Elosulfase alfa

Mechanism of Action

Replaces deficient enzyme N-acetylgalactosamine-6 sulfatase (GALNS) to minimize progressive multisystemic manifestations of Morquio A syndrome

Sulfatase activity deficiency results in the accumulation of the GAG substrates, KS and C6S, in the lysosomal compartment of cells throughout the body; the accumulation leads to widespread cellular, tissue, and organ dysfunction

Enzyme replacement provides the exogenous enzyme GALNS that will be taken up into the lysosomes and increase catabolism of GAGs KS and C6S

Absorption

All measurements at treatment week 22

AUC: 577 min•mcg/mL

Peak plasma time: 202 minutes

Peak plasma concentration: 4.04 mcg/mL

Distribution

All measurements at treatment week 22

Vd: 7.08 mL/min/kg

Elimination

All measurements at treatment week 22

Half-life: 35.9 minutes

Elosulfase alfa may be found in some form under the following brand names:

• Vimizim

If you take too much elosulfase alfa, call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

If elosulfase alfa is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.

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

General

• Prepare and administer under supervision of a clinician capable of managing medical emergencies.1

• To minimize risk of hypersensitivity reactions, administer an antihistamine (with or without an antipyretic) 30–60 minutes prior to each infusion.1 3

Administration

IV Administration

For solution compatibility information, see Compatibility under Stability.

Administer by IV infusion.1

Administer using a low-protein-binding infusion set equipped with a low-protein-binding 0.2-mcm inline filter.1

Contains no preservatives; discard partially used vials.1

Do not infuse through the same IV tubing with other drugs.1

Must dilute commercially available elosulfase alfa concentrate prior to administration.1 Dilute appropriate volume that will provide the recommended dose with 0.9% sodium chloride injection to a final volume of 100 mL (for patients weighing <25 kg) or 250 mL (for patients weighing ≥25 kg).1 Gently rotate infusion bag to mix; avoid shaking or agitation.1

Diluted solutions should be clear to slightly opalescent and colorless to pale yellow.1 Discard solution if discolored or particulate matter other than slight flocculation (e.g., thin translucent fibers) is present.1

Use immediately after dilution.1 If immediate use not possible, may store diluted solution at recommended conditions, but administration should be completed within 48 hours from the time of dilution.1 (See Storage under Stability.)

Administer over a minimum of 3.5–4.5 hours, depending on total infusion volume.1

Patients weighing <25 kg receiving total infusion volume of 100 mL: Infuse at a rate of 3 mL/hour for the first 15 minutes; if tolerated, may increase to 6 mL/hour for the next 15 minutes.1 If patient continues to tolerate the infusion, may increase incrementally by 6 mL/hour every 15 minutes up to a maximum rate of 36 mL/hour.1 Administer total volume over ≥3.5 hours.1

Patients weighing ≥25 kg receiving total infusion volume of 250 mL: Infuse at a rate of 6 mL/hour for the first 15 minutes; if tolerated, may increase to 12 mL/hour for the next 15 minutes.1 If patient continues to tolerate the infusion, may increase incrementally by 12 mL/hour every 15 minutes up to a maximum rate of 72 mL/hour.1 Administer total volume over ≥4.5 hours.1

Observe patients closely for anaphylaxis during and following administration.1 If a hypersensitivity reaction occurs, reduce infusion rate, temporarily interrupt infusion, or discontinue infusion for that visit.1 If a severe hypersensitivity reaction occurs, immediately discontinue infusion and initiate appropriate treatment.1 (See Hypersensitivity Reactions under Cautions.)

Dosage

Dosage is expressed in terms of mg.1 The specific activity of elosulfase alfa is 2.6–6 units/mg; 1 unit is defined as the amount of enzyme that results in the conversion of 1 mcmol of sulfated monosaccharide substrate D-galactopyranoside-6-sulfate to desulfated-galactose and free sulfate per minute at 37°C.1

Pediatric Patients

Children ≥5 years of age: 2 mg/kg by IV infusion once weekly.1

Adults

2 mg/kg by IV infusion once weekly.1

Prescribing Limits

Pediatric Patients

Children ≥5 years of age: Maximum infusion rate of 36 mL/hour for patients receiving total infusion volume of 100 mL or 72 mL/hour for those receiving total infusion volume of 250 mL.1

Adults

Maximum infusion rate of 36 mL/hour for patients receiving total infusion volume of 100 mL or 72 mL/hour for those receiving total infusion volume of 250 mL.1

Special Populations

No special population dosage recommendations at this time.1

• If you have an allergy to elosulfase alfa or any other part of this medicine.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.

This medicine may interact with other drugs or health problems.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take elosulfase alfa with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

• Elosulfase alfa
• N-acetylgalactosamine-6-sulfatase

• Enzyme

Note: Premedicate with antihistamines with or without antipyretics 30 to 60 minutes prior to infusion.

Mucopolysaccharidosis type IVA (MPS IVA): IV: 2 mg/kg once weekly

Dilute calculated dose in NS to a final volume of 100 mL (for patients weighing <25 kg) or 250 mL (for patients weighing ≥25 kg). Gently rotate to distribute. Do not shake or agitate. Use immediately. Vials are for single use only; discard any unused product.

Administer using a low protein-binding infusion set with in-line low protein-binding 0.2 micrometer filter. Pretreatment with antihistamines with or without antipyretics is recommended 30 to 60 minutes prior to infusion.

Patients <25 kg: Infuse 100 mL solution at 3 mL/hour for the first 15 minutes. If well-tolerated, increase to 6 mL/hour for the next 15 minutes. If well-tolerated, increase rate every 15 minutes in 6 mL/hour increments; maximum infusion rate: 36 mL/hour. The total volume of the infusion should be delivered over ≥3.5 hours.

Patients ≥25 kg: Infuse 250 mL solution at 6 ml/hour for the first 15 minutes. If well-tolerated, increase to 12 mL/hour for the next 15 minutes. If well-tolerated, increase rate every 15 minutes in 12 mL/hour increments; maximum infusion rate: 72 mL/hour. The total volume of the infusion should be delivered over ≥4.5 hours.

The infusion can be slowed, temporarily stopped, or discontinued if a hypersensitivity reaction occurs. Discontinue immediately if severe reaction occurs. Do not infuse with other products in the infusion tubing. Administration should be completed within 48 hours from time of dilution.

Prior to use, store intact vials under refrigeration at 2°C to 8°C (36°F to 46°F); do not freeze or shake. Protect from light. Following dilution in NS, use immediately. If unable to use immediately, may store for up to 24 hours under refrigeration followed by up to 24 hours at 23°C to 27°C (73°F to 81°F) during administration.

• 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 headache or loss of strength and energy. Have patient report immediately to prescriber signs of infusion reaction (cough, skin redness, tightness in throat, flushing, blue/gray skin discoloration, severe dizziness, passing out, shortness of breath, angina, vomiting, or severe abdominal pain), swelling of arms or legs, cough, back pain, difficulty moving, or urinary or fecal incontinence (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 health care 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.

Data not available

Animal studies have failed to reveal evidence of embryofetal toxicity. There are no controlled data in human pregnancy. Pregnancy can adversely affect the health of patients with mucopolysaccharidosis type IVA (MPS IVA) and lead to adverse pregnancy outcomes. A Morquio A Registry collects data on pregnant women with MPS IVA treated with this drug. For additional information and enrollment: MARS@bmrn.com US FDA pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

This drug should be used during pregnancy only if the benefit outweighs the risk to the fetus. US FDA pregnancy category: C