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OnabotulinumtoxinA

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Nov.14.2023

OnabotulinumtoxinA

Indications/Dosage

Labeled

  • blepharospasm
  • cervical dystonia
  • facial wrinkles
  • hyperhidrosis
  • migraine prophylaxis
  • neurogenic bladder
  • overactive bladder (OAB)
  • spasticity
  • strabismus
  • urinary incontinence

Off-Label

  • achalasia
  • anal fissures
  • sialorrhea
  • Tourette's syndrome
† Off-label indication

For the treatment of blepharospasm associated with dystonia, including benign essential blepharospasm or VII nerve disorders

Intramuscular dosage

Adults, Adolescents, and Children >= 12 years

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.

For the treatment of cervical dystonia in adults to decrease the severity of abnormal head position and neck pain associated with cervical dystonia

Intramuscular dosage

Adults and Adolescents >= 16 years

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.

For the treatment of strabismus

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.

for vertical muscles, and for horizontal strabismus of less than 20 prism diopters

Intramuscular dosage

Adults, Adolescents, and Children >= 12 years

1.25—2.5 units in any 1 muscle.

for horizontal strabismus of 20 prism diopters to 50 prism diopters

Intramuscular dosage

Adults, Adolescents, and Children >= 12 years

2.5—5 units in any 1 muscle.

for persistent VI nerve palsy of 1 month or longer duration

Intramuscular dosage

Adults, Adolescents, and Children >= 12 years

1.25—2.5 units in the medial rectus muscle.

for subsequent dosing for residual or recurrent strabismus

Intramuscular dosage

Adults, Adolescents, and Children >= 12 years

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.

For temporary improvement in the appearance of facial wrinkles

for temporary improvement in the appearance of moderate to severe glabellar lines associated with corrugators and/or procerus muscle activity

Intramuscular dosage

Adults

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]

for the treatment of moderate to severe forehead lines associated with frontalis muscle activity

Intramuscular dosage

Adults

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]

for temporary improvement in the appearance of moderate to severe lateral canthal lines associated with orbicularis oculi activity (crow's feet)

Intramuscular dosage

Adults

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]

for temporary improvement in the appearance of other wrinkles such as melolabial folds† and other hyperkinetic facial lines†

Subcutaneous dosage†

Adults

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]

For the treatment of achalasia†

Endoscopic injection dosage

Adults

A usual dose is 20 to 25 units per injection, diluted in 0.5 to 1 mL of preservative-free saline, injected 1 cm above the squamocolumnar junction into 4 or more quadrants of the lower esophageal sphincter (LES); total dosage not to exceed 100 units/treatment.[66609] A sclerotherapy needle is used to achieve placement during upper-gastrointestinal endoscopy.[55875] A systematic review has shown initial (1-month) response to therapy is 78.7%, however long-term (12-month) success rate is 40.6%. Repeat injections were needed in 46.6% of patients and 30% of patients required additional treatments for symptom relief. Doses higher than 100 units/treatment have not been shown to be more effective.[66609] Authors of a small (n = 30) study concluded that if the initial response to the first injection is symptomatic, then sustained response is likely, whereas no initial response suggests poor response to additional injections. They also indicated that a residual LES tone of less than 18 mm Hg after botulinum injection is a predictor of a good response.[26410] Guidelines recommend against the use of botulinum toxin injection as definitive therapy for achalasia; it may be reserved for patients who are not candidates for other definitive therapies.[65920] [66609]

For the treatment of spasticity

for upper limb spasticity

Intramuscular dosage

Adults

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]

Children and Adolescents 2 to 17 years

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]

for lower limb spasticity

Intramuscular dosage

Adults

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]

Children and Adolescents 2 to 17 years

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]

for the chronic management of focal spasticity† in pediatric patients with cerebral palsy and concurrent equinus gait (tiptoeing)

Intramuscular dosage

Children and Adolescents 2 to 17 years

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]

For the treatment of severe primary axillary hyperhidrosis (excessive underarm sweating)

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.

Intradermal dosage

Adults

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]

Neonates, Infants, Children, and Adolescents

Safety and efficacy have not been established.

For the treatment of sialorrhea†

for the treatment of sialorrhea† associated with Parkinson disease

Intraglandular dosage

Adults

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]

for the treatment of sialorrhea† associated with amyotrophic lateral sclerosis (ALS)

Intraglandular dosage

Adults

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]

for sialorrhea† associated with cerebral palsy†

Intraglandular dosage

Children and Adolescents 21 months to 17 years

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]

For chronic migraine prophylaxis

Intramuscular dosage

Adults

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]

For the treatment of urinary incontinence due to detrusor overactivity associated with a neurologic condition (e.g., as occurs with neurogenic bladder in spinal cord injury, multiple sclerosis) in patients with an inadequate response or intolerance to an anticholinergic medication

Intramuscular dosage

Adults

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]

Children and Adolescents 5 to 17 years weighing 34 kg or more

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]

Children and Adolescents 5 to 17 years weighing less than 34 kg

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]

For the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and frequency in adults intolerant to or with inadequate response from anticholinergic medications

Intramuscular dosage

Adults

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 third-line treatment for patients refractory to first- and second-line OAB treatments who are able and willing to return for frequent post-void residual evaluation and able and willing to perform self-catheterization if necessary.[64178]

For the treatment of Tourette's syndrome† or chronic tic disorders†

Intramuscular dosage

Adults

Treatment must be individualized and is based on the target muscles injected. In 4 open-label studies of patients 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 in only 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 patients with Tourette's 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]

Children and Adolescents 8 years and older

Treatment must be individualized and is based on the target muscles injected. In 4 open-label studies of patients 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 in only 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 patients with Tourette's 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]

For the treatment of anal fissures†

Intra-Anal dosage

Adults

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]

Therapeutic Drug Monitoring

Maximum Dosage Limits

  • Adults

    400 units per 3 month period.

  • Geriatric

    400 units per 3 month period.

  • Adolescents

    10 units/kg (Max: 340 units) per 3 month period.

  • Children

    2 to 12 years: 10 units/kg (Max: 340 units) per 3 month period.

    1 year: Safety and efficacy have not been established.

  • Infants

    Safety and efficacy have not been established.

  • Neonates

    Safety and efficacy have not been established.

Patients with Hepatic Impairment Dosing

No dosage adjustment needed.

Patients with Renal Impairment Dosing

No dosage adjustment needed.

† Off-label indication
Revision Date: 11/14/2023, 09:19:59 AM

References

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Diagnosis and Treatment of Overactive Bladder (Non-Neurogenic) in Adults: AUA/SUFU Guideline Amendment 2019. J Urol. 2019;202:558-563.65080 - Pringsheim T, Okun MS, Muller-Vahl K, et al. Practice guideline recommendations summary: Treatment of tics in people with Tourette syndrome and chronic tic disorders. Neurology 2019;92:896-906.65920 - Khashab MA, Vela MF, Thosani N, et al. ASGE guideline on the management of achalasia. Gastrointest Endosc 2020;91:213-227.66609 - Vaezi MF, Pandolfino JE, Yadlapati RH. ACG Clinical Guidelines: Diagnosis and Management of Achalasia. Am J Gastroenterol 2020;115:1393-1411.67105 - Wald A, Bharucha A, Limketkai B, et al. Clinical Guidelines: Management of Benign Anorectal Disorders. Am J Gastroenterol 2021; 116:1987-2008.68164 - Yiannakopoulou E. Botulinum toxin and anal fissure: efficacy and safety systematic review. Int J Colorectal Dis. 2012 Jan;27:1-9.68165 - Davids JS, Hawkins AT, Bhama AR, et al; Prepared on behalf of the Clinical Practice Guidelines Committee of the American Society of Colon and Rectal Surgeons. The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Management of Anal Fissures. Dis Colon Rectum. 2023 Feb 1;66(2):190-199.69288 - Ailani J, Burch RC, Robbins MS; Board of Directors of the American Headache Society. The American Headache Society Consensus Statement: Update on integrating new migraine treatments into clinical practice. Headache 2021 ;61:1021-1039.69817 - Banfi P, Ticozzi N, Lax A, et al. A review of options for treating sialorrhea in amyotrophic lateral sclerosis. Respir Care 2015;60:446-54.69839 - Gilio F, Iacovelli E, Frasca V, et al. Botulinum toxin type A for the treatment of sialorrhoea in amyotrophic lateral sclerosis: a clinical and neurophysiological study. Amyotroph Lateral Scler. 2010;11:359-63.69840 - Giess R, Naumann M, Werner E, et al. Injections of botulinum toxin A into the salivary glands improve sialorrhoea in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry. 2000;69:121-3.

How Supplied

OnabotulinumtoxinA Powder for solution for injection

Botox 100unit Powder for Injection (00023-1145) (Allergan USA, Inc.) nullBotox 100unit Powder for Injection package photo

OnabotulinumtoxinA Powder for solution for injection

Botox 200unit Powder for Injection (00023-3921) (Allergan USA, Inc.) null

OnabotulinumtoxinA Powder for solution for injection [Cosmetic Use]

Botox Cosmetic 50unit Powder for Injection (00023-3919) (Allergan USA, Inc.) null

OnabotulinumtoxinA Powder for solution for injection [Cosmetic Use]

Botox Cosmetic 100unit Powder for Injection (00023-9232) (Allergan USA, Inc.) null

Description/Classification

Description

OnabotulinumtoxinA (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 reduce local muscle activity, albeit temporarily. 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. Originally, onabotulinumtoxinA was approved for use in treating cervical dystonia in adults (to reduce the severity of abnormal head position and neck pain), and blepharospasm and strabismus (to reduce excessive, abnormal contractions and correct alignment of the eye) associated with dystonia in adolescents and adults. Additional indications added since initial approval include treatment of overactive bladder (OAB) in patients with an inadequate response to anticholinergics or beta3 adrenoreceptor agonists, treatment of urinary incontinence due to detrusor overactivity associated with neurologic conditions, chronic migraine prophylaxis, treatment of severe primary axillary hyperhidrosis (severe underarm sweating), and treatment of upper and lower limb spasticity.[29334] Per adult guidelines for OAB, intradetrusor onabotulinumtoxina is a third-line treatment for patients refractory to first- and second-line OAB treatments who are able and willing to return for frequent post-void residual evaluation and able and willing to perform self-catheterization if necessary.[64178] A formulation of onabotulinumtoxinA (Botox Cosmetic) was approved in December 1991 for the temporary improvement in the appearance of moderate to severe glabellar lines. It is also approved for the temporary improvement in the appearance of lateral canthal lines, also known as crow's feet.[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.[53596]

Classifications

  • Dermatologicals
    • Other Dermatological Agents
      • Agents for Hyperhidrosis
        • Injectable Agents for Hyperhidrosis
      • Anti-wrinkle Agents, Rx
  • Musculo-Skeletal System
    • Muscle Relaxants
      • Muscle Relaxants, Other Neuromuscular Blockers
Revision Date: 02/11/2021, 12:33:55 PM

References

26404 - Sloop RR, Cole BA, Escutin RO. Human response to botulinum toxin injection; type B compared with type A. Neurology 1997;49:189-194.29334 - Botox (onabotulinumtoxinA) injection package insert. Madison, NJ: Allergan USA, Inc.; 2022 Aug.41123 - Botox Cosmetic (onabotulinumA) package insert. Irvine, CA: Allergan, Inc.; 2018 May.53596 - Camilleri M, Parkman HP, Shafi MA, et al. Clinical guideline: Management of gastroparesis. Am J Gastroenterol 2013;108:18-37.64178 - Lightner DJ, Gomelsky A, Souter L, et al. Diagnosis and Treatment of Overactive Bladder (Non-Neurogenic) in Adults: AUA/SUFU Guideline Amendment 2019. J Urol. 2019;202:558-563.

Administration Information

General Administration Information

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]

Route-Specific Administration

Injectable Administration

  • Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
  • OnabotulinumtoxinA is administered by local intradermal or intramuscular injection and, for specific applications, by specialized local injection techniques adjacent to the appropriate muscle groups.

 

Reconstitution/Dilution

  • Reconstitute with preservative-free 0.9% Sodium Chloride Injection.
  • Draw up the proper amount of diluent (see Dilutions below) in the appropriate size syringe, and slowly inject the diluent into the vial. Discard the vial if a vacuum does not pull the diluent into the vial.
  • Gently mix by rotating the vial.
  • Storage: Administer within 24 hours of reconstitution. Store unused reconstituted solution in a refrigerator (2 to 8 degrees C) until the time of use. Vials are single-dose only; discard unused portion.[29334]

 

50 unit onabotulinumtoxinA vial dilution: Add diluent as shown below for desired final concentration.[41123]

  • 1.25 mL of diluent = 4 units/0.1 mL

 

100 unit onabotulinumtoxinA vial dilution: Add diluent as shown below for desired final concentration.[29334] [41123]

  • 1 mL of diluent = 10 units/0.1 mL
  • 2 mL of diluent = 5 units/0.1 mL
  • 2.5 mL of diluent = 4 units/0.1 mL
  • 4 mL of diluent = 2.5 units/0.1 mL
  • 8 mL of diluent = 1.25 units/0.1 mL
  • 10 mL of diluent = 1 unit/0.1 mL

 

200 unit onabotulinumtoxinA vial dilution: Add diluent as shown below for desired final concentration.[29334]

  • 1 mL of diluent = 20 units/0.1 mL
  • 2 mL of diluent = 10 units/0.1 mL
  • 4 mL of diluent = 5 units/0.1 mL
  • 8 mL of diluent = 2.5 units/0.1 mL
  • 10 mL of diluent = 2 units/0.1 mL

Intramuscular Administration

Blepharospasm

  • Use a sterile 27- to 30-gauge needle without electromyographic guidance.
  • Inject into the medial and lateral pre-tarsal orbicularis oculi of the upper lid and into the lateral pre-tarsal orbicularis oculi of the lower lid.
  • Avoiding injection near the levator palpebrae superioris may reduce the complication of ptosis. Avoiding medial lower lid injections, and thereby reducing diffusion into the inferior oblique, may reduce the complication of diplopia.
  • Ecchymosis occurs easily in the soft eyelid tissues and can be prevented by applying pressure at the injection site immediately after the injection.[29334]

 

Cervical dystonia

  • A 25-, 27-, or 30-gauge needle may be used for superficial muscles, and a longer 22-gauge needle may be used for deeper musculature.
  • Localization of the involved muscles with electromyographic guidance or nerve stimulation techniques is recommended.[29334]

 

Chronic migraine prophylaxis

  • A 30-gauge 0.5 inch needle may be used for IM injections; use a 1 inch needle for thick neck muscles if needed.
  • Dilute to a final concentration of 5 units per 0.1 mL.
  • Divide the dose to be administered across 7 specific head/neck muscle areas; administer an equal number of injections to each the right and left side of the head and neck with the exception of the procerus muscle, which is injected once at the midline. See product full prescribing information for specific recommendations for sites to be injected and the exact dose to be injected at each site.[29334]

 

Glabellar facial wrinkles

  • Use the 50 or 100 unit vial diluted to a final concentration of 4 units per 0.1 mL.
  • Administer injections with patients in the seated position.
  • To treat glabellar furrows, the patient is first asked to frown in order to isolate the corrugator superciliaris muscle. Once the patient is relaxed, the toxin is injected into the corrugator muscle by passing the needle inferoposteriorly from just above the brow. The needle tip lines up vertically with the inner canthus. About one-half of the needle length will be in the skin and subcutaneous tissue if it is correctly positioned. At this point, 5 units of the toxin are injected directly into the muscle. With care taken to keep it in the same puncture site, the needle is then almost completely withdrawn and repositioned perpendicular to the skin. After advancing the needle once again to about half its length, 5 units of toxin is injected to treat the most superomedial part of the orbicularis without compromising normal orbicularis function. The 2 injections are then repeated on the contralateral side with needle reinserted directly midline between the eyebrows just below the brow line. A fifth injection of 5 units is made into the middle of the procerus muscle. In men, 2 additional injections of 5 units on each side into the orbicularis are made just above the eyebrow in the midpupillary line.
  • At the end of therapy, patients should remain vertical and refrain from touching the treated areas for 3 to 4 hours to avoid spread of toxin to adjacent muscle groups.
  • It is important that injections be symmetric so that no unnatural balance is created after therapy. Also, it is important to avoid injection into the eyebrow lateral to the inner canthus because this will increase the likelihood of ptosis.[26405] [26406] [26407] [26408] [26409]

 

Forehead facial lines

  • Use the 50 unit or 100 unit vial diluted to a final concentration of 4 units per 0.1 mL.
  • Treat forehead lines in conjunction with glabellar lines to minimize the potential for brow ptosis.
  • Draw at least 1 mL (for forehead lines treated in conjunction with glabellar lines) of reconstituted toxin into the sterile syringe (preferably tuberculin). Remove the needle used to reconstitute the product and attach a 30- to 33-gauge needle.
  • Locate the horizontal treatment rows by light palpitation of the forehead at rest and maximum eyebrow elevation.
  • Superior margin of frontalis activity: approximately 1 cm above the most superior forehead crease.
  • Lower treatment row: midway between the superior margin of frontalis activity and the eyebrow, at least 2 cm above the eyebrow.
  • Upper treatment row: midway between the superior margin of frontalis activity and lower treatment row.
  • Place 5 injections (4 units each) at the intersection of the horizontal treatment rows.
    • On the lower treatment row at the midline of the face, and 0.5 to 1.5 cm medial to the palpated temporal fusion line (temporal crest); repeat for the other side.
    • On the upper treatment row, midway between the lateral and medial sites on the lower treatment row; repeat for the other side.[41123]

 

Lateral canthal lines

  • Use the 50 unit or 100 unit vial diluted to a final concentration of 4 units per 0.1 mL.
  • Inject with the needle bevel tip up and oriented away from the eye.
  • Inject into (4 units) 3 sites per side in the lateral orbicularis oculi muscle for a total of 24 units.
  • The first injection should be approximately 1.5 to 2 cm temporal to the lateral canthus and just temporal to the orbital rim.[41123]

 

Strabismus

  • OnabotulinumtoxinA is intended for injection into extraocular muscles utilizing the electrical activity recorded from the tip of the injection needle as a guide to placement within the target muscle.
  • Injection without surgical exposure or electromyographic guidance should not be attempted. Physicians should be familiar with electromyographic technique.[29334]

 

Upper limb spasticity

  • A 25-, 27-, or 30-gauge needle may be used for superficial muscles, and a longer 22-gauge needle may be used for deeper musculature.
  • Localization of the involved muscles with electromyographic guidance, nerve stimulation, or ultrasound is recommended.[29334]

 

Bladder detrusor overactivity associated with a neurologic condition

  • Discontinue anti-platelet medications at least 3 days prior to treatment. Manage patients on anticoagulant therapy appropriately to decrease the risk of bleeding.
  • Administer prophylactic antibiotics (excluding aminoglycosides) 1 to 3 days prior to treatment, on treatment day, and 1 to 3 days after treatment. Alternatively, in patients receiving general anesthesia (or conscious sedation), 1 dose of IV prophylactic antibiotics (excluding aminoglycosides) may be administered on the day of treatment.
  • Consider diluted instillation of local anesthetic, use of a sedative, or general anesthesia prior to injection. If local anesthetic instillation is performed, drain and irrigate the bladder with sterile saline before injection.[29334]

Preparation

  • For adult patients, 1 of 2 reconstitution methods may be used depending on the vial strength:
    • Reconstitution of 200 unit vial: Reconstitute one 200 unit vial with 6 mL of preservative-free 0.9% Sodium Chloride Injection and mix the vial gently. Draw 2 mL from the vial into each of three 10 mL syringes. Complete reconstitution by adding 8 mL of preservative-free 0.9% Sodium Chloride Injection into each of the 10 mL syringes and mix gently. Each syringe will then contain 10 mL (approximately 67 units), for a total of 200 units of reconstituted onabotulinumtoxinA.
    • Reconstitution of 100 unit vials: Reconstitute two 100 unit vials, each with 6 mL of preservative-free 0.9% Sodium Chloride Injection and mix the vials gently. Draw 4 mL from each vial into each of two 10 mL syringes. Draw the remaining 2 mL from each vial into a third 10 mL syringe. Complete reconstitution by adding 6 mL of preservative-free 0.9% Sodium Chloride Injection into each of the 10 mL syringes, and mix gently. Each syringe will then contain 10 mL (approximately 67 units), for a total of 200 units of reconstituted onabotulinumtoxinA.
  • For pediatric patients, 1 of 2 reconstitution methods may be used depending on the vial strength:
    • Reconstitution of 200 unit vials: Add 10 mL of preservative-free 0.9% Sodium Chloride Injection and mix the vial gently.
    • Reconstitution of 100 unit vials: Add 5 mL of preservative-free 0.9% Sodium Chloride Injection to each vial and mix gently.
  • For pediatric patients weighing 34 kg or more, draw 10 mL (200 units) from the vial(s) into one 10 mL dosing syringe.
  • For pediatric patients weighing less than 34 kg, further dilute the reconstituted solution with preservative-free Sodium Chloride Injection (diluent) in a 10 mL dosing syringe, based on patient weight:
    • 32 to 33 kg: 9.6 mL of reconstituted solution and 0.4 mL diluent (192 units/10 mL syringe)
    • 30 to 31 kg: 9 mL of reconstituted solution and 1 mL diluent (180 units/10 mL syringe)
    • 28 to 29 kg: 8.4 mL of reconstituted solution and 1.6 mL diluent (168 units/10 mL syringe)
    • 26 to 27 kg: 7.8 mL of reconstituted solution and 2.2 mL diluent (156 units/10 mL syringe)
    • 24 to 25 kg: 7.2 mL of reconstituted solution and 2.8 mL diluent (144 units/10 mL syringe)
    • 22 to 23 kg: 6.6 mL of reconstituted solution and 3.4 mL diluent (132 units/10 mL syringe)
    • 20 to 21 kg: 6 mL of reconstituted solution and 4 mL diluent (120 units/10 mL syringe)
    • 18 to 19 kg: 5.4 mL of reconstituted solution and 4.6 mL diluent (108 units/10 mL syringe)
    • 16 to 17 kg: 4.8 mL of reconstituted solution and 5.2 mL diluent (96 units/10 mL syringe)
    • 14 to 15 kg: 4.2 mL of reconstituted solution and 5.8 mL diluent (84 units/10 mL syringe)
    • 12 to 13 kg: 3.6 mL of reconstituted solution and 6.4 mL diluent (72 units/10 mL syringe)
  • Storage: Use preparation immediately after reconstitution and dispose of any unused saline.[29334]

Administration

  • Inject the reconstituted preparation into the detrusor muscle via a flexible or rigid cystoscope, avoiding the trigone. Instill the bladder with enough saline to achieve adequate visualization for the injections; over-distension should be avoided.
  • Prime the injection needle with about 1 mL of reconstituted onabotulinumtoxinA prior to injection to remove any air.
  • Insert the needle about 2 mm into the detrusor.
  • For adult patients, space 30 injections of 1 mL about 1 cm apart.
  • For pediatric patients, space 20 injections of 0.5 mL about 1 cm apart.
  • Refer to product full prescribing information for visual aide of injection pattern.
  • For the final injection, inject about 1 mL of preservative-free 0.9% Sodium Chloride Injection to assure the full dose is administered.
  • Drain the saline used for bladder wall visualization.
  • Observe the patient for 30 minutes post-injection.[29334]

 

Overactive bladder

  • Use the 100 unit vial reconstituted with 10 mL of preservative-free 0.9% Sodium Chloride for Injection. Use preparation immediately after reconstitution and dispose of any unused saline.
  • Reconstituted preparation should be injected into the detrusor muscle via a flexible or rigid cystoscope, avoiding the trigone. The bladder should be instilled with enough saline to achieve adequate visualization for the injections; over-distension should be avoided.
  • Fill (prime) the injection needle with approximately 1 mL reconstituted onabotulinumtoxinA prior to injection to remove any air. Insert needle approximately 2 mm into the detrusor. Twenty (20) injections of 0.5 mL each (total volume of 10 mL) should be spaced about 1 cm apart. For the final injection, approximately 1 mL of sterile preservative-free 0.9% Sodium Chloride for Injection should be injected so full dose is administered.
  • An intravesical instillation of diluted local anesthetic, with or without sedation, may be used prior to injection. If used, the bladder should be drained and irrigated with sterile saline before injection.
  • Discontinue anti-platelet medications at least 3 days prior to injection in any patients receiving such treatment.
  • Administer prophylactic antibiotics (excluding aminoglycosides) 1 to 3 days prior to treatment, on treatment day, and 1 to 3 days after treatment.
  • May refer to product full prescribing information for visual aide of injection pattern.[29334]

Subcutaneous Administration

Facial wrinkles other than glabellar facial wrinkles (e.g., horizontal forehead lines, melolabial folds, and other hyperkinetic facial lines)

  • NOTE: OnabotulinumtoxinA is not FDA-approved for these indications.
  • Unlike treatment of glabellar facial wrinkles, which are treated via IM injection (see separate Administration instructions), other facial wrinkles are treated with subcutaneous administration of onabotulinumtoxinA. The toxin is used to weaken, not paralyze, related muscles as these wrinkles are the result of physiologically important facial muscles, and complete paralysis may create unacceptable functional deficits.[26405] [26406] [26407] [26408] [26409]

Other Injectable Administration

Intradermal Administration

Primary axillary hyperhidrosis

  • Administer onabotulinumtoxinA intradermally for this indication.
  • Prior to administration, identify the hyperhydrotic area using standard staining techniques (e.g., Minor's Iodine-Starch Test).
  • Dilute to a final onabotulinumtoxinA concentration of 2.5 units/0.1 mL.
  • Using a 30-gauge needle, administer 10 to 15 injections intradermally in 0.1 mL to 0.2 mL aliquots within each axilla. Evenly distribute the injections, spacing them approximately 1 to 2 cm apart.
  • Administer each injection to a depth of approximately 2 mm and at a 45 degree angle to the skin surface, with the bevel side up to minimize leakage and to ensure the injections remain intradermal.
  • If injection sites are marked in ink, do not inject directly through the ink mark to avoid a permanent tattoo effect.[29334]

Clinical Pharmaceutics Information

From Trissel's 2‚Ñ¢ Clinical Pharmaceutics Database
    Revision Date: 08/02/2021, 01:51:12 PM

    References

    26405 - Carruthers JDA, Carruthers JA. Treatment of glabellar frown lines with C. botulinum-A exotoxin. J Dermatol Surg Oncol 1992;18:17-21.26406 - Carruthers A, Carruthers JDA. The use of botulinum toxin to treat glabellar frown lines and other facial wrinkles. Cosmet Dermatol 1994;75:11-5.26407 - Guyuron B, Huddleston SW. Aesthetic indications for botulinum toxin injection. Plast Reconstr Surg 1994;93:913-918.26408 - Keen M, Blitzer A, Aviv J, et al. Botulinum toxin A for hyperkinetic facial lines: results of a double-blind, placebo-controlled study. Plast Reconstr Surg 1994;94:94-9.26409 - Blitzer A, Brin MF, Keen MF, et al. Botulinum toxin for the treatment of hyperfunctional lines of the face. Arch Otolaryngol Head Neck Surg 1993;119:1018-1022.29334 - Botox (onabotulinumtoxinA) injection package insert. Madison, NJ: Allergan USA, Inc.; 2022 Aug.41123 - Botox Cosmetic (onabotulinumA) package insert. Irvine, CA: Allergan, Inc.; 2018 May.

    Adverse Reactions

    Mild

    • abdominal pain
    • anorexia
    • anxiety
    • asthenia
    • back pain
    • blepharedema
    • cough
    • diarrhea
    • diplopia
    • dizziness
    • drowsiness
    • ecchymosis
    • fatigue
    • fever
    • headache
    • hyperhidrosis
    • hypoesthesia
    • infection
    • influenza
    • injection site reaction
    • insomnia
    • lacrimation
    • malaise
    • musculoskeletal pain
    • myalgia
    • nasal congestion
    • nausea
    • ocular irritation
    • paresthesias
    • pharyngitis
    • pruritus
    • ptosis
    • rash
    • rhinitis
    • rhinorrhea
    • syncope
    • tinnitus
    • urticaria
    • vertigo
    • weakness
    • xerophthalmia
    • xerostomia

    Moderate

    • antibody formation
    • constipation
    • dysarthria
    • dysphagia
    • dysphonia
    • dyspnea
    • dysuria
    • edema
    • entropion
    • erythema
    • hematuria
    • hypertension
    • hypertropia
    • hypotropia
    • lagophthalmos
    • myasthenia
    • ocular infection
    • paresis
    • photophobia
    • psoriaform rash
    • urinary retention

    Severe

    • anaphylactoid reactions
    • arrhythmia exacerbation
    • distant spread of toxin effects
    • ectropion
    • erythema multiforme
    • keratitis
    • myocardial infarction
    • ocular hemorrhage
    • ocular hypertension
    • respiratory arrest
    • seizures
    • serum sickness
    • visual impairment

    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.[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 patients taking 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 adult patients 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 adult patients 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 adult patients 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]

    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]

    Revision Date: 02/10/2021, 10:09:36 AM

    References

    29334 - Botox (onabotulinumtoxinA) injection package insert. Madison, NJ: Allergan USA, Inc.; 2022 Aug.41123 - Botox Cosmetic (onabotulinumA) package insert. Irvine, CA: Allergan, Inc.; 2018 May.45602 - Corridan P, Nightingale S, Mashoudi N, et al. Acute angle-closure glaucoma following botulinum toxin injection for blepharospasm. Br J Ophthalmol 1990;74:309-10.

    Contraindications/Precautions

    Absolute contraindications are italicized.

    • infection
    • urinary retention
    • urinary tract infection (UTI)
    • albumin hypersensitivity
    • amyotrophic lateral sclerosis (ALS)
    • anticoagulant therapy
    • autonomic neuropathy
    • breast-feeding
    • cardiac disease
    • children
    • distant spread of toxin effects
    • driving or operating machinery
    • dysphagia
    • hyperthyroidism
    • intravenous administration
    • myasthenia gravis
    • myopathy
    • neuromuscular disease
    • ocular disease
    • pregnancy
    • requires an experienced clinician
    • respiratory insufficiency
    • surgery
    • thyroid disease
    • viral infection
    • visual disturbance

    Previously sedentary patients who will resume activities after administration of onabotulinumtoxinA should do so gradually.

    Use of onabotulinumtoxinA requires an experienced clinician as safe and effective use of onabotulinumtoxinA depends upon proper product storage, dose selection, product reconstitution, and administration technique, in addition to, knowledge of the treated condition. Units of biological activity of onabotulinumtoxinA cannot be compared or converted to other botulinum toxin products. Physicians must understand the relevant neuromuscular and/or orbital anatomy of the area involved and know of any alterations to the anatomy due to prior surgical procedures. An understanding of standard electromyographic techniques is also required for the treatment of strabismus and may be useful for the treatment of cervical dystonia. Serious, sometimes fatal, adverse reactions, including excessive weakness, dysphagia, and aspiration pneumonia, have been reported in patients receiving onabotulinumtoxinA for unapproved uses. Reactions were not necessarily related to distant spread of toxin but may have resulted from the administration of the drug to the site of injection and/or adjacent structures. Several of the cases involved patients with pre-existing difficulty with swallowing or other significant disabilities; however, specific risk factors associated with an increased risk for adverse reactions with the unapproved use onabotulinumtoxinA have not been identified.[29334] The health care professional should have immediate availability of epinephrine (1 mg/mL) injection and other agents used in the treatment of severe anaphylaxis in the event of a serious allergic reaction to onabotulinumtoxinA. Avoid intravenous administration of onabotulinumtoxinA as this can cause distant spread of toxin effects, resulting in serious adverse events, including excessive paralysis, breathing and swallowing difficulties, consistent with botulinum toxicity. In the event of overdose, antitoxin raised against botulinum toxin is available from the U.S. Centers for Disease Control and Prevention (CDC) in Atlanta, GA. However, the antitoxin will not reverse any botulinum toxin-induced effects already apparent by the time of antitoxin administration. In the event of suspected or actual cases of botulinum toxin poisoning, contact the local or state Health Department to process a request for antitoxin through the CDC. If you do not receive a response within 30 minutes, please contact the CDC directly at 1-770-488-7100.

    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. Symptoms have been reported in patients receiving doses comparable to or lower than doses used to treat cervical dystonia and spasticity.[29334] [41123]

    OnabotulinumtoxinA is contraindicated in the presence of infection at ANY proposed injection site(s). For example, intradetrusor injection is contraindicated in patients with urinary tract infection (UTI). It is also contraindicated in individuals with known hypersensitivity to any ingredient in the formulation.[29334]

    Patients should be evaluated for potential causes of secondary hyperhidrosis (e.g., thyroid disease like hyperthyroidism) to avoid symptomatic treatment of hyperhidrosis without the diagnosis and/or treatment of the underlying disease. The safe and effective use of onabotulinumtoxinA for hyperhidrosis in other body areas have not been established. Weakness of hand muscles may occur in patients who receive the drug for palmar hyperhidrosis. Blepharoptosis may occur in patients who receive it for facial hyperhidrosis.

    Commercial preparations of onabotulinumtoxinA contain albumin and should be used cautiously in patients with albumin hypersensitivity. Albumin is also 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. Screening plasma donors for prior exposure to certain viruses, testing for the presence of viruses, and inactivating and/or reducing viruses has reduced the risk of transmission of infectious agents. The manufacturing processes are designed to reduce the risk of transmitting viral infection; however, none of the processes are completely effective. There is also the possibility that unknown infectious agents may be present in this product. 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. Prior to therapy initiation discuss the risks and benefits of this product with the patient and/or the health care surrogate of the patient.[29334] [41123]

    Patients 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, patients with smaller neck muscle mass and patients who require bilateral injections into the sternocleidomastoid muscle have been reported to be at greater risk for dysphagia. 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 patients, 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 patients 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 patients with pre-existing dysphagia or other significant disabilities.[29334]

    There are no human data on the developmental risk associated with the use of onabotulinumtoxinA during human pregnancy. When administered intramuscularly (8 and 16 units/kg) two times to pregnant mice or rats during organogenesis, reductions in fetal weight and decreased fetal skeletal ossification were observed. The no-effect dose for developmental toxicity is approximately equivalent to the human dose of 400 units. No adverse effects were observed when pregnant rats received a single intramuscular injection.[29334] [41123]

    It is not known whether onabotulinumtoxinA is excreted in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for onabotulinumtoxinA and any potential adverse effects on the breastfed infant. OnabotulinumtoxinA is not detectable systemically after intramuscular use, thus excretion into breast milk is considered unlikely.[29334] [41123]

    Use onabotulinumtoxinA cautiously in patients with myopathy associated with neuromuscular disease (e.g., amyotrophic lateral sclerosis (ALS), motor neuropathy (autonomic neuropathy), myasthenia gravis or Lambert-Eaton syndrome). Patients with known or unrecognized neuromuscular disorders 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]

    Clinicians should use onabotulinumtoxinA with caution in patients with ocular disease. The efficacy of onabotulinumtoxinA treatment in deviations over 50 prism diopters, in restrictive strabismus, in Duane's syndrome with lateral rectus weakness, and in secondary strabismus caused by prior surgical over-recession of the antagonist has not been established. The toxin is ineffective in chronic paralytic strabismus except when used in conjunction with surgical repair to reduce antagonist contracture. When using onabotulinumtoxinA to treat blepharospasm, reduced blinking of the orbicularis muscle can lead to corneal exposure, persistent epithelial defect and corneal ulceration, especially in patients with VII nerve disorders. One case of corneal perforation in an aphakic eye requiring corneal grafting has occurred because of this effect. Careful testing of corneal sensation in eyes previously operated upon, avoidance of injection into the lower lid area to avoid ectropion, and vigorous treatment of any epithelial defect should be employed. Protective drops, ointment, therapeutic soft contact lenses, or closure of the eye by patching or other means my be required. Retrobulbar hemorrhages sufficient to compromise retinal circulation have occurred from needle penetrations into the orbit during administration of onabotulinumtoxinA for strabismus. It is recommended that appropriate instruments to decompress the orbit be accessible. Ocular (globe) penetrations by needles have also occurred. An ophthalmoscope to diagnosis the condition should be available. Inducing paralysis in one or more extraocular muscles may produce a visual disturbance such as spatial disorientation, double vision, or past pointing. Covering the affected eye may alleviate these symptoms.

    OnabotulinumtoxinA should be used cautiously in patients with cardiac 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.

    Patients with respiratory insufficiency treated with onabotulinumtoxinA for upper limb spasticity should be monitored closely. In a double-blind, placebo-controlled, parallel group study in patients with stable reduced pulmonary function (defined as FEV1 40% to 80% of predicted value and FEV1/FVC 0.75 or less), 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; it should be noted that differences from placebo were not statistically significant. In addition, in patients with reduced lung function treated for upper limb spasticity, upper respiratory tract infection was reported more frequently as an adverse reaction in patients treated with onabotulinumtoxinA vs. placebo. Caution is also advisable when administering onabotulinumtoxinA to patients with detrusor overactivity associated with a neurologic condition and restrictive lung disease of neuromuscular etiology (defined as FVC 50% to 80% of predicted value in patients with spinal cord injury between C5 and C8, or MS). Study data indicate that the event rate in change of FVC 15% or more or 20% or more was generally greater in patients receiving onabotulinumtoxinA than placebo.[29334]

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

    Administer onabotulinumtoxinA with caution in patients with a history of surgery in the treatment area as this may alter drug distribution within the injected muscles and thus alter the intended effect. Further, ask all patients if they have any planned surgical procedures. Advise patients to tell their other health care practitioners of this therapy prior to any surgeries.[29334] [41123]

    Anti-platelet therapy should be discontinued at least 3 days prior to onabotulinumtoxinA treatment in patients with detrusor overactivity associated with a neurologic condition. Patients on anticoagulant therapy need to be managed appropriately to reduce the risk of bleeding.[29334]

    Intradetrusor injection of onabotulinumtoxinA is contraindicated in patients with urinary retention (post-void residuals (PVR) greater than 200 mL) who are not routinely performing clean intermittent self-catheterization (CIC). Following treatment, patients 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 increase to more than 200 mL and continue until PVR is less than 200 mL. Treatment should be avoided in patients not able or unwilling to begin catheterization, if needed.[29334]

    Revision Date: 06/24/2019, 01:52:14 PM

    References

    29334 - Botox (onabotulinumtoxinA) injection package insert. Madison, NJ: Allergan USA, Inc.; 2022 Aug.41123 - Botox Cosmetic (onabotulinumA) package insert. Irvine, CA: Allergan, Inc.; 2018 May.

    Mechanism of Action

    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: 09/01/2011, 07:57:49 AM

    References

    29334 - Botox (onabotulinumtoxinA) injection package insert. Madison, NJ: Allergan USA, Inc.; 2022 Aug.

    Pharmacokinetics

    OnabotulinumtoxinA 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.

    Route-Specific Pharmacokinetics

    Intramuscular Route

    The onset and duration of action of onabotulinumtoxinA depends on the clinical use of the drug.

    Revision Date: 02/12/2010, 12:08:12 PM

    Pregnancy/Breast-feeding

    pregnancy

    There are no human data on the developmental risk associated with the use of onabotulinumtoxinA during human pregnancy. When administered intramuscularly (8 and 16 units/kg) two times to pregnant mice or rats during organogenesis, reductions in fetal weight and decreased fetal skeletal ossification were observed. The no-effect dose for developmental toxicity is approximately equivalent to the human dose of 400 units. No adverse effects were observed when pregnant rats received a single intramuscular injection.[29334] [41123]

    breast-feeding

    It is not known whether onabotulinumtoxinA is excreted in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for onabotulinumtoxinA and any potential adverse effects on the breastfed infant. OnabotulinumtoxinA is not detectable systemically after intramuscular use, thus excretion into breast milk is considered unlikely.[29334] [41123]

    Revision Date: 06/07/2017, 09:20:01 AM

    References

    29334 - Botox (onabotulinumtoxinA) injection package insert. Madison, NJ: Allergan USA, Inc.; 2022 Aug.41123 - Botox Cosmetic (onabotulinumA) package insert. Irvine, CA: Allergan, Inc.; 2018 May.

    Interactions

    Level 3 (Moderate)

    • Amikacin
    • Anticholinergics
    • Aspirin, ASA; Caffeine; Orphenadrine
    • Aspirin, ASA; Carisoprodol; Codeine
    • Atracurium
    • Atropine
    • Atropine; Difenoxin
    • Baclofen
    • Belladonna; Opium
    • Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate
    • Benztropine
    • Budesonide; Glycopyrrolate; Formoterol
    • Capreomycin
    • Capsaicin; Metaxalone
    • Carisoprodol
    • Chlordiazepoxide; Clidinium
    • Chlorzoxazone
    • Cisatracurium
    • Colistimethate, Colistin, Polymyxin E
    • Colistin
    • Cyclobenzaprine
    • Dantrolene
    • Dicyclomine
    • Diphenoxylate; Atropine
    • Flavoxate
    • Gentamicin
    • Glycopyrrolate
    • Glycopyrrolate; Formoterol
    • Homatropine; Hydrocodone
    • Hyoscyamine
    • Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate
    • Indacaterol; Glycopyrrolate
    • Metaxalone
    • Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine
    • Methscopolamine
    • Neostigmine; Glycopyrrolate
    • Neuromuscular blockers
    • Orphenadrine
    • Oxybutynin
    • Pancuronium
    • Phenobarbital; Hyoscyamine; Atropine; Scopolamine
    • Propantheline
    • Rocuronium
    • Scopolamine
    • Skeletal Muscle Relaxants
    • Solifenacin
    • Streptomycin
    • Succinylcholine
    • Tobramycin
    • Trihexyphenidyl
    • Trospium
    • Vecuronium

    Level 4 (Minor)

    • Neomycin
    • Paromomycin
    Amikacin: (Moderate) The effects of botulinum toxin can be potentiated by systemic aminoglycosides or other drugs that interfere with neuromuscular transmission. Monitor aminoglycoside concentrations, and monitor for evidence of neurotoxicity including systemic neuromuscular blockade. [29875] [35779] [41123] [41461] Anticholinergics: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention). [29334] [29875] [35779] [41461] Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Excessive neuromuscular weakness may be exacerbated by coadministration of a botulinum toxin with skeletal muscle relaxants. Advise patients to seek medical assistance if they develop any unusual symptoms (including difficulty with swallowing, speaking, or breathing or walking), or if any existing symptom worsens during use of a botulinum toxin. [29875] [35779] [41123] [41461] Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Excessive neuromuscular weakness may be exacerbated by coadministration of a botulinum toxin with skeletal muscle relaxants. Advise patients to seek medical assistance if they develop any unusual symptoms (including difficulty with swallowing, speaking, or breathing or walking), or if any existing symptom worsens during use of a botulinum toxin. [29875] [35779] [41123] [41461] Atracurium: (Moderate) Use neuromuscular blockers and botulinum toxins concurrently with caution because the effect of the botulinum toxin may be potentiated. If coadministered, observe the patient closely. [29875] [35779] [41123] [41461] Atropine: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention). [29334] [29875] [35779] [41461] Atropine; Difenoxin: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention). [29334] [29875] [35779] [41461] Baclofen: (Moderate) Excessive neuromuscular weakness may be exacerbated by coadministration of a botulinum toxin with skeletal muscle relaxants. Advise patients to seek medical assistance if they develop any unusual symptoms (including difficulty with swallowing, speaking, or breathing or walking), or if any existing symptom worsens during use of a botulinum toxin. [29875] [35779] [41123] [41461] Belladonna; Opium: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention). [29334] [29875] [35779] [41461] Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention). [29334] [29875] [35779] [41461] Benztropine: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention). [29334] [29875] [35779] [41461] Budesonide; Glycopyrrolate; Formoterol: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention). [29334] [29875] [35779] [41461] Capreomycin: (Moderate) The effects of Botulinum Toxins could be potentiated by drugs that interfere with neuromuscular transmission, such as capreomycin. [29334] [29875] [35779] [44155] Capsaicin; Metaxalone: (Moderate) Excessive neuromuscular weakness may be exacerbated by coadministration of a botulinum toxin with skeletal muscle relaxants. Advise patients to seek medical assistance if they develop any unusual symptoms (including difficulty with swallowing, speaking, or breathing or walking), or if any existing symptom worsens during use of a botulinum toxin. [29875] [35779] [41123] [41461] Carisoprodol: (Moderate) Excessive neuromuscular weakness may be exacerbated by coadministration of a botulinum toxin with skeletal muscle relaxants. Advise patients to seek medical assistance if they develop any unusual symptoms (including difficulty with swallowing, speaking, or breathing or walking), or if any existing symptom worsens during use of a botulinum toxin. [29875] [35779] [41123] [41461] Chlordiazepoxide; Clidinium: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention). [29334] [29875] [35779] [41461] Chlorzoxazone: (Moderate) Excessive neuromuscular weakness may be exacerbated by coadministration of a botulinum toxin with skeletal muscle relaxants. Advise patients to seek medical assistance if they develop any unusual symptoms (including difficulty with swallowing, speaking, or breathing or walking), or if any existing symptom worsens during use of a botulinum toxin. [29875] [35779] [41123] [41461] Cisatracurium: (Moderate) Use neuromuscular blockers and botulinum toxins concurrently with caution because the effect of the botulinum toxin may be potentiated. If coadministered, observe the patient closely. [29875] [35779] [41123] [41461] Colistimethate, Colistin, Polymyxin E: (Moderate) The effects of botulinum toxin type A or botulinum toxin type B can be potentiated by drugs that interfere with neuromuscular transmission, such as colistimethate sodium. If these drugs are used in combination, monitor patients for increased adverse effects. Neuromuscular blockade may be associated with colistimethate sodium, and is more likely to occur in patients with renal dysfunction. [29334] [29875] [30364] [33636] [34040] [41461] Colistin: (Moderate) The effects of botulinum toxin type A or botulinum toxin type B can be potentiated by drugs that interfere with neuromuscular transmission, such as colistimethate sodium. If these drugs are used in combination, monitor patients for increased adverse effects. Neuromuscular blockade may be associated with colistimethate sodium, and is more likely to occur in patients with renal dysfunction. [29334] [29875] [30364] [33636] [34040] [41461] Cyclobenzaprine: (Moderate) Excessive neuromuscular weakness may be exacerbated by coadministration of a botulinum toxin with skeletal muscle relaxants. Advise patients to seek medical assistance if they develop any unusual symptoms (including difficulty with swallowing, speaking, or breathing or walking), or if any existing symptom worsens during use of a botulinum toxin. [29875] [35779] [41123] [41461] Dantrolene: (Moderate) Excessive neuromuscular weakness may be exacerbated by coadministration of a botulinum toxin with skeletal muscle relaxants. Advise patients to seek medical assistance if they develop any unusual symptoms (including difficulty with swallowing, speaking, or breathing or walking), or if any existing symptom worsens during use of a botulinum toxin. [29875] [35779] [41123] [41461] Dicyclomine: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention). [29334] [29875] [35779] [41461] Diphenoxylate; Atropine: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention). [29334] [29875] [35779] [41461] Flavoxate: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention). [29334] [29875] [35779] [41461] Gentamicin: (Moderate) The effects of botulinum toxin can be potentiated by systemic aminoglycosides or other drugs that interfere with neuromuscular transmission. Monitor aminoglycoside concentrations, and monitor for evidence of neurotoxicity including systemic neuromuscular blockade. [29875] [35779] [41123] [41461] Glycopyrrolate: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention). [29334] [29875] [35779] [41461] Glycopyrrolate; Formoterol: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention). [29334] [29875] [35779] [41461] Homatropine; Hydrocodone: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention). [29334] [29875] [35779] [41461] Hyoscyamine: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention). [29334] [29875] [35779] [41461] Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention). [29334] [29875] [35779] [41461] Indacaterol; Glycopyrrolate: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention). [29334] [29875] [35779] [41461] Metaxalone: (Moderate) Excessive neuromuscular weakness may be exacerbated by coadministration of a botulinum toxin with skeletal muscle relaxants. Advise patients to seek medical assistance if they develop any unusual symptoms (including difficulty with swallowing, speaking, or breathing or walking), or if any existing symptom worsens during use of a botulinum toxin. [29875] [35779] [41123] [41461] Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention). [29334] [29875] [35779] [41461] Methscopolamine: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention). [29334] [29875] [35779] [41461] Neomycin: (Minor) The effects of botulinum toxin can be potentiated by systemic aminoglycosides or other drugs that interfere with neuromuscular transmission. However, neomycin oral and topical products are not well absorbed systemically; interactions are not expected. [35779] [41461] [6072] [6622] Neostigmine; Glycopyrrolate: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention). [29334] [29875] [35779] [41461] Neuromuscular blockers: (Moderate) Use neuromuscular blockers and botulinum toxins concurrently with caution because the effect of the botulinum toxin may be potentiated. If coadministered, observe the patient closely. [29875] [35779] [41123] [41461] Orphenadrine: (Moderate) Excessive neuromuscular weakness may be exacerbated by coadministration of a botulinum toxin with skeletal muscle relaxants. Advise patients to seek medical assistance if they develop any unusual symptoms (including difficulty with swallowing, speaking, or breathing or walking), or if any existing symptom worsens during use of a botulinum toxin. [29875] [35779] [41123] [41461] Oxybutynin: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention). [29334] [29875] [35779] [41461] Pancuronium: (Moderate) Use neuromuscular blockers and botulinum toxins concurrently with caution because the effect of the botulinum toxin may be potentiated. If coadministered, observe the patient closely. [29875] [35779] [41123] [41461] Paromomycin: (Minor) The effects of botulinum toxin can be potentiated by systemic aminoglycosides or other drugs that interfere with neuromuscular transmission. However, paromomycin is not well absorbed following oral administration; interactions are not expected. [35779] [41461] [6072] [6622] [7645] Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention). [29334] [29875] [35779] [41461] Propantheline: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention). [29334] [29875] [35779] [41461] Rocuronium: (Moderate) Use neuromuscular blockers and botulinum toxins concurrently with caution because the effect of the botulinum toxin may be potentiated. If coadministered, observe the patient closely. [29875] [35779] [41123] [41461] Scopolamine: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention). [29334] [29875] [35779] [41461] Skeletal Muscle Relaxants: (Moderate) Excessive neuromuscular weakness may be exacerbated by coadministration of a botulinum toxin with skeletal muscle relaxants. Advise patients to seek medical assistance if they develop any unusual symptoms (including difficulty with swallowing, speaking, or breathing or walking), or if any existing symptom worsens during use of a botulinum toxin. [29875] [35779] [41123] [41461] Solifenacin: (Moderate) Systemic anticholinergic effects (e.g., blurred vision) may be potentiated if antimuscarinics are administered after administration of botulinum toxins. [35779] Streptomycin: (Moderate) The effects of botulinum toxin can be potentiated by systemic aminoglycosides or other drugs that interfere with neuromuscular transmission. Monitor aminoglycoside concentrations, and monitor for evidence of neurotoxicity including systemic neuromuscular blockade. [29875] [35779] [41123] [41461] Succinylcholine: (Moderate) Use neuromuscular blockers and botulinum toxins concurrently with caution because the effect of the botulinum toxin may be potentiated. If coadministered, observe the patient closely. [29875] [35779] [41123] [41461] Tobramycin: (Moderate) The effects of botulinum toxin can be potentiated by systemic aminoglycosides or other drugs that interfere with neuromuscular transmission. Monitor aminoglycoside concentrations, and monitor for evidence of neurotoxicity including systemic neuromuscular blockade. [29875] [35779] [41123] [41461] Trihexyphenidyl: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention). [29334] [29875] [35779] [41461] Trospium: (Moderate) Systemic anticholinergic effects (e.g., blurred vision) may be potentiated if antimuscarinics are administered after administration of botulinum toxins. [35779] Vecuronium: (Moderate) Use neuromuscular blockers and botulinum toxins concurrently with caution because the effect of the botulinum toxin may be potentiated. If coadministered, observe the patient closely. [29875] [35779] [41123] [41461]
    Revision Date: 01/11/2024, 04:54:00 PM

    References

    6072 - Botox (onabotulinumtoxinA) injection package insert. Madison, NJ: Allergan USA, Inc.; 2022 Aug.6622 - Myobloc (rimabotulinumtoxinB) package insert. Louisville, KY: Solstice Neurosciences, Inc.; 2020 Sept.7645 - Chambers HF. Antimicrobial Agents: the aminoglycosides. In: Gilman AG, Hardman JG, Limbird LE, eds. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 10th ed. New York: McGraw-Hill Companies 2001:1219-38.29334 - Botox (onabotulinumtoxinA) injection package insert. Madison, NJ: Allergan USA, Inc.; 2022 Aug.29875 - Myobloc (rimabotulinumtoxinB) package insert. Louisville, KY: Solstice Neurosciences, Inc.; 2020 Sept.30364 - Taylor P. Agents acting at the neuromuscular junction and autonomic ganglia. Gilman AG, Hardman JG, Limbird LE, (eds.) In: Goodman and Gilman's The Pharmacological Basis of Therapeutics. 10th ed., New York, McGraw-Hill Companies. 2001:193-213.33636 - Coly-Mycin M Parenteral (colistimethate sodium) package insert. Chestnut Ridge, NY: Par Pharmaceutical Companies, Inc.; 2015 Jul.34040 - Falagas ME, Kasiakou SK. Toxicity of polymyxins: a systematic review of the evidence from old and recent studies. Crit Care 2006;10:R27.35779 - Dysport (abobotulinumtoxinA) package insert. Cambridge, MA: Ipsen Biopharmaceuticals, Inc.; 2023 Sep.41123 - Botox Cosmetic (onabotulinumA) package insert. Irvine, CA: Allergan, Inc.; 2018 May.41461 - Xeomin (incobotulinumtoxinA) package insert. Raleigh, NC: Merz Pharmaceuticals, LLC; 2023 Sep.44155 - Capastat (capreomycin sulfate injection) package insert. Lake Forest, IL: Akorn, Inc.; 2023 Jan.

    Monitoring Parameters

    • laboratory monitoring not necessary

    US Drug Names

    • Botox
    • Botox Cosmetic
    ;