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Cervical dystonia: I.M.: Initial: 500 units divided among affected muscles in toxin-naïve or toxin-experienced patients. May re-treat at intervals of ≥12 weeks Dosage adjustments: Adjust dosage in 250-unit increments; do not administer at intervals <12 weeks; dosage range used in studies: 250-1000 units

Glabellar lines: Adults <65 years: I.M.: Inject 10 units (0.05 mL or 0.08 mL) into each of 5 sites (2 injections in each corrugator muscle and 1 injection in the procerus muscle) for a total dose of 50 units; do not administer at intervals <3 months; efficacy has been demonstrated up to 4 repeated administrations Dosing: Geriatric

Glabellar lines: Not recommended in patients ≥65 years of age. Dosing: Renal Impairment No adjustment necessary. Dosing: Hepatic Impairment No adjustment necessary. Dosage Forms: U.S. Excipient information presented when available (limited, particularly for generics); consult specific product labeling. Injection, powder for reconstitution: Dysport™: 500 units [contains albumin (human), lactose 2.5 mg] Generic Equivalent Available: U.S. No Medication Guide An FDA-approved patient medication guide, which is available with the product information and at file://www.fda.gov/downloads/Drugs/DrugSafety/UCM165110.pdf , must be dispensed with this medication. Administration Cervical dystonia: Use 23- or 25-gauge needle to administer intramuscularly. Glabellar lines: Use a 30-gauge needle to administer intramuscularly. Inject into each of 5 sites (2 injections in each corrugator muscle and 1 in the procerus muscle). Ensure injected volume/dose is accurate and where feasible keep to a minimum. Avoid injection near the levator palpebrae superioris. Medial corrugator injections should be at least 1 cm above the bony supraorbital ridge. Do not inject toxin closer than 1 cm above the central eyebrow. Use Treatment of cervical dystonia in both toxin-naive and previously treated patients; temporary improvement in the appearance of moderate-severe glabellar lines associated with procerus and corrugator muscle activity Medication Safety Issues Other safety concerns: Botulinum products are not interchangeable; potency differences may exist between the products. Adverse Reactions Significant >10%: Cervical dystonia: Central nervous system: Dysphonia (≤28%), fatigue (12%), headache (11%) Gastrointestinal: Dysphagia (15% to 39%), xerostomia (13% to 39%) Local: Injection site discomfort/pain (5% to 22%) Neuromuscular & skeletal: Weakness (11% to 56%), facial paresis (≤11%) Ocular: Eye disorders (≤17%, includes accommodation disorder, blurred vision, diplopia, dryness, pain, pruritus, visual acuity decreased) Miscellaneous: Infection (13%) 1% to 10%: Cervical dystonia: Cardiovascular: Heart rate decreased Central nervous system: Dizziness (≤4%) Endocrine & metabolic: Blood glucose increased Neuromuscular & skeletal: Pain (7%), muscle atrophy (1%) Respiratory: Breathing difficulties/dyspnea (~3%; onset: ~1 week; duration: ~3 weeks) Miscellaneous: Antibody formation (3%) Glabellar lines: Central nervous system: Headache (9%)

Cardiovascular: Heart rate decreased Central nervous system: Dizziness (≤4%) Endocrine & metabolic: Blood glucose increased Neuromuscular & skeletal: Pain (7%), muscle atrophy (1%) Respiratory: Breathing difficulties/dyspnea (~3%; onset: ~1 week; duration: ~3 weeks) Miscellaneous: Antibody formation (3%) Glabellar lines: Central nervous system: Headache (9%) Dermatologic: Contact dermatitis (2% to 3%) Gastrointestinal: Nausea (2%) Local: Injection site pain/reaction (2% to 3%) Ocular: Eyelid edema (2%), eyelid ptosis (2%) Renal: Hematuria (2%) Respiratory: Nasopharyngitis (10%), upper respiratory tract infection (3%), cough (2% to 3%), pharyngolaryngeal pain (2% to 3%), bronchitis (2% to 3%), sinusitis (2%) Miscellaneous: Flu-like syndrome (2% to 3%)

Any indication: <1% (Limited to important or life-threatening): Amyotrophy, antibody formation, blurred vision, burning sensation, diplopia, dizziness, dysphagia, facial paresis, hypersensitivity, hypoesthesia, erythema, granulation tissue formation (excessive), malaise, photophobia, vertigo Contraindications Hypersensitivity to botulinum toxin or any component of the formulation, including milk protein; infection at the proposed injection site(s) Warnings/Precautions

Concerns related to adverse effects: • Anaphylaxis/hypersensitivity reactions: Hypersensitivity and anaphylactic reactions may occur rarely; immediate treatment (including epinephrine 1:1000) should be available. • Antibody formation: Higher doses or more frequent administration may result in neutralizing antibody formation and loss of efficacy. • Cardiovascular events: Rarely, arrhythmia and myocardial infarction have been reported with use of onabotulinumtoxinA (another botulinum toxin formulation), sometimes in patients with preexisting cardiovascular disease. • Dysphagia: Common when used for cervical dystonia and may persist anywhere from 2 weeks up to 5 months after administration. In severe cases, patients may require alternative feeding methods. Risk factors include smaller neck muscle mass, bilateral injections into the sternocleidomastoid muscle, or injections into the levator scapulae. • Systemic toxicity: [U.S. Boxed Warning]: Distant spread of botulinum toxin beyond the site of injection has been reported; dysphagia and breathing difficulties have occurred and may be life threatening; other symptoms reported include blurred vision, diplopia, dysarthria, dysphonia, generalized muscle weakness, ptosis, and urinary incontinence which may develop within hours or weeks following injection. Risk likely greatest in children treated for the unapproved use of spasticity. Systemic effects have occurred following use in approved and unapproved uses, including low doses. Immediate medical attention required if respiratory, speech, or swallowing difficulties appear.

Disease-related concerns: • Neuromuscular disease: Use with caution in patients with neuromuscular diseases (eg, myasthenia gravis, Eaton-Lambert syndrome) and neuropathic disorders (eg, amyotrophic lateral sclerosis). • Ocular diseases: Reduced blinking from injection of the orbicularis muscle can lead to corneal exposure and ulceration when treating blepharospasm. Retrobulbar hemorrhages may occur from needle penetration into orbit when treating strabismus; spatial disorientation, double vision, or past-pointing may occur if one or more extraocular muscles are paralyzed. Covering the affected eye may help. Careful testing of corneal sensation, avoidance of lower lid injections, and treatment of epithelial defects are necessary. Use caution in patients with angle closure glaucoma. • Respiratory disease: Use extreme caution in patients with pre-existing respiratory disease; treatment of cervical dystonia using botulinum toxin may weaken accessory muscles that are necessary for these patients to maintain adequate ventilation. Risk of aspiration resulting from severe dysphagia is increased in patients with decreased respiratory function.

Concurrent drug therapy issues: • Neuromuscular transmission: Use with extreme caution in patients receiving other agents that may interfere with neuromuscular transmission (eg, aminoglycosides, neuromuscular-blocking agents).

Dosage form specific issues: • Albumin: Product contains albumin and may carry a remote risk of virus transmission. • Lactose: Product contains lactose; do not administer to patients allergic to cow’s milk protein. • Product interchangeability: Botulinum products (abobotulinumtoxinA, onabotulinumtoxinA, rimabotulinumtoxinB) are not interchangeable; potency units are specific to each preparation and cannot be compared or converted to any other botulinum product.

Special populations: • Elderly: Temporary reduction in glabellar lines: Efficacy was not observed in older adults (≥65 years of age) and an increased frequency of ocular adverse events was reported in older adults compared to younger adults.

Other warnings/precautions: • Chronic therapy: Long-term effects of chronic therapy unknown. • Injection site: Use with caution if there is excessive weakness or atrophy at the proposed injection site(s); use is contraindicated if infection is present. • Hyperhidrosis: Safety in the treatment of hyperhidrosis has not been established. The possibility of an immune reaction resulting from an intradermal injection is unknown. • Temporary reduction in glabellar lines: Appropriate use: Do not use more frequently than every 3 months. Patients with marked facial asymmetry, ptosis, excessive dermatochalasis, deep dermal scarring, thick sebaceous skin, or the inability to substantially lessen glabellar lines by physically spreading them apart were excluded from clinical trials. Use with caution in patients with surgical alterations to the facial anatomy. Reduced blinking from injection of the orbicularis muscle can lead to corneal exposure and ulceration. Spatial disorientation, double vision, or past pointing may occur if one or more extraocular muscles are paralyzed. Metabolism/Transport Effects None known. Drug Interactions (For additional information: Launch Lexi-Interact™ Drug Interactions Program ) Aminoglycosides: May enhance the neuromuscular-blocking effect of AbobotulinumtoxinA. Risk C: Monitor therapy Anticholinergic Agents: May enhance the anticholinergic effect of AbobotulinumtoxinA. Risk C: Monitor therapy Neuromuscular-Blocking Agents: AbobotulinumtoxinA may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy OnabotulinumtoxinA: May enhance the adverse neuromuscular effect of AbobotulinumtoxinA. Risk C: Monitor therapy RimabotulinumtoxinB: AbobotulinumtoxinA may enhance the adverse neuromuscular effect of RimabotulinumtoxinB. Risk C: Monitor therapy Pregnancy Risk Factor C ( show table ) Pregnancy Implications Embryo-fetal toxicity has been observed in animal studies. There are no adequate and well-controlled studies in pregnant women. Use during pregnancy only if benefits justify the risk to the fetus. Lactation Excretion in breast milk unknown/use caution Dietary Considerations Contains lactose; patients allergic to cow’s milk protein should not receive product. Pricing: U.S. (Medi-Span®)

Solution (reconstituted) (Dysport Intramuscular) 300 unit (1): $511.20 500 unit (1): $852.00 Mechanism of Action AbobotulinumtoxinA (previously known as botulinum toxin type A) is a neurotoxin produced by Clostridium botulinum , spore-forming anaerobic bacillus, which appears to affect only the presynaptic membrane of the neuromuscular junction in humans, where it prevents calcium-dependent release of acetylcholine and produces a state of denervation. Muscle inactivation persists until new fibrils grow from the nerve and form junction plates on new areas of the muscle-cell walls. Pharmacodynamics/Kinetics Onset of action: Peak effect: Cervical dystonia: 2-4 weeks Duration: Cervical dystonia: Up to 4 months Absorption: Not expected to be present in peripheral blood at recommended doses following intramuscular (I.M.) injection Use of UpToDate is subject to the Subscription and License Agreement . Topic 9195 Version 30.0 © 2013 UpToDate, Inc. All rights reserved. | Subscription and License Agreement | Release: 21.6- C21.56 Licensed to: AsanBook Dig. Med. Lib. | Support Tag: [0604-125.39.66.147-08BE826B45-S244013.14]