PreHevbrio

Medical Editor: John P. Cunha, DO, FACOEP Last updated on RxList: 12/20/2021
PreHevbrio Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

What Is PreHevbrio?

PreHevbrio [hepatitis B vaccine (recombinant)] is a vaccine indicated for prevention of infection caused by all known subtypes of hepatitis B virus. 

What Are Side Effects of PreHevbrio?

Side effects of PreHevbrio include:

  • injection site reactions (pain, tenderness, itching, redness, swelling),
  • headache,
  • fatigue, 
  • muscle aches, 
  • diarrhea,
  • nausea,
  • vomiting, and
  • fever.

Dosage for PreHevbrio

The dose of PreHevbrio is a series of three doses (1.0 mL each) administered by intramuscular injection. on a 0-, 1- and 6-month schedule.

PreHevbrio In Children

Safety and effectiveness of PreHevbrio have not been established in individuals less than 18 years of age. 

What Drugs, Substances, or Supplements Interact with PreHevbrio?

PreHevbrio may interact with other medicines such as:

  • immune globulin.

Tell your doctor all medications and supplements you use.

PreHevbrio During Pregnancy and Breastfeeding

Tell your doctor if you are pregnant or plan to become pregnant before using PreHevbrio; it is unknown how it might affect a fetus. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to PreHevbrio during pregnancy. It is unknown if PreHevbrio passes into breast milk or how it might affect a nursing infant. Consult your doctor before breastfeeding. 

Additional information

Our PreHevbrio [hepatitis B vaccine (recombinant)] Injectable suspension, for Intramuscular Use Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

SLIDESHOW

Digestive Disorders: Common Misconceptions See Slideshow
PreHevbrio Professional Information

SIDE EFFECTS

Individuals 18 through 44 years of age: The most common local reactions following each dose of PREHEVBRIO were injection site pain (52.0 – 58.3%) and tenderness (52.6 – 59.6%). The most common systemic reactions following each dose of PREHEVBRIO were headache (17.2 – 25.8%), fatigue (20.1- 28.3%) and myalgia (22.2 – 29.9%).

Individuals 45 through 64 years of age: The most common local reactions following each dose of PREHEVBRIO were injection site pain (42.2 – 48.8%) and tenderness (43.2 – 50.5%). The most common systemic reactions following each dose of PREHEVBRIO were headache (13.8 – 21.3%), fatigue (14.3 – 19.7%) and myalgia (16.7 – 24.1%).

Individuals ≥ 65 years of age: The most common local reactions following each dose of PREHEVBRIO were injection site pain (26.7 – 34.8%) and tenderness (30.2 – 32.8%). The most common systemic reactions following each dose of PREHEVBRIO were headache (7.3 – 12.2%), fatigue (11.5 – 14.5%) and myalgia (11.5 - 16.6%).

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 PREHEVBRIO was evaluated in 2 active-controlled clinical studies (Studies 1 and 2) involving 4,443 subjects who received at least 1 dose of PREHEVBRIO (n = 2,920) or Engerix-B [Hepatitis B Vaccine (Recombinant)] (n = 1,523) administered according to a 0-, 1- and 6-months schedule.

Study 1 In Adults ≥18 Years Of Age

Study 1 was a randomized, double-blind, active-controlled, multicenter study that enrolled subjects in the United States (US), Canada, Belgium and Finland in which 796 subjects received at least 1 dose of PREHEVBRIO and 811 subjects received at least 1 dose of Engerix-B. In the total study population at baseline the mean age was 57 years, 81% were age ≥45 years; 62% were women; 90% were White, 8% Black, 1% Asian, and 10% Hispanic/Latino; 37% were obese (body mass index [BMI] >30 kg/m2), 14% were current smokers and 8% had Type 2 diabetes mellitus. Demographic and baseline characteristics were similar in both vaccine groups.

Solicited Local and Systemic Adverse Reactions

Subjects 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 reported local and systemic reactions in Study 1 are shown by age subgroup in Table 1 to Table 3.

Table 1: Study 1: Percent of Subjects Who Reported Local or Systemic Reactions Within 7 Days of Vaccination (18 through 44 years of age)

PREHEVBRIO
Dose 1
(N=145)
%
PREHEVBRIO
Dose 2
(N=141)
%
PREHEVBRIO
Dose 3
(N= 134)
%
Engerix-B
Dose 1
(N=154)
%
Engerix-B
Dose 2
(N=152)
%
Engerix-B
Dose 3
(N=148)
%
Local Reaction
Pain 58.6 50.4 46.3 33.8 28.9 31.8
Pain, Grade 3 or greatera 0 0 0 0 0 0
Tenderness 53.8 50.4 42.5 32.5 32.2 36.5
Tenderness, Grade 3 or greater b 0.7 0 0.7 0.6 0.7 0.7
Itching 2.1 3.5 6.0 7.1 3.9 7.4
Itching, Grade 3 or greater c 0 0 0 0 0.7 1.4
Redness (≥ 2.5 cm) 0.7 1.4 1.5 0.6 1.3 0
Redness, Grade 3 or greaterd 0 0 0 0 0 0
Swelling (≥ 2.5 cm) 2.8 1.4 0.7 0 1.3 2.0
Swelling, Grade 3 or greater e 0 0 0 0 0.7 1.4
Systemic Reaction
Headache 33.8 24.1 20.9 29.9 19.1 13.5
Headache, Grade 3 or greater a 1.4 0.7 0 1.3 0.7 0
Fatigue 29.7 22.0 22.4 31.8 20.4 20.3
Fatigue, Grade 3 or greater c 1.4 0.7 0 0.6 2.0 1.4
Myalgia 27.6 24.1 21.6 20.8 11.8 10.1
Myalgia, Grade 3 or greater c 0.7 0 0 0 1.3 0
Diarrhea 9.7 5.7 4.5 9.7 5.9 7.4
Diarrhea, Grade 3 or greater f 0.7 0 0 0 0.7 0
Nausea/Vomiting 8.3 4.3 4.5 7.8 6.6 6.1
Nausea/Vomiting, Grade 3 or greater f 0 0.7 0 0 0.7 0
Fever (≥100.4°F) 0.7 0.7 0 1.3 0 0.7
Fever, Grade 3 or greater (≥102.1°F) 0.7 0 0 0 0 0
a Grade 3 or greater pain and headache: defined as use of narcotic pain reliever or prevents daily activity; or ER visit or hospitalization
b Grade 3 or greater tenderness: defined as significant discomfort at rest; or ER visit or hospitalization
c Grade 3 or greater itching, fatigue and myalgia: defined as prevents daily activity; or ER visit or hospitalization
d Grade 3 or greater redness: defined as > 10 cm or skin necrosis or exfoliative dermatitis
e Grade 3 or greater swelling: defined as > 10 cm or prevents daily activity; or skin necrosis.
f Grade 3 or greater diarrhea and nausea/vomiting: defined as prevents daily activity or requires outpatient IV hydration; or ER visit or hospitalization.

Table 2: Study 1: Percent of Subjects Who Reported Local or Systemic Reactions Within 7 Days of Vaccination (45 through 64 years of age)

PREHEVBRIO
Dose 1
(N=355)
%
PREHEVBRIO
Dose 2
(N=350)
%
PREHEVBRIO
Dose 3
(N= 343)
%
Engerix-B
Dose 1
(N=361)
%
Engerix-B
Dose 2
(N=357)
%
Engerix-B
Dose 3
(N=349)
%
Local Reaction
Pain 46.8 44.9 39.4 22.2 15.4 17.2
Pain, Grade 3 or greatera 0 0 0.3 0 0 0
Tenderness 48.7 42.6 40.5 23.8 16.5 17.5
Tenderness, Grade 3 or greater b 0.8 0.6 0.3 0 0 0.3
Itching 4.5 3.1 3.8 3.9 2.0 3.4
Itching, Grade 3 or greater c 0 0.3 0 0 0.7 1.4
Redness (≥ 2.5 cm) 1.7 0.6 0.3 1.1 0.3 1.1
Redness, Grade 3 or greaterd 0 0 0 0.8 0.3 0.6
Swelling (≥ 2.5 cm) 1.4 0.3 0.9 0 0.6 0.3
Swelling, Grade 3 or greater e 0 0 0.3 0 0 0
Systemic Reaction
Headache 21.4 13.7 15.7 20.5 11.2 14.0
Headache, Grade 3 or greater a 0 0 0.3 0.3 0.3 0.3
Fatigue 16.6 16.9 12.5 22.2 11.5 12.3
Fatigue, Grade 3 or greater c 0.6 0 0.3 0.6 0.3 0.6
Myalgia 21.4 20.0 15.5 16.1 8.4 9.5
Myalgia, Grade 3 or greater c 0.6 0 0 0 0 0
Diarrhea 4.8 4.0 3.2 6.4 3.6 3.7
Diarrhea, Grade 3 or greater f 0 0 0 0 0 0
Nausea/Vomiting 4.2 2.9 2.3 6.4 3.6 2.6
Nausea/Vomiting, Grade 3 or greater f 0 0 0 0 0 0
Fever (≥100.4°F) 0.6 0 0 0.3 0.3 0.6
Fever, Grade 3 or greater (≥102.1°F) 0 0 0 0 0 0.3
a Grade 3 or greater pain and headache: defined as use of narcotic pain reliever or prevents daily activity; or ER visit or hospitalization
b Grade 3 or greater tenderness: defined as significant discomfort at rest; or ER visit or hospitalization
c Grade 3 or greater itching, fatigue and myalgia: defined as prevents daily activity; or ER visit or hospitalization
d Grade 3 or greater redness: defined as > 10 cm or skin necrosis or exfoliative dermatitis
e Grade 3 or greater swelling: defined as > 10 cm or prevents daily activity; or skin necrosis.
f Grade 3 or greater diarrhea and nausea/vomiting: defined as prevents daily activity or requires outpatient IV hydration; or ER visit or hospitalization.

Table 3: Study 1: Percent of Subjects Who Reported Local or Systemic Reactions Within 7 Days of Vaccination (Age ≥ 65 years of age)

PREHEVBRIO
Dose 1
(N=296)
%
PREHEVBRIO
Dose 2
(N=288)
%
PREHEVBRIO
Dose 3
(N= 281)
%
Engerix-B
Dose 1
(N=296)
%
Engerix-B
Dose 2
(N=292)
%
Engerix-B
Dose 3
(N=288)
%
Local Reaction
Pain 34.8 28.8 26.7 16.2 12.0 11.1
Pain, Grade 3 or greatera 0 0 0 0.3 0 0
Tenderness 32.8 30.2 31.0 14.2 12.0 10.1
Tenderness, Grade 3 or greater b 0 0 0 0 0 0
Itching 6.1 3.8 5.0 4.1 1.4 2.4
Itching, Grade 3 or greater c 0 0 0 0 0 0
Redness (≥ 2.5 cm) 1.0 0.3 1.4 0.7 0.3 0
Redness, Grade 3 or greaterd 0.3 0 0.4 0 0.3 0
Swelling (≥ 2.5 cm) 1.0 0.7 1.1 1.4 0.3 0.3
Swelling, Grade 3 or greater e 0.3 0 0 0 0.3 0
Systemic Reaction
Headache 12.2 7.3 7.8 12.8 5.8 6.9
Headache, Grade 3 or greater a 0 0 0 0 0 0
Fatigue 14.5 11.5 12.5 17.9 9.9 10.1
Fatigue, Grade 3 or greater c 0 0 0 0.7 0 0.3
Myalgia 16.6 11.5 13.2 12.8 8.2 6.9
Myalgia, Grade 3 or greater c 0 0 0 0 0.3 0
Diarrhea 6.4 4.2 1.1 6.4 2.4 3.5
Diarrhea, Grade 3 or greater f 0.3 0 0 0.3 0 0
Nausea/Vomiting 3.7 0.7 1.1 1.7 1.7 0.7
Nausea/Vomiting, Grade 3 or greater f 0 0 0 0.3 0 0.3
Fever (≥100.4°F) 0 0 0.7 0 0 0.7
Fever, Grade 3 or greater (≥102.1°F) 0 0 0 0 0 0
a Grade 3 or greater pain and headache: defined as use of narcotic pain reliever or prevents daily activity; or ER visit or hospitalization
b Grade 3 or greater tenderness: defined as significant discomfort at rest; or ER visit or hospitalization
c Grade 3 or greater itching, fatigue and myalgia: defined as prevents daily activity; or ER visit or hospitalization
d Grade 3 or greater redness: defined as > 10 cm or skin necrosis or exfoliative dermatitis
e Grade 3 or greater swelling: defined as > 10 cm or prevents daily activity; or skin necrosis.
f Grade 3 or greater diarrhea and nausea/vomiting: defined as prevents daily activity or requires outpatient IV hydration; or ER visit or hospitalization.

The median duration of local and systemic solicited adverse reactions was 1-2 days in both treatment groups. Among all subjects who received PREHEVBRIO, the frequencies of the most commonly reported solicited reactions extending beyond the 7-day assessment period were as follows: fatigue (4.1%), injection site pain (2.0%), headache (1.9%) and myalgia (1.9%).

Study 2 In Adults 18 Through 45 Years Of Age

Study 2 was a randomized, double-blind, active-controlled, multicenter study that enrolled subjects in the US, Canada, Belgium, Finland, Germany and the United Kingdom in which 2,124 subjects received at least 1 dose of PREHEVBRIO and 712 subjects received at least 1 dose of Engerix-B. In the total study population at baseline, the mean age was 34 years; 58% were women; 92% were White, 6% Black, 2% Asian, and 10% Hispanic/Latino; 18% were obese (BMI >30 kg/m2) and 19% were current smokers. Demographic and baseline characteristics were similar in both vaccine groups.

Solicited Local and Systemic Adverse Reactions

Subjects 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 reported local and systemic reactions in Study 2 are shown in Table 4.

Table 4: Study 2: Percent of Subjects Who Reported Local or Systemic Reactions Within 7 Days of Vaccination (18 through 45 years of age)

PREHEVBRIO
Dose 1
(N=2122)a
%
PREHEVBRIO
Dose 2
(N=2071)
%
PREHEVBRIO
Dose 3
(N= 1967)
%
Engerix-B
Dose 1
(N=712)
%
Engerix-B
Dose 2
(N=701)
%
Engerix-B
Dose 3
(N=671)
%
Local Reaction
Pain 58.2 52.2 52.5 35.1 29.2 32.5
Pain, Grade 3 or greaterb 0.3 0.3 0.4 0.1 0 0.3
Tenderness 59.9 52.9 55.5 37.6 30.4 33.8
Tenderness, Grade 3 or greater c 0.8 0.9 0.8 0.6 0.1 0.1
Itching 5.7 5.7 6.7 6.6 5.3 5.4
Itching, Grade 3 or greaterd 0 0 0.1 0.3 0.1 0
Redness (≥ 2.5 cm) 1.1 1.1 1.3 0.6 0.4 1.0
Redness, Grade 3 or greatere 0.2 0 0.2 0.1 0.1 0.1
Swelling (≥ 2.5 cm) 1.2 0.9 1.1 0.6 0 0.4
Swelling, Grade 3 or greater f 0.1 0 0.1 0 0 0
Systemic Reaction
Headache 25.1 16.7 17.4 24.2 15.0 18.3
Headache, Grade 3 or greater b 0.3 0.2 0.5 0.4 0.4 0.6
Fatigue 28.4 19.8 20.2 27.1 17.8 22.1
Fatigue, Grade 3 or greater d 0.5 0.8 0.6 0.4 0.6 0.6
Myalgia 30.3 21.9 23.6 17.7 13.0 18.5
Myalgia, Grade 3 or greater d 0.3 0.6 0.5 0.4 0.1 0.4
Diarrhea 7.4 5.0 4.4 9.6 4.9 5.4
Diarrhea, Grade 3 or greaterg 0.2 0.1 0.1 0 0 0
Nausea/Vomiting 6.7 3.7 4.7 7.0 3.6 3.9
Nausea/Vomiting, Grade 3 or greater g 0 0 0.2 0 0.1 0
Fever (≥100.4°F) 0.3 0.3 0.6 0.4 0.3 0.9
Fever, Grade 3 or greater (≥102.1°F) 0 0.1 0.1 0.1 0 0
a Two subjects without solicited adverse event data following dose 1 of PREHEVBRIO were excluded from this analysis.
b Grade 3 or greater tenderness: defined as significant discomfort at rest; or ER visit or hospitalization
c Grade 3 or greater tenderness: defined as significant discomfort at rest; or ER visit or hospitalization
d Grade 3 or greater itching, fatigue and myalgia: defined as prevents daily activity; or ER visit or hospitalization
e Grade 3 or greater redness: defined as > 10 cm or skin necrosis or exfoliative dermatitis
f Grade 3 or greater swelling: defined as > 10 cm or prevents daily activity; or skin necrosis
g Grade 3 or greater diarrhea and nausea/vomiting: defined as prevents daily activity or requires outpatient IV hydration; or ER visit or hospitalization.

The median duration of local and systemic solicited adverse reactions was 1-2 days in both treatment groups. Among all subjects who received PREHEVBRIO, the frequencies of the most commonly reported solicited reactions extending beyond the 7-day assessment period were as follows: fatigue (3.5%), injection site pain (2.0%), headache (1.9%) and myalgia (1.8%).

Unsolicited Adverse Events (AEs)

In both studies, unsolicited adverse events, including serious and non-serious events, that occurred within 28 days following each vaccination were recorded on a diary card by all subjects.

In both studies combined, unsolicited AEs that occurred within 28 days of any vaccination were reported by 48.3% and 48.4% of subjects who received PREHEVBRIO or Engerix-B, respectively. Unsolicited AEs in subjects who received PREHEVBRIO for which available information suggests a causal relationship to vaccination include injection site bruising (1.4%), dizziness/vertigo (1.1%), general pruritus/itchiness (0.2%), arthralgia (0.2%), urticaria/hives (0.2%) and lymphadenopathy/lymph node pain (0.1%).

Serious Adverse Events (SAEs)

In both studies, SAEs were collected from first vaccination through 6 months following the last vaccination. In both studies combined, SAEs were reported by 0.9% and 0.6% within 28 days of vaccination with PREHEVBRIO or Engerix-B, respectively. SAEs were reported by 2.5% of subjects in the PREHEVBRIO group and 1.6% in the Engerix-B group from the first vaccination through 6 months following the third vaccination. There were no notable patterns or numerical imbalances between vaccination groups for specific categories of serious adverse events that would suggest a causal relationship to PREHEVBRIO.

DRUG INTERACTIONS

Concomitant Administration With Immune Globulin

There are no data to assess the concomitant use of PREHEVBRIO with immune globulin. When concomitant administration of PREHEVBRIO and immune globulin is required, they should be given with different syringes at different injection sites.

Interference With Laboratory Tests

Hepatitis B surface antigen (HBsAg) derived from hepatitis B vaccines has been transiently detected in blood samples following vaccination. Serum HBsAg detection may not have diagnostic value within 28 days after receipt of PREHEVBRIO.

Read the entire FDA prescribing information for PreHevbrio (Hepatitis B Vaccine (Recombinant) Injectable Suspension)

© PreHevbrio Patient Information is supplied by Cerner Multum, Inc. and PreHevbrio Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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