Aldurazyme Side Effects

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

Side Effects of Aldurazyme - for the Consumer

Aldurazyme

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Aldurazyme:

Flushing; headache; mild redness, stinging, or pain at the injection site.

Seek medical attention right away if any of these SEVERE side effects occur when using Aldurazyme:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue; unusual hoarseness); chest pain; cough; diarrhea; dizziness; fast or slow heartbeat; fever, chills, or sore throat; joint pain; nausea; numbness or tingling of the skin; rapid breathing; severe headache; stomach pain; unusual bruising or bleeding; unusual swelling; vision changes; vomiting.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

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Aldurazyme Side Effects - for the Professional

Aldurazyme

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

The most serious adverse reactions reported with Aldurazyme treatment during clinical trials were anaphylactic and allergic reactions.  Most adverse reactions reported in clinical trials were considered disease-related and unrelated to study drug.  The most common adverse reactions were infusion reactions.  The frequency of infusion 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 reactions requiring intervention were ameliorated with slowing of the infusion rate, temporarily stopping the infusion, with or without administering additional treatments including antihistamines, antipyretics, or both.

Clinical Trials in Patients 6 Years and Older

A 26-week, double-blind, placebo-controlled clinical study (Study 1) of Aldurazyme was conducted in 45 patients with MPS I, ages 6 to 43 years old, gender evenly distributed (N=23 females and 22 males).  Of these 45 patients, 1 was clinically assessed as having Hurler form, 37 Hurler-Scheie, and 7 Scheie.  Patients were randomized to receive either 0.58 mg/kg IV of Aldurazyme per week for 26 weeks or placebo.  All patients were treated with antipyretics and antihistamines prior to the infusions.  Infusion reactions were reported in 32% (7 of 22) of Aldurazyme-treated patients. The most commonly reported infusion reactions regardless of treatment group were flushing, pyrexia, headache, and rash.  Flushing occurred in 5 patients (23%) receiving Aldurazyme; the other reactions were less frequent.  Less common infusion reactions included angioedema (including face edema), hypotension, paresthesia, feeling hot, hyperhidrosis, tachycardia, vomiting, back pain, and cough.  Other reported adverse reactions included bronchospasm, dyspnea, urticaria and pruritus.

Table 3 enumerates adverse reactions and selected laboratory abnormalities that occurred during the placebo-controlled study (Study 1) that were reported in at least 2 patients more in the Aldurazyme group than in the placebo group.

Table 3: Summary of Adverse Reactions that Occurred in 2 Patients More in the Aldurazyme® Group than in the Placebo Group in the 26-Week Placebo-controlled Study (Study 1)

MedDRA System Organ Class (SOC)          MedDRA Preferred Term	(N=22) Aldurazyme n (%)	(N=23) Placebo n (%)
Blood and lymphatic system disorders
Thrombocytopenia	2 (9) )	0
Eye disorders
Corneal opacity	2(9)	0
General disorders and administration site conditions
Chest pain	2 (9)	0
Face edema	2 (9)	0
Gravitational edema	2 (9)	0
Injection site pain	2 (9)	0
Injection site reaction	4 (18)	2 (9)
Hepatobiliary disorders
Hyperbilirubinemia	2 (9)	0
Infections and infestations
Abscess	2 (9)	0
Upper respiratory tract infection	7 (32)	4 (17)
Nervous system disorders
Hyperreflexia	3 (14)	0
Paresthesia	3 (14)	1 (4)
Rash	8 (36)	5 (22)
Vascular disorders
Hypotension	2(9)	0
Poor venous access	3 (14)	0

All 45 patients who completed the placebo-controlled study (Study 1) continued treatment in an open-label, uncontrolled extension study (Study 2).  All patients received Aldurazyme 0.58 mg/kg of body weight once weekly for up to 182 weeks.  The most serious adverse reactions reported with Aldurazyme infusions in Study 2 were anaphylactic and allergic reactions [see Warnings and Precautions (5)]. The most common adverse reactions requiring intervention were infusion reactions reported in 49% (22 of 45) of patients treated with Aldurazyme.  The most commonly reported infusion reactions included rash (13%), flushing (11%), pyrexia (11%), headache (9%), abdominal pain or discomfort (9%), and injection site reaction (9%).  Less commonly reported infusion reactions included nausea (7%), diarrhea (7%), feeling hot or cold (7%), vomiting (4%), pruritus (4%), arthralgia (4%), and urticaria (4%).  Additional common adverse reactions included back pain and musculoskeletal pain.

Clinical Trials in Patients 6 Years and Younger

Study 3 was a 52-week, open-label, uncontrolled study of 20 MPS I patients, ages 6 months to 5 years old (at enrollment).  Sixteen patients were clinically assessed as having the Hurler form, and 4 had the Hurler-Scheie form.  All 20 patients received Aldurazyme at 0.58 mg/kg of body weight once weekly for 26 weeks and up to 52 weeks.  All patients were treated with antipyretics and antihistamines prior to the infusions.

The most commonly reported serious adverse events (regardless of relationship) reported with Aldurazyme infusions in Study 3 were otitis media (20%), and central venous catheterization required for Aldurazyme infusion (15%).

The nature and severity of infusion reactions were similar between the older and less severely affected patients in Studies 1 and 2, and the younger, more severely affected patients in Study 3.  The most commonly reported adverse reactions in Study 3 were infusion reactions reported in 35% (7 of 20) of patients and included pyrexia (30%), chills (20%), blood pressure increased (10%), tachycardia (10%), and oxygen saturation decreased (10%).  Other commonly reported infusion reactions occurring in ≥ 5% of patients were pallor, tremor, respiratory distress, wheezing, crepitations (pulmonary), pruritis, and rash.

Immunogenicity

In clinical trials, 99 of 102 patients (97%) treated with Aldurazyme were positive for IgG antibodies to Aldurazyme.  The clinical significance of antibodies to Aldurazyme, including the potential for product neutralization, is not known.  Potential for antibody neutralization of cellular uptake has not been assessed.

The data reflect the percentage of patients whose test results were considered positive for antibodies to Aldurazyme using an enzyme-linked immunosorbent assay (ELISA) for Aldurazyme-specific IgG binding antibodies reported as titers (57 patients) or optical density units per uL (OD/uL) (42 patients), and confirmed by radio-immunoprecipitation (RIP).  The relationship of Aldurazyme antibody concentration in titer units and OD/uL units has not been established.

Nine patients in Study 1 and Study 2, collectively, who experienced severe infusion reactions were tested for Aldurazyme-specific IgE antibodies and complement activation.  IgE testing was performed by ELISA, and complement activation was measured by the Quidel Enzyme Immunoassay.  One of the nine patients had an anaphylactic reaction consisting of urticaria and airway obstruction and tested positive for both Aldurazyme-specific IgE binding antibodies and complement activation.  None of the patients in the open-label clinical study of patients 5 years old or younger (Study 3) tested positive for IgE.

Other allergic reactions were also seen in patients receiving Aldurazyme [see Adverse Reactions (6)].

In the postmarketing setting, approximately 1% of patients experienced severe or serious infusion allergic reactions and tested positive for IgE.  Of these IgE-positive patients, some have discontinued treatment, but some have been successfully re-challenged.  The clinical significance of IgE antibodies has not been established.

As with all the therapeutic proteins, there is potential for immunogenicity.  The incidence of antibody formation is highly dependent on the sensitivity and specificity of the assay.  Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease.  For these reasons, comparison of the incidence of antibodies to Aldurazyme with the incidence of antibodies to other products may be misleading.

Postmarketing Experience

The following adverse reactions have been identified during post approval use of Aldurazyme.  Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

In postmarketing experience with Aldurazyme, severe and serious infusion reactions have been reported, some of which were life-threatening, including anaphylactic shock [see Boxed Warning and Warnings and Precautions (5)].

Adverse reactions resulting in death reported in the postmarketing setting with Aldurazyme treatment included cardio-respiratory arrest, respiratory failure, cardiac failure, and pneumonia.  These events have been reported in MPS I patients with significant underlying disease.

Additional common adverse reactions included erythema and cyanosis.

There have been a small number of reports of extravasation in patients treated with Aldurazyme.  There have been no reports of tissue necrosis associated with extravasation.

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Side Effects by Body System - for Healthcare Professionals

Dermatologic

Dermatologic side effects have included rash, urticaria, pruritus, cold sweat, alopecia, and hyperhidrosis.

Facial edema has occurred in a few patients who had MPS I-related upper airway and pulmonary involvement

Respiratory

Respiratory side effects have included upper respiratory tract infection (32%), bronchospasm, dyspnea, and cough.

Local

Local side effects have included injection site reactions (18%) and injection site pain (9%).

Cardiovascular

Cardiovascular side effects have included flushing (13%), increased blood pressure (10%), angioedema, and tachycardia.

Nervous system

Nervous system side effects have included headache (7%), paraesthesia, and dizziness.

Immunologic

Immunologic side effects have included development of IgG antibodies to laronidase, and abscesses (9%).

In the phase III double-blind study and the open-label extension study, almost all of the patients were observed to develop laronidase-specific IgG antibodies.

Hematologic

Hematologic side effects have included thrombocytopenia (9%).

Hepatic

Hepatic side effects have included bilirubinemia (9%).

Ocular

Ocular side effects have included corneal opacity (9%).

Hypersensitivity

Hypersensitivity side effects have included anaphylactic reactions.

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