Section 09 · Monograph
OnabotulinumtoxinA
Reviewed Nov 2026FDA label
BotoxNeurotoxin · injectable
- Forms
- IM, unit-dosed per muscle group
- Dose
- per muscle group, q12 weeks
- MOA
- Blocks presynaptic ACh release at NMJ
Black Box Warning
- DISTANT SPREAD OF TOXIN EFFECT: The effects of Botox and all botulinum toxin products may spread from the area of injection to produce symptoms consistent with botulinum toxin effects, including asthenia, generalized muscle weakness, diplopia, ptosis, dysphagia, dysphonia, dysarthria, urinary incontinence, and breathing difficulties.
- 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 related to spread of toxin effect, including in some cases associated with unapproved (off-label) use.
- 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 those with underlying conditions that predispose them to these effects.
- Postmarketing cases of spread of effect have been reported at doses comparable to or lower than doses used to treat cervical dystonia and spasticity.
- Instruct patients/caregivers to seek immediate medical attention if swallowing, speech, or respiratory disorders occur after treatment.
Indications
- Treatment of spasticity in patients ≥2 years of age (upper limb and lower limb, adult and pediatric).FDA-labeled
- Prophylaxis of headaches in adult patients with CHRONIC migraine (≥15 days per month with headache lasting 4 hours a day or longer); not indicated for episodic migraine (14 or fewer headache days per month) or for other headache types.FDA-labeled
- Other FDA-approved indications (Botox is a multi-indication product): overactive bladder with urge incontinence in adults; neurogenic detrusor overactivity in adults and pediatric patients ≥5 years; cervical dystonia in adults; severe primary axillary hyperhidrosis inadequately managed with topical agents; blepharospasm and strabismus (patients ≥12 years) associated with dystonia/other neurologic conditions.FDA-labeled
- Note: Botox Cosmetic (same molecule, separate BLA/branding) is approved for temporary improvement of moderate to severe glabellar lines, lateral canthal lines, and forehead lines — cosmetic use is distinct from the neurologic/spasticity indications covered here.FDA-labeled
Off-Label Uses
- Chronic sialorrhea (adult and pediatric) — off-label for Botox (Xeomin holds this FDA-approved indication).Off-label
- Post-stroke hemiplegic shoulder pain.Off-label
- Focal spasticity muscle groups/patterns beyond those specifically tabulated in labeling (clinician-directed, individualized).Off-label
- Achalasia (lower esophageal sphincter injection) and chronic anal fissure — off-label GI uses.Off-label
Mechanism of Action
- OnabotulinumtoxinA is a purified neurotoxin complex produced from Clostridium botulinum type A, formulated with human serum albumin and sodium chloride.
- Functions as an acetylcholine release inhibitor and neuromuscular blocking agent: binds to high-affinity presynaptic receptors at peripheral cholinergic nerve terminals, is internalized, and its light chain enzymatically cleaves SNAP-25, blocking calcium-dependent release of acetylcholine and producing localized chemodenervation.
- Reduces excessive muscle contraction/tone (spasticity) or, at other injection targets, reduced glandular/autonomic secretion (e.g., sweat glands in hyperhidrosis) or nociceptive neurotransmitter release (migraine).
- Precise mechanism for chronic migraine prevention is not fully established; proposed to inhibit peripheral sensitization of nociceptors and reduce afferent trigeminal signaling implicated in migraine pathophysiology.
- Effect is temporary and reversible as new nerve terminal axonal sprouting restores neuromuscular transmission over time (clinical effect for spasticity typically lasts approximately 12 weeks).
Full Dosing
Adult / usual
- NOT INTERCHANGEABLE with other botulinum toxin products (abobotulinumtoxinA/Dysport, incobotulinumtoxinA/Xeomin, rimabotulinumtoxinB/Myobloc) — Botox Units are specific to this preparation/assay method.
- Adult upper limb spasticity: individualized by muscle(s), pattern, and severity (per FDA label Table 4) — biceps brachii 60-200 Units, brachialis 30-50 Units, brachioradialis 45-75 Units, pronator teres 15-25 Units, flexor carpi radialis 12.5-50 Units, flexor digitorum profundus/superficialis 30-50 Units, adductor pollicis ~20 Units; total dose up to 400 Units per treatment session.
- Adult lower limb spasticity: representative muscle doses (per FDA label Table 5) — gastrocnemius medial/lateral heads, soleus, tibialis posterior ~75 Units each, flexor hallucis longus and flexor digitorum longus ~50 Units each; total dose typically 300-400 Units divided among up to 5 muscles per session.
- Re-treatment interval: no sooner than every 12 weeks for spasticity indications.
- Reconstitute lyophilized powder with preservative-free 0.9% sodium chloride injection per labeling; use promptly (within 24 hours if refrigerated) after reconstitution.
- Chronic migraine — PREEMPT protocol: total recommended dose of 155 Units administered intramuscularly (up to 195 Units total if 'follow-the-pain' optional sites are used).
- Chronic migraine: 31 fixed-site, fixed-dose injections divided across 7 specific head/neck muscle groups, 0.1 mL (5 Units) per site, using a sterile 30-gauge, 0.5-inch needle.
- Chronic migraine site doses — Frontalis: 20 Units (4 sites); Corrugator: 10 Units (2 sites); Procerus: 5 Units (1 midline site); Occipitalis: 30 Units (6 sites); Temporalis: 40 Units (8 sites); Trapezius: 30 Units (6 sites); Cervical paraspinal muscle group: 20 Units (4 sites).
- Chronic migraine injections are administered bilaterally in equally divided doses across the above muscles, except the procerus, which receives a single midline injection; re-treatment recommended at intervals of approximately 12 weeks.
Pediatric
- Pediatric upper limb spasticity: 3-6 Units/kg divided among affected muscles, not to exceed 200 Units per treatment session.
- Pediatric lower limb spasticity: 4-8 Units/kg divided among affected muscles, not to exceed 300 Units per treatment session.
Contraindications
- Known hypersensitivity to any botulinum toxin preparation or to any component of the formulation.
- Infection at the proposed injection site(s).
- For intradetrusor (bladder) injection specifically: urinary tract infection or urinary retention with post-void residual volume >200 mL.
Drug Interactions
- Aminoglycoside antibiotics and other agents that interfere with neuromuscular transmission (e.g., curare-like agents) may potentiate the toxin's effect.
- Anticholinergic drugs may potentiate systemic anticholinergic-type effects.
- Other muscle relaxants may exacerbate excessive muscle weakness.
- Concurrent use with other botulinum toxin products is not recommended; effects are unknown — avoid administering different botulinum toxin products within the same treatment interval.
- Anticoagulants/antiplatelet agents: not a specific labeled interaction, but increased risk of bruising/bleeding at injection sites should be anticipated clinically.
Adverse Effects
- Upper limb spasticity: pain in extremity, muscular weakness, bronchitis, nausea, fall, upper respiratory tract infection.
- Lower limb spasticity: arthralgia, back pain, upper respiratory tract infection, fall, muscular weakness.
- Cervical dystonia: dysphagia, upper respiratory infection, neck pain, headache, injection-site pain.
- Chronic migraine: neck pain (9% vs 3% placebo), headache (5%), eyelid ptosis (4% vs <1% placebo), musculoskeletal stiffness (4%), muscular weakness (4% vs <1% placebo), myalgia (3%), facial paresis (2% vs 0% placebo), injection site pain; worsening/severe migraine requiring hospitalization in approximately 1% of treated patients vs 0.3% with placebo.
- Overactive bladder/neurogenic detrusor overactivity: urinary tract infection, urinary retention, dysuria, bacteriuria, elevated post-void residual urine volume.
- Class effects: dysphagia (risk of aspiration), injection-site pain/bruising, generalized weakness, hypersensitivity reactions (rare), development of neutralizing antibodies with repeated high-dose use (~0.5% of adult upper limb spasticity patients in trials).
Monitoring Parameters
- Monitor for signs/symptoms of distant spread of toxin effect (dysphagia, dysphonia, dysarthria, respiratory difficulty), especially in pediatric spasticity patients and those with pre-existing neuromuscular disease.
- Monitor respiratory function closely in spasticity patients with reduced pulmonary reserve, dysphagia at baseline, or neuromuscular disease (ALS, myasthenia gravis, Lambert-Eaton syndrome).
- For bladder indications: monitor post-void residual urine and watch for urinary retention/UTI.
- For chronic migraine: assess clinical response approximately 2-4 weeks post-injection and reassess headache frequency and severity before each re-treatment (approximately every 12 weeks).
- Assess treatment response and adverse effects before each re-treatment; observe minimum 12-week re-treatment interval.
- Monitor for reduced clinical response over time, which may suggest neutralizing antibody development.
- Check for active infection at proposed injection site prior to each treatment.
Pregnancy & Lactation
- Pregnancy: No adequate human data. Animal reproduction studies have shown adverse effects (reduced fetal weight, decreased fetal skeletal ossification) at clinically relevant doses associated with maternal toxicity. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus.
- Lactation: No data on presence in human milk, effects on the breastfed infant, or on milk production.