Drug Description
One vial contains 200 Units* of velaglucerase alfa.After reconstitution, one ml of the solution contains 100 Units of velaglucerase alfa.*An enzyme unit is defined as the amount of enzyme that is required to convert one micromole of p-nitrophenyl ?-D-glucopyranoside to p-nitrophenol per minute at 37ºC.Velaglucerase alfa is produced in an HT-1080 human fibroblast cell line by recombinant DNA technology.ExcipientsOne vial contains 6.07 mg sodium

Presentation
Powder for solution for infusionWhite to off-white powder

Indications
VPRIV is indicated for long-term enzyme replacement therapy (ERT) in patients with type 1 Gaucher disease.

Adult Dosage
VPRIV treatment should be supervised by a physician experienced in the management of patients with Gaucher disease. Home administration under the supervision of a healthcare professional may be considered only for patients who have received at least three infusions and were tolerating their infusions well.PosologyThe recommended dose is 60 Units/kg administered every other week.Dose adjustments can be made on an individual basis based on achievement and maintenance of therapeutic goals. Clinical studies have eva luated doses ranging from 15 to 60 Units/kg every other week. Doses higher than 60 Units/kg have not been studied.Special populationsCurrent enzyme replacement therapyPatients currently treated with imiglucerase enzyme replacement therapy for type 1 Gaucher disease may be switched to VPRIV, using the same dose and frequency.Renal or hepatic impairmentNo dosing adjustment is recommended in patients with renal or hepatic impairment based on current knowledge of the pharmacokinetics and pharmacodynamics of velaglucerase alfa.Elderly (≥65 years old)Four of the 94 patients (5%) who received velaglucerase alfa during clinical studies were age 65 years or older. The limited data do not indicate a need for a dose adjustment in this age group.Paediatric populationTwenty of the 94 patients (21%) who received velaglucerase alfa during clinical studies were in the paediatric and adolescent age range (4 to ≤17 years). The safely and efficacy profiles were similar between paediatric and adult patients.Method of administrationFor intravenous infusion use only.To be administered as a 60-minute intravenous infusion.Must be administered through a 0.22 μm filter.For instructions on reconstitution and dilution of VPRIV, see section 6.6 and the end of the leaflet.

Contra Indications
Severe allergic reaction to the active substance or to any of the excipients.

Special Precautions
HypersensitivityHypersensitivity reactions have been reported in patients in clinical studies. As with any intravenous protein medicinal product, hypersensitivity reactions are possible. Therefore, appropriate medical support should be readily available when velaglucerase alfa is administered. If a severe reaction occurs, current medical standards for emergency treatment are to be followed.Treatment should be approached with caution in patients who have exhibited symptoms of hypersensitivity to other enzyme replacement therapy.Infusion related-reactionsInfusion-related reactions were the most commonly observed adverse reactions in patients treated in clinical studies. Most of the infusion-related reactions were mild. The most commonly observed symptoms of infusion-related reactions were: headache, dizziness, hypotension, hypertension, nausea, fatigue/asthenia, and pyrexia/body temperature increased. 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.Pre-treatment with antihistamines and/or corticosteroids may prevent subsequent reactions in those cases where symptomatic treatment was required. Patients were not routinely pre-medicated prior to infusion of velaglucerase alfa during clinical studies.ImmunogenicityAntibodies may play a role in treatment-related reactions found with the use of velaglucerase alfa. To further eva luate 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.SodiumThis medicinal product contains 6.07 mg sodium per vial. To be taken into consideration by patients on a controlled sodium diet.

Interactions
No interaction studies have been performed.

Adverse Reactions
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. 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) and common (1/100 to <1/10). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.Table 1: Adverse reactions reported with VPRIV observed in patients with type 1 Gaucher disease.System organ classVery commonCommonImmune system disordershypersensitivity reactionsNervous system disordersheadache, dizzinessCardiac disorderstachycardiaVascular disordershypertension, hypotension, flushingGastrointestinal disordersabdominal pain/abdominal pain upper, nauseaSkin and subcutaneous tissue disordersrash, urticariaMusculoskeletal and connective tissue disordersbone pain, arthralgia, back painGeneral disorders and administration site conditionsinfusion-related reaction, asthenia/fatigue, pyrexia/body temperature increasedInvestigationsactivated partial thromboplastin time prolonged, neutralizing antibody positivePaediatric populationThe safety profile of VPRIV in clinical studies involving children and adolescents aged 4 to ≤17 years was similar to that observed in adult patients.

Drug Availability
POM- Prescription Only Medicine

Updated
17 September 2010