Botulinum Toxin

Serious and/or immediate hypersensitivity reactions (eg, anaphylaxis, serum sickness, urticaria, soft tissue edema, dyspnea) have occurred. If a reaction occurs, discontinue and institute immediate treatment.

Higher doses or more frequent administration may result in neutralizing antibody formation and loss of efficacy.

Has been observed with therapy in patients with detrusor overactivity associated with a neurologic condition; acts as stimuli to trigger an exaggerated sympathetic and parasympathetic response. Clinical presentation often includes headache, a marked increase in blood pressure, and diaphoresis; prompt treatment may be required in patients presenting with severe symptoms (eg, hypertensive crisis).

Arrhythmia and MI (some fatal) have been reported following administration. Some of these patients had risk factors including preexisting cardiovascular disease. The exact relationship to onabotulinumtoxinA has not been established.

Common when used for cervical dystonia and may persist anywhere from 2 weeks up to 5 months after administration. In severe cases (some fatal), patients may require alternative feeding methods (eg, feeding tube). Risk factors include smaller neck muscle mass, bilateral injections into the sternocleidomastoid muscle, or injections into the levator scapulae. Risk of aspiration resulting from severe dysphagia is increased in patients when swallowing is already compromised. Limiting the dose injected into the sternocleidomastoid muscle may reduce the occurrence of dysphagia.

Use with caution in patients with bleeding disorders and/or receiving anticoagulation therapy.

Bronchitis and upper respiratory infection have been reported more frequently in patients treated for upper or lower limb spasticity.

Distant spread of botulinum toxin beyond the site of injection has been reported; dysphagia and breathing difficulties have occurred and may be life threatening; other symptoms reported include blurred vision, diplopia, dysarthria, dysphonia, generalized muscle weakness, ptosis, and urinary incontinence, which may develop within hours or weeks following injection. The risk is likely greatest in children treated for the unapproved use of spasticity, but symptoms can also occur in adults treated for spasticity and other conditions. Systemic effects have occurred following use in approved and unapproved uses, including doses comparable to or lower than doses used to treat cervical dystonia and upper limb spasticity. Immediate medical attention required if respiratory disorders, speech, or swallowing difficulties appear.

An increased incidence of urinary retention and need for catheterization has been observed in patients receiving therapy for bladder dysfunction (overactive bladder or detrusor overactivity associated with a neurologic condition); due to the risk of urinary retention, treatment should only be used in patients able and willing to initiate post-treatment catheterization, if required. Patients with diabetes had an increased incidence of urinary retention. Patients experiencing difficulty in voiding should be instructed to consult their health care provider.

Therapy in patients with overactive bladder increases the incidence of UTIs; clinical trials for overactive bladder excluded patients with >2 UTIs in the previous 6 months and those taking chronic antibiotics for prophylaxis of recurrent UTIs. Consider risks versus benefits when contemplating use in these patients or patients experiencing recurrent UTIs during treatment. Patients with diabetes had an increased incidence of UTI. Disease-related concerns:

Safety and efficacy have not been established in patients with 14 or fewer headaches per month.

Use with caution in patients with peripheral motor neuropathic diseases, amyotrophic lateral sclerosis, or neuromuscular junction disorders (eg, myasthenia gravis, Lambert-Eaton syndrome). Risk of adverse events including generalized muscle weakness, diplopia, ptosis, dysphonia, dysarthria, severe dysphagia, and respiratory compromise may be increased.

Reduced blinking from injection of the orbicularis muscle can lead to corneal exposure and ulceration when treating blepharospasm. Retrobulbar hemorrhages may occur from needle penetration into orbit when treating strabismus; spatial disorientation, double vision, or past-pointing may occur if one or more extraocular muscles are paralyzed. Covering the affected eye may help. Careful testing of corneal sensation, avoidance of lower lid injections, and treatment of epithelial defects are necessary. Use caution in patients with angle closure glaucoma.

Use extreme caution in patients with preexisting respiratory disease; treatment with botulinum toxin may weaken accessory muscles that are necessary for these patients to maintain adequate ventilation. Serious breathing difficulties, including respiratory failure, have been reported. Risk of aspiration resulting from severe dysphagia is increased in patients with decreased respiratory function. Concurrent drug therapy issues:

Use with extreme caution in patients receiving other agents that may interfere with neuromuscular transmission (eg, aminoglycosides, neuromuscular-blocking agents) Dosage form specific issues:

Product may contain albumin; albumin carries an extremely remote risk for transmission of viral diseases, Creutzfeldt-Jakob disease (CJD) and variant CJD (vCJD). No cases of transmission of viral diseases, CJD, or vCJD have been identified for licensed albumin or albumin contained in other licensed products.

Botulinum products (abobotulinumtoxinA, onabotulinumtoxinA, rimabotulinumtoxinB) are not interchangeable; potency units are specific to each preparation and cannot be compared or converted to any other botulinum product. Other warnings/precautions:

Appropriate use: Rule out acute UTI prior to treatment; appropriate prophylactic antimicrobial therapy is required prior to, during, and following treatment. Discontinue antiplatelet therapy at least 3 days prior to administration.

May impair ability to drive and/or operate machinery due to the intended effects of treatment; if loss of strength, muscle weakness, or impaired vision occurs, patients should avoid driving or engaging in other hazardous activities.

Use with caution if there is inflammation or excessive weakness or atrophy at the proposed injection site(s); use is contraindicated if infection is present. Serious events (including fatalities) have been observed with direct injection into the esophagus, stomach, salivary glands, and oro-lingual-pharyngeal region. Use caution when administering in close proximity to the lungs (especially the apices); pneumothorax has been reported following administration near the thorax.

Appropriate use: Evaluate for secondary causes prior to treatment (eg, hyperthyroidism). Safety and efficacy for treatment of hyperhidrosis in other areas of the body have not been established.

Appropriate use: Do not use more frequently than every 3 months (Canadian labeling states not to use more frequently than every 2 months). Patients with 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 were excluded from clinical trials. Use with caution in patients with surgical alterations to the facial anatomy. Reduced blinking from injection of the orbicularis muscle can lead to corneal exposure and ulceration. Spatial disorientation, double vision, or past pointing may occur if one or more extraocular muscles are paralyzed.

Serious adverse reactions, including excessive weakness, dysphagia, and aspiration pneumonia, including fatalities, have been reported in patients who have received injections for unapproved uses. In these cases, the reactions were not necessarily related to distant spread of toxin, but may have resulted from administration to the site of injection and/or adjacent structures; several patients had preexisting dysphagia or other significant disabilities.

Appropriate use: Safety and effectiveness of other upper or lower limb muscle groups have not been established. Treatment has not been shown to improve upper extremity functional abilities or range of motion at a joint affected by a fixed contracture.