Agalsidase beta

Name: Agalsidase beta

What Is Agalsidase Beta?

Agalsidase beta is a man-made form of the naturally-occurring alpha-galactosidase A enzyme. A deficiency of this enzyme is called Fabry disease. Agalsidase beta reduces deposits of globotriaosylceramide (GL-3) in the kidneys and certain other cells in the body.

Agalsidase beta is used in the treatment of Fabry disease.

Agalsidase beta may also be used for purposes other than those listed here.

Many people have a severe reaction to agalsidase beta. Tell your caregiver right away if you have a side effect such as: skin rash or hives, fever, chills, headache, muscle pain, dizziness, numbness, swelling, vomiting, diarrhea, chest pain, trouble swallowing or breathing, fast or slow heart rate, or feeling light-headed.

To make sure agalsidase beta is safe for you, tell your doctor if you have:

  • heart problems; or
  • if you have ever had an allergic reaction to agalsidase beta or have antibodies to the medication.

FDA pregnancy category B. Agalsidase beta is not expected to harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment.

It is not known whether agalsidase beta passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

Your name may be listed on a Fabry disease patient registry. This is to track the progress of your disease and to evaluate the treatment effects of agalsidase beta. Taking part in this registry is especially important if you are pregnant or breast-feeding.

Agalsidase Beta Dosage

Agalsidase beta is injected into a vein through an IV. A healthcare provider will give you this injection.

Agalsidase beta is usually given once every 2 weeks. Follow your doctor's instructions.

While using agalsidase beta, you may need frequent medical tests.

Since this medication is given by a healthcare professional in a medical setting, an overdose is unlikely to occur.

Call your doctor for instructions if you miss an appointment for your agalsidase beta injection.

Uses of Agalsidase beta

Agalsidase beta is a prescription medication used to treat Fabry disease. Fabry disease is an inherited condition that can cause kidney failure, heart problems, and stroke.

This medication may be prescribed for other uses.  Ask your doctor or pharmacist for more information.

What is agalsidase beta?

Agalsidase beta is a man-made form of the naturally-occurring alpha-galactosidase A enzyme. A deficiency of this enzyme is called Fabry disease. Agalsidase beta reduces deposits of globotriaosylceramide (GL-3) in the kidneys and certain other cells in the body.

Agalsidase beta is used in the treatment of Fabry disease.

Agalsidase beta may also be used for purposes other than those listed here.

What should I discuss with my health care provider before using agalsidase beta?

To make sure agalsidase beta is safe for you, tell your doctor if you have:

  • heart problems; or

  • if you have ever had an allergic reaction to agalsidase beta or have antibodies to the medication.

FDA pregnancy category B. Agalsidase beta is not expected to harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment.

It is not known whether agalsidase beta passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

Your name may be listed on a Fabry disease patient registry. This is to track the progress of your disease and to evaluate the treatment effects of agalsidase beta. Taking part in this registry is especially important if you are pregnant or breast-feeding.

What happens if I overdose?

Since this medication is given by a healthcare professional in a medical setting, an overdose is unlikely to occur.

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Intravenous:

Fabrazyme: 5 mg (1 ea); 35 mg (1 ea) [contains mouse (murine) and/or hamster protein]

Dosing Hepatic Impairment

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing Adjustment for Toxicity

Patient with IgE antibodies or a positive skin test to agalsidase beta (rechallenge): IV: 0.5 mg/kg every 2 weeks at an initial maximum infusion rate of 0.01 mg/minute; may gradually escalate dose (to maximum of 1 mg/kg every 2 weeks) and/or infusion rate (doubling the infusion rate every 30 minutes to a maximum rate of 0.25 mg/minute) as tolerated.

Reconstitution

IV: Allow vials and diluent to reach room temperature prior to reconstitution (~30 minutes). Each 35 mg vial should be reconstituted with 7.2 mL SWFI; reconstitute 5 mg vials with 1.1 mL SWFI; inject down internal side wall of vial; roll and tilt gently; do not shake. Resulting solution contains 5 mg/mL. Do not use filter needle to prepare. To make final infusion solution, add the desired amount of reconstituted solution to NS to make a final volume based on patient weight (see table for dilution volumes). Prior to adding the volume of agalsidase beta dose to the NS, remove an equal volume of NS. Avoid vigorous shaking or agitation.

Recommended Minimum Volumes for Dilution

Patient Weight

(kg)

Minimum Total Volume

(mL)

≤35

50

35.1 - 70

100

70.1 - 100

250

>100

500

Table has been converted to the following text:

Recommended minimum total volume for dilution

Patient weight ≤35 kg: 50 mL

Patient weight 35.1 - 70 kg: 100 mL

Patient weight 70.1 - 100 kg: 250 mL

Patient weight >100 kg: 500 mL

Administration

Antipyretics should be administered prior to infusion. Infuse through a low protein binding 0.2 micron in-line filter. Initial infusion rate should not exceed 0.25 mg/minute (15 mg/hour). Interrupt or decrease rate in the event of an infusion reaction; may be restarted after resolution of symptoms and/or after administration of antipyretics, antihistamines, and/or steroids. After patient tolerance to the infusion is established, rate may be increased in increments of 0.05-0.08 mg/minute (3-5 mg/hour) with each subsequent infusion. Maximum infusion rate: Patients <30 kg: 0.25 mg/minute; patients ≥30 kg: Infuse over at least 1.5 hours. An initial maximum infusion rate of 0.01 mg/minute should be used for rechallenge in patients with IgE antibodies or who have had a positive skin test to agalsidase beta; may increase infusion rate (doubling the infusion rate every 30 minutes) to a maximum rate of 0.25 mg/minute as tolerated.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience common cold symptoms, cough, anxiety, or back pain. Have patient report immediately to prescriber signs of allergic reaction with organ failure (fever, rash, fatigue, flu-like signs, nausea, vomiting, diarrhea, abdominal pain, pharyngitis, cough, or difficulty breathing), signs of depression (suicidal ideation, anxiety, emotional instability, or confusion), hearing impairment, tinnitus, severe dizziness, passing out, difficulty swallowing, or signs of infusion reactions (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

Adverse Effects

>10%

Infusion Reactions (50-55%)

  • Decrease frequency with continued treatment
  • Bradycardia, flushing, hypertension, hypotension, peripheral edema, tachycardia
  • Chills, dizziness, fatigue, feeling hot or cold, headache, pain in extremity, paresthesia, pyrexia, somnolence
  • Abdominal pain, diarrhea, nausea, vomiting
  • Pruritus, Urticaria
  • Myalgia
  • Chest pain, dyspnea, nasal congestion, throat tightness

Upper respiratory tract infections (44%)

Chills (43%)

Headache (39%)

Pyrexia (39%)

Paresthesia (31%)

Fatigue (24%)

Dizziness (21%)

Edema peripheral (21%)

Cough (20%)

Pain in extremity (19%)

Lower respiratory tract infection (18%)

Back pain (16%)

Pain (16%)

Myalgia (14%)

Hypertension (14%)

Feeling cold (11%)

1-10%

Pruitus (10%)

Excoriation (9%)

Sinusitis (9%)

Sr creatinine increased (9%)

Tachycardia (9%)

Dyspnea (8%)

Respiratory tract congestion (8%)

Tinnitus (8%)

Anxiety (6%)

Burning sensation (6%)

Depression (6%)

Fall (6%)

Pharyngitis (6%)

Toothache (6%)

Wheezing (6%)

Chest discomfort (5%)

Fungal infection (5%)

Hot flash (5%)

Hypoacusis (5%)

Muscle spasms (5%)

Ventricular wall thickening (5%)

Viral infections (5%)

Confusion (4%)

Dry mouth (4%)

Localized infection (4%)

Thermal burn (4%)

What happens if i miss a dose (fabrazyme)?

Contact your doctor if you miss a dose of agalsidase beta.

For Healthcare Professionals

Applies to agalsidase beta: intravenous powder for injection

General

The most serious adverse reactions were anaphylactic/anaphylactoid and allergic reactions.

The most frequently reported adverse reactions were infusion reactions and consisted of chills, fever, feeling hot or cold, dyspnea, nausea, flushing, headache, vomiting, paresthesia, fatigue, pruritus, pain in extremity, hypertension, chest pain, throat tightness, abdominal pain, dizziness, tachycardia, nasal congestion, diarrhea, peripheral edema, back pain, pallor, bradycardia, hypotension, face edema, rash, and somnolence.[Ref]

Cardiovascular

Very common (10% or more): Hypertension (14%)
Common (1% to 10%): Tachycardia, ventricular wall thickening, hot flush, palpitations, blood pressure increased, heart rate increased, blood pressure increased, flushing, pallor, bradycardia
Uncommon (0.1% to 1%): Sinus bradycardia, peripheral coldness
Frequency not reported: Cardiac arrhythmia, cardiac arrest, cardiac output decreased, aortic valve incompetence, supraventricular arrhythmia, right bundle branch block, cardiac valve disease, atrial dilation, ventricular dilation, mitral valve disease, mitral valve incompetence, mitral valve sclerosis, pulmonary valve incompetence, supraventricular extrasystoles, ventricular extrasystoles, ventricular hypokinesia, cardiac imaging procedure abnormal, ejection fraction decreased, ECG PR shortened, ECG ST segment abnormal, ECG T wave abnormal, heart rate irregular, right ventricular systolic pressure increased, orthostatic hypotension, poor peripheral circulation, poor venous access, vasoconstriction, vasospasm
Postmarketing reports: Cardiorespiratory arrest, cardiac failure, myocardial infarction[Ref]

Gastrointestinal

Very common (10% or more): Nausea, vomiting
Common (1% to 10%): Toothache, dry mouth, abdominal pain/discomfort, stomach discomfort, hypoesthesia oral, upper abdominal pain, diarrhea
Uncommon (0.1% to 1%): Dyspepsia, dysphagia
Frequency not reported: gastroenteritis, gingivitis, retching
Postmarketing reports: Lip swelling, tongue swelling[Ref]

Dermatologic

Very common (10% or more): Rash (20%), pruritus (10%)
Common (1% to 10%): Urticaria, erythema, angioneurotic edema, maculopapular rash
Uncommon (0.1% to 1%): Livedo reticularis, rash erythematosus, pruritic rash, skin discoloration, skin discomfort
Frequency not reported: Leukocytoclastic vasculitis, pustular rash, excoriation, acne, eczema, hair growth abnormal
Postmarketing reports: Hyperhidrosis, localized angioedema[Ref]

Immunologic

During clinical trials, 95 of 121 adult patients and 11 of 16 pediatric patients developed antidrug IgG antibodies; the majority of patients developed antibodies within the first 3 months of exposure. In pediatric patients, IgG seroconversion in pediatric patients was attributed to prolonged half-life, which was likely due to the ability of antibodies to act as carriers for their antigens. The clinical significance of binding and/or inhibitory antibodies to this drug is unknown.

Testing for IgE antibodies occurred in about 60 patients during clinical trials who experienced moderate to severe infusion reactions or in whom mast cell activation was suspected. Of the 60 patients tested, 7 tested positive for antidrug IgE antibodies or had a positive skin test specific to this drug.[Ref]

Very common (10% or more): Antidrug IgG antibody development (74%)
Frequency not reported: Anaphylaxis/anaphylactoid reaction, seasonal allergy, skin test positive
Postmarketing reports: Anaphylactic shock[Ref]

Nervous system

Very common (10% or more): Headache (39%), paresthesia (31%), dizziness (21%)
Common (1% to 10%): Burning sensation, somnolence, hypoesthesia, lethargy, syncope
Uncommon (0.1% to 1%): Hyperesthesia, tremor
Frequency not reported: Stroke, ataxia, cerebrovascular accident, ischemic stroke, migraine, psychomotor hyperactivity, sinus headache, vasovagal syncope, restless leg syndrome, balance disorder, dyskinesia[Ref]

Musculoskeletal

Very common (10% or more): Pain in extremity (19%), back pain (16%), myalgia (14%)
Common (1% to 10%): Muscle spasms, arthralgia, muscle tightness, musculoskeletal stiffness, musculoskeletal pain
Frequency not reported: Chest wall pain, flank pain, groin pain, joint stiffness, musculoskeletal chest pain, pain in jaw, shoulder pain[Ref]

Other

Very common (10% or more): Chills (43%), pyrexia (39%), procedural pain (25%), fatigue (24%), peripheral edema (21%), pain (16%), feeling cold (11%), adverse event (10%), post procedural complication (10%)
Common (1% to 10%): Tinnitus, hypoacusis, chest discomfort, fungal infection, viral infection, localized infection, fall, contusion, thermal burn, feeling hot, asthenia, chest pain, face edema, malaise, hyperthermia, body temperature increased, vertigo
Uncommon (0.1% to 1%): Auricular swelling, ear pain/discomfort, influenza-like illness
Frequency not reported: Oxygen saturation decreased, hypoacousia, axillary pain, discomfort, feeling jittery, gait disturbance, sluggishness, thirst, gingival infection, infection, tooth infection, fall, post procedural nausea, vascular access complication, blood alkaline phosphatase increased
Postmarketing reports: Infusion-related reaction, sepsis, edema[Ref]

Respiratory

Very common (10% or more): Upper respiratory tract infection (44%), cough (33%), nasal congestion (19%), lower respiratory tract infection (18%)
Common (1% to 10%): Sinusitis, pharyngitis, dyspnea, exacerbated dyspnea, respiratory tract congestion, wheezing, throat tightness, nasopharyngitis
Uncommon (0.1% to 1%): Rhinitis, bronchospasm, pharyngolaryngeal pain, rhinorrhea, tachypnea, upper respiratory tract congestion
Frequency not reported: Hypoxia, pulmonary edema, respiratory distress, allergic rhinitis, rhonchi, throat irritation
Postmarketing reports: Respiratory failure, pneumonia, pharyngeal edema[Ref]

Psychiatric

Common (1% to 10%): Anxiety, depression
Frequency not reported: Agitation, confessional state, visual hallucination, flat affect, restlessness[Ref]

Metabolic

Frequency not reported: Hypocalcemia[Ref]

Ocular

Common (1% to 10%): Lacrimation increased
Uncommon (0.1% to 1%): Eye pruritus, ocular hyperemia
Frequency not reported: Diplopia, eye edema, night blindness, blurred vision, visual acuity reduced, visual disturbance, intraocular pressure increased
Postmarketing reports: Eye swelling[Ref]

Renal

Common (1% to 10%): Blood creatinine increased
Frequency not reported: Nephrotic syndrome, creatinine clearance decreased, cystatin C increased, renal failure, renal impairment[Ref]

Local

Frequency not reported: Catheter site rash, catheter site related reaction, infusion site pain, infusion site thrombosis
Postmarketing reports: Infusion site reaction[Ref]

Hepatic

Frequency not reported: Alanine aminotransferase increased, aspartate aminotransferase increased, hepatic enzyme increased[Ref]

Hematologic

Frequency not reported: Anemia, eosinophilia, leukopenia, hematocrit decreased, hemoglobin decreased
Postmarketing reports: Lymphadenopathy[Ref]

Genitourinary

Frequency not reported: Prostate examination abnormal, albuminuria, proteinuria, dysuria, hematuria, benign prostatic hyperplasia, dysmenorrhea, nipple pain, erectile dysfunction[Ref]

Some side effects of agalsidase beta may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

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