4.1. Therapeutic indications

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

4.2. Posology and method of administration

VPRIV treatment should be supervised by a physician experienced in the management of patients with Gaucher disease.

Posology

The 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 evaluated doses ranging from 15 to 60 Units/kg every other week. Doses higher than 60 Units/kg have not been studied.

Patients currently treated with imiglucerase enzyme replacement therapy for type 1 Gaucher disease may be switched to VPRIV, using the same dose and frequency.

Special populations

Elderly (≥ 65 years old)

Elderly patients may be treated within the same dose range (15 to 60 Units/kg) as other adult patients (see section 5.1).

Renal impairment

No dosing adjustment is recommended in patients with renal impairment based on current knowledge of the pharmacokinetics and pharmacodynamics of velaglucerase alfa (see section 5.2).

Hepatic impairment No dosing adjustment is recommended in patients with hepatic impairment based on current knowledge of the pharmacokinetics and pharmacodynamics of velaglucerase alfa (see section 5.2).

Paediatric population

Twenty 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 safety and efficacy profiles were similar between paediatric and adult patients (see section 5.1 for further information). Data on home infusion in the paediatric population by the patient or a patient's caregiver are very limited.

The safety and efficacy of velaglucerase alfa in children below the age of 4 years have not yet been established. No data are available.

Method of administration

For intravenous infusion use only.

To be administered as a 60-minute intravenous infusion.

Must be administered through a 0.2 or 0.22 µm filter.

Home administration by a healthcare professional or self-administration (i.e. administration by the patient's caregiver or by the patients themselves) may be considered for patients who have received at least three infusions and who tolerated their infusions well. The decision to have a patient move to home infusion should be made after evaluation and recommendation by the treating physician. Self-administration in particular should be closely monitored by the treating physician and should occur in the presence of a responsible adult.

The treating physician has to make sure that the one who will administer velaglucerase alfa in the home setting is appropriately trained. Dose and infusion rate should remain constant while at home, and not be changed without supervision of the treating physician. Appropriate medical support, including personnel adequately trained in emergency measures, should be readily available when velaglucerase alfa is administered. If anaphylactic or other acute reactions occur, immediately discontinue the infusion and initiate appropriate medical treatment (see section 4.4). Subsequent infusions may need to occur in a clinical setting.

For instructions on reconstitution and dilution of the medicinal product before administration, see section 6.6.

4.3. Contraindications

Severe allergic reaction to the active substance or to any of the excipients listed in section 6.1.

4.4. Special warnings and precautions for use

Traceability

In order to improve the traceability of biological medicinal products, the name and batch number of the administered medicinal product should be clearly recorded.

Hypersensitivity

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.

Infusion-related reactions

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, vision blurred, or vomiting. In treatment-naïve patients, the majority of infusion-related reactions occurred during the first 6 months of treatment.

Prevention and management of infusion related reactions including hypersensitivity reactions

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.

Immunogenicity

Development of antibodies to velaglucerase alfa may be associated with infusion-related reactions including allergic-type hypersensitivity reactions.

In the clinical studies for Marketing Authorisation 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 patients developed IgE antibodies to velaglucerase alfa.

Post-marketing phase

During a post marketing extension study, one patient developed IgG antibodies to VPRIV. In addition, a few events of positive neutralising antibodies and lack of effect were reported post marketing.

If the physician suspects a lack/loss of effect that may be related to antibody formation the patient may be tested for antibodies at the physician's discretion. For further information on requesting antibody testing services, please contact [email protected].

Sodium

This medicinal product contains 12.15 mg sodium per vial. This is equivalent to 0.6% of the WHO recommended maximum daily intake of 2 g sodium for an adult.

4.5. Interaction with other medicinal products and other forms of interaction

No interaction studies have been performed.

4.6. Fertility, pregnancy and lactation

Women of childbearing potential

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.

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.

Breast-feeding

There is insufficient information on the excretion of velaglucerase alfa or its metabolites in human milk. Velaglucerase is a synthetic form of beta-glucocerebrosidase, which is a normal component of human milk. Studies with other forms of the enzyme have found very low levels of the enzyme in breastmilk. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from VPRIV taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Fertility

Animal studies show no evidence of impaired fertility (see section 5.3).

4.7. Effects on ability to drive and use machines

VPRIV has no or negligible influence on the ability to drive or use machines.

4.8. Undesirable effects

Summary of the safety profile

The most serious adverse reactions in patients in clinical studies were hypersensitivity reactions (2.1%).

The most common adverse reactions were infusion-related reactions (39.4%). 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.

Tabulated list of adverse reactions

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.

Table 1: Adverse reactions reported with VPRIV in patients with type 1 Gaucher disease

System organ class

Adverse reaction

Very common

Common

Uncommon

Immune system disorders

hypersensitivity reactions (includes dermatitis allergic and anaphylactic*/anaphylactoid reactions)

Nervous system disorders

headache, dizziness

Eye disorders

vision blurred*

Cardiac disorders

tachycardia

Respiratory, thoracic and mediastinal disorders

dyspnoea*

Vascular disorders

hypertension, hypotension, flushing

Gastrointestinal disorders

abdominal pain/abdominal pain upper

nausea

vomiting*

Skin and subcutaneous tissue disorders

rash, urticaria, pruritus*

Musculoskeletal and connective tissue disorders

bone pain, arthralgia, back pain

General disorders and administration site conditions

infusion-related reaction, asthenia/fatigue, pyrexia/body temperature increased

chest discomfort*

Investigations

activated partial thromboplastin time prolonged, neutralizing antibody positive

*Adverse reactions derived from post-marketing reports

Description of selected adverse reactions

Vomiting

In some cases vomiting can be serious and severe. Vomiting most often occurs during the infusion and up to 24 hours after the infusion.

Other special populations

Elderly population (≥ 65 years)

The safety profile of VPRIV in clinical studies involving patients aged 65 years and above was similar to that observed in other adult patients.

Paediatric population

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.

Reporting of suspected adverse reactions

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 Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

There is limited information available regarding overdose with velaglucerase alfa. In the majority of the cases reporting overdose, no additional adverse events were observed. However, in the event of accidental or intentional overdose, patients should be carefully observed and treatment should be symptomatic and supportive. There is no antidote available. The maximum dose of velaglucerase alfa in clinical studies was 60 Units/kg (see section 4.4).