Dosing & Uses
Dosage Forms & Strengths
injectable, powder for reconstitution
- 50 units/vial (Botox, Botox Cosmetic)
- 100 units/vial (Botox, Botox Cosmetic)
- 200 units/vial (Botox)
Blepharospasm and Strabismus
Indicated for the treatment of strabismus and blepharospasm associated with dystonia (eg, benign essential blepharospasm, VII nerve disorders)
Blepharospasm
- 1.25-2.5 units injected into medial and lateral pretarsal orbicularis oculi of upper lid and lateral pretarsal orbicularis oculi of lower lid; not to exceed 200 units in 30 days
- May increase dose 2-fold if response to initial treatment dose does not last longer than 2 months
- Little benefit obtained from injecting >5 units per site
- Tolerance may develop if treatment given more than every 3 months; effect not usually permanent
Strabismus
- 1.25-5 units IM; <25 units per injection
- Vertical muscles, and horizontal strabismus of <20 prism diopters: 1.25-2.5 units in any one muscle
- Persistent VI nerve palsy of >1 month of duration: 1.25-2.5 units in the medial rectus muscle
- Horizontal strabismus of 20-50 prism diopters: 2.5-5 units in any one muscle
- Incomplete paralysis of target muscle: May increase dose 2-fold if patient experience incomplete paralysis of the target
Primary Axillary Hyperhidrosis
Indicated for severe primary axillary hyperhidrosis that is inadequately managed with topical agents
50 units injected intradermally to each axilla evenly distributed in multiple sites approximately 1-2 cm apart
Cervical Dystonia
Indicated for adults with cervical dystonia, to reduce the severity of abnormal head position and neck pain associated with cervical dystonia
Not to exceed 50 units per site
Clinical improvement generally begins within the first 2 weeks after injection with maximum clinical benefit at ~6 weeks post-injection
Upper and Lower Limb Spasticity
Indicated for the treatment of upper and lower limb spasticity in adults to decrease the severity of increased muscle stiffness
Select dose based on muscles affected, severity of muscle activity, prior response to treatment, and adverse event history (EMG guidance recommended)
Do not exceed a cumulative dose of 400 units in 3-month interval when treating adults for 1 or more indications
Upper limb spasticity
- Selected muscles: Elbow flexors (biceps), wrist flexors (flexor carpi radialis and flexor carpi ulnaris), finger flexors (flexor digitorum profundus and flexor digitorum sublimis), and thumb flexors (adductor pollicis and flexor pollicis longus)
- In clinical trials, doses ranging from 75 units to 400 units were divided among selected muscles to treat upper limb spasticity at a given treatment session
- Recommended dose per muscle for upper limb spasticity
- Biceps brachii: 100-200 units divided in 4 sites
- Flexor carpi radialis: 12.5-50 units in 1 site
- Flexor carpi ulnaris: 12.5-50 units in 1 site
- Flexor digitorum profundus: 30-50 units in 1 site
- Flexor digitorum sublimis: 30-50 units in 1 site
- Adductor pollicis: 20 units in 1 site
- Flexor pollicis longus: 20 units in 1 site
Lower limb spasticity
- Selected muscles: Gastrocnemius, soleus, tibialis posterior, flexor hallucis longus, and flexor digitorum longus
- Recommended dose for treating lower limb spasticity is 300 units to 400 units divided among 5 muscles
- Recommended dose per muscle for lower limb spasticity
- Gastrocnemius medial head: 75 units divided in 3 sites
- Gastrocnemius lateral head: 75 units divided in 3 sites
- Soleus: 75 units divided in 3 sites
- Tibialis Posterior: 75 units divided in 3 sites
- Flexor hallucis longus: 50 units divided in 2 sites
- Flexor digitorum longus: 50 units divided in 2 sites
Chronic Migraine
Indicated for the prophylaxis of headaches in adults with chronic migraine (≥15 days per month with headache lasting 4 hours a day or longer)
Recommended total dose 155 units, as 0.1 mL (5 units) IM injections per each site divided across 7 head/neck muscles q12wk
Recommended dose per muscle site (totaling 155 units)
- Frontalis: 20 units divided in 4 sites
- Corrugator: 10 units divided in 2 sites
- Procerus: 5 units in 1 site
- Occipitalis: 30 units divided in 6 sites
- Temporalis: 40 untied divided in 8 sites
- Trapezius: 30 units divided in 6 sites
- Cervical paraspinal muscle group: 20 units divided in 4 sites
Detrusor Overactivity
Indicated for urinary incontinence caused by detrusor overactivity in patients with neurologic conditions (eg, spinal cord injury, multiple sclerosis) in adults who have an inadequate response to or are intolerant to anticholinergic medication
200 units (divided into 30 intradetrusor injections) administered using cystoscopy
Duration of effect may last up to 10 months; may repeat procedure when effect of previous injection diminishes, but no sooner than 12 weeks from the prior bladder injection
Overactive Bladder
Indicated for adults with overactive bladder symptoms (urge incontinence, urgency, frequency) who cannot use or do not adequately respond to anticholinergic medication
100 units (divided into 20 intradetrusor injections of 5 units each) administered using cystoscopy
Requirements for repeating procedure
- 12 weeks have elapsed since prior treatment
- Post-void residual urine volume >200 mL
- At least 2 reported urinary incontinence episodes over 3 days
Cosmetic Uses
Botox Cosmetic only
Indicated for temporary improvement in the appearance of moderate-to-severe glabellar lines (ie, frown lines) associated with corrugators and/or procerus muscle activity; lateral canthal lines (ie, crow’s feet) associated with orbicularis oculi activity; forehead lines associated with frontalis muscle activity
Dosing
- Glabellar lines: Inject 4 units (0.1 mL) into each of 5 sites, 2 in each corrugator muscle and 1 in procerus muscle for a total dose of 20 units
- Lateral canthal lines: Inject 4 units (0.1 mL) into 3 sites per side (6 total injection points) in the lateral orbicularis oculi muscle for a total of 24 units/0.6 mL (12 units per side)
- Forehead lines: Inject 4 units (0.1 mL) into each of 5 forehead line sites (20 units); treat in conjunction with glabellar lines with 0.1 mL (4 units) into each of 5 glabellar line sites (20 units), for a recommended total of 40 units
Dosing Considerations
Botox
- Lower initial dose if no prior botulinum toxin treatment
- Adjust dose based on response
- When treating adult patients for 1 or more indications, the maximum cumulative dose should generally not exceed 400 Units in a 3 month interval
- Bladder dysfunction indications: Administer prophylactic antibiotics (except aminoglycosides) beginning 1-3 days pretreatment and continue 1-3 days post treatment to reduce risk for procedure-related UTI
Botox Cosmetic
- Treatment for both glabellar and lateral canthal lines can be given at the same time
- Do not exceed a cumulative dose of 400 units per 3 months when treating patients for 1 or more indication
- Duration of activity is approximately 3-4 months
- More frequent dosing not recommended
Dosage Forms & Strengths
injectable, powder for reconstitution
- 50 units/vial (Botox, Botox Cosmetic)
- 100 units/vial (Botox, Botox Cosmetic)
- 200 units/vial (Botox)
Blepharospasm and Strabismus
Indicated for the treatment of strabismus and blepharospasm associated with dystonia, including benign essential blepharospasm or VII nerve disorders in children aged ≥12 years
Blepharospasm
- <12 years: Safety and efficacy not established
- ≥12 years:1.25-2.5 units IM; < 200 units in 30 days
- May increase dose 2-fold if response to initial treatment dose does not last longer than 2 months
- Little benefit obtained from injecting >5 units per site
Strabismus
- <12 years: Safety and efficacy not established
- ≥12 years: 1.25-5 units IM; <25 units per injection
- Vertical muscles, and horizontal strabismus of <20 prism diopters: 1.25-2.5 units in any one muscle
- Persistent VI nerve palsy of >1 month of duration: 1.25-2.5 units in the medial rectus muscle
- Horizontal strabismus of 20-50 prism diopters: 2.5-5 units in any one muscle
- Incomplete paralysis of target muscle: May increase dose 2-fold if response to initial treatment dose
Upper Limb Spasticity
Indicated for treatment of upper limb spasticity in children aged 2-17 yr with upper limb spasticity
3-6 units/kg divided among the affected muscles; not to exceed 6 units/kg or 200 Units, whichever is lower
Recommended dose per muscle for upper limb spasticity
- Biceps brachii: 1.5-3 units/kg divided in 4 sites
- Brachialis: 1-2 units/kg divided in 2 sites
- Brachioradialis: 0.5-1 units/kg divided in 2 sites
- Flexor carpi radialis: 1-2 units in 2 sites
- Flexor carpi ulnaris: 1-2 units in 2 sites
- Flexor digitorum profundus: 0.5-1 units/kg divided in 2 sites
- Flexor digitorum sublimis: 0.5-1 units/kg divided in 2 sites
Dosing Considerations
Follow indication specific dosage and administration recommendations
Cumulative dose limits
- Use lowest recommended dose when initiating treatment
- When treating children for ≥1 indications, do not exceed a total dose of the lower of 8 units/kg body weight or 300 units, in a 3-month interval
Upper limb spasticity
- Limitation of use: Not intended to substitute for usual standard of care rehabilitation regimens
Muscle Contractures (Orphan)
Treatment of dynamic muscle contractures in pediatric cerebral palsy patients
Orphan indication sponsor
- Allergan, Inc; 2525 Dupont Drive, P.O. Box 19534; Irvine, CA 92713
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Adverse Effects
>10% (Botox)
Urinary tract infection (26-31%)
Residual urine volume (3-17%)
Urinary retention (17-18%)
Somnolence and sedation (16%)
Urinary retention (6-15%)
Dizziness (4-12%)
1-10% (Botox Cosmetic)
Headache (9%)
Eyelid ptosis (2-3%)
Brow ptosis (2%)
Skin tightness (2%)
Facial paresis (1%)
Muscular weakness (1%)
Eyelid edema (1%)
1-10% (Botox)
Bacteriuria (9%)
Dysuria (5-9%)
Neck pain (8-9%)
Headache (5%)
Migraine (4%)
Eyelid ptosis (4%)
Hematuria (4%)
Musculoskeletal stiffness (4%)
Muscular weakness (4%)
Myalgia (3%)
Bronchitis (3%)
Musculoskeletal pain (3%)
Muscle spasms (2%)
Hypertension (2%)
Postmarketing Reports
Botox Cosmetic
- Ear and labyrinth disorders: Hypoacusis; tinnitus; vertigo
- Eye disorders: Diplopia; dry eye; lagophthalmos; strabismus; visual disturbances; vision blurred
- Gastrointestinal disorders Abdominal pain; diarrhea; dry mouth; nausea; vomiting
- General disorders and administration site conditions: Denervation; malaise; pyrexia
- Metabolism and nutrition disorders: Anorexia
- Musculoskeletal and connective tissue disorders: Localized muscle twitching/involuntary muscle contractions; muscle atrophy; myalgia
- Nervous system disorders: Brachial plexopathy; dysarthria; facial palsy; hypoaesthesia; localized numbness; myasthenia gravis; paresthesia; peripheral neuropathy; radiculopathy; syncope
- Respiratory, thoracic and mediastinal disorders: Aspiration pneumonia; dyspnea; respiratory depression and/or respiratory failure
- Skin and subcutaneous tissue disorders: Alopecia, including madarosis; hyperhidrosis; pruritus; skin rash (eg, erythema multiforme, dermatitis psoriasiform, psoriasiform eruption)
Botox
- Abdominal pain; alopecia, including madarosis; anorexia; brachial plexopathy; denervation/muscle atrophy; diarrhea; dry eye; hyperhidrosis; hypoacusis; hypoaesthesia; localized muscle twitching; malaise; paresthesia; peripheral neuropathy; radiculopathy; erythema multiforme, dermatitis psoriasiform, and psoriasiform eruption; strabismus; tinnitus; visual disturbance, diplopia, strabismus, vision blurred, involuntary muscle contractions, myalgia
Warnings
Black Box Warnings
Effects of all botulinum toxin products may spread from the area of injection to produce symptoms consistent with botulinum toxin effects
These symptoms may include asthenia, generalized muscle weakness, diplopia, blurred vision, 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 death have been reported
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 been reported at doses comparable to those used to treat cervical dystonia and at lower doses
Contraindications
Hypersensitivity
Neuromuscular disease
Infection at the proposed injection site
Intradetrusor injection: Urinary tract infection or urinary retention (post-void residual >200 mL)
Cautions
Avoid injections near the levator palpebrae superioris minimize the risk of ptosis, especially in individuals with larger brow-depressor complexes
Risk of respiratory compromise & death esp in children treated for cerebral palsy-associated spasticity
Effects of the botulinum toxin may spread from the area of injection to other areas of the body, causing symptoms similar to those of botulism - watch for dyspnea, dysphagia or speech impairment
The different botulinum toxin products are not interchangeable
Pre-existing neuromuscular disorders
Only consider for treatment of urinary incontinence for patients willing and able to initiate catheterization post-treatment, if required (due to risk of urinary retention); patients with diabetes mellitus more likely to develop urinary retention than non-diabetics
Increased risk for UTI; do not use for treatment of urinary incontinence with present UTI, routine catheterization, or if patient is unable to empty bladder without assistance
Use with caution in patients with compromised respiratory function
Corneal exposure and ulceration due to reduced blinking may occur when treating blepharospasm
Retrobulbar hemorrhages and compromised retinal circulation may occur when treating strabismus
Bronchitis and upper respiratory tract infections in patients treated for upper limb spasticity reported
Serious adverse reactions, including excessive weakness, dysphagia, and aspiration pneumonia, with some adverse reactions associated with fatal outcomes, reported in patients who received injections for unapproved uses
Tailor dosing in initial and sequential treatment sessions to the individual based on the size, number and location of muscles involved, severity of spasticity, presence of local muscle weakness, patient’s response to previous treatment, or adverse event history with this therapy
Product contains albumin, a derivative of human blood; based on effective donor screening and product manufacturing processes, it carries an extremely remote risk for transmission of viral diseases and variant Creutzfeldt-Jakob disease (vCJD); risk for transmission of CJD is theoretical; no cases of transmission of viral diseases, CJD or vCJD have ever been identified for licensed albumin or albumin contained in other licensed products
Patients with known or unrecognized neuromuscular disorders or 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 therapy
Adverse events involving the cardiovascular system, including arrhythmia and myocardial infarction, some with fatal outcomes reported; risk factors including pre- existing cardiovascular disease may increase risk; use caution when administering to patients with pre-existing cardiovascular disease Adverse events involving the cardiovascular system, including arrhythmia and myocardial infarction, some with fatal outcomes reported; risk factors including pre- existing cardiovascular disease may increase risk; use caution when administering to patients with pre-existing cardiovascular disease
Drug interactions overview
- Coadministration of abobotulinumtoxin A and aminoglycosides or other agents interfering with neuromuscular transmission (eg, curare-like compounds) should only be performed with caution as the effect of the toxin may be potentiated
- Anticholinergic drugs: Use of anticholinergic drugs after abobotulinumtoxin A administration may potentiate systemic anticholinergic effects
- Administration of different botulinum neurotoxin products concomitantly or within several months of each other is unknown; excessive neuromuscular weakness may be exacerbated by administration of another botulinum toxin prior to the resolution of the effects of a previously administered botulinum toxin
- Muscle Relaxants: Excessive weakness may also be exaggerated by administration of a muscle relaxant before or after administration of abobotulinumtoxin A
Pregnancy & Lactation
Pregnancy
There are no adequate data from postmarketing surveillance on the developmental risk associated with use in pregnant women
In animal studies, administrations during pregnancy resulted in adverse effects on fetal growth (decreased fetal body weight and skeletal ossification) at clinically relevant doses, which were associated with maternal toxicity
Lactation
Not known if excreted in breast milk; effect on nursing infant not known
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.
Pharmacology
Mechanism of Action
Neurotoxin from Clostridium botulinum; prevents ACh release from presynaptic membrane, causing temporary calming of muscle contractions by blocking the transmission of nerve impulses
Pharmacokinetics
Metabolism: unknown
Excretion: unknown
Minimal levels in circulation after IM injection
Onset of action
- Blepharospasm: 3-4 days
- Strabismus: 1-2 days
- Cervical Dystonia: 2 weeks
- Detrusor overactivity: 2 weeks
Duration
- Blepharospasm: 3-4 months
- Strabismus: 1-2 days
- Cervical Dystonia: 3-4 months
- Detrusor overactivity: 42-48 weeks
Administration
IM Preparation
Vacuum dried powder for reconstitution only with sterile, non-preserved 0.9% Sodium Chloride Injection USP prior to injection
Chronic migraine: The recommended dilution is 200 Units/4 mL or 100 Units/2 mL, with a final concentration of 5 Units per 0.1 mL
IM Preparation (Botox Cosmetic)
Reconstitute 1.25 mL (50 unit/vial) or 2.5 mL (100 unit/vial) of 0.9% NaCl, preservative free (concentration: 4 units/0.1 mL)
Slowly inject diluent into the vial; discard vial if vacuum does not pull the diluent into the vial
Gently mix; administered within 24 hr after reconstitution
Discard any remaining solution
IM Administration
Blepharospasm: use sterile, 27- or 30-gauge needle without EMG guidance to inject into the medial & lateral pretarsal orbicularis oculi of upper lid and into the lateral pretarsal orbicularis oculi of lower lid
Axillary Hyperhidrosis: standard staining techniques (eg, Minor's iodine starch test) are used to identify the hyperhidrotic area to be injected; pts should shave their underarms & refrain from using OTC deodorants/antiperspirants for 24 hr prior to such staining tests
Strabismus: Inject into extraocular muscles
Do not use Botox Cosmetic and contact Allergan (1-800-890-4345) if
- Carton labeling does not contain an intact seal with a translucent silver Allergan logo (on both ends of the carton) or the seal has a black circle with a diagonal line through it (ie, prohibition sign) Vial label does not contain a holographic film containing the name “Allergan” within rainbow colored horizontal lines, OR
- The U.S. License number 1145 is not present on the vial label and carton labeling
- Carefully examine package to detect fraudulent products
Storage
Unused and reconstituted vials: Store in a refrigerator 2- 8°C (36-46ºF)
Reconstituted vials: Use within 24 hr
Images
Patient Handout
Formulary
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