b'USMAd_v1.pdf 2 11/30/21 7:55 AMBRIEF SUMMARY OF FULL PRESCRIBING INFORMATION Table 1HEPLISAV-B [Hepatitis B Vaccine (Recombinant), Adjuvanted] Solution forStudy 1: Percent of Subjects Who Reported Local or Intramuscular Injection Systemic Reactions Within 7 Days of Vaccination1INDICATIONS AND USAGE HEPLISAV-B % Engerix-B %HEPLISAV-B is indicated for prevention of infection caused by all known subtypes ofPost-Dose* Post-Dose*hepatitis B virus. HEPLISAV-B is approved for use in adults 18 years of age and older.2DOSAGE AND ADMINISTRATIONReaction 1 2 1 2 3For intramuscular administration. Headache 16.9 12.8 19.2 12.3 9.52.1Dose and Regimen Malaise 9.2 7.6 8.9 6.5 6.4Administer two doses (0.5 mL each) of HEPLISAV-B one month apart.2.2Administration N=1784 N=1764 N=596 N=590 N=561HEPLISAV-B is a clear to slightly opalescent, colorless to slightly yellow solution. Fever 1.1 1.5 1.8 1.7 1.8Parenteral drug products should be inspected visually for particulate matter andNote: only subjects having data are included. Clinical trial number: NCT00435812discoloration prior to administration, whenever solution and container permit. If either of*HEPLISAV-B was given as a 2-dose regimen at 0 and 1 month followed by saline placebothese conditions exists, the vaccine should not be administered. at 6 months. Engerix-B was given at 0, 1, and 6 monthsAdminister HEPLISAV-B by intramuscular injection in the deltoid region using a sterile Redness and swelling2.5 cm.needle and syringe.Oral temperature100.4F (38.0C).3DOSAGE FORMS AND STRENGTHS Unsolicited Adverse Events:Unsolicited adverse events within 28 days following any injection, including placebo, were syringes. [see How Supplied/Storage and Handling (16.1)]. reported by 42.0% of HEPLISAV-B recipients and 41.3% of Engerix-B recipients.4CONTRAINDICATIONS Serious Adverse Events (SAEs)Do not administer HEPLISAV-B to individuals with a history of severe allergic reaction (e.g. anaphylaxis) after a previous dose of any hepatitis B vaccine or to any component ofvaccine. The percentage of subjects reporting serious adverse events was 1.5% in the HEPLISAV-B, including yeast [see Description (11)]. HEPLISAV-B group and 2.1% in the Engerix-B group. No acute myocardial infarctions were 5WARNINGS AND PRECAUTIONS reported. No deaths were reported.5.1Managing Allergic Reactions Potentially Immune-mediated Adverse EventsAppropriate medical treatment and supervision must be available to manage possible anaphylactic reactions following administration of HEPLISAV-B. dose of vaccine were reported in 0.2% (n = 4) of HEPLISAV-B recipients and 0.7% (n = 4) 5.2Immunocompromised Individuals of Engerix-B recipients. The following events were reported in the HEPLISAV-B group in one Immunocompromised persons, including individuals receiving immunosuppressant therapy,subject each: granulomatosis with polyangiitis, lichen planus, Guillain-Barr syndrome, and may have a diminished immune response to HEPLISAV-B. Graves disease. The following events were reported in the Engerix-B group in one subject each: Bells palsy, Raynauds phenomenon, and Graves disease. One additional Engerix-B 5.3Limitations of Vaccine Effectiveness recipient with a history of mixed connective tissue disease had p-ANCA-positive vasculitis.Hepatitis B has a long incubation period. HEPLISAV-B may not prevent hepatitis B infectionStudy 2 in Subjects 40 through 70 Years of Agein individuals who have an unrecognized hepatitis B infection at the time ofvaccine administration. Study 2 was a randomized, observer-blind, active-controlled, multicenter study in Canada 6ADVERSE REACTIONS and the United States in which 1968 subjects received at least 1 dose of HEPLISAV-B and 6.1Clinical Trials Experience 481 subjects received at least 1 dose of Engerix-B. HEPLISAV-B was given as a 2-dose Because clinical trials are conducted under widely varying conditions, adverse reactionregimen at 0 and 1 month followed by saline placebo at 6 months. Enrolled subjectsrates observed in the clinical trials of a vaccine cannot be directly compared to rates in thehad no history of hepatitis B vaccination or infection. Engerix-B was given at 0, 1, and6 months. In the total population, the mean age was 54 years; 48% of subjects were men; 82% were white, 15% black, 1% Asian and 6% Hispanic; 44% were obese, 30% had A total of 9597 individuals 18 through 70 years of age received at least 1 dose of HEPLISAV-Bhypertension, 30% had dyslipidemia, and 8% had diabetes mellitus. These demographic in 5 clinical trials conducted in the United States, Canada, and Germany. Data from 3 of theseand baseline characteristics were similar in both vaccine groups.trials are provided below. Solicited Local and Systemic Adverse ReactionsStudy 1 in Subjects 18 through 55 Years of Age Subjects were monitored for local and systemic adverse reactions using diary cards Study 1 was a randomized, observer-blind, active-controlled, multicenter study in Canadafor a 7-day period starting on the day of vaccination. The percentages of subjects who and Germany in which 1810 subjects received at least 1 dose of HEPLISAV-B and experienced local and systemic reactions are shown in Table 2.605 subjects received at least 1 dose of Engerix-B [Hepatitis B Vaccine (Recombinant)]. Enrolled subjects had no history of hepatitis B vaccination or infection. HEPLISAV-B wasTable 2given as a 2-dose regimen at 0 and 1 month followed by saline placebo at 6 months.Study 2: Percent of Subjects Who Reported Local or Engerix-B was given at 0, 1, and 6 months. In the total study population, the mean ageSystemic Reactions Within 7 Days of Vaccinationwas 40 years; 46% of the subjects were men; 93% were white, 2% black, 3% Asian andHEPLISAV-B % Engerix-B %3% Hispanic; 26% were obese, 10% had hypertension, 8% had dyslipidemia, and 2% had diabetes mellitus. These demographic and baseline characteristics were similar in bothPost-Dose* Post-Dose*vaccine groups. Reaction 1 2 1 2 3Solicited Local and Systemic Adverse Reactions Local N=1952 N=1905 N=477 N=464 N=448Subjects were monitored for local and systemic adverse reactions using diary cards for a 7-day period starting on the day of vaccination. The percentages of subjects who reportedInjection Site Pain 23.7 22.8 18.4 15.9 13.8local and systemic reactions are shown in Table 1. Injection Site Redness 0.9 0.7 0.6 0.2 0.2Table 1 Injection Site Swelling 0.9 0.6 0.6 0.6 0.2Study 1: Percent of Subjects Who Reported Local orSystemicSystemic Reactions Within 7 Days of VaccinationHEPLISAV-B % Engerix-B % Fatigue 12.6 10.8 12.8 12.1 9.4Post-Dose* Post-Dose* Headache 11.8 8.1 11.9 9.5 8.5Reaction 1 2 1 2 3 Malaise 7.7 7.0 8.6 7.1 5.1Local N=1810 N=1798 N=605 N=603 N=598 Myalgia 8.5 6.4 9.6 8.0 4.5Injection Site Pain 38.5 34.8 33.6 24.7 20.2 N=1923 N=1887 N=472 N=459 N=438Injection Site Redness 4.1 2.9 0.5 1.0 0.7 Fever 0.6 0.6 0.6 0.9 0.7Injection Site Swelling 2.3 1.5 0.7 0.5 0.5 Note: only subjects having data are included. Clinical Trial Number: NCT01005407*HEPLISAV-B was given as a 2-dose regimen at 0 and 1 month followed by saline placeboSystemic at 6 months. Engerix-B was given at 0, 1, and 6 monthsFatigue 17.4 13.8 16.7 11.9 10.0Redness and swelling 2.5 cm. Oral temperature100.4F (38.0C).'