Fabrazyme (Page 2 of 6)

5.2 Infusion-Associated Reactions

In clinical trials of Fabrazyme, 59% of patients experienced infusion-associated reactions during Fabrazyme administration, some of which were severe. Infusion-associated reactions are defined as adverse reactions occurring on the same day as the infusion. The incidence of infusion-associated reactions was higher in patients who were positive for anti-Fabrazyme antibodies than in patients who were negative for anti-Fabrazyme antibodies [see Adverse Reactions (6.2)].

Severe infusion-associated reactions experienced by more than one patient in clinical trials of Fabrazyme included chills, vomiting, hypotension, and paresthesia. Other infusion-associated reactions included pyrexia, feeling hot or cold, dyspnea, nausea, flushing, headache, fatigue, pruritus, pain in extremity, hypertension, chest pain, throat tightness, abdominal pain, dizziness, tachycardia, nasal congestion, diarrhea, edema peripheral, myalgia, urticaria, bradycardia, and somnolence [see Warnings and Precautions (5.1) and Adverse Reactions (6.1)].

Most patients in clinical trials were pretreated with acetaminophen. In patients experiencing infusion-associated reactions, pretreatment with an antipyretic and antihistamine is recommended. Infusion-associated reactions occurred in some patients after receiving pretreatment with antipyretics, antihistamines, and oral steroids. Infusion-associated reactions tended to decline in frequency with continued use of Fabrazyme. However, infusion-associated reactions may still occur despite extended duration of Fabrazyme treatment. If an infusion-associated reaction occurs, decrease the infusion rate, temporarily stop the infusion, and consider administrating additional antipyretics, antihistamines, and/or steroids. If severe infusion-associated reactions occur, discontinue administration of Fabrazyme immediately and initiate appropriate medical treatment. Severe reactions are generally managed with administration of antihistamines, corticosteroids, intravenous fluids, and/or oxygen, when clinically indicated. Because of the potential for severe infusion-associated reactions, ensure appropriate medical support measures are readily available when Fabrazyme is administered. Monitor closely patients who have experienced infusion-associated reactions when readministering Fabrazyme. Patients with advanced Fabry disease may have compromised cardiac function, which may predispose them to a higher risk of severe complications from infusion-associated reactions. Monitor closely patients with compromised cardiac function if Fabrazyme is administered to these patients [see Warnings and Precautions (5.1)].

6 ADVERSE REACTIONS

The following clinically significant adverse reactions are described elsewhere in labeling:

6.1 Clinical Trials Experience

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

The data described below reflect exposure of 80 patients, ages 16 to 61 years, to 1 mg/kg Fabrazyme every two weeks in two separate double-blind, placebo-controlled clinical trials, for periods ranging from 1 to 35 months (mean 15.5 months). All 58 patients enrolled in one of the two studies continued into an open-label extension study of Fabrazyme treatment for up to 54 additional months. Patients were treated with antipyretics and antihistamines prior to the infusions.

Most Common Adverse Reactions

Table 2 enumerates adverse reactions that occurred during the double-blind treatment periods of the two placebo-controlled trials (Study 1 and Study 2) [see Clinical Studies (14)]. The most common adverse reactions reported with Fabrazyme were infusion-associated reactions, (Fabrazyme 59% vs placebo 27%) some of which were severe (Fabrazyme 5.0% vs placebo 1.7%). Infusion-associated reactions are defined as adverse reactions occurring on the same day as the infusion.

Common adverse reactions which occurred in ≥20% of patients treated with Fabrazyme and >2.5% compared to placebo are: upper respiratory tract infection, chills, pyrexia, headache, cough, paresthesia, fatigue, peripheral edema, dizziness and rash. Table 2 lists the common adverse reactions (≥5%).

Table 2: Summary of Common Adverse Reactions * in Clinical Trials (study 1 and 2) of Patients with Fabry Disease
Adverse Reaction Fabrazyme(n=80)% Placebo(n=60)%
*
Reported at rate of at least 5% in Fabrazyme-treated patients and greater than 2.5% compared to placebo-treated patients.
Includes reports of upper respiratory infection, nasal congestion, sinusitis, respiratory tract congestion, and pharyngitis.
Includes reports of chills and feeling cold.
§
Includes reports of myalgia and muscle spasms.
Upper respiratory tract infection 53 42
Chills 49 13
Pyrexia 39 22
Headache 39 28
Cough 33 25
Paresthesia 31 18
Fatigue 24 17
Peripheral edema 21 7
Dizziness 21 8
Rash 20 10
Pain in extremity 19 8
Myalgia § 18 7
Lower respiratory tract infection 18 7
Pain 16 13
Back pain 16 10
Hypertension 14 5
Pruritus 10 3
Tachycardia 9 3
Excoriation 9 2
Increased blood creatinine 9 5
Tinnitus 8 3
Dyspnea 8 2
Fall 6 3
Burning sensation 6 0
Anxiety 6 3
Depression 6 2
Wheezing 6 0
Hypoacusis 5 0
Chest discomfort 5 2
Fungal infection 5 0
Viral infection 5 0
Hot flush 5 0

Most infusion-associated reactions requiring intervention were ameliorated with slowing of the infusion rate, temporarily stopping the infusion, and/or administration of antipyretics, antihistamines, or steroids.

Adverse Reactions in Pediatric Patients

In Study 3, the safety profile of Fabrazyme in pediatric Fabry disease patients, ages 8 to 16 years, was similar to that seen in adults. The most common adverse reactions (>20%) were headache, abdominal pain, pharyngitis, fever, nausea, vomiting, rhinitis, diarrhea, arthralgia, and dizziness [see Use in Specific Populations (8.4) and Clinical Studies (14)].

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