Included as part of the PRECAUTIONS section.
Severe hypersensitivity reactions may occur [see CONTRAINDICATIONS].
In case of hypersensitivity, discontinue the Privigen infusion immediately and
institute appropriate treatment. Medications such as epinephrine should be
available for immediate treatment of acute hypersensitivity reactions.
Privigen contains trace amounts of IgA ( ≤ 25 mcg/mL)
[see DESCRIPTION]. Individuals with IgA deficiency can develop anti-IgA
antibodies and anaphylactic reactions (including anaphylaxis and shock) after
administration of blood components containing IgA. Patients with known
antibodies to IgA may have a greater risk of developing potentially severe hypersensitivity
and anaphylactic reactions with administration of Privigen. Privigen is contraindicated
in patients with antibodies against IgA and a history of hypersensitivity.
Renal Dysfunction And Acute Renal Failure
Renal dysfunction, acute renal failure, osmotic
nephrosis, and death may occur with immune globulin intravenous (IGIV) products
in predisposed patients. Renal dysfunction and acute renal failure occur more
commonly in patients receiving IGIV products containing sucrose.4 Privigen
does not contain sucrose. Ensure that patients are not volume depleted and
assess renal function, including measurement of blood urea nitrogen (BUN) and
serum creatinine, before the initial infusion of Privigen and at appropriate
intervals thereafter. Periodic monitoring of renal function and urine output is
particularly important in patients judged to be at increased risk of developing
acute renal failure.4 If renal function deteriorates, consider
discontinuing Privigen. For patients judged to be at risk of developing renal
dysfunction because of pre-existing renal insufficiency, or predisposition to
acute renal failure (such as those with diabetes mellitus or hypovolemia, those
who are obese, those who use concomitant nephrotoxic medicinal products, or
those who are over 65 years of age), administer Privigen at the minimum rate of
infusion practicable [see BOXED WARNING, Administration].
Thrombosis may occur following treatment with immune
globulin products1-3, including Privigen. 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 Privigen
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].
Hyperproteinemia, Increased Serum Viscosity, And Hyponatremia
Hyperproteinemia, increased serum viscosity, and
hyponatremia may occur following treatment with IGIV products, including
Privigen. The hyponatremia is likely to be a pseudohyponatremia, as
demonstrated by a decreased calculated serum osmolality or elevated osmolar
gap. It is critical to distinguish true hyponatremia from pseudohyponatremia,
as 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.5
Aseptic Meningitis Syndrome (AMS)
AMS may occur infrequently following treatment with
Privigen [see ADVERSE REACTIONS] and other human immune globulin
products. Discontinuation of treatment has resulted in remission of AMS within
several days without sequelae.6 AMS usually begins within several
hours to 2 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. Cerebrospinal fluid (CSF) studies are
frequently positive with pleocytosis up to several thousand cells per cubic
millimeter, 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 signs
and symptoms, 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.
Privigen may contain blood group antibodies that can act
as hemolysins and induce in vivo coating of red blood cells (RBCs) with
immunoglobulin, causing a positive direct antiglobulin test (DAT) (Coombs'
test) result and hemolysis.7-9 Delayed hemolytic anemia can develop
subsequent to Privigen therapy due to enhanced RBC sequestration, and acute hemolysis,
consistent with intravascular hemolysis, has been reported.10 Cases
of severe hemolysis-related renal dysfunction/failure or disseminated
intravascular coagulation have occurred following infusion of Privigen.
The following risk factors may be associated with the
development of hemolysis: high doses (e.g., ≥ 2 g/kg), given either as a
single administration or divided over several days, and non-O blood group.11
Other individual patient factors, such as an underlying inflammatory state (as
may be reflected by, for example, elevated C-reactive protein or erythrocyte sedimentation
rate), have been hypothesized to increase the risk of hemolysis following administration
of IGIV,12 but their role is uncertain. Hemolysis has been reported
following administration of IGIV for a variety of indications, including ITP
Closely monitor patients for clinical signs and symptoms
of hemolysis, 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 following
treatment with IGIV products, including Privigen.13 TRALI is
characterized by severe respiratory distress, pulmonary edema, hypoxemia,
normal left ventricular function, and fever. Symptoms typically appear within 1
to 6 hours following treatment.
Monitor patients for pulmonary adverse reactions. If
TRALI is suspected, perform appropriate tests for the presence of
anti-neutrophil antibodies and anti-human leukocyte antigen (HLA) antibodies in
both the product and the patient's serum. TRALI may be managed using oxygen
therapy with adequate ventilatory support.
Carefully consider the relative risks and benefits before
prescribing the high dose regimen (for chronic ITP) in patients at increased
risk of thrombosis, hemolysis, acute kidney injury, or volume overload.
Transmissible Infectious Agents
Because Privigen 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). The risk of infectious agent
transmission has been reduced by screening plasma donors for prior exposure to
certain viruses, testing for the presence of certain current virus infections,
and including virus inactivation/removal steps in the manufacturing process for
Privigen. Report any infection thought to be possibly transmitted by Privigen
to CSL Behring Pharmacovigilance at 1-866-915-6958.
Interference With Laboratory Tests
Various passively transferred antibodies in
immunoglobulin preparations may lead to misinterpretation of the results of
Use In Specific Populations
Pregnancy Category C. Animal reproduction studies
have not been conducted with Privigen. It is not known whether Privigen can
cause fetal harm when administered to a pregnant woman or can affect
reproduction capacity. Privigen should be given to pregnant women only if
clearly needed. Immunoglobulins cross the placenta from maternal circulation
increasingly after 30 weeks of gestation.16,17
Use of Privigen in nursing mothers has not been
Treatment Of Primary Humoral Immunodeficiency
Privigen was evaluated in 31 pediatric subjects (19
children and 12 adolescents) with PI (pivotal study). There were no apparent
differences in the safety and efficacy profiles as compared to those in adult
subjects. No pediatric-specific dose requirements were necessary to achieve the
desired serum IgG levels. The safety and effectiveness of Privigen have not
been established in pediatric patients with PI who are under the age of 3.
Treatment Of Chronic Immune Thrombocytopenic Purpura
The safety and effectiveness of Privigen have not been
established in pediatric patients with chronic ITP who are under the age of 15.
Clinical studies of Privigen did not include sufficient
numbers of subjects age 65 and over to determine whether they respond differently
from younger subjects.
Use caution when administering Privigen to patients age
65 and over who are judged to be at increased risk of developing acute renal
insufficiency and thrombosis [see BOXED WARNING, WARNINGS AND
PRECAUTIONS]. Do not exceed recommended doses, and administer Privigen at
the minimum dose and infusion rate practicable.
1. Dalakas MC. High-dose intravenous immunoglobulin and
serum viscosity: risk of precipitating thromboembolic events. Neurology 1994;44:223-226.
2. Woodruff RK, Grigg AP, Firkin FC, Smith IL. Fatal
thrombotic events during treatment of autoimmune thrombocytopenia with
intravenous immunoglobulin in elderly patients. Lancet 1986;2:217-218.
3. Wolberg AS, Kon RH, Monroe DM, Hoffman M. Coagulation
factor XI is a contaminant in intravenous immunoglobulin preparations. Am J
4. 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 1997;8:1788-1793.
5. Steinberger BA, Ford SM, Coleman TA. Intravenous
immuneglobulin therapy results in post-infusional hyperproteinemia, increased
serum viscosity, and pseudohyponatremia. Am J Hematol 2003;73:97-100.
6. Gabor EP. Meningitis and skin reaction after
intravenous immune globulin therapy. Ann Intern Med 1997;127:1130.
7. Copelan EA, Strohm PL, Kennedy MS, Tutschka PJ.
Hemolysis following intravenous immune globulin therapy. Transfusion 1986;26:410-412.
8. Thomas MJ, Misbah SA, Chapel HM, Jones M, Elrington G,
Newsom-Davis J. Hemolysis after high-dose intravenous Ig. Blood 1993;15:3789.
9. Wilson JR, Bhoopalam N, Fisher M. Hemolytic anemia
associated with intravenous immunoglobulin. Muscle Nerve 1997;20:1142-1145.
10. Kessary-Shoham H, Levy Y, Shoenfeld Y, Lorber M,
Gershon H. In vivo administration of intravenous immunoglobulin (IVIg) can lead
to enhanced erythrocyte sequestration. J Autoimmun 1999;13:129-135.
11. 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;4:1993-1997.
12. Daw Z, Padmore R, Neurath D, et al. Hemolytic
transfusion reactions after administration of intravenous immune (gamma)
globulin: A case series analysis. Transfusion 2008;48:1598-1601.
13. Rizk A, Gorson KC, Kenney L, Weinstein R.
Transfusion-related acute lung injury after the infusion of IVIG. Transfusion 2001;41:264-268.
15. Siber GA, Werner BG, Halsey NA, et al. Interference
of immune globulin with measles and rubella immunization. J Pediatr 1993;122:204-211.
16. Hammarström L, Smith CIE. Placental transfer of
intravenous immunoglobulin. Lancet 1986;1:681.
17. Sidiropoulos D, Herrmann U, Morell A, von Muralt G,
Barandun S. Transplacental passage of intravenous immunoglobulin in the last
trimester of pregnancy. J Pediatr 1986;109:505-508.