CSL Behring's Privigen

Privigen, Immune Globulin Intravenous (Human), is available as a 10% liquid preparation of polyvalent human immunoglobulin. Indications include the treatment of primary humoral immunodeficiency (PI) associated with defects in humoral immunity, including but not limited to common variable immunodeficiency (CVID), X-linked agammaglobulinemia (XLA), congenital agammaglobulinemia, Wiskott-Aldrich syndrome, and severe combined immunodeficiencies.1-3

Privigen is also indicated to rapidly raise platelet counts to prevent bleeding in patients with chronic immune thrombocytopenic purpura (ITP).1-3 Mechanism of Action Privigen is an antibody replacement therapy for PI, and supplies a broad spectrum of opsonic and neutralizing immunoglobulin G antibodies against bacterial, viral, parasitic, and mycoplasma agents and their toxins.1-3 The specific mechanism of action in the treatment of PI or the use of high doses of immunoglobulins in the treatment of chronic ITP has not been fully elucidated, however.1-3

Clinical Trials

Privigen has been studied in patients with both PI and chronic ITP.1-5 The efficacy, safety, and pharmacokinetics of Privigen in patients with PI was investigated in a prospective, open-label, single-arm, multicenter, phase III study.4,5 The study was performed involving 80 subjects with XLA or CVID who had been receiving intravenous immunoglobulin (IVIG) replacement therapy for at least 6 months prior to study entry.3-5 Patients received Privigen at individually adjusted doses ranging from 200 to 888 mg/kg for 12 months.3-5 Efficacy was determined by the rate of acute serious bacterial infections (aSBIs). The annual aSBI rate during the 12-month study period was 0.08 per subject, and met the predefined success rate of less than one aSBI per patient per year.

A prospective, open-label, single-arm, multicenter study evaluated the efficacy of Privigen in 57 subjects with chronic ITP and a baseline platelet count of 20 x 109/L or less.3,7 Subjects received a cumulative 2-g/ kg dose of Privigen, administered as two 1-g/kg intravenous infusions for 2 consecutive days and were observed for 29 days.2,3,6 The primary end point was the response rate, defined as the percentage of subjects with an increase in platelet counts to at least 50 x 109/L within 7 days after the first infusion.2,3,6 Of the 57 subjects in the efficacy analysis, 46 (80.7%) responded to Privigen. Median time to response was 2.5 days.

Safety and efficacy of Privigen have not been evaluated in nursing mothers. Privigen is listed as pregnancy category C.1-3 Privigen should be given to pregnant women only if clearly needed. The safety and effectiveness of Privigen has not been established in pediatric subjects with PI who are under the age of 3 years1,2 or in pediatric subjects with chronic ITP who are under the age of 15 years.1-3

Dosage and Administration

Privigen is available as a solution in the following strengths: 5 g in 50 mL solution, 10 g in 100 mL solution, and 20 g in 200 mL solution, and is intended for intravenous administration only.1-3

Recommended dosing for PI is 200 to 800 mg/kg intravenously (IV) every 3 to 4 weeks. The recommended initial infusion rate is 0.5 mg/kg/min (0.005 mL/kg/min) and, if well-tolerated, may be gradually increased to a maximum of 8 mg/kg/min (0.08 mL/kg/min.)1-3 Dosing for ITP is 1 g/kg IV daily for 2 consecutive days, for a total of 2 g/kg. Recommended initial infusion rate is 0.5 mg/kg/min (0.005 mL/kg/min) and, if well tolerated, may be gradually increased to 4 mg/kg/min (0.04 mL/kg/min). In patients at risk of developing renal insufficiency, do not exceed the recommended dose, and infuse Privigen at a rate less than 2 mg/kg/min (0.02 mL/kg/min).1-3 Privigen does not contain sucrose and is stabilized with the amino acid proline, which allows Privigen to remain stable for 36 months at room temperature.

Warning/Precautions

In clinical studies, the most common adverse reactions reported among patients receiving treatment for PI were headache (44%), pain (25%), nausea (13%), fatigue (16%), and chills (11%).1,3,4 Common adverse effects associated with treatment for ITP include headache (65%), pyrexia/hyperthermia (37%), and anemia (11%).1,3,4 Renal function should be monitored, including blood urea nitrogen, serum creatinine, and urine output, in patients at risk of developing acute renal failure.1-4 Patients should be monitored for hyperproteinemia, hyponatremia, hemolysis/transfusionrelated acute lung injury, hemolytic anemia, and pulmonary adverse reactions. Patients should also be monitored for thrombotic events, especially those patients with risk factors for thrombosis, including those with a history of atherosclerosis, multiple cardiovascular risk factors, advanced age, impaired cardiac output, hypercoagulable disorders, prolonged periods of immobilization, and/or known or suspected hyperviscosity.1-4 Caution should also be used because aseptic meningitis syndrome (AMS) may occur infrequently with Privigen and other IVIG treatments.1-3,5 AMS may occur more frequently in association with high doses (2 g/kg) and/or rapid infusion of immune globulin intravenous products.1-3

Contraindications

Privigen is contraindicated in patients who have had an anaphylactic or severe systemic reaction to the administration of human immune globulin, in patients with hyperprolinemia, and in immunoglobulin A (IgA)-deficient patients with antibodies to IgA and a history of hypersensitivity.1,2,7

References:

1. Privigen Prescribing Information. CLS Behring Web site. Available at: www.privigen.com/pdf/Privigen_PI.pdf. Accessed September 27, 2010.

2. Privigen IV Monograph. Medscape Web site. Available at: www.medscape.com/druginfo/monograph?cid=med&drugid=149963&drugname=Privigen+IV&monotype=monograph&print=1#Pharmacology. Accessed September 27, 2010.

3. Privigen (human immunoglobulin g) liquid. National Institutes of Health Daily Med Web site. http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=17108#nlm34090-1. Accessed September 27, 2010.

4. Stein MR, Nelson RP, Church JA, et al. IgPro10 in PID Study Group. Safety and efficacy of Privigen, a novel 10% liquid immunoglobulin preparation for intravenous use, in patients with primary immunodeficiencies. J Clin Immunol. 2009; 29(1):137-144.

5. Efficacy and Safety in Patients with Primary Immunodeficiency Disease (PIDD). CLS Behring Web site. Available at: www.privigen.com/Professional/Efficacy-Safety/Primary-Immunodeficiency.aspx. Accessed September 27, 2010.

6. Efficacy and Safety in Patients with Immune Thrombocytopenic Purpura (ITP). CLS Behring Web site. Available at: www.privigen.com/Professional/Efficacy-Safety/Immune-Thrombocytopenic.aspx. Accessed September 27, 2010.

7. Important Safety Information Regarding Privigen. CLS Behring Web site. Available at: www.privigen.com/Professional/default.aspx. Accessed September 27, 2010.

About the Author

Ms. Terrie is a clinical pharmacy writer based in Haymarket, Virginia.