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 IV 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 [Immune Globulin Infusion (Human)] 10% can be stored for 36 months at refrigerated temperature 2°-8° C (36°-46°F) or for 24 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. Do not use past the applicable expiration date.1
- Example 1: If the product is taken out of the refrigerator after 2 months from date of manufacture, it can be stored for 22 months at room temperature. Total storage time is 24 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 thrombosis or renal dysfunction, administer GAMMAGARD LIQUID [Immune Globulin Infusion (Human)] 10% at the minimum dose and infusion rate practicable.1 In patients who are at risk of developing renal dysfunction, the maximal rate should be less than 3.3 mg/kg/min (<2 ml />kg/hr), and consider discontinuation of infusion 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 increases as tolerated.
What steps are taken to improve the margin of safety of
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 [Immune Globulin Infusion (Human)] 10% 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 35nm nanofiltration, and a low pH incubation at elevated temperature 30°C-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 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:1
- S/D treatment inactivates the lipid-enveloped viruses investigated to below detection limits within minutes.1
- 35 nm nanofiltration removes lipid-enveloped viruses to below detection limits and reduces the non-lipid enveloped viruses Hepatitis A virus (HAV) and B19 virus (B19V). As determined by a polymerase chain reaction assay, nanofiltration reduced B19V by a mean log10 reduction factor of 4.8 genome equivalents.1
- 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).1
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, e.g., viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent, and theoretically, the Creutzfeldt-Jakob disease agent.1
What are the most common adverse reactions observed with intravenous administration of GAMMAGARD LIQUID?
In the phase III, multicenter, clinical trial, adverse reactions occurring in ≥5% of study subjects (rate by infusion), were1,a: headache (5.2%), fatigue (1.8%), pyrexia (1.5%), nausea (0.9%), chills (0.8%), rigors (0.8%), pain in extremity (0.7%).
This is not a complete list. Please see GAMMAGARD LIQUID Full Prescribing Information for more details
There were 400 non-serious adverse reactions. Of these, 217 were rated as mild (transient discomfort that resolves spontaneously or with minimal intervention), 164 were rated as moderate (limited impairment of function and resolves spontaneously or with minimal intervention with no sequelae), and 19 were rated as severe (marked impairment of function or can lead to temporary inability to resume normal life pattern; requires prolonged intervention or results in sequelae).1
Fifteen adverse reactions in 8 subjects were serious. Of these, two episodes of aseptic meningitis in one patient were deemed possibly related to the infusion of GAMMAGARD LIQUID [Immune Globulin Infusion (Human)] 10%.1
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 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 minute to a rate of 5 mL/kg/hour (8.0 mg/kg/minute) if it was well tolerated. For patients at risk of thrombosis, administer GAMMAGARD LIQUID at the minimum dose and infusion rate practicable. It is recommended that patients at risk of renal dysfunction 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 adequate hydration in patients before administration. Monitor for signs and symptoms of thrombosis and assess blood viscosity in patients at risk of hyperviscosity.
- Ensure that patients with pre-existing renal insufficiency are not volume depleted; discontinue GAMMAGARD LIQUID [Immune Globulin Infusion (Human)] 10% 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 clinical study, adverse reactionsa occurring in the ≥5% of study subjects were: local infusion site reactions, such as swelling, redness, or pain (2.4% of infusions), headache (1.4%), fatigue (0.5%), heart rate increase (0.5%), pyrexia (0.5%), and upper abdominal pain (0.4%).1
This is not a complete list. Please see GAMMAGARD LIQUID Full Prescribing Information for more details.
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 treatment.1
What are the recommendations for selecting subcutaneous infusion sites?1
Suggested areas for subcutaneous infusion of GAMMAGARD LIQUID [Immune Globulin Infusion (Human)] 10% 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 if 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 x 4 sites = 120 mL/hr). The number of simultaneous sites should be limited to 8, or maximum infusion rate of 160 mL/hr or 240 mL/hr depending on the patient's weight.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:
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
To see patient examples, visit our Dosing page.
GAMMAGARD S/D [Immune Globulin Intravenous (Human)] IgA less than 1 μg/mL in a 5% solution
Is using an administration set with a filter required for infusion of GAMAMGARD 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 IgA less than 1 μg/mL in a 5% solution still be available for patients?
Shire will continue to provide GAMMAGARD S/D for patients who require a low IgA content in their IV treatment.6
Severe hypersensitivity reactions and anaphylactic reactions with a fall in blood pressure have occurred in patients receiving GAMMAGARD S/D, including patients who tolerated previous treatments with GAMMAGARD S/D, even though it contains low levels of IgA.
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 < 1 μg/mL in a 5% solution. Moving forward, please call Shire Customer Service at 1-800-423-2090 to place your orders as you do for other Immunoglobulin products.
References: 1. GAMMAGARD LIQUID [Immune Globulin Infusion (Human)] 10% [Prescribing Information]. Westlake Village, CA: Baxalta US Inc. 2. Lemm G. Composition and properties of IVIG preparations that affect tolerability and therapeutic efficacy. Neurology. 2002;59(6):S28-S32. 3. Greenbaum BH. Differences in immunoglobulin preparations for intravenous use: a comparison of six products. Am J Pediatr Hematol. 1990;12(4):490-496. 4. 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. 5. 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. 6. GAMMAGARD S/D [Immune Globulin Intravenous (Human)] IgA less than 1 µg/mL in a 5% solution [Prescribing Information]. Westlake Village, IL. Baxter Healthcare Corporation. April 2014.
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