.2%) participants were White, 14.1% were Black and 5.2% were multi-racial. Most (91.4%) participants were of non-Hispanic or non-Latin ethnicity.

Antibody responses to diphtheria, tetanus, pertussis (PT, FHA, PRN and FIM), poliovirus types 1, 2 and 3, hepatitis B and H. influenzae type b antigens were measured in sera obtained one month following the third dose of VAXELIS or Pentacel + RECOMBIVAX HB vaccines. VAXELIS was non-inferior to Pentacel + RECOMBIVAX HB administered concomitantly at separate sites, as demonstrated by the proportions of participants achieving seroprotective levels of antibodies to diphtheria, tetanus, poliovirus, hepatitis B and PRP antigens, and pertussis vaccine response rates and GMCs (except FHA), following 3 doses of the vaccine. See Table 3.

To complete the 4-dose pertussis primary vaccination series, participants in both groups received DAPTACEL at 15 months of age and were evaluated for immune responses to pertussis antigens one month later. The non-inferiority criteria for vaccine response rates and GMCs for all pertussis antigens were met following the fourth dose.

Study 006 (Table 1) was a lot consistency study conducted in the US, where infants were randomized to receive 3 doses of VAXELIS at 2, 4, and 6 months of age and Pentacel at 15 months of age (N=2,406), or control group vaccines (4 doses of Pentacel at 2, 4, 6, and 15 months of age + RECOMBIVAX HB at 2 and 6 months of age; N=402). All subjects received concomitant vaccines: RotaTeq at 2, 4 and 6 months and Prevnar 13 at 2, 4, 6, and 15 months of age. All infants had received a dose of hepatitis B vaccine prior to study initiation, from birth up to one month of age.

Antibody responses to diphtheria, tetanus, pertussis (PT, FHA, PRN and FIM), poliovirus types 1, 2 and 3, hepatitis B and H. influenzae type b antigens were measured in sera obtained one month following the third dose of VAXELIS or Pentacel + RECOMBIVAX HB. VAXELIS was non-inferior to Pentacel + RECOMBIVAX HB administered concomitantly at separate sites, as demonstrated by the proportions of participants achieving seroprotective levels of antibodies to diphtheria, tetanus, poliovirus, hepatitis B and PRP antigens, and pertussis vaccine response rates and GMCs, except for GMCs for FHA (lower bound of 2-sided 95% CI for GMC ratio [VAXELIS group/Control group vaccines] was 0.62, which was below the non-inferiority criterion >0.67).

To complete the 4-dose pertussis primary vaccination series, participants in both groups received Pentacel at 15 months of age and were evaluated for immune responses to pertussis antigens one month later. The non-inferiority criteria for antibody vaccine response rates and GMCs for all pertussis antigens were met following the fourth dose except for GMCs for PRN (lower bound of 2-sided 95% CI for GMC ratio [VAXELIS group/Control group vaccines] was 0.66, which was below the non-inferiority criterion >0.67).

14.3 Concomitantly Administered Vaccines

In Study 006 conducted in the US (Table 1), the immune responses to Prevnar 13 were measured one month after the third dose. Non-inferiority criteria were met for GMCs to 12 of the 13 serotype antigens in Prevnar 13 for participants who received VAXELIS relative to Control vaccines. For serotype 6B, the non-inferiority criterion was not met (lower bound of 2-sided 95% CI for GMC ratio [VAXELIS group/Control vaccines group] is 0.64, which is below the non-inferiority criterion >0.67).

16.1 How Supplied

Single-dose vial (NDC 63361-243-58) in packages of 10 vials (NDC 63361-243-10).

Single-dose, prefilled syringe with Luer lock connection and a tip cap, without needle, 0.5 mL (NDC 63361-243-88). Supplied as package of 10 (NDC 63361-243-15).

The vial stopper, syringe plunger stopper, and syringe tip cap are not made with natural rubber latex.

16.2 Storage and Handling

VAXELIS should be stored at 2°C to 8°C (36°F to 46°F). Do not freeze. Product which has been exposed to freezing should not be used. Protect from light. Do not use after expiration date shown on the label. Discard unused portion.