Aldurazyme

Name: Aldurazyme

Laronidase Side Effects

Some people receiving a laronidase have had a reaction to the infusion (when the medicine is injected into the vein). Tell your caregiver right away if you have a headache, skin rash or itching, warmth or tingly feeling, pale skin, or trouble breathing when laronidase is injected.

Get emergency medical help if you have any of these signs of an allergic reaction: hives; wheezing, difficult breathing; slow heartbeats; feeling like you might pass out; swelling of your face, lips, tongue, or throat.

Tell your caregivers at once if you have a serious side effect such as:

  • chest pain;
  • easy bruising, unusual bleeding (nose, mouth, vagina, or rectum), purple or red pinpoint spots under your skin;
  • fever, chills, rapid heart rate; or
  • dangerously high blood pressure (severe headache, blurred vision, buzzing in your ears, anxiety, confusion, shortness of breath, uneven heartbeats, seizure).

Less serious side effects may include:

  • mild skin rash;
  • overactive reflexes;
  • numbness or tingling;
  • cold symptoms such as runny or stuffy nose, sneezing, sore throat; or
  • pain, redness, swelling, or other irritation where the medicine was injected.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What is laronidase?

Laronidase is used to treat some of the symptoms of a genetic condition called Hurler syndrome, also called mucopolysaccharidosis (MYOO-koe-pol-ee-SAK-a-rye-DOE-sis), or MPS I. Forms of MPS I include Hurler syndrome, Hurler-Scheie syndrome, and Scheie syndrome."

MPS I is a metabolic disorder in which the body lacks the enzyme needed to break down certain sugars and proteins. These substances can build up in the body, causing enlarged organs, abnormal bone structure, changes in facial features, breathing problems, heart problems, vision or hearing loss, and changes in mental or physical abilities.

Laronidase may improve breathing and walking ability in people with this condition. However, this medication is not a cure for MPS I.

Laronidase may also be used for purposes not listed in this medication guide.

What is the most important information I should know about laronidase?

You should not use laronidase if you are allergic to it.

Before you receive laronidase, tell your doctor if you have heart disease, kidney disease, lung disease, seizures, migraine headaches, or sleep apnea.

Tell your doctor if you have been sick with a fever, head cold, or chest cold. You may need to wait until you get better before receiving your dose of laronidase.

Some people receiving a laronidase have had a reaction to the infusion (when the medicine is injected into the vein). Tell your caregiver right away if you have a headache, skin rash or itching, warmth or tingly feeling, or trouble breathing when laronidase is injected.

Your doctor may also prescribe other medications to help prevent an allergic reaction to laronidase. Take all of your medications as directed.

What should I avoid while receiving laronidase?

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

Uses for Aldurazyme

Mucopolysaccharidosis I

Replacement therapy in patients with Hurler’s or Hurler-Scheie forms of mucopolysaccharidosis I (MPS I),2 3 as well as in patients with Scheie’s form of MPS I2 who have moderate to severe symptoms1 (designated an orphan drug by FDA for this use).4

Risks and benefits of laronidase therapy in mildly affected patients with Scheie’s syndrome not established.1

Commonly used brand name(s)

In the U.S.

  • Aldurazyme

Available Dosage Forms:

  • Solution

Therapeutic Class: Endocrine-Metabolic Agent

Pharmacologic Class: Enzyme

Aldurazyme Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur:

More common
  • Abdominal or stomach pain
  • accumulation of pus
  • back pain
  • black, tarry stools
  • bleeding gums
  • blood in urine or stools
  • blurred vision
  • chest pain
  • chest tightness
  • chills
  • clay-colored stools
  • confusion
  • dark urine
  • dizziness
  • drowsiness
  • facial swelling
  • faintness
  • fast, pounding, or irregular heartbeat or pulse
  • fever
  • flushing
  • headache
  • hives, infection, inflammation, itching, lumps, numbness, pain, rash, redness, scarring, soreness, stinging, swelling, tenderness, tingling, ulceration, or warmth at injection site
  • itching
  • lightheadedness when getting up from a lying or sitting position suddenly
  • loss of appetite
  • nausea or vomiting
  • pale skin
  • pinpoint red spots on skin
  • shortness of breath
  • skin rash
  • sweating
  • swollen, red, or tender area of infection
  • trouble breathing
  • unpleasant breath odor
  • unusual bleeding or bruising
  • unusual tiredness or weakness
  • vomiting of blood
  • yellow eyes or skin
Less common
  • Cough
  • difficulty breathing
  • itching skin
  • large, hive-like swelling on face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
  • noisy breathing
  • redness of skin
  • tightness in chest
  • wheezing

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common
  • Bleeding, blistering, burning, coldness, or discoloration of skin
  • blindness
  • body aches or pain
  • burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
  • decreased vision
  • diarrhea
  • difficulty in moving
  • ear congestion
  • feeling of pressure
  • loss of voice
  • muscle pain or stiffness
  • nasal congestion
  • overactive reflexes
  • pain in joints
  • runny nose
  • sneezing
  • sore throat
  • swelling of legs and feet
  • swelling or puffiness of face
  • varicose or spider veins

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

What are some side effects that I need to call my doctor about right away?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Chest pain or pressure or a fast heartbeat.
  • Shortness of breath.
  • Very bad dizziness or passing out.
  • Fever or chills.
  • A burning, numbness, or tingling feeling that is not normal.
  • Fast breathing.
  • Any unexplained bruising or bleeding.
  • Swelling.
  • Change in eyesight.
  • Redness or swelling where the shot is given.

Aldurazyme Description

Aldurazyme (laronidase) is a polymorphic variant of the human enzyme α‑l‑iduronidase that is produced by recombinant DNA technology in a Chinese hamster ovary cell line.  α-l-iduronidase (glycosaminoglycan α-l-iduronohydrolase, EC 3.2.1.76) is a lysosomal hydrolase that catalyzes the hydrolysis of terminal α-l-iduronic acid residues of dermatan sulfate and heparan sulfate.

Laronidase is a glycoprotein with a molecular weight of approximately 83 kD. The predicted amino acid sequence of the recombinant form, as well as the nucleotide sequence that encodes it, are identical to a polymorphic form of human α-L-iduronidase. The recombinant protein is comprised of 628 amino acids after cleavage of the N-terminus and contains 6 N-linked oligosaccharide modification sites. Two oligosaccharide chains terminate in mannose-6-phosphate sugars. Aldurazyme has a specific activity of approximately 172 U/mg.

Aldurazyme, for IV infusion, is supplied as a sterile, nonpyrogenic, colorless to pale yellow, clear to slightly opalescent solution that must be diluted prior to administration in 0.9% Sodium Chloride Injection, USP. The solution in each vial contains a nominal laronidase concentration of 0.58 mg/mL and a pH of approximately 5.5. The extractable volume of 5.0 mL from each vial provides 2.9 mg laronidase, 43.9 mg sodium chloride, 63.5 mg sodium phosphate monobasic monohydrate, 10.7 mg sodium phosphate dibasic heptahydrate, and 0.05 mg polysorbate 80. Aldurazyme does not contain preservatives; vials are for single use only.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Studies to assess the mutagenic and carcinogenic potential of laronidase have not been conducted.

Laronidase at IV doses up to 3.6 mg/kg (6.2 times the human dose) was found to have no effect on the fertility and reproductive performance of male and female rats.

Package label

NDC 58468-0070-1

Aldurazyme®
(LARONIDASE)

Aldurazyme carton

2.9 mg/5 mL
(0.58 mg/mL)

Concentrated Solution For
Intravenous Infusion Only

Rx Only

genzyme

Package contains
one vial of Aldurazyme®

For single use only

Must be diluted prior to use.

Store refrigerated at 2-8°C (36-46°F)
Do not freeze or shake

Contains No Preservatives

See package insert for
dosage and administration.

No U.S. Standard of Potency

Manufactured by:
BioMarin Pharmaceutical Inc.
Novato, CA 94949, USA
U.S. License No. 1649

Distributed by:
Genzyme Corporation
Cambridge, MA 02142, USA

591808

genzyme

NDC 58468-0070-1

Aldurazyme®
(LARONIDASE)

Each vial contains
Laronidase 2.9 mg,
Sodium Chloride 43.9 mg,
Sodium Phosphate Monobasic Monohydrate 63.5 mg,
Sodium Phosphate Dibasic Heptahydrate 10.7 mg,
Polysorbate 80, 0.05 mg, in 5mL

Concentrated Solution For
Intravenous Infusion Only

Rx Only

genzyme

LOT
 
EXP
 
7070 (10/12)

For single use only

See package insert for
dosage and administration

Store at 2-8°C (36-46°F)

Manufactured by:
BioMarin Pharmaceutical Inc.
Novato, CA 94949
U.S. License No. 1649

Distributed by:
Genzyme Corporation
Cambridge, MA 02142

genzyme

NDC 58468-0070-1

Aldurazyme®
(LARONIDASE)

2.9 mg/5 mL (0.58 mg/mL)
Concentrated Solution For
Intravenous Infusion Only

Must be diluted prior to use.

Rx Only

LOT: 

EXP: 

5648(02/09)

Aldurazyme 
laronidase injection, solution, concentrate
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:58468-0070
Route of Administration INTRAVENOUS DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
LARONIDASE (LARONIDASE) LARONIDASE 2.9 mg  in 5 mL
Inactive Ingredients
Ingredient Name Strength
SODIUM CHLORIDE 43.9 mg  in 5 mL
SODIUM PHOSPHATE, MONOBASIC, MONOHYDRATE 63.5 mg  in 5 mL
SODIUM PHOSPHATE, DIBASIC, HEPTAHYDRATE 10.7 mg  in 5 mL
POLYSORBATE 80 0.05 mg  in 5 mL
WATER  
Packaging
# Item Code Package Description
1 NDC:58468-0070-1 5 mL in 1 VIAL, GLASS
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
BLA BLA125058 04/30/2003
Labeler - Genzyme Corporation (025322157)
Establishment
Name Address ID/FEI Operations
BioMarin Pharmaceutical Inc. 010004135 ANALYSIS(58468-0070)
Establishment
Name Address ID/FEI Operations
Genzyme Corporation 050424395 LABEL(58468-0070), PACK(58468-0070)
Establishment
Name Address ID/FEI Operations
Jubilant HollisterStier LLC 069263643 ANALYSIS(58468-0070), MANUFACTURE(58468-0070)
Establishment
Name Address ID/FEI Operations
Vetter Pharma Fertigung GmbH & Co. KG 344217323 ANALYSIS(58468-0070), MANUFACTURE(58468-0070)
Establishment
Name Address ID/FEI Operations
Vetter Pharma Fertigung GmbH & Co. KG 316126754 ANALYSIS(58468-0070)
Establishment
Name Address ID/FEI Operations
Vetter Pharma-Fertigung Gmbh & Co. KG 312670654 ANALYSIS(58468-0070)
Revised: 06/2017   Genzyme Corporation

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pregnancy

Information about this laronidase-intravenous-route
Pregnancy Category Explanation
All Trimesters B Animal studies have revealed no evidence of harm to the fetus, however, there are no adequate studies in pregnant women OR animal studies have shown an adverse effect, but adequate studies in pregnant women have failed to demonstrate a risk to the fetus.

Where can i get more information?

Your doctor or pharmacist can provide more information about laronidase.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2013 Cerner Multum, Inc. Version: 3.01. Revision date: 10/15/2012.

Your use of the content provided in this service indicates that you have read,understood and agree to the End-User License Agreement,which can be accessed by clicking on this link.

What happens if I miss a dose?

Contact your doctor if you miss an appointment for your injection.

What should I avoid?

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

For Healthcare Professionals

Applies to laronidase: intravenous solution

General

The most frequently reported infusion reactions included pyrexia, chills, blood pressure, increased, tachycardia, and oxygen saturation decreased.

The most frequently reported adverse reactions included rash, upper respiratory tract infection, injection site reaction, hyperreflexia, paresthesia, flushing, and poor venous access.[Ref]

Hypersensitivity

Common (1% to 10%): Anaphylactic reaction[Ref]

Other

Very common (10% or more): Infusion reactions (up to 49%), pyrexia (up to 30%), otitis media (20%), chills (up to 20%), central venous catheterization required for infusion (15%), oxygen saturation decreased (up to 10%)
Common (1% to 10%): Chest pain, face edema, gravitational/dependent edema, abscess, feeling hot, feeling cold, influenza-like illness, body temperature increased
Frequency not reported: Laryngeal edema, extravasation
Postmarketing reports: Fatigue[Ref]

The most common adverse reactions were infusion reactions; the frequency decreased over time with continued use, and most were classified as mild to moderate in severity. The majority of infusion reactions requiring intervention were ameliorated with slowing of the infusion rate, temporarily stopping the infusion, with or without administering additional antihistamines and/or antipyretics.[Ref]

Gastrointestinal

Very common (10% or more): Nausea, abdominal pain/discomfort
Common (1% to 10%): Vomiting, diarrhea[Ref]

Immunologic

In clinical trials, 99 of 102 patients developed IgG antidrug antibodies. No correlation was demonstrated between presence of antidrug antibodies and therapeutic response or the occurrence of allergic reactions. There was also no consistent association between presence of antibodies that neutralize enzymatic activity and therapeutic response. The potential for antibody neutralization of cellular uptake has not been evaluated. There were 9 patients collectively in clinical studies who experienced severe infusion reactions and were subsequently tested for drug specific IgE antibodies and complement activation. Following testing, 1 of the 9 patients had an anaphylactic reaction consisting of urticaria and airway obstruction and tested positive for both drug specific IgE binding antibodies and complement activation. In a separate open-label study of patients 5 years and younger, none tested positive for IgE. The clinical significance of IgE antibodies has not been established.[Ref]

Very common (10% or more): Antidrug antibody development (97%)
Postmarketing reports: Anaphylactic shock, IgE antibody development, compliment activation[Ref]

Dermatologic

Very common (10% or more): Rash (up to 36%)
Common (1% to 10%): Angioedema, urticaria, pruritus, hyperhidrosis, alopecia, cold sweat
Frequency not reported: Erythema[Ref]

Local

Very common (10% or more): Injection site reaction (up to 18%)
Common (1% to 10%): Injection site pain[Ref]

Respiratory

Very common (10% or more): Upper respiratory tract infection (32%)
Common (1% to 10%): Respiratory distress, dyspnea, cough, wheezing, pulmonary crepitation
Frequency not reported: Bronchospasm, hypoxia, tachypnea, respiratory arrest
Postmarketing reports: Respiratory failure, pneumonia[Ref]

Cardiovascular

Very common (10% or more): Flushing (up to 23%), poor venous access/vein disorder (14%), blood pressure increased (up to 10%), tachycardia (up to 10%)
Common (1% to 10%): Hypotension, pallor, peripheral coldness
Frequency not reported: Cyanosis
Postmarketing reports: Cardiorespiratory arrest, cardiac failure[Ref]

Nervous system

Very common (10% or more): Hyperreflexia (14%), paresthesia (14%), headache
Common (1% to 10%): Dizziness, tremor[Ref]

Hematologic

Common (1% to 10%): Thrombocytopenia[Ref]

Hepatic

Common (1% to 10%): Hyperbilirubinemia, bilirubinemia[Ref]

Ocular

Common (1% to 10%): Corneal opacity[Ref]

Musculoskeletal

Very common (10% or more): Arthropathy, arthralgia, back pain, pain in extremity
Common (1% to 10%): Musculoskeletal pain[Ref]

Psychiatric

Common (1% to 10%): Restlessness[Ref]

Some side effects of Aldurazyme may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

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