The following adverse reactions to BOTOX Cosmetic (onabotulinumtoxinA) for injection are discussed in greater detail in other sections of the labeling:
- Spread of Toxin Effects [see WARNINGS AND PRECAUTIONS]
- Hypersensitivity [see CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS]
- Dysphagia and Breathing Difficulties in Treatment of Cervical Dystonia [see WARNINGS AND PRECAUTIONS]
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, the 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.
BOTOX and BOTOX Cosmetic contain the same active ingredient in the same formulation, but have different labeled Indications and Usage. Therefore, adverse events observed with the use of BOTOX also have the potential to be observed with the use of BOTOX Cosmetic.
In general, adverse reactions occur within the first week following injection of BOTOX Cosmetic and while generally transient, may have a duration of several months or longer. Localized pain, infection, inflammation, tenderness, swelling, erythema, and/or bleeding/bruising may be associated with the injection. Needle-related pain and/or anxiety may result in vasovagal responses (including e.g., syncope, hypotension), which may require appropriate medical therapy.
Local weakness of the injected muscle(s) represents the expected pharmacological action of botulinum toxin. However, weakness of nearby muscles may also occur due to spread of toxin [see WARNINGS AND PRECAUTIONS].
Table 2 lists selected adverse reactions reported by ≥ 1% of BOTOX Cosmetic treated subjects (N=405) aged 18 to 75 who were evaluated in the randomized, placebo-controlled clinical studies to assess the use of BOTOX Cosmetic in the improvement of the appearance of glabellar lines.
Table 2: Adverse Reactions Reported by ≥ 1% of the BOTOX Cosmetic treated Patients and More Frequent than in Placebo-treated Patients in Double-blind, Placebo-controlled Clinical Studies of Treatment of Glabellar Lines
|Adverse Reactions by System Organ Class||BOTOX Cosmetic
|General Disorders and Administration Site Conditions Facial pain||6 (1%)||0 (0%)|
|Nervous System Disorders Facial paresis||5 (1%)||0 (0%)|
|Eye Disorders Eyelid ptosis||13 (3%)||0 (0%)|
|Musculoskeletal and Connective Tissue Disorders Muscular Weakness||6 (1%)||0 (0%)|
Lateral Canthal Lines
Table 3 lists selected adverse reactions reported within 90 days following injection by ≥ 1% of BOTOX Cosmetic treated subjects (N=526) aged 18 to 75 who were evaluated in two randomized, double-blind, placebo-controlled clinical studies to assess the use of BOTOX Cosmetic in the improvement of the appearance of lateral canthal lines alone.
Table 3: Adverse Reaction Reported by ≥ 1% of BOTOX Cosmetic treated Patients and More Frequent than in Placebo-treated Patients Within 90 Days, in Double-blind, Placebo-controlled Clinical Studies of Treatment of Lateral Cantal Lines
|Adverse Reactions by System Organ Class||BOTOX Cosmetic 24 Units
|Eyelid edema||5 (1%)||0 (0%)|
As with all therapeutic proteins, there is a potential for immunogenicity. Treatment with botulinum toxins may result in the formation of neutralizing antibodies that may reduce the effectiveness of subsequent treatments by inactivating biological activity of the toxin.
In three Lateral Canthal Line trials, 916 subjects (517 subjects at 24 Units and 399 subjects at 44 Units) treated with BOTOX Cosmetic had specimens analyzed for antibody formation. Among the 916 BOTOX Cosmetic treated subjects, 14 subjects (1.5%) developed binding antibodies and no subjects (0%) developed the presence of neutralizing antibodies.
The data reflect the subjects whose test results were considered positive or negative for neutralizing activity to BOTOX Cosmetic in a mouse protection assay. The results of these tests are 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 BOTOX Cosmetic with the incidence of antibodies to other products may be misleading.
The critical factors for neutralizing antibody formation have not been well characterized. The results from some studies suggest that botulinum toxin injections at more frequent intervals or at higher doses may lead to greater incidence of antibody formation. The potential for antibody formation may be minimized by injecting with the lowest effective dose given at the longest feasible intervals between injections.
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.
There have been spontaneous reports of death, sometimes associated with dysphagia, pneumonia, and/or other significant debility or anaphylaxis, after treatment with botulinum toxin [see WARNINGS AND PRECAUTIONS].
There have also been reports of adverse events involving the cardiovascular system, including arrhythmia and myocardial infarction, some with fatal outcomes. Some of these patients had risk factors including cardiovascular disease.
New onset or recurrent seizures have also been reported, typically in patients who are predisposed to experiencing these events.
The following adverse reactions by System Organ Class have been identified during post-approval use of BOTOX/BOTOX Cosmetic:
Ear and labyrinth disorders
Hypoacusis; tinnitus; vertigo
Diplopia; strabismus; visual disturbances; vision blurred
Abdominal pain; diarrhea; dry mouth; nausea; vomiting
General disorders and administration site conditions
Denervation; malaise; pyrexia
Metabolism and nutrition disorders
Musculoskeletal and connective tissue disorders
Muscle atrophy; myalgia
Nervous system disorders
Brachial plexopathy; dysarthria; facial palsy; hypoaesthesia; localized numbness; myasthenia gravis; paresthesia; peripheral neuropathy; radiculopathy; syncope
Respiratory, thoracic and mediastinal disorders
Aspiration pneumonia; dyspnea; respiratory depression and/or respiratory failure
Skin and subcutaneous tissue disorders
Alopecia, including madarosis; hyperhidrosis; pruritus; skin rash (including erythema multiforme, dermatitis psoriasiform, and psoriasiform eruption)