Adverse reactions : תופעות לוואי

 8. ADVERSE REACTIONS
Adverse reactions overview
The most common expected adverse drug reactions for intravenous immunoglobulins like HepaGam B™ are chills, fever, headaches, vomiting, allergic reactions, nausea, arthralgia and moderate low back pain.

Although anaphylactic reactions to HepaGam B are very rare they have been reported following the administration of other forms of intravenous immunoglobulin (human) products (see WARNINGS AND PRECAUTIONS, General).

Post-exposure Prophylaxis
In clinical trial HB-004, 253 infants born to HBsAg-positive mothers received a single dose of HepaGam B™ and hepatitis B vaccine intramuscularly within 12 hours of birth. A total of 531 adverse events were reported for 159 of the infants (63%). The most common adverse events were diarrhea (57 events) and pyrexia (52 events).
The majority of adverse events were mild in intensity. Only one adverse event, indurations of the right and left thighs, was reported as possibly treatment-related. A total of 43 serious adverse event terms were captured on Case Report Forms (CRFs) for 38 infants during the study. None of the serious adverse events were related to HepaGam B™ administration. In addition, 42 adult males and females were administered a single dose of HepaGam B™ along with hepatitis B vaccine within 48 hours of possible exposure to hepatitis B virus (needle stick, bite, sharps, etc). A total of 69 adverse events were reported for 25 of the patients (60%). The most frequent adverse event was headache (12 events). The majority of events were reported as mild. Nineteen adverse events were reported as possibly related to HepaGam B™ administration. The most common related adverse events were nausea, pyrexia, arthralgia, myalgia and headache.


Prevention of Hepatitis B Recurrence Following Liver Transplantation
In clinical trial HB-005 with 27 liver transplant patients who received intravenous infusions of HepaGam B™, one adverse drug reaction of hypotension was reported. In studies with healthy volunteers, only one adverse drug reaction of nausea had been reported in the 70 adult subjects who received an intramuscular administration of HepaGam B™.

In an open-label extension study (HB-006), four HBsAg-negative post-transplant patients who participated in HB-005 received 47 infusions of HepaGam B in total. Seventeen adverse events were reported. None considered as related to study drug.

In clinical trial HB-009, with 11 liver transplant patients who received total of 194 infusions of HepaGam B, 212 adverse events were reported. Only five adverse events were deemed related to study drug, all affecting a single participant. These five AEs were hypertension, dyspnea, pyrexia, infusion related reaction, and increased respiratory rate. All were deemed mild in intensity and consistent with a faster than usual infusion rate. A total of 25 serious adverse events were reported by six participants. None of the serious adverse events were deemed related to study drug.

Healthy Volunteer Studies
Seventy healthy male and female volunteers received a single dose of HepaGam B™, Hepatitis B Immunoglobulin (Human), intramuscularly in clinical trials. Seventeen subjects reported 30 adverse events following administration of HepaGam B™. The most frequently reported adverse events included four subjects (6%) who experienced headache, seven subjects (10%) who had cold symptoms or flu and two subjects (3%) who experienced lightheadedness/fainted. The majority of events were reported as mild. 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.

Clinical trials adverse reactions
Clinical trials are conducted under very specific conditions. The adverse reaction rates observed in the clinical trials, therefore may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. Adversereaction information from clinical trials May be useful in identifying and approximating rates of adverse drug reactions in real-world use.

Hepatitis B-Related Liver Transplantation:
A single adverse drug reactions of hypotension occurred following a total of 578 (<1%) HepaGam B™ infusions administered to 27 subjects in a Phase III clinical trial examining HepaGam B™ for the prevention of hepatitis B recurrence following liver transplantation. This study utilized the recommended dosing regimen outlined in Table 2 [See DOSAGE AND ADMINISTRATION]. The reaction was recorded during the first week post-transplant and resolved on the same day and did not recur with subsequent HepaGam B™ infusions.

In clinical trial HB-009, with 11 liver transplant patients who received total of 194 infusions of HepaGam B, 212 adverse events were reported. Five adverse events were deemed related to study drug, all affecting a single patient. These five adverse events were hypertension, dyspnea, pyrexia, infusion related reaction, and increased respiratory rate.

Healthy Volunteer Studies
Seventy healthy male and female volunteers received a single dose of Hepatitis B Immunoglobulin (Human), intramuscularly, in clinical trials. One adverse event, an episode of nausea, was considered to be drug related.

Clinical Trial Adverse Reactions – Pediatrics
Please refer to Adverse Reaction Overview, Post-exposure Prophylaxis

Abnormal Laboratory Findings: Hematologic, Clinical Chemistry and Other Quantitative Data Clinical Trial Findings
There have been no abnormal hematology or clinical chemistry values reported to be related to HepaGam B™ administration.

Post-Market Adverse Reactions
The following adverse reactions have been identified during post-approval use of HepaGam B™. Because these reactions 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 drug exposure.
The system organ classification of reported adverse reactions is provided below: 
Table 5: Adverse Reactions identified during post-approval use of HepaGam B.
Organ system/Disorder                                        Adverse Reaction Cardiac Disorders:                                    Sinus tachycardia Gastrointestinal Disorders:                           Abdominal pain
Nausea
General Disorders and Administration Site Conditions: Asthenia
Chest pain
Chills
Feeling cold
Feeling hot
Influenza like illness
Malaise
Pain
Pyrexia
Immune System Disorders:                                  Anaphylactoid reaction Anaphylactic shock
Hypersensitivity
Investigations:                                           Lipase increased Transaminases increased
Musculoskeletal and Connective Tissue Disorders:          Back pain
Groin pain
Nervous System Disorders:                                 Dizziness
Headache
Respiratory, Thoracic and Mediastinal Disorders:          Dyspnoea
Skin and Subcutaneous Tissue Disorders:                   Cold sweat
Rash erythematous
Vascular Disorders:                                       Flushing

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.
Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form https://sideeffects.health.gov.il