hepatitis a vaccine, inactivated
Dosage Form: injection, suspension
FULL PRESCRIBING INFORMATION
Indications and Usage for Vaqta
Indications and Use
Vaqta1 [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.
Vaqta may be administered along with immune globulin (IG) at a separate site with a separate syringe for post-exposure prophylaxis [see Clinical Studies (14.5)].
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Registered trademark of MERCK & CO., Inc.
COPYRIGHT © 2001, 2005, 2010 MERCK & CO., Inc.
All rights reserved
Limitations of Use
Vaqta will not prevent hepatitis caused by infectious agents other than hepatitis A virus. Because of the long incubation period (approximately 20 to 50 days) for hepatitis A, it is possible for unrecognized hepatitis A infection to be present at the time the vaccine is given. The vaccine may not prevent hepatitis A in such individuals.
Vaccination with Vaqta may not result in a protective response in all susceptible vaccinees.
Vaqta Dosage and Administration
Dosage and Schedule
Children/Adolescents (12 months through 18 years of age): Vaccination 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): Vaccination consists of a primary 1.0-mL dose administered intramuscularly, and a 1.0-mL booster dose administered intramuscularly 6 to 18 months later.
Interchangeability of the Booster Dose: A booster dose of Vaqta may be given at 6 to 12 months following the primary dose of another inactivated hepatitis A vaccine (i.e., HAVRIX2) [see Clinical Studies (14.6)].
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Registered trademark of GlaxoSmithKline
Method of Administration
For intramuscular use only.
- Shake well to obtain a slightly opaque, white suspension before withdrawal and use.
- Thoroughly agitate to maintain suspension of the vaccine.
- Discard if the suspension does not appear homogenous or if extraneous particulate matter remains or discoloration is observed.
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.
Single-Dose Vial Use
- Withdraw dose of vaccine from the single-dose vial using a sterile needle and syringe.
Prefilled Syringe Use
The following are instructions for using the prefilled single-dose syringes:
- Shake well before use.
- Attach the needle by twisting in a clockwise direction until the needle fits securely on the syringe.
- Administer the entire dose as per standard protocol as stated above under DOSAGE AND ADMINISTRATION.
- Dispose of the syringe and needle in approved sharps container.
Dosage Forms and Strengths
Sterile suspension available in four presentations:
- 0.5-mL pediatric dose in single-dose vials and prefilled syringes
- 1.0-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).]
Contraindications
Do not administer Vaqta to individuals with a history of immediate 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)].
Warnings and Precautions
Prevention and Management of Allergic Vaccine Reactions
Have appropriate medical treatment and supervision available to manage possible immediate-type hypersensitivity reactions, such as anaphylaxis, should an acute reaction occur.
Hypersensitivity to Latex
Use caution when vaccinating latex-sensitive individuals since the vial stopper and the syringe plunger stopper contain dry natural latex rubber that may cause allergic reactions.
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 Drug Interactions (7.3) and Use in Specific Populations (8.6)].
Adverse Reactions
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 most common local adverse reactions and systemic adverse events reported in different clinical trials across different age groups were:
- Children — 12 through 23 months of age: injection-site pain/tenderness (6.8%-42.1%) and fever (12.3%-18.5%)
- Children/Adolescents — 2 through 18 years of age: injection-site pain (18.7%) and headache (2.3%)
- Adults — 19 years and older: injection-site pain, tenderness, or soreness (67.0%) and headache (16.1%) (6.1)
Clinical Trials Experience
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.
Children — 12 through 23 Months of Age
In two open-label clinical trials involving 706 healthy children 12 through 23 months of age who received one or two 25U doses of Vaqta, subjects were monitored for local adverse reactions and fever for 5 days and systemic adverse events for 14 days after each vaccination by diary cards. In one trial, 89 children were enrolled and received Vaqta alone. In the other trial, children were randomized to receive the first dose of Vaqta with or without M-M-R® II1 (Measles, Mumps, and Rubella Virus Vaccine, Live) and VARIVAX®1 (Varicella Virus Vaccine Live) (N=617) and the second dose of Vaqta with or without Tripedia3 (Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed) (DTaP) and optionally either ORIMUNE4 (Poliovirus vaccine live oral trivalent) (OPV) or IPOL3 (Poliovirus Vaccine Inactivated) (IPV) (N=555). The race distribution of the study subjects who received at least one dose of Vaqta in these studies was as follows: 62.2% Caucasian; 15.3% Hispanic-American; 12.4% African-American; 6.1% Native American; 3.0% other; 0.7% Oriental, 0.1% Asian; and 0.1% Indian. The distribution of subjects by gender was 53.2% male and 46.8% female. Listed below are the solicited local adverse reactions and systemic adverse events (with 95% Confidence Interval (CI)) (Table 1) and unsolicited local adverse reactions and systemic adverse events (Table 2) reported at ≥1.0% in children who received one or two doses of Vaqta alone and for subjects who received Vaqta concomitantly with other vaccines.
| Adverse Event | Vaqta administered alone (N=241) | Vaqta + vaccines administered concomitantly* (N=706) |
Rate (n/total n) (95% CI) | ||
| ||
| Injection-site† | ||
| Pain/tenderness/soreness | 6.8% (16/236) (3.9%, 10.8%) | 8.6% (59/683) (6.6%, 11.0%) |
| Swelling | 4.2% (10/236) (2.1%, 7.7%) | 5.1% (35/683) (3.6%, 7.1%) |
| Erythema | 3.8% (9/236) (1.8%, 7.1%) | 5.9% (40/683) (4.2%, 7.9%) |
| Warmth | 2.5% (6/236) (0.9%, 5.5%) | 3.2% (22/683) (2.0%, 4.8%) |
| Systemic‡ | ||
| Fever§ | ||
| ≥100.4°F, Oral | 12.3% (29/236) (8.4%, 17.2%) | 14.6% (99/679) (12.0%, 17.5%) |
| ≥102.0°F, Oral | 3.4% (8/236) (1.5%, 6.6%) | 4.9% (33/679) (3.4%, 6.8%) |
| Abnormal | 1.7% (4/236) (0.5%, 4.3%) | 0.9% (6/679) (0.3%, 1.9%) |
| Rash (measles-like, rubella-like, varicella-like) | 0.0% (0/236) (0.0%, 1.5%) | 1.8% (12/683) (0.9%, 3.1%) |
| N=Number of subjects enrolled/randomized. n=Number of subjects in each category. | ||
Body System Adverse Event | Vaqta administered alone (N=241) | Vaqta + vaccines administered concomitantly* (N=706) |
Rate (n/total n) (95% CI) | ||
| ||
| Eye disorders† | ||
| Conjunctivitis | 0.4% (1/236) (0.0%, 2.3%) | 1.3% (9/683) (0.6%, 2.5%) |
| Respiratory, thoracic and mediastinal disorders† | ||
| Rhinorrhea | 3.7% (9/236) (1.8%, 7.1%) | 5.7% (39/683) (4.1%, 7.7%) |
| Cough | 3.7% (9/236) (1.8%, 7.1%) | 5.1% (35/683) (3.6%, 7.1%) |
| Asthma | 1.2% (3/236) (0.3%, 3.7%) | 0.7% (5/683) (0.2%, 1.7%) |
| Respiratory congestion | 0.4% (1/236) (0.0%, 2.3%) | 1.6% (11/683) (0.8%, 2.9%) |
| Nasal congestion | 0.4% (1/236) (0.0%, 2.3%) | 1.2% (8/683) (0.5%, 2.3%) |
| Laryngotracheobronchitis | 0.4% (1/236) (0.0%, 2.3%) | 1.2% (8/683) (0.5%, 2.3%) |
| Gastrointestinal disorders† | ||
| Diarrhea | 3.3% (8/236) (1.5%, 6.6%) | 5.9% (40/683) (4.2%, 7.9%) |
| Vomiting | 2.9% (7/236) (1.2%, 6.0%) | 4.0% (27/683) (2.6%, 5.7%) |
| Skin and subcutaneous tissue disorders† | ||
| Rash | 1.7% (4/236) (0.5%, 4.3%) | 4.5% (31/683) (3.1%, 6.4%) |
| Metabolism and nutrition disorders† | ||
| Anorexia | 1.7% (4/236) (0.5%, 4.3%) | 1.2% (8/683) (0.5%, 2.3%) |
| Infections and infestations† | ||
| Upper respiratory infection | 10.0% (24/236) (6.6%, 14.8%) | 10.1% (69/683) (8.0%, 12.6%) |
| Otitis Media | 4.1% (10/236) (2.1%, 7.7%) | 7.6% (52/683) (5.7%, 9.9%) |
| Otitis | 0.8% (2/236) (0.1%, 3.0%) | 1.8% (12/683) (0.9%, 3.1%) |
| Viral exanthema | 0.4% (1/236) (0.0%, 2.3%) | 1.0% (7/683) (0.4%, 2.1%) |
| General disorders and administration site conditions† | ||
| Irritability | 7.1% (17/236) (4.3%, 11.3%) | 10.8% (74/683) (8.6%, 13.4%) |
| Injection-site ecchymosis‡ | 0.0% (0/236) (0.0%, 1.6%) | 1.0% (7/683) (0.4%, 2.2%) |
| Psychiatric disorders† | ||
| Insomnia | 1.7% (4/236) (0.5%, 4.3%) | 0.7% (5/683) (0.2%, 1.7%) |
| Crying | 1.2% (3/236) (0.3%, 3.7%) | 1.8% (12/683) (0.9%, 3.1%) |
| N=Number of subjects enrolled/randomized. n=Number of subjects in each category. | ||
Serious Adverse Events: Subjects in an open-label study were randomized to receive Vaqta (Dose 1) alone (N=308) or Vaqta concomitantly with M-M-R II and VARIVAX (N=309). Seven children experienced a total of 9 seizures between 9 days and 81 days following the administration of the vaccines. None of the events was considered to be related to Vaqta by the investigator. Other serious events that occurred during the study included bronchiolitis (N=1), dehydration (N=2), RLL (Right Lower Lobe) pneumonia and asthma (N=1), and asthma exacerbation (N=1), which occurred 9 days to 46 days following the administration of Vaqta and were also considered by the investigator to be unrelated to Vaqta.
In an open-label clinical trial of 1800 subjects, 699 healthy children 12 to 23 months of age were randomized to receive two doses of Vaqta (N=352) or two doses of Vaqta concomitantly with two doses of ProQuad1 (Measles, Mumps, Rubella and Varicella Virus Vaccine Live) (N=347) at least 6 months apart. An additional 1101 subjects received two doses of Vaqta alone at least 6 months apart (non-randomized), resulting in 1453 subjects receiving two doses of Vaqta alone (1101 non-randomized and 352 randomized) and 347 subjects receiving two doses of Vaqta concomitantly with ProQuad (all randomized). The race distribution of the study subjects who received Vaqta with or without ProQuad was as follows: 66.4% Caucasian; 19.7% Hispanic-American; 6.7% African-American; 5.0% other; 2.1% Asian; and 0.1% Native American. The distribution of subjects by gender was 51.2% male and 48.8% female. Tables 3 and 4 present injection-site adverse reactions and fever ≥100.4°F (≥38.0°C) and ≥102.2°F (≥39.0°C) (Days 1 to 5 postvaccination) and systemic adverse events, including fever or feverish >98.6°F (>37.0°C) (Days 1 to 14 postvaccination) observed among recipients of Vaqta alone or concomitantly with ProQuad at a rate of at least 1% following any dose of Vaqta. Among all subjects, fever (>98.6°F (>37.0°C) or feverish) was the most common systemic adverse event and injection-site pain/tenderness was the most common injection-site adverse reaction. Based on a post-hoc analysis, the rate of fever (>98.6°F (>37.0°C) or feverish) after any dose of Vaqta was increased in subjects who received Vaqta with ProQuad as compared to Vaqta alone in the 14 days after vaccination {risk difference (11.8% [95% CI: 6.8, 17.2]) and relative risk (1.72 [95% CI: 1.40, 2.12])}. The difference in rate of fever (>98.6°F (>37.0°C) or feverish) was higher after Dose 1 (11.5%) as compared to Dose 2 (4.0%). The rates of fever ≥100.4°F (≥38.0°C) and ≥102.2°F (≥39.0°C) in the 5 days after any dose of Vaqta were similar in both treatment groups.
| Adverse Reaction | Vaqta administered alone (N=1453) | Vaqta + ProQuad (N=347) |
| Rate (n/total n) | ||
| ||
| Injection-site erythema* | 21.2% (300/1415) | 17.7% (59/334) |
| Injection-site pain/tenderness* | 42.1% (596/1415) | 35.9% (120/334) |
| Injection-site swelling* | 12.6% (178/1415) | 13.5% (45/334) |
| Injection-site bruising*,† | 2.6% (37/1415) | 3.0% (10/334) |
| N=Number of subjects enrolled/randomized. n=Number of subjects in each category. | ||
Body System Adverse Event | Vaqta administered alone (N=1453) | Vaqta + ProQuad (N=347) |
| Rate (n/total n) | ||
| ||
| Eye disorders* | ||
| Conjunctivitis | 0.9% (13/1415) | 1.5% (5/334) |
| Gastrointestinal disorders* | ||
| Constipation | 1.1% (15/1415) | 0.3% (1/334) |
| Diarrhea | 10.1% (143/1415) | 6.9% (23/334) |
| Vomiting | 6.4% (90/1415) | 4.8% (16/334) |
| General disorders and administration site conditions* | ||
| Irritability | 11.2% (158/1415) | 10.8% (36/334) |
| Fever ≥102.2°F (≥39.0°C) (Days 1-5 postvaccination)† | 4.0% (56/1383) | 4.1% (13/320) |
| Fever ≥100.4°F (≥38.0°C) (Days 1-5 postvaccination)† | 16.3% (226/1383) | 15.9% (51/320) |
| Fever >98.6°F or feverish (>37.0°C) (Days 1-14 postvaccination)‡ | 16.3% (231/1415) | 28.1% (94/334) |
| Infections and infestations* | ||
| Ear infection | 1.1% (15/1415) | 0.0% (0/334) |
| Gastroenteritis | 1.1% (16/1415) | 0.6% (2/334) |
| Gastroenteritis viral | 0.8% (11/1415) | 1.8% (6/334) |
| Nasopharyngitis | 4.7% (66/1415) | 4.8% (16/334) |
| Otitis media | 4.0% (56/1415) | 3.3% (11/334) |
| Rhinitis | 3.2% (45/1415) | 0.3% (1/334) |
| Upper respiratory tract infection | 6.6% (93/1415) | 9.0% (30/334) |
| Viral infection | 1.1% (16/1415) | 0.9% (3/334) |
| Metabolism and nutrition disorders* | ||
| Anorexia | 1.1% (15/1415) | 0.9% (3/334) |
| Respiratory, thoracic and mediastinal disorders* | ||
| Cough | 7.8% (111/1415) | 6.0% (20/334) |
| Nasal congestion | 2.6% (37/1415) | 2.1% (7/334) |
| Rhinorrhea | 7.6% (107/1415) | 6.6% (22/334) |
| Skin and subcutaneous tissue disorders* | ||
| Dermatitis diaper | 1.7% (24/1415) | 5.7% (19/334) |
| Rash | 2.0% (29/1415) | 5.7% (19/334) |
| Rash morbilliform | 0.0% (0/1415) | 4.8% (16/334) |
| N=Number of subjects enrolled/randomized. n=Number of subjects in each category. | ||
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 Prevnar4 (Pneumococcal 7-valent Conjugate Vaccine) concomitantly (N=330) or a first dose of ProQuad and pneumococcal 7-valent conjugate vaccine concomitantly and then vaccinated with 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 who received Vaqta with or without ProQuad and pneumococcal 7-valent conjugate vaccine 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.
Tables 5 and 6 present injection-site adverse reactions (Days 1 to 5 postvaccination with Vaqta) and systemic adverse events (Days 1 to 14 postvaccination with Vaqta) observed among recipients of Vaqta concomitantly with ProQuad and pneumococcal 7-valent conjugate vaccine and Vaqta administered separately from ProQuad and pneumococcal 7-valent conjugate vaccine at a rate of at least 1% following any dose of Vaqta. Among all subjects, fever (>98.6°F or feverish) was the most common systemic adverse event, and injection-site pain/tenderness was the most common injection-site adverse reaction.
In the 14 days after vaccination with any dose of Vaqta, the rate of fever (>98.6°F or feverish) was increased in subjects who received Vaqta with ProQuad and pneumococcal 7-valent conjugate vaccine as compared to Vaqta alone {risk difference (20.0% [95% CI: 13.0, 26.8]) and relative risk (2.10 [95% CI: 1.59, 2.79] in post-hoc analysis)}. A difference in rates of fever was noted after Dose 1 of Vaqta with ProQuad and pneumococcal 7-valent conjugate vaccine, but not after Dose 2 of Vaqta with ProQuad. The rates of fever ≥100.4°F and ≥102.2°F in the five days after vaccination were similar in both treatment groups (Table 6).
In the 28 days after vaccination, the administration of Dose 1 of Vaqta with Dose 1 of ProQuad and Dose 4 of pneumococcal 7-valent conjugate vaccine does not increase incidence rates of fever (>98.6°F or feverish) as compared to when ProQuad is administered with pneumococcal 7-valent conjugate vaccine alone {38.6% and 42.7%, respectively; relative risk (0.9 [95% CI: 0.75, 1.09])} in post-hoc analysis). Similarly, the administration of Dose 2 of Vaqta with Dose 2 of ProQuad does not increase incidence rates of fever (>98.6°F or feverish) as compared to when Dose 2 of ProQuad is administered alone {17.4% and 17.0%, respectively; relative risk (1.02 [95% CI: 0.70, 1.51])}.
| Adverse Reaction | Vaqta alone (N=323) | Vaqta with ProQuad + PCV7 (N=330) |
| Rate (n/total n) | ||
| ||
| Injection-site erythema† | 17.8% (51/286) | 13.3% (44/330) |
| Injection-site pain/tenderness† | 25.5% (73/286) | 25.8% (85/330) |
| Injection-site swelling† | 13.3% (38/286) | 9.7% (32/330) |
| Injection-site bruising†,‡ | 2.4% (7/286) | 1.8% (6/330) |
| Injection-site rash †,‡ | 0.3% (1/286) | 1.2% (4/330) |
| N=Number of subjects enrolled/randomized. n=Number of subjects in each category. | ||
Body System Adverse Event† | Vaqta alone (N=323) | Vaqta with ProQuad + PCV7 (N=330) |
| Rate (n/total n) | ||
| ||
| Eye disorders‡ | ||
| Conjunctivitis | 1.4% (4/286) | 0.9% (3/330) |
| Gastrointestinal disorders‡ | ||
| Diarrhea | 2.8% (8/286) | 4.8% (16/330) |
| Vomiting | 2.1% (6/286) | 3.0% (10/330) |
| General disorders and administration site conditions‡ | ||
| Irritability | 5.9% (17/286) | 7.3% (24/330) |
| Fever ≥102.2°F (≥39.0°C) (Days 1-5 postvaccination)§ | 3.9% (10/257) | 5.5% (16/293) |
| Fever ≥100.4°F (≥38.0°C) (Days 1-5 postvaccination)§ | 16.7% (43/257) | 18.1% (53/293) |
| Fever >98.6°F or feverish (Days 1-14 postvaccination)¶ | 18.5% (53/286) | 38.2% (126/330) |
| Infections and infestations‡ | ||
| Croup infectious | 1.4% (4/286) | 0.9% (3/330) |
| Ear infection | 0.3% (1/286) | 1.8% (6/330) |
| Gastroenteritis | 1.0% (3/286) | 0.9% (3/330) |
| Gastroenteritis viral | 1.0% (3/286) | 0.6% (2/330) |
| Nasopharyngitis | 2.4% (7/286) | 3.6% (12/330) |
| Otitis media | 5.9% (17/286) | 7.6% (25/330) |
| Otitis media acute | 1.0% (3/286) | 0.6% (2/330) |
| Pharyngitis | 1.0% (3/286) | 0.9% (3/330) |
| Pharyngitis streptococcal | 1.0% (3/286) | 0.6% (2/330) |
| Rhinitis | 2.4% (7/286) | 2.1% (7/330) |
| Roseola | 0.3% (1/286) | 1.5% (5/330) |
| Upper respiratory tract infection | 6.6% (19/286) | 10.3% (34/330) |
| Viral infection | 0.3% (1/286) | 2.7% (9/330) |
| Respiratory, thoracic and mediastinal disorders‡ | ||
| Cough | 3.1% (9/286) | 4.5% (15/330) |
| Nasal congestion | 1.0% (3/286) | 2.1% (7/330) |
| Rhinorrhea | 3.1% (9/286) | 4.8% (16/330) |
| Skin and subcutaneous tissue disorders‡ | ||
| Dermatitis diaper | 3.1% (9/286) | 7.9% (26/330) |
| Rash | 1.4% (4/286) | 3.0% (10/330) |
| Rash morbilliform | 0.3% (1/286) | |
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