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

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

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

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

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

Storage

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

Reconstituted vials: Use within 24 hr