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OnabotulinumtoxinA
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The initial recommended dose is 1.25—2.5 units (0.05—0.1 mL) injected at each site. Generally, the initial effect of the injections is seen within 3 days and reaches a peak 1—2 weeks posttreatment. Each treatment lasts approximately 3 months, after which the procedure can be repeated. At repeat treatment sessions, the dose may be increased up to 2-fold if the response from the initial treatment is considered insufficient, which is usually defined as an effect that does not last longer than 2 months. Little benefit appears to be obtained from injecting more than 5 units per site. Some tolerance may be observed when the toxin is administered any more frequently than every 3 months, and it is rare to have the effect be permanent. The cumulative dose in a 30-day period should not exceed 200 units.
Phase III studies for cervical dystonia involved patients who had extended histories of receiving and tolerating onabotulinumtoxinA injections, with prior individualized dosage adjustments. The mean dose in phase III studies was 236 units IM (range: 198—300 units) divided among the affected muscles. Dosing in initial and sequential treatment sessions should be tailored to the individual patient based on head and neck position, localization of pain, muscle hypertrophy, patient response, and adverse event history. Patients without prior use of botulinum toxin should be started with a lower initial dose, with subsequent dosing adjusted based on individual response. Limiting the total dose injected into the sternocleidomastoid muscles to 100 units or less may decrease the occurrence of dysphagia.
NOTE: Injection should be carried out only with electromyographic guidance. The toxin must be suitably diluted, and the volume injected should be between 0.05—0.15 mL per muscle, dependent on the extent of strabismus. Use the lower doses for small deviations and the larger doses only for large deviations. Initial doses typically create paralysis of injected muscles beginning 1—2 days after injection and increasing in intensity during the first week. The paralysis lasts for 2—6 weeks and gradually resolves over a similar time period. Overcorrections lasting longer than 6 months rarely occur. About 50% of patients will require subsequent doses because of inadequate paralytic response to the initial dose, because of mechanical factors such as large deviations or restrictions, or because of the lack of binocular motor fusion to stabilize the alignment.
1.25—2.5 units in any 1 muscle.
2.5—5 units in any 1 muscle.
1.25—2.5 units in the medial rectus muscle.
Patients should be reexamined 7—14 days after each injection to assess the effect of that dose. Patients experiencing adequate paralysis of the target muscle who require subsequent injections should receive a dose comparable to the initial dose. For patients experiencing incomplete paralysis of the target muscle, subsequent doses may be increased up to 2-fold compared to the previously administered dose. Subsequent injections should not be given until the effects of the previous dose have dissipated as evidenced by substantial function in the injected and adjacent muscles. The maximum recommended dose as a single injection for any 1 muscle is 25 units.
The approved dose is 20 units total dose divided equally (4 units/injection) and injected intramuscularly at 5 sites, 2 injections in each corrugator muscle and 1 injection in the procerus muscle; the duration of effect is expected to last 3 to 4 months; more frequent use is not recommended. For simultaneous treatment with glabellar lines, the dose is 24 units for lateral canthal lines and 20 units for glabellar lines, with a total dose of 44 units. The response rate was lower in subjects aged 65 years and older compared with younger subjects in clinical studies.[41123] Higher doses have been used in clinical practice; women typically receive 25 units of onabotulinumtoxinA per session in a 5-step process consisting of 2 injections on each side: 1 injection each to paralyze the corrugator superciliaris muscle and the orbicularis muscle and a fifth injection of 5 units made into the middle of the procerus muscle. Men require 2 additional injections of 5 units on each side into the orbicularis, just above the eyebrow in the mid pupillary line making the total dose 35 units. Successful therapy is indicated by muscle weakening 24 to 48 hours after injection and peaking at up to 7 days. Retreatment depends upon how deep and pronounced the glabellar furrow is. Patients without deep furrows typically should return for reinjection when they notice return of brow wrinkling. For those with deep glabellar furrow, reinjection every 3 to 4 months is recommended to allow the furrow to drop out, which generally requires 12 months. Once the forehead is smooth, these patients should return only when they notice a return of muscle movement.[26405] [26406] [26407] [26408] [26409]
Inject 4 units into 5 sites in the frontalis muscle, for a total of 20 units. Place the 5 injections at the intersection of the horizontal treatment. Treat forehead lines in conjunction with glabellar lines to minimize the potential for brow ptosis. The total recommended dose for forehead lines (20 units) in conjunction with glabellar lines (20 units) is 40 units. For simultaneous treatment with lateral canthal lines, the total dose is 64 units, comprised of 20 units for forehead lines, 20 units for glabellar lines, and 24 units for lateral canthal lines.[41123]
Inject 4 units into 3 sites per side (6 total injection points) in the lateral orbicularis oculi muscle for a total of 24 units, or 12 units per side. The first injection should be approximately 1.5 to 2 cm temporal to the lateral canthus and just temporal to the orbital rim. For simultaneous treatment with glabellar lines, the dose is 24 units for lateral canthal lines and 20 units for glabellar lines, with a total dose of 44 units. The safety and efficacy of dosing more frequently than every 3 months has not been evaluated. The response rate was lower in subjects aged 65 years and older compared with younger subjects in clinical studies.[41123]
Inject 2 units into 4 sites in the upper segment of platysma muscle, below the jawline on each side. For each side, administer the 4 jawline injections to the upper platysma muscle, approximately 1 to 2 cm inferior and parallel to the lower mandibular border. Ensure the anterior injection site is in line with the oral commissure, and the posterior injection is slightly anterior to the angle of the mandible. Administer the remaining 2 injections equidistant (approximately 1 to 2 cm apart) between the anterior and posterior injection points. In addition, inject 1 unit into 5 sites along each vertical neck band, 1 to 2 vertical neck bands per side. Distribute 5 injections vertically approximately 1 to 2 cm apart. Ensure the most superior injection site is approximately 1 to 2 cm inferior to the jawline injections. Depending on severity, the total dose may be 26 units (1 band per side), 31 units (1 band on one side, 2 bands on the other side), or 36 units (2 bands per side).[41123]
OnabotulinumtoxinA is used as a muscle weakener in treating wrinkles in areas other than the glabella. These wrinkles are the result of physiologically important facial muscles and complete paralysis may create unacceptable functional deficits. Typically, 1 to 2 units per site is injected subcutaneously.[26405] [26406] [26407] [26408] [26409]
20 to 25 units by prograde or retrograde injection into each of the 4 lower esophageal sphincter (LES) quadrants. Max: 100 units/course; higher doses have not been shown to be more effective. Repeat injections may be needed.[26410] [55875] [65920] [66609] Residual LES tone of less than 18 mmHg after botulinum injection is a predictor of a good response.[26410] Reserve botulinum injections for individuals who are not candidates for other definitive therapies.[65920] [66609]
75 to 400 units IM divided among the affected muscles. Individualize dose based on size, number and location of muscles involved, severity of spasticity, presence of local muscle weakness, response to previous treatment, and history of adverse events. Use the lowest recommended starting dose; no more than 50 units/site should generally be administered. The recommended dosage per muscle area is as follows: biceps brachii: 60 to 200 units IM divided in 2 to 4 sites; brachialis: 30 to 50 units IM divided in 1 to 2 sites; brachioradialis: 45 to 75 units IM divided in 1 to 2 sites; flexor capri radialis and ulnaris: 12.5 to 50 units IM in 1 site; flexor digitorum profundus and sublimis: 30 to 50 units IM in 1 site; flexor pollicis brevis/opponens pollicis: 5 to 25 units IM in 1 site; flexor pollicis longus and adductor pollicis: 20 units IM in 1 site; lumbricals/interossei: 5 to 10 units IM in 1 site; pronator quadratus: 10 to 50 units IM in 1 site; pronator teres: 15 to 25 units IM in 1 site. May repeat treatment when the effect of a previous injection has diminished, but generally no sooner than 12 weeks after the previous injection; alterations in the dose and the muscles to be injected may be necessary based on the degree and pattern of muscle spasticity at the time of re-injection.[29334] Guidelines consider onabotulinumtoxinA to be effective for the treatment of upper limb spasticity and probably superior to tizanidine for reducing upper extremity tone. In a placebo-controlled trial, onabotulinumtoxinA was superior to tizanidine for improving wrist and finger flexor tone.[61468]
3 to 6 units/kg (Max: 200 units) IM divided among the affected muscles. Max cumulative dose per 3-month period: 10 units/kg or 340 units, whichever is less. Individualize dosage based on size, number and location of muscles involved, severity of spasticity, presence of local muscle weakness, response to previous treatment, and history of adverse events. Use the lowest recommended starting dose; no more than 50 units/site should generally be administered. The recommended dosage per muscle area is as follows: biceps brachii: 1.5 to 3 units/kg IM divided in 4 sites; brachialis, flexor carpi radialis, or flexor carpi ulnaris: 1 to 2 units/kg IM divided in 2 sites; brachioradialis, flexor digitorum profundus, or flexor digitorum sublimis: 0.5 to 1 unit/kg IM divided in 2 sites. May repeat treatment when the effect of a previous injection has diminished, but generally no sooner than 12 weeks after the previous injection; alterations in the dose and the muscles to be injected may be necessary based on the degree and pattern of muscle spasticity at the time of re-injection.[29334]
300 to 400 units IM divided among 5 muscles. Individualize dosage based on size, number and location of muscles involved, severity of spasticity, presence of local muscle weakness, response to previous treatment, and history of adverse events. Use the lowest recommended starting dose; no more than 50 units/site should generally be administered. The recommended dosage per muscle area is as follows: gastrocnemius medial head and lateral head, soleus, and tibialis posterior: 75 units IM divided in 3 sites; flexor hallucis longus and digitorum longus: 50 units IM divided in 2 sites. May repeat treatment when the effect of a previous injection has diminished, but generally no sooner than 12 weeks after the previous injection; alterations in the dose and the muscles to be injected may be necessary based on the degree and pattern of muscle spasticity at the time of re-injection.[29334] OnabotulinumtoxinA has demonstrated significant reductions in lower extremity muscle tone but inconsistent results with functional outcomes, suggesting that functional gains are highly patient-specific. Guidelines consider onabotulinumtoxinA to be effective for the treatment of lower extremity spasticity.[61468]
4 to 8 units/kg (Max: 300 units) IM divided among the affected muscles. Max cumulative dose per 3-month period: 10 units/kg or 340 units, whichever is less. Individual dosage based on size, number and location of muscles involved, severity of spasticity, presence of local muscle weakness, patient response to previous treatment, and history of adverse events. Use the lowest recommended starting dose; no more than 50 units/site should generally be administered. The recommended dosage per muscle area is as follows: gastrocnemius medial and lateral head, soleus, and tibialis posterior: 1 to 2 units/kg IM divided in 2 sites. May repeat treatment when the effect of a previous injection has diminished, but generally no sooner than 12 weeks after the previous injection; alterations in the dose and the muscles to be injected may be necessary based on the degree and pattern of muscle spasticity at the time of re-injection.[29334]
4 units/kg/dose IM (Max: 200 units/treatment) every 3 months was used in a study of 207 pediatric patients with cerebral palsy exhibiting equinus foot deformity; 155 patients received at least 1 year of treatment. The total calculated dose was diluted to a volume of 4 mL for hemiplegic patients and 8 mL for diplegic patients in order to keep the total volume injected constant. At 6 weeks, 46% of patients (n = 185) had improvement in their gait pattern and ankle position. After 2 years, the improvements were maintained in nearly 50% of patients.[26756] Based on previous studies by the lead author, an injection of 2 mL was injected per muscle site (2 mL in the medial and 2 mL in the lateral gastrocnemius of each involved leg).[26757] [26758]
NOTE: Safety and efficacy for the treatment of hyperhidrosis in other body areas have not ben established. Use for palmar hyperhidrosis may lead to weakness of hand muscles and use for facial hyperhidrosis may lead to blepharoptosis.[29334]
NOTE: Evaluate patients for potential causes of secondary hyperhidrosis (e.g. hyperthyroidism) prior to initiating therapy.
50 units (diluted to 25 units/mL) injected intradermally to each axilla; distribute dose in 0.1—0.2 mL aliquots at multiple (10—15) sites approximately 1—2 cm apart. Re-treat when clinical effect of previous injection diminishes. Prior to dose administration, define hyperhidrotic area to be injected using standard staining techniques, e.g., Minor's Iodine-Starch Test.[29334]
Safety and efficacy have not been established.
In one randomized, placebo-controlled trial, a single treatment of 50 units was injected into each parotid gland without ultrasound guidance. Compared to baseline measurements, there was significant improvement at 1 month in the objective measure of saliva production as well as subjective outcome measures including the visual analogue score of drooling frequency (VAS-D), the assessment of patient embarrassment within the familial (VAS-FD) and social (VAS-SD) context, and the drooling subscore of the Unified Parkinson Disease Rating Scale (UPDRS), but not the UPDRS dysphagia subscore. Assessment of global satisfaction also favored the active treatment group (88% vs. 31%). Duration of treatment effect beyond 1 month and efficacy of repeated treatments were not examined.[58100] In a separate study including 2 patients with Parkinson disease, parotid gland doses ranged from 15 to 40 units (mean: 28 units/gland) into 2 injection sites. The dose administered in the submandibular glands ranged from 10 to 15 units/gland (mean: 12 units/gland) using ultrasound guidance. The total dose for each patient was calculated based on the rate of salivation before treatment and the patient's body weight, and ranged from 50 to 100 units (mean: 77 units). Nine patients (90%) reported a lessening in hypersalivation after treatment.[28130] In one dose-finding study including 12 patients with Parkinson disease, low intraparotid doses (i.e., 18.75 to 37.5 units) had a less robust effect, with only the 75-unit total dose achieving the primary end point of a significant reduction in sialorrhea (approximately 50%). Injections were repeated 3 months later. There was a stable reduction of drooling for 1 month after the injection with a partial relapse about 3 months after treatment.[28128] Ultrasound-guided injections appear to be associated with superior results compared to administration without ultrasound guidance as measured by quantitative saliva assessments.[58577]
7.5 to 40 units intraglandular in each parotid gland and 5 to 30 units intraglandular in each submandibular gland. May repeat treatment based on clinical response, but generally no sooner than every 12 to 16 weeks.[28130] [69817] [69839] [69840]
In one controlled trial of children aged 6 to 16 years, a total of 2 units/kg up to a maximum of 70 units total dose was distributed into the parotid and submandibular glands as follows: 1.4 units/kg divided between the 2 parotid glands, and 0.6 units/kg divided between the 2 submandibular glands with ultrasound guidance. The dose used was weight based and ranged from 31.4 to70 units (mean: 50.9 units) per child. Each child received 6 injections: 1 into the center of each submandibular gland and 2 into each parotid gland. Drooling frequency and severity showed statistically significant reductions at 4 weeks and 12 weeks.[58576] In a separate trial (n = 24), children aged 21 months to 7 years received treatment with 50 units of botulinum toxin A or placebo into each parotid gland (total 100 units) without ultrasound guidance. A second injection of either 70 units of botulinum toxin A or placebo into each parotid gland (total 140 units) was given 4 months later. There was a significant reduction in the frequency and severity of drooling in the active treatment group compared to placebo. Only 2 patients experienced a transient increase in drooling after treatment with the drug.[58575]
155 units IM as 5 units/injection divided across 7 specific head and neck muscle areas and 31 injection sites. The recommended doses per muscle area are as follows: frontalis: 20 units divided in 4 sites; corrugator: 10 units divided in 2 sites; procerus: 5 units in 1 site; occipitalis: 30 units divided in 6 sites; temporalis: 40 units divided in 8 sites; trapezius: 30 units divided in 6 sites; cervical paraspinal muscle group: 20 units divided in 4 sites. Administer bilaterally to each muscle/muscle group except to the procerus muscle, which is injected once at the midline. Repeat every 12 weeks.[29334] Guidelines classify onbotulinumtoxinA as having established efficacy for chronic migraine prophylaxis.[57981] [61468] [69288] [70645]
200 units IM per treatment injected into the detrusor muscle via a flexible or rigid cystoscope, avoiding the trigone. Insert the needle approximately 2 mm into the detrusor, and space 30 injections of 1 mL (approximately 67 units/mL) each about 1 cm apart. Inject approximately 1 mL of sterile normal saline for the final injection to assure the full dose is delivered to the bladder. Consider re-injection when the clinical effect diminishes (median time to retreatment: 42 to 48 weeks), but no sooner than 12 weeks.[29334]
200 units IM per treatment injected into the detrusor muscle via a flexible or rigid cystoscope, avoiding the trigone. Insert the needle approximately 2 mm into the detrusor, and space 20 injections of 0.5 mL (10 units/0.5 mL) each about 1 cm apart. Inject approximately 1 mL of sterile normal saline for the final injection to assure the full dose is delivered to the bladder. Consider re-injection when the clinical effect diminishes (median time to retreatment: 30 weeks), but no sooner than 12 weeks.[29334]
6 units/kg IM per treatment injected into the detrusor muscle via a flexible or rigid cystoscope, avoiding the trigone. Insert the needle approximately 2 mm into the detrusor, and space 20 injections of 0.5 mL each about 1 cm apart. Inject approximately 1 mL of sterile normal saline for the final injection to assure the full dose is delivered to the bladder. Consider re-injection when the clinical effect diminishes (median time to retreatment: 30 weeks), but no sooner than 12 weeks.[29334]
The recommended and maximum dose is 100 units IM per treatment injected into the detrusor muscle via a flexible or rigid cystoscope, avoiding the trigone. The injection needle should be filled (primed) with approximately 1 mL of reconstituted drug prior to the start of the injection to remove any air. The needle should be inserted approximately 2 mm into the detrusor, and 20 injections of 0.5 mL each should be spaced about 1 cm apart. For the final injection, approximately 1 mL of sterile normal saline should be injected so the full dose is administered. The bladder should be instilled with enough saline to achieve adequate visualization for the injection, but avoid overdistention. Following the injections, the saline used for visualization should be drained. The patient should be observed for at least 30 minutes after the injection and until a spontaneous void has occurred. Per individual site practice, intravesical installation of diluted local anesthetic, with or without sedation, may be administered prior to the injection. Retreatment for diminished effectiveness should be considered no sooner than 12 weeks from the previous bladder injection. Intradetrusor injection is contraindicated in patients with urinary tract infection (UTI), and patients with urinary retention or postvoid residuals (PVR) greater than 200 mL who are not routinely performing clean intermittent self-catheterizations (CIC).[29334] Per guidelines, intradetrusor onabotulinumtoxina is a treatment option for patients with an inadequate response or intolerable side effects to pharmacotherapy or behavioral therapy and who are able and willing to return for frequent post-void residual evaluation and able and willing to perform self-catheterization if necessary.[71250]
Treatment must be individualized and is based on the target muscles injected. In 4 open-label studies of indivudals 8 to 84 years of age, doses ranged from 2.5 to 300 units IM per treatment session. The effects last 12 to 16 weeks, after which treatment needs to be repeated. Experts recommend use only in very specific situations, such as severely disabling vocal tics (e.g., coprolalia) or very distressing motor tics of the upper face or neck. The American Academy of Neurology (AAN) practice guideline states that onabotulinumtoxinA is probably more likely than placebo to reduce tic severity in individuals with Tourette syndrome or chronic tic disorders when used for localized and bothersome simple motor tics or severely disabling or aggressive vocal tics. Premonitory urges may also be improved.[58800] [65080]
Treatment must be individualized and is based on the target muscles injected. In 4 open-label studies of individuals 8 to 84 years of age, doses ranged from 2.5 to 300 units IM per treatment session. The effects last 12 to 16 weeks, after which treatment needs to be repeated. Experts recommend use only in very specific situations, such as severely disabling vocal tics (e.g., coprolalia) or very distressing motor tics of the upper face or neck. The American Academy of Neurology (AAN) practice guideline states that onabotulinumtoxinA is probably more likely than placebo to reduce tic severity in individuals with Tourette syndrome or chronic tic disorders when used for localized and bothersome simple motor tics or severely disabling or aggressive vocal tics. Premonitory urges may also be improved.[58800] [65080]
5 to 100 units by injection in the internal anal sphincter as a single dose. May consider retreatment if anal fissure persists.[67105] [68164] [68165] Guidelines suggest botulinum toxin for persons who fail calcium channel blocker therapy or as an alternative to calcium channel blocker therapy.[67105] [68165]
400 units per 3 month period.
400 units per 3 month period.
10 units/kg (Max: 340 units) per 3 month period.
2 to 12 years: 10 units/kg (Max: 340 units) per 3 month period.
1 year: Safety and efficacy have not been established.
Safety and efficacy have not been established.
Safety and efficacy have not been established.
No dosage adjustment needed.
No dosage adjustment needed.
† Off-label indicationOnabotulinumtoxinA (formerly known as botulinum toxin type A) is an intramuscular toxin produced from fermentation of Clostridium botulinum type A. It is one of 7 toxic serotypes of botulinum (A through G) that have been purified. Two of the serotypes are available commercially in the United States, type A and type B; both are used to temporarily reduce local muscle activity. Type A toxins are more potent and longer acting than type B; approximately 7.5 to 10 units of type A is roughly equivalent in the degree of muscle paralysis to 320 to 480 units of type B.[26404] Patients who develop antibodies to type A toxins may benefit from type B toxin injections because there is no cross reactivity between type A and type B toxins. OnabotulinumtoxinA is approved for use in treating cervical dystonia in adults (to reduce the severity of abnormal head position and neck pain); blepharospasm and strabismus (to reduce excessive, abnormal contractions and correct alignment of the eye) associated with dystonia; overactive bladder (OAB) in patients with an inadequate response to anticholinergics or beta3 adrenoreceptor agonists; urinary incontinence due to detrusor overactivity associated with neurologic conditions; chronic migraine prophylaxis, severe primary axillary hyperhidrosis (severe underarm sweating), and treatment of upper and lower limb spasticity.[29334] Per adult guidelines for idiopathic OAB, intradetrusor onabotulinumtoxinA is a treatment option for patients with inadequate response or intolerable side effects from behavioral therapy or pharmacotherapy and who are able and willing to return for frequent post-void residual evaluation and able and willing to perform self-catheterization if necessary.[71250] A formulation of onabotulinumtoxinA (Botox Cosmetic) is approved for the temporary improvement in the appearance of moderate to severe glabellar lines associated with corrugator and/or procerus muscle activity; moderate to severe lateral canthal lines (crow's feet) associated with orbicularis oculi activity; moderate to severe forehead lines associated with frontalis muscle activity; and moderate to severe platysma bands associated with platysma muscle activity.[41123] OnabotulinumtoxinA has been studied in patients with documented pylorospasm and associated gastroparesis; however, while some improvement occurred in gastric emptying compared with placebo, no symptom improvements were found. Therefore, guidelines do not recommend its use in the treatment of gastroparesis. OnabotulinumtoxinA was FDA-approved in 1989.[53596]
For storage information, see the specific product information within the How Supplied section.
NOTE: The potency units are not interchangeable with other preparations of botulinum toxin products. Therefore, units of biological activity of onabotulinumtoxinA cannot be compared or converted into units of any other botulinum toxin products assessed with any other specific assay method.[29334]
Reconstitution/Dilution
50 unit onabotulinumtoxinA vial dilution: Add diluent as shown below for desired final concentration.[41123]
100 unit onabotulinumtoxinA vial dilution: Add diluent as shown below for desired final concentration.[29334][41123]
200 unit onabotulinumtoxinA vial dilution: Add diluent as shown below for desired final concentration.[29334]
Blepharospasm
Cervical dystonia
Chronic migraine prophylaxis
Glabellar facial wrinkles
Forehead facial lines
Lateral canthal lines
Platysma bands
Strabismus
Upper limb spasticity
Bladder detrusor overactivity associated with a neurologic condition
Preparation
Administration
Overactive bladder
Facial wrinkles other than glabellar facial wrinkles (e.g., horizontal forehead lines, melolabial folds, and other hyperkinetic facial lines)
Intradermal Administration
Primary axillary hyperhidrosis
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]
The coadministration of certain medications may lead to harm and require avoidance or therapy modification; review all drug interactions prior to concomitant use of other medications.
This medication is contraindicated in patients with a history of hypersensitivity to it or any of its components. OnaborulinumtoxinA is contraindicated in people with hypersensitivity to any botulinum toxin preparation or to human albumin, which is found in these products.[29334][41123]
OnabotulinumtoxinA is contraindicated in the presence of infection at any proposed injection site(s).[29334][41123]
Use caution when onabotulinumtoxinA is used in the presence of inflammation at the proposed injection site(s), ptosis, or when excessive weakness or atrophy is present in the targeted muscle(s).[29334][41123]
Individuals with hyperhidrosis should be evaluated for potential causes of secondary hyperhidrosis (e.g., hyperthyroidsm) prior to receiving onabotulinumtoxinA for the treatment of hyperhidrosis.[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]
OnabotulinumtoxinA blocks neuromuscular conduction by binding to receptor sites on motor nerve terminals, entering nerve terminals, and inhibiting the release of acetylcholine. Inhibition occurs as the neurotoxin cleaves a protein (SNAP-25) integral to the successful docking and release of acetylcholine from vesicles situated within nerve endings. After intramuscular injection of a therapeutic dose, onabotulinumtoxinA produces partial chemical denervation of the muscle resulting in a localized reduction in muscle activity. Additionally, the muscle may atrophy, axonal sprouting may occur, and extrajunctional acetylcholine receptors may develop. Evidence exists that suggests that reinnervation of the muscle may occur thereby slowly reversing muscle denervation produced by the neurotoxin.[29334]
A reduction in sialorrhea may also occur by blocking the liberation of acetylcholine in autonomic nerve terminals in the parotid and submandibular glands. There is no evidence of axonal sprouting and consecutive innervation in autonomic nerve fibers in sialorrhea studies.[29334]
For treatment of neurogenic bladder, after injection into the detrusor muscle the efferent pathways of detrusor activity are affected via inhibition of acetylcholine release; inhibition of afferent neurotransmitters and sensory pathways is also thought to occur.[29334] Therapy increases maximal bladder capacity, reduces maximum detrusor pressure, reduces incontinence episodes, and may reduce the need for anticholinergics in patients with neurogenic overactive bladder.
Revision Date: 07/23/2025, 03:46:38 PMOnabotulinumtoxinA is administered by local intramuscular injection. The recommended quantities of neurotoxin administered at each treatment session are not expected to result in systemic, overt distant clinical effects, i.e. muscle weakness, in patients without other neuromuscular dysfunction. Onset and duration of action depend on the clinical use of the drug.
The onset and duration of action of onabotulinumtoxinA depends on the clinical use of the drug.
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]
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