Botulinum Toxin Type A

Pronunciation: BOT-ue-lin-um
Class: Botulinum toxin

Trade Names:
Botox
- Injection, lyophilized powder for solution 100 units of onabotulinumtoxinA
- Injection, lyophilized powder for solution 200 units of onabotulinumtoxinA

Trade Names:
Botox Cosmetic
- Injection, lyophilized powder for solution 50 units of onabotulinumtoxinA
- Injection, lyophilized powder for solution 100 units of onabotulinumtoxinA

Trade Names:
Dysport
- Injection, lyophilized powder for solution 300 units of abobotulinumtoxinA
- Injection, lyophilized powder for solution 500 units of abobotulinumtoxinA

Trade Names:
Xeomin
- Injection, lyophilized powder for solution 50 units of incobotulinumtoxinA
- Injection, lyophilized powder for solution 100 units of incobotulinumtoxinA

Pharmacology

Blocks neuromuscular transmission by binding to acceptor sites on motor or sympathetic nerve terminals, entering the nerve terminals, and inhibiting the release of acetylcholine.

Produces temporary chemical denervation of sweat glands and local reduction in sweating when injected intradermally.

Pharmacokinetics

Absorption

Not expected to be present in peripheral blood at measurable levels following IM or intradermal injection at recommended doses.

Indications and Usage

Treatment of cervical dystonia in adults to decrease severity of abnormal head position and neck pain associated with cervical dystonia ( Botox , Dysport , and Xeomin ); treatment of strabismus and blepharospasm associated with dystonia, including benign essential blepharospasm or VII nerve disorder in patients 12 y of age and older ( Botox ); treatment of adults with blepharospasm who were previously treated with Botox ( Xeomin ); treatment of severe primary axillary hyperhidrosis inadequately managed with topical agents ( Botox ); temporary improvement in appearance of moderate to severe glabellar lines associated with corrugator or procerus muscle activity in patients 65 y of age or younger ( Botox Cosmetic and Dysport ); treatment of upper limb spasticity in adults, to decrease the severity of increased muscle tone in elbow, wrist, and finger flexors ( Botox ).

Unlabeled Uses

Achalasia; acquired nystagmus; facial lines and wrinkles; gustatory sweating; hand dystonia; headache; palmar hyperhidrosis; sialorrhea; Tourette syndrome.

Contraindications

Infection at the proposed injection site(s); hypersensitivity to any botulinum toxin preparation or ingredient in the formulations, including cow's milk protein ( Dysport ).

Dosage and Administration

Botox
Axillary Hyperhidrosis Adults

Intradermally 50 units (2 mL of reconstituted solution) injected into defined hyperhidrotic area in 0.1 to 0.2 mL aliquots to each axilla, evenly distributed in multiple sites (10 to 15) approximately 1 to 2 cm apart. Administer repeat injections when clinical effect of previous injection diminishes.

Blepharospasm Adults and Children 12 y of age and older

IM Initially, inject 1.25 to 2.5 units (0.05 to 0.1 mL at each site) into the medial and lateral pretarsal orbicularis oculi of the upper lid and into the lateral pretarsal orbicularis oculi of the lower lid. Cumulative dose in a 30-day period should not exceed 200 units.

Cervical Dystonia Adults and Children 16 y of age and older

IM In patients with known history of tolerance, tailor dosing in initial and sequential treatments to the individual patient based on patient's head and neck position, localized pain, muscle hypertrophy, patient response, and adverse reaction history. In patients without prior use, use lower dose than in patients with known history of tolerance, adjusting subsequent doses based on individual response. No more than 50 units per site should be administered.

Strabismus Adults and Children 12 y of age and older

IM Inject between 0.05 and 0.15 mL per muscle into extraocular muscles utilizing electrical activity recorded from tip of injection needle as guide to placement within target muscle. Maximum dose is 25 units as a single injection for any 1 muscle.

Upper Limb Spasticity Adults

IM The lowest recommended starting dose should be used. Tailor dosing based on size, number, and location of muscles involved; severity of spasticity; presence of local muscle weakness; and response to previous treatment or adverse reaction history. Recommended dose range per muscle is as follows: biceps brachii, 100 to 200 units divided in 4 sites; flexor carpi radialis or flexor carpi ulnaris, 12.5 to 50 units in 1 site; flexor digitorum profundus or flexor digitorum sublimis, 30 to 50 units in 1 site. No more than 50 units per site should be administered.

Botox Cosmetic
Glabellar Lines Adults 65 y of age or younger

IM Total treatment dose is 20 units in 0.5 mL (0.1 mL into each of 5 sites, 2 in each corrugator muscle and 1 in the procerus muscle) at intervals no more frequently than every 3 mo (duration of activity of botulinum toxin type A is approximately 3 to 4 mo).

Dysport
Cervical Dystonia Adults

IM 500 units initially as a divided dose among affected muscles. Make dosage adjustments in 250 unit steps according to patient's response, with retreatment every 12 wk or longer. Usual dosage 250 to 1,000 units every 12 wk or longer.

Glabellar Lines Adults

IM 50 units in 5 equal aliquots of 10 units each. Administer no more frequently than every 3 mo.

Xeomin
Blepharospasm Adults

IM Initial total dose should be the same dose as the patient's previous treatment of Botox . If previous Botox dose is unknown, use 1.25 to 2.5 units per injection site as the initial dose. Base the number and location of injection sites on severity of blepharospasm, and previous dose and response to Botox . Total initial dose in both eyes should not exceed 70 units (35 units per eye). Subsequent dosing should be tailored to the individual patient based on response, up to a max dose of 35 units per eye, and should be no more frequent than every 12 wk.

Cervical dystonia Adults

IM Recommended initial total dose is 120 units. Individualize dose and number of injection sites in each treated muscle based on the number and location of the muscle(s) to be treated, degree of spasticity/dystonia, muscle mass, and body weight. Consider past dose, response to treatment, duration of effect, and adverse event history in patients previously treated with botulinum toxin type A. Repeat treatments should generally be no more frequent than every 12 wk.

General Advice

  • Reconstitute powder for injection following manufacturer's guidelines for dilution using sterile, nonpreserved saline injection. Record date and time of reconstitution on vial.
  • Discard vial if vacuum does not pull diluent into vial.
  • Do not reconstitute with diluents other than sterile, nonpreserved saline, or add other medications to vial.
  • Do not administer if particulate matter, cloudiness, or discoloration is noted.
  • Use a new sterile needle and syringe to enter vial on each occasion for removal of medication. Ensure that epinephrine or another precautionary method is available should an anaphylactic reaction occur.
  • Discard any unused solution that is not used within 4 h of reconstitution (24 h for Xeomin and Botox 100 unit vial).
  • Follow institutional or organizational procedures for discarding medical waste and disposing of unused solution, vials, and equipment used for drug administration.
  • Do not exceed recommended dosages or frequencies of administration.
  • When using Botox for 1 or more indications, the max cumulative dose should not exceed 360 units in a 3-mo interval.

Storage/Stability

Store unopened vials in refrigerator (36° to 46°F) for up to 24 mo ( Botox 200 unit vial, Botox Cosmetic 50 unit vial, Dysport ) or 36 mo ( Botox and Botox Cosmetic 100 unit vial). Xeomin may be stored at 68° to 77°F, in a refrigerator at 36° to 46°F, or in a freezer at −4° to 14°F for up to 36 mo. Reconstituted solution may be stored for up to 4 h if refrigerated (24 h for Botox 100 unit vial or Xeomin ). Do not freeze reconstituted solution.

Drug Interactions

Aminoglycosides, drugs interfering with neuromuscular transmission (eg, lincomycin, quinidine, succinylcholine)

The effects of botulinum toxin may be potentiated. Use with caution.

Botulinum neurotoxin (eg, botulinum toxin type B)

Administration of a different botulinum neurotoxin at the same time or within several months of each other may exacerbate excessive neuromuscular weakness. Use with caution.

Muscle relaxants (eg, metaxalone)

Excessive weakness may be exaggerated. Use with caution.

Nondepolarizing muscle relaxants (eg, tubocurarine)

Neuromuscular action may be enhanced, resulting in protracted respiratory depression. Use with caution.

Adverse Reactions

Cardiovascular

Hypertension (1%); arrhythmia, MI, syncope (postmarketing).

CNS

Fatigue (12%); headache (11%); anxiety, asthenia, dizziness, drowsiness, hypertonia, paresthesia (2% to 10%); hypoesthesia, malaise, new-onset or recurrent seizures, vertigo with nystagmus (postmarketing).

Dermatologic

Pruritus, sweating (3% to 10%); skin tightness (1%); allergic dermatitis, erythema, erythema multiforme, excessive granulation tissue, psoriasiform eruption (postmarketing).

EENT

Ptosis (21%); dry eye (16%); visual impairment (12%); nasopharyngitis (10%); pharyngitis, rhinitis (2% to 10%); eye disorders (7%); superficial punctuate keratitis (6%); blepharoptosis (3%); eyelid edema (2%); blurred vision, decreased hearing, diplopia, dysarthria, ear noise, eye swelling, glaucoma, hypoacusis, retinal vein occlusion, tinnitus (postmarketing).

GI

Dysphagia (19%); dry mouth (16%); nausea, oral dryness (2% to 10%); diarrhea (8%); dyspepsia, tooth disorder (1%); abdominal pain, anorexia, loss of appetite, vomiting (postmarketing).

Genitourinary

Blood in urine (2%).

Local

Discomfort (13%); hemorrhage, pain (3% to 10%); soreness (2% to 10%); erythema, facial pain (less than 3%); bruising, infection, inflammation, localized numbness, swelling, tenderness, weakness (postmarketing).

Musculoskeletal

Muscle weakness (16%); neck pain (15%); back pain (2% to 10%); pain in extremity (9%); musculoskeletal pain (7%); muscle atrophy (1%); amyotrophy, muscle spasm, myalgia, myasthenia gravis (postmarketing).

Respiratory

Upper respiratory tract infection (12%); cough (2% to 10%); dysphonia (6%); dyspnea, respiratory tract infection (5%); breathing difficulties, bronchitis (3%); sinusitis (2%); dyspnea, pneumonia.

Miscellaneous

Infections and infestations (20%); fever, flu syndrome, speech disorder (2% to 10%); transient ptosis (5%); anaphylaxis; brachial plexopathy, burning sensation, facial palsy, facial paralysis, herpes zoster, hypersensitivity, localized numbness, photophobia, radiculopathy (postmarketing).

Precautions

Warnings

The effects of all botulinum toxin products may spread from the area of injection to produce symptoms consistent with botulinum toxin effects. These may include asthenia, blurred vision, breathing difficulties, diplopia, dysarthria, dysphagia, dysphonia, generalized muscle weakness, ptosis, and urinary incontinence. These symptoms have been reported hours to weeks after injection. Swallowing and breathing difficulties can be life-threatening, and there have been reports of death. The risk of symptoms is probably greatest in children treated for spasticity, but symptoms can also occur in adults treated for spasticity and other conditions, particularly in those patients who have underlying conditions that would predispose them to these symptoms. In unapproved uses, including spasticity in children and adults, and in approved indications, cases of spread of effect have occurred at doses comparable with those used to treat cervical dystonia and at lower doses.


Monitor

Closely monitor individuals with peripheral motor neuropathic diseases, amyotrophic lateral sclerosis (ALS), or neuromuscular junction disorders when administering botulinum toxin. Closely monitor patients with compromised respiratory status treated with Botox for upper limb spasticity.


Pregnancy

Category C .

Lactation

Undetermined.

Children

Botox Cosmetic , Dysport , and Xeomin are not recommended for use in children.

Blepharospasm and strabismus

Safety and efficacy in children younger than 12 y of age not established.

Cervical dystonia

Safety and efficacy in children younger than 16 y of age not established.

Hyperhidrosis and upper limb spasticity

Safety and efficacy in children younger than 18 y of age not established.

Elderly

Use with caution, reflecting higher frequency of decreased hepatic, renal, or cardiac function, and of comorbidity.

Hypersensitivity

Serious and/or immediate hypersensitivity reactions have occurred.

Albumin

Because this product contains albumin, a derivative of human blood, it carries a remote risk of viral disease transmission.

Cardiovascular

Rare reports of CV adverse reactions, including arrhythmia and MI, some with fatal outcomes, have occurred.

Dermatologic

Use with caution in patients who have an inflammatory skin problem at injection site or in those with marked facial asymmetry, ptosis, dermatochalasis, deep dermal scarring, or thick sebaceous skin, or when atrophy is present in the target muscles.

Dysphagia

Risk may be increased in patients requiring injections into the levator scapulae, patients with smaller neck muscle mass, and patients requiring bilateral injections into sternocleidomastoid muscle.

Immunogenicity

Treatment with botulinum toxin type A may cause formation of neutralizing antibodies that may reduce the efficacy of subsequent botulinum toxin type A treatments.

Neuropathic disorders

Use with caution in patients with peripheral motor neuropathic disease (eg, ALS) or neuromuscular junctional disorders (eg, myasthenia gravis) because of increased risk of systemic effects, including dysphagia and respiratory compromise.

Ophthalmic

Retrobulbar hemorrhage has occurred from needle penetration into the orbit. Ocular penetrations also have occurred. Spatial disorientation, double vision, or past pointing may occur. Covering the affected eye may alleviate these symptoms. Use with caution in patients at risk of developing narrow angle glaucoma.

Reduced blinking

Reduced blinking from injection of the orbicularis muscle can lead to corneal exposure, persistent epithelial defect, and corneal ulceration.

Respiratory effects

Bronchitis and upper respiratory tract infections have been reported in patients treated for upper limb spasticity. Decreases in forced vital capacity were greater in botulinum toxin type A–treated patients. Closely monitor patients with compromised respiratory status who are treated with Botox for upper limb spasticity.

Secondary hyperhidrosis

Evaluate patient for secondary causes of hyperhidrosis (eg, hyperthyroidism) before initiating therapy.

Vasovagal response

Needle-related pain and/or anxiety may result in vasovagal responses that may require appropriate medical therapy.

Overdosage

Symptoms

Muscle paralysis, systemic weakness.

Patient Information

  • Advise patient or caregiver that medication will be prepared and administered by a health care provider in a health care setting.
  • Advise patient being treated for cervical dystonia that improvement should occur within the first 2 wk following treatment, and max improvement should occur within about 6 wk. Advise patient that beneficial effects may last 3 mo before retreatment is needed.
  • Advise patient being treated for blepharospasm that improvement should occur within the first 3 days following treatment, and max improvement should occur within about 1 to 2 wk. Advise patient that beneficial effects may last 3 mo before retreatment is needed.
  • Advise patient being treated for strabismus that improvement should occur within the first 2 days following treatment, and max improvement should occur within the first week. Advise patient that beneficial effects may last 2 to 6 wk before the effects begin to wear off.
  • Advise patient being treated for glabellar lines that improvement should occur within the first 2 days following treatment, and max improvement should occur within the first week. Advise patient that beneficial effects may last 3 to 4 mo.
  • Advise patient or caregiver to immediately seek medical assistance if swallowing, speech, or breathing problems develop.
  • Advise patient to report intolerable injection-site reactions or unusual symptoms to health care provider.
  • Counsel patients to avoid driving or engaging in other potentially hazardous activities if loss of strength, muscle weakness, blurred vision, or drooping eyelids occur.
  • Advise previously immobile or sedentary patients to gradually resume activities following botulinum toxin injection.
  • Inform patients that botulinum toxin injections may cause dyspnea or mild to severe dysphagia, with risk of aspiration.
  • Advise patients to seek immediate medical attention if eye pain or irritation occurs following injection.

Copyright © 2009 Wolters Kluwer Health.

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