Dosing & Uses
Dosage Forms & Strengths
injectable solution
- 2.9mg/5mL
Mucopolysaccharidosis I
0.58 mg/kg IV (3-4 hours infusion) qWeek; may administer total volume 100 mL if body weight < 20 kg or 250 mL if body weight >20 kg
Initial infusion rate 10 mcg/kg/hr; may increase q15min during 1st hour, as tolerated, to maximum 200 mcg/kg/hr
See infusion rate in Administration section
Dosage Forms & Strengths
injectable solution
- 2.9mg/5mL
Mucopolysaccharidosis I
<5 years
- Safety & efficacy not established
≥5 years
- <20 kg: 0.58 mg/kg IV (3-4 hr infusion) qWeek; total volume 100 mL
- ≥20 kg: As in adults; 0.58 mg/kg IV (3-4 hr infusion) qWeek; total volume 250 mL
- Initial infusion rate 10 mcg/kg/hr; may increase q15min during 1st hr, as tolerated, to maximum 200 mcg/kg/hr
- See infusion rate in Administration section
Adverse Effects
>10%
Development of anti-laronidase antibodies (91% in one study) - clinical significance unknown
Rash (36%)
Injection site reaction (18%)
Poor venous access (14%)
Hyperreflexia (14%)
Paresthesia (14%)
Chills (20%; children 6 months to 5 years)
Otitis media (20%; children 6 months to 5 years)
Upper respiratory tract infection (32%)
Infusion reactions (49%)
- Rash (13%)
- Flushing (11%)
- Pyrexia (11%)
- Headache (9%)
- Abdominal pain or discomfort (9%)
- Nausea (7%)
- Diarrhea (7%)
- Feeling hot or cold (7%)
- Vomiting (4%)
- Pruritus (4%)
- Arthralgia (4%)
- Urticaria (4%)
1-10%
Thrombocytopenia (9%)
Corneal opacity (9%)
Chest pain (9%)
Face edema (9%)
Gravitational edema (9%)
Injection site pain (9%)
Hyperbilirubinemia (9%)
Hypotension (9%)
< 1%
Anaphylactic shock
Laryngeal edema
Fatigue
Peripheral edema
Erythema
Cyanosis
Angioedema
Warnings
Black Box Warning
Anaphylactoid reactions, which may be life threatening, have been observed in some patients during infusions
Patients with compromised respiratory function or acute respiratory distress may be at risk of serious acute exacerbation of their respiratory compromise due to infusion reactions and require additional monitoring
Contraindications
Hypersensitivity
Cautions
Consider registration in the MPS I Registry, www.MPSIregistry.com or 1-800-745-4447
Consider delaying treatment in patients with acute febrile/respiratory illness; may increase risk of infusion related reactions; premedication with antihistamines and antipyretics recommended; decrease infusion rate temporarily; manage reactions by administering additional antipyretics and antihistamines
Use caution in patients with fluid overloads or in conditions where fluid restriction is indicated; exacerbation of such conditions may occur during infusions
Not indicated for CNS manifestations of the disorder
Use caution in patients with sleep apnea; apnea treatment options should be readily available during infusion or with use of sedating antihistamines including supplemental oxygen and CPAP
Pregnancy & Lactation
Pregnancy
An MPS I Registry has been established and pregnant women with MPS I should be encouraged to enroll; for more information, visit www.registrynxt.com or call 1-800-745-4447 ext. 15500
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
- No evidence of fetal harm observed in rats when laronidase was administered during organogenesis at doses up to 6.2 times the recommended human dose
Clinical considerations
- Pregnancy can exacerbate preexisting clinical manifestations of MPS and lead to adverse pregnancy outcomes for both mother and fetus
Lactation
Data are not available on the presence of laronidase in human milk or the effects on milk production
No adverse effects have been reported in breastfed infants in a few postmarketing cases of laronidase use in lactating women
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.Pharmacology
Mechanism of Action
Recombinant alpha-L-iduronidase, an enzyme (deficient in mucopolysaccharidosis I) involved in the breakdown of glycosaminoglycans within lysosomes; walking capacity and pulmonary function improves in patients treated with this recombinant product
Absorption
Peak plasma concentration: 1.2-1.7 mcg/mL
AUC: 4.5-6.9 mcg•hr/mL
Onset: 3-6 wk (initial effect); 26 wk (max effect)
Distribution
Vd: 0.24-0.6 L/kg
Elimination
Half-life: 1.5-3.6 hr
Plasma clearance: 1.7-2.7 mL/min/kg
Administration
IV Incompatibilities
Do not mix with other drugs in same infusion solution
IV Preparation
Dilute commercially available injection concentrate in NS containing 0.1% human albumin prior to administration
Pretreatment with antipyretics &/or antihistamines is recommended 60 min before start of laronidase infusions
Prepare solutions using PVC containers
Vial calculation
- Appropriate number of laronidase vials should be diluted based on body weight and dose determined using the equations listed below
- Patient's weight (kg) x 1 mL/kg of laronidase = Total # mL of laronidase
- Total # mL/5 mL per vial = Total # of vials, rounded up to the nearest whole vial
Prepare infusion bag of NS containing human albumin 0.1% based on total infusion volume
Prior to addition of albumin to the infusion bag, remov & discard an amount of NS equal to volume of albumin
For a total infusion volume of 100 mL, add 2 or 0.4 mL of human albumin 5% or 25%; for a total infusion volume of 250 mL, add 5 or 1 mL of albumin 5% or 25%
Gently rotate to ensure proper distribution of albumin
Prior to addition of calculated volume of laronidase to infusion bag, remove & discard an equal volume of NS containing albumin 0.1%
Calculated volume of laronidase injection concentrate should be withdrawn slowly from appropriate number of vials & added slowly to infusion bag, followed by gentle rotation for even distribution; do not use filter needle since it may cause agitation & denature laronidase
IV Administration
Premedicate with antipyretics &/or antihistamines 1 hr before infusion
Infuse over 3-4 hr (see infusion rate schedule below)
Peds: <20 kg: give a total volume of 100 mL; >20 kg: give a total volume of 250 mL
Administer with PVC infusion set equipped with an inline, low-protein-binding filter with a pore diameter of 0.2 microns
Infusion rates for body Weight <20 kg
- 2 mL/h for 15 min (10 mcg/kg/hr); if vital signs stable increase rate to
- 4 mL/h for 15 min (20 mcg/kg/hr); if vital sign stable, increase rate to
- 8 mL/h for 15 min (50 mcg/kg/hr); if vital sign stable, increase rate to
- 16 mL/h for 15 min (100 mcg/kg/hr); if vital sign stable, increase rate to
- 32 mL/h for 3 hr (200 mcg/kg/hr); continue at this rate for the remainder of the infusion
Infusion rates for body weight >20 kg
- 5 mL/h for 15 min (10 mcg/kg/hr); if vital signs stable increase rate to
- 10 mL/h for 15 min (20 mcg/kg/hr); if vital sign stable, increase rate to
- 20 mL/h for 15 min (50 mcg/kg/hr); if vital sign stable, increase rate to
- 40 mL/h for 15 min (100 mcg/kg/hr); if vital sign stable, increase rate to
- 80 mL/h for 3 hr (200 mcg/kg/hr); continue at this rate for the remainder of the infusion
Storage
Store at 2-8°C
Protect from freezing
Do not shake
Images
Patient Handout
laronidase intravenous
LARONIDASE - INJECTION
(lar-ON-i-dase)
COMMON BRAND NAME(S): Aldurazyme
WARNING: Laronidase can rarely cause a very serious (sometimes fatal) allergic reaction. This reaction may occur during or up to 3 hours after the infusion. Get medical help right away if you notice any symptoms of a serious allergic reaction, including: itching/swelling (especially of the face/tongue/throat), trouble breathing, severe dizziness, fainting, or rash/hives. Your health care professional will monitor you closely for any signs of allergic reactions during your infusion and for some time after.Before you start your infusion, tell your doctor if you have a fever or an infection (such as cold or flu) or if you have a history of heart problems (such as heart failure), breathing problems, interrupted breathing during sleep (such as sleep apnea), or swelling. Your health care professional will monitor you closely to prevent these problems from getting worse, and may delay your infusion if necessary.
USES: Laronidase is used to treat a certain rare genetic problem (mucopolysaccharidosis-MPS I). It works by replacing a certain natural substance (lysosomal enzyme) that is missing in people with this genetic problem. This medication improves lung function and how far you can walk. Laronidase is not a cure and treatment must be continued for life.
HOW TO USE: Read the Patient Information Leaflet if available from your pharmacist before you start using laronidase and each time you get a refill. If you have any questions, ask your doctor or pharmacist.This medication is given by injection into a vein as directed by your doctor, usually every week. The injection is given by a health care professional, usually over 3 to 4 hours. The dosage is based on your medical condition, weight, and response to treatment.Infusion reactions may occur while you are receiving laronidase. Tell your doctor or nurse right away if any of these side effects occur: flushing, fever, headache, or abdominal pain. Your infusion may be slowed down or stopped depending on your symptoms. To prevent infusion reactions, your doctor may prescribe other medications 60 minutes before each infusion. Carefully follow your doctor's directions for all your medications. See also Warning section.Use this medication regularly to get the most benefit from it. To help you remember, it may help to mark your calendar with a reminder.Tell your doctor if your condition gets worse.
SIDE EFFECTS: See also How to Use section and Warning section.Cold symptoms (such as stuffy/runny nose, cough) may occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.
PRECAUTIONS: See Warning section.Before using laronidase, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history.Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.It is unknown if this medication passes into breast milk. Consult your doctor before breast-feeding.
DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.
OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.
NOTES: Lab and/or medical tests (such as lung function, urine tests, immunoglobulin levels) should be done before you start using this medication and while you are using it. Keep all medical and lab appointments. Consult your doctor for more details.
MISSED DOSE: It is important to get each dose of this medication as scheduled. If you miss a dose, ask your doctor or pharmacist right away for a new dosing schedule.
STORAGE: Not applicable. This medication is given in a hospital or clinic and will not be stored at home.
Information last revised February 2023. Copyright(c) 2023 First Databank, Inc.
IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.
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