1 Adverse Reaction Overview The most common adverse drug reactions (incidence ≥ 10%) reported in the clinical trials were abdominal pain/abdominal pain upper, arthralgia, asthenia/fatigue, back pain, bone pain, dizziness, headache, infusion-related reactions, pyrexia/body temperature increased, and upper respiratory tract infections.
The only adverse reaction leading to discontinuation of VPRIV was an infusion-related reaction. The most serious adverse drug reactions in patients in clinical trials were arthralgia, hypersensitivity reactions, and urticaria. Serious adverse drug reactions observed post-market were anaphylactic reaction, chest discomfort, dyspnea, pruritis, and vomiting.
2 Clinical Trial Adverse Reactions Because clinical trials are conducted under very specific conditions, the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.
Adverse reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates. The data described below reflect exposure of 94 patients with type 1 Gaucher disease who received VPRIV at doses ranging from 15 to 60 U/kg every other week in 5 clinical studies.
Fifty- four (54) patients were naïve to ERT and 40 patients switched from imiglucerase to VPRIV. Patients were between 4 and 71 years old at the time of first treatment with VPRIV, and included 46 male and 48 female patients. The most serious adverse reactions in patients in clinical trials were hypersensitivity reactions.
See Warnings and Precautions, Immune and Adverse Reaction Overview, Table 4. Adverse drug reactions considered related to VPRIV are shown in Table 4. Information is presented by system organ class and frequency (very common ≥10%; common ≥1% and <10%;).
5) * See Warnings and Precautions, Immune † Reactions occurring up to 24 hours after the start of the infusion § Includes dermatitis and anaphylactoid reaction In clinical studies, 1 of 94 patients treated with VPRIV developed IgG-class antibodies to velaglucerase alfa.
In this one event the antibodies were determined to be neutralizing in an in vitro assay. No infusion-related reactions were reported for this patient. One additional patient developed IgG antibodies to velaglucerase alfa that were reported as having neutralizing activity during an extension study.
No adverse events considered related to velaglucerase alfa were reported for this patient. It is unknown if the presence of IgG antibodies to velaglucerase alfa is associated with a higher risk of infusion reactions. No patients developed IgE antibodies to velaglucerase alfa.
6 Post-Market Adverse Reactions The following adverse reactions have been identified during post approval use of VPRIV. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Gastrointestinal Disorders:
Vomiting * General Disorders and Administration Site Conditions: Chest discomfort Immune System Disorders: Anaphylactic reaction Respiratory, Thoracic and Mediastinal Disorder: Dyspnea Skin and Subcutaneous Tissue Disorders: Pruritis * In some cases vomiting can be serious.