Weight-Based Dosing Calculator for Mucopolysaccharidosis I Therapy

Please refer to the Summary of Product Characteristics for full information on the use of Aldurazyme^® for the treatment of MPS I.
^* The activity unit (U) is defined as the hydrolysis of one micromole of substrate (4-MUI) per minute.¹

Administration

Administering the Aldurazyme^® infusion

Recommended Aldurazyme^® infusion rate and speed:

The initial infusion rate of 2 U/kg/h may be incrementally increased every fifteen minutes, if tolerated, to a maximum of 43 U/kg/h.¹

For the initial administration of Aldurazyme^® or upon re-administration following interruption of treatment, it is recommended that patients be administered pre-treatment medicines (antihistamines and/or antipyretics) approximately 60 minutes prior to the start of the infusion, to minimize the potential occurrence of infusion-associated reactions.¹

If clinically indicated, administration of pre-treatment medications with subsequent infusions of Aldurazyme^® should be considered.¹

Support optimal ALDURAZYME^® treatment by regularly monitoring your patient’s weight and adjusting their dose as required. Always ensure to administer the indicated and appropriate ALDURAZYME^® dose.

IAR: Infusion associated reactions; MPS I: Mucopolysaccharidosis 1.

Safety

Safety information

Infusion associated reactions (IAR)

IARs, defined as any related adverse event occurring during the infusion or until the end of the infusion day have been reported in patients treated with ALDURAZYME^®.¹

Severe IARs have been reported in patients with pre-existent severe underlying upper airway involvement.1 These patients should be closely monitored and only be infused in an appropriate clinical setting where resuscitation equipment is available.¹

Hypersensitivity reactions, including anaphylaxis, have been reported with ALDURAZYME^®.¹

Some of these reactions were life- threatening and included respiratory failure/distress, stridor, obstructive airways disorder, hypoxia, hypotension, bradycardia and urticaria. If severe hypersensitivity reactions occur, the infusion of ALDURAZYME^® should be discontinued immediately.¹

In case of a:¹

	Mild or moderate IAR, treatment with antihistamines and paracetamol/ibuprofen should be considered and/or a reduction in the infusion rate to half the infusion rate at which the reaction occurred.
	Single severe IAR, the infusion should be stopped until the symptoms are resolved and treatment with antihistamines and paracetamol/ ibuprofen should be considered. The infusion can be restarted with a reduction of the infusion rate to 1/2 – 1/4 the rate of the infusion at which the reaction occurred.
	Recurrent moderate IAR or re-challenge after a single severe IAR, pre-treatment should be considered (antihistamines and paracetamol/ ibuprofen and/or corticosteroids) and a reduction of the infusion rate to 1/2 – 1/4 the rate of the infusion at which the previous reaction occurred.

Most frequent adverse drug reactions (ADRs)

The most frequent ADRs in clinical trials were: headache, nausea, abdominal pain, rash, arthralgia, backpain, pain at extremity, flushing, pyrexia, infusion site reactions, blood pressure increased, oxygen saturation decreased, tachycardia and chills^.1

Post-marketing experience of infusion-associated reactions revealed reporting of cyanosis, hypoxia, tachypnea, pyrexia, vomiting, chills and erythema, in which some of these reactions were severe.¹

ADR: adverse drug reactions; IAR: infusion associated reactions; MPS I: mucopolysaccharidosis I.

ALDURAZYME^® abbreviated prescribing information

Aldurazyme^® 100 U/ml concentrate for solution for infusion laronidase

What Aldurazyme^® is and what it is used for:

Aldurazyme® is used to treat patients with MPS I disease (Mucopolysaccharidosis 1). It is given to treat the non-neurological manifestations of the disease.People with MPS I disease have either a low level or no level of an enzyme called α-L-iduronidase, which breaks down specific substances (glycosaminoglycans) in the body. As a result, these substances do not get broken down and processed by the body as they should. They accumulate in many tissues in the body, which causes the symptoms of MPS I. Aldurazyme is an artificial enzyme called laronidase. This can replace the natural enzyme which is lacking in MPS I disease.

What you need to know before you are given Aldurazyme^®

CONTRAINDICATIONS

You should not be given Aldurazyme^®

If you are allergic (hypersensitive) to laronidase or any of the other ingredients of this medicine.

WARNINGS AND PRECAUTIONS

Talk to your doctor before using Aldurazyme^®.

Contact your doctor immediately if treatment with Aldurazyme^® causes:

• Allergic reactions, including anaphylaxis (a severe allergy reaction). Some of these reactions may be life-threatening. Symptoms may include respiratory failure/distress (inability of lungs to work properly), stridor (high-pitched breathing sound) and other disorders due to obstruction of airways, rapid breathing, excessive contraction of the airway muscles causing breathing difficulty (bronchospasm), lack of oxygen in body tissues (hypoxia), low blood pressure, slow heart rate, or itchy rash (urticaria).
• Infusion-associated reactions i.e. any side effect occurring during the infusion or until the end of the infusion day.

If these reactions occur, the Aldurazyme^® infusion should be stopped immediately and appropriate treatment will be started by your doctor.

These reactions may be particularly severe if you have a pre-existing MPS I-related upper airway obstruction.

You may be given additional medications to help prevent allergic-type reactions, such as antihistamines, medicine to reduce fever (e.g. paracetamol) and/or corticosteroids.

Your doctor will also decide if you can continue receiving Aldurazyme^®.

PREGNANCY, BREAST-FEEDING AND FERTILITY

There is not enough experience of the use of Aldurazyme^® in pregnant women. You should not be given Aldurazyme^® during pregnancy unless clearly necessary.

It is not known whether Aldurazyme^® appears in breast milk. It is recommended to stop breast-feeding during treatment with Aldurazyme^®.

No information is available on the effects of Aldurazyme® on fertility.

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine.

DRIVING AND USING MACHINES
The effects on the ability to drive and to use machines have not been studied.

POSSIBLE SIDE EFFECTS
Like all medicines, this medicine can cause side effects, although not everybody gets them.

Side effects were mainly seen while patients were being given the medicine or shortly after (infusion-associated reactions). If you experience any reaction like this, you should contact your doctor immediately. The number of these reactions decreased the longer that patients were on Aldurazyme^®.

The majority of these reactions were mild or moderate in intensity. However, severe systemic allergic reaction (anaphylactic reaction) has been observed in patients during or up to 3 hours after Aldurazyme^® infusions. Some of the symptoms of such a severe allergic reaction were life-threatening and included extreme difficulty breathing, swelling of the throat, low blood pressure, and low oxygen level in the body. A few patients who had a prior history of severe MPS I related upper airway and pulmonary involvement, experienced severe reactions including bronchospasm (airway constriction), respiratory arrest, and swelling of the face. The frequency of bronchospasm and respiratory arrest is unknown. The frequency of severe allergic reaction (anaphylactic reaction) and swelling of the face is considered common and may affect up to 1 in 10 people.

Very common symptoms (may affect more than 1 in 10 people): Which were not serious include headache, nausea, abdominal pain, rash, joint disease, joint pain, back pain, pain in arms or legs, flushing, fever, chills, increased heart rate, increased blood pressure and reaction at the infusion site, such as swelling, redness, build-up of fluid, discomfort, itchy rash, pale colour of the skin, discoloured skin, or sensation of being warm.

Common (may affect up to 1 in 10 people):

Increased body temperature, tingling, dizziness, cough, difficulty in breathing, vomiting, diarrhoea, rapid swelling under the skin in areas such as the face, throat, arms and legs which can be life-threatening if throat swelling blocks the airway, hives, itching, hair loss, cold sweat, heavy sweating, muscle pain, paleness, cold hands or feet, feeling hot, feeling cold, fatigue, influenza like illness, pain at injection site, restlessness.