Hypersensitivity Reactions Including Anaphylaxis

Life-threatening hypersensitivity reactions, including anaphylaxis, have occurred in patients treated with enzyme replacement therapies (ERTs) including pegzilarginase. Hypersensitivity reactions that were mild to moderate in severity occurred in 13% (6/48) of pegzilarginase-treated patients in clinical trials [see Adverse Reactions (6)]. Hypersensitivity reactions have included facial swelling, rash, flushing and dyspnea. The reactions generally occurred with the first few doses, but may also occur later in treatment.

Pegzilarginase-treated patients who developed anti-drug antibodies (ADA) generally had a greater incidence of hypersensitivity reactions compared to those who did not develop ADA [see Adverse Reactions (6.1)].

Anaphylaxis has occurred during the early course of ERT and after extended duration of ERT.

Administration of pegzilarginase should be supervised by a healthcare provider knowledgeable in the management of hypersensitivity reactions including anaphylaxis. Consider pre‑medication with an antihistamine. Corticosteroids can be considered in patients who have previously developed a hypersensitivity reaction. Initiate pegzilarginase in a healthcare setting with appropriate medical monitoring and support measures, including access to cardiopulmonary resuscitation equipment.

• If a severe hypersensitivity reaction (e.g., anaphylaxis) occurs, discontinue pegzilarginase and immediately initiate appropriate medical treatment, including use of epinephrine. Consider the risks and benefits of re-administering pegzilarginase following a severe hypersensitivity reaction (including anaphylaxis). Caution should be exercised upon rechallenge. Inform patients of the symptoms of life-threatening hypersensitivity reactions, including anaphylaxis and to seek immediate medical care should symptoms occur.
• If a mild or moderate hypersensitivity reaction occurs, consider treatment with antihistamines and/or corticosteroids. For intravenous administration, consider temporarily holding the infusion or slowing the infusion rate.