Critical Care and Immunology Therapies

Immune-mediated disorders occur when the body's immune system, which normally protects us against infection and foreign substances, doesn’t function properly. People affected by such conditions are more susceptible to disease. Some immune-mediated disorders are referred to as autoimmune diseases in which the immune system does not recognize the person’s own tissues and mistakenly attacks them.

A wide variety of immune-mediated disorders have been identified; two of these are primary immunodeficiency (PI) and immune/idiopathic thrombocytopenic purpura (ITP).

Primary Immunodeficiency

The immune system acts to protect the body against infections. These infections may be due to various forms of living entities, including bacteria, viruses, fungi, and parasites. The immune system uses lymphocytes (or other types of white blood cells such as neutrophils and macrophages) and immunoglobulins (also known as antibodies) to fight off these foreign invaders.

In some people, one or more parts of the immune system fail to work properly or adequately. This is called primary immunodeficiency (PI). There are many different types of primary immunodeficiencies. People with primary humoral immune deficiency have difficulty fighting off infections due to inadequate antibody production.

When a person's body lacks immunoglobulin or has an insufficient quantity, replacement immunoglobulin therapy is typically given. This replacement immunoglobulin is extracted from donated human plasma (the liquid portion of blood). When a person is given replacement immunoglobulin, it is called immunoglobulin therapy or immunotherapy. This replacement immunoglobulin helps to restore a person's immune system, and is given chronically (for life).

Immune/Idiopathic Thrombocytopenic Purpura

Another type of immune-mediated disorder is immune/idiopathic thrombocytopenic purpura (ITP), a bleeding disorder that often causes purple bruises on the skin, and in its most severe manifestation could also cause life-threatening bleeding, eg, a bleed in the brain. ITP affects platelets, the blood components involved in the clotting process.

To understand ITP, it's best to define each of the terms that make up its name. Immune means that the condition is caused by the immune system, which normally defends our body against infection and foreign substances. In the case of ITP, the immune system mistakenly attacks certain cellular components (platelets) in a person's own blood, which leads to a low level of platelets. Thrombocytopenic indicates that the illness is related to low levels of thrombocytes, also called platelets, which help stop bleeding. And purpura refers to the purplish areas of the skin where bleeding has occurred.

There are two forms of ITP: acute, which occurs most commonly in children and lasts for less than six months; and chronic, which generally affects adults between the ages of 20 and 40. Chronic ITP lasts longer than six months, as patients suffer from repeated bleeding attacks (relapses). Treatment is generally needed for chronic ITP.

Intravenous Immunoglobulin therapy is used as a treatment to elevate platelet counts in order to help control bleeding.

CSL Behring offers a number of high-quality products for the treatment of these conditions. Please see the following CSL Behring web resources:

AlbuRx^® 5, AlbuRx^® 25

Albuminar^® 5, Albuminar^®

Carimune^® NF

www.cytogam.com

www.hizentra.com

www.privigen.com

www.TreatingPI.com

www.rhophylac.com

Important Safety Information for AlbuRx 5 and AlburRx 25

The use of AlbuRx 5 and 25 is contraindicated in patients with a history of an incompatibility reaction to human albumin. AlbuRx 5 may be contraindicated in patients with cardiac failure or severe anemia due to the risk of acute circulatory overload.

Reported adverse reactions include nausea, chills, fever, urticaria, headache, and hypotension.

AlbuRx is derived from human plasma. The risk of transmission of infectious agents, including viruses and, theoretically, the Creutzfeldt-Jakob (CJD) disease agent, cannot be completely eliminated.

Please see full prescribing information for AlbuRx 5 and AlbuRx 25.

Important Safety Information for Albuminar 5 and Albuminar 25

Albuminar is contraindicated in patients with severe anemia or cardiac failure and in patients with a history of allergic reactions to human albumin.

Reports have been received of anaphylaxis, which may be severe, and hypersensitivity reactions, including urticaria, skin rash, pruritus, edema, erythema, hypotension and bronchospasm. Nausea, vomiting, increased salivation, chills and febrile reactions have also been reported.

Albuminar is derived from human plasma. The risk of transmission of infectious agents, including viruses, and theoretically, the Creutzfeldt-Jakob (CJD) disease agent, cannot be completely eliminated.

Please see full prescribing information for Albuminar 5 and Albuminar 25.

Important Safety Information for Carimune NF

Carimune^® NF, Nanofiltered Immune Globulin Intravenous (Human) is indicated for the maintenance treatment of patients with primary immunodeficiencies (PI), such as common variable immunodeficiency, X-linked agammaglobulinemia, and severe combined immunodeficiency, as well as for for acute and chronic immune thrombocytopenic purpura (ITP).

Immune Globulin Intravenous (Human) (IGIV) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include those over age 65, those receiving known nephrotoxic drugs and those with preexisting renal insufficiency, diabetes mellitus, volume depletion, sepsis, or paraproteinemia. In such patients, IGIV products should be administered at the minimum concentration available and the minimum rate of infusion practicable. While reports of renal dysfunction and acute renal failure have been associated with the use of many licensed IGIV products, those containing sucrose as a stabilizer accounted for a disproportionate share of reports. See PRECAUTIONS and DOSAGE AND ADMINISTRATION sections of full prescribing information for important information intended to reduce the risk of acute renal failure.

Increases in creatinine and blood urea nitrogen with progression to oliguria or anuria requiring dialysis have been observed with IVIG products. Severe renal adverse events have included acute renal failure, acute tubular nephrosis, proximal tubular nephropathy, and osmotic nephrosis. Monitoring of renal function and urine output is advised in patients at risk for renal events.

There have been reports of aseptic meningitis, hemolysis, transfusion-related acute lung injury, and thrombotic events with use of IVIG. Slow or temporarily stop infusion if patient experiences facial flushing, tightness in chest, chills, fever, nausea, dizziness or other unusual response; stop infusion immediately if anaphylaxis or severe reaction occurs.

Carimune NF is contraindicated in patients who have had anaphylactic or severe systemic reactions to the administration of human immune globulin. Individuals with selective IgA deficiency who possess antibody to IgA should only receive Carimune NF with utmost caution due to risk of severe, immediate hypersensitivity reactions, including anaphylaxis.

Carimune^® NF is derived from human plasma. The risk of transmission of infectious agents, including viruses and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent, cannot be completely eliminated.

Please see full prescribing information, including boxed warning on Acute Renal Failure.

Important Safety Information for Cytogam

Cytogam^®, Cytomegalovirus Immune Globulin Intravenous (Human), is indicated for the prophylaxis of cytomegalovirus disease associated with transplantation of kidney, lung, liver, pancreas, and heart. In transplants of these organs other than kidney from CMV seropositive donors into seronegative recipients, prophylactic CMV-IGIV should be considered in combination with ganciclovir.

Cytogam is contraindicated in individuals with a history of a prior severe reaction associated with the administration of this or other human immunoglobulin preparations and in persons with selective immunoglobulin A deficiency who have known antibodies to IgA.

Immune Globulin Intravenous (Human) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis and death. Patients predisposed to acute renal failure include patients with any degree of preexisting renal insufficiency, diabetes mellitus, age greater than 65, volume depletion, sepsis, paraproteinemia or patients receiving known nephrotoxic drugs. Especially in such patients, IGIV products should be administered at the minimum concentrations available and the minimum rate of infusion practicable.

Increases in serum creatinine and blood urea nitrogen (BUN) have been observed as soon as one to two days following IGIV infusion. Progression to oliguria or anuria requiring dialysis has been observed.

Cytogam is derived from human plasma. The risk of transmission of infectious agents, including viruses and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent, cannot be completely eliminated.

Minor reactions, such as flushing, chills, muscle cramps, back pain, fever, nausea, vomiting, arthralgia, and wheezing, were the most frequent adverse reactions observed during the clinical trials for Cytogam

Please see full prescribing information for Cytogam

Important Safety Information for Hizentra

Immune Globulin Subcutaneous (Human), Hizentra^®, treats various forms of primary immunodeficiency (PI) in patients age 2 and over.

Hizentra should not be used if you have had serious negative reactions to immune globulin (Ig) preparations or a deficiency of an Ig known as IgA. Because Hizentra contains the amino acid proline as stabilizer, patients with hyperprolinemia (too much proline in the blood) should not take Hizentra.

Infuse Hizentra under your skin only; do not inject into a blood vessel.

Allergic reactions can occur with Hizentra. If your doctor suspects you are having a bad allergic reaction or are going into shock, treatment will be discontinued. Immediately tell your doctor or go to the emergency room if you have signs of such a reaction, including hives, trouble breathing, wheezing, dizziness, or fainting.

Tell your doctor about any side effects that concern you. Your doctor will monitor for potentially serious reactions that have been seen with Ig treatment, including thrombotic events (blood clotting); aseptic meningitis syndrome (brain swelling); osmotic nephropathy (a kidney condition); hemolysis (a blood problem) and transfusion-related acute lung injury.

The most common drug-related adverse reactions in the clinical trial for Hizentra were injection-site reactions (swelling, pain, redness, heat or itching); headache; back pain; diarrhea; tiredness; cough; rash; itching; nausea and vomiting.

Hizentra is made from components of human blood. The risk of transmission of infectious agents, including viruses and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent, cannot be completely eliminated.

Vaccines (such as measles, mumps and rubella) might not work as well if you are using Hizentra. Before receiving a vaccination, tell the healthcare professional that you are being treated with Hizentra. Also tell your doctor if you are pregnant or nursing, or if you plan to become pregnant.

Please see full prescribing information for Hizentra, including the patient product information.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

Important Safety Information for Privigen

Immune Globulin Intravenous (Human), 10% Liquid, Privigen^®, is approved for the treatment of primary immunodeficiency (PI), and to raise platelet counts in patients with chronic immune thrombocytopenic purpura (ITP).

WARNING: Kidney dysfunction, including acute renal failure and possibly leading to death, have been associated with the administration of Immune Globulin Intravenous (Human) (IVIg) products. Kidney dysfunction and failure have been more commonly associated with IVIg products containing sucrose. Privigen does not contain sucrose. If you have kidney dysfunction, your doctor should administer IVIg products at the minimum infusion rate possible. See your doctor for a full explanation and the full prescribing information for complete boxed warning.

If you have previously had a severe reaction to the administration of human immune globulin, or have hyperprolinemia or selective IgA deficiency, tell your doctor, as you should not be treated with Privigen. Inform your physician if you notice early signs of hypersensitivity reactions (including hives, tightness of the chest, wheezing, or shock); administration of Privigen may be discontinued.

If you notice a decrease in urine output, sudden weight gain, fluid retention, and/or shortness of breath following infusion with Privigen, contact your doctor immediately. Also inform your doctor if you experience any of the following: severe headache; a stiff neck; drowsiness or fatigue; fever; sensitivity to light or painful eye movements; nausea; increased heart rate; yellowing of the skin or eyes, and/or dark-colored urine.

Privigen is made from human blood. The risk that a blood-derived product might contain infectious agents that can cause disease–such as viruses, and, theoretically, the Creutzfeldt-Jakob disease agent—cannot be completely eliminated.

Privigen use can impair the effectiveness of live virus vaccines (eg, measles, mumps, and rubella). Before receiving any vaccine, tell the immunizing physician that you have had recent therapy with Privigen.

In clinical studies of Privigen in patients with PI, adverse reactions seen in more than 5% of patients included headache, pain, nausea, fever, fatigue, chills, joint swelling, vomiting, and hives. In studies of patients being treated with Privigen for chronic ITP, the most common side effects included headache, fever, anemia, vomiting, and nausea, as well as increases in bilirubin and certain liver enzymes.

Please see full prescribing information for Privigen.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

Important Safety Information for Rhophylac

Rhophylac^®, Rho(D), Immune Globulin Intravenous (Human), is a blood-derived injection given to women with an Rh-negative blood type who might have an incompatible pregnancy—that is, might be carrying a child with Rh-positive blood. If a woman in such a pregnancy is not treated, the result could be “isoimmunization,” a condition in which the mother’s Rh-negative blood produces antibodies that could attack the unborn child’s Rh-positive blood cells, potentially creating serious health problems for the unborn child and any future children.

Rhophylac is given by physicians as routine protection against isoimmunization,with administration during pregnancy and often repeated within 72 hours following childbirth. It is also given in cases of obstetric complications, invasive procedures during pregnancy, or obstetric manipulative procedures, as well as in incomplete pregnancies. Rhophylac is also used in Rh-negative individuals who have received blood components containing Rho(D)-positive red blood cells. For suppression of Rh isoimmunization, Rhophylac can be administered intravenously or intramuscularly, but must not be given to the newborn infant.

You should not be given Rhophylac if you have had a previous serious allergic reaction to Rhophylac or other human blood products. It should also not be given if your blood has an insufficient quantity of a protein called IgA, has produced antibodies to IgA, and you have known hypersensitivity to IgA. Your physician will do a blood test to assess your situation regarding IgA.

Some women have experienced mild and temporary reactions after receiving Rhophylac, such as fever; overall discomfort or uneasiness; headache, skin reactions (such as hives or welts); and/or chills. If you received Rhophylac as a shot (intramuscularly), you could experience pain or tenderness at the injection site; adverse reactions to Rhophylac typically do not last long. This list is not complete, so discuss with your doctor any reaction or symptom you experience, and see full prescribing information for a more complete list.

Rhophylac is made from donated human blood. The risk of transmission of infectious agents, including viruses, cannot be completely eliminated.

Immunoglobulin administration can transiently interfere with your response to live virus vaccines, such as measles, mumps and rubella (note that most influenza vaccines are not “live” vaccines). Tell your doctor if you plan to receive a vaccine after receiving Rhophylac.

Please see full prescribing information for Rhophylac, which includes a boxed warning that does not apply to use of Rhophylac in pregnancy or cases of incompatible transfusion.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.