Rabies immune globulin (KedRab)
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Black Box Warning
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Warning Title
See full prescribing information for complete Boxed Warning.
Condition Name: (Content)
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Overview
Rabies immune globulin (KedRab) is a Acetylcholine release inhibitor, Adrenergic receptor agonist that is FDA approved for the (type of indication of drug) of a list of indications, separated by commas.. There is a Black Box Warning for this drug as shown here. Common adverse reactions include a list of adverse reactions, separated by commas..
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
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Condition 2
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Off-Label Use and Dosage (Adult)
Guideline-Supported Use
Condition 1
- Developed by: (Organisation)
- Class of Recommendation: (Class) (Link)
- Strength of Evidence: (Category A/B/C) (Link)
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Condition 2
- Developed by: (Organisation)
- Class of Recommendation: (Class) (Link)
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Non–Guideline-Supported Use
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Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
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Condition 2
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Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
Condition 1
- Developed by: (Organisation)
- Class of Recommendation: (Class) (Link)
- Strength of Evidence: (Category A/B/C) (Link)
- Dosing Information/Recommendation
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Condition 2
- Developed by: (Organisation)
- Class of Recommendation: (Class) (Link)
- Strength of Evidence: (Category A/B/C) (Link)
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Non–Guideline-Supported Use
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Contraindications
CONTRAINDICATIONS
Warnings
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Warning Title
See full prescribing information for complete Boxed Warning.
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Conidition 1
(Description)
Conidition 2
(Description)
Conidition 3
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Adverse Reactions
Clinical Trials Experience
Central Nervous System
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Cardiovascular
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Respiratory
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Gastrointestinal
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Hypersensitive Reactions
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Miscellaneous
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Condition 2
Central Nervous System
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Cardiovascular
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Respiratory
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Gastrointestinal
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Hypersensitive Reactions
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Miscellaneous
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Postmarketing Experience
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Drug Interactions
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Drug 4
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Use in Specific Populations
Pregnancy
Pregnancy Category (FDA):
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Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Rabies immune globulin (KedRab) in women who are pregnant.
Labor and Delivery
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Nursing Mothers
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Pediatric Use
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Geriatic Use
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Gender
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Race
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Renal Impairment
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Hepatic Impairment
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Females of Reproductive Potential and Males
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Immunocompromised Patients
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Others
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Administration and Monitoring
Administration
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Monitoring
Condition 1
(Description regarding monitoring, from Warnings section)
Condition 2
(Description regarding monitoring, from Warnings section)
Condition 3
(Description regarding monitoring, from Warnings section)
IV Compatibility
There is limited information regarding the compatibility of Rabies immune globulin (KedRab) and IV administrations.
Overdosage
Acute Overdose
Signs and Symptoms
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Management
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Chronic Overdose
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Management
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Pharmacology
Rabies immune globulin (KedRab)
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Mechanism of Action
- Rabies is a zoonotic disease caused by RNA viruses in the family Rhabdoviridae, genus Lyssavirus. Virus is typically present in the saliva of rabid mammals and is transmitted primarily through a bite. KEDRAB is infiltrated into the inoculation site (i.e., at the beginning of anti-rabies PEP) to previously unvaccinated persons, to provide immediate passive rabies virus neutralizing antibody protection until the patient's immune system responds to vaccination by actively producing antibodies.
Structure
(Description with picture)
Pharmacodynamics
- A protective threshold for rabies virus neutralizing activity (RVNA) has never been established. However, the WHO has generally accepted a RVNA of at least 0.5 IU/mL measured 14 days after initiation of PEP as protective. By comparison, the ACIP recommends complete neutralization of rabies virus at a 1:5 serum dilution by a rapid fluorescent focus inhibition test (RFFIT) from 1 to 2 weeks after prophylaxis; this corresponds to RVNA ~0.1-0.2 IU/mL. In support of these recommendations, there has been almost no documented clinical disease when the current rabies PEP regimen is administered appropriately (ACIP) 1.
- KEDRAB has the potential to attenuate the patient's immune response to rabies vaccine. This was evaluated in a double-blind, randomized study where 16 healthy subjects were administered either KEDRAB (20 IU/kg IM) or saline placebo followed by three doses of a rabies vaccine (TABLE 3). Lower RVNA levels were seen in the KEDRAB + vaccine group compared to the placebo + vaccine group at all time-points beginning on Day 14, confirming that KEDRAB interferes with the host immune response to rabies vaccine.
Pharmacokinetics
- A randomized, single-dose, two-period, two-treatment, two-sequence, double-blind, crossover study assessed the pharmacokinetics of KEDRAB. Twenty-six healthy volunteer subjects were randomized to receive a single IM injection of 20 IU/kg HRIG on two separate occasions (KEDRAB or Comparator HRIG). Subjects received the second treatment (A or B) following the 42-day test period and a 21-day washout period. Single dose IM injection of KEDRAB resulted in maximum plasma RVNA levels of 0.25 IU/mL. The median Tmax was 7 days (range: 3 – 14 days). The elimination half-life was approximately 17.9 days. A statistical analysis of the pharmacokinetic parameters showed that KEDRAB was not bioequivalent to the Comparator HRIG (TABLE 3).
_Pharmacokinetics_Table_1.png)
- A plot of plasma rabies virus neutralizing antibody titer concentration versus time (FIGURE 1) demonstrated that, in both treatment groups, plasma rabies virus neutralizing antibody concentrations declined in a biphasic manner after the absorption phase was complete.
_Pharmacokinetics_Figure_1.png)
- Additionally, a prospective, randomized, double-blind, non-inferiority, study evaluated the pharmacokinetics, safety and effectiveness of simulated post-exposure prophylaxis with KEDRAB with co-administration of active rabies vaccine in 118 healthy subjects. Subjects were randomized into two treatment groups (59 per treatment group) to receive intramuscular KEDRAB or comparator HRIG at a dose of 20 IU/kg on Day 0, and rabies vaccine on Days 0, 3, 7, 14 and 28. The peak plasma RVNA was 71.9 IU/mL and 53.9 IU/mL for KEDRAB and comparator HRIG respectively. For both treatment groups, the median Tmax was 14 days (range: 14 – 49 days). The half-lives were 48.6 hours and 52.7 hours for KEDRAB and comparator HRIG respectively.
- Bioequivalent assessment showed that KEDRAB was not bioequivalent to the comparator HRIG when co-administered with a five-dose rabies vaccine regimen (TABLE 4). Furthermore, the RVNA on Day 3 was lower in the KEDRAB with rabies vaccine group relative to the Comparator HRIG with vaccine group (0.188±0.051 vs 0.229±0.054, P=0.0005). However, these pharmacokinetic differences are not expected to affect clinical outcomes.
_Pharmacokinetics_Table_2.png)
Nonclinical Toxicology
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.
Clinical Studies
- The efficacy of KEDRAB administered concurrently with rabies vaccine was studied in a single-center, randomized, comparator HRIG-controlled clinical study. Study subjects were healthy adults 18 to 72 years of age who were without significant acute or chronic illness. A total of 118 subjects (59 per treatment group) received intramuscular KEDRAB or comparator HRIG at a dose of 20 IU/kg on Day 0, and rabies vaccine on Days 0, 3, 7, 14 and 28. The mean age of study subjects was 45 years; subjects were, predominantly white (93%), and 64% were women. The efficacy variable was RVNA, as assessed by RFFIT, on Day 14. Efficacy analyses were performed on the As-Treated Population, which comprised the 116 study subjects who received KEDRAB or comparator HRIG and at least 3 of the 5 doses of rabies vaccine before Day 14.
- Efficacy, considered when RVNA titer is 0.5 IU/mL or higher on Day 14 (as established by the WHO), was met by 56/57 subjects (98.2%) in the KEDRAB group and 59/59 subjects in the comparator HRIG group (TABLE 5). The lower limit of the 90% CI was greater than the pre-specified non-inferiority margin of -10%; thus, KEDRAB was non-inferior to comparator HRIG.
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- Additional efficacy analyses included pharmacokinetics.
How Supplied
- Each carton of KEDRAB contains a single-use vial containing 2 mL or 10 mL of ready-to-use solution with a potency of 150 IU/mL.
- The 2-mL vial contains a total of 300 IU which is sufficient for a child weighing 15 kg (33 lb). (NDC 76125-150-02). The 10-mL vial contains a total of 1500 IU which is sufficient for an adult weighing 75 kg (165 lb). (NDC 76125-150-10).
Storage
- Store KEDRAB at 2-8 °C (36-46 °F). Do not freeze.
- Keep vial in carton until use.
- KEDRAB may be stored at room temperatures not exceeding 25 °C (77 °F) for up to one month.
- Use within one month after removal from refrigeration, Do not return to refrigeration.
- Do not use after the expiration date printed on the label.
Images
Drug Images
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Package and Label Display Panel
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Patient Counseling Information
- The KEDRAB manufacturing process includes three valid and effective viral elimination steps. In addition, the process allows the removal of thrombogenic activity.
- Inform patients that KEDRAB is made from human plasma and may contain infectious agents that can cause disease (e.g., viruses and, theoretically, the CJD agent). Explain that the risk of KEDRAB transmitting an infectious agent has been reduced by screening the plasma donors, by testing the donated plasma for certain virus infections, and by a process demonstrated to inactivate and/or remove certain viruses during manufacturing. Inform patients of symptoms of a possible viral infection, including headache, fever, nausea, vomiting, weakness, malaise, diarrhea, or, in the case of hepatitis, jaundice.
Precautions with Alcohol
Alcohol-Rabies immune globulin (KedRab) interaction has not been established. Talk to your doctor regarding the effects of taking alcohol with this medication.
Brand Names
- KedRab
Look-Alike Drug Names
There is limited information regarding Rabies immune globulin (KedRab) Look-Alike Drug Names in the drug label.
Drug Shortage Status
Drug Shortage
Price
References
The contents of this FDA label are provided by the National Library of Medicine.