Clinical use of BOTOX® (onabotulinumtoxinA) is the result of more than 100 years of study into botulinum toxin type A. BOTOX® is one of the world's most widely-researched medicines with approximately 2,300 publications in peer-reviewed scientific and medical journals. BOTOX® is currently approved in approximately 85 countries for 25 different indications to help patients worldwide suffering from such serious or debilitating conditions as cervical dystonia, blepharospasm, strabismus, increased muscle stiffness in elbow, wrist, and finger muscles in adults with upper limb spasticity and symptoms of severe primary axillary hyperhidrosis (excessive underarm sweating) when medicines on the skin (topical) do not work well enough, the preventative treatment of headaches in adult patients with Chronic Migraine (please see Indication and Important Limitations below) (≥15 or more days per month with headache lasting four hours a day or longer) and urinary incontinence due to detrusor overactivity associated with a neurologic condition, such as multiple sclerosis (MS) or spinal cord injury (SCI), in adults who have an inadequate response to or are intolerant of an anticholinergic medication.1 Millions of patients worldwide have been treated therapeutically with BOTOX® neurotoxin over the course of more than 22 years since the approval of Blephorospasm and Strabismus, and Allergan is honoring its commitment to these patients through the provision of quality product, patient and physician education, and the continued pursuit of neurotoxin-based therapeutics. In the United States, BOTOX® is currently being investigated for the treatment of other medical conditions.
BOTOX® is a purified protein that works by blocking overactive nerve impulses that trigger excessive muscle contractions. The effect is temporary and lasts from approximately three to ten months, depending on the individual patient and indication. BOTOX® therapy should only be administered by a trained and qualified physician. Approved therapeutic indications for BOTOX® in the United States include the following:
Patients suffering from the condition experience an involuntary clenching of the muscles that control the eyelid, causing uncontrollable blinking which generally affects both eyes. Blepharospasm can diminish a patient's ability to perform everyday activities by interfering with their ability to see due to the lid blocking their eyes. This can progress from increased blinking to inability to open the eyelids, and finally, to functional blindness. Blepharospasm affects an estimated 20,000–50,000 people in the United States, with 2,000 new cases diagnosed annually.1 In 1989, the U.S. Food and Drug Administration (FDA) approved BOTOX® neurotoxin for the treatment of blepharospasm (abnormal spasm of the eyelids) associated with dystonia in people 12 years of age and older. Therapy with BOTOX® is a generally accepted standard of care for blepharospasm, and involves the injection of small therapeutic doses directly in the affected muscles around the eye to temporarily reduce the excessive muscle contractions.
Cervical dystonia, also called spasmodic torticollis, is a chronic, often painful neurological disorder. Cervical dystonia is a type of movement disorder – conditions that are characterized by loss of control in the neck area – which is estimated to affect approximately 125,000 people in the United States2, yet awareness of the condition is extremely limited. Cervical dystonia is characterized by involuntary contractions of the neck muscles that cause twisting, repetitive movements, or abnormal postures of the head. The mean age of symptom onset in patients with cervical dystonia is approximately 41 years – although it may occur in all ages – and women are twice as likely to be affected as men.3 BOTOX® (onabotulinumtoxinA) was approved by the FDA in 2000 for the treatment of the abnormal head position and neck pain that happens with cervical dystonia (CD) in people 16 years and older.
Chronic Migraine is a distinct and severe neurological disorder impacting an estimated 3.2 million* Americans4 and characterized by patients who have a history of migraine and suffer from headaches on 15 or more days per month with headaches lasting four hours a day or longer. BOTOX® is the first clinically studied prophylactic treatment to be approved by the FDA specifically for this debilitated patient population. It is not known whether BOTOX® is safe or effective to prevent headaches in patients with migraine who have 14 or fewer headaches each month (episodic migraine). The recommended retreatment schedule for BOTOX® is every 12 weeks.
Although Chronic Migraine occurs in both men and women, women are three times more likely than men to suffer from migraines.5 Sufferers often experience depression and anxiety as part of the condition.6 Chronic Migraine also can be influenced by life stress, sleep habits, diet and overuse of acute medications that relieve pain associated with symptoms of headache.7
It is estimated that approximately 80 percent of those who meet the definition of Chronic Migraine have not received an accurate diagnosis8 and, as a result, may be unaware of their treatment options. This may be due to mischaracterization of Chronic Migraine as a less severe headache disorder.8
Severe Primary Axillary Hyperhidrosis
Hyperhidrosis is the medical term for severe sweating, where patients with hyperhidrosis may sweat up to four or five times more than normal, far exceeding what is needed to regulate body temperature. Severe underarm sweating may be exacerbated by stress, emotion or exercise, but often occurs spontaneously. BOTOX® injection is a minimally invasive treatment approved by the U.S. Food and Drug Administration (FDA) in 2004 to treat the symptoms of severe underarm sweating (severe primary axillary hyperhidrosis) when medicines used on the skin do not work well enough in people 18 years and older. The effects of treatment are temporary, lasting approximately 6.7 months, and treatment is often covered by insurance.9 BOTOX® is also injected into the skin to treat the symptoms of severe underarm sweating (severe primary axillary hyperhidrosis) when medicines used on the skin (topical) do not work well enough in people 18 years and older. It is not known whether BOTOX® is safe or effective for severe sweating anywhere other than your armpits.
Strabismus is a visual defect that results when the eyes do not properly align with each other. One eye may look straight ahead but the other may turn in (“crossed eyes”), out (“wall eyes”), upward, or downward. Strabismus usually develops during childhood but can occur at any age, affecting nearly four in every 100 adults.10 BOTOX® therapy was granted approval in 1989 by the U.S. Food and Drug Administration (FDA) to treat certain types of eye muscle problems (strabismus) and abnormal spasm of the eyelids (blepharospasm) in people 12 years and older. Therapy with BOTOX® involves the injection of small therapeutic doses of purified botulinum toxin protein directly into the muscles surrounding the eye.
Upper Limb Spasticity
Spasticity is a debilitating condition impacting approximately 1 million Americans11, many of whom suffer from spasticity in the upper limbs following a stroke. Upper limb spasticity may also occur following a spinal cord or traumatic brain injury or in patients affected by multiple sclerosis or adults with a history of cerebral palsy. Although not a life-threatening condition, upper limb spasticity can be debilitating, producing muscle contractions that can result in stiff, tight muscles in the elbow, wrist and fingers, or a clenched fist. This stiffness hinders a patient’s ability to perform simple tasks, such as dressing or washing the hand, and often leaves the patient dependent on a caregiver to help with simple activities. In patients diagnosed with upper limb spasticity, BOTOX® is injected by a trained specialist directly into the affected muscles blocking overactive nerve impulses that trigger these contractions to reduce the severity of increased muscle tone in the elbow, wrist and fingers. In clinical studies, the efficacy of BOTOX® persisted up to three months on average. BOTOX® is the first and only neurotoxin approved by the FDA for the treatment of upper limb spasticity.
It is not known whether BOTOX® is safe or effective to treat increased stiffness in upper-limb muscles other than those in the elbow, wrist, and fingers, or to treat increased stiffness in lower-limb muscles. BOTOX® has not been shown to help people perform task-specific functions with their upper limbs or increase movement in joints that are permanently fixed in position by stiff muscles. Treatment with BOTOX® is not meant to replace your existing physical therapy or other rehabilitation that your doctor may have prescribed.
Urinary incontinence due to detrusor overactivity associated with a neurologic condition, such as multiple sclerosis (MS) or spinal cord injury (SCI), results when the spinal cord and bladder do not communicate effectively. For people living with MS, this occurs because they develop lesions on the spinal cord, while people with SCI have irreversible nerve damage, resulting in the inability of the spinal cord and bladder to communicate effectively.12,13 As a result, the bladder muscle involuntarily contracts, increasing the pressure in the bladder and decreasing the volume of urine the bladder can hold, which causes the individual to leak urine frequently and unexpectedly.14 More than half of patients with MS, SCI, Parkinson’s disease or stroke may have overactive bladder.15,16 BOTOX® has been approved by the FDA for injection into muscles for the treatment of leakage of urine (incontinence) in adults with overactive bladder due to neurologic disease (e.g. multiple sclerosis (MS) or spinal cord injury (SCI)) who still have leakage or experience too many side effects after trying an anticholinergic medication in people 18 years and older.17
BOTOX® (onabotulinumtoxinA) & BOTOX® Cosmetic (onabotulinumtoxinA) Important Information
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 18 years and older when another type of medicine (anticholinergic) does not work well enough or cannot be taken.
- to treat leakage of urine (incontinence) in adults 18 years and older with overactive bladder due to neurologic disease who still have leakage or cannot tolerate the side effects after trying an anticholinergic medication
- 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 in people 18 years or older
- to treat increased muscle stiffness in elbow, wrist, and finger muscles in people 18 years and older with upper limb spasticity
- to treat the abnormal head position and neck pain that happens with cervical dystonia (CD) in people 16 years and older
- to treat certain types of eye muscle problems (strabismus) or abnormal spasm of the eyelids (blepharospasm) in people 12 years and older
BOTOX® is also injected into the skin to treat the symptoms of severe underarm sweating (severe primary axillary hyperhidrosis) when medicines used on the skin (topical) do not work well enough in people 18 years and older.
BOTOX® Cosmetic is a prescription medicine that is injected into muscles and used to improve the look of moderate to severe frown lines between the eyebrows (glabellar lines) in adults younger than 65 years of age for a short period of time (temporary).
It is not known whether BOTOX® and BOTOX® Cosmetic is safe or effective to prevent headaches in patients with migraine who have 14 or fewer headache days each month (episodic migraine).
It is not known whether BOTOX® and BOTOX® Cosmetic is safe or effective to treat increased stiffness in upper-limb muscles other than those in the elbow, wrist, and fingers, or to treat increased stiffness in lower-limb muscles. BOTOX® has not been shown to help people perform task-specific functions with their upper limbs or increase movement in joints that are permanently fixed in position by stiff muscles. Treatment with BOTOX® is not meant to replace your existing physical therapy or other rehabilitation that your doctor may have prescribed.
It is not known whether BOTOX® and BOTOX® Cosmetic are safe or effective for severe sweating anywhere other than your armpits.
IMPORTANT SAFETY INFORMATION
BOTOX® and BOTOX® Cosmetic may cause serious side effects that can be life threatening. Call your doctor or get medical help right away if you have any of these problems any time (hours to weeks) after injection of BOTOX® or BOTOX® Cosmetic:
- Problems swallowing, speaking, or breathing, due to weakening of associated muscles, can be severe and result in loss of life. You are at the highest risk if these problems are pre-existing before injection. Swallowing problems may last for several months
- Spread of toxin effects. The effect of botulinum toxin may affect areas away from the injection site and cause serious symptoms including: loss of strength and all-over muscle weakness, double vision, blurred vision and drooping eyelids, hoarseness or change or loss of voice (dysphonia), trouble saying words clearly (dysarthria), loss of bladder control, trouble breathing, trouble swallowing. If this happens, do not drive a car, operate machinery, or do other dangerous activities
There has not been a confirmed serious case of spread of toxin effect away from the injection site when BOTOX® has been used at the recommended dose to treat chronic migraine, severe underarm sweating, blepharospasm, strabismus, or when BOTOX® Cosmetic has been used at the recommended dose to treat frown lines.
Do not take BOTOX® or BOTOX® Cosmetic if you:
are allergic to any of the ingredients in BOTOX® (see Medication Guide for ingredients); had an allergic reaction to any other botulinum toxin product such as
Dysport® (abobotulinumtoxinA), or
Xeomin® (incobotulinumtoxinA); have a skin infection at the planned injection site.
Do not take BOTOX® for the treatment of urinary incontinence if you:
have a urinary tract infection (UTI) or cannot empty your bladder on your own and are not routinely catheterizing.
Due to the risk of urinary retention (not being able to empty the bladder), only patients who are willing and able to initiate catheterization post-treatment, if required, should be considered for treatment.
Patients treated for overactive bladder
In clinical trials, 6.5% of patients (36/552) initiated clean intermittent catheterization for urinary retention following treatment with BOTOX® 100 Units as compared to 0.4% of patients (2/542) treated with placebo. The median duration of catheterization for these patients treated with BOTOX® 100 Units was 63 days (minimum 1 day to maximum 214 days) as compared to a median duration 11 days (minimum 3 days to maximum 18 days) for patients receiving placebo.
Patients with diabetes mellitus treated with BOTOX® were more likely to develop urinary retention than non-diabetics.
Patients treated for overactive bladder due to neurologic disease
In clinical trials, 30.6% of patients (33/108) who were not using clean intermittent catheterization (CIC) prior to injection, required catheterization for urinary retention following treatment with BOTOX® 200 Units as compared to 6.7% of patients (7/104) treated with placebo. The median duration of post-injection catheterization for these patients treated with BOTOX® 200 Units (n=33) was 289 days (minimum 1 day to maximum 530 days) as compared to a median duration 358 days (minimum 2 days to maximum 379 days) for patients receiving placebo (n=7).
Among patients not using CIC at baseline, those with MS were more likely to require CIC post-injection than those with SCI.
The dose of BOTOX® and BOTOX® Cosmetic is not the same as, or comparable to, another botulinum toxin product.
Serious and/or immediate allergic reactions have been reported. These reactions include itching, rash, red itchy welts, wheezing, asthma symptoms, or dizziness or feeling faint. Tell your doctor or get medical help right away if you experience any such symptoms; further injection of BOTOX® or BOTOX® Cosmetic should be discontinued.
Tell your doctor about all your muscle or nerve conditions such as amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease), myasthenia gravis, or Lambert-Eaton syndrome, as you may be at increased risk of serious side effects including severe dysphagia (difficulty swallowing) and respiratory compromise (difficulty breathing) from typical doses of BOTOX® or BOTOX® Cosmetic.
Tell your doctor if you have any breathing-related problems. Your doctor will want to monitor you for any breathing problems during your treatment with BOTOX® for upper limb spasticity or for detrusor overactivity associated with a neurologic condition. The risk of pulmonary effects in patients with compromised respiratory status is increased in patients receiving BOTOX®.
Cornea problems have been reported. Cornea (surface of the eye) problems have been reported in some people receiving BOTOX® for their blepharospasm, especially in people with certain nerve disorders. BOTOX® may cause the eyelids to blink less, which could lead to the surface of the eye being exposed to air more than is usual. Tell your doctor if you experience any problems with your eyes while receiving BOTOX®. Your doctor may treat your eyes with drops, ointments, contact lenses, or with an eye patch.
Bleeding behind the eye has been reported. Bleeding behind the eyeball has been reported in some people receiving BOTOX® for their strabismus. Tell your doctor if you notice any new visual problems while receiving BOTOX®.
Bronchitis and upper respiratory tract infections (common colds) have been reported. Bronchitis was reported more frequently in people receiving BOTOX® for their upper limb spasticity. Upper respiratory infections (common colds) were also reported more frequently in people with prior breathing-related problems.
Autonomic Dysreflexia in Patients Treated for Detrusor Overactivity Associated With a Neurologic Condition
Autonomic dysreflexia associated with intradetrusor injections of BOTOX® could occur in patients treated for detrusor overactivity associated with a neurologic condition and may require prompt medical therapy. In clinical trials, the incidence of autonomic dysreflexia was greater in patients treated with BOTOX® 200 Units compared with placebo (1.5% versus 0.4%, respectively).
Human albumin and spread of viral diseases. BOTOX® and BOTOX® Cosmetic contains albumin, a protein component of human blood. The potential risk of spreading viral diseases (eg, Creutzfeldt-Jakob disease [CJD]) via human serum albumin is extremely rare. No cases of viral diseases or CJD have ever been reported in association with human serum albumin.
Tell your doctor about all your medical conditions, including if you: have or have had bleeding problems; have plans to have surgery; had surgery on your face; weakness of forehead muscles, such as trouble raising your eyebrows; drooping eyelids; any other abnormal facial change; have symptoms of a urinary tract infection (UTI) and are being treated for urinary incontinence. Symptoms of a urinary tract infection may include pain or burning with urination, frequent urination, or fever; have problems emptying your bladder on your own and are being treated for urinary incontinence; are pregnant or plan to become pregnant (it is not known if BOTOX® or BOTOX® Cosmetic can harm your unborn baby); are breastfeeding or plan to breastfeed (it is not known if BOTOX® or BOTOX® Cosmetic passes into breast milk).
Tell your doctor about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal products. Using BOTOX® or BOTOX® Cosmetic with certain other medicines may cause serious side effects.
Do not start any new medicines until you have told your doctor that you have received BOTOX® or BOTOX® Cosmetic in the past.
Especially tell your doctor if you: have received any other botulinum toxin product in the last 4 months; have received injections of botulinum toxin such as
Xeomin® in the past (be sure your doctor knows exactly which product you received); have recently received an antibiotic by injection; take muscle relaxants; take an allergy or cold medicine; take a sleep medicine; take anti-platelets (aspirin-like products) or anti-coagulants (blood thinners).
Other side effects of BOTOX® and BOTOX® Cosmetic include:
dry mouth, discomfort or pain at the injection site, tiredness, headache, neck pain, and eye problems: double vision, blurred vision, decreased eyesight, drooping eyelids, swelling of your eyelids, and dry eyes. In people being treated for urinary incontinence other side effects include: urinary tract infection, painful urination, and/or inability to empty your bladder on your own. If you have difficulty fully emptying your bladder after receiving BOTOX®, you may need to use disposable self-catheters to empty your bladder up to a few times each day until your bladder is able to start emptying again.
For more information refer to the Medication Guide or talk with your doctor.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.
Please see BOTOX® full Product Information including Boxed Warning and Medication Guide.
Please see BOTOX® Cosmetic full Product Information including Boxed Warning and Medication Guide.