daxibotulinumtoxinA (Rx)

1-10%

Headache (5-6%)

Injection site reactions (6%)

Injection site pain (4%)

Injection site erythema (3%)

Injection site edema (3%)

Injection site bruising (1%)

Eyelid ptosis (1-2%)

Edema (2%)

Erythema (2%)

Facial paresis (1%)

<1%

Injection site papule (<1%)

Injection site pruritus (<1%)

Contraindications

Hypersensitivity to any botulinum toxin preparation, daxibotulinumtoxinA or its excipients

Presence of infection at proposed injection sites

Cautions

Not interchangeable with other botulinum toxin products

Serious adverse reactions, including excessive weakness, dysphagia, and aspiration pneumonia, with some adverse reactions associated with fatal outcomes, have been reported in patients who received botulinum toxin injections for unapproved uses

Serious and/or immediate hypersensitivity reactions have been reported for botulinum toxin products; reactions include anaphylaxis, serum sickness, urticaria, soft tissue edema, and dyspnea; if such a reaction occurs, discontinue further injection, and immediately institute appropriate medical therapy

Adverse events involving the cardiovascular system, including arrhythmia and myocardial infarction, some with fatal outcomes have been reported for botulinum toxin products; use caution when administering to patients with pre-existing cardiovascular disease

Monitor with peripheral motor neuropathic diseases, amyotrophic lateral sclerosis, or neuromuscular junctional disorders (eg, myasthenia gravis or Lambert-Eaton syndrome) for increased neuromuscular compromise following botulinum toxin treatment; patients with neuromuscular disorders may be at increased risk of clinically significant effects including generalized muscle weakness, diplopia, ptosis, dysphonia, dysarthria, severe dysphagia, and respiratory compromise from administration

Use caution when administering to patients with surgical alterations to the facial anatomy, marked facial asymmetry, excessive dermatochalasis, deep dermal scarring, thick sebaceous skin, inflammation at injection site(s), pre-existing eyelid, or eyebrow ptosis, when excessive weakness or atrophy is present in the target muscles, or the inability to substantially lessen glabellar lines even by physically spreading them apart

Reduced tear production, reduced blinking, and corneal disorders may occur with use of botulinum toxins, including daxibotulinumtoxinA; dry eye has been reported with the use of botulinum toxin products in the treatment of glabellar lines; if symptoms of dry eye (eg, eye irritation, photophobia, or visual changes) persist, consider referring patient to an ophthalmologist

Spread of Toxin Effect

• Postmarketing safety data from other approved botulinum toxins suggest that botulinum toxin effects may be observed beyond local injection site
• Symptoms include asthenia, generalized muscle weakness, diplopia, blurred vision, ptosis, dysphagia, dysphonia, dysarthria, urinary incontinence, and breathing difficulties
• Risk of symptoms is greatest in children treated for spasticity, but symptoms can occur in adults treated for spasticity and other conditions, and particularly in those patients who have underlying conditions that would predispose them to these

Dysphagia and breathing difficulties

• Treatment may result in swallowing or breathing difficulties
• These reactions can occur within hours to weeks after injection with botulinum toxin
• Patients with pre-existing swallowing or breathing difficulties may be more susceptible to these complications
• May be a consequence of weakening of muscles in injection area that are involved in breathing or swallowing
• Deaths as a complication of severe dysphagia have been reported after treatment with botulinum toxin products
• When distant effects occur, additional respiratory mechanisms may be involved
• Patients with respiratory disorders who may have become dependent upon accessory muscles may experience critical loss of breathing capacity
• If problems with swallowing, speech or respiratory disorders develop, immediately seek medical attention

Drug interaction overview

• No formal drug interaction studies conducted

• Use with caution owing to potential risk with the following

  • Aminoglycosides or other agents interfering with neuromuscular transmission
  • Anticholinergic drugs
  • Botulinum neurotoxin products
  • Muscle relaxants

Pregnancy

No available data are available on use in pregnant female to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes

Animal data

• IM administration during pregnancy resulted in adverse effects on fetal growth (decreased fetal body weight and skeletal ossification) at maternally toxic doses approximately equivalent to 40x the maximum recommended human dose

Lactation

There are no data on presence in human or animal milk, effects on the breastfed infant, or effects on milk production

Consider developmental and health benefits of breastfeeding along with the mother’s clinical need and any potential adverse effects on the breastfed infant or from the underlying maternal condition

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Blocks cholinergic transmission at neuromuscular junction by inhibiting the release of acetylcholine

When injected into skeletal muscle, drug is internalized into nerve terminal, translocates into the neuronal cytosol where it cleaves SNAP25, a protein necessary for synaptic vesicle membrane docking and subsequent release of acetylcholine which produces a dose dependent decrease of muscle function

Recovery of activity is gradual and results from the degradation of neurotoxin light chain in the neurons with a contribution from the formation of axonal sprouts

IM Preparation

• Reconstitution

  • Slowly inject diluent into vial, discard of any unused diluent
  • 50-unit vial: Reconstitute with 0.6 mL of preservative-free 0.9% NaCl
  • 100-unit vial: Reconstitute with 1.2 mL of preservative-free 0.9% NaCl
  • Resulting concentration is 8 units/ 0.1 mL for either dilution
  • Discard vial if a vacuum does not pull diluent into vial
  • Gently mix by rotating vial

IM Administration

Reconstituted solutions are for IM administration only

Administer within 72 hours after reconstitution

Inspect visually the reconstituted solution for particulate matter and discoloration prior to administration; donot use if solution is cloudy or discolored or contains flakes or particles

Use each reconstituted vial for only 1 injection session and for only 1 patient; discard any remaining solution in vial immediately after administering

Carefully examine upper eyelid margin position for separation or weakness of levator palpebrae superioris muscle; evaluate range of upper eyelid excursion while manually immobilizing the frontalis

Clean vial stopper with an alcohol swab

Draw up aseptically at least 0.5 mL of reconstituted solution with a sterile syringe, preferably a tuberculin syringe, and expel any air bubbles

Remove needle and attach a 30–33-gauge needle; confirm patency of needle

Advance needle through skin into underlying muscle while applying finger pressure on superior medial orbital rim

Inject 8 units (0.1 mL) into each of 5 injection sites: 2 injections into medial corrugator and lateral corrugator muscles respectively, and 1 injection in the procerus muscle

To reduce complication of ptosis, follow these steps

• Avoid injection near levator palpebrae superioris, particularly in patients with larger brow depressor complexes
• Ensure injected volume/dose is accurate and administer in a steady controlled manner
• Do not inject drug <1 cm above superior orbital rim

Storage

Unopened vials

• Store at room temperature 20-25ºC (68-77ºF) or refrigerate at 2-8ºC (36-46ºF)

Diluted vials

• Refrigerate at 2-8ºC (36-46ºF) for up to 72 hr
• Protect from light
• Do not freeze
• Discard of any unused drug