Side Effects of Havrix, Vaqta (Hepatitis A vaccine)

Havrix, Vaqta (Hepatitis A vaccine) is an immunization used to prevent hepatitis A, a type of liver disease that is caused by the hepatitis A virus (HAV), in persons 12 months of age and older.

Drug interactions of hepatitis A vaccine include fingolimod, belimumab, anakinra, adalimumab, infliximab, antineoplastic agents (anti-cancer medications), and other drugs that suppress the immune system.

There are no adequate or well-controlled trials of hepatitis A vaccine use in pregnant women.

Hepatitis A vaccine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not known if the hepatitis A vaccine is excreted into human milk after administration to the mother. The manufacturer recommends caution when given it to nursing mothers.

Mild side effects include:

• Soreness where the shot was given
• Headache
• Loss of appetite
• Tiredness

Other reported side effects include:

• Allergic reactions
• Belly pain
• Taste changes
• Nausea
• Vomiting
• Sensitivity to light
• Seizures
• Dizziness
• Difficulty sleeping

Concomitant Administration With Vaccines And Immune Globulin

In clinical studies HAVRIX was administered concomitantly with the following vaccines:

• INFANRIX (DTaP);
• Hib conjugate vaccine;
• pneumococcal 7-valent conjugate vaccine;
• MMR vaccine;
• varicella vaccine.

HAVRIX may be administered concomitantly with immune globulin.

When concomitant administration of other vaccines or immune globulin is required, they should be given with different syringes and at different injection sites. Do not mix HAVRIX with any other vaccine or product in the same syringe or vial.

Immunosuppressive Therapies

Immunosuppressive therapies, including irradiation, antimetabolites, alkylating agents, cytotoxic drugs, and corticosteroids (used in greater than physiologic doses), may reduce the immune response to HAVRIX.

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 HAVRIX has been evaluated in 61 clinical trials involving more than 34,000 individuals receiving doses of 360 EL.U., 720 EL.U., or 1440 EL.U.

Of solicited adverse events in clinical trials of adults, who received HAVRIX 1440 EL.U., and children (2 years of age and older), who received either HAVRIX 360 EL.U. or 720 EL.U., the most frequently reported was injection-site soreness (56% of adults and 21% of children); less than 0.5% of soreness was reported as severe. Headache was reported by 14% of adults and less than 9% of children. Other solicited and unsolicited events occurring during clinical trials are listed below.

Incidence 1% to 10% of Injections

Metabolism and Nutrition Disorders: Anorexia.

Gastrointestinal Disorders: Nausea.

General Disorders and Administration Site Conditions: Fatigue, fever > 99.5°F (37.5°C), induration, redness, and swelling of the injection site; malaise.

Incidence < 1% of Injections

Infections and Infestations: Pharyngitis, upper respiratory tract infections.

Blood and Lymphatic System Disorders: Lymphadenopathy.

Psychiatric Disorders: Insomnia.

Nervous System Disorders: Dysgeusia, hypertonia.

Eye Disorders: Photophobia.

Ear and Labyrinth Disorders: Vertigo.

Gastrointestinal Disorders: Abdominal pain, diarrhea, vomiting.

Skin and Subcutaneous Tissue Disorders: rash.

Musculoskeletal and Connective Tissue Disorders: Arthralgia, myalgia.

General Disorders and Administration Site Conditions: Injection site hematoma.

Investigations: Creatine phosphokinase increased.

Studies of HAVRIX 720 EL.U./0.5 mL in Children 11 to 25 Months of Age

In 4 studies, 3,152 children 11 to 25 months of age received at least one dose of HAVRIX 720 EL.U. administered alone or concomitantly with other routine childhood vaccinations. The studies included HAV 210 (N = 1,084), HAV 232 (N = 394), HAV 220 (N = 433), and HAV 231 (N = 1,241).

In the largest of these studies (HAV 231) conducted in the US, 1,241 children 15 months of age were randomized to receive: Group 1) HAVRIX alone; Group 2) HAVRIX concomitantly with measles, mumps, and rubella (MMR) vaccine (manufactured by Merck and Co.) and varicella vaccine (manufactured by Merck and Co.); or Group 3) MMR and varicella vaccines.

Subjects in Group 3 who received MMR and varicella vaccines received the first dose of HAVRIX 42 days later. A second dose of HAVRIX was administered to all subjects 6 to 9 months after the first dose of HAVRIX. Solicited local adverse reactions and general events were recorded by parents/guardians on diary cards for 4 days (days 0 to 3) after vaccination.

Unsolicited adverse events were recorded on the diary card for 31 days after vaccination. Telephone follow-up was conducted 6 months after the last vaccination to inquire about serious adverse events, new onset chronic illnesses and medically significant events. A total of 1,035 children completed the 6-month follow-up. Among subjects in all groups combined, 53% were male; 69% of subjects were white, 16% were Hispanic, 9% were black and 6% were other racial/ethnic groups.

Percentages of subjects with solicited local adverse reactions and general adverse events following HAVRIX administered alone (Group 1) or concomitantly with MMR and varicella vaccines (Group 2) are presented in Table 1. The solicited adverse events from the 3 additional coadministration studies conducted with HAVRIX were comparable to those from Study HAV 231.

Table 1: Solicited Local Adverse Reactions and General Adverse Events Occurring Within 4 Days of Vaccination^a in Children 15 to 24 Months of Age With HAVRIX Administered Alone or Concomitantly With MMR and Varicella Vaccines (TVC)

Serious Adverse Events in Children 11 to 25 Months of Age

Among these 4 studies, 0.9% (29/3,152) of subjects reported a serious adverse event within the 31-day period following vaccination with HAVRIX. Among subjects administered HAVRIX alone 1.0% (13/1,332) reported a serious adverse event. Among subjects who received HAVRIX concomitantly with other childhood vaccines, 0.9% (8/909) reported a serious adverse event. In these 4 studies, there were 4 reports of seizure within 31 days post-vaccination: these occurred 2, 9, and 27 days following the first dose of HAVRIX administered alone and 12 days following the second dose of HAVRIX. In one subject who received INFANRIX and Hib conjugate vaccine followed by HAVRIX 6 weeks later, bronchial hyperreactivity and respiratory distress were reported on the day of administration of HAVRIX alone.

Postmarketing Experience

In addition to reports in clinical trials, worldwide voluntary reports of adverse events received for HAVRIX since market introduction of this vaccine are listed below. This list includes serious adverse events or events which have a suspected causal connection to components of HAVRIX or other vaccines or drugs. Because these events 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 the vaccine.

Infections and Infestations: Rhinitis.

Blood and Lymphatic System Disorders: Thrombocytopenia.

Immune System Disorders: Anaphylactic reaction, anaphylactoid reaction, serum sickness-like syndrome.

Nervous System Disorders: Convulsion, dizziness, encephalopathy, Guillain-Barre syndrome, hypoesthesia, multiple sclerosis, myelitis, neuropathy, paresthesia, somnolence, syncope.

Vascular Disorders: Vasculitis.

Respiratory, Thoracic, and Mediastinal Disorders: Dyspnea.

Hepatobiliary Disorders: Hepatitis, jaundice.

Skin and Subcutaneous Tissue Disorders: Angioedema, erythema multiforme, hyperhidrosis.

Congenital, Familial, and Genetic Disorders: Congenital anomaly.

Musculoskeletal and Connective Tissue Disorders: Musculoskeletal stiffness.

General Disorders and Administration Site Conditions: Chills, influenza-like symptoms, injection site reaction, local swelling.