CNJ-016: Package Insert and Label Information (Page 3 of 3)

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity, genotoxicity and fertility studies have not been conducted with VIGIV.

13.2 Animal Toxicology and/or Pharmacology

The efficacy of VIGIV against vaccinia virus in a mouse-tail lesion model was assessed. A range of doses of VIGIV and a previously licensed VIG were compared for their ability to reduce pox formation in this model.

Using this model, it was demonstrated that VIGIV exerted an in vivo protective effect against vaccinia infection when compared to a negative control. In addition, when using the mouse-tail lesion model with two different strains of vaccinia virus, it was observed that the protective effect of VIGIV appeared similar to that of the previously licensed VIG and a CBER reference standard.

A single study in rabbits has demonstrated increased corneal scarring upon intramuscular vaccinia immune globulin administration in vaccinia keratitis (7).

Since VIGIV is a product of human origin, secondary pharmacodynamics, safety pharmacology and pharmacodynamic drug interactions were not investigated in animals.

14 CLINICAL STUDIES

The pharmacokinetic, pharmacodynamic and safety profiles of VIGIV were evaluated in three clinical trials. In these clinical studies, VIGIV was shown to have an acceptable safety profile when administered as single infusions of 6000 Units per kg, 9000 Units per kg or 24,000 Units per kg to healthy subjects. For the safety/pharmacokinetics study, see 12.3 Pharmacokinetics.

14.1 Pharmacodynamic Effect of VIGIV on Immune and Local Responses to Dryvax

In a randomized, single center, double-blind study with three parallel treatment arms, the efficacy of 9000 Units per kg of VIGIV on the immunologic and local response to the smallpox vaccine Dryvax was evaluated. Thirty-two healthy female and male subjects were randomized to receive single IV infusions of either VIGIV (9000 Units per kg) or Placebo (0.9% Sodium Chloride Injection USP) on Day 0, and either Placebo or VIGIV (9000 Units per kg) concurrently with vaccinia (Dryvax) vaccination on Day 4.

In this study, the curves for antibody titre vs. time were similar between administration of VIGIV four days prior to vaccination with Dryvax and concurrent administration of VIGIV with Dryvax.

Based on area under the effective time curve from Day 4 to 32 (AUEC4-32) results, the administration of VIGIV four days prior to vaccination with Dryvax slightly reduced the pox reaction and erythema area by 4 to 9% and 8 to 12%, respectively, as compared to the concurrent administration of VIGIV with the Dryvax vaccine, or with Dryvax alone.

In an additional randomized, single center, double-blind, study with five parallel treatment arms, the efficacy of two different doses of VIGIV (9000 Units per kg and 24,000 Units per kg) on the immunologic and local response to Dryvax was evaluated.

Fifty healthy subjects were randomized to receive a single IV infusion of either VIGIV (9000 Units per kg), VIGIV (24,000 Units per kg), or Placebo (0.9% Sodium Chloride Injection USP) on Day 0, and either placebo or vaccinia (Dryvax) vaccination on Day 4.

The administration of VIGIV four days prior to vaccinia vaccination decreased the endogenous immune response to Dryvax in a dose-dependent manner. In addition, the mean pox reaction and erythema area diameters were smaller in size when 24,000 Units per kg of VIGIV was administered prior to vaccination with Dryvax compared to those when 9000 Units per kg of VIGIV was administered prior to vaccination with Dryvax or to those from administration of Dryvax alone. These data are consistent with the hypothesis of vaccinia virus neutralization in vivo by VIGIV.

15 REFERENCES

1.
Kahwaji J et al., Acute Hemolysis after High-Dose Intravenous Immunoglobulin Therapy in Highly HLA Sensitized Patients. Clin J Am Soc Nephrol. 2009 December 4;1993–97.
2.
Daw Z, Padmore R, Neurath D, et al. Hemolytic transfusion reactions after administration of intravenous immune (gamma) globulin: A case series analysis. Transfusion 2008;48:1598-601.
3.
Bowman JM, Friesen AD, Pollock JM, Taylor WE. WinRho: Rh immune globulin prepared by ion exchange for intravenous use. Canadian Med Assoc J. 1980;123:1121-5.
4.
Friesen AD, Bowman JM, Price HW. Column ion-exchange preparation and characterization of an Rh immune globulin (WinRho) for intravenous use. Journal Appl Biochem. 1981;3:164-75.
5.
Horowitz B. Investigations into the application of tri(n-butyl)phosphate/detergent mixtures to blood derivatives. Curr Stud Hematol Blood Transfus. 1989;56:83-96.
6.
Burnouf T. Value of virus filtration as method for improving the safety of plasma products. Vox Sang. 1996;70:235-6.
7.
Fulginiti VA, Winograd LA, Jackson M, Ellis P. Therapy of experimental vaccinal keratitis: Effect of idoxuridine and VIG. Arch Ophthal. 1965;74:539-44.

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

NDC 60492-0173-1

The product is supplied as a 20 mL single dose vial containing ≥50,000 Units per vial. It is packaged in a shelf carton with 24 vials and four package inserts.

VIGIV does not contain natural rubber latex.

16.2 Storage and Handling

Product may be stored frozen at or below 5°F (≤-15°C) or refrigerated at 36 to 46°F (2 to 8°C); refer to label for appropriate storage conditions. Do not use after expiration date.

If product is received frozen, use within 60 days of thawing at 2 to 8°C. Begin intravenous infusion within 4 hours after entering the vial.

Do not reuse or save VIGIV for future use. This product contains no preservative; therefore, discard partially used vials.

17 PATIENT COUNSELING INFORMATION

Discuss the risks and benefits of VIGIV with the patient before prescribing or administration.

Inform patients of the potential for hypersensitivity reactions, especially in individuals with previous reactions to human immune globulin and in individuals deficient in IgA [see 4 CONTRAINDICATIONS and 5.1 Hypersensitivity]. Advise patients to be aware of the following symptoms associated with allergic reactions: hives, rash, chest tightness, wheezing, shortness of breath, or feeling light headed or dizzy when they stand. Caution patients to seek medical attention immediately should they experience any one or more of the above mentioned symptoms, as well as other side effects including injection site pain, chills, fever, headache, nausea, vomiting, and joint pain.
Advise patients that the maltose contained in VIGIV can interfere with some types of blood glucose monitoring systems. Patients must use testing systems that are glucose-specific for monitoring blood glucose levels as the interference of maltose could result in falsely elevated glucose readings, which could lead to untreated hypoglycemia or to inappropriate insulin administration, resulting in life-threatening hypoglycemia [see 5.2 Interference with Blood Glucose Testing].
Advise patients that VIGIV may impair the effectiveness of certain live virus vaccines such as measles, rubella (i.e. German measles), mumps, and varicella (i.e. chickenpox). Patients recently vaccinated must notify their treating physician [see 7.1 Live, Attenuated Vaccines].
Inform patients that VIGIV is prepared from human plasma. Products made from human plasma may contain infectious agents such as viruses that can cause disease. The risk that such products will transmit an infectious agent has been reduced by screening plasma donors for prior exposure to certain viruses, by testing for the presence of certain current virus infections, and by inactivating and/or removing certain viruses during manufacturing. Despite these measures, such products can still potentially transmit disease. There is also the possibility that unknown infectious agents may be present in such products [see 5.9 Transmission of Infectious Agents from Human Plasma]

Manufactured by:

Emergent BioSolutions Canada Inc.
155 Innovation Drive
Winnipeg, MB CanadaR3T 5Y3

Principal Display Panel — Carton Label

C:\Users\garcian.EMERGENT\Desktop\Vig Carton label.png
(click image for full-size original)

Principal Display Panel — Vial Label

C:\Users\garcian.EMERGENT\Desktop\VIG 20ml US vial label.png
(click image for full-size original)
CNJ-016 vaccinia immune globulin (human) injection
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:60492-0173
Route of Administration INTRAVENOUS DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
HUMAN VACCINIA VIRUS IMMUNE GLOBULIN (HUMAN VACCINIA VIRUS IMMUNE GLOBULIN) HUMAN VACCINIA VIRUS IMMUNE GLOBULIN 1 [iU] in 1 mL
Inactive Ingredients
Ingredient Name Strength
MALTOSE, UNSPECIFIED FORM
POLYSORBATE 80
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:60492-0173-2 24 VIAL, SINGLE-USE in 1 CARTON contains a VIAL, SINGLE-USE (60492-0173-1)
1 NDC:60492-0173-1 12 mL in 1 VIAL, SINGLE-USE This package is contained within the CARTON (60492-0173-2)
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
BLA BLA125109 05/01/2005
Labeler — Emergent BioSolutions Canada Inc. (203508049)

Revised: 05/2019 Emergent BioSolutions Canada Inc.

Page 3 of 3 1 2 3

DrugInserts.com provides trustworthy package insert and label information about marketed drugs as submitted by manufacturers to the US Food and Drug Administration. Package information is not reviewed or updated separately by DrugInserts.com. Every individual package label entry contains a unique identifier which can be used to secure further details directly from the US National Institutes of Health and/or the FDA.

As the leading independent provider of trustworthy medication information, we source our database directly from the FDA's central repository of drug labels and package inserts under the Structured Product Labeling standard. Our material is not intended as a substitute for direct consultation with a qualified health professional.

Terms of Use | Copyright © 2022. All Rights Reserved.