velaglucerase alfa (Rx)

>10%

Fatigue (13%)

Dizziness (8-22%)

Abdominal pain (15-19%)

Headache (30-35%)

Upper respiratory tract infections (30-32%)

Prolonged aPPT (5-11%)

1-10%

Flushing (>2%)

Tachycardia (>2%)

Hypertension/hypotension (>2%)

Urticaria (>2%)

Rash (>2%)

Postmarketing reports

Chest discomfort

Dyspnea

Pruritus

Contraindications

None listed in the manufacturer's label

Cautions

The most common adverse effect are infusion-related reactions; body temperature may increase when hypersensitivity reactions occur

Consider slowing infusion rate, treatment with antihistamines, antipyretics and/or corticosteroids, and/or stopping treatment if hypersensitivity reaction occurs during infusion; consider pre-treatment with antihistamines and/or corticosteroids in patients with prior reactions

Most reactions are mild and occur within the first 6 months; pretreatment or symptomatic treatment with corticosteroids, antihistamines, or antipyretics may help manage the reactions

Ensure that personnel administering product are adequately trained in cardiopulmonary resuscitative measures, and have ready access to emergency medical services

Pregnancy

Available data on use in pregnant females cannot definitively establish or exclude the absence of drug-associated risks during pregnancy

No association was identified with use during pregnancy and major birth defects, miscarriage, or adverse maternal or fetal outcomes

Animal data

• No fetal harm was observed in rats or rabbits when administered IV during organogenesis at doses with exposures up to 1.8 and 4.3x, respectively, the recommended human daily dose

Clinical considerations

• Women with Type 1 Gaucher disease have an increased risk of spontaneous abortion, especially if disease symptoms are not treated and controlled preconception and during pregnancy
• Pregnancy may exacerbate existing Type 1 Gaucher disease symptoms or result in new disease manifestations; these manifestations may lead to adverse pregnancy outcomes including hepatosplenomegaly and thrombocytopenia

Lactation

No data available on drug presence in human milk

Reported cases are insufficient to determine any effects on the breastfed infant or on milk production

Endogenous beta-glucocerebrosidase is present in human milk

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Hydrolytic lysosomal glucocerebroside-specific enzyme catalyzes the hydrolysis of glucocerebroside, reducing the amount of accumulated glucocerebroside

Accumulation of glucocerebroside primarily in the lysosomal compartment of macrophages, giving rise to foam cells or "Gaucher cells”

Absorption

No accumulation from Weeks 1-37 was observed

Distribution

Vd: 82-108 mL/kg

Elimination

Half-life: 11-12 min

Clearance: 6.72-7.56 mL/min/kg

IV Compatibilities

0.9% NaCl

Reconstitution

Determine number of vials needed based on prescribed dose

Reconstitute each vial with 4.3 mL of sterile water for injection

Gently mix; do not shake; final concentration of reconstituted solution (400 units/4 mL)

Visually inspect reconstituted solution; should appear clear to slightly opalescent and colorless; do not use if discolored or if foreign particulate matter is present

IV Preparation

Withdraw calculated dose from reconstituted vials

With a separate syringe, withdraw air from a 100-mL infusion bag of 0.9% NaCl

Inject and dilute calculate dose into prepared 0.9% NaCl bag

Gently mix, do not shake

Diluted solutions may contain slight flocculation (described as white irregular shaped particles) which is acceptable for administration

Discard any unused solution

IV Administration

Administer solution through an in-line low protein-binding 0.2- or 0.22-micron filter over 60 minutes

Premedication

• Consider premedicating with antihistamines and/or corticosteroids in patients history of hypersensitivity associated with prior velaglucerase alfa product infusions
• Appropriate medical support should be readily available when administered

Storage

Unopened vials

• Refrigerate at 2-8ºC (36-46ºF) in the original carton to protect from light, do not freeze
• Do not use after expiration date on vial

Reconstituted vials

• Contains no preservatives
• Once reconstituted, use immediately
• If not used, may be stored at 2-8ºC (36-46ºF) for up to 24 hr; do not freeze
• Protect from light
• Vials are for single-dose vials; discard any unused solution

Diluted infusions

• Store at 2-8ºC (36-46ºF) for up to 24 hr; do not freeze
• Protect from light
• Complete infusion within 24 hr of whence vials were reconstituted