Included as part of the PRECAUTIONS section.
Severe hypersensitivity reactions may occur with IGIV
products, including GAMUNEX-C. In case of hypersensitivity, discontinue
GAMUNEX-C infusion immediately and institute appropriate treatment. Have
medications such as epinephrine available for immediate treatment of acute
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)
Acute renal dysfunction/failure, acute tubular necrosis,
proximal tubular nephropathy, osmotic nephrosis and death may occur upon use of
IGIV products, especially those containing sucrose.(7,8) GAMUNEX-C does not
contain sucrose. Ensure 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 INFORMATION) 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
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
Thrombosis may occur following treatment with immune
globulin products, including GAMUNEX-C.(10-12) Risk factors may include:
advanced age, prolonged immobilization, hypercoagulable conditions, history of
venous or arterial thrombosis, use of estrogens, indwelling central vascular
catheters, hyperviscosity, and cardiovascular risk factors. Thrombosis may
occur in the absence of known risk factors.
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 at risk of thrombosis, administer
GAMUNEX-C at the minimum dose and infusion rate practicable. Ensure adequate
hydration in patients before administration. Monitor for signs and symptoms of
thrombosis and assess blood viscosity in patients at risk for hyperviscosity. (see
BOXED WARNING, DOSAGE AND ADMINISTRATION], PATIENT INFORMATION)
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.
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.(13-16) Delayed hemolytic anemia can develop
subsequent to IGIV therapy due to enhanced RBC sequestration, and acute
hemolysis consistent with intravascular hemolysis, has been reported. (see
The following risk factors may be related to the
development of hemolysis: high doses (e.g., ≥ 2 grams/kg, single
administration or divided over several days) and non-O blood group. (17)
Underlying inflammatory state in an individual patient may increase the risk of
hemolysis, but its role is uncertain.(18)
Monitor patients for clinical signs and symptoms of
hemolysis (see Monitoring: Laboratory Tests), particularly patients with
risk factors noted above. Consider appropriate laboratory testing in higher
risk patients, including measurement of hemoglobin or hematocrit prior to
infusion and within approximately 36 to 96 hours post infusion. If clinical
signs and symptoms of hemolysis or a significant drop in hemoglobin or hematocrit
have been observed, perform additional confirmatory laboratory testing. If
transfusion is indicated for patients who develop hemolysis with clinically
compromising anemia after receiving IGIV, perform adequate cross-matching to
avoid exacerbating on-going hemolysis.
Transfusion-related Acute Lung Injury (TRALI)
Noncardiogenic pulmonary edema may occur in patients
following treatment with IGIV products, including GAMUNEX-C.(19) 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 INFORMATION) 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.
The high dose regimen (1 g/kg x 1-2 days) is not
recommended for individuals with expanded fluid volumes or where fluid volume
may be a concern.
Transmission Of Infectious Agents
Because GAMUNEX-C is made from human blood, 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 (CJD) agent. No cases of transmission of viral
diseases, vCJD 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 Grifols
Therapeutics Inc. [1-800-520-2807]
Do not administer GAMUNEX-C subcutaneously in patients
with ITP because of the risk of hematoma formation.
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 GAMUNEX-C and at appropriate
- 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
- If signs and/or symptoms of hemolysis are present after
an infusion of GAMUNEX-C, perform appropriate laboratory testing for
- 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 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.
Patient Counseling Information
(see BOXED WARNING and WARNINGS AND PRECAUTIONS)
Instruct 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)
- Symptoms of thrombosis which may include: pain and/or
swelling of an arm or leg with warmth over the affected area, discoloration of
an arm or leg, unexplained shortness of breath, chest pain or discomfort that
worsens on deep breathing, unexplained rapid pulse, numbness or weakness on one
side of the body (see WARNINGS AND PRECAUTIONS)
- Severe headache, neck stiffness, drowsiness, fever,
sensitivity to light, painful eye movements, nausea, and vomiting (see WARNINGS
- Increased heart rate, fatigue, yellowing of the skin or
eyes, and dark-colored urine (see WARNINGS AND PRECAUTIONS)
- Trouble breathing, chest pain, blue lips or extremities,
and fever (see WARNINGS AND PRECAUTIONS)
Inform patients that GAMUNEX-C is made from human plasma
and may contain infectious agents that can cause disease. While the risk
GAMUNEX-C can transmit an infectious agent has been reduced by screening plasma
donors for prior exposure, testing donated plasma, and by inactivating or
removing pathogens during manufacturing, patients should report any symptoms
that concern them. (see WARNINGS AND PRECAUTIONS)
Â Inform patients that GAMUNEX-C can interfere with their
immune response to live viral vaccines such as measles, mumps and rubella.
Inform patients to notify their healthcare professional of this potential interaction
when they are receiving vaccinations. (see DRUG INTERACTIONS)
PI: Self-Administration: Subcutaneous Administration Only
Advise the patient to read the FDA-approved patient
labeling (Instructions for Use: Subcutaneous Infusion for Primary Humoral
Provide the patient with instructions on subcutaneous
infusion for home treatment, if the physician believes that home administration
is appropriate for the patient.
- The type of equipment to be used along with its
- proper infusion techniques, selection of appropriate
infusion sites (e.g., abdomen, thighs, upper arms, and/or lateral hip),
- maintenance of a treatment diary, and
- measures to be taken in case of adverse reactions in the
Use In Specific Populations
There is no data with GAMUNEX-C
use in pregnant women to inform a drug-associated risk. Animal reproduction
studies have not been conducted with GAMUNEX-C. It is not known whether
GAMUNEX-C can cause fetal harm when administered to a pregnant woman or can affect
reproduction capacity. GAMUNEX-C should be given to a pregnant woman only if
clearly needed. In the U.S. general population, the estimated background risk
of major birth defect and miscarriage in clinically recognized pregnancies is
2-4% and 15-20%, respectively.
There is no information
regarding the presence of GAMUNEX-C in human milk, the effect on the breastfed
infant, and the effects on milk production. The developmental and health
benefits of breastfeeding should be considered along with the mother's clinical
need for GAMUNEX-C and any potential adverse effects on the breastfed infant
from GAMUNEX-C or from the underlying maternal condition.
GAMUNEX-C was evaluated in 18
pediatric subjects (age range 0-16 years). Twenty-one percent of PI subjects
exposed to GAMUNEX-C were children. Pharmacokinetics, safety and efficacy were
similar to those in adults with the exception that vomiting was more frequently
reported in pediatrics (3 of 18 subjects). No pediatric-specific dose
requirements were necessary to achieve serum IgG levels.
SC GAMUNEX-C was evaluated in
three pediatric subjects (age range 13-15 years) with PI along with adults, and
separately in a second trial in 11 children and adolescents (age range 2-16
years). Pharmacokinetics and safety were similar to those in adults. No
pediatric-specific dose requirements were necessary to achieve circulating IgG
levels. Efficacy and safety in pediatric patients under 2 years of age using
the SC route of administration have not been established.
For treatment of ITP, GAMUNEX-C
must be administered by the intravenous route.
GAMUNEX-C was evaluated in 12
pediatric subjects with acute ITP. Twenty-five percent of the acute ITP
subjects exposed to GAMUNEX-C were children. Pharmacokinetics, safety and
efficacy were similar to those in adults with the exception that fever was more
frequently reported in pediatrics (6 of 12 subjects). No pediatric-specific
dose requirements were necessary to achieve serum IgG levels. One subject, a
10-year-old boy, died suddenly from myocarditis 50 days after his second
infusion of GAMUNEX-C. The death was judged to be unrelated to GAMUNEX-C.
The safety and effectiveness of
GAMUNEX-C have not been established in pediatric subjects with CIDP.
Use caution when administering
GAMUNEX-C to patients age 65 and over who are at increased risk for thrombosis
or renal insufficiency. (see BOXED WARNING, WARNINGS AND
PRECAUTIONS) Do not exceed recommended doses, and
administer GAMUNEX-C at the minimum infusion rate practicable. Clinical studies
of GAMUNEX-C did not include sufficient numbers of subjects aged 65 and over to
determine whether they respond differently from younger subjects.
7. Cayco AV, Perazella MA,
Hayslett JP. Renal insufficiency after intravenous immune globulin therapy: a
report of two cases and an analysis of the literature. J Am Soc Nephrol
8. Pierce LR, Jain N. Risks
associated with the use of intravenous immunoglobulin. Trans Med Rev
9. Steinberger BA, Ford SM,
Coleman TA. Intravenous immunoglobulin therapy results in post-infusional
hyperproteinemia, increased serum viscosity, and pseudohyponatremia. Am J
10. Dalakas MC. High-dose
intravenous immunoglobulin and serum viscosity: risk of precipitating
thromboembolic events. Neurology 1994;44:223-6.
11. Woodruff RK, Grigg AP,
Firkin FC, et al. Fatal thrombotic events during treatment of autoimmune thrombocytopenia with intravenous immunoglobulin in elderly patients. Lancet
12. Wolberg AS, Kon RH, Monroe
DM, et al. Coagulation factor XI is a contaminant in intravenous immunoglobulin
preparations. Am J Hematol 2000;65:30-4.
13. Copelan EA, Strohm PL,
Kennedy MS, et al. Hemolysis following intravenous immune globulin therapy.
14. Thomas MJ, Misbah SA,
Chapel HM, et al. Hemolysis after high-dose intravenous Ig. Blood 1993;15:3789.
15. Wilson JR, Bhoopalam N,
Fisher M. Hemolytic anemia associated with intravenous immunoglobulin. Muscle
& Nerve 1997;20:1142-5.
16. Kessary-Shoham H, Levy Y,
Shoenfeld Y, et al. In vivo administration of intravenous immunoglobulin (IVIg)
can lead to enhanced erythrocyte sequestration. J Autoimmune 1999;13:129-35.
17. Kahwaji J, Barker E,
Pepkowitz S, et al. Acute hemolysis after high-dose intravenous immunoglobulin
therapy in highly HLA sensitized patients. Clin J Am Soc Nephrol 2009;4:1993-7.
18. Daw Z, Padmore R, Neurath
D, et al. Hemolytic transfusion reactions after administration of intravenous
immune (gamma) globulin: A case series analysis. Transfusion 2008;48:1598-601.
19. Rizk A, Gorson KC, Kenney
L, et al. Transfusion-related acute lung injury after the infusion of IVIG.