Children's Hospitals Today - Fall 2023 - 25

KEDRAB Rabies Immune Globulin (Human)
BRIEF SUMMARY OF
FULL PRESCRIBING INFORMATION
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.
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
All KEDRAB
(N=91)
Injection site pain
Headache
Muscle pain
Joint Pain
Dizziness
Fatigue
Abdominal pain
Blood in urine (Hematuria)
Nausea
Feeling faint
30 (33%)
14 (15%)
8 (9%)
5 (6%)
5 (6%)
5 (6%)
4 (4%)
4 (4%)
4 (4%)
4 (4%)
All Comparator
HRIG
(N=84)
26 (31%)
11 (13%)
6 (7%)
0 (0%)
3 (4%)
2 (2%)
1 (1%)
2 (2%)
3 (4%)
1 (1%)
Data are presented as number of subjects (% of subjects).
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.
Saline
Placebo+Vaccine
(N=8)
2 (25%)
3 (38%)
0 (0%)
1 (13%)
0 (0%)
0 (0%)
0 (0%)
0 (0%)
0 (0%)
0 (0%)
Table 3: Adverse Reactions Occurring in >5% of Pediatric Patients within 14 Days
of Post-exposure Prophylaxis with KEDRAB and Active Rabies Vaccine
KEDRAB + Rabies Vaccine
N = 30
Injection site pain
Headache
Fever (Pyrexia)
Pain in extremity
Bruising (hematoma)
Fatigue
Vomiting
8 (27%)
4 (13%)
4 (13%)
3 (10%)
2 (7%)
2 (7%)
2 (7%)
Data are presented as number of patients (% of patients).
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.
7
DRUG INTERACTIONS
* Patients who can document previous complete rabies pre-exposure prophylaxis or
complete post-exposure prophylaxis and have a confirmed adequate rabies antibody
titer should receive only a booster rabies vaccine (without KEDRAB) because KEDRAB
may interfere with the anamnestic response to the vaccine (ACIP)1
.
* KEDRAB can interfere with the immune response to the rabies vaccine. For this
reason, do not exceed the recommended KEDRAB dose or give additional (repeat)
doses of KEDRAB once rabies vaccination has been initiated.
* KEDRAB can inactivate the rabies vaccine. For this reason, do not administer KEDRAB
in the same syringe as the rabies vaccine or near the anatomical site of administration
of the rabies vaccine.
* KEDRAB contains other antibodies that may interfere with the response to live
vaccines such as measles, mumps, polio or rubella. Avoid immunization with live
virus vaccines within 3 months after KEDRAB administration, or in the case of
measles vaccine, within 4 months after KEDRAB administration.
8
USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
KEDRAB has not been studied in pregnant women. Therefore, the risk of major birth
defects and miscarriage in pregnant women who are exposed to KEDRAB is unknown.
Animal developmental or reproduction toxicity studies have not been conducted
with KEDRAB. It is not known whether KEDRAB can cause harm to the fetus when
administered to a pregnant woman or whether KEDRAB can affect reproductive capacity.
In the U.S. general population, the estimated background of major birth defects occurs
in 2-4% of the general population and miscarriage occurs in 15-20% of clinically
recognized pregnancies.
8.2
Lactation
Risk Summary
There is no information regarding the presence of KEDRAB in human milk, the effects
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
KEDRAB and any potential adverse effects on the breastfed infant from KEDRAB or from
the underlying maternal condition.
8.4
Pediatric Use
Safety and effectiveness have been established in children. In a pediatric study of
30 patients ranging in age from 0.5 to 14.9 years, KEDRAB presented no serious
adverse reactions through day 84. Of the 30 patients, 28 (93.3%) achieved a Day-14
RVNA titer ≥0.5 IU/mL, the WHO recommended level. None of the patients who were
followed until the end of the study (28/30 patients) developed rabies infection through
day 84. [see Clinical Trials (14)]
Adverse reactions that occurred in ≥3.3% of patients within the first 14 days of KEDRAB
and the first rabies vaccination administration are listed in Section 6.1.
The clinical trial conducted in the pediatric population is described in Section 14.
Additional evidence to support the use of KEDRAB in children comes from Real World
Evidence. Based on claims data, 172 U.S. children (≤17 years) were treated with
KEDRAB between 2018-2020. Based on Center for Disease Control data, no children in
the U.S. treated with post-exposure prophylaxis have been reported to have had rabies
between 2018-April 2021.
8.5
Geriatric Use
Clinical studies of KEDRAB did not include sufficient numbers of subjects aged 65 years
and over to determine whether they respond differently from younger subjects. Clinical
experience with HRIG products has not identified differences in effectiveness between
elderly and younger patients (ACIP)1.
13
NONCLINICAL TOXICOLOGY
13.2 Animal Toxicology and/or Pharmacology
Intramuscular administration of a single dose of KEDRAB to rats at 60 and 120 IU/kg
(3 fold and 6-fold higher than the recommended human dose of 20 IU/kg) did not result
in any signs of toxicity.
For a copy of the Full Prescribing Information for KEDRAB,
please visit www.KEDRAB.com.
Distributed by:
Kedrion Biopharma Inc.
Parker Plaza, 400 Kelby St.
Fort Lee, NJ 07024
United States
Manufactured by:
Kamada Ltd.
Beit Kama
MP Negev 8532500
Israel
US License No. 1826
©2021 Kedrion Biopharma Inc. All Rights Reserved.
May 2021 KR-0562-01-2021B
http://www.KEDRAB.com
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