Gammagard Liquid

GAMMAGARD LIQUID (immune globulin intravenous (human) 10%) is supplied in single use bottles as follows:  

Storage

Refrigeration: 36 months storage at refrigerated temperature 2° to 8°C (36°-46°F). Do not freeze. Room Temperature: 9 months storage at room temperature 25°C, (77°F) within the first 24 months of the date of manufacture. See below for detailed storage information. The total storage time of GAMMAGARD LIQUID (immune globulin intravenous (human) 10%) depends on the point of time the vial is transferred to room temperature. Examples for total storage times are illustrated in Figure 1. The new expiration date must be recorded on the package when the product is transferred to room temperature.

Figure 1: Storage Guidelines
Months from Date of Manufacture

• Example 1: If the product is taken out of the refrigerator after 3 months from date of manufacture, it can be stored for 9 months at room temperature. Total storage time is 12 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 additional months at room temperature. Total storage time is
  24 months.
• After 24 months from date of manufacture, product cannot be stored at room temperature.

REFERENCES

15. Stiehm ER. Standard and special human immune serum globulins as therapeutic agents. Pediatrics. 1979;63:301-319.

22. Schiff RI, Rudd C. Alterations in the half-life and clearance of IgG during therapy with intravenous gamma-globulin in 16 patients with severe primary humoral immunodeficiency. J Clin Immunol. 1986;6:256-264.

46. Tan E, Hajinazarian M, Bay W, Neff J, Mendell JR. Acute renal failure resulting from intravenous immunoglobulin therapy. Arch Neurol. 1993;50:137-139.

47. Morbidity and Mortality Weekly Report. Measles, Mumps, and Rubella; Vaccine use and strategies for elimination of measles, rubella, and congenital rubella syndrome and control of mumps. Recommendations for the Advisory Committee on Immunization Practices (ACIP). 98 A.D.;47.

48. Peter G. Summary of major changes in the 1994 Red Book: American Academy of Pediatrics. Report of the Committee on Infectious Disease. Pediatrics. 1994;93:1000-1002.

49. Siber GR, Werner BG, Halsey NA, et al. Interference of immune globulin with measles and rubella immunization. J Pediatr. 1993;122:204-211.

50. Data on file, Baxter Healthcare Corporation.

To enroll in the confi dential, industry-wide Patient Notifi cation System, call 1-888-UPDATE U (1-888-873-2838).
Baxter Healthcare Corporation, Westlake Village, CA 91362 USA. april 2005. FDA rev date: n/a

Immune globulin can harm your kidneys, and this effect is increased when you also use certain other medicines harmful to the kidneys. Before using immune globulin, tell your doctor about all other medications you use. Many other drugs (including some over-the-counter medicines) can be harmful to the kidneys.

Before using immune globulin intravenous, tell your doctor if you have kidney disease, diabetes (especially if you use insulin), a history of stroke or blood clot, heart disease, high blood pressure, a condition called paraproteinemia, or if you are over 65 years old.

To be sure this medicine is helping your condition and is not causing harmful effects, your blood will need to be tested often. Your kidney function may also need to be tested. Visit your doctor regularly.

This medication can cause unusual results with certain blood glucose tests. Tell any doctor who treats you that you are using immune globulin.

Immune globulin is made from human plasma (part of the blood) which may contain viruses and other infectious agents. Donated plasma is tested and treated to reduce the risk of it containing infectious agents, but there is still a small possibility it could transmit disease. Talk with your doctor about the risks and benefits of using this medication.

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Read the Gammagard Liquid User Reviews »

© Gammagard Liquid Patient Information is supplied by Cerner Multum, Inc. and Gammagard Liquid Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

Dosage

 Adjust dose according to IgG levels and clinical response, as the frequency and dose of immune globulin may vary from patient to patient.

No randomized controlled clinical trials are available to determine an optimum trough serum IgG level for intravenous treatment. If a patient misses a dose, administer the missed dose as soon as possible, and then resume scheduled treatments every 3 or 4 weeks, as applicable.

Prior to switching from intravenous to subcutaneous treatment, obtain the patient’s serum IgG trough level to guide subsequent dose adjustments. Start the initial subcutaneous dose approximately one week after the last intravenous infusion.

Dose Adjustments for Subcutaneous Administration

Based on the results of clinical studies, the expected increase in serum IgG trough level while on weekly subcutaneous treatment, at the dose adjusted to provide a comparable AUC, is projected to be approximately 281 mg/dL higher than the last trough level during prior stable intravenous treatment. To calculate the target trough IgG level for subcutaneous treatment, add 281 mg/dL to the IgG trough level obtained after the last intravenous treatment.

To guide dose adjustment, calculate the difference between the patient’s target serum IgG trough level and the IgG trough level during subcutaneous treatment. Find this difference in the columns of Table 2 and the corresponding amount (in mL) by which to increase (or decrease) the weekly dose based on the patient's body weight. If the difference between measured and target trough levels is less than 100 mg/dL then no adjustment is necessary. However, the patient's clinical response should be the primary consideration in dose adjustment.

Example 1: A patient with a body weight of 80 kg has a measured IgG trough level of 800 mg/dL and the target trough level is 1000 mg/dL. The desired target trough level difference is 200 mg/dL (1000 mg/dL minus 800 mg/dL). The weekly dose of Gammagard Liquid should beincreased by 30 mL (3.0 gm).

Example 2: A patient with a body weight of 60 kg has a measured IgG trough of 1000 mg/dL and the target trough level is 800 mg/dL. The desired target trough level difference is 200 mg/dL (800 mg/dL minus 1000 mg/dL). The weekly dose of Gammagard Liquid should bedecreased by 23 mL (2.3 gm).

Preparation and Handling

• Inspect the drug product visually for particulate matter and discoloration prior to administration. Gammagard Liquid is a clear or slightly opalescent, colorless or pale yellow solution. Do not use if the solution is cloudy, turbid, or if it contains particulates.
• Gammagard Liquid vial is for single use only. Any vial that has been entered should be used promptly. Partially used vials should be discarded. Gammagard Liquid contains no preservative.
• Allow refrigerated product to come to room temperature before use.
• DO NOT MICROWAVE.
• Do not shake.
• Do not mix with other products.
• Do not use normal saline as a diluent. If dilution is desired, 5% dextrose in water (D5W) should be used as a diluent.
• The infusion line may be flushed with normal saline. An in-line filter is optional.
• Record the name and lot number of the product in the recipient's records.

Administration

Intravenous

Monitor patient vital signs throughout the infusion. Certain adverse reactions such as headaches, flushing and changes in pulse rate and blood pressure may be related to the rate of 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.

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 infusion2. In such cases, start at lower infusion rates and gradually increase as tolerated.

Ensure that patients with pre-existing renal insufficiency are not volume depleted. For patients over 65 years of age or judged to be at risk for renal dysfunction or thrombotic events, administer Gammagard Liquid at the minimum infusion rate practicable. In such cases, the maximal rate should be less than 3.3 mg/kg/min (< 2mL/kg/hr), and consider discontinuation of administration if renal function deteriorates. (see WARNINGS AND PRECAUTIONS [5.2, 5.4] and USE IN SPECIFIC POPULATION [8.5]).

Subcutaneous

Selection of Infusion Site: 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.

Volume per Site: The weekly dose (mL) should be divided by 30 or 20, based on patient weight above, to determine the number of sites required. Simultaneous subcutaneous infusion at multiple sites can be facilitated by use of a multi-needle administration set.

Rate of Infusion for Patients 40 kg and greater (88 lbs):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 240 mL/hr.

Rate of Infusion for Patients under 40 kg (88 lbs): 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 x 3 sites = 60 mL/hr). The number of simultaneous sites should be limited to 8, or maximum infusion rate of 160 mL/hr.

Instructions for Subcutaneous Administration: Instruct patients to observe the following procedures:

1. Aseptic technique- Use aseptic technique when preparing and infusing Gammagard Liquid.

2. Assemble supplies - Set up a clean work area and gather all supplies necessary for the subcutaneous infusion: vial(s) of Gammagard Liquid, ancillary supplies, sharps container and pump. If Gammagard Liquid has already been pooled into a bag or a syringe, skip to Step 5.

3. Product preparation - Remove the protective cap from the vial to expose the center of the vial. Wipe the stopper with an alcohol pad and allow to dry. 

4. Withdraw Gammagard Liquid from the vials - Attach a sterile syringe to a needle and draw air into the syringe barrel equal to the amount of product to be withdrawn. Inject the air into the vial and withdraw the desired volume of Gammagard Liquid. If multiple vials are required to achieve the desired dose, repeat this step. 

5. Prepare the infusion pump and tubing - Follow the manufacturer’s instructions for preparing the pump and administration tubing, if needed. Be sure to prime the pump tubing to ensure that no air is left in the tubing and needle.

6. Select the infusion sites - Select the number of infusion sites depending on the volume of the total dose. See Administration[2.3] for recommended maximum volumes and rates. Potential sites for infusion include the back of arms, abdomen, thighs, and lower back (see Figure below). Ensure sites are at least 2 inches apart; avoid bony prominences.

7. Cleanse the infusion site(s) - Cleanse the infusion site(s) with an antiseptic skin preparation (e.g., alcohol pad) using a circular motion working from the center of the site and moving to the outside. Allow to dry.

8. Insert the needle - Choose the correct needle length to assure that Gammagard Liquid is delivered into the subcutaneous space. Grasp the skin and pinch at least one inch of skin between two fingers. Insert needle at a 90 degree angle with a darting motion into the subcutaneous tissue. Secure the needle.

9. Check for proper needle placement – Prior to the start of infusion, check each needle for correct placement to make sure that a blood vessel has not been punctured. Gently pull back on the attached syringe plunger and monitor for any blood return in the needle set. If you see any blood, remove and discard the needle set. Repeat priming and needle insertion steps in a different infusion site with a new needle set.

10. Secure the needle to the skin - Secure the needle(s) in place by applying a sterile protective dressing over the site.

11. Start infusion of Gammagard Liquid – Follow the manufacturer’s instructions to turn pump on.

12. Document the infusion - Remove the peel-off label with product lot number and expiration date from the Gammagard Liquid vial and place in treatment diary/log book to keep track of the product lots used. Keep the treatment diary/log book current by recording the time, date, dose, product label and any reactions after each infusion.

13. Remove needle set – After the infusion is complete, remove the needle set and gently press a small piece of gauze over the needle insertion site and cover with a protective dressing. Discard any unused solution and disposable supplies in accordance with local requirements.

Hypersensitivity

Severe hypersensitivity reactions may occur, even in patients who had tolerated previous treatment with human normal immune globulin. In case of hypersensitivity, discontinue Gammagard Liquid infusion immediately and institute appropriate treatment.

Gammagard Liquid contains trace amount of IgA (average concentration of 37μg/mL). Patients with antibodies to IgA have a greater risk of developing potentially severe hypersensitivity and anaphylactic reactions. Gammagard Liquid is contraindicated in patients with antibodies against IgA and a history of hypersensitivity reaction (see CONTRAINDICATIONS[4] )

Renal Dysfunction/Failure

Acute renal dysfunction/failure, acute tubular necrosis, proximal tubular nephropathy, osmotic nephrosis and death may occur upon use of IGIV treatment, especially those containing sucrose3. Acute renal dysfunction/failure has been reported in association with infusions of Gammagard Liquid. Assure that patients are not volume depleted prior to the initiation of infusion of Gammagard Liquid. In patients who are at risk of developing renal dysfunction, because of pre-existing renal insufficiency or predisposition to acute renal failure (such as diabetes mellitus, age greater than 65, volume depletion, sepsis, paraproteinemia, or patients receiving known nephrotoxic drugs, etc.), administer Gammagard Liquid intravenously at the minimum rate of infusion practicable (not exceeding 3.3 mg IgG/kg/min (< 2 mL/kg/hr) (see DOSAGE AND ADMINISTRATION [2.3]).

Periodic monitoring of renal function and urine output is particularly important in patients judged to be at increased risk for developing acute renal failure. Assess renal function, including measurement of blood urea nitrogen (BUN) and serum creatinine, before the initial infusion of Gammagard Liquid and again at appropriate intervals thereafter. If renal function deteriorates, consider discontinuation of Gammagard Liquid (see DOSAGE AND ADMINISTRATION[2]).

Hyperproteinemia, Increased Serum Viscosity, and Hyponatremia

 Hyperproteinemia, increased serum viscosity and hyponatremia may occur in patients receiving Gammagard Liquid. It is critical to distinguish true hyponatremia from a pseudohyponatremia that is temporally or causally related to hyperproteinemia 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 predisposition to thromboembolic events4.

Thrombotic Events

Thrombotic events, including myocardial infarction, cerebral vascular accident, deep vein thrombosis, and pulmonary embolism, have been reported in association with intravenous use of Gammagard Liquid (see ADVERSE REACTIONS [6]). Thrombotic events have also been reported with subcutaneous administration of immune globulin. Patients at risk for thrombotic events include those with a history of atherosclerosis, multiple cardiovascular risk factors, advanced age, impaired cardiac output, coagulation disorders, prolonged periods of immobilization, obesity, diabetes mellitus, acquired or inherited thrombophilic disorder, a history of vascular disease, or a history of a previous thrombotic or thromboembolic event.
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 (see WARNINGS AND PRECAUTIONS [5.9]). For patients judged to be at risk of developing thrombotic events, administer Gammagard Liquid intravenously at the minimum rate of infusion practicable, not exceeding 3.3 mg IgG/kg/min (< 2 mL/kg/hr) (see DOSAGE AND ADMINISTRATION [2.3]). When administering subcutaneously monitor the patients for signs and symptoms of thrombotic events.

Aseptic Meningitis Syndrome (AMS)

AMS may occur with IGIV treatment, and has been reported with intravenous use of Gammagard Liquid. 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 signs and symptoms: severe headache, nuchal rigidity, drowsiness, fever, photophobia, painful eye movements, nausea and vomiting. (see PATIENT COUNSELING INFORMATION [17]). Cerebrospinal fluid (CSF) studies frequently reveal pleocytosis up to several thousand cells per mm3, predominantly from the granulocytic series, and 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 with high dose (2 g/kg) IGIV treatment and/or rapid infusion of IGIV.

Hemolysis

Gammagard Liquid contains blood group antibodies which may act as hemolysins and induce in vivo coating of red blood cells (RBC) with immune globulin. These antibodies may cause a positive direct antiglobulin reaction and hemolysis3,5. Acute intravascular hemolysis has been reported, and  delayed hemolytic anemia can develop due to enhanced RBC sequestration (see ADVERSE REACTIONS [6]).

Monitor patients for clinical signs and symptoms of hemolysis (see WARNINGS AND PRECAUTIONS [5.9]). If signs and/or symptoms of hemolysis such as dark colored urine, swelling, fatigue or difficulty breathing, are present after Gammagard Liquid infusion, perform appropriate confirmatory laboratory testing (see PATIENT COUNSELING INFORMATION [17]).

Transfusion-Related Acute Lung Injury (TRALI)

Non-cardiogenic pulmonary edema (TRALI) has been reported in patients following treatment with IGIV products, including Gammagard Liquid. 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.

Transmittable Infectious Agents

Because 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 classic Creutzfeldt-Jakob disease agent. This also applies to unknown or emerging viruses and other pathogens. No cases of transmission of viral diseases or vCJD have been associated with Gammagard Liquid.

ALL infections thought by a physician to possibly have been transmitted by this product should be reported by the physician or other healthcare provider to Baxter Healthcare Corporation, at 1-800-423-2862 (in the U.S.).

Monitoring: Laboratory Tests

• Periodic monitoring of renal function and urine output is particularly important in patients judged to be at increased risk of developing acute renal failure. Assess renal function, including measurement of BUN and serum creatinine, before the initial infusion of Gammagard Liquid and at appropriate intervals thereafter.
• 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, because of the potentially increased risk of thrombosis3.
• If signs and/or symptoms of hemolysis are present after an infusion of Gammagard Liquid, perform appropriate laboratory testing for confirmation.
• If TRALI is suspected, perform appropriate tests for the presence of anti-neutrophil antibodies and anti-HLA antibodies in both the product and patient’s serum.

Interference with Laboratory Tests

After infusion of IgG, the transitory rise of the various passively transferred antibodies in the patient’s blood may yield false 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.

Mechanism of Action

Gammagard Liquid supplies a broad spectrum of opsonizing and neutralizing IgG antibodies against a wide variety of bacterial and viral agents. Gammagard Liquid also contains a spectrum of antibodies capable of interacting with and altering the activity of cells of the immune system as well as antibodies capable of reacting with cells such as erythrocytes. The role of these antibodies and the mechanisms of action of IgG in Gammagard Liquid have not been fully elucidated.

Pharmacokinetics

Intravenous Administration

Following intravenous infusion, IGIV products show a biphasic decay curve. The initial (α) phase is characterized by an immediate post-infusion peak in serum IgG and is followed by rapid decay due to equilibration between the plasma and extravascular fluid compartments. The second (β) phase is characterized by a slower and constant rate of decay. The commonly cited “normal” half-life of 18 to 25 days is based on studies in which tiny quantities of radiolabeled IgG are injected into healthy individuals.  When radiolabeled IgG was injected into patients with hypogammaglobulinemia or agammaglobulinemia, highly variable half-lives ranging from 12 to 40 days were observed.     In other radiolabeled studies, high serum concentrations of IgG, and hypermetabolism associated with fever and infection, have been seen to coincide with a shortened half-life of IgG.

In contrast, however, pharmacokinetic studies in immunodeficient patients are based on the decline of IgG concentrations following infusions of large quantities of immune globulin. In such trials, investigators have reported uniformly prolonged half-lives of 26 to 35 days. Pharmacokinetic parameters for Gammagard Liquid were determined from total IgG levels following the fourth infusion in 61 subjects with primary humoral immunodeficiency treated intravenously with the product every 3 or 4 weeks according to the regimen used prior to entering the study. Of these, 57 had sufficient pharmacokinetic data to be included in the dataset. The median weight-adjusted dose per subject was 455 mg/kg/4 weeks with a range of 262 to 710. Pharmacokinetic parameters are presented in Table 11.

Median IgG trough levels were maintained between 960 to 1120 mg/dL. These dosing regimens maintained serum trough IgG levels generally considered adequate to prevent bacterial infections. The elimination half-life of Gammagard Liquid of 35 days was similar to the half-lives reported for other IGIV products. 

Subcutaneous Administration

Pharmacokinetic (PK) parameters of subcutaneously administered Gammagard Liquid were evaluated in subjects with primary immunodeficiency (PI) who were 12 years and older during a clinical study (see CLINICAL STUDIES [14]). Subjects were treated intravenously for 12 weeks with Gammagard Liquid and then switched to weekly subcutaneous Gammagard Liquid infusions. Initially, all subjects were treated for a minimum of 12 weeks at a subcutaneous dose that was 130% of the intravenous dose. A comparison of the area under the curve (AUC) for intravenous and subcutaneous infusions done on the first 15 adult subjects determined that the subcutaneous dose required to provide an exposure from subcutaneous administration that was not inferior to the exposure from intravenous administration was 137% of the intravenous dose. Subsequently, all subjects were treated with this dose for 6 weeks after which the dose was individualized for all subjects using the trough IgG levels, as described below. After a minimum of 8 weeks at this subcutaneous dose, the PK evaluation was conducted on 32 subjects 12 years of age or older.

The mean adjusted dose at the end of the study was 137.3% (125.7-150.8) of the intravenous dose for subjects 12 years and older, and 141.0% (100.5 to 160.0) for subjects under the age of 12. Thus, there was not a significant dosing difference required for children. At this dose adjustment, the geometric mean ratio of the AUC for subcutaneous vs. intravenous Gammagard Liquid administration was 95.2% (90% confidence limit 92.3 to 98.2).  The peak IgG level occurred 2.9 (1.2 to 3.2) days after subcutaneous administration.

The pharmacokinetic parameters of Gammagard Liquid administered intravenously compared to subcutaneously in the clinical trial are shown in Table 12.  The mean peak IgG levels were lower (1393 ± 289 mg/dL) during subcutaneous treatment with Gammagard Liquid compared to when it was administered intravenously (2240 ± 536 mg/dL), consistent with the lower weekly dose compared to the dose administered every 3 or 4 weeks intravenously. In contrast, the mean trough levels were higher with Gammagard Liquid given subcutaneously (1202 ± 282 mg/dL), compared to those when given intravenously (1050 ± 260 mg/dL), a result of both higher monthly dose and more frequent dosing. The median IgG trough level during intravenous treatment in this clinical trial, 1010 mg/dL (95% CI: 940-1240), was similar to the median value of 1030 mg/dL (95% CI: 939 to 1110) during the intravenous clinical trial shown above in Table 11. By contrast, the median trough IgG level during subcutaneous treatment for the study was higher, at 1260 mg/dL (95% CI: 1060 to 1400).

See FDA approved patient labeling (Information for Patients) and instructions for use

Inform patients to immediately report the following signs and symptoms to their healthcare provider:

• Decreased urine output, sudden weight gain, fluid retention/edema, and/or shortness of breath  (see WARNINGS AND PRECAUTIONS [5.2])
• Acute chest pain, shortness of breath, leg pain, and swelling of the legs/feet, numbness in the face or extremities, weakness or paralysis, severe headache, confusion, visual disturbances

  (see WARNINGS AND PRECAUTIONS [5.4]).

• Severe headache, neck stiffness, drowsiness, fever, sensitivity to light, painful eye movements, nausea, and vomiting (see WARNINGS AND PRECAUTIONS [5.5]).
• Increased heart rate, fatigue, yellowing of the skin or eyes, and dark-colored urine (see WARNINGS AND PRECAUTIONS [5.6]).
• Trouble breathing, chest pain, blue lips or extremities, or fever that can occur 1 to 6 hours after an infusion of Gammagard Liquid (see WARNINGS AND PRECAUTIONS [5.7]).

Prior to starting Gammagard Liquid ask about a history of IgA deficiency, allergic reactions to immune globulin or other blood products. Patients with a history of allergic reactions should not be treated subcutaneously at home until several treatments have been administered and tolerated under medical supervision.

Inform patients that Gammagard Liquid is made from human plasma and may contain infectious agents that can cause disease (e.g., viruses and, theoretically, the vCJD agent). The risk of Gammagard Liquid transmitting an infectious agent has been reduced by screening plasma donors for prior exposure, testing donated plasma, and inactivating or removing certain viruses during manufacturing. Patients should report any symptoms that concern them which might be caused by virus infections (see WARNINGS AND PRECAUTIONS [5.8]).

Inform patients that Gammagard Liquid can interfere with their immune response to live viral vaccines such as measles, mumps, rubella and varicella, and instruct patients to notify their healthcare professional of this potential interaction when they are receiving vaccinations (see DRUG INTERACTIONS [7]).

Subcutaneous (SC) Administration Only

Self-administration – If self-administration is deemed to be appropriate by the physician, clear instructions and training on subcutaneous infusion should be given to the patient/caregiver, and the demonstration of their ability to independently administer subcutaneous infusions should be documented.

• Ensure the patient understands the importance of consistent weekly subcutaneous infusion to maintain appropriate steady IgG levels.
• Instruct the patient to keep a treatment diary/log book. This diary/log book should include information about each infusion such as, the time, date, dose, lot number(s) and any reactions.
• Inform the patient that mild to moderate local infusion-site reactions (e.g., swelling and redness) are a common side effect of subcutaneous treatment, but to contact their healthcare professional if a local reaction increases in severity or persists for more than a few days.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of kidney problems like unable to pass urine, change in how much urine is passed, blood in the urine, or a big weight gain.
• Fever or chills.
• Change in color of skin to a bluish color like on the lips, nail beds, fingers, or toes.
• Feeling very tired or weak.
• Seizures.
• Bloating.
• Feeling confused.
• Swelling.
• Very bad dizziness or passing out.
• A heartbeat that does not feel normal.
• Any unexplained bruising or bleeding.
• Mood changes.
• Muscle or joint pain.
• Change in speech.
• Change in eyesight.
• Blurred eyesight.
• Shakiness.
• Sweating a lot.
• Very bad belly pain.
• Dark urine or yellow skin or eyes.
• Very bad irritation where the shot was given.
• Lung problems have happened with this drug. Call your doctor right away if you have lung or breathing problems like trouble breathing, shortness of breath, or a cough that is new or worse.
• This drug may raise the chance of a very bad brain problem called aseptic meningitis. Call your doctor right away if you have a headache, fever, chills, very upset stomach or throwing up, stiff neck, rash, bright lights bother your eyes, feeling sleepy, or feeling confused.

Applies to immune globulin intravenous and subcutaneous: injectable solution

General

The most common adverse events were headache and injection/infusion site reactions.[Ref]

Local

Very common (10% or more): Infusion site reaction (75%)
Common (1% to 10%): Injection site reaction
Frequency not reported: Hives/urticaria, itching

Nervous system

Very common (10% or more): Headache (58%)
Common (1% to 10%): Dizziness
Postmarketing reports: Aseptic meningitis, coma, loss of consciousness, seizures/convulsions, tremor[Ref]

Dermatologic

Very common (10% or more): Ecchymosis/purpura (40%), petechiae (21%), rash (10%)
Common (1% to 10%): Pruritus, urticaria
Frequency not reported: Hives
Postmarketing reports: Stevens-Johnson syndrome, epidermolysis, erythema multiforme, bullous dermatitis[Ref]

Hematologic

Very common (10% or more): Hemorrhage (all systems) (29%), thrombocytopenia (15%)
Common (1% to 10%): Anemia
Uncommon (0.1% to 1%): Coombs negative hypochromic anemia, autoimmune pure red cell aplasia, exacerbation of autoimmune pure red cell aplasia
Postmarketing reports: Hemolytic anemia, pancytopenia, leukopenia, hemolysis, positive direct antiglobulin (Coombs test)[Ref]

Gastrointestinal

Very common (10% or more): Diarrhea (28%), nausea (21%), vomiting (21%)
Common (1% to 10%): Abdominal pain, dyspepsia[Ref]

Respiratory

Very common (10% or more): Cough increased (54%), rhinitis (51%), pharyngitis (41%), asthma (29%), epistaxis (23%)
Common (1% to 10%): Influenza, flu syndrome, sinusitis
Postmarketing reports: Apnea, acute respiratory distress syndrome (ARDS), transfusion related acute lung injury (TRALI), cyanosis, hypoxemia, pulmonary edema, dyspnea, bronchospasm[Ref]

Cardiovascular

Common (1% to 10%): Hypertension
Frequency not reported: Myocarditis
Postmarketing reports: Cardiac arrest, thromboembolism, vascular collapse, hypotension[Ref]

Hepatic

Very common (10% or more): Elevated ALT (18%), alkaline phosphatase elevated (13%)
Common (1% to 10%): AST elevated, low alkaline phosphatase
Postmarketing reports: Hepatic dysfunction[Ref]

Other

Very common (10% or more): Fever (28%), ear pain (18%), accidental injury (13%), asthenia (10%)
Common (1% to 10%): Fatigue
Postmarketing reports: Rigors

Musculoskeletal

Common (1% to 10%): Arthralgia, back pain, neck pain
Uncommon (0.1% to 1%): Severe chills[Ref]

Psychiatric

Frequency not reported: Anxiety

Some side effects of immune globulin intravenous and subcutaneous may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.