laronidase

la-RON-i-dase

Therapeutic Classification: replacement enzyme

Pharmacologic Classification: enzymes

REMS

Mucopolysaccharidosis 1 (MPS 1; specifically Hurler and Hurler-Scheie form or Scheie form) with moderate to severe symptoms.

Replaces the naturally occurring enzyme α-L-iduronidase, which is deficient in MPS 1. Without replacement, the glucosaminoglycans dermatan and heparan accumulate in tissues.

Therapeutic effects:

Decreased cellular, tissue, and organ damage due to mucopolysaccharide accumulation resulting in improved pulmonary function and walking capacity.

Absorption: IV administration results in complete bioavailability.

Distribution: Unknown.

Metabolism/Excretion: Unknown.

Half-Life: 1.5–3.6 hr.

ROUTE	ONSET	PEAK	DURATION
IV	unknown	unknown	1 wk

Contraindicated in:

None.

Use Cautiously in:

OB: Safety not established in pregnancy;
Lactation: Safety not established in breastfeeding.

CV: edema

Derm: rash

Local: injection site reactions

Neuro: fatigue

Resp: respiratory tract infections

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS), infusion-related reactions

Drug-drug:

None reported.

IV (Adults and Children ): 0.58 mg/kg (actual body weight) once weekly.

Solution for injection: 0.58 mg/mL

Assess vital signs every 15 min during the first hr of the infusion and frequently during remainder of infusion. Cardiopulmonary resuscitation equipment should be readily available during laronidase administration.
Monitor for signs of hypersensitivity reactions including anaphylaxis (dyspnea, rash, urticaria) and infusion-related reactions (pyrexia, hypertension, flushing) during and for up to 3 hr following infusion.If mild to moderate reactions occur,consider temporarily holding the infusion for 15–30 min or slowing the infusion rate by 25%–50% and initiating appropriate medical treatment. If symptoms subside after holding or slowing the infusion,resume infusion at a 25% to 50% reduced rate or complete infusion at the reduced rate as tolerated.If symptoms persist despite holding or slowing infusion, stop the infusion and monitor the patient. Consider reinitiating the infusion within 7–14 days. See the incremental rate steps table in the FDA label. With the next infusion, ↑ the infusion rate by increments of 25% as tolerated until the recommended infusion rate is reached. If severe hypersensitivity reactions occur, immediately discontinue laronidase and initiate appropriate medical treatment. Use caution if epinephrine is considered in treatment, as patients with MPS 1 have an increased prevalence of cardiovascular disease. Desensitization measures may be initiated after severe hypersensitivity reactions when considering risks and benefits of treatment with laronidase.

Premedicate with antipyretics and antihistamines 60 min prior to infusion to prevent hypersensitivity reactions.

IV Administration:

Intermittent Infusion: Diluent: Dilute concentrated solution with 0.1% albumin and 0.9% NaCl using PVC containers. Determine number of vials needed based on patient weight and round to nearest whole vial. Remove required number of vials from refrigerator and allow to reach room temperature; do not heat or microwave vials. Solution in vials should be slightly opalescent and colorless to pale yellow and may contain a few translucent particles; do not use if solution is discolored or contains particulate matter. Refrigerate; do not freeze. If the diluted laronidase solution is not used immediately, refrigerate for up to 36 hr. Infuse within 8 hr of removal from the refrigerator, inclusive of the total infusion time. Do not use after expiration.
- Determine total volume of infusion based on weight. Final volume should be 50 mL if patient weighs ≥2–4 kg, 100 mL if patient weighs ≥4–<20 kg, and 250 mL if patient weighs ≥20 kg.
- To prepare infusion, remove and discard amount of 0.9% NaCl from infusion bag equal to amount of laronidase to be added. Gently rotate infusion bag to ensure distribution of laronidase; do not shake.
Rate: Administer with a low-protein-binding infusion set equipped with an in-line, low-protein-binding 0.2 micrometer filter over 3–4 hr. Initial infusion rate of 10 mcg/kg/hr can be increased every 15 min during first hr, as tolerated, until a maximum rate of 200 mcg/kg/hr is reached; then maintain maximum infusion rate for remainder of infusion (2–3 hr).
Y-Site Incompatibility: Do not mix with other medications.
Additive Incompatibility: Do not mix or administer with other medications.

Explain MPS 1 registry to patient and encourage participation. Purpose is to better understand the variability and progression of MPS 1 disease and to continue to monitor and evaluate treatments. Advise patients that participation may involve long-term follow-up. Information regarding the registry program can be found at https://www.mps1disease.com/patients/mpsi-registry.
Advise patient of risk of hypersensitivity reactions including anaphylaxis and infusion-related reactions. Caution patient to inform health care professional immediately if side effects occur.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Encourage pregnant patients to enroll in the Pregnancy Exposure Registry by visiting www.registrynxt.com or call 1-800-745-4447 ext. 15500.

Improvement in pulmonary function and walking capacity. Full benefits may not be evident for several mo to several years.

Aldurazyme

NDC Code

58468- Genzyme Corporation
- 58468-0070- ALDURAZYME
  - 58468-0070-1- 5 mL in 1 VIAL, GLASS (58468-0070-1)

68135- BioMarin Pharmaceutical Inc.
- 68135-000-
  - 68135-000-99- 20000 mL in 1 BAG (68135-000-99)

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