HepaGam B

Overall Adverse Reaction Profile

The most common expected adverse drug reactions for intravenous immune globulins like HepaGam B (hepatitis b immune globulin (human)) are chills, fever, headaches, vomiting, allergic reactions, nausea, arthralgia and moderate low back pain.7-8 In a clinical trial in liver transplant patients, 2 adverse drug reactions of tremor and hypotension were reported in 2 of 14 patients who received intravenous infusions of HepaGam B.8 In studies with healthy volunteers, only 1 adverse drug reaction of nausea was reported in the 70 adult subjects who received an intramuscular administration of HepaGam B (hepatitis b immune globulin (human)) .8

Although no anaphylactic reactions have been reported following HepaGam B (hepatitis b immune globulin (human)) administration, anaphylactic reactions have been reported following the administration of other immune globulin products on rare occasions [see WARNINGS AND PRECAUTIONS].

Adverse Reactions in Clinical Trials

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In an ongoing clinical trial, only 2 adverse drug reactions occurred following the 313 (<1%) HepaGam B (hepatitis b immune globulin (human)) infusions in 14 liver transplant patients. A listing of all adverse events (including those assessed as unrelated to study drug) occurring in >10% of patients are summarized in Table 4 below. These adverse events were reported in an interim analysis from a one-year Phase 3 clinical trial examining HepaGam B (hepatitis b immune globulin (human)) for the prevention of hepatitis B recurrence following liver transplantation. This study utilized the recommended dosing regimen outlined in Table 1 [See DOSAGE AND ADMINISTRATION]. The 2 attributed adverse drug reactions of tremor and hypotension were reported in 2 patients. All reactions were associated with a single HepaGam B (hepatitis b immune globulin (human)) infusion during the first week post-transplant. All reactions resolved on the same day and did not recur with subsequent HepaGam B (hepatitis b immune globulin (human)) infusions.

Table 4 - Adverse Events (AEs) Occurring in >10% of Liver Transplant Patients

Seventy healthy male and female volunteers received a single dose of HepaGam B™ (Hepatitis B Immune Globulin Intravenous [Human]) intramuscularly in clinical trials.8 Seventeen (17) subjects reported 30 adverse events following administration of HepaGam B (hepatitis b immune globulin (human)) . The most frequently reported adverse events included 4 subjects (6%) who experienced headache. 7 subjects (10%) who had cold symptoms or flu and 2 subjects (3%) who experienced lightheadeness/ fainted. The majority of events were reported as mild and were not related to study drug. One adverse event, an episode of nausea, was considered to be drug related. There were no serious adverse events reported. A similar number of subjects in the comparator groups reported adverse events.

Postmarketing Experience

As of April 2007, there have been no postmarketing adverse events reported for HepaGam B (hepatitis b immune globulin (human)) administered i.m.

• Apotex Inc.

• Cangene bioPharma, Inc.

Call your doctor for instructions if you miss a dose, or if you miss an appointment to have your injection given.

Call your doctor for instructions if you miss an appointment for your hepatitis B immune globulin injection.

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of hepatitis B immune globulin injection in the pediatric population. However, safety and efficacy have been established in children who are receiving similar medicines for prevention of hepatitis B infection after exposure to hepatitis B virus.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of hepatitis B immune globulin injection in the elderly. However, elderly patients are more likely to have age-related kidney, liver, or heart problems, which may require caution and an adjustment in the dose for patients receiving hepatitis B immune globulin injection.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Allergy (severe) to human globulin, history of or
• Immunoglobulin (IgA) deficiency—Should not be given to patients with these conditions.

• Atherosclerosis (hardening of the arteries), history of or
• Blood clotting problems, history of or
• Diabetes or
• Heart or blood vessel disease or
• Hyperviscosity (thick blood), known or suspected or
• Prolonged periods of immobilization—Use with caution. May cause side effects to become worse.

• Blood clotting problems or
• Thrombocytopenia (low number of platelets), severe—Should not be given to patients who are receiving this medicine for postexposure prophylaxis unless the benefits outweigh the risks.

• HepaGam B is a sterile solution of purified gamma globulin (5% or 50 milligrams per milliliter) that contains greater than 312 International Units per milliliter of anti-HBs.
• The measured potency of each lot is stamped on the vial label.
• To ensure that the label claim of >312 International Units per milliliter is maintained over the product shelf life, a higher potency of 550 International Units per milliliter is targeted at the time of manufacture.
  • This higher target potency is a manufacturing requirement to account for variability in the potency assay and changes in potency over time.
  • The potency assay has a relative standard deviation (RSD) of approximately 10%.
  • The actual potency test result may vary from approximately 400 to 700 International Units per milliliter (3x RSD) based on statistical assessment of manufactured lots with a target potency of 550 International Units per milliliter.
• Calculate the dosing for the prevention of hepatitis B recurrence following liver transplantation from the measured potency of the particular lot of HepaGam B as stamped on the vial label.

Mechanism of Action

HepaGam B provides passive immunization for individuals exposed to the hepatitis B virus, by binding to the surface antigen and reducing the rate of hepatitis B infection13-16.

Pharmacokinetics

The pharmacokinetic profile of HepaGam B has been evaluated in two 84-day clinical trials in which 70 healthy subjects received an intramuscular injection of 0.06 milliliter per kilogram of HepaGam B. The mean peak concentrations (Cmax) in both studies were comparable and occurred within 4-5 days of administration. Both studies demonstrated mean elimination half-lives (t½) following IM administration of 22 to 25 days. The mean clearance rate was 0.21 to 0.24 liter per day and the volume of distribution was approximately 7.5 liter. Thus, HepaGam B demonstrates pharmacokinetic parameters similar to those reported by Scheiermann and Kuwert17.

The maximum concentration of anti-HBs achieved by HepaGam B was consistent with that of two other licensed comparator Hepatitis B Immune Globulin (Human) products6. Comparability of pharmacokinetics between HepaGam B and a commercially available hepatitis B immune globulin product administered IM indicates that comparable efficacy of HepaGam B should be inferred.

NDC 70504-0052-2; a carton containing a 1.0 milliliter single dose vial (>312 IU per milliliter; measured potency of each lot is stamped on the vial label) and a package insert.

NDC 70504-0051-2; a carton containing a 5.0 milliliter single dose vial (>312 IU per millileter; measure potency of each lot is stamped on the vial label) and a package insert.

Store at 36 to 46 °F (2 to 8 °C). Do not freeze. Do not use after expiration date. Use within 6 hours after the vial has been entered.

HepaGam B may increase your risk of blood clots, especially if you have heart disease or a history of blood clots, or if you need to use a blood thinner, if you are an older adult, if you are bedridden, if you take birth control pills or hormone replacement, or if you use certain types of catheters.

Call your doctor at once if you have: sudden numbness or weakness (especially on one side of the body); chest pain, trouble breathing, rapid heart rate, coughing up blood; or if you have pain, swelling, warmth, or redness in your arms or legs.

You should not receive HepaGam B if you are allergic to human globulins, or if you have an immunoglobulin A deficiency. HepaGam B should not be injected into your muscle if you have a bleeding or blood clotting disorder such as hemophilia.

HepaGam B is made from human plasma (part of the blood) and may contain viruses and other infectious agents that can cause disease. Although donated human plasma is screened, tested, and treated to reduce the risk of it containing anything that could cause disease, there is still a small possibility it could transmit disease. Talk with your doctor about the risks and benefits of using HepaGam B.

HepaGam B is injected into a muscle or into a vein through an infusion pump. A healthcare professional will give you this injection.

For prevention after exposure to contaminated blood: HepaGam B is usually given as soon as possible after exposure to an infected person, preferably within 7 days. A booster medication is then given 24 hours later. Your doctor may also recommend that you receive a hepatitis B vaccine when you start treatment with HepaGam B.

For liver transplant: HepaGam B is given as part of the transplant procedure, and then for several weeks or months afterward. The medication is usually given to transplant patients every day for 7 days, then every 2 weeks for the next 11 weeks, followed by monthly injections from then on.

For prevention after sexual contact with an infected person: HepaGam B is given as a single dose within 14 days after the last contact. You should also receive a hepatitis B vaccine if you will continue to have contact with the infected person.

For prevention in people sharing the home of an infected person: HepaGam B should be given to infants younger than 12 months old, caregivers who may come into contact with the infected person's blood, and people who share razors, toothbrushes, or other personal items with the infected person. Household members may also need to receive hepatitis B vaccine.

For babies born to mothers infected with hepatitis B: This medicine is usually given within 12 hours after birth, or when the baby is medically stable.

In addition to HepaGam B, the baby should also receive hepatitis B vaccine, which is given in a series of 3 shots.

• The first hepatitis B vaccine is usually given when the child is 7 days old. The booster shots are then given 1 month and 6 months after the first hepatitis B vaccine.

• If the baby does not receive the first hepatitis B vaccine before the age of 3 months, a second dose of HepaGam B must be given.

• Your child's individual booster schedule may be different from these guidelines. Follow your doctor's instructions or the schedule recommended by the health department of the state you live in.

• If the baby does not receive hepatitis B vaccine at all, a second and third dose of HepaGam B must be given 3 and 6 months after the first dose. Follow your doctor's instructions.

While using HepaGam B, you may need frequent blood tests.

This medication can cause unusual results with certain lab tests for glucose (sugar) in the blood. Tell any doctor who treats you that you are using HepaGam B.

Since this medication is given by a healthcare professional in a medical setting, an overdose is unlikely to occur.

Other drugs may interact with HepaGam B, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.