onabotulinumtoxinA (Rx)

>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, eyelid edema

  • Pediatrics

    • Lower limb spasticity

Contraindications

Hypersensitivity

Neuromuscular disease

Infection at the proposed injection site

Intradetrusor injection: Urinary tract infection or urinary retention (post-void residual >200 mL, who are not routinely performing clean intermittent self-catheterizationwho are not routinely performing clean intermittent self-catheterization)

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

Patients with pre-existing neuromuscular disorders should be monitored when given botulinum toxin; patients with known or unrecognized neuromuscular disorders or neuromuscular junction disorders may be at increased risk of clinically significant effects including generalized muscle weakness, diplopia, ptosis, dysphonia, dysarthria, severe dysphagia and respiratory compromise from therapeutic doses

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

Autonomic dysreflexia associated with intradetrusor injections could occur in patients treated for detrusor overactivity associated with a neurologic condition; may require prompt medical therapy

Use for the treatment of overactive bladder in patients taking antibiotics chronically due to recurrent UTIs and in patients with multiple recurrent UTIs during treatment should only be considered when the benefit is likely to outweigh potential risk

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

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.

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

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

Preparation for detrusor administration (Botox

Reconstitute vials to result in a final concentration of 20 units/mL

• 200-unit vials: Add 10 mL of preservative-free 0.9% NaCl
• 100-unit vials: Add 5 mL of preservative-free 0.9% NaCl to one 100-unit vial (BW <34kg) or each of two 100-unit vials (BW ≥34 kg)
• Gently mix vial(s)

Further dilution

• BW <34 kg: Refer to prescribing information dilution instructions
• BW ≥34 kg: Draw 10 mL from vial(s) into one 10-mL syringe
• Use immediately; dispose of any unused saline

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

Detrusor administration via injection (Botox)

UTI prophylaxis

• Oral antibiotics, except aminoglycosides: Administer 1-3 days pretreatment, on treatment day, and 1-3 days posttreatment
• Alternative for patients receiving general anesthesia (or conscious sedation): On treatment day, administer 1 dose of IV prophylactic antibiotics, except aminoglycosides, before treatment

Local anesthesia

• Age 5 to <12 years: Consider general anesthesia (or conscious sedation) before injection, per local site practice
• Age ≥12 years: Consider an intravesical instillation of diluted local anesthetic with or without sedation, or general anesthesia before injection, per local site practice
• All age groups: At a minimum, consider a diluted instillation of local anesthetic; if a local anesthetic instillation is performed, drain and irrigate bladder with sterile saline before injection

Administration

• Prime injection needle with ~1 mL of diluted solution before start of injections (depending on needle length) to remove any air
• Insert needle ~2 mm into detrusor and 20 injections of 0.5 mL each (total volume: 10 mL) should be spaced ~1 cm apart
• For final injection, inject ~1 mL of sterile normal saline so that any remaining drug in the needle is delivered to bladder
• After injections are given, saline used for bladder wall visualization should be drained
• Observe for at least 30 minutes post-injection

Storage

Unused and reconstituted vials: Store in a refrigerator 2- 8°C (36-46ºF)

Reconstituted vials: Use within 24 hr