ADVERSE REACTIONS
The following adverse reactions to XEOMIN are discussed in greater detail in other sections of the labeling.
Hypersensitivity [ see Contraindications (4) ]
Dysphagia and Breathing Difficulties in Treatment of cervical dystonia [ see Warnings and Precautions
]
Spread of Effects from Toxin [see Warnings and Precautions]
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions and for various lengths of time, adverse event rates observed in the clinical trials of a drug cannot be directly compared with rates in other clinical trials of another drug, and may not reflect the rates observed in practice.
Cervical Dystonia
The data described below reflect exposure to a single intramuscular dose of XEOMIN in a placebo-controlled, Phase 3 trial in patients with cervical dystonia [ see Clinical Studies
]. In this study, 159 patients received XEOMIN (78 were randomized to receive a total dose of 120 Units, and 81 were randomized to receive a total dose of 240 Units). XEOMIN-treated patients were 18 to 79 years old (mean 53 years), and were predominantly female (66%) and Caucasian (91%). At study baseline, approximately 25% had mild, 50% had moderate, and 25% had severe cervical dystonia. Approximately 61% of XEOMIN-treated patients had previously received another botulinum toxin type A product. Common adverse events (≥5% in any XEOMIN treatment group) observed in patients who received XEOMIN (120 Units or 240 Units) included dysphagia, neck pain, muscle weakness, injection site pain, and musculoskeletal pain.
Table 2: Most Common TEAEs (≥5%) and Greater than Placebo: Double-Blind Phase of Clinical Trial
|
Double-Blind Phase |
| System Organ Class |
XEOMIN 120 Units |
XEOMIN 240 Units |
Placebo |
| Preferred Term |
(N=77) |
(N=82) |
(N=74) |
| Any TEAEs |
57% |
55% |
42% |
| Musculoskeletal and connective tissue disorders |
23% |
32% |
11% |
| Neck pain |
7% |
15% |
4% |
| Muscular weakness |
7% |
11% |
1% |
| Musculoskeletal pain |
7% |
4% |
1% |
| Gastrointestinal disorders |
18% |
24% |
4% |
| Dysphagia |
13% |
18% |
3% |
| Nervous system disorders |
16% |
17% |
7% |
| General disorders and administration site conditions |
16% |
11% |
11% |
| Injection site pain |
9% |
4% |
7% |
| Infections and infestations |
14% |
13% |
11% |
| Respiratory, thoracic and mediastinal disorders |
13% |
10% |
3% |
Blepharospasm
In the placebo-controlled Phase 3 trial in patients with blepharospasm previously treated with onabotulinumtoxinA (Botox) [see Clinical Studies], 74 patients received XEOMIN at a mean dose of approximately 33 Units per eye (minimum 10 Units, maximum 50 Units). XEOMIN-treated patients were 22 to 79 years of age (mean 62 years), predominantly female (65%), Caucasian (79%), and had a mean time since diagnosis of approximately 5 years.
The adverse events occurring in ≥5% of XEOMIN-treated patients and greater than placebo in the Phase 3 study were eyelid ptosis, dry eye, dry mouth, diarrhea, headache, visual impairment, dyspnea, nasopharyngitis, and respiratory tract infection. No serious adverse events occurred in patients who received XEOMIN; one placebo-treated patient experienced a serious adverse event (dyspnea).
Table 3: Most Common TEAEs (≥5%) and Greater than Placebo: Double-Blind Phase of Clinical Trial
|
Double-Blind Phase |
| System Organ Class |
XEOMIN |
Placebo |
| Preferred Term |
(N=74) |
(N=34) |
| Subjects with TEAEs |
70% |
62% |
| Eye disorders |
38% |
21% |
| Eyelid ptosis |
19% |
9% |
| Dry eye |
16% |
12% |
| Visual impairmentincluding vision blurred
|
12% |
6% |
| Gastrointestinal disorders |
30% |
15% |
| Dry mouth |
16% |
3% |
| Diarrhoea |
8% |
- |
| Infections and infestations |
20% |
15% |
| Nasopharyngitis |
5% |
3% |
| Respiratory tract infection |
5% |
3% |
| Nervous system disorders |
14% |
9% |
| Headache |
7% |
3% |
| General disorders and administration site conditions |
11% |
9% |
| Respiratory, thoracic and mediastinal disorders |
11% |
3% |
| Dyspnoea |
5% |
3% |
Post-Marketing Experience
The following adverse reactions have been reported during post-approval use with XEOMIN: eye swelling, eyelid edema, dysphagia, nausea, injection site pain, injection site reaction, allergic dermatitis, localized allergic reactions like swelling, edema, erythema, pruritus or rash, herpes zoster, muscular weakness, muscle spasm, dysarthria, myalgia and hypersensitivity.
Immunogenicity
As with all therapeutic proteins, there is a potential for immunogenicity. Neutralizing antibody titers were assessed in all clinical studies of XEOMIN, using the hemidiaphragm assay. In the XEOMIN development program, twelve of 1080 subjects (1.1%) who were antibody negative at baseline developed neutralizing antibodies to botulinum toxin during the course of their respective study. Each of these 12 subjects had been treated with another botulinum toxin prior to exposure to XEOMIN. Because the majority of patients had previously been exposed to other botulinum neurotoxins, and because most trials were of short duration with controlled intervals between treatments, the potential for antibody formation has not been fully characterized. The significance of these antibodies is unknown since in the presence of neutralizing antibodies some patients may continue to experience clinical benefit. A single subject with a twenty year history of cervical dystonia who was reported as botulinum toxin-naive and treated with 240 Units of XEOMIN demonstrated transiently positive neutralizing antibodies which reverted to negative at study termination. This subject was determined to be a primary non-responder.
The incidence of antibody formation is highly dependent on the sensitivity and specificity of the assay. In addition, the observed incidence of 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 across products in this class may be misleading.
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REPORTS OF SUSPECTED XEOMIN SIDE EFFECTS / ADVERSE REACTIONS
Below is a sample of reports where side effects / adverse reactions may be related to Xeomin. The information is not vetted and should not be considered as verified clinical evidence.
Possible Xeomin side effects / adverse reactions in 66 year old female
Reported by a physician from France on 2011-10-25
Patient: 66 year old female
Reactions: Oedema Peripheral
Adverse event resulted in: hospitalization
Suspect drug(s):
Xeomin
Other drugs received by patient: Aspirin
Possible Xeomin side effects / adverse reactions in 51 year old female
Reported by a consumer/non-health professional from United States on 2011-11-01
Patient: 51 year old female weighing 81.6 kg (179.5 pounds)
Reactions: Dysphagia, Dizziness
Suspect drug(s):
Xeomin
Dosage: (1 in 1 total), intramuscular
Indication: Torticollis
Start date: 2011-07-14
End date: 2011-07-14
Fluoxetine Hydrochloride
Dosage: 60 mg (20 mg, 3 in 1 d), oral
Administration route: Oral
Indication: Depression
Start date: 2004-01-01
Other drugs received by patient: Baclofen; Balsalazide (Balsalazide)
Possible Xeomin side effects / adverse reactions in 56 year old female
Reported by a individual with unspecified qualification from United States on 2011-11-01
Patient: 56 year old female weighing 59.0 kg (129.8 pounds)
Reactions: Neck Pain
Suspect drug(s):
Xeomin
Dosage: 100; 50 iu, 1 in 1 total, intramuscular
Indication: Torticollis
Start date: 2011-09-02
End date: 2011-09-02
Xeomin
Other drugs received by patient: Flexeril; Restasis; Plavix; Clonazepam
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