Velaglucerase Alfa

Registered South African indications:

• Type 1 Gaucher disease

Contraindications

• Severe hypersensitivity to the active ingredient or any of its excipients

Cautions

International manufacturer recommendations

• Pregnancy
• Breastfeeding
• Porphyria
• Prior hypersensitivity to velaglucerase alfa or other enzyme replacement therapy
• Presence of antibodies to velaglucerase alfa
• Sodium restricted diet

South African manufacturer recommendations

• Pregnancy
• Breastfeeding
• Renal impairment
• Hepatic impairment
• Prior hypersensitivity to velaglucerase alfa or other enzyme replacement therapy
• Presence of antibodies to velaglucerase alfa
• Diabetes mellitus
• Sodium restricted diet
• Fructose intolerance
• Glucose-galactose malabsorption
• Sucrase-isomaltase insufficiency
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: inf

Type 1 Gaucher disease
- Long-term enzyme replacement therapy (ERT)

• IV: 60 units/kg, as an infusion over 60mins, every other week; Maintenance: 15-60 units/kg, every other week

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Dose adjustments can be made on an individual basis based on achievement and maintenance of therapeutic goals. Clinical studies have evaluated doses ranging from 15-60 units/kg every other week. Doses higher than 60 units/kg have not been studied

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

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Home administration under the supervision of a healthcare professional may be considered only for those patients who have received at least 3 infusions and were tolerating their infusions well

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, immediately discontinue the infusion and initiate appropriate medical treatment

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See additional prescribing points for instructions on reconstitution and dilution

Paed. forms avail. in SA and covered in this monograph: inf

Type 1 Gaucher disease
- Long-term enzyme replacement therapy (ERT)

Younger than 4 years

• Not established for use

4 years and older

• See adult dosage

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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

Pregnancy

International manufacturer recommendations

• Caution
• 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
• 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

South African manufacturer recommendations

• Caution
• Safety in pregnancy has not been established
• Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development
• Patients who have Gaucher disease and become pregnant may experience a period of increased disease activity during pregnancy and the puerperium
• Close monitoring of the pregnancy and clinical manifestations of Gaucher disease is necessary for the individualisation of therapy

Breastfeeding

International manufacturer recommendations

• Caution; not recommended
• 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 breastfeeding or to discontinue/abstain from velaglucerase alfa taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman

South African manufacturer recommendations

• Caution; not recommended
• There are no data from studies in breastfeeding women. It is not known whether velaglucerase alfa is excreted in human milk. Women who are receiving velaglucerase alfa are advised not to breastfeed their infants

Fertility

• Animal studies show no evidence of impaired fertility

Renal Impairment

International manufacturer recommendations

• No dose adjustment recommended

South African manufacturer recommendations

• Caution; no information available

Hepatic Impairment

International manufacturer recommendations

• No dose adjustment recommended

South African manufacturer recommendations

• Caution; no information available

Elderly

• No dose adjustment recommended

Porphyria Information

• Not yet classified (NC)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Headache
• Dizziness
• Fatigue

Cardiovascular Disorders

• Tachycardia
• Hypertension
• Hypotension
• Flushing
• Chest discomfort
  - Chest tightness

Respiratory Disorders

• Dyspnoea

Gastrointestinal Disorders

• Abdominal pain (including upper abdominal pain)
• Nausea and vomiting

Musculoskeletal Disorders

• Bone pain
• Arthralgia
• Back pain

Skin and Subcutaneous Tissue Disorders

• Rash
• Urticaria
• Pruritus

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity reactions
  - Allergic dermatitis
  - Anaphylactic/anaphylactoid reaction
• Infusion-related reaction
• Fever
• Prolonged activated partial thromboplastin time
• Positive neutralizing antibody

Sensory Disorders

• Blurred vision

None known

• Full blood count
• Hepatic function
• lgG antibodies
• Magnetic resonance imaging
• Computed tomography (CT) scan
• Ultrasound of the liver and spleen
• Bone density

Specific cases may require

• Antibody monitoring

Preparation

• Velaglucerase alfa requires reconstitution and dilution and is intended for intravenous infusion only. It is for single use only and is administered through a 0.2 or 0.22µm filter
• Aseptic technique must be used
• Velaglucerase alfa has to be prepared as follows:
  - The number of vials to be reconstituted is determined based on the individual patient's weight and the prescribed dose
  - The required vials are removed from the refrigerator. Each 400 unit vial is reconstituted with 4.3ml of sterile water for injections
  - Upon reconstitution, vials should be mixed gently. Vials should not be shaken. Each vial will contain an extractable volume of 4.0ml (100 units/ml)
  - Prior to further dilution, the solution in the vials should be visually inspected; the solution should be clear to slightly opalescent and colourless; the solution should not be used if it is discoloured or if foreign particulate matter is present
  - The calculated volume of medicinal product is withdrawn from the appropriate number of vials and the total volume required is diluted in 100ml of sodium chloride 9mg/ml (0.9%) solution for infusion. The diluted solution should be mixed gently. It should not be shaken. The infusion should be initiated within 24 hours from the time of reconstitution
• Any unused medicinal product or waste material should be disposed of in accordance with local requirements

Reconstituted and diluted solution for infusion:

• Chemical and physical in-use stability has been demonstrated for 24 hours at 2°C to 8°C under protection from light
• From a microbiological point of view, the medicinal product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and must not exceed 24 hours at 2°C to 8°C

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

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
• Pre-treatment with antihistamines and/or corticosteroids may prevent subsequent reactions in those cases where symptomatic treatment was required 

Velaglucerase alfa is produced by gene activation technology in a human cell line. Velaglucerase alfa is a glycoprotein. The monomer is approximately 63 kDa, has 497 amino acids, and the same amino acid sequence as the naturally occurring human enzyme, glucocerebrosidase. There are 5 potential N-linked glycosylation sites, four of which are occupied. Velaglucerase alfa is manufactured to contain predominantly high-mannose-type glycans to facilitate internalisation of the enzyme by the phagocytic target cells via the mannose receptor.

Velaglucerase alfa supplements or replaces beta-glucocerebrosidase, the enzyme that catalyses the hydrolysis of glucocerebroside to glucose and ceramide in the lysosome, reducing the amount of accumulated glucocerebroside and correcting the pathophysiology of Gaucher disease. Velaglucerase alfa increases haemoglobin concentration and platelet counts and reduces liver and spleen volumes in patients with type 1 Gaucher disease. 

Injection (per vial) 400 IU

• Vpriv (Takeda) originator