KEDRAB: Package Insert and Label Information

KEDRAB- human rabies virus immune globulin injection, solution
Kedrion Biopharma Inc.

1 INDICATIONS AND USAGE

KEDRAB is a human rabies immune globulin (HRIG) indicated for passive, transient post-exposure prophylaxis (PEP) of rabies infection to persons of all ages when given immediately after contact with a rabid or possibly rabid animal. KEDRAB should be administered concurrently with a full course of rabies vaccine.

2 DOSAGE AND ADMINISTRATION

For wound infiltration and intramuscular use.

2.1 Dosage

Post-exposure prophylaxis consists of a single 20 IU/kg body weight dose of KEDRAB and a full course of rabies vaccine (See Table 1).

Table 1: Rabies Post-exposure Prophylaxis Schedule*

* Adapted from reference 1.

These regimens are applicable for all age groups, including children.

ǂ Day 0 is the day the first dose of vaccine is administered. Refer to vaccine manufacturer’s instructions or to the recommendations of the Advisory Committee on Immunization Practices (ACIP)1,2 for appropriate rabies vaccine formulations, schedules, and dosages.

§ Any person with a history of rabies vaccination and a documented history of antibody response to the prior vaccination.

Vaccination Status Intervention Regimen†
Not previouslyvaccinated Wound Cleansing
  • Cleanse all wounds immediately and thoroughly with soap and water.
  • Irrigate the wounds with a viricidal agent such as a povidone-iodine solution, if available.
KEDRAB® 20 IU/kg body weight
  • Administer KEDRAB as soon as possible after exposure, preferably at the time of the first rabies vaccine dose. However, should a delay occur, administer KEDRAB at any time up to and including seven days after the first dose of rabies vaccine.
  • If there is a delay, initiate post-exposure prophylaxis at any time after exposure.
  • Infiltrate the area around and into the wound(s), if anatomically feasible, with the full dose of KEDRAB.
  • Inject the remainder, if any, intramuscularly at an anatomical site distant from the site of rabies vaccine administration.
  • Do not exceed the recommended dose of KEDRAB because this can partially suppress active production of rabies virus antibodies. [see Drug Interactions (7)]
  • Do not administer additional doses of KEDRAB, even if the antibody response to vaccination is delayed. (7)
  • Use separate syringes, needles, and anatomical injection sites for KEDRAB and for rabies vaccine.
Rabies Vaccine
  • Administer rabies vaccine on Day 0 and on subsequent vaccine administration daysǂ at an anatomical site that is distant from the KEDRAB administration site(s).
  • Complete a rabies vaccination series
Previously vaccinated§ Wound cleansing
  • Cleanse all wounds immediately and thoroughly with soap and water.
  • Irrigate the wounds with a viricidal agent such as povidone-iodine solution if available.
KEDRAB®
  • Do not administer KEDRAB. [see Warnings and Precautions (5.1)]
Rabies Vaccine
  • Administer rabies vaccine on Day 0.ǂ
  • Complete a rabies vaccination series for previously vaccinated persons.†
Other Considerations Tetanus prophylaxis and/or antibiotics
  • Provide treatment if medically indicated

2.2 Administration

Infiltrate as much of the KEDRAB dose as possible into and around any detectable bite wounds if infiltration at the bite site is feasible. Administer any remaining KEDRAB intramuscularly into anatomical site(s) distant from the site of the rabies vaccine.

  • When the bite site is unknown or indeterminate (undetectable) or if infiltration is difficult at the bite site (e.g., lips, fingers, knee), administer the full KEDRAB dose by the intramuscular route at a site distant from the site of rabies vaccination.
  • If a large intramuscular volume is required (>2 mL for children or >5 mL for adults), administer the total volume in divided doses at different sites.
  • Do not mix KEDRAB with the rabies vaccine or administer in the same syringe with the rabies vaccine.
  • Discard unused portion of the product in the vial.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. Do not use if either of these conditions exists, and contact Kedrion Biopharma Inc. at 1-855-353-7466. Do not discard the vial.

3 DOSAGE FORMS AND STRENGTHS

KEDRAB is supplied in single-dose vials containing 2 mL or 10 mL of ready-to-use solution with a nominal potency of 150 IU/mL (Note that more than one vial may be required for a single patient treatment).

  • The 2 mL vial contains a total of 300 IU, which is sufficient for a child weighing 15 kg (33 lb)
  • The 10 mL vial contains a total of 1500 IU, which is sufficient for an adult weighing 75 kg (165 lb)

The final product is assayed with human rabies immunoglobulin reference standard that is calibrated against the WHO International Standard.

4 CONTRAINDICATIONS

None.

5 WARNINGS AND PRECAUTIONS

5.1 Previous Rabies Vaccination

Patients who can document previous complete rabies pre-exposure prophylaxis or complete post-exposure prophylaxis should only receive a booster rabies vaccine without KEDRAB because KEDRAB may interfere with the anamnestic response to the vaccine (ACIP)1.

5.2 Hypersensitivity Reactions

Hypersensitivity reactions, including anaphylaxis, may occur with KEDRAB. History of prior systemic allergic reactions to human immunoglobulin preparations places patients at greater risk. Have epinephrine available for treatment of acute allergic symptoms. Patients with isolated immunoglobulin A (IgA) deficiency may develop severe hypersensitivity reactions to KEDRAB or, subsequently, to the administration of blood products that contain IgA.

5.5 Live Attenuated Virus Vaccines

KEDRAB administration may interfere with the development of an immune response to live attenuated virus vaccines. If feasible, delay immunization with measles vaccine for 4 months, and other live attenuated virus vaccines for 3 months, after KEDRAB administration.

5.6 Interference with Serologic Testing

  • A transient rise of the various passively transferred antibodies in the patient’s blood may result in misleading positive results of serologic tests after KEDRAB administration.
  • Passive transmission of antibodies to erythrocyte antigens, e.g., A, B, and D, may interfere with serologic tests for red cell antibodies such as the antiglobulin test (Coombs’ test).

5.7 Transmissible Infectious Agents

Because KEDRAB is made from human plasma donors hyper-immunized with rabies vaccine, it 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. All infections suspected by a physician possibly to have been transmitted by this product should be reported by the physician or other healthcare provider to Kedrion Biopharma Inc. at 1-855-353-7466.

6 ADVERSE REACTIONS

The most common adverse reactions (>5%) observed in adult subjects were injection site pain, headache, muscle pain, joint pain, dizziness, and fatigue.

The most common adverse reactions (>5%) observed in pediatric patients were injection site pain, headache, pyrexia, plain in extremity, bruising, fatigue and vomiting.

6.1 Clinical Trials Experience

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

KEDRAB was evaluated in three single-center, controlled clinical trials in adults. Subjects in these clinical studies of KEDRAB were healthy adults, primarily white, and ranged in age from 18 to 72 years. A total of 160 adult subjects were treated in these three studies, including 91 subjects who received single intramuscular doses of KEDRAB (20 IU/kg) with or without rabies vaccine.

Table 2 summarizes adverse reactions occurring in >3% of adult subjects in the clinical trials of KEDRAB. (Table 2).

Table 2: Adverse Reactions Occurring in >3% of Subjects in All Combined Studies in Adults

Data are presented as number of subjects (% of subjects).

All KEDRAB (N=91) All Comparator HRIG (N=84) Saline Placebo+Vaccine (N=8)
Injection site pain 30 (33%) 26 (31%) 2 (25%)
Headache 14 (15%) 11 (13%) 3 (38%)
Muscle pain 8 (9%) 6 (7%) 0 (0%)
Joint Pain 5 (6%) 0 (0%) 1 (13%)
Dizziness 5 (6%) 3 (4%) 0 (0%)
Fatigue 5 (6%) 2 (2%) 0 (0%)
Abdominal pain 4 (4%) 1 (1%) 0 (0%)
Blood in urine (Hematuria) 4 (4%) 2 (2%) 0 (0%)
Nausea 4 (4%) 3 (4%) 0 (0%)
Feeling faint 4 (4%) 1 (1%) 0 (0%)

Less frequent adverse reactions (≤3%) in adult subjects were diarrhea, vomiting, decreased appetite, musculoskeletal stiffness, malaise, weakness (asthenia), fainting (syncope), itching (pruritis), tingling sensation (paresthesia), rash, sunburn and elevation in liver function.

KEDRAB was also evaluated in a two-center, open-label clinical trial in 30 pediatric patients exposed or possibly exposed to rabies virus. They ranged in age from 0.5 to 14.9 years. Study treatment included a single dose of KEDRAB (20 IU/kg) and active rabies vaccine on Days 0, 3, 7 and 14 administered as per ACIP1 recommendations for rabies post-exposure prophylaxis.

Twelve pediatric patients (40%) experienced adverse reactions within 14 days of receipt of KEDRAB and first dose of rabies vaccine. There were no serious adverse reactions. Table 3 summarizes the adverse reactions that occurred in >5% of patients in the pediatric clinical trial within 14 days of receipt of KEDRAB and the first dose of the rabies vaccine.

Table 3: Adverse Reactions Occurring in >5% of Pediatric Patients within 14 Days of Post-exposure Prophylaxis with KEDRAB and Active Rabies Vaccine

Data are presented as number of patients (% of patients).

KEDRAB + Rabies Vaccine N = 30
Injection site pain 8 (27%)
Headache 4 (13%)
Fever (Pyrexia) 4 (13%)
Pain in extremity 3 (10%)
Bruising (hematoma) 2 (7%)
Fatigue 2 (7%)
Vomiting 2 (7%)

Less common adverse reactions (≤5%) in pediatric patients were injection site redness (erythema), injection site swelling (edema), muscle pain, oral pain, and wound complication.

Insomnia was reported as a less common adverse reactions (<5%) in pediatric patients occurring after 14 days of administration.

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