Botulinum Toxin Type A

Pronunciation: (BOT-yoo-lin-um)Class: Botulinum toxin, Ophthalmic surgical adjunct

Trade Names:Botox- Powder for injection 100 units vacuum-dried Clostridium botulinum toxin type A neurotoxin complex

Trade Names:Botox Cosmetic- Powder for injection 100 units vacuum-dried C. botulinum toxin type A neurotoxin complex

Trade Names:Dysport- Powder for injection 300 units freeze-dried abobotulinum toxin A- Powder for injection 500 units freeze-dried abobotulinum toxin A

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 and Dysport ); treatment of strabismus and blepharospasm associated with dystonia, including benign essential blepharospasm or VII nerve disorder in patients 12 yr of age and older ( Botox ); treatment of severe primary axillary hyperhidrosis inadequately managed with topical agents ( Botox ); for temporary improvement in appearance of moderate to severe glabellar lines associated with corrugator or procerus muscle activity in patients 65 yr of age or younger ( Botox Cosmetic and Dysport ).

Contraindications

Infection at the proposed injection site(s); hypersensitivity to any ingredient in the formulations.

Dosage and Administration

BotoxAxillary Hyperhidrosis Adults

Intradermally Inject 50 units (2 mL of reconstituted solution) intradermally 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 yr of age and older

IM Initially, inject 1.25 to 2.5 units (0.05 to 0.1 mL volume 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.

Cervical Dystonia Adults and children 16 yr 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.

Glabellar Lines ( Botox Cosmetic only) Adults (65 yr of age or younger)

IM Total treatment dose is 20 units in 0.5 mL at intervals no more frequently than every 3 mo (duration of activity of botulinum toxin type A is approximately 3 to 4 mo).

Strabismus Adults and children 12 yr of age and older

IM Inject between 0.05 to 0.15 mL per muscle into extraocular muscles utilizing electrical activity recorded from tip of injection needle as guide to placement within target muscle.

DysportCervical 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 unit each. Administer no more frequently than every 3 mo.

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 noted.
• Use a new, sterile needle and syringe to enter vial on each occasion for removal of medication. Epinephrine should be available or other precautionary method should an anaphylactic reaction occur.
• Discard any unused solution that is not used within 4 h of reconstitution.
• Follow institutional or organizational procedures for discarding medical waste and disposing unused solution, vials, and equipment used with the drug administration.
• Do not exceed recommended dosages or frequencies of administration.

Storage/Stability

Store unopened vials in refrigerator (36° to 46°F) for up to 24 mo. Reconstituted solution may be stored for up to 4 h if refrigerated. 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.

Botulinum neurotoxin

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

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

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

CNS

Anxiety, asthenia, dizziness, drowsiness, hypertonia (2% to 10%); headache (13%); dizziness, paresthesia (1%); malaise, vertigo with nystagmus (postmarketing).

Dermatologic

Pruritus, sweating (3% to 10%); erythema (2%); skin tightness (1%); skin rash (including erythema multiforme, psoriasiform eruption, urticaria) (postmarketing).

EENT

Eye dryness, superficial punctuate keratitis (6%); diplopia, pharyngitis, rhinitis (2% to 10%); blepharoptosis (3%); blurred vision, decreased hearing, ear noise, glaucoma, retinal vein occlusion (postmarketing).

GI

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

Genitourinary

UTI (1%).

Hematologic-Lymphatic

Ecchymosis (2%).

Local

Hemorrhage (3% to 10%); soreness (2% to 10%); bruising; tenderness; weakness; erythema, facial pain (less than 3%); pain and edema at injection site (2%); localized numbness (postmarketing).

Musculoskeletal

Neck pain (11%); back pain (2% to 10%); muscle weakness (2%); chest discomfort, myalgia, myasthenia gravis (postmarketing).

Respiratory

Upper respiratory infection (12%); cough, dyspnea (2% to 10%); pneumonia; infection (4%); bronchitis, sinusitis (2%).

Miscellaneous

Ptosis (21%); fever, infection, numbness, speech disorder, stiffness (2% to 10%); anaphylaxis; transient ptosis (5%); flu syndrome (2%); allergic reaction, brachial plexopathy, facial paralysis, fever (postmarketing).

Precautions

Pregnancy

Category C .

Lactation

Undetermined.

Children

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

Blepharospasm and strabismus

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

Cervical dystonia

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

Hyperhidrosis

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

Elderly

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

Bleeding disorders

Use with caution in patients who have bleeding disorders or are taking anticoagulants.

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. Marked facial asymmetry, ptosis, dermatochalasis, deep dermal scarring, 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, amyotrophic lateral sclerosis) 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 affected eye may alleviate these symptoms.

Reduced blinking

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

Secondary hyperhidrosis

Evaluate patient for secondary causes of hyperhidrosis (eg, hyperthyroidism) before initiating 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.
• Caution sedentary patient to resume activity gradually following treatment with botulinum toxin.
• Remind patient that office visits will be required to monitor therapy and to keep appointments.

Copyright © 2009 Wolters Kluwer Health.