KINRIX: Package Insert and Label Information

KINRIX- corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated), clostridium tetani toxoid antigen (formaldehyde inactivated), bordetella pertussis filamentous hemagglutinin antigen (formaldehyde inactivated), bordetella pertussis pertactin antigen (formaldehyde inactivated), bordetella pertussis toxoid antigen (formaldehyde, glutaraldehyde inactivated), poliovirus type 1 antigen (formaldehyde inactivated), poliovirus type 2 antigen (formaldehyde inactivated) and poliovirus type 3 antigen (formaldehyde inactivated) injection, suspension
GlaxoSmithKline Biologicals SA

1 INDICATIONS AND USAGE

A single dose of KINRIX is indicated for active immunization against diphtheria, tetanus, pertussis, and poliomyelitis as the fifth dose in the diphtheria, tetanus, and acellular pertussis (DTaP) vaccine series and the fourth dose in the inactivated poliovirus vaccine (IPV) series in children aged 4 through 6 years (prior to the 7^th birthday) whose previous DTaP vaccine doses have been with INFANRIX (Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed) and/or PEDIARIX [Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Hepatitis B (Recombinant) and Inactivated Poliovirus Vaccine] for the first 3 doses and INFANRIX for the fourth dose.

2 DOSAGE AND ADMINISTRATION

2.1 Preparation for Administration

Shake vigorously to obtain a homogeneous, turbid, white suspension. Do not use if resuspension does not occur with vigorous shaking. 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 exists, the vaccine should not be administered.

For the prefilled syringes, attach a sterile needle and administer intramuscularly.

For the vials, use a sterile needle and sterile syringe to withdraw the 0.5-mL dose and administer intramuscularly. Changing needles between drawing vaccine from a vial and injecting it into a recipient is not necessary unless the needle has been damaged or contaminated. Use a separate sterile needle and syringe for each individual.

Do not administer this product intravenously, intradermally, or subcutaneously.

2.2 Recommended Dose and Schedule

KINRIX is to be administered as a 0.5-mL dose by intramuscular injection. The preferred site of administration is the deltoid muscle of the upper arm.

KINRIX may be used for the fifth dose in the DTaP immunization series and the fourth dose in the IPV immunization series in children aged 4 through 6 years (prior to the 7th birthday) whose previous DTaP vaccine doses have been with INFANRIX and/or PEDIARIX for the first 3 doses and INFANRIX for the fourth dose [see Indications and Usage (1)].

3 DOSAGE FORMS AND STRENGTHS

KINRIX is a suspension for injection available in 0.5-mL single-dose vials and 0.5-mL single-dose prefilled TIP‑LOK syringes.

4 CONTRAINDICATIONS

4.1 Hypersensitivity

Severe allergic reaction (e.g., anaphylaxis) after a previous dose of any diphtheria toxoid-, tetanus toxoid-, pertussis- or poliovirus-containing vaccine, or to any component of KINRIX, including neomycin and polymyxin B, is a contraindication to administration of KINRIX [see Description (11)]. Because of the uncertainty as to which component of the vaccine might be responsible, no further vaccination with any of these components should be given. Alternatively, such individuals may be referred to an allergist for evaluation if immunization with any of these components is considered.

4.2 Encephalopathy

Encephalopathy (e.g., coma, decreased level of consciousness, prolonged seizures) within 7 days of administration of a previous dose of a pertussis-containing vaccine that is not attributable to another identifiable cause is a contraindication to administration of any pertussis-containing vaccine, including KINRIX.

4.3 Progressive Neurologic Disorder

Progressive neurologic disorder, including infantile spasms, uncontrolled epilepsy, or progressive encephalopathy, is a contraindication to administration of any pertussis-containing vaccine, including KINRIX. Pertussis vaccine should not be administered to individuals with such conditions until a treatment regimen has been established and the condition has stabilized.

5 WARNINGS AND PRECAUTIONS

5.1 Guillain-Barré Syndrome

If Guillain-Barré syndrome occurs within 6 weeks of receipt of a prior vaccine containing tetanus toxoid, the decision to give any tetanus toxoid-containing vaccine, including KINRIX, should be based on careful consideration of the potential benefits and possible risks. When a decision is made to withhold tetanus toxoid, other available vaccines should be given, as indicated.

5.2 Latex

The tip caps of the prefilled syringes contain natural rubber latex which may cause allergic reactions.

5.3 Syncope

Syncope (fainting) can occur in association with administration of injectable vaccines, including KINRIX. Syncope can be accompanied by transient neurological signs such as visual disturbance, paresthesia, and tonic-clonic limb movements. Procedures should be in place to avoid falling injury and to restore cerebral perfusion following syncope.

5.4 Adverse Reactions following Prior Pertussis Vaccination

If any of the following reactions occur in temporal relation to receipt of a pertussis-containing vaccine, the decision to give any pertussis-containing vaccine, including KINRIX, should be based on careful consideration of the potential benefits and possible risks:

•

Temperature of ≥40.5^o C (105^o F) within 48 hours not due to another identifiable cause;

•

Collapse or shock-like state (hypotonic-hyporesponsive episode) within 48 hours;

•

Persistent, inconsolable crying lasting ≥3 hours, occurring within 48 hours;

•

Seizures with or without fever occurring within 3 days.

When a decision is made to withhold pertussis vaccination, other available vaccines should be given, as indicated.

5.5 Children at Risk for Seizures

For children at higher risk for seizures than the general population, an appropriate antipyretic may be administered at the time of vaccination with a pertussis-containing vaccine, including KINRIX, and for the ensuing 24 hours to reduce the possibility of post-vaccination fever.

5.6 Preventing and Managing Allergic Vaccine Reactions

Prior to administration, the healthcare provider should review the patient’s immunization history for possible vaccine sensitivity and previous vaccination-related adverse reactions to allow an assessment of benefits and risks. Epinephrine and other appropriate agents used for the control of immediate allergic reactions must be immediately available should an acute anaphylactic reaction occur.

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a vaccine cannot be directly compared with rates in the clinical trials of another vaccine and may not reflect the rates observed in practice.

A total of 4,013 children were vaccinated with a single dose of KINRIX in 4 clinical trials. Of these, 381 children received a non-U.S. formulation of KINRIX (containing ≤2.5 mg 2‑phenoxyethanol per dose as preservative).

The primary study (Study 048), conducted in the United States, was a randomized, controlled clinical trial in which children aged 4 to 6 years were vaccinated with KINRIX (n = 3,156) or control vaccines (INFANRIX and IPOL vaccine [IPV, Sanofi Pasteur SA]; n = 1,053) as a fifth DTaP vaccine dose following 4 doses of INFANRIX and as a fourth IPV dose following 3 doses of IPOL. Subjects also received the second dose of U.S.‑licensed measles, mumps, and rubella (MMR) vaccine (Merck & Co., Inc.) administered concomitantly, at separate sites.

Data on adverse events were collected by parents/guardians using standardized forms for 4 consecutive days following vaccination with KINRIX or control vaccines (i.e., day of vaccination and the next 3 days). The reported frequencies of solicited local reactions and general adverse reactions in Study 048 are presented in Table 1.

In 3 studies (Studies 046, 047, and 048), children were monitored for unsolicited adverse events, including serious adverse events that occurred in the 31-day period following vaccination, and in 2 studies (Studies 047 and 048), parents/guardians were actively queried about changes in the child’s health status, including the occurrence of serious adverse events, through 6 months post-vaccination.

Table 1. Percentage of Children Aged 4 to 6 Years Reporting Solicited Local or General Adverse Reactions within 4 Days of Vaccination^a with KINRIX or Separate Concomitant Administration of INFANRIX and IPV when Coadministered with MMR Vaccine (Study 048) (Total Vaccinated Cohort)

IPV = Inactivated poliovirus vaccine (Sanofi Pasteur SA); MMR = Measles, mumps, and rubella vaccine (Merck & Co., Inc.). Total Vaccinated Cohort = All vaccinated subjects for whom safety data were available. n = Number of children with evaluable data for the reactions listed. a Within 4 days of vaccination defined as day of vaccination and the next 3 days. b Local reactions at the injection site for KINRIX or INFANRIX. c Statistically higher than comparator group (P <0.05). d Grade 2 defined as painful when the limb was moved; Grade 3 defined as preventing normal daily activities. e Grade 3 defined as preventing normal daily activities. f Grade 3 defined as not eating at all.
Adverse Reaction	KINRIX	INFANRIX + IPV
Localb	n = 3,121-3,128	n = 1,039-1,043
Pain, any	57c	53
Pain, Grade 2 or 3d	14	12
Pain, Grade 3d	2c	1
Redness, any	37	37
Redness, ≥50 mm	18	20
Redness, ≥110 mm	3	4
Arm circumference increase, any	36	38
Arm circumference increase, >20 mm	7	7
Arm circumference increase, >30 mm	2	3
Swelling, any	26	27
Swelling, ≥50 mm	10	12
Swelling, ≥110 mm	1	2
General	n = 3,037-3,120	n = 993-1,036
Drowsiness, any	19	18
Drowsiness, Grade 3e	1	1
Fever, ≥99.5°F	16	15
Fever, >100.4°F	7c	4
Fever, >102.2°F	1	1
Fever, >104°F	0	0
Loss of appetite, any	16	16
Loss of appetite, Grade 3f	1	1

In Study 048, KINRIX was non-inferior to INFANRIX with regard to swelling that involved >50% of the injected upper arm length and that was associated with a >30 mm increase in mid-upper arm circumference within 4 days following vaccination (upper limit of 2-sided 95% Confidence Interval for difference in percentage of KINRIX [0.6%, n = 20] minus INFANRIX [1.0%, n = 11] ≤2%).

Serious Adverse Events

Within the 31-day period following study vaccination in 3 studies (Studies 046, 047, and 048) in which all subjects received concomitant MMR vaccine (U.S.‑licensed MMR vaccine [Merck & Co., Inc.] in Studies 047 and 048, non—U.S.-licensed MMR vaccine in Study 046), 3 subjects (0.1% [3/3,537]) who received KINRIX reported serious adverse events (dehydration and hypernatremia; cerebrovascular accident; dehydration and gastroenteritis) and 4 subjects (0.3% [4/1,434]) who received INFANRIX and inactivated poliovirus vaccine (Sanofi Pasteur SA) reported serious adverse events (cellulitis, constipation, foreign body trauma, fever without identified etiology).

6.2 Postmarketing Experience

In addition to reports in clinical trials for KINRIX, the following adverse reactions have been identified during postapproval use of KINRIX. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to vaccination.

General Disorders and Administration Site Conditions

Injection site vesicles.

Nervous System Disorders

Syncope.

Skin and Subcutaneous Tissue Disorders

Pruritus.

Additional adverse reactions reported following postmarketing use of INFANRIX, for which a causal relationship to vaccination is plausible, are: Allergic reactions, including anaphylactoid reactions, anaphylaxis, angioedema, and urticaria; apnea; collapse or shock-like state (hypotonic-hyporesponsive episode); convulsions (with or without fever); lymphadenopathy; and thrombocytopenia.