Dosage Form: injection
FULL PRESCRIBING INFORMATION
GAMUNEX®-C, [Immune Globulin Injection (Human) 10% Caprylate/Chromatography Purified]
- Renal dysfunction, acute renal failure, osmotic nephrosis, and death may occur with immune globulin intravenous (IGIV) products in predisposed patients. Patients predisposed to renal dysfunction include those with any degree of pre-existing renal insufficiency, diabetes mellitus, age greater than 65, volume depletion, sepsis, paraproteinemia, or patients receiving known nephrotoxic drugs.
- Renal dysfunction and acute renal failure occur more commonly in patients receiving IGIV products containing sucrose. [1] Gamunex-C does not contain sucrose.
- For patients at risk of renal dysfunction or failure, administer Gamunex-C at the minimum concentration available and the minimum infusion rate practicable. (see Warnings and Precautions [5.2])
Indications and Usage for Gamunex-C
Gamunex-C is an immune globulin injection (human) 10% liquid that is indicated for the treatment of:
Primary Humoral Immunodeficiency (PI)
Gamunex-C is indicated as replacement therapy of primary humoral immunodeficiency. This includes, but is not limited to, congenital agammaglobulinemia, common variable immunodeficiency, X-linked agammaglobulinemia, Wiskott-Aldrich syndrome, and severe combined immunodeficiencies. [2-5]
Idiopathic Thrombocytopenic Purpura (ITP)
Gamunex-C is indicated for the treatment of patients with Idiopathic Thrombocytopenic Purpura to raise platelet counts to prevent bleeding or to allow a patient with ITP to undergo surgery [6-7].
Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)
Gamunex-C is indicated for the treatment of CIDP to improve neuromuscular disability and impairment and for maintenance therapy to prevent relapse.
Gamunex-C Dosage and Administration
Gamunex-C consists of 9%–11% protein in 0.16–0.24 M glycine. The buffering capacity of Gamunex-C is 35.0 mEq/L (0.35 mEq/g protein). A dose of 1 g/kg body weight therefore represents an acid load of 0.35 mEq/kg body weight. The total buffering capacity of whole blood in a normal individual is 45–50 mEq/L of blood, or 3.6 mEq/kg body weight. Thus, the acid load delivered with a dose of 1 g/kg of Gamunex-C would be neutralized by the buffering capacity of whole blood alone, even if the dose was infused instantaneously.
Preparation and Handling
- Gamunex-C should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use if turbid.
- Do not freeze. Solutions that have been frozen should not be used.
- The Gamunex-C vial is for single use only. Gamunex-C contains no preservative. Any vial that has been entered should be used promptly. Partially used vials should be discarded.
- Gamunex-C should be infused using a separate line by itself, without mixing with other intravenous fluids or medications the subject might be receiving.
- Gamunex-C is not compatible with saline. If dilution is required, Gamunex-C may be diluted with 5% dextrose in water (D5/W). No other drug interactions or compatibilities have been evaluated.
- Content of vials may be pooled under aseptic conditions into sterile infusion bags and infused within 8 hours after pooling.
- Do not mix with immune globulin intravenous (IGIV) products from other manufacturers.
- Do not use after expiration date.
Treatment of Primary Humoral Immunodeficiency
As there are significant differences in the half-life of IgG among patients with primary humoral immunodeficiencies, the frequency and amount of immunoglobulin therapy may vary from patient to patient. The proper amount can be determined by monitoring clinical response.
Intravenous (IV)
The dose of Gamunex-C for patients with PI is 300 to 600 mg/kg body weight (3-6 mL/kg) administered every 3 to 4 weeks. The dosage may be adjusted over time to achieve the desired trough levels and clinical responses.
The recommended initial infusion rate is 1 mg/kg/min (0.01 mL/kg/min). If the infusion is well-tolerated, the rate may be gradually increased to a maximum of 8 mg/kg/min (0.08 mL/kg/min). For patients judged to be at risk for renal dysfunction or thrombotic events, administer Gamunex-C at the minimum infusion rate practicable. (see Warnings and Precautions [5.2,5.5])
If a patient routinely receives a dose of less than 400 mg/kg of Gamunex-C every 3 to 4 weeks (less than 4 mL/kg), and is at risk of measles exposure (i.e., traveling to a measles endemic area), administer a dose of at least 400 mg/kg (4 mL/kg) just prior to the expected measles exposure. If a patient has been exposed to measles, a dose of 400 mg/kg (4 mL/kg) should be administered as soon as possible after exposure.
Subcutaneous (SC)
The dose should be individualized based on the patient’s clinical response to Gamunex-C therapy and serum IgG trough levels. Begin treatment with Gamunex-C one week after the patient’s last IGIV infusion. See below under "Initial Weekly Dose". Prior to switching treatment from IGIV to Gamunex-C, obtain the patient’s serum IgG trough level to guide subsequent dose adjustments. See below under "Dose Adjustment".
Establish the initial weekly dose of Gamunex-C by converting the monthly IGIV dose into a weekly equivalent and increasing it using a dose adjustment factor. The goal is to achieve a systemic serum IgG exposure (Area Under the Concentration-Time Curve [AUC]) not inferior to that of the previous IGIV treatment. If the patient has not been previously treated with IV Gamunex-C, convert the weekly IGIV dose by multiplying by 1.37, then dividing this dose into weekly doses based on the patient’s previous IGIV treatment interval. Monitor the patient’s clinical response, and adjust dose accordingly.
Initial Weekly Dose
To calculate the initial weekly dose of subcutaneous administration of Gamunex-C, multiply the previous IGIV dose in grams by the dose adjustment factor of 1.37; then divide this by the number of weeks between doses during the patient’s IGIV treatment (i.e., 3 or 4).
Initial SC dose = 1.37 × previous IGIV dose (in grams)
Number of weeks between IGIV doses
To convert the Gamunex-C dose (in grams) to milliliters (mL), multiply the calculated dose (in grams) by 10.
Dose adjustment
Over time, the dose may need to be adjusted to achieve the desired clinical response and serum IgG trough level. To determine if a dose adjustment may be considered, measure the patient’s serum IgG trough level on IGIV and as early as 5 weeks after switching from IGIV to subcutaneous. The target serum IgG trough level on weekly SC treatment is projected to be the last IGIV trough level plus 340 mg/dL. To determine if further dose adjustments are necessary, monitor the patients IgG trough level every 2 to 3 months.
To adjust the dose based on trough levels, calculate the difference (in mg/dL) of the patient’s serum IgG trough level from the target IgG trough level (the last IGIV trough level + 340 mg/dL). Then find this difference in Table 1 and the corresponding amount (in mL) by which to increase or decrease the weekly dose based on the patient’s body weight. However, the patient’s clinical response should be the primary consideration in dose adjustment.
| |||||||||||||
| Difference From Target IgG Trough Level (mg/dL) | Body Weight (kg) | ||||||||||||
| 10 | 15 | 20 | 30 | 40 | 50 | 60 | 70 | 80 | 90 | 100 | 110 | 120 | |
| Dose Adjustment (mL per Week)* | |||||||||||||
| 50 | 1 | 1 | 2 | 3 | 3 | 4 | 5 | 6 | 7 | 8 | 8 | 9 | 10 |
| 100 | 2 | 3 | 3 | 5 | 7 | 8 | 10 | 12 | 13 | 15 | 17 | 18 | 20 |
| 150 | 3 | 4 | 5 | 8 | 10 | 13 | 15 | 18 | 20 | 23 | 25 | 28 | 30 |
| 200 | 3 | 5 | 7 | 10 | 13 | 17 | 20 | 23 | 27 | 30 | 33 | 37 | 40 |
| 250 | 4 | 6 | 8 | 13 | 17 | 21 | 25 | 29 | 33 | 38 | 42 | 46 | 50 |
| 300 | 5 | 8 | 10 | 15 | 20 | 25 | 30 | 35 | 40 | 45 | 50 | 55 | 60 |
| 350 | 6 | 9 | 12 | 18 | 23 | 29 | 35 | 41 | 47 | 53 | 58 | 64 | 70 |
| 400 | 7 | 10 | 13 | 20 | 27 | 33 | 40 | 47 | 53 | 60 | 67 | 73 | 80 |
| 450 | 8 | 11 | 15 | 23 | 30 | 38 | 45 | 53 | 60 | 68 | 75 | 83 | 90 |
| 500 | 8 | 13 | 17 | 25 | 33 | 42 | 50 | 58 | 67 | 75 | 83 | 92 | 100 |
For example, if a patient with a body weight of 70 kg has an actual IgG trough level of 900 mg/dL and the target level is 1000 mg/dL, this results in a difference of 100 mg/dL. Therefore, increase the weekly dose of subcutaneous dose by 12 mL.
Monitor the patient’s clinical response, and repeat the dose adjustment as needed.
Dosage requirements for patients switching to Gamunex-C from another Immune Globulin Subcutaneous (IGSC) product have not been studied. If a patient on Gamunex-C does not maintain an adequate clinical response or a serum IgG trough level equivalent to that of the previous IGSC treatment, the physician may want to adjust the dose. For such patients, Table 1 also provides guidance for dose adjustment to achieve a desired IGSC trough level.
Treatment of Idiopathic Thrombocytopenic Purpura
DO NOT ADMINISTER SUBCUTANEOUSLY (see Warnings and Precautions [5.3])
Gamunex-C may be administered at a total dose of 2 g/kg, divided in two doses of 1 g/kg (10 mL/kg) given on two consecutive days or into five doses of 0.4 g/kg (4 mL/kg) given on five consecutive days. If after administration of the first of two daily 1 g/kg (10 mL/kg) doses, an adequate increase in the platelet count is observed at 24 hours, the second dose of 1g/kg (10 mL/kg) body weight may be withheld.
Forty-eight ITP subjects were treated with 2 g/kg Gamunex-C, divided in two 1 g/kg doses (10 mL/kg) given on two successive days. With this dose regimen 35/39 subjects (90%) responded with a platelet count from less than or equal to 20 x109/L to more than or equal to 50 x109/L within 7 days after treatment. The high dose regimen (1 g/kg × 1-2 days) is not recommended for individuals with expanded fluid volumes or where fluid volume may be a concern.
The recommended initial infusion rate is 1 mg/kg/min (0.01 mL/kg/min). If the infusion is well-tolerated, the rate may be gradually increased to a maximum of 8 mg/kg/min (0.08 mL/kg/min). For patients judged to be at risk for renal dysfunction or thrombotic events, Gamunex-C should be administered at the minimum infusion rate practicable (see Warnings and Precautions [5.2,5.5]).
Treatment of Chronic Inflammatory Demyelinating Polyneuropathy
Gamunex-C may be initially administered as a total loading dose of 2 g/kg (20 mL/kg) given in divided doses over two to four consecutive days. Gamunex-C may be administered as a maintenance infusion of 1 g/kg (10 mL/kg) administered over 1 day or divided into two doses of 0.5 g/kg (5 mL/kg) given on two consecutive days, every 3 weeks.
The recommended initial infusion rate is 2 mg/kg/min (0.02 mL/kg/min). If the infusion is well tolerated, the rate may be gradually increased to a maximum of 8 mg/kg/min (0.08 mL/kg/min). For patients judged to be at risk for renal dysfunction or thrombotic events, Gamunex-C should be administered at the minimum infusion rate practicable. (see Warnings and Precautions [5.2,5.5])
Administration
Administer intravenously for treatment of PI, ITP and CIDP.
Gamunex-C may also be administered subcutaneously for the treatment of PI.
Gamunex-C should be at room temperature during administration.
Gamunex-C should be inspected visually for particulate matter and discoloration prior to administration, whenever the solution and container permit. Do not use if turbid and/or if discoloration is observed.
Intravenous
Only 18 gauge needles should be used to penetrate the stopper for dispensing product from the 10 mL vial; 16 gauge needles or dispensing pins should only be used with 25 mL vial sizes and larger. Needles or dispensing pins should only be inserted once and be within the stopper area delineated by the raised ring. The stopper should be penetrated perpendicular to the plane of the stopper within the ring.
| GAMUNEX® -C vial size | Gauge of needle to penetrate stopper |
| 10 mL | 18 gauge |
| 25, 50, 100, 200 mL | 16 gauge |
Any vial that has been opened should be used promptly. Partially used vials should be discarded.
If dilution is required, Gamunex-C may be diluted with 5% dextrose in water (D5/W). Do not dilute with saline.
Subcutaneous for PI only
Instructions for Administration
Prior to use, allow the solution to reach ambient room temperature. DO NOT SHAKE. Do not use if the solution is cloudy or has particulates. Check the product expiration date on the vial. Do not use beyond the expiration date.
- Use aseptic technique when preparing and administering Gamunex-C for injection.
- Remove the protective cap from the vial to expose the central portion of the rubber stopper.
- Wipe the rubber stopper with alcohol and allow to dry.
- Using a sterile syringe and needle, prepare to withdraw Gamunex-C by first injecting air into the vial that is equivalent to the amount of Gamunex-C to be withdrawn. Then withdraw the desired volume of Gamunex-C. If multiple vials are required to achieve the desired dose, repeat this step. (Figure 1)
- Follow the manufacturer’s instructions for filling the pump reservoir and preparing the pump, administration tubing and Y-site connection tubing, if needed. Be sure to prime the administration tubing to ensure that no air is left in the tubing or needle by filling the tubing/needle with Gamunex-C.
- Select the number and location of injection sites. (Figure 2)
- Cleanse the injection site(s) with antiseptic solution using a circular motion working from the center of the site and moving to the outside. Sites should be clean, dry, and at least two inches apart. (Figure 3)
- Grasp the skin between two fingers and insert the needle into the subcutaneous tissue. (Figure 4)
- Repeat priming and needle insertion steps using a new needle, administration tubing and a new infusion site. Secure the needle in place by applying sterile gauze or transparent dressing over the site. (Figure 5)
- If using multiple, simultaneous injection sites, use Y-site connection tubing and secure to the administration tubing.
- Infuse Gamunex-C following the manufacturer’s instructions for the pump. (Figure 6)
Rate of Administration
Intravenous
Following initial infusion (see table below), the infusion rate may be gradually increased to a maximum of 0.08 mL/kg per minute (8 mg/kg per minute) as tolerated.
| Indication | Initial Infusion Rate (first 30 minutes) | Maximum infusion rate (if tolerated) |
| PI | 1 mg/kg/min | 8 mg/kg/min |
| ITP | 1 mg/kg/min | 8 mg/kg/min |
| CIDP | 2 mg/kg/min | 8 mg/kg/min |
Monitor patient vital signs throughout the infusion. Slow or stop infusion if adverse reactions occur. If symptoms subside promptly, the infusion may be resumed at a lower rate that is comfortable for the patient.
Certain severe adverse drug reactions may be related to the rate of infusion. Slowing or stopping the infusion usually allows the symptoms to disappear promptly.
Ensure that patients with pre-existing renal insufficiency are not volume depleted. For patients at risk of renal dysfunction or thromboembolic events, administer Gamunex-C at the minimum infusion rate practicable and discontinue Gamunex-C if renal function deteriorates.
Subcutaneous for PI only
For PI, it is recommended that Gamunex-C is infused at a rate of 20 mL/hr per infusion site.
In the SC clinical study, the mean volume administered per infusion site was 34 mL (17-69 mL) and the majority of infusions were administered at a rate of 20 mL/hr per site. Multiple simultaneous infusion sites were enabled by administration tubing and Y-site connection tubing. Most subjects utilized 4 infusion sites per infusion with abdomen and thighs being the most commonly used sites. The maximum number of infusion sites is 8. Injection sites should be at least 2 inches apart.
Incompatibilities with Saline
Gamunex-C is not compatible with saline. If dilution is required Gamunex-C may be diluted with 5% dextrose in water (D5/W). No other drug interactions or compatibilities have been evaluated.
Dosage Forms and Strengths
Gamunex-C is supplied in 1 g, 2.5 g, 5 g, 10 g, or 20 g single use bottles.
- 1 g protein in 10 mL solution
- 2.5 g protein in 25 mL solution
- 5 g protein in 50 mL solution
- 10 g protein in 100 mL solution
- 20 g protein in 200 mL solution
Contraindications
Hypersensitivity reaction to immune globulins
Gamunex-C is contraindicated in patients who have had an anaphylactic or severe systemic reaction to the administration of human immune globulin.
IgA sensitive patients with history of hypersensitivity reaction
Gamunex-C is contraindicated in IgA deficient patients with antibodies against IgA and history of hypersensitivity.
Warnings and Precautions
Hypersensitivity
Severe hypersensitivity reactions may occur with IGIV products, including Gamunex-C. In case of hypersensitivity, discontinue Gamunex-C infusion immediately and institute appropriate treatment. Medications such as epinephrine should be available for immediate treatment of acute hypersensitivity reaction.
Gamunex-C contains trace amounts of IgA (average 46 micrograms/mL). Patients with known antibodies to IgA may have a greater risk of developing potentially severe hypersensitivity and anaphylactic reactions. It is contraindicated in IgA deficient patients with antibodies against IgA and history of hypersensitivity reaction.(see Contraindications [4])
Renal Failure
Assure that patients are not volume depleted prior to the initiation of the infusion of Gamunex-C. Periodic monitoring of renal function and urine output is particularly important in patients judged to have a potential increased risk for developing acute renal failure. Assess renal function, including measurement of blood urea nitrogen (BUN)/serum creatinine, prior to the initial infusion of Gamunex-C and again at appropriate intervals thereafter. If renal function deteriorates, consider discontinuation of Gamunex-C. (see Patient Counseling Information [17]) For patients judged to be at risk for developing renal dysfunction, including patients with any degree of pre-existing renal insufficiency, diabetes mellitus, age greater than 65, volume depletion, sepsis, paraproteinemia, or patients receiving known nephrotoxic drugs, administer Gamunex-C at the minimum infusion rate practicable [less than 8 mg IG/kg/min (0.08 mL/kg/min)]. (see Dosage and Administration [2.5])
Hematoma Formation
Do not administer Gamunex-C subcutaneously in patients with ITP because of the risk of hematoma formation.
Hyperproteinemia, Increased Serum Viscosity, and Hyponatremia
Hyperproteinemia, increased serum viscosity and hyponatremia may occur in patients receiving IGIV treatment, including Gamunex-C. It is clinically critical to distinguish true hyponatremia from a pseudohyponatremia that is associated with concomitant decreased calculated serum osmolality or elevated osmolar gap, because treatment aimed at decreasing serum free water in patients with pseudohyponatremia may lead to volume depletion, a further increase in serum viscosity and a possible predisposition to thromboembolic events. [8]
Thrombotic Events
Thrombotic events have been reported following IGIV treatment and may occur in patients receiving IGIV treatment, including Gamunex-C. [9-11] Patients at risk may include those with a history of atherosclerosis, multiple cardiovascular risk factors, advanced age, impaired cardiac output, coagulation disorders, prolonged periods of immobilization and/or known or suspected hyperviscosity. Consider baseline assessment of blood viscosity in patients at risk for hyperviscosity, including those with cryoglobulins, fasting chylomicronemia/markedly high triacylglycerols (triglycerides), or monoclonal gammopathies. For patients judged to be at risk of developing thrombotic events, administer Gamunex-C at the minimum rate of infusion practicable. (see Dosage and Administration [2.5])
Aseptic Meningitis Syndrome (AMS)
AMS may occur infrequently with IGIV treatment, including Gamunex-C. Discontinuation of IGIV treatment has resulted in remission of AMS within several days without sequelae. The syndrome usually begins within several hours to two days following IGIV treatment. AMS is characterized by the following symptoms and signs: severe headache, nuchal rigidity, drowsiness, fever, photophobia, painful eye movements, nausea and vomiting. Cerebrospinal fluid (CSF) studies are frequently positive with pleocytosis up to several thousand cells per cu mm, predominantly from the granulocytic series, and with elevated protein levels up to several hundred mg/dL, but negative culture results. Conduct a thorough neurological examination on patients exhibiting such symptoms and signs including CSF studies, to rule out other causes of meningitis. AMS may occur more frequently in association with high doses (2 g/kg) and/or rapid infusion of IGIV.
Hemolysis
IGIV products, including Gamunex-C, may contain blood group antibodies which may act as hemolysins and induce in vivo coating of red blood cells (RBCs) with immunoglobulin, causing a positive direct antiglobulin reaction and, rarely, hemolysis.[12-14] Delayed hemolytic anemia can develop subsequent to IGIV therapy due to enhanced RBC sequestration, and acute hemolysis consistent with intravascular hemolysis, has been reported. Monitor patients for clinical signs and symptoms of hemolysis. [15] (see Patient Counseling Information [17]) If signs and/or symptoms of hemolysis are present after Gamunex-C infusion, perform appropriate confirmatory laboratory testing.
Transfusion-related Acute Lung Injury (TRALI)
Noncardiogenic pulmonary edema may occur in patients following treatment with IGIV products, including Gamunex-C. [16] TRALI is characterized by severe respiratory distress, pulmonary edema, hypoxemia, normal left ventricular function, and fever. Symptoms typically occur within 1 to 6 hours after treatment.
Monitor patients for pulmonary adverse reactions. (see Patient Counseling Information [17]) If TRALI is suspected, perform appropriate tests for the presence of anti-neutrophil and anti-HLA antibodies in both the product and patient serum. TRALI may be managed using oxygen therapy with adequate ventilatory support.
Volume Overload
The high dose regimen (1g/kg x 1-2 days) is not recommended for individuals with expanded fluid volumes or where fluid volume may be a concern.
Transmissible Infectious Agents
Because Gamunex-C is made from human blood, it may carry a risk of transmitting infectious agents, e.g., viruses, and theoretically, the Creutzfeldt-Jakob disease (CJD) agent. No cases of transmission of viral diseases or CJD have ever been identified for Gamunex-C. ALL infections suspected by a physician possibly to have been transmitted by this product should be reported by the physician or other healthcare provider to Talecris Biotherapeutics, Inc. [1-800-520-2807]
Laboratory Tests
After infusion of IgG, the transitory rise of the various passively transferred antibodies in the patient’s blood may yield positive serological testing results, with the potential for misleading interpretation.
Passive transmission of antibodies to erythrocyte antigens (e.g., A, B, and D) may cause a positive direct or indirect antiglobulin (Coombs’) test. Patients with known renal dysfunction or renal failure, including patients with pre-existing renal insufficiency, diabetes mellitus, age greater than 65, volume depletion, sepsis, paraproteinemia, or those receiving nephrotoxic agents, should be clinically assessed and monitored (BUN, creatinine), as appropriate, during therapy with Gamunex-C.
Consider baseline assessment of blood viscosity in patients at risk for hypervisocosity, including those with cryoglobulins, fasting chylomicronemia/markedly high triacylglycerols (triglycerides), or monoclonal gammopathies.
Adverse Reactions
The most common adverse reactions observed at a rate ≥5% in subjects treated with IV Gamunex-C for PI were headache, cough, injection site reaction, nausea, pharyngitis and urticaria.
The most common adverse reactions observed at a rate ≥5% of subjects treated with SC Gamunex-C for PI were infusion site reactions, headache, fatigue, arthralgia and pyrexia.
The most common adverse reactions observed at a rate ≥5% in subjects treated with Gamunex-C for ITP were headache, vomiting, fever, nausea, back pain and rash.
The most common adverse reactions observed at a rate ≥5% in subjects with Gamunex-C for CIDP were headache, fever, chills, hypertension, rash, nausea and asthenia.
Clinical Trials Experience
Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of one drug cannot be directly compared to rates in other clinical trials of another drug and may not reflect the rates observed in clinical practice.
Treatment of Primary Humoral Immunodeficiency by the Intravenous Route
The most serious adverse event observed in clinical study subjects receiving Gamunex-C IV for PI was an exacerbation of autoimmune pure red cell aplasia in one subject.
In four different clinical trials to study PI, out of 157 subjects treated with Gamunex-C, 4 subjects discontinued due to the following adverse events: Coombs negative hypochromic anemia, Autoimmune pure red cell aplasia, arthralgia/hyperhidrosis/fatigue/myalgia/nausea and migraine.
In a study of 87 subjects, 9 subjects in each treatment group were pretreated with non-steroidal medication prior to infusion, such as diphenhydramine and acetaminophen.
Table 2 lists all adverse events occurring in greater than 10% of subjects irrespective of the causality assessment.
| Adverse Event | Gamunex-C® | GAMIMUNE® N, 10% |
| No. of subjects: 87 | No. of subjects: 85 | |
| No. of subjects with AE | No. of subjects with AE | |
| (percentage of all subjects) | (percentage of all subjects) | |
| Cough increased | 47 (54%) | 46 (54%) |
| Rhinitis | 44 (51%) | 45 (53%) |
| Pharyngitis | 36 (41%) | 39 (46%) |
| Headache | 22 (25%) | 28 (33%) |
| Fever | 24 (28%) | 27 (32%) |
| Diarrhea | 24 (28%) | 27 (32%) |
| Asthma | 25 (29%) | 17 (20%) |
| Nausea | 17 (20%) | 22 (26%) |
| Ear Pain | 16 (18%) | 12 (14%) |
| Asthenia | 9 (10%) | 13 (15%) |
Table 3 lists the adverse reactions reported by at least 5% of subjects during the 9-month treatment.
| Adverse Reactions | Gamunex-C® | GAMIMUNE® N, 10% |
| No. of subjects: 87 | No. of subjects: 85 | |
| No. of subjects with adverse reaction | No. of subjects with adverse reaction | |
| (percentage of all subjects) | (percentage of all subjects) | |
| Headache | 7 (8%) | 8 (9%) |
| Cough increased | 6 (7%) | 4 (5%) |
| Injection site reaction | 4 (5%) | 7 (8%) |
| Nausea | 4 (5%) | 4 (5%) |
| Pharyngitis | 4 (5%) | 3 (4%) |
| Urticaria | 4 (5%) | 1 (1%) |
Table 4 lists the frequency of adverse reactions, which were reported by at least 5% of subjects, and their relationship to infusions administered.
GAMUNEX® -C | GAMIMUNE® N, 10% | |
| Adverse Experience | No. of infusions: 825 | No. of infusions: 865 |
| Number (percentage of all infusions) | (percentage of all subjects) | |
| Cough increased | ||
| All | 154 (18.7%) | 148 (17.1%) |
| Drug related | 14 (1.7%) | 11 (1.3%) |
| Pharyngitis | ||
| All | 96 (11.6%) | 99 (11.4%) |
| Drug related | 7 (0.8%) | 9 (1.0%) |
| Headache | ||
| All | 57 (6.9%) | 69 (8.0%) |
| Drug related | 7 (0.8%) | 11 (1.3%) |
| Fever | ||
| All | 41 (5.0%) | 65 (7.5%) |
| Drug rela ted | 1 (0.1%) | 9 (1.0%) |
| Nausea | ||
| All | 31 (3.8%) | 43 (5.0%) |
| Drug related | 4 (0.5%) | 4 (0.5%) |
Urticaria | ||
| All | 5 (0.6%) | 8 (0.9%) |
| Drug related | 4 (0.5%) | 5 (0.6%) |
The mean number of adverse reactions per infusion that occurred during or on the same day as an infusion was 0.21 in both the Gamunex-C and GAMIMUNE®N, Immune Globulin Intravenous (Human), 10%, treatment groups.
In all three trials in primary humoral immundeficiencies, the maximum infusion rate was 0.08 mL/kg/min (8 mg/kg/min). The infusion rate was reduced for 11 of 222 exposed subjects (7 Gamunex-C, 4 GAMIMUNE N, 10%) at 17 occasions. In most instances, mild to moderate hives/urticaria, itching, pain or reaction at infusion site, anxiety or headache was the main reason. There was one case of severe chills. There were no anaphylactic or anaphylactoid reactions to Gamunex-C or GAMIMUNE N, 10% in clinical trials.
In the IV efficacy and safety study, serum samples were drawn to monitor the viral safety at baseline and one week after the first infusion (for parvovirus B19), eight weeks after first and fifth infusion, and 16 weeks after the first and fifth infusion of IGIV (for hepatitis C) and at any time of premature discontinuation of the study. Viral markers of hepatitis C, hepatitis B, HIV-1, and parvovirus B19 were monitored by nucleic acid testing (NAT, Polymerase Chain Reaction (PCR)), and serological testing.
Treatment of Primary Humoral Immunodeficiency by the Subcutaneous Route (SC PK and Safety Study)
Adverse experiences were divided into 2 types: 1) Local infusion site reactions, and 2) Non-infusion site adverse events. Table 5 lists those adverse events occurring in ≥ 2% of infusions during the SC phase of the study.
| |
| Adverse Experience | |
| (≥2% of infusions) | Number |
| (Number of infusions: 725) | (Rate*) |
| Local Infusion Site reactions | 427 (0.59) |
| Mild | 389 (0.54) |
| Moderate | 29 (0.04) |
| Severe | 9 (0.01) |
| Non-infusion site adverse events | |
| Headache | 37 (0.05) |
| Sinusitis | 11 (0.02) |
Table 6 lists the adverse reactions occurring in ≥5% of subjects and the frequency of adverse reactions per infusion. All local infusion site reactions were a priori considered drug-related.
| ||
| Adverse Reactions | No. of Subjects | No. of Adverse Reactions |
| (≥5% of subjects) | n=32 (% ) | (Rate*) |
| Local Infusion Site Reactions | 24 (75%) | 427 (0.59) |
| Non-infusion Site Adverse Reactions | ||
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