The Details of Tolerability and Safety

Hypersensitivity Reactions

• Hypersensitivity reactions have been reported in patients in clinical studies with VPRIV. As with any intravenous protein product, hypersensitivity reactions are possible, therefore appropriate medical support should be readily available when VPRIV is administered. If a severe reaction occurs, medical standards for emergency treatment are to be followed.
• Treatment with VPRIV should be used with caution in patients who have exhibited symptoms of hypersensitivity to the active ingredient, drug product excipients, or to other enzyme replacement therapies.

Infusion-Related Reactions

• Infusion-related reactions were the most commonly observed adverse reactions in patients treated with VPRIV in clinical studies. The most commonly observed symptoms of infusion-related reactions were: headache, dizziness, hypotension, hypertension, nausea, asthenia/fatigue, and pyrexia. Generally the infusion-related 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.
• Management of infusion-related reactions should be based on severity of the reaction, such as slowing the infusion rate, treatment with medications such as antihistamines, antipyretics and/or corticosteroids, and/or stopping and resuming treatment with increased infusion time.

Adverse reactions observed in ≥10% of patients with type 1 Gaucher disease treated with VPRIV

• Less common adverse reactions affecting more than 1 patient (>3% in the treatment-naïve group and >2% in patients switched from imiglucerase to VPRIV) were bone pain, tachycardia, rash, urticaria, flushing, hypertension, and hypotension.

Pediatric Patients

• All adult adverse reactions to VPRIV are considered relevant to pediatric patients (ages 4 to 17 years). Adverse reactions more common in pediatric patients (>10% difference) included upper respiratory tract infection, rash, aPTT prolonged, and pyrexia.
• The safety of VPRIV has not been established in pediatric patients younger than 4 years of age.

Immunogenicity

• In clinical studies, 1 of 54 treatment-naïve patients treated with VPRIV developed IgG class antibodies to VPRIV.
• In this patient, the antibodies were determined to be neutralizing in an in vitro assay. No infusion-related reactions were reported for this patient. It is unknown if the presence of IgG antibodies to VPRIV is associated with a higher risk of infusion reactions.
• Patients with an immune response to other enzyme replacement therapies who are switching to VPRIV should continue to be monitored for antibodies.

Immunogenicity assay results are highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to VPRIV with the incidence of antibodies to other products may be misleading.

For more information, please see the full Prescribing Information or call Shire Human Genetic Therapies, Inc. at 1-866-888-0660. To report suspected adverse events contactShire Human Genetic Therapies, Inc., at 1-866-888-0660, or the FDA at 1-800-FDA-1088, or www.fda.gov/medwatch