NDC 13533-634 Hypertet

Tetanus Immune Globulin (human)

NDC Product Code 13533-634

NDC CODE: 13533-634

Proprietary Name: Hypertet What is the Proprietary Name?
The proprietary name also known as the trade name is the name of the product chosen by the medication labeler for marketing purposes.

Non-Proprietary Name: Tetanus Immune Globulin (human) What is the Non-Proprietary Name?
The non-proprietary name is sometimes called the generic name. The generic name usually includes the active ingredient(s) of the product.

Product Characteristics

Color(s):
YELLOW (C48330 - COLORLESS OR PALE YELLOW OR LIGHT BROWN)

NDC Code Structure

  • 13533 - Grifols Usa, Llc

NDC 13533-634-02

Package Description: 1 SYRINGE, GLASS in 1 BOX > 1 mL in 1 SYRINGE, GLASS (13533-634-20)

NDC Product Information

Hypertet with NDC 13533-634 is a a plasma derivative product labeled by Grifols Usa, Llc. The generic name of Hypertet is tetanus immune globulin (human). The product's dosage form is injection and is administered via intramuscular form. The RxNorm Crosswalk for this NDC code indicates multiple RxCUI concepts are associated to this product: 1087391 and 1087395.

Dosage Form: Injection - A sterile preparation intended for parenteral use; five distinct classes of injections exist as defined by the USP.

Product Type: Plasma Derivative What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

Hypertet Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.


Inactive Ingredient(s)

About the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • GLYCINE (UNII: TE7660XO1C)
  • WATER (UNII: 059QF0KO0R)

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Intramuscular - Administration within a muscle.

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Grifols Usa, Llc
Labeler Code: 13533
FDA Application Number: BLA101142 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: BLA - A product marketed under an approved Biologic License Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 08-14-1996 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2021 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N - NO What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA"s requests for correction to deficient or non-compliant submissions ("Y"), or because the listing certification is expired ("E"), or because the listing data was inactivated by FDA ("I"). Values = "Y", "N", "E", or "I".

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Hypertet Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

Description

  • Tetanus Immune Globulin (Human) — HyperTET® is a clear or slightly opalescent, and colorless or pale yellow or light brown sterile solution of human tetanus immune globulin for intramuscular administration. HyperTET contains no preservative.  HyperTET is prepared from pools of human plasma collected from healthy donors by a combination of cold ethanol fractionation, caprylate precipitation and filtration, caprylate incubation, anion exchange chromatography, nanofiltration and low pH incubation. HyperTET consists of a 15% to 18% protein solution at a pH of 4.1 to 4.8 in 0.16 M to 0.26 M glycine. The product is standardized against the U.S. Standard Antitoxin and the U.S. Control Tetanus Toxin and contains not less than 250 tetanus antitoxin units per 1 mL.When medicinal biological products are administered, the risk of 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 epidemiological surveillance of the donor population and selection of individual donors by medical interview; testing of individual donations and plasma pools; and the presence in the manufacturing processes of steps with demonstrated capacity to inactivate/remove pathogen.In the manufacturing process of HyperTET, there are several steps with the capacity for viral inactivation or removal.(1) The main steps of the manufacturing process that contribute to the virus clearance capacity are as follows:Caprylate precipitation/depth filtrationCaprylate incubationDepth filtrationColumn chromatographyNanofiltrationLow pH final container incubationTo provide additional assurance of the pathogen safety of the final product, the capacity of the HyperTET manufacturing process to remove and/or inactivate viruses has been demonstrated by laboratory spiking studies on a scaled down process model using a wide range of viruses with diverse physicochemical properties.The caprylate/chromatography manufacturing process was also investigated for its capacity to decrease the infectivity of an experimental agent of transmissible spongiform encephalopathy (TSE), considered as a model for the variant Creutzfeldt-Jakob disease (vCJD), and Creutzfeldt-Jakob disease (CJD) agents.(1) These studies provide reasonable assurance that low levels of vCJD/CJD agent infectivity, if present in the starting material, would be removed by the caprylate/chromatography manufacturing process.

Clinical Pharmacology

The occurrence of tetanus in the United States has decreased dramatically from 560 reported cases in 1947, when national reporting began, to a record low of 48 reported cases in 1987.(2) The decline has resulted from widespread use of tetanus toxoid and improved wound management, including use of tetanus prophylaxis in emergency rooms.(3)HyperTET supplies passive immunity to those individuals who have low or no immunity to the toxin produced by the tetanus organism, Clostridium tetani. The antibodies act to neutralize the free form of the powerful exotoxin produced by this bacterium. Historically, such passive protection was provided by antitoxin derived from equine or bovine serum; however, the foreign protein in these heterologous products often produced severe allergic manifestations, even in individuals who demonstrated negative skin and/or conjunctival tests prior to administration. Estimates of the frequency of these foreign protein reactions following antitoxin of equine origin varied from 5%–30%.(4-7) If passive immunization is needed, human tetanus immune globulin (TIG) is the product of choice. It provides protection longer than antitoxin of animal origin and causes few adverse reactions.(3)Several studies suggest the value of human tetanus antitoxin in the treatment of active tetanus.(8,9) In 1961 and 1962, Nation et al,(8) using Hyper-Tet treated 20 patients with tetanus using single doses of 3,000 to 6,000 antitoxin units in combination with other accepted clinical and nursing procedures. Six patients, all over 45 years of age, died of causes other than tetanus. The authors felt that the mortality rate (30%) compared favorably with their previous experience using equine antitoxin in larger doses and that the results were much better than the 60% national death rate for tetanus reported from 1951 to 1954.(10) Blake et al,(11) however, found in a data analysis of 545 cases of tetanus reported to the Centers for Disease Control from 1965 to 1971 that survival was no better with 8,000 units of TIG than with 500 units; however, an optimal dose could not be determined.Serologic tests indicate that naturally acquired immunity to tetanus toxin does not occur in the United States. Thus, universal primary vaccination, with subsequent maintenance of adequate antitoxin levels by means of appropriately timed boosters, is necessary to protect persons among all age groups. Tetanus toxoid is a highly effective antigen; a completed primary series generally induces protective levels of serum antitoxin that persist for ≥10 years.(3)Passive immunization with HyperTET may be undertaken concomitantly with active immunization using tetanus toxoid in those persons who must receive an immediate injection of tetanus antitoxin and in whom it is desirable to begin the process of active immunization. Based on the work of Rubbo,(12) McComb and Dwyer,(13) and Levine et al,(14) the physician may thus supply immediate passive protection against tetanus, and at the same time begin formation of active immunization in the injured individual which upon completion of a full toxoid series will preclude future need for antitoxin.Peak blood levels of IgG are obtained approximately 2 days after intramuscular injection. The half-life of IgG in the circulation of individuals with normal IgG levels is approximately 23 days.(15)In a clinical study in 12 healthy human adults receiving another hyperimmune immune globulin product, Rabies Immune Globulin (Human), HyperRAB® , prepared by the same manufacturing process, detectable passive antibody titers were observed in the serum of all subjects by 24 hours post injection and persisted through the 21 day study period.

Indications And Usage

HyperTET is indicated for prophylaxis against tetanus following injury in patients whose immunization is incomplete or uncertain (see below). It is also indicated, although evidence of effectiveness is limited, in the regimen of treatment of active cases of tetanus.(8,9,16)A thorough attempt must be made to determine whether a patient has completed primary vaccination. Patients with unknown or uncertain previous vaccination histories should be considered to have had no previous tetanus toxoid doses. Persons who had military service since 1941 can be considered to have received at least one dose, and although most of them may have completed a primary series of tetanus toxoid, this cannot be assumed for each individual. Patients who have not completed a primary series may require tetanus toxoid and passive immunization at the time of wound cleaning and debridement.(3)The following table is a summary guide to tetanus prophylaxis in wound management:Guide to Tetanus Prophylaxis in Wound Management(3 )History of Tetanus Immunization (Doses)Clean, Minor WoundsAll Other WoundsSuch as, but not limited to, wounds contaminated with dirt, feces, soil, and saliva; puncture wounds; avulsions; and wounds resulting from missiles, crushing, burns and frostbite.Td Adult type tetanus and diphtheria toxoids. If the patient is less than 7 years old, DT or DTP is preferred to tetanus toxoid alone. For persons ≥7 years of age, Td is preferred to tetanus toxoid alone. (see Dosage and Administration)TIGTetanus Immune Globulin (Human).TdTIG    Uncertain or less than 3YesNoYesYes    3 or moreIf only three doses of fluid tetanus toxoid have been received, a fourth dose of toxoid, preferably an adsorbed toxoid, should be given.NoYes if more than 10 years since the last dose.NoNoYes if more than 5 years since the last dose. (More frequent boosters are not needed and can accentuate side effects).No

Contraindications

None known.

Warnings

HyperTET is made from human plasma. Products made from human plasma may contain infectious agents, such as viruses, and, theoretically, the Creutzfeldt-Jakob Disease (CJD) agent 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. 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. Individuals who receive infusions of blood or plasma products may develop signs and/or symptoms of some viral infections, particularly hepatitis C. 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 physician should discuss the risks and benefits of this product with the patient, before prescribing or administering it to the patient.HyperTET should be given with caution to patients with a history of prior systemic allergic reactions following the administration of human immunoglobulin preparations.In patients who have severe thrombocytopenia or any coagulation disorder that would contraindicate intramuscular injections, HyperTET should be given only if the expected benefits outweigh the risks.

General

HyperTET should not be given intravenously. Intravenous injection of immunoglobulin intended for intramuscular use can, on occasion, cause a precipitous fall in blood pressure, and a picture not unlike anaphylaxis. Injections should only be made intramuscularly and care should be taken to draw back on the plunger of the syringe before injection in order to be certain that the needle is not in a blood vessel. Intramuscular injections are preferably administered in the deltoid muscle of the upper arm or lateral thigh muscle. The gluteal region should not be used as an injection site because of the risk of injury to the sciatic nerve.(17)Chemoprophylaxis against tetanus is neither practical nor useful in managing wounds. Wound cleaning, debridement when indicated, and proper immunization are important. The need for tetanus toxoid (active immunization), with or without TIG (passive immunization), depends on both the condition of the wound and the patient’s vaccination history. Rarely has tetanus occurred among persons with documentation of having received a primary series of toxoid injections.(3) See table under See table under INDICATIONS AND USAGE.Skin tests should not be done. The intradermal injection of concentrated IgG solutions often causes a localized area of inflammation which can be misinterpreted as a positive allergic reaction. In actuality, this does not represent an allergy; rather, it is localized tissue irritation. Misinterpretation of the results of such tests can lead the physician to withhold needed human antitoxin from a patient who is not actually allergic to this material. True allergic responses to human IgG given in the prescribed intramuscular manner are rare.Although systemic reactions to human immunoglobulin preparations are rare, epinephrine should be available for treatment of acute anaphylactic reactions.

Drug Interactions

Antibodies in immunoglobulin preparations may interfere with the response to live viral vaccines such as measles, mumps, polio, and rubella. Therefore, use of such vaccines should be deferred until approximately 3 months after Tetanus Immune Globulin (Human) — HyperTET® administration. No interactions with other products are known.

Pregnancy

Animal reproduction studies have not been conducted with HyperTET. It is also not known whether HyperTET can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. HyperTET should be given to a pregnant woman only if clearly needed.

Pediatric Use

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

Adverse Reactions

Slight soreness at the site of injection and slight temperature elevation may be noted at times. Sensitization to repeated injections of human immunoglobulin is extremely rare.In the course of routine injections of large numbers of persons with immunoglobulin there have been a few isolated occurrences of angioneurotic edema, nephrotic syndrome, and anaphylactic shock after injection.

Overdosage

Although no data are available, clinical experience with other immunoglobulin preparations suggests that the only manifestations would be pain and tenderness at the injection site.

Directions For Syringe Usage

  • Remove the prefilled syringe from the package. Lift syringe by barrel, not by plunger. Twist the plunger rod clockwise until the threads are seated. With the needle shield secured on the syringe tip, push the plunger rod forward a few millimeters to break any friction seal between the stopper and the glass syringe barrel. Remove the needle shield and expel air bubbles. [Do not remove the needle shield to prepare the product for administration until immediately prior to the anticipated injection time.] Proceed with hypodermic needle puncture. Aspirate prior to injection to confirm that the needle is not in a vein or artery. Inject the medication. Keeping your hands behind the needle, grasp the guard with free hand and slide forward toward needle until it is completely covered and guard clicks into place. If audible click is not heard, guard may not be completely activated. (See Diagrams A and B) Place entire prefilled glass syringe with guard activated into an approved sharps container for proper disposal. (See Diagram C) A number of factors could reduce the efficacy of this product or even result in an ill effect following its use. These include improper storage and handling of the product after it leaves our hands, diagnosis, dosage, method of administration, and biological differences in individual patients. Because of these factors it is important that this product be stored properly and that the directions be followed carefully during use.

How Supplied

HyperTET is supplied in 250 unit prefilled disposable syringes with attached needles. HyperTET contains no preservative and is not made with natural rubber latex.NDC NumberSize13533-634-02250 unit syringe

Storage

Store at 2–8°C (36–46°F). Solution that has been frozen should not be used.  Discard unused portion.

Caution

Rx onlyU.S. federal law prohibits dispensing without prescription.

References

  • Barnette D, Roth NJ, Hotta J, et al. Pathogen safety profile of a 10% IgG preparation manufactured using a depth filtration-modified process. Biologicals 2012;40:247-53.Tetanus — United States, 1987 and 1988, MMWR 39(3): 37-41, 1990.Diphtheria, Tetanus, and Pertussis: Recommendations for Vaccine Use and Other Preventive Measures. Recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR 40 (RR-10): 1-28, 1991.Moynihan NH: Tetanus prophylaxis and serum sensitivity tests. Br Med J 1:260-4, 1956.Scheibel I: The uses and results of active tetanus immunization. Bull WHO 13:381-94, 1955.Edsall G: Specific prophylaxis of tetanus. JAMA 171(4):417-27, 1959.Bardenwerper HW: Serum neuritis from tetanus antitoxin. JAMA 179(10):763-6, 1962.Nation NS, Pierce NF, Adler SJ, et al: Tetanus: the use of human hyperimmune globulin in treatment. Calif Med 98(6):305-6, 1963.Ellis M: Human antitetanus serum in the treatment of tetanus. Br Med J 1(5338):1123-6, 1963.Axnick NW, Alexander ER: Tetanus in the United States: A review of the problem. Am J Public Health 47(12):1493-1501, 1957.Blake PA, Feldman RA, Buchanan TM, et al: Serologic therapy of tetanus in the United States, 1965-1971. JAMA 235(1):42-4, 1976.Rubbo SD: New approaches to tetanus prophylaxis. Lancet 2(7461):449-53, 1966.McComb JA, Dwyer RC: Passive-active immunization with tetanus immune globulin (human). N Engl J Med 268(16):857-62, 1963.Levine L, McComb JA, Dwyer RC, et al: Active-passive tetanus immunization; choice of toxoid, dose of tetanus immune globulin and timing of injections. N Engl J Med 274(4):186-90, 1966.Waldmann TA, Strober W, Blaese RM: Variations in the metabolism of immunoglobulins measured by turnover rates. In Merler E (ed.): Immunoglobulins: biologic aspects and clinical uses. Washington, DC, Nat Acad Sci, 1970, p. 33-51.McCracken GH Jr., Dowell DL, Marshall FN: Double-blind trial of equine antitoxin and human immune globulin in tetanus neonatorum. Lancet 1(7710):1146-9, 1971.Recommendations of the Advisory Committee on Immunization Practices (ACIP) and the American Academy of Family Physicians (AAFP): General recommendations on immunization. MMWR 2002: 51(RR02), 1-36.Tetanus-Rates by year, United States, 1955-1984. Annual Summary 1984. MMWR 33 (54):61, 1986.Rev. 12/2020Grifols Therapeutics LLCResearch Triangle Park, NC 27709 USAU.S. License No. 18713059641

Package Label

Tetanus Immune Globulin (Human)HyperTET® 250 Units/ 1 mLSolution for Intramuscular Injection Contents: One single-dose disposable syringe with attached needle.Tetanus Immune Globulin (Human) is a sterile solution of immunoglobulin containing 15%–18% protein stabilized with 0.16 M to 0.26 M glycine. The pH is adjusted with sodium carbonate.The potency of each syringe is not less than 250 antitoxin units based on the U.S. Standard Antitoxin and the U.S. Control Tetanus Toxin.FOR INTRAMUSCULAR INJECTION ONLY. DO NOT GIVE INTRAVENOUSLY.Store at 2 to 8°C (36 to 46°F).Do not freeze.1 mL      1 mLNDC 13533-634-02GRIFOLSThe patient and physician should discuss the risks and benefits of this product. For complete dosage and administration information, read enclosed package insert.For directions for syringe usage, see enclosed package insert.Do not use if the syringe is prematurely engaged.Not returnable for credit or exchange.Rx onlyNot made with natural rubber latex.No preservativeThe potency of each syringe is not less than 250 antitoxin units based on the U.S. Standard Antitoxin and the U.S. Control Tetanus Toxin.Discard unused portion.1 mL       1 mLGrifols Therapeutics LLCResearch Triangle Park, NC 27709 USAU.S. License No. 1871Carton: 3056385GTIN 00313533634025LOT XXXXXXXXXX EXP DDMMMYYYY SN XXXXXXXXXXXXXXXXTetanus Immune Globulin (Human).HyperTET®    250 Units/1 mL●  One 1 mL Single DoseGrifols Therapeutics LLCResearch Triangle Park,NC 27709 USAU.S. License No. 1871The patient and physician should discuss the risks and benefits of this product. 3056220LotExp.

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