HYPERRAB Solution for injection Ref.[10828] Active ingredients: Human rabies immunoglobulin

5.1 Hypersensitivity Reactions

Severe hypersensitivity reactions may occur with HYPERRAB. Patients with a history of prior systemic allergic reactions to human immunoglobulin preparations are at a greater risk of developing severe hypersensitivity and anaphylactic reactions. Have epinephrine available for treatment of acute allergic symptoms, should they occur.

Patients with isolated immunoglobulin A (IgA) deficiency may develop severe hypersensitivity reactions to HYPERRAB, or subsequently, to the administration of blood products that contain IgA.(4)

5.2 Transmissible Infectious Agents

HYPERRAB is made from human blood and may carry a risk of transmitting infectious agents, e.g., viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent, and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent. HYPERRAB is purified from human plasma obtained from healthy donors. When medicinal biological products are administered, infectious diseases due to transmission of pathogens cannot be totally excluded. However, in the case of products prepared from human plasma, the risk of transmission of pathogens is reduced by: (1) epidemiological controls on the donor population and selection of individual donors by a medical interview and screening of individual donations and plasma pools for viral infection markers; (2) testing of plasma for hepatitis C virus (HCV), human immunodeficiency virus (HIV), hepatitis B virus (HBV), HAV and human parvovirus (B19V) genomic material; and (3) manufacturing procedures with demonstrated capacity to inactivate/remove pathogens.

ALL infections thought by a physician possibly to have been transmitted by this product should be reported by the physician or other healthcare provider to Grifols Therapeutics LLC [1-800-520-2807].

The most common adverse reactions in >5% of subjects during clinical trials were injection site pain, headache, injection site nodule, abdominal pain, diarrhea, flatulence, nasal congestion, and oropharyngeal pain.

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.

The new formulation for HYPERRAB is manufactured using caprylate/chromatography purification and has a rabies antibody concentration of 300 IU/mL. The previous formulation, HYPERRAB S/D, was manufactured using a solvent detergent process and had a rabies antibody concentration of 150 IU/mL. These products were evaluated in 2 clinical trials in a total of 20 healthy subjects using a 20 IU/kg single dose. The initial study evaluated the original 150 IU/mL HYPERRAB S/D in 8 subjects and the second study evaluated HYPERRAB in 12 subjects. The original study of HYPERRAB S/D reported headache (1/8; 13%).

In the study with HYPERRAB at 300 IU/mL, 5 subjects (5/12; 42%) experienced at least 1 adverse reaction. These were: injection site pain (4/12; 33%), injection site nodule (1/12; 8%), abdominal pain (1/12; 8%), diarrhea (1/12; 8%), flatulence (1/12; 8%), headache (1/12; 8%), nasal congestion (1/12; 8%), and oropharyngeal pain (1/12; 8%).

There are no data on the postmarketing use of HYPERRAB (300 IU/mL). The following adverse reactions have been identified during post approval use of the predecessor formulation, HYPERRAB S/D. 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.

Among patients treated with HYPERRAB S/D, cases of allergic/hypersensitivity reactions including anaphylaxis have been reported. Soreness at the site of injection (injection site pain) may be observed following intramuscular injection of immune globulins. Sensitization to repeated injections has occurred occasionally in immunoglobulin-deficient patients.

The following have been identified as the most frequently reported post-marketing adverse reactions:

Immune system disorder: Anaphylactic reaction*, hypersensitivity*

Nervous system disorders: Hypoesthesia

Gastrointestinal disorders: Nausea

Musculoskeletal and connective tissue disorders: Arthralgia, myalgia, pain in extremity

^* These reactions have been manifested by dizziness, paresthesia, rash, flushing, dyspnea, tachypnea, oropharyngeal pain, hyperhidrosis, and erythema.

• Do not administer repeated doses of HYPERRAB once vaccine treatment has been initiated as this could prevent the full expression of active immunity expected from the rabies vaccine.(1)
• Other antibodies in the HYPERRAB preparation may interfere with the response to live vaccines such as measles, mumps, polio or rubella. Defer immunization with live vaccines for 4 months after HYPERRAB administration.(5)

Risk Summary

There are no data with HYPERRAB use in pregnant women to inform a drug-associated risk. Animal reproduction studies have not been conducted with HYPERRAB. It is not known whether HYPERRAB can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. HYPERRAB should be given to a pregnant woman only if clearly needed. In the U.S. general population, the estimated backgrounds risk of major birth defect and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Risk Summary

There is no information regarding the presence of HYPERRAB in human milk, the effect on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for HYPERRAB and any potential adverse effects on the breastfed infant from HYPERRAB.

Safety and effectiveness in the pediatric population have not been established.

Safety and effectiveness in geriatric population have not been established.