Dosing and uses of Aldurazyme (laronidase)
Adult dosage forms and 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
Pediatric dosage forms and 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
Aldurazyme (laronidase) adverse (side) 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 and lactation
Pregnancy category: B
Lactation: Not known if distributed into breast milk, use caution
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 of Aldurazyme (laronidase)
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
