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Aldurazyme
Classes
Mucopolysaccharidosis (MPS) Agents
Administration
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
For intravenous (IV) infusion only; do not administer as an IV bolus injection.
DO not mix laronidase infusion with other medications; compatibility has not been evaluated.
Premedicate with antipyretics and/or antihistamines 1 hour prior to beginning each infusion.[49453]
Dilution
Use aseptic technique.
Determine the number of laronidase vials to be diluted based on patient's weight. Round up to the nearest whole vial. Allow vials to reach room temperature prior to dilution; do not heat or microwave vials.
Visually inspect each vial prior to dilution. The undiluted solution should be clear to slightly opalescent and colorless to pale yellow. A few translucent particles may be present. Do not use if the solution is discolored or contains opaque particulate matter.
Prepare laronidase infusions using only low-protein binding containers. There is no information on glass compatibility.
Dilute with 0.9% Sodium Chloride Injection to a total volume of 100 mL (patients weighing 20 kg or less) or 250 mL (patients weighing more than 20 kg). For patients with underlying cardiac or respiratory compromise and weighing up to 30 kg, a total volume of 100 mL may be utilized.
Prior to the addition of laronidase, remove and discard a volume equal to the volume of laronidase to be added to the bag. Using a needle without a filter, slowly withdraw the calculated volume of laronidase from the appropriate number of vials and add to 0.9% Sodium Chloride Injection; use caution to avoid excess agitation. After the addition of laronidase, gently rotate the infusion bag to ensure proper distribution; do not shake.
Storage: If immediate use is not possible once the infusion is prepared, the infusion bag may be stored under refrigeration at 2 to 8 degrees C (36 to 46 degrees F) for no longer than 36 hours. Discard any partially used vials of laronidase.[49453]
Intermittent IV Infusion
Administer laronidase using only low-protein binding containers and infusion sets. The infusion set should be equipped with an in-line, low-protein binding (0.2 micron) filter. There is no information on glass compatibility.
Administer the diluted IV infusion solution immediately via slow IV infusion over 3 to 4 hours.
The initial infusion rate of 10 mcg/kg/hour may be increased incrementally every 15 minutes over the first hour, as tolerated and if vital signs are stable, to a maximum rate of 200 mcg/kg/hour. The maximum rate is then maintained for the duration of the infusion. Pump infusion rates may be found in the laronidase package labeling.
After infusion, immediately dispose of any unused product due to lack of preservative.[49453]
Adverse Reactions
angioedema / Rapid / 9.0-9.0
corneal opacification / Delayed / 9.0-9.0
serious hypersensitivity reactions or anaphylaxis / Rapid / 1.0-1.0
laryngeal edema / Rapid / Incidence not known
bradycardia / Rapid / Incidence not known
bronchospasm / Rapid / Incidence not known
antibody formation / Delayed / 97.0-97.0
infusion-related reactions / Rapid / 32.0-49.0
hyperreflexia / Delayed / 14.0-14.0
sinus tachycardia / Rapid / 10.0-10.0
edema / Delayed / 9.0-9.0
chest pain (unspecified) / Early / 9.0-9.0
hypotension / Rapid / 9.0-9.0
thrombocytopenia / Delayed / 9.0-9.0
hyperbilirubinemia / Delayed / 9.0-9.0
wheezing / Rapid / 5.0
peripheral edema / Delayed / Incidence not known
tachypnea / Early / Incidence not known
dyspnea / Early / Incidence not known
hypoxia / Early / Incidence not known
infection / Delayed / 20.0-32.0
fever / Early / 11.0-30.0
flushing / Rapid / 11.0-23.0
chills / Rapid / 20.0-20.0
injection site reaction / Rapid / 9.0-18.0
paresthesias / Delayed / 14.0-14.0
abdominal pain / Early / 9.0-9.0
headache / Early / 9.0-9.0
nausea / Early / 7.0-7.0
diarrhea / Early / 7.0-7.0
arthralgia / Delayed / 4.0-4.0
vomiting / Early / 4.0-4.0
urticaria / Rapid / 4.0-4.0
pruritus / Rapid / 4.0
pallor / Early / 5.0
rash / Early / 5.0
tremor / Early / 5.0
fatigue / Early / Incidence not known
back pain / Delayed / Incidence not known
musculoskeletal pain / Early / Incidence not known
cough / Delayed / Incidence not known
hyperhidrosis / Delayed / Incidence not known
Common Brand Names
Aldurazyme
Dea Class
Rx
Description
Intravenous enzyme replacement therapy
Indicated for deficiency of alpha-L-iduronidase in mucopolysaccharidosis I (MPS I) in patients 6 months of age and older
Generates catabolism of glycosaminoglycans; improves lung function and endurance
Dosage And Indications
NOTE: Laronidase has been designated as an orphan drug for this indication by the FDA.
0.58 mg/kg/dose IV infused over 3 to 4 hours once weekly. The initial infusion rate is 10 mcg/kg/hour and may be increased incrementally every 15 minutes during the first hour of infusion to the maximum infusion rate of 200 mcg/kg/hour. Pretreatment with antipyretics and/or antihistamines is recommended 60 minutes prior to the start of each infusion. Laronidase has been administered once weekly for up to 182 weeks in clinical trials.[49453]
0.58 mg/kg/dose IV infused over 3 to 4 hours once weekly. The initial infusion rate is 10 mcg/kg/hour and may be increased incrementally every 15 minutes during the first hour of infusion to the maximum infusion rate of 200 mcg/kg/hour. Pretreatment with antipyretics and/or antihistamines is recommended 60 minutes prior to the start of each infusion. Laronidase has been administered once weekly for up to 182 weeks in clinical trials.[49453]
Dosing Considerations
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
Drug Interactions
There are no drug interactions associated with Laronidase products.
How Supplied
Aldurazyme Intravenous Sol: 2.9mg, 5mL
Maximum Dosage
0.58 mg/kg/dose IV once weekly.
Maximum dosage information is not available.
0.58 mg/kg/dose IV once weekly.
0.58 mg/kg/dose IV once weekly.
>= 6 months: 0.58 mg/kg/dose IV once weekly.
< 6 months: Safety and efficacy have not been established.
Safety and efficacy have not been established.
Mechanism Of Action
Mechanism of Action: Laronidase is an exogenous enzyme replacement for a-L-iduronidase and is used in mucopolysaccharidosis I (MPS 1), rare autosomal recessive storage disorders. MPS I disorders are caused by the deficiency of a-L-iduronidase, a lysosomal hydrolase required for catabolism of the glycosaminoglycans (GAG) substrates dermatan sulfate and heparan sulfate. Accumulation of these substrates lead to widespread cellular, tissue and organ dysfunction. Laronidase uptake into lysosomes is most likely mediated by the mannose-6-phosphate-terminated oligosaccharide chains of laronidase binding to specific mannose-6-phosphate receptors. Clinically, the patient may notice improvement in breathing and endurance as a result of enzyme replacement. The drug has been shown to biochemically reduce the excess carbohydrates that are stored in the organs of patients with MPS I; however, the clinical significance of this carbohydrate reduction at the biochemical level is not certain. Laronidase has not been evaluated to see if it improves the central nervous system manifestations of the disorder.
Pharmacokinetics
Laronidase is administered as an intravenous infusion. It is not known if laronidase will cross into the CNS or breast milk. In patients 6 years and older, the mean volume of distribution ranged from 0.24 to 0.6 L/kg, mean plasma clearance ranged from 1.7 to 2.7 mL/minute/kg, and the elimination half-life ranged from 1.5 to 3.6 hours. In patients 6 months to 5 years, the mean volume of distribution ranged from 0.12 to 0.56 L/kg, mean plasma clearance ranged from 2.2 to 7.7 mL/minute/kg, and the elimination half-life ranged from 0.3 to 1.9 hours.[49453]
The pharmacokinetics of laronidase were evaluated in a study including patients 6 years and older (n = 10 to 12) with MPS I who received a 4-hour infusion of 0.58 mg/kg once per week. Mean maximum plasma concentrations (Cmax) were evaluated at weeks 1, 12, and 26 and ranged from 1.2 to 1.7 mcg/mL. The mean AUC ranged from 4.5 to 6.9 mcg x hour/mL. The majority of patients receiving weekly infusions developed antibodies to laronidase by week 12 of therapy. Between weeks 1 to 12, increases in the plasma clearance of laronidase were observed in some patients and appeared to be proportional to the antibody titer. At week 26, plasma clearance of laronidase was comparable to that at week 1, in spite of the continued and, in some cases, increased titers of antibodies. In a separate study, the pharmacokinetics of laronidase were evaluated in patients 6 months to 5 years (n = 7 to 9) who received a 4-hour infusion of 0.58 mg/kg once per week. After the 26th weekly infusion, maximum plasma concentrations (Cmax) ranged from 0.6 to 1.6 mcg/mL. The mean AUC ranged from 1.3 to 4.4 mcg x hour/mL.[49453]
Pregnancy And Lactation
There are no adequate and well-controlled studies of laronidase use in human pregnancy, and its ability to cause fetal harm or affect reproductive capacity is unknown. Animal studies in rats at doses 6.2 times the human dose have not revealed evidence of impaired fertility or harm to the fetus; however, animal studies are not always predictive of human response. Use laronidase during pregnancy only if clearly needed. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to laronidase; information about the registry can be obtained at www.registrynxt.com or by calling 1-800-745-4447 (ext. 15500) or 1-800-633-1610.[49453]
Data are limited regarding the use of laronidase during breast-feeding, and its excretion in human milk is unknown. Use caution when administering laronidase to lactating women. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, health care providers are encouraged to report the adverse effect to the FDA. Nursing women with mucopolysaccharidosis I (MPS I) are encouraged to enroll in the MPS I registry by visiting www.registrynxt.com or by calling 1-800-745-4447 (ext. 15500).[49453]