Drug information of Agalsidase beta

Agalsidase beta is a recombinant form of the enzyme alpha-galactosidase-A, which is required for the hydrolysis of GL-3 and other glycosphingolipids. The compounds may accumulate (over many years) within the tissues of patients with Fabry disease, leading to renal and cardiovascular complications. In clinical trials of limited duration, agalsidase been noted to reduce tissue inclusions of a key sphingolipid (GL-3). It is believed that long-term enzyme replacement may reduce clinical manifestations of renal failure, cardiomyopathy, and stroke. However, the relationship to a reduction in clinical manifestations has not been established.

Distribution

V_dss: Children: 247 to 1097 mL/kg; Adults: 81 to 570 mL/kg

Excretion

Clearance: Children: 1.1 to 5.8 mL/minute/kg; Adults: 0.8 to 4.9 mL/minute/kg

Half-Life Elimination

Dose dependent: Children: 86 to 151 minutes; Adults: 45 to 119 minutes

Fabry disease: For use in patients with Fabry disease. Agalsidase beta reduces globotriaosylceramide (GL-3) deposition in capillary endothelium of the kidney and certain other cell types.

1 mg/kg via IV infusion every 2 weeks
-Initial infusion rate should not exceed 0.25 mg/min (15 mg/hr); once tolerance to the infusion is well established, may increase infusion rate in increments of 0.05 to 0.08 mg/min with each subsequent infusion
Maximum infusion rate (weight less than 30 kg): 0.25 mg/minute
Minimum infusion duration (weight 30 kg or greater): 1.5 hours (based on individual patient tolerability)

Comments:
-Antipyretics are recommended prior to infusions; anti-histamines should also be given in patients who have had an infusion-associated reaction.
-For patients who have had a positive skin test, see dose adjustment section for rechallenge administration.

Use: For treatment of patients with Fabry disease; this drug reduced globotriaosylceramide (GL-3) deposition in capillary endothelium of the kidney and certain other cell types,.

8 years or older:
1 mg/kg via IV infusion every 2 weeks
-Initial infusion rate should not exceed 0.25 mg/min (15 mg/hr); once tolerance to the infusion is well established, may increase infusion rate in increments of 0.05 to 0.08 mg/min with each subsequent infusion
Maximum infusion rate (weight less than 30 kg): 0.25 mg/minute
Minimum infusion duration (weight 30 kg or greater): 1.5 hours (based on individual patient tolerability)

Comments:
-Antipyretics are recommended prior to infusions; anti-histamines should also be given in patients who have had an infusion-associated reaction.
-For patients who have had a positive skin test, see dose adjustment section for rechallenge administration.

Side effects requiring immediate medical attention

Along with its needed effects, agalsidase beta may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking agalsidase beta:

More common

• Blurred vision
• chest pain or discomfort
• confusion
• cough producing mucus
• difficulty breathing
• difficulty in moving
• dizziness;
• fatigue
• faintness or lightheadedness when getting up from a lying or sitting position suddenly
• feeling unusually cold shivering
• headache
• hives or welts
• irregular heartbeat
• itching
• joint pain
• muscle aching or cramping
• muscle pains or stiffness
• nervousness
• pain
• pounding in the ears
• redness of skin
• shortness of breath
• skin rash
• stomach pain
• sweating
• swelling of ankles, feet, and lower legs
• swollen joints
• tightness in chest
• unusual tiredness or weakness
• wheezing

Incidence unknown

• Cloudy or bloody urine
• decreased cardiac output
• difficulty in speaking
• double vision
• feeling of constant movement of self or surroundings
• high blood pressure
• inability to move arms, legs, or facial muscles
• inability to speak
• no blood pressure or pulse
• partial loss of hearing
• pounding or rapid pulse
• problems with muscle control or coordination
• sensation of spinning
• shakiness and unsteady walk
• slow speech
• stopping of heart
• swelling of face
• swelling of the lip or ear
• throat tightness
• trembling
• unconsciousness

Side effects not requiring immediate medical attention

Some side effects of agalsidase beta may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More Common

• Acid or sour stomach
• belching
• body aches or pain
• body produces substance that can bind to drug making it less effective or cause side effects
• burning, crawling, itching, numbness, prickling, "pins and needles" , or tingling feelings
• congestion
• discouragement
• dryness or soreness of throat
• fear
• feeling sad or empty
• fever, not related to infusion
• heartburn
• hoarseness
• indigestion
• irritability
• lack of appetite
• loss of interest or pleasure
• nausea
• pain or tenderness around eyes and cheekbones
• paleness of skin
• runny nose
• sensation of change in temperature
• skeletal pain
• sneezing
• stuffy nose; swelling of testes
• tender, swollen glands in neck
• trouble concentrating
• trouble sleeping
• trouble in swallowing
• voice changes

Concerns related to adverse effects:

• Anaphylaxis/allergic reactions: Life-threatening anaphylactic and severe allergic reactions have been reported. Reactions may include angioedema, bronchospasm, chest discomfort, dysphagia, dyspnea, flushing, hypotension, nasal congestion, pruritus, rash, and urticaria. Stop infusion if severe reactions occur; immediate medical support should be readily available. Use caution when administering to patients with history of an anaphylactic or severe allergic reaction.
• Antibody formation: Development of IgG antibodies is common and has been observed within 3 months from the onset of therapy. Some patients may also develop IgE antibodies or skin test reactivity; consider IgE testing in patients with allergic reaction. Rechallenge of patients with IgE-mediated reaction or who have had a positive skin test may be done with caution.
• Infusion reactions: Infusion-related reactions are common, and may be severe (chills, vomiting, hypotension, paresthesia); pretreatment with antipyretics and antihistamines is advised. Decrease infusion rate, temporarily discontinue infusion, and/or administer additional antipyretics, antihistamines, and/or steroids to manage infusion reactions. Immediate discontinuation of infusion should be considered for severe reactions. Appropriate medical support for the management of infusion reactions should be readily available. Infusion reactions have occurred despite premedication. Use with caution when readministering to patients with history of infusion reactions.

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with compromised cardiac function; may have increased risk of complications from infusion reactions; monitor closely.

Agalsidase beta is given as an infusion into a vein. A healthcare provider will give you this injection.

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

You may need frequent medical tests.

Before taking this medicine Tell your doctor if you have ever had:

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

Tell your doctor if you are pregnant or breast-feeding.

Store intact vials between 2°C and 8°C (36°F and 46°F). Product is preservative free; use reconstituted and solutions diluted in NS immediately. If not used immediately, reconstituted and diluted solutions are stable for 24 hours at 2°C and 8°C (36°F and 46°F).

Benefit should outweigh risk
AU TGA pregnancy category: B2
US FDA pregnancy category: Not assigned
Risk Summary: Available data from postmarketing case reports and case series have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes; animal studies have not shown evidence of adverse effects on embryofetal development.
Comments:
-Pregnant women and women of reproductive potential should be encouraged to enroll in the Fabry patient registry; this registry monitors the effect of this drug on pregnant women and their offspring