Hypersensitivity Reactions Including Anaphylaxis

Life-threatening hypersensitivity reactions, including anaphylaxis, have occurred in patients treated with enzyme replacement therapies, including VPRIV. VPRIV-treated patients have had these reactions occur in clinical studies and postmarketing experience [see Adverse Reactions (6.1) and Clinical studies (14)]. Hypersensitivity reactions were the most commonly observed adverse reactions in patients treated with VPRIV in clinical studies. Patients were not routinely pre-medicated prior to infusion of VPRIV during clinical studies. The most commonly observed symptoms of hypersensitivity reactions were: headache, dizziness, hypotension, hypertension, nausea, fatigue/asthenia, and pyrexia/body temperature increased. Generally the reactions were mild and, in treatment-naïve patients, onset occurred mostly during the first 6 months of treatment and tended to occur less frequently with time. Additional hypersensitivity reactions of chest discomfort, dyspnea, pruritus and vomiting have been reported in post-marketing experience.

Anaphylaxis has occurred during the early course of enzyme replacement therapy and after extended duration of therapy. Administration of VPRIV should be supervised by a healthcare provider knowledgeable in the management of hypersensitivity reactions including anaphylaxis. Initiate VPRIV in a healthcare setting with appropriate medical monitoring and support measures, including access to cardiopulmonary resuscitation equipment.

The management of hypersensitivity reactions should be based on the severity of the reaction, e.g., slowing the infusion rate, treatment with medications such as antihistamines, antipyretics and/or corticosteroids, and/or stopping and resuming treatment with increased infusion time. If a severe hypersensitivity reaction (e.g., anaphylaxis) occurs, discontinue VPRIV and immediately initiate appropriate medical treatment, including use of epinephrine.

In cases where patients have exhibited symptoms of hypersensitivity to velaglucerase alfa or excipients in the drug product or to other enzyme replacement therapy, pre-treatment with antihistamines and/or corticosteroids may prevent subsequent reactions. Inform patients of the symptoms of life-threatening hypersensitivity reactions, including anaphylaxis and to seek immediate medical care should symptoms occur.