Class: Other Miscellaneous Therapeutic Agents
Chemical Name: Complex with hemagglutinin (Clostridium botulinum A strain Hall) and neurotoxin (Clostridium botulinum A strain Hall light chain) and protein NTNH (non-toxin non-hemagglutinin) (Clostridium botulinum A strain Hall) neurotoxin (Clostridium botulinum A strain Hall heavy chain)
CAS Number: 953397-35-8
- Distant Spread of Toxin Effects
Effects of any botulinum toxin may spread from local sites of injection, producing symptoms consistent with the mechanism of action of botulinum toxin.381 383 384 (See Distant Spread of Toxin Effects under Cautions.)
Symptoms reported hours to weeks following injection.384
Uses for AbobotulinumtoxinA
Currently, 3 botulinum toxin type A preparations (abobotulinumtoxinA [Dysport], incobotulinumtoxinA [Xeomin], and onabotulinumtoxinA [Botox, Botox Cosmetic]) and one botulinum toxin type B preparation (rimabotulinumtoxinB [Myobloc]) are commercially available in the US.1 2 5 384 403 These preparations are not interchangeable; assay methods used to determine potency of botulinum toxins are specific to each individual manufacturer and/or formulation.1 2 5 381 384 385 391 396 399 403 410
Botulinum toxins considered first-line therapy for cervical dystonia.387 391 AbobotulinumtoxinA shown to produce objective and subjective improvements in functional impairment and/or disability.384 385 387 Evidence supporting use largely based on clinical trials of short duration using single injection cycles; additional studies needed to establish long-term efficacy and safety, optimum treatment intervals, and administration techniques (e.g., use of electromyogram [EMG] guidance versus palpation).387
Glabellar Facial Lines
AbobotulinumtoxinA Dosage and Administration
Do not exceed recommended dose and frequency; excessive and/or unintended neuromuscular weakness may occur if higher than recommended dosages are given.384 Use minimum effective dosage whenever possible to reduce risk of adverse effects.384 388
Administer by IM injection into affected muscles.384
Instructions for reconstitution and administration are specific to each vial size and condition being treated; consult manufacturer's labeling for detailed instructions regarding reconstitution, preparation, and administration.384
Monitor patients for respiratory distress or other possible adverse effects related to spread of botulinum toxin (e.g., dysphagia, dysphonia, unexpected muscle weakness, urinary incontinence, ptosis, double vision, blurred vision, dysarthria).381 384 (See Distant Spread of Toxin Effects under Cautions.)
For cervical dystonia, reconstitute vial labeled as containing 300 or 500 units of lyophilized drug with 0.6 or 1 mL of preservative-free 0.9% sodium chloride injection to provide a solution containing 250 units per 0.5 mL or 500 units per mL, respectively.384 Gently rotate vial until powder is completely dissolved.384
For glabellar facial lines, reconstitute vial labeled as containing 300 units of abobotulinumtoxinA with 1.5 or 2.5 mL of preservative-free 0.9% sodium chloride injection to provide a solution containing 10 units per 0.05 mL or 10 units per 0.08 mL, respectively.384 Use a 21-gauge needle to draw an appropriate amount of diluent into a syringe.384 Insert needle into drug vial at a 45° angle and allow partial vacuum to draw in diluent; do not use vial if vacuum is absent.384 Gently rotate vial until powder is completely dissolved.384
Injection Techniques (Cervical Dystonia)
EMG-guided injections may be helpful in locating target injection sites, particularly for muscles that are difficult to identify by physical examination alone.384
Injection Techniques (Glabellar Facial Lines)
Identify injection sites by palpating for areas of tense muscle mass in the lateral corrugator and vertical procerus muscles while patient is frowning; location, size, and use of such muscles may vary considerably among individuals.384
Injections into the medial corrugator muscle should be ≥1 cm above the supraorbital ridge and should not be injected <1 cm above the central eyebrow.384
Avoid injections near the levator palpebrae superioris, especially in individuals with larger brow-depressor complexes.384
Assay methods used to determine potency of various botulinum toxin preparations are specific to each individual preparation; units of biologic activity of abobotulinumtoxinA cannot be compared with or converted to units of other botulinum toxin preparations.381 384 385 391 396 397 399
Toxin-naive and previously treated patients: Initially, 500 units as a divided dose among affected muscles.384
In clinical studies, median initial doses injected into the sternocleidomastoid, splenius capitis, trapezius, levator scapulae, scalenus (medius and anterior), semispinalis capitis, and longissimus muscles were 125 units (range 50–350), 200 units (range 75–450), 102.6 units (range 50–300), 105.3 units (range 50–200), 115.5 units (range 50–300), 131.6 units (range 50–250), and 150 units (range 100–200), respectively.384
Adjust total dosage administered in subsequent treatment sessions by increments of 250 units based on patient response.384
Usual duration of response 12–16 weeks or longer; may repeat treatments every 12–16 weeks or longer if symptoms return.384
Glabellar Facial Lines
Manufacturer recommends a total dose of 50 units per treatment session, administered as 10 units (0.05 or 0.08 mL depending on concentration of reconstituted solution) into each of 5 sites: 2 in each corrugator muscle and one in procerus muscle.384
Limit total dose injected into sternocleidomastoid muscle to minimize risk of dysphagia.384 (See Dysphagia/Breathing Difficulties under Cautions.)
Do not repeat treatments more frequently than once every 12 weeks.384
Glabellar Facial Lines
Do not repeat treatments more frequently than once every 3 months.384
Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy.384 (See Geriatric Use under Cautions.)
Cautions for AbobotulinumtoxinA
Known hypersensitivity to any botulinum toxin preparation or any ingredient in their formulations.384
Allergy to cow milk protein.384
Infection at proposed injection site(s).384
Distant Spread of Toxin Effects
Serious adverse effects consistent with mechanism of botulinum toxin action (e.g., asthenia, generalized muscle weakness, diplopia, ptosis, dysphagia, dysphonia, dysarthria, urinary incontinence, breathing difficulties) reported.371 381 382 383 384 (See Advice to Patients.)
In some cases, severe swallowing and breathing difficulties required hospitalization, mechanical ventilation, or feeding tubes and/or resulted in death.381 384 (See Dysphagia/Breathing Difficulties under Cautions.)
Potential risk of hypersensitivity.384 (See Contraindications under Cautions.) Serious hypersensitivity reactions (including anaphylaxis) reported rarely with another preparation of botulinum toxin type A (Botox).1
Possibility of immune reaction following intradermal administration of abobotulinumtoxinA not known.384 Manufacturer states that safety and efficacy of abobotulinumtoxinA for treatment of hyperhidrosis not established.384
Lack of Interchangeability Among Botulinum Toxin Preparations
The method used to determine potency (“units”) of abobotulinumtoxinA is specific to the Dysport preparation;381 384 388 391 396 399 therefore, units of biologic activity for abobotulinumtoxinA cannot be compared with or converted to units of any other botulinum toxin preparation.381 384 385 388 391 393 396 397
Risk of dysphagia in patients receiving a botulinum toxin for cervical dystonia.381 383 384 388 Usually a consequence of cervical muscle weakening from local areas of injection, but also may be related to distant spread of toxin effects.381 384 (See Distant Spread of Toxin Effects under Cautions.)
Botulinum toxins may weaken neck muscles that serve as accessory muscles of ventilation, resulting in critical loss of breathing capacity in patients with respiratory disorders.403 Aspiration and death reported as a complication of severe dysphagia.381 383 384 Patients with compromised swallowing function are at increased risk of aspiration.384
Immediate medical attention may be required if sudden difficulties in speech or swallowing develop during or following treatment; such effects may occur hours to weeks after injection.381 384 Gastric feeding tubes may be required in severe cases.381 384
Administration Precautions in Patients with Glabellar Facial Lines
Administer with caution in patients with surgically altered facial anatomy, excessive weakness or atrophy in target muscles, marked facial asymmetry, inflammation, ptosis, excessive dermatochalasis, deep dermal scarring, thick sebaceous skin, or glabellar lines that cannot be substantially decreased manually.384
Clinicians who administer abobotulinumtoxinA should understand the relevant neuromuscular and/or orbital anatomy of the therapeutic area and effects of any changes from surgical alterations.384
Increased incidence of ptosis observed with use of higher than recommended dosages; do not exceed recommended dose and frequency.384 Minimize risk of ptosis with careful monitoring (e.g., examining upper lid for separation or weakness of the levator palpebrae muscle, evaluating range of eyelid excursion, identifying lash ptosis) and adherence to manufacturer's recommended dosages and injection techniques.384 (See Injection Techniques [Glabellar Facial Lines] under Dosage and Administration.)
Preexisting Neuromuscular Disorders
Risk of adverse effects (e.g., severe dysphagia and/or respiratory compromise) with usual dosages of abobotulinumtoxinA appears to be increased in patients with neuromuscular disorders (e.g., peripheral motor neuropathic diseases [e.g., amyotrophic lateral sclerosis, motor neuropathy] or neuromuscular junction disorders [e.g., myasthenia gravis, Lambert-Eaton syndrome]); closely monitor such patients.384
Risk of Viral Transmission
Preparation contains albumin derived from human blood.384 Remote risk of transmission of Creutzfeldt-Jakob disease (CJD) and other viral diseases via albumin component; however, no cases identified to date.384
Antibodies may reduce therapeutic effect; however, some patients with neutralizing antibodies continue to respond to the drug.384 385 Certain botulinum toxin preparations may be more likely to elicit an immune response.388
Reporting Adverse Effects or Overdosage
If the patient receives an overdose of abobotulinumtoxinA or the drug is injected into the wrong muscle (i.e., misinjection), contact the local or state health department to process a request for botulism antitoxin through the CDC Drug Service.384 If a response is not received within 30 minutes, contact the CDC Emergency Operations Center directly at 770-488-7100.384 Information about the antitoxin is available at .
Botulism antitoxin will not reverse any botulinum toxin-induced muscle weakness evident at the time of antitoxin administration but may stabilize the deficits.384
Not known whether distributed into milk.384
Manufacturer states that safety and efficacy not established in patients <18 years of age with cervical dystonia.384
Not recommended for cosmetic improvement of glabellar lines in patients <18 years of age.384
Insufficient experience in patients ≥65 years of age to determine whether such patients respond differently than younger adults;384 select dosage with caution due to age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy.384
Response rates in African Americans (with Fitzpatrick skin types IV–VI) and Hispanic patients with glabellar facial lines appear to be similar to those observed in the general population.384
Common Adverse Effects
Cervical dystonia: Muscular weakness, dysphagia, dry mouth, injection site discomfort, fatigue, headache, neck pain, musculoskeletal pain, dysphonia, injection site pain, eye disorders (blurred vision, diplopia, reduced visual acuity and accommodation).384 385
Interactions for AbobotulinumtoxinA
No formal drug interaction studies to date.384
Potential for additive anticholinergic effects.384
Anti-infective agents interfering with neuromuscular transmission (e.g., aminoglycosides)
Potential for additive botulinum toxin effects384
Closely monitor for adverse effects384
Botulinum toxin treatment, concurrent or sequential
Possible excessive muscle weakness with concurrent or sequential use within several months of abobotulinumtoxinA384
Data on concurrent or sequential use of botulinum toxins lacking384
Potential for excessive muscular weakness when administered prior to, concurrently with, or following abobotulinumtoxinA384
Not detectable in peripheral circulation following IM administration.384
Cervical dystonia: Usual duration of effect ≥12–16 weeks or more.384
Powder for Injection
2–8°C; protect from light.384
Following reconstitution, store at 2–8°C and use within 4 hours; do not freeze.384
Purified neurotoxin type A complex produced by fermentation of Clostridium botulinum (Hall strain).384 388 391 396 Differs from other currently available preparations of botulinum toxin type A in molecular size, pharmacologic properties, dosing requirements, and adverse effect profile.384 388 391 396 (See Lack of Interchangeability Among Botulinum Toxin Preparations under Cautions.)
Neurotoxic effects occur in 3 phases: binding, internalization, and inhibition of acetylcholine from nerve terminals resulting in neuromuscular blockade.384
May also have a direct analgesic effect through modulation of certain peptide neurotransmitters.391
Advice to Patients
Importance of providing a copy of the FDA-approved medication guide and reviewing its contents with every patient.384 400 Instruct patients to read medication guide prior to initiation of therapy and each time prescription is refilled.384 400
Advise patients and/or caregivers to seek immediate medical attention if unexpected muscle weakness, swallowing, speech, or respiratory disorders occur, or if any existing symptoms worsen or persist.384 400
Advise patients that abobotulinumtoxinA can cause loss of strength, muscle weakness, blurred vision, or drooping eyelids, and that they should not drive a car, operate machinery, or engage in any other potentially hazardous activities during treatment.384 400
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses (e.g., neuromuscular disorders).384 400
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
AHFS DI Essentials. © Copyright, 2016, American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
Last reviewed: April 27, 2015
Date modified: February 08, 2016
Date published: April 27, 2015
1. Allergan. Botox (onabotulinumtoxinA) prescribing information. Irvine, CA; 2013 Sep.
2. Solstice Neurosciences. Myobloc (rimabotulinumtoxinB) injection prescribing information. South San Francisco, CA; 2010 May.
5. Allergan. Botox Cosmetic (onabotulinumtoxinA) for injection prescribing information. Irvine, CA; 2013 Sep.
18. Blackie JD, Lees AJ. Botulinum toxin treatment in spasmodic torticollis. J Neurol Neurosurg Psychiatry. 1990; 53:640-3. [PubMed 2213040]
23. Anderson TJ, Rivest J, Stell R et al. Botulinum toxin treatment of spasmodic torticollis. J R Soc Med. 1992; 85:524-9. [PubMed 1433117]
26. Bhatia KP, Munchau A, Thompson PD et al. Generalised muscular weakness after botulinum toxin injections for dystonia: a report of three cases. J Neurol Neurosurg Psychiatry. 1999; 67:90-3. [PubMed 10369829]
28. Sheean GL, Murray NM, Marsden CD. Pain and remote weakness in limbs injected with botulinum toxin A for writer’s cramp. Lancet. 1995; 346:154-6. [IDIS 349836] [PubMed 7603232]
38. Cobb DB, Watson WA, Fernandez MC. Botulism-like syndrome after injections of botulinum toxin. Vet Hum Toxicol. 2000 Jun; 42:163.
52. Bakheit AM, Ward CD, McLellan DL. Generalised botulism-like syndrome after intramuscular injections of botulinum toxin type A: a report of two cases. J Neurol Neurosurg Psychiatry. 1997; 62:198. [PubMed 9048725]
53. Williams A. Consensus statement for the management of focal dystonias. Br J Hosp Med. 1993; 50:655-9. [PubMed 8124547]
57. Thobois S, Broussolle E, Toureille L et al. Severe dysphagia after botulinum toxin injection for cervical dystonia in multiple system atrophy. Mov Disord. 2001 Jul; 16:764-5.
58. Erbguth F, Claus D, Engelhardt A et al. Systemic effect of local botulinum toxin injections unmasks subclinical Lambert-Eaton myasthenic syndrome. J Neurol Neurosurg Psychiatry. 1993; 56:1235- 6. [PubMed 8229041]
76. Krack P, Deuschl G, Benecke R et al. Dose standardization of botulinum toxin. Mov Disord. 1998; 13:749-51. [PubMed 9686787]
142. Matarasso A, Deva AK. Botulinum toxin. Plast Reconstr Surg. 2002; 109:1191-7. [PubMed 11884859]
298. Allergan. Irvine, CA: Personal communication.
371. Food and Drug Administration. Early communication about an ongoing safety review: Botox and Botox Cosmetic (botulinum toxin type A) and Myobloc (botulinum toxin type B). Rockville, MD; 2008 Feb 8. From FDA website.
372. Food and Drug Administration. FDA notifies public of adverse reactions linked to Botox use. FDA News. February 8, 2008. From FDA website.
373. Food and Drug Administration. Botox, Botox Cosmetic (botulinum toxin type A), Myobloc (botulinum toxin type B). Medwatch safety information alerts 2008. Rockville, MD; February 8, 2008. From FDA website.
379. Tugnoli V, Eleopra R, Quatrale R et al. Botulism-like syndrome after botulinum toxin type A injections for focal hyperhidrosis. Br J Dermatol. 2002; 147:808-9. [PubMed 12366438]
380. Roche N, Schnitzler A, Genet F F et al. Undesirable distant effects following botulinum toxin type A injection. Clin Neuropharmacol 2008; 31:272-80.
381. Food and Drug Administration. Follow-up to the February 8, 2008, early communication about an ongoing safety review of Botox and Botox Cosmetic (Botulinum toxin Type A) and Myobloc (Botulinum toxin Type B). Rockville, MD; 2009 May 1. From FDA website (http: / / www.fda.gov / Drugs / DrugSafety / PostmarketDrugSafetyInformationforPatientsandProviders / DrugSafetyInformationforHeathcareProfessionals / ucm143819.htm)
382. Food and Drug Administration. Botox and Botox Cosmetic (Botulinum toxin type A) and Myobloc (botulinum toxin type B). Medwatch Safety Alerts for Human Medical Products 2009. Rockville, MD; 2009 April 30. From FDA website (http: / / www.fda.gov / Safety / MedWatch / SafetyInformation / SafetyAlertsforHumanMedicalProducts / ucm164255.htm)
383. Woodcock J (US Food and Drug Administration). Response to Public Citizen's petition on botulinum toxin re: docket no: FDA-2008-P-0061. Rockville, MD; 2009 April 30. From FDA website.
384. Ipsen Biopharmaceuticals. Dysport for injection (abobotulinumtoxinA) prescribing information. Basking Ridge, NJ; 2013 Sep.
385. Truong D, Duane DD, Jankovic J et al. Efficacy and safety of botulinum type A toxin (Dysport) in cervical dystonia: results of the first US randomized, double-blind, placebo-controlled study. Mov Disord. 2005; 20:783-91. [PubMed 15736159]
387. Costa J, Espirito-Santo CC, Borges AA et al. Botulinum toxin type A therapy for cervical dystonia (review). Cochrane Database of Systematic Reviews. 2005, Issue 1. Article No: CD003633. DOI: 10.1002/14651858.CD003633.pub2.
388. Wenzel R, Jones D, Borrego JA. Comparing two botulinum toxin type A formulations using manufacturers' product summaries. J Clin Pharm Ther. 2007; 32:387-402. [PubMed 17635341]
389. Food and Drug Administration. Orphan designations pursuant to Section 526 of the Federal Food and Cosmetic Act as amended by the Orphan Drug Act (P.L. 97 414). Rockville, MD. From FDA web site (). Accessed 2009 May 27.
391. Chapman MA, Barron R, Tanis DC et al. Comparison of botulinum neurotoxin preparations for the treatment of cervical dystonia. Clin Ther. 2007; 29:1325-37. [PubMed 17825685]
392. Dong M, Yeh F, Tepp WH et al. SV2 is the protein receptor for botulinum neurotoxin A. Science. 2006; 312:592-6. [PubMed 16543415]
393. Brandt F, Swanson N, Baumann L et al. Randomized, placebo-controlled study of a new botulinum toxin type A for treatment of glabellar lines: efficacy and safety. Dermatol Surg. 2009; :1893-901. [PubMed 19549186]
394. Rubin MG, Dover J, Glogau RG et al. The efficacy and safety of a new U.S. Botulinum toxin type A in the retreatment of glabellar lines following open-label treatment. J Drugs Dermatol. 2009; 8:439-44. [PubMed 19537366]
395. Moy R, Maas C, Monheit G et al. Long-term safety and efficacy of a new botulinum toxin type A in treating glabellar lines. Arch Facial Plast Surg. 2009 Mar-Apr; 11:77-83. [PubMed 19289677]
396. Bell MS, Vermeulen LC, Sperling KB. Pharmacotherapy with botulinum toxin: harnessing nature's most potent neurotoxin. Pharmacotherapy. 2000; 20:1079-91. [PubMed 10999501]
397. Kane MA, Rohrich RJ, Narins RS et al. Evaluation of variable-dose treatment with a new U.S. botulinum toxin type A (Dysport) for correction of moderate to severe glabellar lines: results from a phase III, randomized, double-blind, placebo-controlled study. Plast Reconstr Surg. 2009; :1619-29. [PubMed 19584772]
398. Monheit GD, Cohen JL, the Reloxin Investigational Group. Long-term safety of repeated administrations of a new formulation of botulinum toxin type A in the treatment of glabellar lines: Interim analysis from an open-label extension study. J Am Acad Dermatol. 2009; :. [PubMed 19577326]
399. Cheng CM, Chen JS, Patel RP. Unlabeled uses of botulinum toxins: a review, part 1. Am J Health Syst Pharm. 2006; 63:145-52. [PubMed 16390928]
400. Ipsen Biopharmaceuticals. Dysport for injection (abobotulinumtoxinA) medication guide. Basking Ridge, NJ; 2012 Feb.
403. Merz Pharmaceuticals. Xeomin (incobotulinumtoxinA) for injection, intramuscular use prescribing information. Greensboro, NC; 2013 Jul.
410. Food and Drug Administration. Follow-up to the February 8, 2008, early communication about an ongoing safety review of Botox and Botox Cosmetic (Botulinum toxin Type A) and Myobloc (Botulinum toxin Type B). Rockville, MD; 2009 May 1. From FDA website (http: / / www.fda.gov / Drugs / DrugSafety / PostmarketDrugSafetyInformationforPatientsandProviders / DrugSafetyInformationforHeathcareProfessionals / ucm143819.htm)
More about abobotulinumtoxinA
- Other brands: Dysport