Agalsidase beta

Agalsidase beta may be found in some form under the following brand names:

• Fabrazyme

Contraindications

• No known contraindications.1

Warnings/Precautions

Warnings

Potentially severe infusion reactions (e.g., chills, fever, dyspnea, nausea, vomiting, hypotension, paresthesia, flushing, headache, fatigue, pruritus, pain in extremity, hypertension, chest pain, throat tightness, abdominal pain, dizziness, tachycardia, nasal congestion, diarrhea, peripheral edema) reported.a Infusion reactions may occur in patients pretreated with acetaminophen and in patients pretreated with antipyretics, an antihistamine, and an oral corticosteroid.1

Administer antipyretics prior to infusion.a If an infusion reaction occurs, decrease infusion rate or interrupt infusion; institute appropriate supportive treatment (i.e., additional antipyretics, antihistamines, and/or corticosteroids) as indicated.a

Incidence of infusion reactions decreases with continued infusions; however, such reactions may occur even with extended duration of therapy.a

Sensitivity Reactions

Development of IgG antibodies to agalsidase beta reported in most patients, usually within the first 3 months of therapy; however, antibodies did not appear to affect efficacy and did not have a neutralizing effect.1 2 3 5

Possible development of IgE antibodies or skin test reactivity to agalsidase beta.a Consider testing for IgE antibodies if allergic reaction is suspected; consider risks and benefits of continued treatment in patients with evidence of IgE antibody development.1

Following discontinuance of therapy because of development of positive skin test or IgE antibodies to agalsidase beta, therapy may be reinitiated using a rechallenge protocol.a (See Dosage under Dosage and Administration.)

General Precautions

Increased risk of severe complications from infusion reactions in patients with compromised cardiac function; monitor such patients closely.1 (See Infusion Reactions under Cautions.)

A registry has been established to monitor the variability and progression of Fabry’s disease, to monitor and evaluate the long-term treatment effects of agalsidase beta, to monitor the effect of agalsidase beta on pregnant women and their developing fetuses, and to determine whether the drug is distributed into breast milk.1 Information is available at and 800-745-4447.a

Specific Populations

Category B.a Pregnancy registry at 800-745-4447. 1

Not known whether agalsidase beta is distributed into milk.a Caution if used in nursing women.1

Safety and efficacy not established in children <8 years of age;a however, experts recommend initiation of enzyme replacement therapy in children with clinical manifestations of Fabry’s disease.3 5

IgG seroconversion in pediatric patients associated with increased half-life and plasma agalsidase beta concentrations; this phenomenon is rarely observed in adult patients.a (See Immunologic Reactions and Antibody Formation under Cautions.)

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.1

Response in females does not appear to differ from that in males.a

Common Adverse Effects

Infusion reactions (e.g., vomiting, chills, fever, fatigue, feeling cold, hypertension), anemia, peripheral edema, pain, respiratory tract infection, nasopharyngitis, procedural pain.a

Specific Drugs

Absorption

AUC does not increase proportionately with increased dose.a

Elimination

Half-life

82–199 minutes.1

Special Populations

Half-life is increased in pediatric patients who develop IgG antibodies.a

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of low mood (depression), thoughts of killing yourself, nervousness, emotional ups and downs, thinking that is not normal, anxiety, or lack of interest in life.
• Change in hearing.
• Hearing loss.
• Ringing in ears.
• Very bad dizziness or passing out.
• Trouble swallowing.
• Some patients have very bad side effects during the infusion. Tell your doctor if you have a burning, numbness, or tingling feeling that is not normal; chest pain; fast or slow heartbeat; feeling hot or cold; feeling sleepy; fever or chills; flushing; headache; loose stools (diarrhea); muscle pain or weakness; pain in the arms or legs; pale skin; stomach pain; stuffy nose; swelling; tiredness; upset stomach or throwing up; or any other bad effects during the infusion.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Signs of a common cold.
• Cough.
• Back pain.
• Anxiety.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

(aye GAL si days BAY ta)

• Fabrazyme

Fabry disease: IV: 1 mg/kg every 2 weeks

>10%:

Cardiovascular: Peripheral edema (21%), hypertension (14%)

Central nervous system: Chills (43%), headache (39%), paresthesia (31%), procedural pain (25%), fatigue (24%), dizziness (21%), pain (16%), sensation of cold (11%)

Dermatologic: Skin rash (20%)

Immunologic: Development of IgG Antibodies (69% to 79%)

Local: Infusion site reaction (50% to 55%, severe ≥5%)

Neuromuscular & skeletal: Limb pain (19%), back pain (16%), myalgia (14%)

Respiratory: Upper respiratory tract infection (44%), cough (33%), nasal congestion (19%), lower respiratory tract infection (18%)

Miscellaneous: Fever (39%)

1% to 10%:

Cardiovascular: Tachycardia (9%), bradycardia (≥5%), chest discomfort (≥5%), chest pain (≥5%), facial edema (≥5%), flushing (≥5%), hypotension (≥5%), ventricular hypertrophy (5%)

Central nervous system: Hypoesthesia (9%), anxiety (6%), burning sensation (6%), depression (6%), falling (6%)

Dermatologic: Pruritus (10%), excoriation (9%), pallor (≥5%), urticaria (≥5%), thermal injury (4%)

Gastrointestinal: Toothache (6%), abdominal pain (≥5%), diarrhea (≥5%), nausea (≥5%), vomiting (≥5%), xerostomia (4%)

Hematologic & oncologic: Bruise (4%)

Hypersensitivity: Anaphylaxis, hypersensitivity reaction

Infection: Fungal infection (5%), viral infection (5%), localized infection (4%)

Neuromuscular & skeletal: Muscle spasm (5%)

Otic: Tinnitus (8%), hypoacusis (5%)

Renal: Increased serum creatinine (9%)

Respiratory: Sinusitis (9%), dyspnea (8%), respiratory congestion (8%), pharyngitis (6%), wheezing (6%), pharyngeal edema (≥5%)

Miscellaneous: Procedural complications (postprocedure, 10%)

Frequency not defined:

Cardiovascular: Cardiac arrhythmia, cerebrovascular accident, low cardiac output

Central nervous system: Ataxia, vertigo

Genitourinary: Nephrotic syndrome

<1% (Limited to important or life-threatening): Anaphylactic shock, angioedema (including auricular edema, dysphagia, lip edema, ocular edema, pharyngeal edema, tongue edema), bronchospasm, cardiac failure, hypersensitivity angiitis, hypoxia, lymphadenopathy, myocardial infarction, palpitations, pneumonia, renal failure, respiratory failure, sepsis

Your pharmacist has more information about agalsidase beta written for health professionals that you may read.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

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Data not available

Administration Advice:
-For IV infusion only
-Pretreatment with antipyretics is recommended prior to start of infusion.
-Administer the diluted solution using an in-line low-protein-binding 0.2 micrometer filter; do not administer with other products in infusion tubing.
-Infuse initially at a rate of no more than 0.25 mg/min (15 mg/hr); once tolerance to infusion is well established, may increase in increments of 0.05 to 0.08 mg/min (3 to 5 mg/hr) with each subsequent infusion.
-Infusion rate may be slowed or stopped in the event of an infusion reaction; pretreatment with antipyretics and antihistamines is then recommended.

For patients weighing less than 30 kg:
-Maximum infusion rate of 0.25 mg/min (15 mg/hr)

For patients weighing 30 kg or more:
-Administration duration not less than 1.5 hours (based on individual patient tolerability)

For patients being rechallenged following a positive skin test to this drug or positive for antidrug IgE antibodies:
-Initial infusion rate of 0.01 mg/min; once tolerability is established, may increase by slowly titrating upwards (doubled every 30 minutes) to a maximum rate of 0.25 mg/min, as tolerated

Storage Requirements:
-Store vials at 2C to 8C (36F to 46F); do not shake or agitate.
-Use diluted solution immediately; if cannot use immediately, may store for up to 24 hours at 2C to 8C (36F to 46F).

Reconstitution/Preparation Techniques:
-The manufacturer product information should be consulted.

IV Compatibility:
-Compatible with 0.9% Sodium Chloride Injection

General:
-Clinical studies did not include a sufficient number of patients aged 65 years or older to determine if they respond differently than younger patients.

Monitoring:
-Immunologic: Signs/symptoms of allergic reactions (including anaphylaxis) and/or infusion-related reaction

Patient Advice:
-You are encouraged to participate in the Fabry registry and should visit fabryregistry.com for more information.

Animal studies have failed to reveal evidence of fetal harm or impaired fertility. There are no controlled data in human pregnancy. Women of childbearing potential are encouraged to register themselves in the Fabry patient registry in order to monitor the effects on pregnant women and their offspring. For additional information: fabryregistry.com AU TGA pregnancy category B2: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals are inadequate or may be lacking, but available data show no evidence of an increased occurrence of fetal damage. US FDA pregnancy category B: Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women.

This drug should be used during pregnancy only if clearly needed. AU TGA pregnancy category: B2 US FDA pregnancy category: B