agalsidase beta (Rx)

>10%

Adults

• Upper respiratory tract infection (53%)
• Chills (49%)
• Pyrexia (39%)
• Headache (39%)
• Cough (33%)
• Paresthesia 31%)
• Fatigue (24%)
• Peripheral edema (21%)
• Dizziness (21%)
• Rash (20%)
• Pain in extremity (19%)
• Myalgia (18%)
• Lower respiratory tract infection (18%)
• Pain (16%)
• Back pain (16%)
• Hypertension (14%)

Pediatric patients

• Headache (>20%)
• Abdominal pain (>20%)
• Pharyngitis (>20%)
• Fever (>20%)
• Nausea (>20%)
• Vomiting (>20%)
• Rhinitis (>20%)
• Diarrhea (>20%)
• Arthralgia (>20%)
• Dizziness (>20%)

1-10%

Adults

• Pruritus (10%)
• Tachycardia (9%)
• Excoriation (9%)
• Increased blood creatinine (9%)
• Tinnitus (8%)
• Dyspnea (8%)
• Fall (6%)
• Burning sensation (6%)
• Anxiety (6%)
• Depression (6%)
• Wheezing (6%)
• Hypoacusis (5%)
• Chest discomfort (5%)
• Fungal infection (5%)
• Viral infection (5%)
• Hot flush (5%)

Postmarketing Reports

Cardiovascular: Cardiorespiratory arrest, cardiac failure, myocardial infarction, palpitations

Infections: Sepsis and pneumonia

Infusion-associated reactions: Anaphylaxis, localized angioedema (eg, auricular swelling, eye swelling, dysphagia, lip swelling, edema, pharyngeal edema, face swelling, swollen tongue), and bronchospasm

General: Hyperhidrosis, asthenia, infusion site reaction

Lymphatic: Lymphadenopathy

Musculoskeletal: Arthralgia

Nasopharyngeal: Rhinorrhea

Neurologic: Cerebrovascular accident, hypoesthesia, oral hypoesthesia

Ophthalmologic: Increased lacrimation

Pulmonary: Respiratory failure, hypoxia

Renal: Renal failure

Dermatologic: Erythema

Vascular: Leukocytoclastic vasculitis

Contraindications

None

Cautions

Anaphylaxis and hypersensitivity reactions

• In clinical trials and postmarketing safety experience, anaphylactic or severe hypersensitivity reactions reported
• Higher incidences of hypersensitivity reactions were observed in adults with persistent anti-Fabrazyme antibodies and with high antibody titer compared to that in antibody negative adults
• Consider testing for IgE antibodies in patients who experienced suspected hypersensitivity reactions
• Consider risks and benefits of continued treatment in patients with anti-Fabrazyme IgE antibodies
• No marketed tests for antibodies; if testing is warranted, contact Genzyme Corporation at 1-800-745-4447
• Patients who have had a positive skin test or have tested positive for Fabrazyme-specific IgE antibody have been rechallenged using a rechallenge protocol
• Rechallenge under direct supervision of qualified personnel, with appropriate medical support measures readily available

Infusion-associated reactions

• Infusion-associated reactions, some severe, reported
• Incidence was higher in patients positive for anti-Fabrazyme antibodies compared with those who were negative
• Severe infusion-associated reactions included chills, vomiting, hypotension, and paresthesia
• Other infusion-associated reactions included pyrexia, feeling hot or cold, dyspnea, nausea, flushing, headache, fatigue, pruritus, pain in extremity, hypertension, chest pain, throat tightness, abdominal pain, dizziness, tachycardia, nasal congestion, diarrhea, edema peripheral, myalgia, urticaria, bradycardia, and somnolence
• Ensure appropriate medical support measures are readily available during administration
• Closely monitor with history infusion-associated reactions
• Advanced Fabry disease may compromise cardiac function, which may potentially increase risk of severe complications from infusion-associated reactions; closely monitor with compromised cardiac function

Pregnancy

Registry available and monitors drug effects on pregnant women and their offspring

For more information, visit www.registrynxt.com or call 1-800-745-4447, extension 15500

Encourage patients to enroll for the registry

Available data from postmarketing case reports and case series with use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes

Animal data

• Reproduction studies performed in rats at doses up to 68 times the human dose have revealed no evidence of effects on embryo-fetal development

Lactation

There are no data on the presence of agalsidase beta in either human or animal milk, the effects of the drug on the breastfed infant, or on milk production

Developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy and any potential adverse effects on breastfed child from drug or from underlying maternal condition

Encourage lactating women to enroll in the registry

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

Recombinant alpha-galactosidase A, an enzyme (deficient in Fabry disease) involved in the metabolism of glycosphingolipids (eg, GL-3); corrects abnormal glycosphingolipid metabolism resulting in reduced accumulation of glycosphingolipids and improvement of associated clinical manifestations; reduces GL-3 deposition in capillary endothelium

Absorption

Peak plasma concentration: 0.6-29.7 mcg/mL (0.3-1 mg/kg-dose)

Distribution

Vd (steady-state): 81-330 mL/kg (0.3-1 mg/kg-dose)

Elimination

Half-life: 45-102 min (0.3-1 mg/kg-dose)

Clearance: 0.8-4.6 mL/min/kg (0.3-1 mg/kg-dose)

IV Incompatibilities

Do not in same IV line with other products

IV Compatibilities

0.9% NaCl

IV Preparation

Calculate dose based on patient’s body weight and select a combination of 35-mg and 5-mg vials

Remove vials from refrigerator and allow them to reach room temperature before reconstituting (~30 min)

Reconstitution

• 35-mg vials: Reconstitute with 7.2 mL of sterile water for injection (SWI) (total extractable solution per vial is 7 mL)
• 5-mg vials: Reconstitute with 1.1 mL of SWI (total extractable solution per vial is 1 mL)
• Roll and tilt each vial gently to yield a 5 mg/mL clear, colorless solution
• Visually inspect for particulate matter and discoloration; discard if there is particulate matter or discoloration
• Discard any unused product
• Avoid shaking or agitating this product; do not use filter needles during preparation

Dilution

• Further dilute reconstituted solution with 0.9% NaCl to a total volume based on patient weight
• Slowly withdraw reconstituted solution to required dose volume and inject directly into 0.9% NaCl
• Do not inject in airspace within infusion bag; discard any vial with unused reconstituted solution
• Gently invert infusion bag to mix, avoiding vigorous shaking and agitation

• Minimum total infusion volume based on patient’s weight

  • ≤35 kg: 50 mL
  • 35.1-70 kg: 100 mL
  • 70.1 to 100 kg: 250 mL
  • >100 kg: 500 mL

IV Administration

Administer as an IV infusion using an in-line low protein binding 0.2-micron filter

Do not infuse in the same IV line with other products

Appropriate medical support measures should be readily available

Administer antipyretics before infusion

Infusion rate

• 0.25 mg/min (15 mg/hr) initially; may increase rate based on patient’s weight once tolerance to infusion is well established
• >30 kg: Increase rate in increments of 0.05-0.08 mg/min (increments of 3-5 mg/hr) with each subsequent infusion; minimum infusion duration is 1.5 hr (based on tolerability)
• <30 kg: Maximum infusion rate is 0.25 mg/min (15 mg/hr)
• Slow infusion rate in event of an infusion-associated reaction

Rechallenge procedure

• Patients who have had a positive skin test or tested positive for anti-Fabrazyme IgE may be successfully rechallenged
• Initial rechallenge administration should be a low dose at a lower infusion rate (eg, ½ the therapeutic dose [0.5 mg/kg] at 1/25 of initial standard rate [0.01 mg/min])
• Once tolerated, may increase dose to 1 mg/kg and slowly titrate rate up (doubled q30min up to a maximum rate of 0.25 mg/min), as tolerated

Storage

Does not contain preservatives

Unused vials

• Single use only
• Refrigerate at 2-8ºC (36-46ºF); do not use after expiration date on vial

Reconstituted vials and diluted solutions

• Use immediately
• If immediate use is not possible, refrigerate at 2-8ºC (36-46ºF) for up to 24 hr