for improving resorption of radiopaque agents, in subcutaneous urography. The three naturally-sourced hyaluronidases are orthologs of human HYAL5 (PH20) obtained from testicular preparations. They are sold under the trade names Vitrase (ovine, FDA-approved in May 2004), Amphadase (bovine, October 2004) and Hydase (bovine, October 2005). Human recombinant hyaluronidase (Hylenex)—approved for use in the United States in December 2005—corresponds to the soluble fragment of human HYAL5 (PH20) produced in culture by genetically engineered Chinese hamster ovary (CHO) cells containing a DNA plasmid encoding the enzyme. Combination treatments A human recombinant hyaluronidase kit, HyQvia, was approved for use in the European Union in May 2013, and in the United States in September 2014. It is a dual vial unit with one vial of immune globulin infusion 10% (human) and one vial of recombinant human hyaluronidase. It is an immune globulin with a recombinant human hyaluronidase indicated in the United States for the treatment of primary immunodeficiency in adults. This includes, but is not limited to, common variable immunodeficiency, X-linked agammaglobulinemia, congenital agammaglobulinemia, Wiskott-Aldrich syndrome, and severe combined immunodeficiencies. In the European Union it is indicated as replacement therapy in adults, children and adolescents (0–18 years) in: Primary immunodeficiency syndromes with impaired antibody production. Hypogammaglobulinaemia and recurrent bacterial infections in patients with chronic lymphocytic leukaemia (CLL), in whom prophylactic antibiotics have failed or are contra‑indicated. Hypogammaglobulinaemia and recurrent bacterial infections in multiple myeloma (MM) patients. Hypogammaglobulinaemia in patients pre‑ and post‑allogeneic hematopoietic stem cell transplantation (HSCT). A form of subcutaneous immunoglobulin (SCIG) that uses Hylenex to allow for a far greater volume of SCIG to be administered than would normally be possible to administer subcutaneously, providing a form of SCIG that can be dosed on a monthly basis, a longer period of time than other forms of SCIG allow. HyQvia had a rate of systemic adverse effects higher than traditional subcutaneous forms of immunoglobulin injection, but lower than those typical in IVIG patients. Also in epidural lysis of adhesions for pain management. Hyaluronidase is available in some fixed-dose combination drug products in the United States: rituximab/hyaluronidase (Rituxan Hycela), trastuzumab/hyaluronidase-oysk (Herceptin Hylecta), daratumumab/hyaluronidase-fihj (Darzalex Faspro), and pertuzumab/trastuzumab/hyaluronidase–zzxf (Phesgo). In July 2021, the U.S. Food and Drug Administration (FDA) approved daratumumab and hyaluronidase-fihj in combination with pomalidomide and dexamethasone for adults with multiple myeloma who have received at least one prior line of therapy including lenalidomide and a proteasome inhibitor. Role in cancer The role