WARNING: HYPERSENSITIVITY REACTIONS INCLUDING ANAPHYLAXIS Patients treated with enzyme replacement therapies have experienced life‑threatening hypersensitivity reactions, including anaphylaxis. Anaphylaxis has occurred during the early course of enzyme replacement therapy and after extended duration of therapy. Initiate ELELYSO 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 ELELYSO and immediately initiate appropriate medical treatment, including use of epinephrine. Inform patients of the symptoms of life‑threatening hypersensitivity reactions, including anaphylaxis and to seek immediate medical care should symptoms occur [see Warnings and Precautions (5.1) ] . WARNING: HYPERSENSITIVITY REACTIONS INCLUDING ANAPHYLAXIS See full prescribing information for complete boxed warning. • Anaphylaxis has occurred during the early course of enzyme replacement therapy and after extended duration of therapy. ( 5.1 ) • Initiate ELELYSO in a healthcare setting with appropriate medical monitoring and support measures, including access to cardiopulmonary resuscitation equipment. ( 5.1 ) • If a severe hypersensitivity reaction (e.g., anaphylaxis) occurs, discontinue ELELYSO and immediately initiate appropriate medical treatment, including use of epinephrine. ( 5.1 )
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warnings and cautions
5 WARNINGS AND PRECAUTIONS See boxed warning ( 5.1 ) 5.1 Hypersensitivity Reactions Including Anaphylaxis Life‑threatening h ypersensitivity reactions, including anaphylaxis, have occurred in patients treated with enzyme replacement therapies, including ELELYSO . In clinical trials, (patients were not routinely pretreated with antihistamines and/or corticosteroids prior to ELELYSO infusions during the clinical trials): • 2 of 72 (3%) ELELYSO-treated patients experienced signs and symptoms consistent with anaphylaxis including urticaria, hypotension, flushing, wheezing, chest tightness, nausea, vomiting, and dizziness. These reactions occurred during ELELYSO infusion. • 21 of 72 (29%) ELELYSO-treated patients experienced hypersensitivity reactions, including the 2 ELELYSO‑treated patients who experienced signs and symptoms consistent with anaphylaxis. Signs and symptoms of these hypersensitivity reactions included pruritus, angioedema, flushing, erythema, rash, nausea, vomiting, cough, chest tightness, and throat irritation. These reactions occurred during ELELYSO infusion and up to 3 hours after the start of infusion [see Adverse Reactions (6.1) ] . Anaphylaxis has occurred during the early course of enzyme replacement therapy and after extended duration of therapy. Administration of ELELYSO should be supervised by a healthcare provider knowledgeable in the management of hypersensitivity reactions including anaphylaxis. Initiate ELELYSO in a healthcare setting with appropriate medical monitoring and support measures, including access to cardiopulmonary resuscitation equipment. Observe patients closely during and after the infusion. ELELYSO-treated patients who developed anti-taliglucerase alfa antibodies (referred to as anti-drug antibodies (ADA)) generally had a greater frequency of hypersensitivity reactions compared to those who did not develop ADA [see Adverse Reactions (6.1) ] . Closely monitor for hypersensitivity reactions in patients who develop ADA. Management of hypersensitivity reactions should be based on the severity of the reaction and includes slowing or temporary interruption of the infusion and/or administration of antihistamines, antipyretics, and/or corticosteroids for mild reactions. To reduce the risk of hypersensitivity reactions, consider pretreatment with antihistamines and/or corticosteroids. If a severe hypersensitivity reaction (e.g., anaphylaxis) occurs, discontinue ELELYSO and immediately initiate appropriate medical treatment, including use of epinephrine. Inform patients of the symptoms of life‑threatening hypersensitivity reactions, including anaphylaxis and to seek immediate medical care should symptoms occur. Consider the risks and benefits of re-administering ELELYSO in patients who have experienced a severe hypersensitivity reaction associated with ELELYSO. Caution should be exercised upon rechallenge [see Adverse Reactions (6.2) ].
6 ADVERSE REACTIONS The most common adverse reactions are: • Treatment-Naïve Adults (≥5%): headache, arthralgia, fatigue, nausea, dizziness, abdominal pain, pruritus, flushing, vomiting, urticaria ( 6.1 ). • Patients who Switched from Imiglucerase, after 9 Months on Treatment (≥10%): arthralgia, headache, pain in extremity ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Pfizer Inc. at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adverse Reactions from Clinical Trials of ELELYSO as Initial Therapy • Clinical Trial in Adult Patients The safety of ELELYSO at dosages of either 30 units/kg (n=16) (50% of the recommended dosage) [see Dosage and Administration (2.1) ] or 60 units/kg (n=16) administered intravenously every other week was assessed in 32 adult treatment-naïve patients (aged 19 to 74 years) with Type 1 Gaucher disease in a 9-month double-blind, randomized clinical trial (Trial 1) [see Clinical Studies (14) ] . Table 1 presents the adverse reactions that occurred in these ELELYSO-treated patients. Table 1: Adverse Reactions in ≥5% of Treatment-Naïve Adult Patients Treated with ELELYSO Preferred Term Treatment-Naïve Adults (N=32) n (%) Headache 6 (19) Arthralgia 4 (13) Fatigue 3 (9) Nausea 3 (9) Dizziness 3 (9) Abdominal pain 2 (6) Pruritus 2 (6) Flushing 2 (6) Vomiting 2 (6) Urticaria 2 (6) • Clinical Trial in Pediatric Patients 16 Years of Age and Younger The safety of ELELYSO at dosages of either 30 units/kg (n=4) (50% of the recommended dosage) [see Dosage and Administration (2.1) ] or 60 units/kg (n=5) administered intravenously every other week was assessed in 9 pediatric treatment-naïve patients (aged 2 to 13 years) with Type 1 Gaucher disease in a 12-month randomized clinical trial (Trial 2) [see Clinical Studies (14) ] . The most common adverse reaction (≥10%) was vomiting, which occurred in 4 of 9 patients. Two patients developed hypersensitivity reactions; 1 patient experienced severe vomiting and gastrointestinal inflammation, and 1 experienced mild throat irritation and chest discomfort. Both patients responded to treatment with antihistamines and continued ELELYSO treatment. Adverse Reactions in a Clinical Trial in Patients Who Switched from Imiglucerase to ELELYSO The safety of ELELYSO was assessed in 31 patients (26 adult and 5 pediatric patients), ages 6 to 66 years old, with Type 1 Gaucher disease who had previously been receiving imiglucerase treatment for a minimum of 2 years (Trial 3). ELELYSO was administered intravenously every other week for 9 months at the same number of units as each patient's previous imiglucerase dose. Table 2 presents the adverse reactions in these ELELYSO-treated patients. Table 2: Adverse Reactions in ≥10% of ELELYSO-Treated Patients Who Switched from Imiglucerase to ELELYSO (after 9 months on treatment) Preferred Term Adult and Pediatric Patients Switched from Imiglucerase (N=31) n (%) Arthralgia 4 (13) Headache 4 (13) Pain in extremity 3 (10) Immunogenicity: Anti-Drug Antibody-Associated Adverse Reactions Trials 1, 2, and 3 evaluated ELELYSO enzyme replacement therapy (ERT)-naïve and ERT-experienced adult and pediatric patients with Gaucher disease [see Clinical Studies (14.1, 14.2) ] . In patients with Type 1 Gaucher disease, hypersensitivity reactions occurred in 36% (9/25) of ELELYSO-treated patients who developed ADA during the treatment period and in 15% (6/41) of ELELYSO-treated patients who did not develop ADA during the treatment period [see Warnings and Precautions (5.1) and Clinical Pharmacology (12.6) ] . Of the 9 ELELYSO-treated patients who tested positive for ADA and who developed hypersensitivity reactions, 2 patients had anaphylaxis and 1 additional patient discontinued ELELYSO due to hypersensitivity reactions. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of ELELYSO. Because these reactions include those reported voluntarily from a population of uncertain size in addition to those from postmarketing studies, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: • Gastrointestinal disorders : Vomiting, diarrhea • General disorders and administration site conditions : Fatigue • Immune system disorders : Anaphylaxis [see Warnings and Precautions (5.1) ] , Type III immune mediated fixed drug eruption • Musculoskeletal and connective tissue disorders : Back pain