Fabrazyme

agalsidase beta

Fabrazyme, Fibrazyme

Pharmacologic class: Homodimeric glycoprotein

Therapeutic class: Recombinant human alpha-galactosidase enzyme

Pregnancy risk category B

Action

Provides exogenous source of alpha-galactosidase A (which is deficient in Fabry disease) and reduces deposits of globotriaosylceramide in kidney and other body tissues

Availability

Powder for reconstitution: for injection, lyophilized: 5 mg, 35 mg

Indications and dosages

➣ Fabry disease

Adults: 1 mg/kg I.V. q 2 weeks. Infuse no faster than 0.25 mg/minute; if tolerated, increase rate by 0.05 to 0.08 mg/minute in subsequent infusions.

Contraindications

None

Precautions

Use cautiously in:

• advanced Fabry disease, cardiac dysfunction

• pregnant or breastfeeding patients

• children.

Administration

• Premedicate with antipyretics, as prescribed.

• To reconstitute, slowly inject 7.2 ml of sterile water for injection into vial; then roll and tilt vial gently to mix drug.

• Don't shake drug, and don't use filter needles.

• Dilute reconstituted solution with normal saline injection to a final volume of 500 ml.

• Infuse through separate I.V. line; don't mix with other drugs.

Adverse reactions

CNS: anxiety, depression, dizziness, paresthesias

CV: dependent edema, chest pain, cardiomegaly

EENT: rhinitis, sinusitis, laryngitis, pharyngitis

GI: nausea, dyspepsia

GU: testicular pain

Musculoskeletal: arthrosis, bone pain

Respiratory: bronchitis, bronchospasm

Skin: pallor

Other: pain, allergic reactions, infusion reactions (hypertension, chest tightness, dyspnea, fever, rigors, hypotension, abdominal pain, pruritus, myalgia, headache, urticaria)

Interactions

Drug-drug. Amiodarone, chloroquine, gentamicin, monobenzone: inhibition of intracellular agalsidase activity

Patient monitoring

• Watch closely for signs and symptoms of allergic or infusion reaction.

• Monitor vital signs and fluid intake and output. Stay alert for dependent edema, blood pressure changes, and chest pain.

• Measure temperature. Watch for signs and symptoms of infection (particularly EENT and respiratory infections).

• Evaluate patient's mood. Report significant anxiety or depression.

Patient teaching

See Teach patient to recognize and immediately report signs and symptoms of allergic or infusion reaction.

• Caution patient to avoid driving and other hazardous activities until he knows how drug affects mood, balance, and blood pressure.

• Advise patient to report signs and symptoms of infection (particularly EENT and respiratory infections).

• Inform patient that drug can cause depression and anxiety. Instruct him to notify prescriber if these effects occur.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs mentioned above.

agalsidase beta

(a-gal-si-dase) agalsidasebeta,

Fabrazyme

(trade name)

Classification

Therapeutic: replacement enzyme
Pharmacologic: enzymes
Pregnancy Category: B

Indications

Fabry disease.

Action

Replaces a deficient enzyme.

Therapeutic effects

Prevents damage from accumulation of globotriaosylceramide in capillary endothelium.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.Distribution: Widely distributed.Metabolism and Excretion: Unknown.Half-life: 45–102 min.

Time/action profile

ROUTEONSETPEAKDURATION
IVunknownend of infusion2 wk

Contraindications/Precautions

Contraindicated in: None noted.Use Cautiously in: Compromised cardiac function (may have ↑ risk of infusion reactions); Obstetric / Lactation / Pediatric: Safety not established.

Adverse Reactions/Side Effects

Central nervous system

  • anxiety
  • depression
  • dizziness
  • headache

Respiratory

  • bronchospasm

Cardiovascular

  • edema (most frequent)
  • cardiomegaly
  • hypotension (most frequent)
  • hypertension

Gastrointestinal

  • dyspepsia
  • nausea

Genitourinary

  • testicular pain

Dermatologic

  • pallor

Musculoskeletal

  • skeletal pain (most frequent)
  • arthrosis

Miscellaneous

  • infusion reactions
  • rigors (most frequent)
  • fever

Interactions

Drug-Drug interaction

None noted.

Route/Dosage

Intravenous (Adults) 1 mg/kg every 2 wk.

Availability

Lyophilized powder for injection: 5 mg/mL in 5– and 35–mL vials

Nursing implications

Nursing assessment

  • Assess for infusion reactions (fever, rigors, chest tightness, hypertension, hypotension, pruritus, myalgia, dyspnea, urticaria, abdominal pain, headache). Pre-treat patients with antipyretics. If an infusion reaction occurs, regardless of pre-treatment, decrease infusion rate, temporarily stop the infusion, and/or administer additional antipyretics, antihistamines, and/or oral corticosteroids. Infusion reactions decline in frequency with continued use; serious reactions may still occur with extended of therapy.
  • Monitor cardiac function during treatment in patients with previously compromised cardiac function.

Potential Nursing Diagnoses

Deficient knowledge, related to medication regimen (Patient/Family Teaching)

Implementation

  • Intravenous Administration
  • Administer antipyretics prior to infusion.
  • Intermittent Infusion: Allow refrigerated agalsidase and diluent to reach room temperature prior to reconstitution (30 min). Determine number of 35 mg and 5 mg vials needed for dose. Reconstitute each vial by slowly injecting 7.2 mL and 1.1 mL of Sterile Water for Injection into each 35 mg vial and 5 mg vial, respectively. Inject down the inside wall of vial. Roll and tilt each vial gently. Solution is clear and colorless; do not administer solutions that are discolored or contain particulate matter. Diluent: Remove an equal volume of 0.9% NaCl from a 500 mL infusion bag, then dilute further with 0.9% NaCl for a final volume of 500 mL. Inject reconstituted agalsidase directly into 0.9% NaCl, do not inject into air space. Discard unused portion of vial. Gently invert bag to mix solution, avoid vigorous shaking or agitation. Diluted solution may be filtered through an in-line low protein-binding 0.2 micrometer filter during administration. Use reconstituted and diluted solutions immediately or within 24 hrs..
  • Rate: Initial infusion rate should not exceed 0.25 mg/min (15 mg/hr). Infusion rate may be slowed if infusion reaction occurs. After tolerance to rate is well established, infusion may be increased in increments of 0.05–0.08 mg/min (increments of 3–5 mg/hr)each subsequent infusion.
  • Y-Site Incompatibility: Do not infuse agalsidase in the same IV line with other products.

Patient/Family Teaching

  • Inform patients that a Registry has been established to better understand Fabry disease and to monitor the effects of agalsidase. Encourage patients to participate; participation is voluntary and may be long term. For information visit www.fabryregistry.com or call 800–745–4447.

Evaluation/Desired Outcomes

  • Reduction of globotriaosylceramide deposition in capillary endothelium of the kidney and certain other cell types.