OnabotulinumtoxinA

What is OnabotulinumtoxinA?

OnabotulinumtoxinA (BOTOX) is an acetylcholine release inhibitor and a neuromuscular blocking agent used to treat:

• overactive bladder
• to prevent headaches
• to treat increased muscle stiffness
• to treat the abnormal head position and neck pain
• to treat certain types of eye muscle problems.

What are the uses of this medicine?

BOTOX is a prescription medicine that is injected into muscles and used:

• to treat overactive bladder symptoms such as a strong need to urinate with leaking or wetting accidents (urge urinary incontinence), a strong need to urinate right away (urgency), and urinating often (frequency) in adults when another type of medicine (anticholinergic) does not work well enough or cannot be taken.
• to treat leakage of urine (incontinence) in adults with overactive bladder due to neurologic disease when another type of medicine (anticholinergic) does not work well enough or cannot be taken.
• to treat overactive bladder due to a neurologic disease in children 5 years of age and older when another type of medicine (anticholinergic) does not work well enough or cannot be taken.
• to prevent headaches in adults with chronic migraine who have 15 or more days each month with headache lasting 4 or more hours each day.
• to treat increased muscle stiffness in people 2 years of age and older with spasticity.
• to treat the abnormal head position and neck pain that happens with cervical dystonia (CD) in adults.
• to treat certain types of eye muscle problems (strabismus) or abnormal spasm of the eyelids (blepharospasm) in people 12 years of age and older.

How does this medicine work?

• BOTOX blocks neuromuscular transmission by binding to acceptor sites on motor or autonomic nerve terminals, entering the nerve terminals, and inhibiting the release of acetylcholine.
• This inhibition occurs as the neurotoxin cleaves SNAP-25, a protein integral to the successful docking and release of acetylcholine from vesicles situated within nerve endings.
• When injected intramuscularly at therapeutic doses, BOTOX produces partial chemical denervation of the muscle resulting in a localized reduction in muscle activity.
• In addition, the muscle may atrophy, axonal sprouting may occur, and extrajunctional acetylcholine receptors may develop.
• There is evidence that reinnervation of the muscle may occur, thus slowly reversing muscle denervation produced by BOTOX.
• When injected intradermally, BOTOX produces temporary chemical denervation of the sweat gland resulting in local reduction in sweating.
• Following intradetrusor injectionBold, BOTOX affects the efferent pathways of detrusor activity via inhibition of acetylcholine release.

Who Should Not Use this medicine ?

This medicine cannot be used in patients who:

• are allergic to any of the ingredients in BOTOX or BOTOX Cosmetic. See the end of this Medication Guide for a complete list of ingredients in BOTOX and BOTOX Cosmetic.
• had an allergic reaction to any other botulinum toxin product such as Myobloc®, Dysport®, or Xeomin®.
• have a skin infection at the planned injection site.
• are being treated for urinary incontinence and have a urinary tract infection (UTI).
• are being treated for urinary incontinence and find that you cannot empty your bladder on your own (only applies to people who are not routinely catheterizing).

What drug interactions can this medicine cause?

• Patients receiving concomitant treatment of BOTOX and aminoglycosides or other agents interfering with neuromuscular transmission (e.g., curare-like agents), or muscle relaxants, should be observed closely because the effect of BOTOX may be potentiated.

Is this medicine FDA approved?

• Initial U.S. Approval: 1989

How should this medicine be used?

Recommended Dosage: In a 3 month interval, do not exceed a total dose of: • Adults: 400 Units • Pediatrics: the lesser of 10 Units/kg or 340 Units

• Overactive Bladder: Recommended total dose 100 Units, as 0.5 mL (5 Units) injections across 20 sites into the detrusor
• Adult Detrusor Overactivity associated with a Neurologic Condition: Recommended total dose 200 Units, as 1 mL (~6.7 Units) injections across 30 sites into the detrusor

• Pediatric Detrusor Overactivity associated with a Neurologic Condition: 0.5 mL injections across 20 sites into the detrusor

Greater than or equal to 34 kg: Recommended total dose is 200 Units Less than 34 kg: Recommended total dose is 6 Units/kg

• Chronic Migraine: Recommended total dose 155 Units, as 0.1 mL (5 Units) injections per each site divided across 7 head/neck muscles
• Adult Upper Limb Spasticity: Recommended total dose up to 400 Units divided among affected muscles
• Adult Lower Limb Spasticity: Recommended total dose 300 Units to 400 Units divided across ankle and toe muscles
• Pediatric Upper Limb Spasticity: Recommended total dose 3 Units/kg to 6 Units/kg (maximum 200 Units) divided among affected muscles
• Pediatric Lower Limb Spasticity: Recommended total dose 4 Units/kg to 8 Units/kg (maximum 300 Units) divided among affected muscles
• Cervical Dystonia: Base dosing on the patient’s head and neck position, localization of pain, muscle hypertrophy, patient response, and adverse event history; use lower initial dose in botulinum toxin naïve patients
• Axillary Hyperhidrosis: 50 Units per axilla
• Blepharospasm: 1.25 Units-2.5 Units into each of 3 sites per affected eye
• Strabismus: The dose is based on prism diopter correction or previous response to treatment with BOTOX

Administration

• BOTOX or BOTOX Cosmetic is an injection that your doctor will give you.
• BOTOX is injected into your affected muscles, skin, or bladder.
• BOTOX Cosmetic is injected into your affected muscles.
• Your doctor may change your dose of BOTOX or BOTOX Cosmetic, until you and your doctor find the best dose for you.
• Your doctor will tell you how often you will receive your dose of BOTOX or BOTOX Cosmetic injections.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Injection: 100 Units or 200 Units vacuum-dried powder in a single-dose vial

This medicine is available in fallowing brand namesː

• BOTOX

What side effects can this medication cause?

The most common side effects of this medicine include:

• dry mouth.
• discomfort or pain at the injection site.
• tiredness.
• headache.
• neck pain.
• eye problems: double vision, blurred vision, decreased eyesight, drooping eyelids, swelling of your eyelids, and dry eyes.
• drooping eyebrows.
• urinary tract infection in both children and adults being treated for urinary incontinence.
• painful urination in adults being treated for urinary incontinence.
• bacteria in the urine of children being treated for urinary incontinence.
• inability to empty your bladder on your own and are being treated for urinary incontinence.
• allergic reactions. Symptoms of an allergic reaction to BOTOX or BOTOX Cosmetic may include: itching, rash, red itchy welts, wheezing, asthma symptoms, or dizziness or feeling faint.
• upper respiratory tract infection.

BOTOX and BOTOX Cosmetic can cause serious side effects:

• Problems breathing or swallowing
• Spread of toxin effects

What special precautions should I follow?

• Botulinum toxin effects may, in some cases, be observed beyond the site of local injection. The symptoms are consistent with the mechanism of action of botulinum toxin and may include asthenia, generalized muscle weakness, diplopia, ptosis, dysphagia, dysphonia, dysarthria, urinary incontinence, and breathing difficulties. Seek immediate medical attention if respiratory, speech or swallowing difficulties occur.
• Potency Units of BOTOX are not interchangeable with other preparations of 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 BOTOX injections for unapproved uses.
• Serious and/or immediate hypersensitivity reactions have been reported. These reactions include anaphylaxis, serum sickness, urticaria, soft tissue edema, and dyspnea.
• 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 of BOTOX.
• Treatment with BOTOX and other botulinum toxin products can result in swallowing or breathing difficulties. Patients treated with botulinum toxin may require immediate medical attention should they develop problems with swallowing, speech or respiratory disorders. These reactions can occur within hours to weeks after injection with botulinum toxin.
• Corneal exposure and ulceration due to reduced blinking may occur with BOTOX treatment of blepharospasm.
• During the administration of BOTOX for the treatment of strabismus, retrobulbar hemorrhages sufficient to compromise retinal circulation have occurred.
• Bronchitis and upper respiratory tract infections in patients treated for spasticity.
• Urinary tract infections in patients treated for OAB.
• Post-void residual urine volume should be monitored in patients treated for OAB or adult detrusor overactivity associated with a neurologic condition who do not catheterize routinely, particularly patients with multiple sclerosis or diabetes mellitus.

What to do in case of emergency/overdose?

• Excessive doses of BOTOX (onabotulinumtoxinA) for injection may be expected to produce neuromuscular weakness with a variety of symptoms.
• If the musculature of the oropharynx and esophagus are affected, aspiration may occur which may lead to development of aspiration pneumonia.

Management of overdosage:

• If the respiratory muscles become paralyzed or sufficiently weakened, intubation and assisted respiration may be necessary until recovery takes place. Supportive care could involve the need for a tracheostomy and/or prolonged mechanical ventilation, in addition to other general supportive care.
• In the event of overdose, antitoxin raised against botulinum toxin is available from the Centers for Disease Control and Prevention (CDC) in Atlanta, GA.
• In the event of suspected or actual cases of botulinum toxin poisoning, please contact your local or state Health Department to process a request for antitoxin through the CDC. If you do not receive a response within 30 minutes, please contact the CDC directly at 1-770-488-7100.

Can this medicine be used in pregnancy?

• There are no studies or adequate data from postmarketing surveillance on the developmental risk associated with use of BOTOX in pregnant women.

Can this medicine be used in children?

It is not known whether BOTOX is safe and effective in people younger than:

• 18 years of age for treatment of urinary incontinence
• 18 years of age for treatment of chronic migraine
• 16 years of age for treatment of cervical dystonia
• 18 years of age for treatment of hyperhidrosis
• 12 years of age for treatment of strabismus or blepharospasm
• 2 years of age for treatment of spasticity
• BOTOX Cosmetic is not recommended for use in children younger than 18 years of age.
• It is not known whether BOTOX and BOTOX Cosmetic are safe and effective to prevent headaches in people with migraine who have 14 or fewer headache days each month (episodic migraine).

What are the active and inactive ingredients in this medicine?

• Active ingredient: onabotulinumtoxinA
• Inactive ingredients: human albumin and sodium chloride

Who manufactures and distributes this medicine?

• Manufactured by: Allergan Pharmaceuticals Ireland a subsidiary of: Allergan, Inc.
• Distributed by: Allergan USA, Inc. Madison, NJ

What should I know about storage and disposal of this medication?

• Unopened vials of BOTOX should be stored in a refrigerator between 2° to 8°C (36º to 46ºF) for up to 36 months.
• Do not use after the expiration date on the vial.
• Reconstituted BOTOX may be stored in a refrigerator (2° to 8°C) for up to 24 hours until time of use.

• Dailymed label info on OnabotulinumtoxinA
• FDA OnabotulinumtoxinA

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