What Is Gammaplex and What Is It Used For?
Gammaplex is a highly purified human intravenous immunoglobulin G (IVIG). It is used to prevent infection in primary immunodeficiency diseases (PIDDs) and prevent bleeding in immune thrombocytopenic purpura (ITP). Gammaplex is provided as an intravenous liquid solution and is available at different concentrations.
What Is Gammaplex?
Gammaplex infusion is manufactured using plasma from paid, healthy US subjects. The plasmas of approximately 3,000 to 10,000 donors are used to obtain human immunoglobulin derivatives (1).
Gammaplex is available in two concentrations: 5% and 10% liquid high pure formulations (>95% for Gammaplex 5% and >98% for Gammaplex 10%) (2).
These formulations differ in the stabilizer that is utilized. For example, Gammaplex 10% is stabilized with glycine and doesn’t contain carbohydrate-reducing stabilizers, whereas Gammaplex 5% is stabilized with sorbitol.
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The distribution of IgG subclasses in Gammaplex products reflects that of normal plasma (3).
In addition, the IgA content is very low, reducing the risk of hypersensitivity reactions in IgA-deficient patients.
During Gammaplex treatment, anti-D and anti-A/anti-B hemagglutinin contents are very strictly controlled to reduce the risk of hemolytic reactions.
There is very low or undetectable procoagulant activity, as shown by testing multiple batches from the starting plasma pool to the final product.
Overview of IVIG Products
These products are different in many aspects such as:
- The manufacturing process
- The formulation (liquid versus dry powder)
- The stabilizer used
- Viral inactivation
- Volume load
- Sodium content
- Method of administration
Gamunex is given either intravenously (abbreviated as IVIG) or subcutaneously (abbreviated as SCIG), while Gammaplex is given only as an intravenous immunoglobulin IVIG infusion.
The IVIG products are formulated as either liquid (such as Gammaplex) or dry powder (lyophilized, like Gammagard S/D).
For the manufacturing process, immune globulin products differ in the isolation and purification of IgG, and the antibody fraction.
All these factors affect the final product’s shelf life, efficacy, and tolerability. As a result, certain products may be selected for a specific group of patients.
For example, patients with cardiovascular risk factors or small infants should be given products with low sodium content and osmolality (4).
Another example would be that patients with diabetes shouldn’t be given IVIG products that contain glucose, and those with preexisting renal conditions shouldn’t be given products that contain sucrose.
What Is Gammaplex Used For?
Gammaplex is an FDA-approved product for the management of primary humoral immunodeficiency diseases (PIDDs) in adults and pediatric patients 2 years of age and older.
In addition, Gammaplex is indicated for preventing bleeding in idiopathic thrombocytopenic purpura (ITP).
Immunodeficiency disorders result from the absence or dysfunction of a certain element of the immune system. Immunodeficiency disorders can be divided into two categories: primary or secondary.
The principal clinical manifestation of primary humoral immunodeficiency PI diseases is an increased risk of infection.
In fact, almost all patients suffered serious or unusual infections, and a large population of them reported suffering from permanent functional impairment (5).
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Primary Humoral Immunodeficiency (PI)
Primary immunodeficiency is subdivided into several types according to the dysfunctional element:
- T-cell deficiency
- B-cell deficiency
- Both T-cell and B-cell deficiency
- Complement deficiency
- Phagocyte deficiency
- Immunoglobulin A deficiency (6)
Primary Humoral Immunodeficiency often has an underlying genetic cause.
For example, in primary immunodeficiency, the B-cell deficiency is an X-linked disorder and is referred to as X- linked agammaglobulinemia (Bruton disease) (7).
Babies with X-linked agammaglobulinemia suffer from recurrent bacterial infections, including otitis media, bronchitis, septicemia, pneumonia, arthritis, and giardia lamblia, which causes intestinal malabsorption.
By administering intravenous immune globulins such as Gammaplex, patients with X- linked agammaglobulinemia can be kept alive by replacing low levels of immunoglobulins.
Another subcategory of primary humoral immunodeficiency are T-cell Immunodeficiencies, including Hyper-IgM syndrome, where immunoglobulin therapy is also recommended.
Gammaplex is also indicated for congenital agammaglobulinemia, Wiskott-Aldrich syndrome, and severe combined immunodeficiencies.
Chronic Immune Thrombocytopenic Purpura (ITP)
Immune thrombocytopenia purpura (ITP) is isolated thrombocytopenia (platelet count <100,000/microL) with normal white blood cells and normal hemoglobin. It occurs in the setting of a generalized purpuric rash as defined by the American Society of Hematology (8).
ITP is also known as idiopathic thrombocytopenic purpura or immune thrombocytopenic purpura.
According to lab tests, the white blood count, hemoglobin concentration, red cell indices, and differential white blood cells are usually normal. The only abnormality seen is a platelet count less than 100,000/microL (9).
The etiology of ITP includes the development of autoantibodies against platelet membrane proteins, leading to thrombocytopenia and an elevated risk of bleeding. ITP is an autoantibody-mediated disorder, usually mediated by immunoglobulin G.
The 2019 American Society of Hematology guidelines recommends the use of intravenous immunoglobulin (IVIG) for patients for whom corticosteroids are contraindicated or not preferred.
Researchers believe immune globulin intravenous human liquids such as Gammaplex raise platelet counts for patients with chronic immune thrombocytopenic purpura.
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Mechanism of Action of Gammaplex
In primary humoral immunodeficiency, Gammaplex acts as an IgG replacement therapy by replacing the low levels of opsonic and neutralizing IgG antibodies, thus boosting the immune system against pathogens and their toxins.
In chronic ITP, Gammaplex may downregulate antiplatelet antibody production and block Fc receptors, but the exact mechanism is still unclear (10).
The dosage of Gammaplex infusion varies according to the indication and the concentration administered.
Treatment of Primary Humoral Immunodeficiency
For the treatment of primary humoral immunodeficiency disease, the frequency and the dose of immunoglobulin may vary from patient to patient. This is because the half-life of IgG varies among patients.
The proper amount can be adjusted according to the patient’s clinical response.
However, according to the Gammaplex package insert, Gammaplex 5% (100 ml) is given intravenously at a dose of 300 to 800 mg/kg (6-16 mL/kg) every 3 to 4 weeks for managing PI.
Gammaplex 10% (50 ml) is administered intravenously at similar doses but this higher concentration allows a 34% reduction in infusion time without compromising safety and tolerability.
Treatment of Chronic Immune Thrombocytopenic Purpura
The recommended dose of GAMMAPLEX 5% for patients with ITP is 1 g/kg (20 mL/kg) on two consecutive days, providing a total dose of 2 g/kg.
For patients at increased risk of thrombosis, hemolysis, acute kidney injury, or volume overload, there should be a careful evaluation of the risks and benefits of prescribing this regimen.
What are the infusion rates for managing PI using Gammaplex 5%?
Initially, the rate of infusion should be 0.5 mg/kg/min for 15 minutes and increased gradually every 15 minutes to 4 mg/kg/min as a maintenance infusion rate.
What are the infusion rates for managing ITP using Gammaplex 5%?
Initially, the rate of infusion should be 0.5 mg/kg/min for 15 minutes and increased gradually every 15 minutes to 4 mg/kg/min as a maintenance infusion rate until the total dose is administered.
What are the infusion rates for treating PI using Gammaplex 10%?
For managing PI using Gammaplex 10%, the starting infusion rate is set at 0.5 mg/kg/min for 15 minutes and increased gradually every 15 minutes to 8 mg/kg/min.
What are the infusion rates for treating ITP using Gammaplex 10%?
For managing ITP, the initial gammaplex infusion rate is set at 0.5 mg/kg/min (0.005 mL/kg/min) for 15 minutes and increased gradually every 15 minutes to 8 mg/kg/min (0.08 mL/kg/min).
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Before administering a Gammaplex infusion, the patient should drink plenty of water to ensure adequate hydration.
The patient’s vital signs should be monitored throughout the infusion session.
If the patient shows any signs of adverse reactions, the infusion rate should be decreased. If the adverse reaction subsides, the infusion should be resumed but at a lower rate that is comfortable for the patient.
If the adverse reaction persists, the infusion should be stopped altogether.
It is important to ensure that patients with preexisting renal insufficiency are not volume depleted.
For patients predisposed to renal dysfunction, thrombotic events, or volume overload, Gammaplex infusion should be administered at the minimum practicable rate.
Gammaplex Adverse Reactions
The use of IVIG, including Gammaplex, may be accompanied by adverse reactions.
According to some reports, as many as 21% of patients discontinued their immunoglobulin therapy due to adverse reactions (low tolerability) or concerns about product safety.
Generally speaking, IVIGs are well tolerated, and most adverse reactions are mild, transient, and reversible by slowing or temporarily stopping the infusion.
More specifically, Gammaplex IV is well tolerated, as reflected by the low rate of treatment discontinuations due to side effects.
Similarly, patients with ITP completed 90 of 94 infusions at the maximum recommended rate, indicating that Gammaplex infusions were well tolerated even at high doses.
Gammaplex Adverse Reactions Associated With Subjects With PI
According to the Gammaplex package insert, The most common adverse reactions reported in primary immune deficiency clinical trials were:
Gammaplex Adverse Reactions Associated With Subjects With ITP
The most common adverse reactions reported in immune thrombocytopenic purpura clinical trials were:
- Joint pain
The frequency of Gammaplex adverse reactions tends to be directly proportional to the rate and dose of infusion.
Fortunately, most of these side effects tend to be self-limited, mild, and transient.
Usually, these adverse reactions occur during or within 6 hours of infusion, especially after the first infusion session.
Adverse reactions can also be associated with rapid infusion rates, higher doses, switching to a new product, waiting for longer intervals between infusion sessions, and intercurrent infections.
Managing Gammaplex Side Effects
Some simple methods can help prevent Gammaplex side effects.
For example, drinking plenty of water before or after the infusion can often be enough to minimize the occurrence of adverse reactions (11).
If side effects still occur, simple pharmacological approaches can be used, such as administering paracetamol 500 mg orally or acetylsalicylic acid 500 mg intravenously.
Another option can be administering non-steroidal anti-inflammatory drugs (e.g., ibuprofen 10 mg/kg), second-generation antihistamines, or corticosteroids.
However, both the patient and health care provider should be aware that in rare cases, serious adverse reactions may occur.
These adverse reactions include renal dysfunction/failure, thrombotic events, hypersensitivity, hyperproteinemia, increased serum viscosity, and hyponatremia.
Renal Dysfunction/Failure Adverse Reactions
The risk of renal dysfunction associated with IVIG occurs mostly due to the stabilizer utilized.
Renal dysfunction related to IVIGs stabilized with sucrose include acute renal failure, osmotic nephrosis, and renal insufficiency. Reports of renal dysfunction with sucrose-free IVIGs are relatively rare.
Patients at risk of developing acute renal failure can be classified into two distinct populations:
- Patients with preexisting conditions
- Patients at an increased risk for developing renal insufficiencies. This includes patients with pre-existing renal insufficiency, diabetes mellitus, advanced age (>65 years old), volume depletion (dehydration or hypervolemia), sepsis, or paraproteinemia. Patients receiving known nephrotoxic drugs are also at risk.
Since Gammaplex 10% is stabilized with glycine and Gammaplex 5% is stabilized with sorbitol, both products are less prone to cause renal dysfunction or acute renal failure.
Minimizing Risk of Renal Dysfunction or Acute Renal Failure
Healthcare authorities including the FDA and clinical experts recommend several precautionary measures to minimize the risk of renal dysfunction or acute renal failure for at-risk patients.
Patients should be hydrated well to ensure that they aren’t hypovolemic before a Gammaplex infusion.
A Gammaplex infusion at the minimum infusion rate practicable should be administered for patients at risk of developing renal dysfunction.
This includes patients predisposed to acute renal failure.
In addition, patients at risk of developing renal dysfunction should be assessed periodically for their renal function. Gammaplex infusions should be discontinued if there is any deterioration in renal function.
Thrombotic Adverse Reactions
IVIG products including Gammaplex may increase blood viscosity, possibly impairing blood flow and triggering a cardiovascular or cerebrovascular thromboembolic event.
In one clinical trial, serum viscosity was measured before and immediately after each of three consecutive monthly infusions of IVIG. Serum viscosity increased after IVIG in all 13 patients who participated in the study (12).
Patients at risk of developing thromboembolic events include patients:
- Of advanced age
- With prolonged immobilization
- With hypercoagulable conditions
- With a history of venous or arterial thrombosis
- Who use estrogen
- Who have indwelling central vascular catheters
- With hyperviscosity
- With cardiovascular risk factors
However, thromboembolic events may still occur in the absence of these known risk factors
Minimizing Risk of Thromboembolic Events
Patients should be properly hydrated prior to administration.
It is important to assess blood viscosity in patients at risk for hyperviscosity, including those with high triacylglycerols (triglycerides), cryoglobulins, and monoclonal gammopathies.
For patients at risk of thrombosis, Gammaplex infusion should be administered at the minimum dose and at a practicable infusion rate.
Like any other medicinal product, the administration of Gammaplex infusion may be accompanied by hypersensitivity adverse reactions.
Hypersensitivity reactions may be due to the trace amounts of IgA contained in Gammaplex infusions.
Patients with known antibodies to IgA are at increased risk of developing hypersensitivity and anaphylactic reactions, so they should be monitored closely.
If a hypersensitivity reaction occurs, the Gammaplex infusion should be discontinued immediately, and proper management should follow.
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Hyperproteinemia, Increased Serum Viscosity, and Hyponatremia
Hyperproteinemia, increased serum viscosity, and hyponatremia are rare adverse reactions that may accompany IVIG infusions.
Patients should be assessed carefully for signs and symptoms of hyponatremia, and it should be distinguished clinically from pseudohyponatremia.
Pseudohyponatremia may accompany hyperproteinemia, and any management procedure for correcting pseudohyponatremia may further deplete volume and increase the risk of thrombotic events.
Aseptic Meningitis Syndrome
Aseptic Meningitis Syndrome (AMS) may occur in patients upon receiving IVIG treatment, especially at high doses (2 g/kg) and rapid infusion rates.
Aseptic meningitis syndrome (AMS) should be suspected if the following signs and symptoms are noticed within several hours to 2 days following IVIG treatment:
- Nuchal rigidity
- Painful eye movements
- Severe headache
Patients experiencing these symptoms should receive an extensive neurological examination to rule out other causes of meningitis.
Fortunately, discontinuation of IVIG treatment usually is enough for the remission of aseptic meningitis syndrome, without adverse consequences.
IVIG including Gammaplex may cause hemolysis due to the content of blood groups antibodies that can act as hemolysins.
Acute hemolysis may develop into delayed hemolytic anemia, which has been reported upon the use of IVIG therapy.
Severe acute hemolysis may also develop into renal dysfunction or disseminated intravascular coagulation.
Some of the main reasons patients may develop hemolysis with the use of IVIG products are:
- Administration of high doses (i.e., ≥2 g/kg).
- Being other than O-blood type.
Hemolysis can develop in patients with either PI or ITP.
Minimizing Risk of Hemolysis
Patients at risk of developing hemolysis should be closely monitored.
Other measures to minimize the risk of hemolysis should include baseline laboratory testing (such as level of hemoglobin and hematocrit) for patients predisposed to developing hemolysis. These tests should be conducted 36 to 96 hours after infusion.
If hemolysis is suspected, confirmatory laboratory tests should be conducted.
Transfusion-Related Acute Lung Injury (TRALI):
Transfusion-related acute lung injury (TRALI) is one of the adverse reactions that may accompany the transfusion of blood products, including intravenous immune globulin products.
Transfusion-related acute lung injury is a clinical syndrome in which there is acute, noncardiogenic pulmonary edema that may occur during or after the transfusion session and is associated with hypoxia.
The signs and symptoms of TRALI may include fever, hypotension, and exudative bilateral infiltrates on a chest radiograph.
Transfusion-related acute lung injury is suspected when there are other risk factors for acute lung injury, and symptoms usually appear within 1 to 6 hours following treatment.
When transfusion-related acute lung injury is suspected, anti-neutrophil antibody tests should be performed for both the product’s and the patient’s serum.
The price for Gammaplex intravenous solution 5% is between $890 and $940 for a supply of 100 milliliters, depending on the pharmacy you visit (9).
The price for Gammaplex intravenous solution 10% is between $1,780 and $1,950 for a supply of 100 milliliters, depending on the pharmacy you visit.
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Gammaplex Copay Assistance Programs
There are multiple Patient Assistance Programs (PAPs) that support low-income, uninsured, or underinsured people, who can receive medication for free or at a discounted price.
These programs are sponsored by pharmaceutical companies such as the Patient Access Network Foundation (PAN), HealthWell Foundation Copay Program, and Bio Products Laboratory (BPL) Reimbursement Support Program.
In the Bio Products Laboratory reimbursement support program, for example, patients can receive up to $2,000 in assistance yearly if they prove that they need financial assistance.
The manufacturer of Gammaplex is Bio Products Laboratory.
Is Gammaplex the Same as Gammagard?
Both Gammaplex and Gammagard are immune globulin products. However, Gammagard infusions can be administered either intravenously or subcutaneously, while Gammaplex can only be administered through an IV.
Another difference between these immune globulin products is their indications for use.
Gammaplex is used as replacement therapy for PIDDs and for managing ITP.
Gammagard is also indicated as replacement therapy for PIDD but also can be used as a maintenance therapy to improve muscle strength and disability in adult patients with Multifocal Motor Neuropathy (MMN).
In general, Gammagard costs less than Gammaplex.
For example, Gammagard 10% (100 ml) would cost nearly $1,600 while a comparable amount of Gammaplex 10% would cost $1,800.
In addition, these products are manufactured differently.
Gammaplex is manufactured by Bio Products Laboratory, while Gammagard is manufactured by Baxalta.
Gammaplex is an immunoglobulin product currently licensed in the United States. It is a safe, effective replacement therapy for primary humoral immunodeficiency (PIDD) patients, and also a management therapy in chronic immune thrombocytopenic purpura (ITP).
Gammaplex is available at two concentrations: 5% and 10%. The higher concentration ensures shorter infusion times.
Gammaplex is a well-tolerated medication with mild, self-limited side effects that can be managed successfully using simple measures. However, more serious adverse reactions are possible, and caution should be exercised.
Gammaplex is not the same as Gammagard; each one is formulated in a particular manner and has different indications.
- Gelfand E. W. (2005). Critical decisions in selecting an intravenous immunoglobulin product. Journal of infusion nursing : the official publication of the Infusion Nurses Society, 28(6), 366–374. https://doi.org/10.1097/00129804-200511000-00003
- DailyMed – GAMMAPLEX- human immunoglobulin g solution. Dailymed.nlm.nih.gov. (2021). Retrieved 17 July 2021, from https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6c3ce068-59f0-413b-9f93-85fb597d55e5.
- Roberts, P. L., Dolan, T., Paddick, M., Stagg, S., & More, J. E. (2015). Development of an intravenous immunoglobulin with improved safety and functional activity. Biologicals : journal of the International Association of Biological Standardization, 43(2), 123–129. https://doi.org/10.1016/j.biologicals.2014.11.005
- Saeedian, M., & Randhawa, I. (2014). Immunoglobulin replacement therapy: a twenty-year review and current update. International archives of allergy and immunology, 164(2), 151–166. https://doi.org/10.1159/000363445
- Wasserman R. L. (2017). Gammaplex® 5 and 10% in the treatment of primary immunodeficiency and chronic immune thrombocytopenic purpura. Immunotherapy, 9(13), 1071–1088. https://doi.org/10.2217/imt-2017-0071
- Justiz Vaillant AA, Qurie A. Immunodeficiency. [Updated 2021 Jun 30]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK500027/
- Hernandez-Trujillo, V. P., Scalchunes, C., Cunningham-Rundles, C., Ochs, H. D., Bonilla, F. A., Paris, K., Yel, L., & Sullivan, K. E. (2014). Autoimmunity and inflammation in X-linked agammaglobulinemia. Journal of clinical immunology, 34(6), 627–632. https://doi.org/10.1007/s10875-014-0056-x
- Rodeghiero, F., Stasi, R., Gernsheimer, T., Michel, M., Provan, D., Arnold, D. M., Bussel, J. B., Cines, D. B., Chong, B. H., Cooper, N., Godeau, B., Lechner, K., Mazzucconi, M. G., McMillan, R., Sanz, M. A., Imbach, P., Blanchette, V., Kühne, T., Ruggeri, M., & George, J. N. (2009). Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood, 113(11), 2386–2393. https://doi.org/10.1182/blood-2008-07-162503
- Neunert C, Terrell DR, Arnold DM, et al. American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv. 2019;3(23):3829-3866. (2020). Blood advances, 4(2), 252. https://doi.org/10.1182/bloodadvances.2019001380
- Jin, F., & Balthasar, J. P. (2005). Mechanisms of intravenous immunoglobulin action in immune thrombocytopenic purpura. Human immunology, 66(4), 403–410. https://doi.org/10.1016/j.humimm.2005.01.029
- Šutová, I., Chovancová, Z., & Litzman, J. (2019). Adverse effects of immunoglobulin therapy. Nežádoucí účinky imunoglobulinové léčby. Vnitrni lekarstvi, 65(2), 131–132.
- Dalakas M. C. (1994). High-dose intravenous immunoglobulin and serum viscosity: risk of precipitating thromboembolic events. Neurology, 44(2), 223–226. https://doi.org/10.1212/wnl.44.2.223
Dr. Mina Azer, RPh, attended University of Alexandria in Egypt. The most rewarding part of his job is helping others, especially when he gets to collaborate with his coworkers to achieve shared goals. Mina is a proud coffee enthusiast. He also enjoys keeping up with the latest tech gadgets.