Naglazyme Side Effects

Generic Name: galsulfase

Please note - some side effects for Naglazyme 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 Naglazyme - for the Consumer

Naglazyme

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 Naglazyme:

Cough; diarrhea; ear pain; headache.

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

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); chest pain; chills; decreased reflexes; difficulty swallowing; eye redness or irritation; fever; hoarseness; joint pain; nausea; pain, swelling, or redness at the injection site; shortness of breath; sore throat; stomach pain; sudden, severe headache or dizziness; swelling of hands or legs; vision problems; 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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Naglazyme Side Effects - for the Professional

Naglazyme

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 observed in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Naglazyme was studied in a randomized, double-blind, placebo-controlled trial in which 19 patients received weekly infusions of 1 mg/kg Naglazyme and 20 patients received placebo; of the 39 patients  66% were female, and 62% were White, non-Hispanic.  Patients were aged 5 years to 29 years.  Naglazyme-treated patients were approximately 3 years older than placebo-treated patients (mean age 13.7 years versus 10.7 years, respectively).

Serious adverse reactions experienced in this trial include, apnea, pyrexia, and, respiratory distress. Severe adverse reactions include chest pain, dyspnea, laryngeal edema, and conjunctivitis. The most common adverse reactions requiring interventions were infusion reactions.

Table 1 summarizes the adverse reactions that occurred in the placebo-controlled trial in at least 2 patients more in the Naglazyme‑treated group than in the placebo-treated group.

Table 1: Adverse Reactions that Occurred in the Placebo-Controlled Trial in at least 2 Patients More in the Naglazyme Group than in the Placebo Group

MedDRA Preferred Term	Naglazyme (n  =  19)	Placebo (n  = 20* )
	No. Patients (%)	No. Patients (%)
* One of the 20 patients in the placebo group dropped out after Week 4 infusion
All	19 (100)	20 (100)
Abdominal Pain	9 (47)	7 (35)
Ear Pain	8 (42)	4 (20)
Arthralgia	8 (42)	5 (25)
Pain	6 (32)	1 (5)
Conjunctivitis	4 (21)	0
Dyspnea	4 (21)	2 (10)
Rash	4 (21)	2 (10)
Chills	4 (21)	0
Chest Pain	3 (16)	1 (5)
Pharyngitis	2 (11)	0
Areflexia	2 (11)	0
Corneal Opacity	2 (11)	0
Gastroenteritis	2 (11)	0
Hypertension	2 (11)	0
Malaise	2 (11)	0
Nasal Congestion	2 (11)	0
Umbilical Hernia	2 (11)	0
Hearing Impairment	2 (11)	0

Four open-label clinical trials were conducted in  MPS VI patients aged 3 months to 29 years with Naglazyme administered at doses of 0.2 mg/kg (n = 2), 1 mg/kg (n = 55), and 2 mg/kg (n = 2). The mean exposure to the recommended dose of Naglazyme (1 mg/kg) was 138 weeks (range = 54 to 261 weeks). Two infants (12.1 months and 12.7 months) were exposed to 2 mg/kg of Naglazyme for 105 and 81 weeks, respectively.

In addition to those listed in Table 1, common adverse reactions observed in the open-label trials include pruritus, urticaria, pyrexia, headache, nausea, and vomiting. The most common adverse reactions requiring interventions were infusion reactions.  Serious adverse reactions included laryngeal edema, urticaria, angioedema, and other allergic reactions. Severe adverse reactions included urticaria, rash, and abdominal pain.

Observed adverse events in four open-label studies (up to 261 weeks treatment) were not different in nature or severity to those observed in the placebo-controlled study. No patients discontinued during open-label treatment with Naglazyme due to adverse events.

Immunogenicity

Ninety-eight percent (53/54) of patients treated with Naglazyme and evaluable for the presence of antibodies to galsulfase developed anti-galsulfase IgG antibodies within 4 to 8 weeks of treatment (in four clinical studies). In 19 patients treated with Naglazyme from the placebo-controlled study, serum samples were evaluated for a potential relationship of anti-galsulfase antibody development to clinical outcome measures. All 19 patients treated with Naglazyme developed antibodies specific to galsulfase; however, the analysis revealed no consistent predictive relationship between total antibody titer, neutralizing or IgE antibodies, and infusion‑associated reactions, urinary glycosaminoglycan (GAG) levels, or endurance measures.  Antibodies were assessed for the ability to inhibit enzymatic activity but not cellular uptake.

The data reflect the percentage of patients whose test results were considered positive for antibodies to galsulfase using specific assays and are highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibodies in an assay may be influenced by several factors including sample handling, timing of sample collection, concomitant medications, and underlying disease.  For these reasons, comparison of the incidence of antibodies to galsulfase with the incidence of antibodies to other products may be misleading.

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of Naglazyme. 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 addition to infusion reactions reported in clinical trials, serious reactions which occurred during Naglazyme infusion in the worldwide marketing experience include anaphylaxis, shock, hypotension, bronchospasm, and respiratory failure.

Additional infusion reactions included pyrexia, erythema, pallor, bradycardia. tachycardia, hypoxia, cyanosis, tachypnea, and paresthesia.

During postmarketing surveillance, there has been a single case of membranous nephropathy and rare cases of thrombocytopenia reported.   In the case of membranous nephropathy, renal biopsy revealed galsulfase‑immunoglobulin complexes in the glomeruli.  With both membranous nephropathy and thrombocytopenia, patients have been successfully rechallenged and have continued to receive Naglazyme.

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Side Effects by Body System - for Healthcare Professionals

General

During a double-blind, placebo-controlled trial, 19 patients received galsulfase and 20 patients received placebo. Serious side effects included apnea, pyrexia, and respiratory distress. Severe side effects included chest pain, dyspnea, laryngeal edema, and conjunctivitis.

During 4 open-label clinical trials, common side effects included pruritus, urticaria, pyrexia, headache, nausea, and vomiting. Serious side effects included laryngeal edema, urticaria, angioedema, and other allergic reactions. Severe side effects included urticaria, rash, and abdominal pain.

During each trial, the most common side effects requiring interventions were infusion reactions.

Other

Other side effects have included abdominal pain (47%), ear pain (42%), pain (32%), chills/rigors (21%), chest pain (16%), malaise (11%), umbilical hernia (11%), pyrexia, and facial edema. Infusion reactions (some severe) have been reported in 56% of patients despite routine pretreatment with antihistamines. Serious symptoms reported during infusion have included angioedema, laryngeal edema, pyrexia, anaphylactoid reaction, respiratory distress, apnea, and urticaria. Severe symptoms of infusion reactions have included chest pain, dyspnea, apnea, laryngeal edema, conjunctivitis, rash, and urticaria. The most common infusion reaction symptoms have included pyrexia, chills, rash, urticaria, dyspnea, nausea, vomiting, pruritus, erythema, hypertension, abdominal pain, and headache. Symptoms of infusion reactions have also included respiratory distress, chest pain, hypotension, angioedema, conjunctivitis, tremor, cough, retrosternal pain, and joint pain. Recurrent infusion reactions have been reported in 70% of patients during multiple infusions, but not always in consecutive weeks. Serious reactions occurring during galsulfase infusion (including anaphylaxis, shock, hypotension, bronchospasm, and respiratory failure) have been reported during postmarketing experience. Additional infusion reactions (including pyrexia, erythema, pallor, bradycardia, tachycardia, hypoxia, cyanosis, tachypnea, and paresthesia) have been reported during postmarketing experience.

Infusion reactions have been reported as early as the first week and as late as the 146th week of galsulfase therapy.

Infusion reaction symptoms generally abated with slowing or temporary interruption of the infusion along with administration of additional antihistamines, antipyretics, and occasionally corticosteroids. Most patients were able to complete their infusions. Subsequent infusions were managed with a slower rate of galsulfase administration and treatment with additional prophylactic antihistamines. In patients who had more severe reactions, treatment included prophylactic corticosteroids.

Hypersensitivity

Hypersensitivity side effects have included anaphylaxis and severe allergic reactions. Some reactions have been life-threatening and have included anaphylaxis, shock, respiratory distress, dyspnea, bronchospasm, laryngeal edema, and hypotension. Angioedema and other allergic reactions (unspecified) have been reported.

Respiratory

Respiratory side effects have included dyspnea (21%), pharyngitis (11%), nasal congestion (11%), apnea, respiratory distress, and laryngeal edema. Acute respiratory complications associated with administration have been reported.

Musculoskeletal

Musculoskeletal side effects have included arthralgia (42%).

Dermatologic

Dermatologic side effects have included rash (21%), pruritus, and urticaria.

Ocular

Ocular side effects have included conjunctivitis (21%) and corneal opacity/increased corneal opacification (11%).

Gastrointestinal

Gastrointestinal side effects have included gastroenteritis (11%), nausea, and vomiting.

Nervous system

Nervous system side effects have included areflexia (11%), hearing impairment (11%), and headache.

Cardiovascular

Cardiovascular side effects have included hypertension (11%). A risk of acute cardiorespiratory failure and the possible development of congestive heart failure have been reported.

Immunologic

Immunologic side effects have included type III immune complex-mediated reactions (including membranous glomerulonephritis). The development of anti-galsulfase IgG antibodies have been reported in 98% of patients within 4 to 8 weeks of therapy.

Renal

Renal side effects have included at least once case of membranous nephropathy during postmarketing experience. Renal biopsy revealed galsulfase-immunoglobulin complexes in the glomeruli.

A patient with membranous nephropathy was successfully rechallenged and continued to receive galsulfase.

Hematologic

Patients with thrombocytopenia have been successfully rechallenged and have continued to receive galsulfase.

Hematologic side effects have included rare cases of thrombocytopenia during postmarketing experience.

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