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BOTOX® and BOTOX® Cosmetic (onabotulinumtoxina for injection) contain the same active ingredient in the same formulation. Therefore, adverse events observed with the use of BOTOX® also have the potential to be associated with the use of BOTOX® Cosmetic (onabotulinumtoxina for injection) .

The recommended dosage and frequency of administration for BOTOX® Cosmetic (onabotulinumtoxina for injection) should not be exceeded. Risks resulting from administration at higher dosages are not known.

Lack of Interchangeability between Botulinum Toxin Products

The potency Units of BOTOX® Cosmetic (onabotulinumtoxina for injection) are specific to the preparation and assay method utilized. They are not interchangeable with other preparations of botulinum toxin products and, therefore, units of biological activity of BOTOX® Cosmetic (onabotulinumtoxina for injection) cannot be compared to or converted into units of any other botulinum toxin products assessed with any other specific assay method (see DESCRIPTION).

Spread of Toxin Effect

Postmarketing safety data from BOTOX® Cosmetic (onabotulinumtoxina for injection) and other approved botulinum toxins suggest that botulinum toxin effects may, in some cases, be observed beyond the site of local injection. The symptoms are consistent with the mechanism of action of botulinum toxin and may include asthenia, generalized muscle weakness, diplopia, blurred vision, ptosis, dysphagia, dysphonia, dysarthria, urinary incontinence, and breathing difficulties. These symptoms have been reported hours to weeks after injection. Swallowing and breathing difficulties can be life threatening and there have been reports of death related to spread of toxin effects. The risk of symptoms is probably greatest in children treated for spasticity but symptoms can also occur in adults treated for spasticity and other conditions, and particularly in those patients who have underlying conditions that would predispose them to these symptoms. In unapproved uses, including spasticity in children and adults, and in approved indications, symptoms consistent with spread of toxin effect have been reported at doses comparable to or lower than doses used to treat cervical dystonia.

No definitive serious adverse event reports of distant spread of toxin effect associated with dermatologic use of BOTOX®/BOTOX® Cosmetic (onabotulinumtoxina for injection) at the labeled dose of 20 Units (for glabellar lines) or 100 Units (for severe primary axillary hyperhidrosis) have been reported.

No definitive serious adverse event reports of distant spread of toxin effect associated with BOTOX® for blepharospasm at the recommended dose (30 Units and below) or for strabismus at the labeled doses have been reported.

Hypersensitivity Reactions

Serious and/or immediate hypersensitivity reactions have been reported. These reactions include anaphylaxis, urticaria, soft tissue edema, and dyspnea. If such a reaction occurs, further injection of BOTOX® Cosmetic (onabotulinumtoxina for injection) should be discontinued and appropriate medical therapy immediately instituted. One fatal case of anaphylaxis has been reported in which lidocaine was used as the diluent, and consequently the causal agent cannot be reliably determined.

Pre-Existing Neuromuscular Disorders

Individuals with peripheral motor neuropathic diseases, amyotrophic lateral sclerosis, or neuromuscular junctional disorders (e.g., myasthenia gravis or Lambert-Eaton syndrome) should be monitored particularly closely when given botulinum toxin. Patients with neuromuscular disorders may be at increased risk of clinically significant effects including severe dysphagia and respiratory compromise from typical doses of BOTOX® Cosmetic (see ADVERSE REACTIONS).

Dysphagia and Breathing Difficulties in Treatment of Cervical Dystonia

Treatment with BOTOX® and other botulinum toxin products can result in swallowing or breathing difficulties. Patients with pre-existing swallowing or breathing difficulties may be more susceptible to these complications. In most cases, this is a consequence of weakening of muscles in the area of injection that are involved in breathing or swallowing. When distant effects occur, additional respiratory muscles may be involved (see WARNINGS).

Deaths as a complication of severe dysphagia have been reported after treatment with botulinum toxin. Dysphagia may persist for several months, and require use of a feeding tube to maintain adequate nutrition and hydration. Aspiration may result from severe dysphagia and is a particular risk when treating patients in whom swallowing or respiratory function is already compromised.

Treatment of cervical dystonia with botulinum toxins may weaken neck muscles that serve as accessory muscles of ventilation. This may result in a critical loss of breathing capacity in patients with respiratory disorders who may have become dependent upon these accessory muscles. There have been postmarketing reports of serious breathing difficulties, including respiratory failure, in cervical dystonia patients.

Patients treated with botulinum toxin may require immediate medical attention should they develop problems with swallowing, speech, or respiratory disorders. These reactions can occur within hours to weeks after injection with botulinum toxin (see WARNINGS, ADVERSE REACTIONS, CLINICAL PHARMACOLOGY).

Cardiovascular System

There have been reports following administration of BOTOX® of adverse events involving the cardiovascular system, including arrhythmia and myocardial infarction, some with fatal outcomes. Some of these patients had risk factors including pre-existing cardiovascular disease.

Human Albumin

This product contains albumin, a derivative of human blood. Based on effective donor screening and product manufacturing processes, it carries an extremely remote risk for transmission of viral diseases. A theoretical risk for transmission of Creutzfeldt-Jakob disease (CJD) also is considered extremely remote. No cases of transmission of viral diseases or CJD have ever been identified for albumin.

The safe and effective use of BOTOX® Cosmetic (onabotulinumtoxina for injection) depends upon proper storage of the product, selection of the correct dose, and proper reconstitution and administration techniques. Physicians administering BOTOX® Cosmetic (onabotulinumtoxina for injection) must understand the relevant neuromuscular and/or orbital anatomy of the area involved, as well as any alterations to the anatomy due to prior surgical procedures and avoid injection into vulnerable anatomic areas.

Caution should be used when BOTOX® Cosmetic (onabotulinumtoxina for injection) treatment is used in the presence of inflammation at the proposed injection site(s) or when excessive weakness or atrophy is present in the target muscle(s).

Reduced blinking from BOTOX® Cosmetic (onabotulinumtoxina for injection) injection of the orbicularis muscle can lead to corneal exposure, persistent epithelial defect and corneal ulceration, especially in patients with VII nerve disorders. In the use of BOTOX® for the treatment of blepharospasm, one case of corneal perforation in an aphakic eye requiring corneal grafting has occurred because of this effect. Careful testing of corneal sensation in eyes previously operated upon, avoidance of injection into the lower lid area to avoid ectropion, and vigorous treatment of any epithelial defect should be employed. This may require protective drops, ointment, therapeutic soft contact lenses, or closure of the eye by patching or other means.

Inducing paralysis in one or more extraocular muscles may produce spatial disorientation, double vision or past pointing. Covering the affected eye may alleviate these symptoms.

Caution should be used when BOTOX® Cosmetic (onabotulinumtoxina for injection) treatment is used in patients who have an inflammatory skin problem at the injection site, marked facial asymmetry, ptosis, excessive dermatochalasis, deep dermal scarring, thick sebaceous skin or the inability to substantially lessen glabellar lines by physically spreading them apart as these patients were excluded from the Phase 3 safety and efficacy trials.

Needle-related pain and/or anxiety may result in vasovagal responses, (including e.g., syncope, hypotension) which may require appropriate medical therapy.

Injection intervals of BOTOX® Cosmetic (onabotulinumtoxina for injection) should be no more frequent than every three months and should be performed using the lowest effective dose (see ADVERSE REACTIONS, Immunogenicity).

Patient Information

The physician should provide a copy of the FDA-Approved Patient Medication Guide and review the contents with the patient. Patients should be advised to inform their doctor or pharmacist if they develop any unusual symptoms (including difficulty with swallowing, speaking, or breathing), or if any existing symptom worsens.

Patients should be counseled that if loss of strength, muscle weakness, or impaired vision occur, they should avoid driving a car or engaging in other potentially hazardous activities.

Pregnancy

Pregnancy Category C

Administration of BOTOX® Cosmetic (onabotulinumtoxina for injection) is not recommended during pregnancy. There are no adequate and well-controlled studies of BOTOX® Cosmetic (onabotulinumtoxina for injection) in pregnant women. When pregnant mice and rats were injected intramuscularly during the period of organogenesis, the developmental NOEL (No Observed Effect Level) of BOTOX® Cosmetic (onabotulinumtoxina for injection) was 4 Units/kg. Higher doses (8 Units/kg or 16 Units/kg) were associated with reductions in fetal body weights and/or delayed ossification.

In a range finding study in rabbits, daily injection of 0.125 Units/kg/day (days 6 to 18 of gestation) and 2 Units/kg (days 6 and 13 of gestation) produced severe maternal toxicity, abortions and/or fetal malformations. Higher doses resulted in death of the dams. The rabbit appears to be a very sensitive species to BOTOX® Cosmetic (onabotulinumtoxina for injection) .

If the patient becomes pregnant after the administration of this drug, the patient should be apprised of the potential risks, including abortion or fetal malformations that have been observed in rabbits.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long term studies in animals have not been performed to evaluate carcinogenic potential of BOTOX® Cosmetic (onabotulinumtoxina for injection) .

The reproductive NOEL following intramuscular injection of 0, 4, 8, and 16 Units/kg was 4 Units/kg in male rats and 8 Units/kg in female rats. Higher doses were associated with dose-dependent reductions in fertility in male rats (where limb weakness resulted in the inability to mate), and testicular atrophy or an altered estrous cycle in female rats. There were no adverse effects on the viability of the embryos.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when BOTOX® Cosmetic (onabotulinumtoxina for injection) is administered to a nursing woman.

Pediatric Use

Use of BOTOX® Cosmetic (onabotulinumtoxina for injection) is not recommended in children.

Geriatric Use

The two clinical studies of BOTOX® Cosmetic (onabotulinumtoxina for injection) did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. However, the responder rates appeared to be higher for patients younger than age 65 than for patients 65 years or older (see Clinical Studies).

There were too few patients (N=3) over the age of 75 to allow any meaningful comparisons.

REFERENCE

1. Wang YC, Burr DH, Korthals GJ, Sugiyama H. Acute toxicity of aminoglycoside antibiotics as an aid in detecting botulism. Appl Environ Microbiol 1984; 48:951-955.

Last reviewed on RxList: 8/12/2009
This monograph has been modified to include the generic and brand name in many instances.