elosulfase alfa (Rx)

>10%

Pyrexia (33%)

Vomiting (31%)

Headache (26%)

Nausea (24%)

Abdominal pain (21%)

Hypersensitivity, including anaphylaxis (18.7%)

Chills (10.3%)

Fatigue (10.3%)

1-10%

Anaphylaxis (7.7%)

Contraindications

None

Cautions

Anaphylaxis reported and may occur as early as 30 minutes from the start of infusion and up to 3 hr after completing the infusion (see Black Box Warnings)

Increased risk of acute respiratory complications; monitor patients with acute febrile or respiratory illness at the time of infusion (higher risk of life-threatening complications from hypersensitivity reaction)

Sleep apnea is common in patients with MPS IVA, evaluate airway patency before initiating treatment with elosulfase alfa

Pregnancy

There is a Morquio A Registry that collects data on pregnant women with MPS IVA who are treated with elosulfase alfa; contact MARS@bmrn.com or call 1-800-983-4587 for information and enrollment

Available data from published case reports and postmarketing experience in pregnant women are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes

Animal studies

• In animal reproduction studies, no effects on embryo-fetal development were observed in rats given daily administration of elosulfase alfa up to 33 times the human steady-state AUC at the recommended human weekly dose premating and through the period of organogenesis
• No effects on embryo-fetal development were observed in rabbits given daily administration of elosulfase alfa at doses up to 8 times the human steady-state AUC at the recommended weekly dose during organogenesis, which produced maternal toxicity
• A dose dependent increase in stillbirths was observed when elosulfase alfa was administered daily in rats during organogenesis through lactation at doses 5 times the human steady-state AUC at the recommended human weekly dose; an increase in pup mortality was observed at doses producing maternal toxicity

Clinical considerations

• Pregnancy can exacerbate preexisting clinical manifestations of MPS and lead to adverse outcomes for both mother and fetus

Lactation

Data are not available on the presence of elosulfase alfa in human milk or the effects on milk production

Elosulfase alfa is present in milk from treated rats; when a drug is present in animal milk, it is likely that the drug will be present in human milk

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

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

IV Compatibilities

Do not infuse with other products in the infusion tubing

Compatibility with other products has not been evaluated

IV Preparation

Determine the number of vials to be diluted based on the individual patient’s weight and the recommended dose of 2 mg/kg

The solution should be clear to slightly opalescent and colorless to pale yellow when diluted

Do not use if the solution is discolored or if there is particulate matter in the solution

Note that a diluted solution with slight flocculation (eg, thin translucent fibers) is acceptable for administration

Avoid agitation during preparation; gently rotate the bag to ensure proper distribution

Do NOT shake the solution

Dilute the calculated dose to a final volume of 100 mL or 250 mL using 0.9% NaCl

Final volume is based on the patient’s weight

• <25 kg: 100 mL
• ≥25 kg: 250 mL

IV Administration

Administer diluted solution IV using a low-protein binding infusion set equipped with a low-protein binding 0.2 micrometer in-line filter

The infusion rate may be slowed, temporarily stopped, or discontinued for that visit in the event of hypersensitivity reactions

Weight <25 kg

• Diluted volume totals 100 mL
• 3 mL/hr IV initially for the first 15 minutes, and if tolerated, increased to 6 mL/hr for the next 15 minutes
• If this rate is tolerated, then the rate may be increased every 15 minutes in 6 mL/hr increments, not to exceed 36 mL/hr
• The total volume of the infusion should be delivered over a minimum of 3.5 hr

Weight ≥25 kg

• Diluted volume totals 250 mL
• 6 mL/hr IV initially for the first 15 minutes, and if tolerated, increased to 12 mL/hr for the next 15 minutes
• If this rate is tolerated, then the rate may be increased every 15 minutes in 12 mL/hr increments, not to exceed 72 mL/hr
• The total volume of the infusion should be delivered over a minimum of 4.5 hr

Storage

Contains no preservatives; discard partially used vials

Do not freeze

Do not shake

Protect from light

Unopened vials

• Store refrigerated between 2-8°C [36-46°F]) in original carton and protect from light

Diluted solution

• If immediate use is not possible, store refrigerated for up to 24 hr at 2-8°C (36-46°F) followed by up to 24 hr at 23-27°C (73-81°F) during administration
• Administration should be completed within 48 hr from the time of dilution