Source: European Medicines Agency (EU) Revision Year: 2020 Publisher: Shire Pharmaceuticals Ireland Limited, Block 2 & 3 Miesian Plaza, 50–58 Baggot Street Lower, Dublin 2, Ireland
Severe allergic reaction to the active substance or to any of the excipients listed in section 6.1.
Hypersensitivity reactions, including symptoms consistent with anaphylaxis, have been reported in patients in clinical studies and in post-marketing experience. The majority of hypersensitivity reactions usually occur up to 12 hours post infusion. The most frequently reported symptoms of hypersensitivity include nausea, rash dyspnoea, back pain, chest discomfort (including chest tightness), urticaria, arthralgia, and headache.
An infusion-related reaction is defined as any adverse drug reaction occurring within 24 hours after the initiation of velaglucerase alfa infusion. Infusion-related reactions (IRR) were the most commonly observed adverse reactions in patients treated in clinical studies. An IRR often appears as a hypersensitivity reaction. The most frequently reported symptoms of hypersensitivity include nausea, rash, dyspnoea, back pain, chest discomfort (including chest tightness), urticaria, arthralgia, and headache. Symptoms consistent with anaphylaxis have been reported in patients in clinical studies and in post-marketing experience. Apart from symptoms associated with hypersensitivity reactions IRRs might show as fatigue, dizziness, pyrexia, blood pressure increase, pruritus, or vision blurred. In treatment-naïve patients, the majority of infusion-related reactions occurred during the first 6 months of treatment.
The management of infusion-related reactions should be based on the severity of the reaction, and include slowing the infusion rate, treatment with medicinal products such as antihistamines, antipyretics and/or corticosteroids, and/or stopping and resuming treatment with increased infusion time.
Due to the risk for hypersensitivity reactions including anaphylaxis appropriate medical support, including adequately trained personnel in emergency measures, should be readily available when velaglucerase alfa is administered. If anaphylactic or other acute reactions occur, in the clinic or home setting, immediately discontinue the infusion and initiate appropriate medical treatment. For patients developing anaphylaxis in a home setting it should be considered to continue treatment in a clinical setting.
Treatment should be approached with caution in patients who have exhibited symptoms of hypersensitivity to velaglucerase alfa or other enzyme replacement therapy.
Pre-treatment with antihistamines and/or corticosteroids may prevent subsequent reactions in those cases where symptomatic treatment was required.
Antibodies may play a role in treatment-related reactions found with the use of velaglucerase alfa. To further evaluate the relationship, in cases of severe infusion-related reactions and in cases of lack or loss of effect patients should be tested for the presence of antibodies and the results reported to the company.
In the clinical trials, one of 94 (1%) patients developed IgG-class antibodies to velaglucerase alfa. In this one event, the antibodies were determined to be neutralising in an in vitro assay. No infusion-related reactions were reported for this patient. No patients developed IgE antibodies to velaglucerase alfa.
This medicinal product contains 12.15 mg sodium per vial. To be taken into consideration by patients on a controlled sodium diet.
No interaction studies have been performed.
Patients who have Gaucher disease and become pregnant may experience a period of increased disease activity during pregnancy and the puerperium. A risk-benefit assessment is required for women with Gaucher disease who are considering pregnancy.
There are no or limited amount of data from the use of velaglucerase alfa in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development. Close monitoring of the pregnancy and clinical manifestations of Gaucher disease is necessary for the individualisation of therapy. Caution should be exercised when prescribing to pregnant women.
There are no data from studies in breast-feeding women. It is not known whether velaglucerase alfa is excreted in human milk. Caution should be exercised when prescribing to a breast-feeding woman.
Animal studies show no evidence of impaired fertility.
VPRIV has no or negligible influence on the ability to drive or use machines.
The data described below reflect exposure of 94 patients with type 1 Gaucher disease who received velaglucerase alfa at doses ranging from 15 to 60 Units/kg every other week in 5 clinical studies. Fifty-four 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.
The most common adverse reactions were infusion-related reactions. The most commonly observed symptoms of infusion-related reactions were: headache, dizziness, hypotension, hypertension, nausea, fatigue/asthenia, and pyrexia/body temperature increased (see section 4.4 for further information). The only adverse reaction leading to discontinuation of treatment was an infusion-related reaction.
Adverse reactions reported in patients with type 1 Gaucher disease are listed in Table 1. Information is presented by system organ class and frequency according to MedDRA convention. Frequency is defined as very common (≥1/10), common (≥1/100 to <1/10), and uncommon (≥1/1,000 to <1/100). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. Adverse drug reactions derived from post-marketing reports other than interventional clinical trials are printed in italics.
Table 1. Adverse reactions reported with VPRIV observed in patients with type 1 Gaucher disease. Italic text denotes post-marketing event:
Common: hypersensitivity reactions (includes dermatitis allergic and anaphylactic/anaphylactoid reactions)
Very common: headache, dizziness
Uncommon: vision blurred
Common: tachycardia
Common: dyspnea
Common: hypertension, hypotension, flushing
Very common: abdominal pain/abdominal pain upper
Common: nausea
Uncommon: vomiting
Common: rash, urticaria, pruritus
Very common: bone pain, arthralgia, back pain
Very common: infusion-related reaction, asthenia/fatigue, pyrexia/body temperature increased
Common: chest discomfort
Common: activated partial thromboplastin time prolonged, neutralizing antibody positive
In some cases vomiting can be serious (reported from post-marketing experience).
The safety profile of VPRIV in clinical studies involving children and adolescents aged 4 to 17 years was similar to that observed in adult patients.
The safety profile of VPRIV in clinical studies involving patients aged 65 years and above was similar to that observed in other adult patients.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
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