Aldurazyme

Laronidase is injected into a vein through an IV. You will receive this injection in a clinic or hospital setting.

The medicine must be given slowly through an IV infusion, and can take up to 4 hours to complete.

Laronidase is usually given once per week. Follow your doctor's instructions very carefully.

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

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

Your doctor will need to check your progress on a regular basis. Do not miss any scheduled appointments.

Since laronidase is given by a healthcare professional in a medical setting, an overdose is unlikely to occur.

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

ALDURAZYME (laronidase) is a polymorphic variant of the human enzyme αliduronidase 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.

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

To make sure laronidase is safe for you, tell your doctor if you have any of these other conditions:

• fever or cold symptoms (cough, sore throat, chest congestion, sinus pain, runny or stuffy nose, sneezing);

• heart disease;

• kidney disease;

• asthma or other lung disease;

• epilepsy or other seizure disorder;

• migraine headaches; or

• if you have sleep apnea and you use a continuous positive airway pressure (CPAP) machine.

You may be encouraged to join a patient registry while you are using this medication. The purpose of this registry is to track the progression of this disorder and the effects that laronidase has on long-term treatment of MPS I.

FDA pregnancy category B. Laronidase is not expected to harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment.

If you are pregnant, your name may be listed on a pregnancy registry. This is to track the outcome of the pregnancy and to evaluate any effects of laronidase on the baby.

It is not known whether laronidase passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

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

Since laronidase is given by a healthcare professional in a medical setting, an overdose is unlikely to occur.

General

• To minimize the risk of infusion-related reactions, administer antipyretics and/or antihistamines 60 minutes prior to each infusion.1

• Infusion should be slowed or temporarily discontinued and appropriate supportive treatment initiated if signs or symptoms of an infusion reaction occur. 1 (See Infusion Reactions under Cautions.)

Administration

IV Administration

Administer by IV infusion.1

Laronidase injection concentrate contains no preservative; vials are for single use only.1

Do not mix with other drugs in the same infusion solution.1

Laronidase solutions should be prepared using PVC containers and administered with a PVC infusion set equipped with an inline, low-protein-binding filter with a pore diameter of 0.2 mcm.1

Use strict aseptic technique since drug product contains no preservative.a

Laronidase vials should be allowed to reach room temperature before dilution; do not heat (e.g., in a microwave).1

Determine appropriate number of vials to be diluted based on patient’s body weight and recommended dosage.1

Patients weighing ≤20 kg should receive a total infusion volume of 100 mL; patients weighing >20 kg should receive a total infusion volume of 250 mL.1

Laronidase injection concentrate must be diluted in 0.9% sodium chloride containing 0.1% albumin human prior to administration.1

Prepare infusion bag of 0.9% sodium chloride containing albumin human 0.1% based on the total infusion volume.1 Remove and discard the volume of 0.9% sodium chloride equal to the volume of albumin human to be added (see Table 1).1 Add appropriate volume of albumin human to the infusion bag; gently rotate to ensure proper distribution of the albumin.1

Prior to addition of calculated volume of laronidase injection concentrate to infusion bag, remove and discard an equal volume of 0.9% sodium chloride containing albumin human 0.1%.1 Slowly withdraw the calculated volume of laronidase injection concentrate from the appropriate number of vials and add slowly to the infusion bag; gently rotate bag.1 Do not use a filter needle, since it may cause agitation, which may denature laronidase and render the drug biologically inactive.1

Administer total volume of the infusion over 3–4 hours.1

Initially, infuse at a rate of 10 mcg/kg per hour; rate may be increased incrementally every 15 minutes during the first hour of the infusion, as tolerated, up to a maximum rate of 200 mcg/kg per hour.1 Maximum rate should be continued for the remainder of the infusion (2–3 hours).1

Recommended infusion protocols are summarized in Table 2 and Table 3.a

Monitor patient’s vital signs; if stable at the end of the 15-minute infusion time, increase infusion rate to the next recommended level.

Monitor patient’s vital signs; if stable at the end of the 15-minute infusion time, increase infusion rate to the next recommended level.a

Dosage

Dosage of laronidase is expressed in mg.1 The specific activity of laronidase is 172 units/mg.1

Pediatric Patients

Children ≥5 years of age: 0.58 mg/kg administered once weekly.1

Adults

0.58 mg/kg administered once weekly.1

Distribution

Extent

Not known whether laronidase crosses the blood-brain barrier or distributes into milk.a

Elimination

Half-life

1.5–3.6 hours.1

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

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.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of laronidase in children younger than 5 years of age. Safety and efficacy have not been established .

Geriatric

Appropriate studies on the relationship of age to the effects of laronidase have not been performed in the geriatric population .

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Breathing problems or
• Lung disease—Use with caution. May make these conditions worse .

Use Aldurazyme as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given as a shot into a vein.
• Your doctor will give this medicine.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

Recommended Dose

The recommended dosage regimen of Aldurazyme is 0.58 mg/kg of body weight administered once weekly as an intravenous (IV) infusion.  Pretreatment is recommended 60 minutes prior to the start of the infusion and may include antihistamines, antipyretics, or both [see Warnings and Precautions (5)].

Each vial of Aldurazyme provides 2.9 milligrams (mg) of laronidase in 5.0 milliliters (mL) of solution and is intended for single use only.  Do not use the vial more than one time.  The concentrated solution for infusion must be diluted with 0.9% Sodium Chloride Injection, USP, to a final volume of 100 mL or 250 mL, using aseptic techniques.  The final volume of the infusion is determined by the patient’s body weight.  Patients with a body weight of 20 kg or less should receive a total volume of 100 mL.  Patients with a body weight greater than 20 kg should receive a total volume of 250 mL [see Dosage and Administration (2.2)].  For patients with underlying cardiac or respiratory compromise and weighing up to 30 kg, physicians may consider diluting Aldurazyme in a volume of 100 mL and administering at a decreased infusion rate [see Dosage and Administration (2.2), Warnings and Precautions (5.3) and Adverse Reactions (6.3)].

Instructions for Use

Prepare and use Aldurazyme according to the following steps. Use aseptic techniques. Prepare Aldurazyme using low-protein-binding containers and administer with a low-protein-binding infusion set equipped with an in-line, low-protein-binding 0.2 micrometer (µm) filter. There is no information on the compatibility of diluted Aldurazyme with glass containers.

• Determine the number of vials to be diluted based on the patient's weight and the recommended dose of 0.58 mg/kg, using the following equation:
                      Patient's weight (kg) x 1 mL/kg of Aldurazyme = Total number mL of Aldurazyme
                            Total number mL of Aldurazyme ÷ 5 mL per Vial = Total number of Vials.
  
  
• Round up to the next whole vial.  Remove the required number of vials from the refrigerator to allow them to reach room temperature.  Do not heat or microwave vials.
• 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.  Some translucency may be present in the solution.  Do not use if the solution is discolored or if there is particulate matter in the solution.
• Withdraw and discard a volume of the 0.9% Sodium Chloride Injection, USP from the infusion bag, equal to the volume of Aldurazyme concentrate to be added.
• 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.
• Slowly add the Aldurazyme solution to the 0.9% Sodium Chloride Injection, USP using care to avoid agitation of the solutions. Do not use a filter needle.
• Gently rotate the infusion bag to ensure proper distribution of Aldurazyme. Do not shake the solution.
• The entire infusion volume (100 mL for patients weighing 20 kg or less and 250 mL for patients weighing greater than 20 kg) should be delivered over approximately 3 to 4 hours. 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), as outlined in Tables 1  and 2.
• Administer the diluted Aldurazyme solution to patients using a low-protein-binding infusion set equipped with a low-protein-binding 0.2 µm in-line filter.

Aldurazyme does not contain any preservatives; therefore, after dilution with saline, the infusion bags should be used immediately.  If immediate use is not possible, the diluted solution should be stored refrigerated at 2° to 8°C (36° to 46°F) for up to 36 hours.  Other than during infusion, room temperature storage of diluted solution is not recommended.  Any unused product or waste material should be discarded and disposed of in accordance with local requirements.

Aldurazyme must not be administered with other medicinal products in the same infusion. The compatibility of Aldurazyme in solution with other products has not been evaluated.

Aldurazyme is supplied as a sterile solution in single-use, clear Type I glass 5 mL vials, containing 2.9 mg laronidase per 5 mL solution.  The closure consists of a siliconized butyl stopper and an aluminum seal with a plastic flip-off cap.

NDC 58468-0070-1, 5 mL vial

Refrigerate vials of Aldurazyme at 2° to 8°C (36° to 46°F).  Do not freeze or shake.  Protect from light.  Do not use Aldurazyme after the expiration date on the vial.  This product contains no preservatives.

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.

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

To make sure laronidase is safe for you, tell your doctor if you have any of these other conditions:

• fever or cold symptoms (cough, sore throat, chest congestion, sinus pain, runny or stuffy nose, sneezing);
• heart disease;
• kidney disease;
• asthma or other lung disease;
• epilepsy or other seizure disorder;
• migraine headaches; or
• if you have sleep apnea and you use a continuous positive airway pressure (CPAP) machine.

You may be encouraged to join a patient registry while you are using this medication. The purpose of this registry is to track the progression of this disorder and the effects that laronidase has on long-term treatment of MPS I.

FDA pregnancy category B. Laronidase is not expected to harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment.

If you are pregnant, your name may be listed on a pregnancy registry. This is to track the outcome of the pregnancy and to evaluate any effects of laronidase on the baby.

It is not known whether laronidase passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

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

Before you receive Aldurazyme, 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 Aldurazyme.

Some people receiving a Aldurazyme 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 Aldurazyme. Take all of your medications as directed.

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

To make sure Aldurazyme is safe for you, tell your doctor if you have any of these other conditions:

• fever or cold symptoms (cough, sore throat, chest congestion, sinus pain, runny or stuffy nose, sneezing);

• heart disease;

• kidney disease;

• asthma or other lung disease;

• epilepsy or other seizure disorder;

• migraine headaches; or

• if you have sleep apnea and you use a continuous positive airway pressure (CPAP) machine.

You may be encouraged to join a patient registry while you are using this medication. The purpose of this registry is to track the progression of this disorder and the effects that Aldurazyme has on long-term treatment of MPS I.

FDA pregnancy category B. Aldurazyme is not expected to harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment.

If you are pregnant, your name may be listed on a pregnancy registry. This is to track the outcome of the pregnancy and to evaluate any effects of Aldurazyme on the baby.

It is not known whether laronidase passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

This drug should be used during pregnancy only if clearly needed. AU TGA pregnancy category: B2 US FDA pregnancy category: B

Animal studies have failed to reveal evidence of fetal harm or impaired fertility. There are no controlled data in human pregnancy. Pregnant women are encouraged to register themselves in the MPS I registry. For additional information: MPSIregistry.com AU TGA pregnancy category B2: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals are inadequate or may be lacking, but available data show no evidence of an increased occurrence of fetal damage. US FDA pregnancy category B: Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women.