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ALDURAZYME is a brand name for Laronidase, supplied as a solution. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: AND CLINICAL USE ............................................................................. 3 CONTRAINDICATIONS .................................................................................................. 4 WARNINGS AND PRECAUTIONS…
Verbatim from this product's HC label. Tap a section to expand.
Dosing Considerations ▪ Aldurazyme® (laronidase for injection) treatment should be supervised by a physician experienced in the management of patients with MPS I or other inherited metabolic diseases. ▪ Administration of Aldurazyme® should be carried out in an appropriate clinical setting where resuscitation equipment to manage medical emergencies is readily available.
▪ The safety and efficacy of Aldurazyme® in patients older than 65 years have not been established and no dosage regimen can be recommended in these patients. ▪ The safety and efficacy of Aldurazyme® in patients with renal or hepatic insufficiency have not been evaluated and no dosage regimen can be recommended in these patients.
58 mg/kg body weight administered once weekly as an intravenous infusion. Pretreatment with antipyretics and/or antihistamines is recommended 60 minutes prior to the start of the infusion (see WARNINGS AND PRECAUTIONS: General). The initial infusion rate of 10 μg/kg/hr may be incrementally increased every 15 minutes during the first hour, as tolerated, until a maximum infusion rate of 200 μg/kg/hr is reached.
The maximum rate is then maintained for the remainder of the infusion (2-3 hours). The total volume of the infusion is determined by the patient’s body weight and should be delivered over approximately 3 to 4 hours. Patients with a body weight of 20 kg or less should receive a total volume of 100 mL.
Patients with a body weight of greater than 20 kg should receive a total volume of 250 mL. The following tables provide infusion regimens and volumetric pump settings designed to administer the total volume over the recommended infusion time: For Patients weighing 20 kg or Less Total Volume of Aldurazyme® Infusion = 100 mL 2 mL/hr x 15 minutes Obtain vital signs, if stable then increase the rate to … 4 mL/hr x 15 minutes Obtain vital signs, if stable then increase the rate to … 8 mL/hr x 15 minutes Obtain vital signs, if stable then increase the rate to … 16 mL/hr x 15 minutes Obtain vital signs, if stable then increase the rate to … 32 mL/hr x ~ 3 hours For the remainder of the infusion Aldurazyme® (laronidase for injection) Product Monograph Page 22 of 41 For Patients weighing Greater than 20 kg Total Volume of Aldurazyme® Infusion = 250 mL 5 mL/hr x 15 minutes Obtain vital signs, if stable then increase the rate to … 10 mL/hr x 15 minutes Obtain vital signs, if stable then increase the rate to … 20 mL/hr x 15 minutes Obtain vital signs, if stable then increase the rate to … 40 mL/hr x 15 minutes Obtain vital signs, if stable then increase the rate to … 80 mL/hr x ~ 3 hours For the remainder of the infusion Administration Instructions for Use (With Aseptic Techniques and Sterile Preparation) 1.
Adverse Drug Reaction Overview The most serious adverse reactions reported with Aldurazyme® (laronidase for injection) during clinical trials and the post-marketing period were anaphylactic and allergic reactions (see WARNINGS AND PRECAUTIONS: General, and ADVERSE REACTIONS: Infusion-Related Reactions and Immunogenicity).
During clinical studies, the most common adverse reactions were infusion-related reactions (IARs). Among each of the clinical studies the most common adverse reactions associated with Aldurazyme® treatment in the clinical studies were upper respiratory tract infection, rash, and injection site reaction (placebo-controlled study ALID-003-99), arthralgia and rash (open-label extension study ALID-006-01) and pyrexia and chills (open-label study ALID-014-02).
The most common adverse reactions requiring intervention were infusion-related reactions. The frequency of infusion-related reactions decreased over time with continued use of Aldurazyme®, and the majority of reactions were classified as being mild to moderate in severity.
Most infusion-related reactions requiring intervention were ameliorated with slowing of the infusion rate, temporarily stopping the infusion, and/or administering additional antipyretics and/or antihistamines. One patient experienced 2 severe IARs (anaphylaxis-induced airway obstruction that required emergent tracheotomy) during the Week 62 infusion despite negative skin testing, and withdrew from the study.
Among patients who received Aldurazyme in the placebo controlled study and continued in the extension study, nearly all of the IARs (414 of the 458 IARs, 90%) were reported in a single patient, beginning at extension study Week 13.
Clinical Trial Adverse Drug Reactions Because clinical trials are conducted under very specific conditions the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.
Patients who are severely hypersensitive to Aldurazyme® (laronidase for injection) or to any ingredient in the formulation or component of the container (see WARNINGS AND PRECAUTIONS: General). For a complete listing of the ingredients in the formulation and components of the container, refer to the table in the SUMMARY PRODUCT INFORMATION section of the product monograph.
WARNINGS AND PRECAUTIONS LIFE-THREATENING ANAPHYLACTIC REACTIONS HAVE BEEN OBSERVED IN SOME PATIENTS DURING ALDURAZYME® (LARONIDASE FOR INJECTION) INFUSIONS. THEREFORE, APPROPRIATE MEDICAL SUPPORT SHOULD BE IMMEDIATELY AVAILABLE DURING ALDURAZYME ADMINISTRATION AND POST-INFUSION.
PATIENTS WITH COMPROMISED RESPIRATORY FUNCTION OR ACUTE RESPIRATORY DISEASE MAY BE AT RISK OF SERIOUS ACUTE EXACERBATION OF THEIR RESPIRATORY COMPROMISE DUE TO INFUSION REACTIONS, AND MAY REQUIRE WITHHOLDING ALDURAZYME, AND/OR ADDITIONAL TREATMENT AND MONITORING (see ANAPHYLAXIS AND ALLERGIC REACTIONS).
General Anaphylaxis and Allergic Reactions Life-threatening anaphylactic reactions have been observed in some patients during or up to 3 hours after Aldurazyme® infusions. Reactions have included: respiratory failure, respiratory distress, stridor, tachypnea, bronchospasm, airway obstruction, hypoxia, hypotension, bradycardia, and urticaria.
Appropriate medical support should be immediately available when Aldurazyme is administered. If anaphylactic or other severe allergic reactions occur, immediately discontinue the infusion and initiate appropriate treatment. Interventions have included; resuscitation, mechanical ventilatory support, emergency tracheotomy, hospitalization, and treatment with inhaled beta-adrenergic agonists, epinephrine, and intravenous corticosteroids.
Severe reactions have been observed up to 62 weeks after initiation of therapy. Patients with compromised respiratory function or acute respiratory disease may be at risk of serious acute exacerbation of their respiratory disease and symptoms due to infusion reactions, and may require withholding Aldurazyme, and/or additional treatment and monitoring (see BLACK BOX, GENERAL WARNINGS AND PRECAUTIONS, and ADVERSE REACTIONS).
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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58 mg/kg: Patient's weight (kg) x 1 mL/kg of Aldurazyme® = Total # mL of Aldurazyme® Total # mL of Aldurazyme® 5 mL per Vial = Total # of Vials Round up to the nearest whole vial. Remove the required number of vials from the refrigerator to allow them to reach room temperature.
Do not heat or microwave the vials. 2. Before withdrawing the Aldurazyme® from the vial, visually inspect each vial for particulate matter and discoloration. The Aldurazyme® 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 if there is particulate matter in the solution. 3. Determine the total volume of the infusion to be used based on the patient's body weight. 9% Sodium Chloride Injection, USP.
4. 9% Sodium Chloride Injection, USP from the infusion bag, equal to the volume of Aldurazyme® concentrate to be added. 5. Slowly withdraw the calculated volume of Aldurazyme® from the appropriate number of vials using caution to avoid excessive agitation.
Do not use a filter needle, as this may cause agitation. Agitation may denature Aldurazyme®, rendering it biologically inactive. 6. 9% Sodium Chloride Injection, USP using care to avoid agitation of the solutions. Do not use a filter needle.
Aldurazyme® (laronidase for injection) Product Monograph Page 23 of 41 7. Gently rotate the infusion bag to ensure proper distribution of Aldurazyme®. Do not shake the solution. Aldurazyme® does not contain any preservatives; therefore, after dilution with saline in the infusion bags, any unused product or waste material should be discarded and disposed of in accordance with local requirements.
Aldurazyme® must not be mixed with other medicinal products in the same infusion. The compatibility of Aldurazyme® in solution with other products has not been evaluated. Storage and Stability Store Aldurazyme® (laronidase for injection) under refrigeration at 2 to 8ºC (36 to 46ºF).
DO NOT FREEZE OR SHAKE. DO NOT USE Aldurazyme® after the expiration date on the vial. This product contains no preservatives. It is recommended that once Aldurazyme® is diluted, the infusion should start immediately (within 3 hours) as there is no preservative in either Aldurazyme® or in the infusion bag.
Although not recommended, physicochemical stability studies have shown that the diluted solution may be stored at 2 to 8ºC for up to 36 hours if aseptic technique is used throughout the procedure. Special Handling Instructions Do not use the vial more than one time.
2 micrometer (μm) filter. There is no information on the compatibility of diluted Aldurazyme® with glass containers. OVERDOSAGE […]
Adverse drug reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates. The following safety information is based on 3 clinical studies: a placebo-controlled study (ALID-003-99), open-label extension study (ALID-006-01) and an open-label study of patients under 5 years (ALID-014-02).
58 mg/kg of Aldurazyme® for 26 weeks in a placebo-controlled study (ALID-003-99) in 45 patients with MPS I (N=22 Aldurazyme®, and N=23 placebo). Table 2 is the subset of the pediatric patients (6 years to 18 years of age) in ALID-003-99 (Table 1).
The population in the placebo-controlled study (ALID-003-99) was evenly distributed for gender (N=23 females and 22 males) and ranged in age from 6 to 43 years. Of the 45 patients in the placebo-controlled study, 1 was clinically assessed as having the Hurler form, 37 Hurler-Scheie, and 7 Scheie.
Reported adverse reactions have been classified using WHOART terminology.
Table 1:
Summary of Adverse Drug Reactions Considered Possibly, Probably or Definitely Related to Treatment (≥ 5% of Patients in Either Group) that Occurred in the Total Population in the Placebo-Controlled Study ALID-003-99 WHOART Body System WHOART Preferred Term Treatment Group Placebo (N=23) Aldurazyme (N=22) Any AE 16 (70) 12 (55) Body as a Whole- General Disorders Fever 3 (13) 1 (5) Back Pain 1 (4) 2 (9) Temperature Changed Sensation 1 (4) 1 (5) Centr & Periph Nervous System Disorders Headache 6(26) 2(9) Gait abnormal 2 (9) 0 (0) Hyperreflexia 0 (0) 1 (5) Migraine 0 (0) 1 (5) Paraesthesia 0 (0) 1 (5) Skin and Appendages Disorders Rash 2 (9) 3 (14) Alopecia 1 (4) 1 (5) Sweating increased 1 (4) 1 (5) Pruritus 0 (0) 1 (5) Vascular (extracardiac) Disorders Flushing 4 (17) 5 (23) Gastro-intestinal system disorders Abdominal pain 1 (4) 1 (5) Diarrhoea 2 (9) 0 (0) Vomiting 1 (4) 1 (5) Tooth discolouration 0 (0) 1 (5) Musculo-skeletal system Arthropathy 4 (17) 2 (9) Aldurazyme® (laronidase for injection) Product Monograph Page 9 of 41 WHOART Body System WHOART Preferred Term Treatment Group Placebo (N=23) Aldurazyme (N=22) disorders Arthralgia 1 (4) 1 (5) Liver and biliary system disorders SGOT Increased 1 (4) 1 (5) SGPT Increased 1 (4) 1(5) Bilirubinaemia 0 (0) 1 (5) Cardiovascular disorders, general Hypotension 0 (0) 1 (5) Respiratory system disorders Coughing 0 (0) 1 (5) Heart rate and rhythm disorders Tachycardia 0 (0) 1 (5) Urinary system disorders Face Oedema 0 (0) 1 (5) White cell and res disorders Lymphadenopathy cervical 0(0) 1 (5) Aldurazyme® (laronidase for injection) Product Monograph Page 10 of 41 Table 2: Summary of Adverse Drug Reactions Considered Possibly, Probably or Definitely Related to Treatment (≥ 5% of Patients in Either Group) that Occurred in the Pediatric Population in Population in the Placebo-Controlled Study ALID-003-99 (Subset of the total population as noted in Table 1) WHOART Body System WHOART Preferred Term Treatment Group Placebo (N=18) Aldurazyme (N=15) Any AE 12 (67) 9 (60) Vascular (extracardiac) Disorders Flushing 4 (22) 5 (33) Centr & Periph Nervous System Disorders Headache 3 (17) 2(13) Gait abnormal 2 (11) 0 (0) Hyperreflexia 0 (0) 1 (7) Migraine 0 (0) 1 (7) Paraesthesia 0 (0) 1 (7) Skin and Appendages Disorders Rash 2 (11) 2 (13) Alopecia 1 (6) 1 (7) Sweating increased 1 (6) 1 (7) Body as a Whole- General Disorders Back Pain 1 (6) 2 (13) Temperature Changed Sensation 1 (6) 1 (7) Fever 1 (6) 0 (0) Rigors 1 (6) 0 (0) Liver and biliary system disorders SGTO Increased 1 (6) 1 (7) SGPT Increased 1 (6) 1(7) Bilirubinaemia 0 (0) 1 (7) Hepatic function abnormal 1 (6) 0 (0) Hepatomegaly 1 (6) 0 (0) Musculo-skeletal system disorders Arthropathy 3 (17) 2 (13) Arthralgia 1 (6) 0 (0) Gastro-intestinal system disorders Vomiting 1 (6) 1 (7) Diarrhoea 1 (6) 0 (0) Tooth discolouration 0 (0) 1 (7) Cardiovascular disorders, general […]
In clinical trials and post-marketing safety experience with Aldurazyme®, approximately 1% of patients experienced severe or serious allergic reactions. In patients with MPS I, pre-existing upper airway obstruction may have contributed to the severity of some reactions.
Due to the Aldurazyme® (laronidase for injection) Product Monograph Page 5 of 41 potential for severe allergic reactions, appropriate medical support should be readily available when Aldurazyme® is administered. Because of the potential for severe allergic reactions and recurrent reactions, some patients who experience initial severe reactions may require prolonged observation.
Patients with an acute illness at the time of Aldurazyme® infusion may be at greater risk for infusion-related reactions. Careful consideration should be given to the patient’s clinical status prior to administration of Aldurazyme®.
Patients should receive antipyretics and/or antihistamines prior to infusion (see ADVERSE REACTIONS). If anaphylactic or other severe allergic reactions occur, immediately discontinue the infusion of Aldurazyme® and initiate appropriate treatment.
Caution should be exercised if epinephrine is being considered for use in patients with MPS I due to the increased prevalence of coronary artery disease in these patients. If an infusion reaction occurs, regardless of pretreatment, decreasing the infusion rate, temporarily stopping the infusion, and/or administering corticosteroids, additional antipyretics and/or antihistamines may ameliorate the symptoms (see ADVERSE REACTIONS).
The risks and benefits of re-administering Aldurazyme® following an anaphylactic or severe allergic reaction should be considered. Extreme care should be exercised, with appropriate resuscitation measures available, if the decision is made to re-administer the product.
Carcinogenesis and Mutagenesis Studies to assess the carcinogenic and mutagenic potential of Aldurazyme® have not been conducted. Hepatic The safety and efficacy of Aldurazyme® in patients with hepatic insufficiency have not been evaluated and no dosage regimen can be recommended in these patients.
Immune Patients treated with Aldurazyme® may develop infusion-related allergic reactions (see GENERAL WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS). Renal The safety and efficacy of Aldurazyme® in patients with renal insufficiency have not been evaluated and no dosage regimen can be recommended in these patients.
Aldurazyme® (laronidase for injection) Product Monograph Page 6 of 41 Special Populations All patients should be informed that a registry for MPS I patients has been established and should be encouraged to participate in order to better understand and continue to monitor and evaluate MPS I disease and treatments.
The MPS I Registry allows for the collection of data to further understand the long-term effectiveness and safety profile of Aldurazyme® treatment in this patient population. This should apply to those special populations listed below treated with Aldurazyme® (see PART III, CONSUMER INFORMATION - MPS I Registry).
com or by calling (800) 745-4447.
Pregnant Women:
There are no adequate and well-controlled studies in pregnant women. 2 times the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to Aldurazyme®. However, because animal reproduction studies are not always predictive of human response, Aldurazyme® should be used during pregnancy only if clearly needed.
(See TOXICOLOGY, Reproductive Toxicity) Nursing Women: It is not known whether the drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised […]