OnabotulinumtoxinA causes varied ophthalmic adverse reactions depending on the indication for use and site of injection. If ocular reactions persist when they occur after injection, consider referring patients to an ophthalmologist. In study patients treated for blepharospasm, the most frequently reported adverse reactions included ptosis (21%), superficial punctate keratitis (6%), and xerophthalmia (6%). Other ocular adverse reactions in decreasing order of incidence included ocular irritation, lacrimation, lagophthalmos, photophobia, ectropion, keratitis, diplopia, and entropion. Bruising also occurred easily in the soft eyelid tissues and was prevented by applying pressure at the injection site immediately after the injection. Xerophthalmia, eye irritation, photophobia, and visual changes have been reported with the injection of onabotulinumtoxinA near the orbicularis oculi muscle. In 2 cases of cranial VII nerve disorder (1 case of an aphakic eye), reduced blinking from onabotulinumtoxinA injection of the orbicularis oculi muscle led to serious corneal exposure, persistent epithelial defect, and corneal ulceration. Corneal perforation occurred in the aphakic eye and required corneal grafting. During clinical trials for chronic migraine, xerophthalmia and eyelid edema (blepharedema) occurred more frequently in patients receiving onabotulinumtoxinA than placebo but with an incidence of less than 1%. Blepharedema was the most frequently reported adverse event reported in clinical trials of onabotulinumtoxinA for the treatment of lateral canthal lines occurring at an incidence of 1% compared to 0% for placebo. During clinical trial evaluation of patients with cervical dystonia, diplopia and ptosis were reported. During treatment of strabismus with onabotulinumtoxinA, extraocular muscles adjacent to the injection site can be affected, causing vertical deviation (hypertropia or hypotropia). In 2,058 adults who received a total of 3,650 injections for horizontal strabismus, vertical deviation was reported in 17% of patients. The incidence of ptosis in patients treated for strabismus is thought to be related to the location of the injected muscles (1% after inferior rectus injection, 16% after horizontal rectus injection, 38% after superior rectus injection). Retrobulbar hemorrhages and compromised retinal circulation may occur during treatment of strabismus with onabotulinumtoxinA. In a series of 5,587 injections, retrobulbar ocular hemorrhage was reported in 0.3% of cases. Visual impairment (unspecified) and eyelid swelling (blepharedema, etc. after periocular injection) have been reported during postmarketing use. One case of acute ocular hypertension consistent with angle closure glaucoma was reported 1 day after injection for blepharospasm. Recovery occurred 4 months later after laser iridotomy and trabeculectomy. Vigorous treatment of any epithelial defect should be employed. Protective drops, ointment, therapeutic soft contact lenses, or closure of the eye by patching or other means may be required.[29334] [41123] [45602]

After using botulinum toxins types A and B, cases of distant spread of toxin effects, including respiratory arrest and death, that are suggestive of systemic botulism have been reported. Breathing difficulties may develop within hours to weeks after an injection. These effects have been seen in patients who received the medication for a variety of conditions and in a wide range of doses. The majority of adverse events in children have occurred after the treatment of cerebral palsy-associated limb spasticity. Several of these children required hospitalization and/or mechanical ventilation, and some cases were fatal. Adult cases have also been reported after use of botulinum toxin for the treatment of spasticity or cervical dystonia. In some cases, hospitalization was required with several patients requiring the placement of feeding tubes or mechanical ventilation. Treatment of cervical dystonia with onabotulinumtoxinA may weaken accessory neck muscles that aide in ventilation, resulting in a vital loss of breathing capacity in patients with respiratory disorders who are reliant upon these accessory muscles. Post-marketing reports have identified serious breathing difficulties, including respiratory failure, in cervical dystonia patients. Patients with pre-existing breathing difficulties may be more susceptible to respiratory complications following onabotulinumtoxinA injection. During evaluation of onabotulinumtoxinA in patients with upper limb spasticity and respiratory insufficiency or patients with detrusor overactivity associated with a neurologic condition and restrictive lung disease of neuromuscular etiology, the event rate in change of Forced Vital Capacity (FVC) 15% or more or 20% or more was generally greater in patients treated with onabotulinumtoxinA than in patients treated with placebo.[29334] The risk of distant spread of botulinum toxin after dermatologic use is not known. No definitive serious adverse events associated with dermatologic use at labeled doses have been identified with onabotulinumtoxinA.[41123]

Treatment with onabotulinumtoxinA may result in swallowing difficulties presenting within hours to weeks after injection. During safety studies in patients being treated for cervical dystonia, dysphagia was the most frequently reported adverse reaction (19%). Dysphagia was typically mild to moderate, but was also the most common severe adverse reaction reported. During clinical trials for chronic migraine, dysphagia was reported more frequently with onabotulinumtoxinA than placebo but at an incidence of less than 1%. Rare consequences of severe dysphagia include aspiration, dyspnea, pneumonitis, and the need to reestablish an airway. Dyspnea was reported in cervical dystonia studies. About 20% of cases of dysphagia were also reported to have dyspnea. Additionally, literature reports include a case of a female patient who developed brachial plexopathy two days after injection of 120 Units of onabotulinumtoxinA, and reports of dysphonia. Dyspnea and brachial plexopathy have been reported during postmarketing use. Dysphagia and symptomatic general weakness may be attributable to an extension of the pharmacology of onabotulinumtoxinA resulting from the spread of the toxin outside the injected muscles. Patients with pre-existing swallowing difficulties may be more susceptible to developing dysphagia and aspiration. Deaths as a result of severe dysphagia have been reported following onabotulinumtoxinA injection. Prolonged swallowing difficulties may require feeding tube assistance. Patients with smaller neck muscle mass or those who require bilateral injections into the sternocleidomastoid muscle are thought to be at higher risk for dysphagia. Injections into the levator scapulae may be associated with an increased risk of dysphagia. In addition, severe, sometimes fatal, adverse reactions including dysphagia and aspiration pneumonia, have been reported with the unapproved use of onobotulinumtoxinA. In several of the cases, patients had pre-existing dysphagia. These adverse reactions were not necessarily related to the spread of toxin but may have resulted from the administration to the site of injection and/or adjacent structures.[29334]

Formation of neutralizing antibodies to onabotulinumtoxinA may reduce the effectiveness of the toxin by inactivating the biological activity of the toxin. The critical factors for neutralizing antibody formation have not been well characterized. The results from some studies suggest that injections at more frequent intervals or at higher doses may lead to a 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. In a long-term study of patients with cervical dystonia (n = 326), 4 patients had positive antibody tests. All 4 of the patients responded to onabotulinumtoxinA treatment at the time of the positive antibody test; however, 3 of the patients developed clinical resistance after subsequent treatment. In pediatric patients with lower limb spasticity, neutralizing antibodies developed in 2 of 264 patients (0.8%); both patients continued to experience clinical benefit.[29334] Patients with antibodies to onabotulinumtoxinA may benefit from rimabotulinumtoxinB injections because there is no cross-reactivity between type A and type B toxins.

There have been reports of serious and/or immediate hypersensitivity reactions after use of onabotulinumtoxinA; these reactions include anaphylactoid reactions, serum sickness, urticaria, soft tissue edema, and dyspnea. One fatal case of anaphylaxis has been reported in which lidocaine was used as the diluent; the causal agent cannot be reliably determined. During clinical trial evaluation for primary axillary hyperhidrosis, pruritus was reported in 3% to 10% of patients. Diffuse skin rash (unspecified) was reported in patients treated with onabotulinumtoxinA for blepharospasm; however, the frequency is unknown. During postmarketing use, there have been spontaneous reports of death, sometimes associated with anaphylaxis. In addition, the following adverse reactions have been reported since the drug has been marketed and a causal relationship to onabotulinumtoxinA is unknown: skin rash (including erythema multiforme, urticaria, and psoriaform rash), pruritus, and allergic reaction. If a hypersensitivity reaction occurs, discontinue onabotulinumtoxinA and institute appropriate medical therapy immediately.[29334]

Upper respiratory tract infections (2% to 12% in adults; 10% to 17% in pediatrics) including bronchitis (2% to 3%) have been reported in people receiving onabotulinumtoxinA for cervical dystonia and limb spasticity. This adverse effect appears to be dose-related; injection into the levator scapulae may be associated with an increased risk. Other infections or related symptoms reported in 2% to 10% of adults treated for cervical dystonia include increased cough, influenza (flu syndrome), rhinitis, and fever. During chronic migraine trials, bronchitis (3%) and ocular infection (less than 1%) were reported. Infections and related symptoms reported in 3% to 10% of adults treated for primary axillary hyperhidrosis were infection (unspecified), pharyngitis, influenza (flu syndrome), and fever. Rhinorrhea (0% to 4%) and nasal congestion (0% to 3%) were reported during pediatric limb spasticity trials. Urinary tract infection (18%) was reported during overactive bladder trials, with a higher incidence observed in patients with diabetes (31% vs. 26%); UTI was also reported in 24% to 49% of adults and 7% of pediatric patients treated for detrusor overactivity. Additionally, bacteriuria (20%) and leukocyturia (7%) were reported in pediatric patients with detrusor overactivity. There have been spontaneous reports of death associated with pneumonia after onabotulinumtoxinA treatment.[29334] Upper respiratory tract infections (10% to 17%) have been reported in onabotulinumtoxinA pediatric upper limb spacticity trials. Rhinorrhea (0% to 4%) and nasal congestion (0% to 3%) were also reported during pediatric limb spasticity trials. Bronchitis was reported in 2% to 3% of adults receiving onabotulinumtoxinA for cervical dystonia, limb spasticity, and chronic migraine prophylaxis. Upper respiratory tract infections appear to be dose-related; injection into the levator scapulae may be associated with an increased risk. Urinary tract infection (7%), bacteriuria (20%), and leukocyturia (7%) were reported in pediatric patients treated for detrusor overactivity. Other infections or related symptoms reported in 2% to 10% of adults treated for cervical dystonia include increased cough, influenza (flu syndrome), rhinitis, and fever. During chronic migraine trials in adults, ocular infection (less than 1%) was reported. Infections and related symptoms reported in 3% to 10% of adults treated for primary axillary hyperhidrosis were infection (unspecified), pharyngitis, influenza (flu syndrome), and fever. There have been spontaneous reports of death associated with pneumonia after onabotulinumtoxinA treatment.[29334] [41123] Commercial preparations of onabotulinumtoxinA contain 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 infection. A theoretical risk for transmission of Creutzfeldt-Jakob disease (CJD) is also considered extremely remote. No cases of transmission of viral diseases or CJD have ever been reported for albumin or albumin contained in other licensed products. Proper screening and testing of donated albumin has reduced the risk of transmission of infectious agents; however, none of the processes are completely effective. There is a possibility that unknown infectious agents may be present. Botulism toxin should be given only if a benefit is expected. All infections thought by a physician to have been possibly transmitted by this medication should be reported to the manufacturer.[29334] [41123]

During controlled trials for the treatment of chronic migraines, hypertension occurred in 2% of patients receiving onabotulinumtoxinA and 1% of patients receiving placebo. There have been rare reports of serious cardiac effects, including arrhythmia exacerbation and myocardial infarction, some with fatal outcomes. Some of these patients had risk factors including cardiovascular disease. The exact relationship of these events to the onabotulinumtoxinA injection has not been established.[29334]

Local weakness of the injected muscle(s) represents the expected pharmacological action of onabotulinumtoxinA. However, weakness of adjacent muscles may also occur due to the spread of toxin. During clinical trials of onabotulinumtoxinA (200 units) for detrusor overactivity associated with a neurologic condition, the following musculoskeletal effects occurred in patients receiving onabotulinumtoxinA at any time after the initial injection and prior to re-injection or study exit (median duration of 44 weeks of exposure): myasthenia (4%) and muscle spasm (2%). During controlled trials for the treatment of chronic migraines, the following musculoskeletal effects occurred in at least 2% of patients receiving onabotulinumtoxinA and more frequently than in patients receiving placebo: neck pain (9% vs. 3%), musculoskeletal stiffness (4% vs. 1%), myasthenia (4% vs. less than 1%), myalgia (3% vs. 1%), musculoskeletal pain (3% vs. 1%), and muscle spasms (2% vs. 1%). Jaw pain was reported more frequently with onabotulinumtoxinA than placebo but at an incidence of less than 1%. Musculoskeletal effects reported in cervical dystonia patients during clinical trials included neck pain (11%), back pain (2% to 10%), hypertonia (2% to 10%), and stiffness (unspecified). Myasthenia was reported more frequently as an adverse reaction in patients treated for upper limb spasticity with onabotulinumtoxinA (0% at 251 to 360 units, 4% at 150 to 250 units, 2% at less than 150 units) versus placebo (1%); extremity pain also occurred more frequently in the active treatment groups (6% at 251 to 360 units, 5% at 150 to 250 units, 9% at less than 150 units) than the placebo group (4%). Oropharyngeal pain was reported in 2% or less of pediatric patients treated for lower limb spasticity. The most frequently reported pain-related effects (3% to 10%) in patients being treated for primary axillary hyperhidrosis were neck pain and back pain. Myasthenia and myalgia have been reported during postmarketing use.[29334]

During clinical trials of onabotulinumtoxinA (200 units) for detrusor overactivity associated with a neurologic condition, fatigue was reported in 4% of patients receiving active treatment versus 1% of patients receiving placebo within the first 12 weeks after injection. General effects observed in study patients at any time after the initial injection and prior to re-injection or study exit (median duration of 44 weeks of exposure) included fatigue (6%) and falls (3%). Fatigue was reported more frequently as an adverse reaction in patients treated for upper limb spasticity with onabotulinumtoxinA (3% at 251 to 360 units, 2% at 150 to 250 units, 2% at less than 150 units) than placebo (0%). During safety studies of onabotulinumtoxinA for cervical dystonia, general effects reported in 2% to 10% of patients in order of decreasing incidence included asthenia and dysarthria (speech disorder); numbness (unspecified) has also been reported. Malaise has occurred during postmarketing use. Asthenia, difficulties with speech or swallowing, or numbness can be symptoms of distal toxin spread in patients receiving onabotulinumtoxinA. In addition, severe adverse reactions including excessive weakness have been reported with the unapproved use of onabotulinumtoxinA; these adverse reactions were not necessarily related to the spread of toxin but may have resulted from the administration to the site of injection and/or adjacent structures.[29334]

During clinical trials of onabotulinumtoxinA for overactive bladder (100 units) and detrusor overactivity associated with a neurologic condition (200 units), the following genitourinary (GU) effects were reported more frequently in adult patients receiving active treatment than placebo within the first 12 weeks after injection: urinary retention (100 units, 6%; 200 units, 17%; placebo, 3%), urinary tract infection (100 units, 18%; 200 units, 24%; placebo, 6% to 17%), dysuria (100 units, 9%; placebo, 7%), and hematuria (200 units, 4%; placebo, 3%). Urinary tract infection (7%), bacteriuria (20%), leukocyturia (7%), and hematuria (3%) were reported in pediatric patients with detrusor overactivity. Other GU effects reported any time during the 200 units neurogenic bladder study (median duration of 44 weeks of exposure) included: urinary tract infection (49%), urinary retention (17%), and dysuria (4%). Intradetrusor injection is contraindicated in patients with urinary tract infection (UTI), and patients with urinary retention (post-void residual (PVR) more than 200 mL) who are not routinely performing clean intermittent self-catheterization (CIC). Two studies have evaluated the need for catheterization after intradetrusor injection of onabotulinumtoxinA. The first study included patients with overactive bladder, in which 6.5% of drug recipients required catheterization (median duration of 63 days) compared to 0.4% of patients receiving placebo (median duration 11 days). The second study included patients with detrusor overactivity associated with multiple sclerosis (MS) or spinal cord injury (SCI); the percentages of patients not using CIC at baseline and then catheterizing for urinary retention post-treatment compared to placebo were as follows: MS patients (31% vs. 5%) and SCI patients (27% vs. 19%). The percentage of patients not using CIC at baseline and then catheterizing for urinary retention at any time during the complete treatment cycle was 30.6% of those receiving the drug and 6.7% of those receiving placebo. Among non-catheterizing MS patients with urinary incontinence due to detrusor overactivity, catheterization for urinary retention was initiated in 15.2% of patients after treatment with 100 units onabotulinumtoxinA compared to 2.6% of those on placebo at any time during the treatment cycle. The median duration for post-injection catheterization for those who developed urinary retention was 64 days for onabotulinumtoxinA and 2 days for placebo.[29334]

Constipation was reported in 4% of adult patients during clinical trials for detrusor overactivity; it was also reported in 0% to 3% of pediatric patients treated for limb spasticity. Xerostomia (2% to 10%), nausea (2% to 10% adults; 0% to 4% pediatrics), and anorexia (2% or less pediatrics) have also been reported. Abdominal pain and diarrhea have been associated with postmarketing use.[29334]

During clinical trials of onabotulinumtoxinA (200 Units) for detrusor overactivity associated with a neurologic condition, insomnia was reported in 2% of patients receiving active treatment versus 0% of patients receiving placebo within 12 weeks after injection. The following CNS effects were reported between the initial injection and prior to re-injection or study exit (median duration of 44 weeks of exposure): gait disturbance (3%) and insomnia (3%). The incidence of autonomic dysreflexia was greater in the active treatment group than the placebo group (1.5% vs. 0.4%). During controlled trials for the treatment of chronic migraines, the following CNS effects occurred in at least 2% of patients receiving onabotulinumtoxinA and more frequently than in patients receiving placebo: headache (5% vs. 3%), migraine (4% vs. 3%), and facial paresis (2% vs. 0%). Severe migraine exacerbation requiring hospitalization occurred in about 1% of patients receiving active treatment versus 0.3% of patients receiving placebo. Vertigo was reported more frequently with onabotulinumtoxinA than placebo but at an incidence of less than 1%. During safety studies of onabotulinumtoxinA for cervical dystonia, CNS effects included headache (11%), dizziness (2% to 10%), and drowsiness (2% to 10%). The most frequently reported CNS effects (3% to 10%) in patients being treated for primary axillary hyperhidrosis were headache and anxiety. In patients being treated for blepharospasm, focal facial paralysis, syncope, and exacerbation of myasthenia gravis have been reported; however, the frequencies are unknown. Facial palsy, facial paresis, hypoesthesia, paresthesias, vertigo, and radiculopathy have occurred during postmarketing use. Distant spread of the toxin during use may result in paresis or other CNS effects not expected with the indication for use and administration techniques. In addition, severe adverse reactions including excessive weakness, difficulty swallowing, and aspiration, with some adverse reactions associated with fatal outcomes, have been reported with the unapproved use of onabotulinumtoxinA; the adverse reactions were not necessarily related to the spread of toxin but may have resulted from the administration to the site of injection and/or adjacent structures.[29334]

An injection site reaction may occur (e.g., localized pain, infection, inflammation, erythema, tenderness and/or bruising or ecchymosis) after injection of onabotulinumtoxinA. Certain injection techniques may minimize bruising in tender areas (see specific injection techniques for the indication).[29334] [41123] Needle-related pain or anxiety may result in vasovagal responses, including syncope or hypotension. Injection site pain (2% to 10% in adults; 2% to 4% in pediatrics) and erythema (2% or less in pediatrics) has been reported during clinical trials. Soreness (2% to 10%) and bleeding (3% to 10%) at the injection site were reported in cervical dystonia and axillary hyperhidrosis trials, respectively. In patients being treated for blepharospasm, local swelling of the eyelid skin lasting for several days after eyelid injection has been reported; however, the frequency is unknown. Ecchymosis can occur easily in the soft eyelid tissue. Localized numbness has been reported with postmarketing use.[29334]

Otic effects, including hypoacusis and tinnitus, have been reported during postmarketing use of onabotulinumtoxinA; causality has not been established.[29334]

During clinical trial evaluation of onabotulinumtoxinA for primary axillary hyperhidrosis, increased non-axillary sweating occurred in 3% to 10% of patients. Hyperhidrosis has been reported during postmarketing use.[29334]

Seizures were reported in 5% of pediatric patients receiving 6 units/kg and 1% of those receiving 3 units/kg onabotulinumtoxinA for limb spasticity during clinical trials. New onset or recurrent seizures have been reported with postmarketing use, typically in patients predisposed to experiencing these events. An exact relationship has not been established. Ligament sprain (1% to 2%) and skin abrasion (2% or less) have been reported during pediatric trials for lower limb spasticity, perhaps due to injury.[29334]

Anti-platelet therapy should be discontinued at least 3 days prior to onabotulinumtoxinA treatment in individuals with bladder dysfunction or with detrusor overactivity associated with a neurologic condition. Individuals on anticoagulant therapy need to be managed appropriately to reduce the risk of bleeding due to the injection procedures.[29334]

Postmarketing safety data suggest injection of botulinum toxins may, in some cases, result in the distant spread of toxin effects resulting in systemic symptoms (e.g., asthenia, generalized muscle weakness, diplopia, ptosis, trouble swallowing, dysphonia, dysarthria, urinary incontinence, breathing difficulties). Advise patients or caregivers to seek immediate medical care if swallowing, speech, or respiratory disorders occur. These symptoms have been reported hours to weeks after injection. There have been reports of death related to the spread of toxin effects. Risk is probably greatest in children treated for spasticity, but symptoms can also occur in adults treated for other indications, especially in those who have underlying conditions predisposing them to these effects. In unapproved uses and in approved indications, cases of spread of effect have been reported at doses comparable to those used to treat cervical dystonia and spasticity and at lower doses.[29334] [41123]

An intradetrusor injection is contraindicated when a urinary tract infection (UTI) is present. Use of onabotulinumtoxinA for the treatment of overactive bladder in people with history of more than 2 UTIs in the past 6 months or those on chronic antibiotics for UTIs should only be considered when the potential benefits outweigh the risks; clinical trials for treating overactive bladder with onabotulinumtoxinA excluded such patients.[29334]

Intradetrusor injection of onabotulinumtoxinA is contraindicated in individuals with urinary retention (post-void residuals (PVR) greater than 200 mL) who are not routinely performing clean intermittent self-catheterization (CIC). Following treatment, individuals who are not catheterizing should have PVR assessed within 2 weeks of injection and periodically as needed for up to 12 weeks. Begin catheterization if PVR increases to more than 200 mL and continue until PVR is less than 200 mL. Treatment should be avoided in individuals not able or unwilling to begin catheterization, if needed. Individuals with diabetes mellitus treated with onabotulinumtoxinA were more likely to develop urinary retention than those without diabetes.[29334]

Treatment with onabotulinumtoxinA can result in swallowing or breathing difficulties. Individuals with pre-existing dysphagia or respiratory insufficiency, such as asthma or emphysema, may be more susceptible to these complications. These reactions can occur within hours to weeks after injection with onabotulinumtoxinA. Individuals with respiratory insufficiency treated with onabotulinumtoxinA for upper limb spasticity should be closely monitored, as they may experience greater, though not statistically significant, declines in pulmonary function and higher incidences of upper respiratory tract infections; caution is also advised when administering to individuals with neuromuscular restrictive lung disease, as they may be at increased risk of significant FVC reductions. Individuals with cervical dystonia should be informed of the possibility of experiencing dysphagia, which is typically mild to moderate, but could be severe after receipt of onabotulinumtoxinA. Additionally, when treating for cervical dystonia, individuals with smaller neck muscle mass or those who require bilateral injections into the sternocleidomastoid muscle are at greater risk. Limiting the dose injected into the sternocleidomastoid muscle may reduce the occurrence of dysphagia. Injections into the levator scapulae may be associated with an increased risk of upper respiratory infection and dysphagia. Rare consequences of severe dysphagia include aspiration, dyspnea, pneumonia, and the need to reestablish an airway. In some individuals, symptoms of dysphagia or dyspnea may be the result of distal toxin spread after administration. Serious, sometimes fatal, adverse reactions, including excessive weakness, dysphagia, and aspiration pneumonia, have been reported in individuals receiving onabotulinumtoxinA for unapproved uses and may be related to the site or technique of administration for the unapproved use; in several of the cases involved individuals with pre-existing dysphagia or other significant disabilities.[29334] [41123]

Use onabotulinumtoxinA with caution in people with peripheral motor neuropathic diseases, amyotrophic lateral sclerosis (ALS), or neuromuscular junction disorders (myasthenia gravis or Lambert-Eaton syndrome). Individuals with known or unrecognized neuromuscular disease or neuromuscular junction disorders may be at increased risk of clinically significant systemic effects including generalized weakness, diplopia, ptosis, dysphonia, dysarthria, severe dysphagia, and respiratory compromise from typical doses of onabotulinumtoxinA.[29334] [41123]

OnabotulinumtoxinA should be used cautiously in individuals with cardiovascular disease. There have been rare reports of adverse reactions involving the cardiovascular system, including arrhythmia and myocardial infarction, some with fatal outcomes. Some of these patients had risk factors including cardiovascular disease. The exact relationship of these events to the botulinum toxin injection has not been established.[29334] [41123]

There are no human data on the developmental risk associated with the use of onabotulinumtoxinA during pregnancy. In animal studies, onabotulinumtoxinA resulted in adverse effects on fetal growth (decreased fetal weight and skeletal ossification) when given at doses of 8 or 16 units/kg. The no-effect dose for developmental toxicity in these studies (4 units/kg) is approximately equal to the human dose of 400 units, on a body weight basis (units/kg).[29334] [41123] A retrospective study of a pharmacovigilance database evaluated 397 onabotulinumtoxinA exposures from 3 months prior to conception through pregnancy. The rate of major fetal defects among live births was consistent with rates observed in the general population.[72339]

There are no data on the presence of onabotulinumtoxinA in human or animal milk, its effects on the breastfed child, or its effects on milk production. Consider the benefits of breast-feeding, the patient's clinical need for treatment, and any potential adverse effects on the breast-fed child from the medication or from the underlying maternal medical condition. OnabotulinumtoxinA is not detectable systemically after intramuscular use, thus excretion into human milk is considered unlikely.[29334] [41123]

Caution all patients to avoid driving or operating machinery or performing other activities requiring coordination and concentration if they experience a loss of strength, muscle weakness, blurred vision, or drooping eyelids as a result of onabotulinumtoxinA therapy.[29334] [41123]