VAQTA- hepatitis a virus strain cr 326f antigen (formaldehyde inactivated) injection, suspension
Merck Sharp & Dohme Corp.
1 INDICATIONS AND USAGE
1.1 Indications and Use
VAQTA� [Hepatitis A Vaccine, Inactivated] is indicated for the prevention of disease caused by hepatitis A virus (HAV) in persons 12 months of age and older. The primary dose should be given at least 2 weeks prior to expected exposure to HAV.
2 DOSAGE AND ADMINISTRATION
FOR INTRAMUSCULAR ADMINISTRATION ONLY.
2.1 Dosage and Schedule
Children/Adolescents (12 months through 18 years of age): The vaccination schedule consists of a primary 0.5-mL dose administered intramuscularly, and a 0.5-mL booster dose administered intramuscularly 6 to 18 months later.
Adults (19 years of age and older): The vaccination schedule consists of a primary 1-mL dose administered intramuscularly, and a 1-mL booster dose administered intramuscularly 6 to 18 months later.
Booster Immunization Following Another Manufacturer's Hepatitis A Vaccine: A booster dose of VAQTA may be given at 6 to 12 months following a primary dose of HAVRIX [see Clinical Studies (14.6)].
2.2 Preparation and Administration
Shake the single-dose vial or single-dose prefilled syringe well to obtain a slightly opaque, white suspension before withdrawal and use. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Discard if the suspension does not appear homogenous or if extraneous particulate matter remains or discoloration is observed.
For single-dose vials, withdraw and administer entire dose of VAQTA intramuscularly using a sterile needle and syringe.
For single-dose prefilled syringes, securely attach a needle by twisting in a clockwise direction and administer dose of VAQTA intramuscularly.
For adults, adolescents, and children older than 2 years of age, the deltoid muscle is the preferred site for intramuscular injection. For children 12 through 23 months of age, the anterolateral area of the thigh is the preferred site for intramuscular injection.
3 DOSAGE FORMS AND STRENGTHS
Suspension for injection available in four presentations:
0.5-mL pediatric dose in single-dose vials and prefilled syringes
1-mL adult dose in single-dose vials and prefilled syringes
[See Description (11) for listing of vaccine components and How Supplied/Storage and Handling (16).]
4 CONTRAINDICATIONS
Do not administer VAQTA to individuals with a history of immediate and/or severe allergic or hypersensitivity reactions (e.g. , anaphylaxis) after a previous dose of any hepatitis A vaccine, or to individuals who have had an anaphylactic reaction to any component of VAQTA, including neomycin [see Description (11)].
5 WARNINGS AND PRECAUTIONS
5.1 Prevention and Management of Allergic Vaccine Reactions
Appropriate medical treatment and supervision must be available to manage possible anaphylactic reactions following administration of the vaccine [see Contraindications (4)].
5.2 Hypersensitivity to Latex
The vial stopper and the syringe plunger stopper and tip cap contain dry natural latex rubber that may cause allergic reactions in latex-sensitive individuals [see How Supplied/Storage and Handling (16)].
5.3 Altered Immunocompetence
Immunocompromised persons, including individuals receiving immunosuppressive therapy, may have a diminished immune response to VAQTA and may not be protected against HAV infection after vaccination [see Use in Specific Populations (8.6)].
5.4 Limitations of Vaccine Effectiveness
Hepatitis A virus has a relatively long incubation period (approximately 20 to 50 days). VAQTA may not prevent hepatitis A infection in individuals who have an unrecognized hepatitis A infection at the time of vaccination. Vaccination with VAQTA may not result in a protective response in all susceptible vaccinees.
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 to rates in the clinical trials of another vaccine and may not reflect the rates observed in practice.
The safety of VAQTA has been evaluated in over 10,000 subjects 1 year to 85 years of age. Subjects were given one or two doses of the vaccine. The second (booster dose) was given 6 months or more after the first dose.
The most common local adverse reactions and systemic adverse events (≥15%) reported in different clinical trials across different age groups when VAQTA was administered alone or concomitantly were:
Children - 12 through 23 months of age: injection-site pain/tenderness (37.0%), injection-site erythema (21.2%), fever (16.4% when administered alone, and 27.0% when administered concomitantly).
Children/Adolescents - 2 through 18 years of age: injection-site pain (18.7%)
Adults - 19 years of age and older: injection-site pain, tenderness, or soreness (67.0%), injection-site warmth (18.2%) and headache (16.1%)
Allergic Reactions
Local and/or systemic allergic reactions that occurred in <1% of over 10,000 children/adolescents or adults in clinical trials regardless of causality included: injection-site pruritus and/or rash; bronchial constriction; asthma; wheezing; edema/swelling; rash; generalized erythema; urticaria; pruritus; eye irritation/itching; dermatitis [see Contraindications (4) and Warnings and Precautions (5.1)].
Children - 12 through 23 Months of Age
Across five clinical trials, 4374 children 12 to 23 months of age received one or two 25U doses of VAQTA, including 3885 children who received 2 doses of VAQTA and 1250 children who received VAQTA concomitantly with one or more other vaccines, including Measles, Mumps, and Rubella Virus Vaccine, Live (M-M-R II�), Varicella Vaccine, Live (VARIVAX�), Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine, Adsorbed (Tripedia or INFANRIX), Measles, Mumps, Rubella, and Varicella Vaccine, Live (ProQuad�), Pneumococcal 7-valent Conjugate Vaccine (Diphtheria CRM197, Prevnar), or Haemophilus B Conjugate Vaccine (Meningococcal Protein Conjugate, PedvaxHIB�). Overall, the race distribution of study subjects was as follows: 64.7% Caucasian; 15.7% Hispanic-American; 12.3% Black; 4.8% other; 1.4% Asian; and 1.1% Native American. The distribution of subjects by gender was 51.8% male and 48.2% female.
In an open-label clinical trial, 653 children 12 to 23 months of age were randomized to receive a first dose of VAQTA with ProQuad and Prevnar concomitantly (N=330) or a first dose of ProQuad and pneumococcal 7-valent conjugate vaccine concomitantly, followed by a first dose of VAQTA 6 weeks later (N=323). Approximately 6 months later, subjects received either the second doses of ProQuad and VAQTA concomitantly or the second doses of ProQuad and VAQTA separately. The race distribution of the study subjects was as follows: 60.3% Caucasian; 21.6% African-American; 9.5% Hispanic-American; 7.2% other; 1.1% Asian; and 0.3% Native American. The distribution of subjects by gender was 50.7% male and 49.3% female.
DESCRIPTION
VAQTA is an inactivated whole virus vaccine derived from hepatitis A virus grown in cell culture in human MRC-5 diploid fibroblasts. It contains inactivated virus of a strain which was originally derived by further serial passage of a proven attenuated strain. The virus is grown, harvested, purified by a combination of physical and high performance liquid chromatographic techniques developed at the Merck Research Laboratories, formalin inactivated, and then adsorbed onto amorphous aluminum hydroxyphosphate sulfate.
VAQTA is a sterile suspension for intramuscular injection. One milliliter of the vaccine contains approximately 50U of hepatitis A virus antigen, which is purified and formulated without a preservative. Within the limits of current assay variability, the 50U dose of VAQTA contains less than 0.1 mcg of non-viral protein, less than 4 � 10�6 mcg of DNA, less than 10�4 mcg of bovine albumin, and less than 0.8 mcg of formaldehyde. Other process chemical residuals are less than 10 parts per billion (ppb), including neomycin.
Each 0.5-mL pediatric dose contains 25U of hepatitis A virus antigen and adsorbed onto approximately 0.225 mg of aluminum provided as amorphous aluminum hydroxyphosphate sulfate, and 35 mcg of sodium borate as a pH stabilizer, in 0.9% sodium chloride.
Each 1-mL adult dose contains 50U of hepatitis A virus antigen and adsorbed onto approximately 0.45 mg of aluminum provided as amorphous aluminum hydroxyphosphate sulfate, and 70 mcg of sodium borate as a pH stabilizer, in 0.9% sodium chloride.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
VAQTA has been shown to elicit antibodies to hepatitis A as measured by ELISA.
Protection from hepatitis A disease has been shown to be related to the presence of antibody. However, the lowest titer needed to confer protection has not been determined.
PATIENT COUNSELING INFORMATION
Information for Vaccine Recipients and Parents or Guardians
Inform the patient, parent or guardian of the potential benefits and risks of the vaccine.
Question the vaccine recipient, parent, or guardian about the occurrence of any symptoms and/or signs of an adverse reaction after a previous dose of hepatitis A vaccine.
Inform the patient, parent, or guardian about the potential for adverse events that have been temporally associated with administration of VAQTA.
Tell the patient, parent, or guardian accompanying the recipient, to report adverse events to the physician or clinic where the vaccine was administered.
Prior to vaccination, give the patient, parent, or guardian the Vaccine Information Statements which are required by the National Childhood Vaccine Injury Act of 1986. These materials are available free of charge at the Centers for Disease Control and Prevention (CDC) website (www.cdc.gov/vaccines).
Tell the patient, parent, or guardian that the United States Department of Health and Human Services has established a Vaccine Adverse Event Reporting System (VAERS) to accept all reports of suspected adverse events after the administration of any vaccine, including but not limited to the reporting of events required by the National Childhood Vaccine Injury Act of 1986. The VAERS toll-free number is 1-800-822-7967. Reporting forms may also be obtained at the VAERS website at (www.vaers.hhs.gov).
Manuf. and Dist. by: Merck Sharp & Dohme Corp., a subsidiary of
MERCK & CO., INC., Whitehouse Station, NJ 08889, USA
