title: Safety of L-proline as a stabilizer for immunoglobulin products.
abstract: Privigen(®) (immune globulin intravenous [human], 10% liquid) and Hizentra(®) (immune globulin subcutaneous [human], 20% liquid) are stabilized by proline. The clinical implications of administering proline-containing immunoglobulin products to patients with defects of proline metabolism have not been addressed; Privigen and Hizentra are contraindicated in these patients. Some patients with chromosome 22q11.2 deletion syndrome have elevated proline levels; however, only 3-4% of patients also have an immunodeficiency that requires IgG therapy. This review summarizes the evidence related to the safety and pharmacokinetics of proline assessed in Privigen and Hizentra preclinical and clinical studies, and subsequent implications for patients with defects in proline metabolism. Clinical data indicate that proline does not accumulate after Privigen or Hizentra treatment and is not associated with adverse events. There is no evidence to suggest that patients with defects of proline metabolism would be affected by transient elevations in plasma proline following Privigen and/or Hizentra treatment.
authors.affiliation: Division of Allergic Diseases, Department of Medicine, Mayo Clinic, 200 First Street S.W., Rochester, MN 55905, USA. hagan.john@mayo.edu
authors.forename: John B
authors.initials: JB
authors.lastname: Hagan
authors.forename: Richard L
authors.initials: RL
authors.lastname: Wasserman
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Baggish
authors.forename: Martin O
authors.initials: MO
authors.lastname: Spycher
authors.forename: Melvin
authors.initials: M
authors.lastname: Berger
authors.forename: Vandana
authors.initials: V
authors.lastname: Shashi
authors.forename: Emanuel
authors.initials: E
authors.lastname: Lohrmann
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Sullivan
mesh_terms: D000818:Animals; D002872:Chromosome Deletion; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D004355:Drug Stability; D064420:Drug-Related Side Effects and Adverse Reactions; D005079:Excipients / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D030342:Genetic Diseases, Inborn / Q000188:drug therapy / Q000235:genetics; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects / Q000627:therapeutic use; D016756:Immunoglobulins, Intravenous / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D011392:Proline / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D005079:Excipients; C558471:Hizentra; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D011392:Proline