GAMMAGARD LIQUID is an immune globulin infusion (human) indicated for the treatment of Primary Immunodeficiency (PI) in adult and pediatric patients two years of age or older.
GAMMAGARD LIQUID – intravenous and subcutaneous administration1
What is the pH of GAMMAGARD LIQUID?
GAMMAGARD LIQUID has a pH of 4.6 to 5.1.1 Studies have shown that low-pH IVIG preparations are rapidly neutralized by blood. When a low pH solution enters the vein, the blood dilutes and reduces the acidity of the solution to a tolerable level.2
What is osmolality?
The term osmolality is used to describe the number of particles in a solution, or solute concentration. Osmolality is the concentration of a solution expressed in osmoles of solute particles per kilogram of solvent (mOsmol/kg).2 The osmolality of GAMMAGARD LIQUID is 240-300 mOsmol/kg, which is similar to physiological osmolality of 285 to 295 mOsmol/kg.1
How should GAMMAGARD LIQUID be stored?
GAMMAGARD LIQUID can be stored for 36 months at refrigerated temperature 2°-8°C (36°-46°F) or for 12 months at room temperature 25°C (77°F) within the first 24 months of the date of processing. After 24 months from date of manufacture, the product cannot be stored at room temperature. The new expiration date must be recorded on the package when the product is transferred to room temperature. DO NOT FREEZE.
Example 1: If the product is taken out of the refrigerator after 3 months from date of manufacture, it can be stored for 12 months at room temperature. Total storage time is 15 months.
Example 2: If the product is taken out of the refrigerator after 21 months from the date of manufacture, it can be stored for 3 months at room temperature. Total storage time is 24 months.1
Is using an administration set with a filter required for infusion of GAMMAGARD LIQUID?
An in-line filter is optional for GAMMAGARD LIQUID. GAMMAGARD LIQUID is not supplied with an administration set.1
Why is the rate of infusion important to consider?
The rate of infusion is an important variable that could influence the occurrence of adverse reactions.3 Certain adverse reactions such as headaches, flushing and changes in pulse rate and blood pressure may be related to the rate of the infusion. Slow or stop infusion if adverse reactions occur. If symptoms subside promptly, the infusion may be resumed at a lower rate that does not result in recurrence of the symptoms.1
For patients at risk of renal dysfunction or thrombotic events, administer GAMMAGARD LIQUID at the minimum infusion rate practicable.1 In such cases, the maximal rate should be less than 3.3 mg/kg/min (<2 mL/kg/hr), and consider discontinuation of administration if renal function deteriorates.
Adverse reactions may occur more frequently in patients receiving immune globulin for the first time, upon switching brands or if there has been a long interval since the previous infusion.4 In such cases, start at lower infusion rates and gradually increase as tolerated.1
What steps are taken to insure the safety of GAMMAGARD LIQUID?
GAMMAGARD LIQUID is manufactured from large pools of human plasma. IgG preparations are purified from plasma pools using a modified Cohn-Oncley cold ethanol fractionation process, as well as cation and anion exchange chromatography.
Screening against potentially infectious agents begins with the donor selection process and continues throughout plasma collection and plasma preparation. Each individual plasma donation used in the manufacture of GAMMAGARD LIQUID is collected only at FDA approved blood establishments and is tested by FDA licensed serological tests for Hepatitis B Surface Antigen (HBsAg), and for antibodies to Human Immunodeficiency Virus (HIV-1/HIV-2) and Hepatitis C Virus (HCV) in accordance with U.S. regulatory requirements. As an additional safety measure, mini-pools of the plasma are tested for the presence of HIV-1 and HCV by FDA licensed Nucleic Acid Testing (NAT) and found to be negative.
To further improve the margin of safety, three dedicated, independent and effective virus inactivation/removal steps have been integrated into the manufacturing and formulation processes, namely solvent/detergent (S/D) treatment,5 35 nm nanofiltration, and a low pH incubation at elevated temperature 30°C to 32°C. The S/D process includes treatment with an organic mixture of tri-n-butyl phosphate, octoxynol 9 and polysorbate 80 at 18°C to 25°C for a minimum of 60 minutes.
In vitro virus spiking studies have been used to validate the capability of the manufacturing process to inactivate and remove viruses. To establish the minimum applicable virus clearance capacity of the manufacturing process, these virus clearance studies were performed under extreme conditions (e.g., at minimum S/D concentrations, incubation time and temperature for the S/D treatment).
Virus clearance studies for GAMMAGARD LIQUID performed in accordance with good laboratory practices have demonstrated that:
- S/D treatment inactivates the lipid-enveloped viruses investigated to below detection limits within minutes.
- 35 nm nanofiltration removes lipid-enveloped viruses to below detection limits and reduces the non-lipid enveloped viruses HAV and B19V. As determined by a polymerase chain reaction assay, nanofiltration reduced B19V by a mean log10 reduction factor of 4.8 genome equivalents.
- Treatment with low pH at elevated temperature of 30°C to 32°C inactivates lipid enveloped viruses and encephalomyocarditis virus (EMCV, model for HAV) to below detection limits, and reduces mice minute virus (MMV, model for B19V).
As with all plasma-derived therapeutics, the potential to transmit infectious agents cannot be totally eliminated. GAMMAGARD LIQUID is made from human plasma. It may carry a risk of transmitting infectious agents, eg, viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent, and theoretically, the Creutzfeldt-Jakob disease (CJD) agent.1
What are the most common adverse reactions observed with intravenous administration of GAMMAGARD LIQUID?
In the phase III, multicenter, pivotal clinical trial, adverse reactions occurring in ≥5% of study subjects (rate by infusion), were1,a: headache (5%), pyrexia (1%), fatigue (1%), rigors (1%), nausea (1%), chills (1%), dizziness (0.4%), vomiting (0.3%), migraine (1%), pain in extremity (1%), urticaria (0.4%), cough (0.2%), pruritus (0.2%), rash (0.2%), and tachycardia (0.2%).
There were 16 severe, non-serious adverse reactions.b All of the nonserious adverse reactions were transient, did not lead to hospitalization, and resolved without complication.
Two serious events (two events of aseptic meningitis in one patient) were deemed to be possibly related to the infusion of GAMMAGARD LIQUID.1
a Excluding infections
b Mild adverse reactions were defined as transient discomfort that resolves spontaneously or with minimal intervention; moderate adverse reactions were defined as limited impairment of function and resolves spontaneously or with minimal intervention with no sequelae; severe adverse reactions were defined as marked impairment of function or can lead to temporary inability to resume normal life pattern; requires prolonged intervention or results in sequelae.
Can GAMMAGARD LIQUID 10% be diluted to a 5% concentration?
GAMMAGARD LIQUID is available as a 10% solution. If dilution is preferred, GAMMAGARD LIQUID may be diluted with 5% dextrose in water (D5W). Normal saline (NS) should not be used as a diluent. The infusion line may be flushed with 0.9% Sodium Chloride.1
What is the recommended rate of infusion when giving a patient GAMMAGARD LIQUID for the first time?
During the pivotal clinical study, GAMMAGARD LIQUID was infused at the initial rate of 0.5 mL/kg/hour (0.8 mg/kg/minute). The rate was gradually increased every 30 minutes to a rate of 5 mL/kg/hour (8.0 mg/kg/minute) if it was well tolerated. It is recommended that patients who are judged to be at risk of renal dysfunction or thrombotic complications be gradually titrated (compare to PI) to a more conservative maximal rate of less than 3.3 mg IgG/kg/minute (2 mL/kg/hour).
- Ensure that patients with pre-existing renal insufficiency are not volume depleted; discontinue GAMMAGARD LIQUID if renal function deteriorates.
- For patients at risk of renal dysfunction or thrombotic events, administer GAMMAGARD LIQUID at the minimum infusion rate practicable.1
What are the most common adverse reactions observed with subcutaneous administration of GAMMAGARD LIQUID?
In the pivotal clinical study, adverse reactionsa occurring in ≥ 5% of study subjects were: local infusion site reactions, such as swelling, redness, or pain (2.7% of infusions), headache (0.9%), increased heart rate (0.4%), fatigue (0.3%), fever (0.3%), increased systolic blood pressure (0.3%), and upper abdominal pain (0.2%).1
a Excluding infections
When should the first subcutaneous dose of GAMMAGARD LIQUID be administered?
Start the initial subcutaneous dose approximately one week after the last intravenous infusion in a patient who has been on stable intravenous therapy.1
What are the recommendations for selecting subcutaneous infusion sites?1
Suggested areas for subcutaneous infusion of GAMMAGARD LIQUID are abdomen, thighs, upper arms, or lower back. Infusion sites should be at least two inches apart, avoiding bony prominences. Rotate sites each week. The number of simultaneous sites should be limited to 8 and can be facilitated by use of a multi-needle administration set.1
What is the recommended volume per site?
The recommended maximum volume is 30 mL/site for patients weighing 40 kg (88 lbs) or more and 20 mL/site for patients under 40 kg (88 lbs). The weekly dose (mL) should be divided by 30 or 20, based on patient weight above, to determine the number of sites required.1
What is the recommended rate of infusion?
Patients 40 kg (88 lbs) and greater: For the first infusion, the recommended maximum rate of infusion of GAMMAGARD LIQUID is 20 mL/hr/site. For subsequent infusions, the flow rate can be adjusted as tolerated to a maximum of 30 mL/hr/site. If multiple sites are used, the rate set on the pump should be the rate per site multiplied by the number of sites (e.g., 30 mL × 4 sites = 120 mL/hr). The number of simultaneous sites should be limited to 8, or maximum infusion rate of 240 mL/hr.
Patients under 40 kg (88 lbs): For the first infusion, the recommended maximum rate of infusion of GAMMAGARD LIQUID is 15 mL/hr/site. For subsequent infusions, the flow rate can be adjusted to a maximum of 20 mL/hr/site. If multiple sites are used, the rate set on the pump should be the rate per site multiplied by the number of sites (e.g., 20 mL × 3 sites = 60 mL/hr). The number of simultaneous sites should be limited to 8, or maximum infusion rate of 160 mL/hr.1
What is the recommended initial subcutaneous dose of GAMMAGARD LIQUID for a patient who has been on intravenous immunoglobulin?
The recommended starting subcutaneous dose of GAMMAGARD LIQUID is:
# of weeks between intravenous doses
Adjust dose according to IgG levels and clinical response, as the frequency and dose of immunoglobulin may vary from patient to patient. The patient’s clinical response should be the primary consideration in dose adjustment.1
GAMMAGARD S/D [Immune Globulin Intravenous (Human)]
Is using an administration set with a filter required for infusion of GAMMAGARD S/D?
Yes. GAMMAGARD S/D is supplied with an administration set which contains an integral airway and a 15 micron filter, along with directions for use. If another administration set is used, ensure that the set contains a similar filter.6
Will GAMMAGARD S/D still be available for patients with IgA sensitivity?
In order to simplify the process for patients, as well as healthcare providers and pharmacists like you, we no longer require an application for access to GAMMAGARD S/D with IgA < 1µg/mL in a 5% solution. Moving forward, please call Baxter Customer Service at 1-800-423-2090 to place your orders as you do for other BioScience products.
GAMMAGARD LIQUID [Immune Globulin Infusion (Human)] 10%
GAMMAGARD LIQUID is indicated as replacement therapy for primary humoral immunodeficiency (PI) in adult and pediatric patients two years of age or older. This includes, but is not limited to, common variable immunodeficiency (CVID), X-linked agammaglobulinemia, congenital agammaglobulinemia, Wiskott-Aldrich syndrome, and severe combined immunodeficiencies.
GAMMAGARD LIQUID is indicated as a maintenance therapy to improve muscle strength and disability in adult patients with Multifocal Motor Neuropathy (MMN).
Important Risk Information
WARNING: THROMBOSIS, RENAL DYSFUNCTION and ACUTE RENAL FAILURE
- Thrombosis may occur with immune globulin products, including GAMMAGARD LIQUID. Risk factors may include advanced age, prolonged immobilization, hypercoagulable conditions, history of venous or arterial thrombosis, use of estrogens, indwelling vascular catheters, hyperviscosity, and cardiovascular risk factors. Thrombosis may occur in the absence of known risk factors.
- Renal dysfunction, acute renal failure, osmotic nephropathy, and death may occur with immune globulin intravenous (IGIV) products in predisposed patients. Renal dysfunction and acute failure occur more commonly in patients receiving IGIV products containing sucrose. GAMMAGARD LIQUID does not contain sucrose.
- For patients at risk of thrombosis, administer GAMMAGARD LIQUID at the minimum dose and infusion rate practicable. Ensure adequate hydration in patients before administration. Monitor for signs and symptoms of thrombosis and assess blood viscosity in patients at risk of hyperviscosity.
- GAMMAGARD LIQUID is contraindicated in patients who have a history of anaphylactic or severe systemic hypersensitivity reactions to the administration of human immune globulin. GAMMAGARD LIQUID is contraindicated in IgA-deficient patients with antibodies to IgA and a history of hypersensitivity.
WARNINGS and PRECAUTIONS
- HYPERSENSITIVITY: IgA deficient patients with antibodies to IgA are at greater risk of developing potentially severe hypersensitivity and anaphylactic reactions. In case of hypersensitivity, discontinue GAMMAGARD LIQUID infusion immediately and institute appropriate treatment.
- RENAL DYSFUNCTION/FAILURE: Monitor renal function, including blood urea nitrogen, serum creatinine, and urine output in patients at risk of acute renal failure. Ensure that patients with pre-existing renal insufficiency are not volume depleted. For patients at risk for renal dysfunction or thrombotic events, administer GAMMAGARD LIQUID at the minimum infusion rate practicable.
- Hyperproteinemia, increased serum viscosity, and hyponatremia may occur in patients receiving GAMMAGARD LIQUID.
- THROMBOSIS: Thrombosis may occur following treatment with immune globulin products, including GAMMAGARD LIQUID. Monitor for signs and symptoms of thrombosis and assess blood viscosity in patients at risk for hyperviscosity.
- Aseptic Meningitis Syndrome (AMS) may occur with IGIV treatment, and has been reported with intravenous (IV) use of GAMMAGARD LIQUID. AMS may occur more frequently with high dose (2 g/kg) IGIV treatment and/or rapid infusion of IGIV.
- Hemolytic anemia can develop subsequent to GAMMAGARD LIQUID treatment due to enhanced RBC sequestration. Risk factors may include: high doses (e.g., ≥2 g/kg cumulative dose), non-O blood group, and underlying inflammation. Monitor patients for clinical signs and symptoms of hemolysis and delayed hemolytic anemia.
- Transfusion-Related Acute Lung Injury (TRALI): Non-cardiogenic pulmonary edema has been reported in patients following treatment with IGIV products, including GAMMAGARD LIQUID. Monitor patients for pulmonary adverse reactions.
- GAMMAGARD LIQUID is made from human plasma. It may carry a risk of transmitting infectious agents, e.g., viruses, and theoretically, the Creutzfeldt-Jakob disease (CJD) agent. No confirmed cases of viral transmission or CJD have been associated with GAMMAGARD LIQUID.
- Passive transfer of antibodies may transiently impair the immune responses to live attenuated virus vaccines such as mumps, rubella, varicella, and measles. It can also lead to a misinterpretation of serological testing.
The serious adverse reaction that occurred during the PI (IV administration) clinical trials was aseptic meningitis. No serious adverse reactions were observed during the PI subcutaneous (SC) administration clinical trial. The serious adverse reactions in the MMN (IV administration) clinical trial were pulmonary embolism and blurred vision. The most common adverse reactions observed in ≥ 5% of patients in the clinical trials were:
PI (IV administration): Headache, fatigue, pyrexia, nausea, chills, rigors, pain in extremity, diarrhea, migraine, dizziness, vomiting, cough, urticaria, asthma, pharyngolaryngeal pain, rash, arthralgia, myalgia, oedema peripheral, pruritus, and cardiac murmur.
PI (SC administration): Infusion site (local) event, headache, fatigue, heart rate increased, pyrexia, abdominal pain upper, nausea, vomiting, asthma, blood pressure systolic increased, diarrhea, ear pain, aphthous stomatitis, migraine, oropharyngeal pain, and pain in extremity.
MMN (IV administration): Headache, chest discomfort, muscle spasms, muscular weakness, nausea, oropharyngeal pain, and pain in extremity.
Please see the accompanying full Prescribing Information, including Boxed Warning.
Send adverse reactions to:
Phone: 1-847-948-4133 (Toll Free 1-800-759-1801)
Voice mail: 1-847-948-4977 (Toll Free 1-866-888-2472)
- GAMMAGARD LIQUID [Immune Globulin Infusion (Human)] 10% [package insert]. Westlake Village, CA. Baxter Healthcare Corporation.
- Lemm G. Composition and properties of IVIG preparations that affect tolerability and therapeutic efficacy. Neurology. 2002;59(6):S28-S32.
- Greenbaum BH. Differences in immunoglobulin preparations for intravenous use: a comparison of six products. Am J Pediatr Hematol. 1990;12(4):490-496.
- Bonilla FA, Bernstein IL, Khan DA, Ballas ZK, Chinen J, Frank MM, Kobrynski LJ, Levinson AI, Mazer B, Nelson RP Jr, Orange JS, Routes JM, Shearer WT, Sorensen RU. Practice parameter for the diagnosis and management of primary immunodeficiency [published correction appears in Ann Allergy Asthma Immunol. 2006;96(3):504]. Ann Allergy Asthma Immunol. 2005;94(suppl 1):S1-63.
- Kreil TR, Berting A, Kistner O, Kindermann J. West Nile virus and the safety of plasma derivatives: verification of high safety margins, and the validity of 731 predictions based on model virus data. Transfusion 2003;43(8):1023-1028.
- GAMMAGARD S/D [Immune Globulin Intravenous (Human)] [package insert]. Westlake Village, CA. Baxter Healthcare Corporation.; December 2011.
- GAMMAGARD S/D [Immune Globulin Intravenous (Human)] IgA less than 1 µg/mL in a 5% solution [package insert]. Westlake Village, IL. Baxter Healthcare Corporation.; December 2011.
Clinical Study Video
Watch Dr. Richard Wasserman, M.D. – lead investigator of the clinical trial – present an overview and key highlights of the pivotal clinical study of the subcutaneous administration of GAMMAGARD LIQUID.
Is IV or SC right for your patient?
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