HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use
BOTOX
®
safely and effectively. See full prescribing information for
BOTOX.
BOTOX
(onabotulinumtoxinA) for injection, for intramuscular,
intradetrusor, or intradermal use
Initial U.S. Approval: 1989
____________________
RECENT MAJOR CHANGES
__________________________
• Indications and Usage, Detrusor Overactivity associated with a
Neurologic Condition (1.1) 8/2011
• Indications and Usage, Chronic Migraine (1.2) 10/2010
• Dosage and Administration, Detrusor Overactivity associated with a
Neurologic Condition (2.3) 8/2011
• Dosage and Administration, Chronic Migraine (2.4) 10/2010
• Contraindications, Acute Urinary Tract Infection and Acute Urinary
Retention (4.3) 8/2011
• Warnings and Precautions, Autonomic Dysreflexia and Urinary Retention
in Patients Treated for Detrusor Overactivity associated with a Neurologic
Condition (5.10) 8/2011
____________________
INDICATIONS AND USAGE
_________________________
BOTOX is an acetylcholine release
inhibitor and a neuromuscular blocking agent
indicated for:
• Treatment of urinary incontinence due to detrusor overactivity associated with a
neurologic condition [e.g., spinal cord injury (SCI), multiple sclerosis (MS)] in
adults who have an inadequate response to or are intolerant of an anticholinergic
medication (1.1)
• Prophylaxis of headaches in adult patients with chronic migraine (≥15 days per
month with headache lasting 4 hours a day or longer) (1.2)
• Treatment of upper limb spasticity in adult patients (1.3)
• Treatment of cervical dystonia in adult patients, to reduce the severity of
abnormal head position and neck pain (1.4)
• Treatment of severe axillary hyperhidrosis that is inadequately managed by
topical agents in adult patients (1.5)
• Treatment of blepharospasm associated with dystonia in patients ≥12 years of
age (1.6)
• Treatment of strabismus in patients ≥12 years of age (1.6)
Important limitations:
• Safety and effectiveness of BOTOX have not been established for the
prophylaxis of episodic migraine (14 headache days or fewer per month).
(1.2)
• Safety and effectiveness of BOTOX have not been established for the
treatment of upper limb spasticity in pediatric patients, and for the
treatment of lower limb spasticity in adult and pediatric patients. (1.3)
• Safety and effectiveness of BOTOX for hyperhidrosis in body areas other
than axillary have not been established. (1.5)
____________________
DOSAGE AND ADMINISTRATION
____________________
• Indication specific dosage and administration recommendations should be
followed; Do not exceed a total dose of 360 Units administered in a 3 month
interval (2)
• See Preparation and Dilution Technique for instructions on BOTOX
reconstitution, storage, and preparation before injection (2.1)
• 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 (2.2)
• Chronic Migraine: Recommended total dose 155 Units, as 0.1 mL (5 Units)
injections per each site divided across 7 head/neck muscles (2.3)
• Upper Limb Spasticity: Select dose based on muscles affected, severity of
muscle activity, prior response to treatment, and adverse event history;
Electromyographic guidance recommended (2.4)
• 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 (2.5)
• Axillary Hyperhidrosis: 50 Units per axilla (2.6)
• Blepharospasm: 1.25 Units-2.5 Units into each of 3 sites per affected eye
(2.7)
• Strabismus: 1.25 Units-2.5 Units initially in any one muscle (2.8)
_________________
DOSAGE FORMS AND STRENGTHS
_________________
Single-use, sterile 50 Units, 100 Units, or 200 Units vacuum-dried powder for
reconstitution only with sterile, non-preserved 0.9% Sodium Chloride Injection
USP prior to injection (3)
_________________________
CONTRAINDICATIONS
____________________________
• Hypersensitivity to any botulinum toxin preparation or to any of the
components in the formulation (4.1, 5.3, 6.2)
• Infection at the proposed injection site (4.2)
• Intradetrusor Injections: Acute Urinary Tract Infection and/or Acute
Urinary Retention (4.3)
__________________
WARNINGS AND PRECAUTIONS
____________________
• Potency Units of BOTOX not interchangeable with other preparations of
botulinum toxin products (5.1, 11)
• Spread of toxin effects; swallowing and breathing difficulties can lead to
death. Seek immediate medical attention if respiratory, speech or
swallowing difficulties occur (5.2, 5.4)
• Concomitant neuromuscular disorder may exacerbate clinical effects of
treatment (5.5)
• Use with caution in patients with compromised respiratory function (5.4,
5.6)
• Corneal exposure and ulceration due to reduced blinking may occur with
BOTOX treatment of blepharospasm (5.7)
• Retrobulbar hemorrhages and compromised retinal circulation circulation
may occur with BOTOX treatment of strabismus (5.8)
• Bronchitis and upper respiratory tract infections in patients treated for
upper limb spasticity (5.9)
• Urinary retention: Post-void residual urine volume should be monitored in
patients treated for detrusor overactivity associated with a neurologic
condition who do not catheterize routinely, particularly patients with MS.
(5.10)
__________________________
ADVERSE REACTIONS
___________________________
The most common adverse reactions (≥5% and >placebo) are (6.1):
• Detrusor Overactivity associated with a neurologic condition: urinary tract
infection, urinary retention
• Chronic Migraine: neck pain, headache
• Spasticity: pain in extremity
• Cervical Dystonia: dysphagia, upper respiratory infection, neck pain, headache,
increased cough, flu syndrome, back pain, rhinitis
• Axillary Hyperhidrosis: injection site pain and hemorrhage, non-axillary
sweating, pharyngitis, flu syndrome
To report SUSPECTED ADVERSE REACTIONS, contact Allergan at 1-
800-433-8871 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
__________________________
DRUG INTERACTIONS
____________________________
• 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 (7)
_____________________
USE IN SPECIFIC POPULATIONS
____________________
• Pregnancy: Based on animal data, may cause fetal harm (8.1)
• Pediatric Use: Safety and efficacy are not established in patients under
18 years of age for the prophylaxis of headaches in chronic migraine, the
treatment of detrusor overactivity associated with a neurologic condition,
upper limb spasticity, and axillary hyperhidrosis, in patients under
16 years of age for the treatment of cervical dystonia, and in patients
under 12 years of age for the treatment of blepharospasm and strabismus
(8.4)
See 17 for PATIENT COUNSELING INFORMATION and Medication
Guide
Revised: 08/2011
WARNING: DISTANT SPREAD OF TOXIN EFFECT
See full prescribing information for complete boxed warning.
The effects of BOTOX
and all botulinum toxin products may spread
from the area of injection to produce symptoms consistent with
botulinum toxin effects. These symptoms have been reported hours to
weeks after injection. Swallowing and breathing difficulties can be life
threatening and there have been reports of death. The risk of
symptoms is probably greatest in children treated for spasticity but
symptoms can also occur in adults, particularly in those patients who
have an underlying condition that would predispose them to these
symptoms. (5.2)
This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda
FULL PRESCRIBING INFORMATION: CONTENTS*
WARNING: DISTANT SPREAD OF TOXIN EFFECT
1 INDICATIONS AND USAGE
1.1 Detrusor Overactivity associated with a Neurologic Condition
1.2 Chronic Migraine
1.3 Upper Limb Spasticity
1.4 Cervical Dystonia
1.5 Primary Axillary Hyperhidrosis
1.6 Blepharospasm and Strabismus
2 DOSAGE AND ADMINISTRATION
2.1 Instructions for Safe Use
2.2 Preparation and Dilution Technique
2.3 Detrusor Overactivity associated with a Neurologic Condition
2.4 Chronic Migraine
2.5 Upper Limb Spasticity
2.6 Cervical Dystonia
2.7 Primary Axillary Hyperhidrosis
2.8 Blepharospasm
2.9 Strabismus
3 DOSAGE FORMS AND STRENGTHS
4 CONTRAINDICATIONS
4.1 Known Hypersensitivity to Botulinum Toxin
4.2 Infection at the Injection Site(s)
4.3 Acute Urinary Tract Infection and/or Acute Urinary Retention
5 WARNINGS AND PRECAUTIONS
5.1 Lack of Interchangeability between Botulinum Toxin Products
5.2 Spread of Toxin Effect
5.3 Hypersensitivity Reactions
5.4 Dysphagia and Breathing Difficulties in Treatment of Cervical
Dystonia
5.5 Pre-Existing Neuromuscular Disorders
5.6 Pulmonary Effects of BOTOX in Patients with Compromised
Respiratory Status Treated for Spasticity or for Detrusor Overactivity
associated with a Neurologic Condition
5.7 Corneal Exposure and Ulceration in Patients Treated with BOTOX for
ospasm Blephar
5.8
Retrobulbar Hemorrhages in Patients Treated with BOTOX for
Strabismus
5.9 Bronchitis and Upper Respiratory Tract Infections in Patients Treated
for Spasticity
5.10 Autonomic Dysreflexia and Urinary Retention in Patients Treated for
Detrusor Overactivity associated with a Neurologic Condition
5.11 Human Albumin and Transmission of Viral Diseases
6 ADVERSE REACTIONS
6.1 Clinical Trials Experience
6.2 Immunogenicity
6.3 Post-Marketing Experience
7 DRUG INTERACTIONS
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
8.3 Nursing Mothers
8.4 Pediatric Use
8.5 Geriatric Use
10 OVERDOSAGE
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.3 Pharmacokinetics
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
13.2 Animal Toxicity
14 CLINICAL STUDIES
14.1 Detrusor Overactivity associated with a Neurologic Condition
14.2 Chronic Migraine
14.3 Upper Limb Spasticity
14.4 Cervical Dystonia
14.5 Primary Axillary Hyperhidrosis
14.6 Blepharospasm
14.7 Strabismus
16 HOW SUPPLIED/STORAGE AND HANDLING
17 PATIENT COUNSELING INFORMATION
17.1 Swallowing, Speaking or Breathing Difficulties, or Other Unusual
Symptoms
17.2 Ability to Operate Machinery or Vehicles
17.3 Voiding Difficulties after Bladder Injections
* Sections or subsections omitted from the full prescribing information are not
listed
FULL PRESCRIBING INFORMATION
1 INDICATIONS AND USAGE
1.1 Detrusor Overactivity associated with a Neurologic Condition
BOTOX (onabotulinumtoxinA) for injection is indicated for the treatment of urinary incontinence due to detrusor overactivity
associated with a neurologic condition (e.g., SCI, MS) in adults who have an inadequate response to or are intolerant of an
anticholinergic medication.
WARNING: DISTANT SPREAD OF TOXIN EFFECT
Postmarketing reports indicate that the effects of BOTOX and all botulinum toxin products may spread from the area of
injection to produce symptoms consistent with botulinum toxin effects. These may include asthenia, generalized muscle
weakness, diplopia, 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 there have been reports of death. 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 an
underlying condition that would predispose them to these symptoms. In unapproved uses, including spasticity in children,
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. [See Warnings and Precautions (5.2)]
This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda
1.2 Chronic Migraine
BOTOX is indicated for the prophylaxis of headaches in adult patients with chronic migraine (≥15 days per month with headache
lasting 4 hours a day or longer).
Important limitations
Safety and effectiveness have not been established for the prophylaxis of episodic migraine (14 headache days or fewer per month) in
seven placebo-controlled studies.
1.3 Upper Limb Spasticity
BOTOX is indicated for the treatment of upper limb spasticity in adult patients, to decrease the severity of increased muscle tone in
elbow flexors (biceps), wrist flexors (flexor carpi radialis and flexor carpi ulnaris) and finger flexors (flexor digitorum profundus and
flexor digitorum sublimis).
Important limitations
Safety and effectiveness of BOTOX have not been established for the treatment of other upper limb muscle groups, or for the
treatment of lower limb spasticity. Safety and effectiveness of BOTOX have not been established for the treatment of spasticity in
pediatric patients under age 18 years. BOTOX has not been shown to improve upper extremity functional abilities, or range of motion
at a joint affected by a fixed contracture. Treatment with BOTOX is not intended to substitute for usual standard of care rehabilitation
regimens.
1.4 Cervical Dystonia
BOTOX is indicated for the treatment of adults with cervical dystonia, to reduce the severity of abnormal head position and neck pain
associated with cervical dystonia.
1.5 Primary Axillary Hyperhidrosis
BOTOX is indicated for the treatment of severe primary axillary hyperhidrosis that is inadequately managed with topical agents.
Important limitations
The safety and effectiveness of BOTOX for hyperhidrosis in other body areas have not been established. Weakness of hand muscles
and blepharoptosis may occur in patients who receive BOTOX for palmar hyperhidrosis and facial hyperhidrosis, respectively.
Patients should be evaluated for potential causes of secondary hyperhidrosis (e.g., hyperthyroidism) to avoid symptomatic treatment of
hyperhidrosis without the diagnosis and/or treatment of the underlying disease.
Safety and effectiveness of BOTOX have not been established for the treatment of axillary hyperhidrosis in pediatric patients under
age 18.
1.6 Blepharospasm and Strabismus
BOTOX is indicated for the treatment of strabismus and blepharospasm associated with dystonia, including benign essential
blepharospasm or VII nerve disorders in patients 12 years of age and above.
2 DOSAGE AND ADMINISTRATION
2.1 Instructions for Safe Use
The potency Units of BOTOX (onabotulinumtoxinA) for injection are specific to the preparation and assay method utilized.
They are not interchangeable with other preparations of botulinum toxin products and, therefore, units of biological activity
of BOTOX cannot be compared to nor converted into units of any other botulinum toxin products assessed with any other
specific assay method [see Warnings and Precautions (5.1) and Description (11)].
Indication specific dosage and administration recommendations should be followed. In treating adult patients for one or more
indications, the maximum cumulative dose should generally not exceed 360 Units, in a 3 month interval.
The safe and effective use of BOTOX depends upon proper storage of the product, selection of the correct dose, and proper
reconstitution and administration techniques. Physicians administering BOTOX must understand the relevant neuromuscular and/or
orbital anatomy of the area involved and any alterations to the anatomy due to prior surgical procedures. An understanding of standard
electromyographic techniques is also required for treatment of strabismus and of upper limb spasticity, and may be useful for the
treatment of cervical dystonia.
Use caution when BOTOX treatment is used in the presence of inflammation at the proposed injection site(s) or when excessive
weakness or atrophy is present in the target muscle(s).
This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda
2.2 Preparation and Dilution Technique
BOTOX is supplied in single-use 50 Units, 100 Units, and 200 Units per vial. Prior to injection, reconstitute each vacuum-dried vial of
BOTOX with sterile, non-preserved 0.9% Sodium Chloride Injection USP. Draw up the proper amount of diluent in the appropriate
size syringe (see Table 1, or for specific instructions for detrusor overactivity associated with a neurologic condition see Section 2.3),
and slowly inject the diluent into the vial. Discard the vial if a vacuum does not pull the diluent into the vial. Gently mix BOTOX
with
the saline by rotating the vial. Record the date and time of reconstitution on the space on the label. BOTOX should be administered
within 24 hours after reconstitution. During this time period, reconstituted BOTOX should be stored in a refrigerator (2° to 8°C).
Table 1: Dilution Instructions for BOTOX Vials (50 Units, 100 Units, and 200 Units)
Diluent*
Added to
50 Unit
Vial
Resulting Dose
Units per 0.1
mL
Diluent*
Added to
100 Unit
Vial
Resulting Dose
Units per 0.1
mL
Diluent*
Added to
200 Unit
Vial
Resulting Dose
Units per 0.1 mL
1 mL
2 mL
4 mL
5 Units
2.5 Units
1.25 Units
1 mL
2 mL
4 mL
8 mL
10 Units
5 Units
2.5 Units
1.25 Units
1 mL
2 mL
4 mL
8 mL
10 mL
20 Units
10 Units
5 Units
2.5 Units
2 Units
*Preservative-free 0.9% Sodium Chloride Injection, USP Only
Note: These dilutions are calculated for an injection volume of 0.1 mL. A decrease or increase in the BOTOX dose is also possible by
administering a smaller or larger injection volume - from 0.05 mL (50% decrease in dose) to 0.15 mL (50% increase in dose).
An injection of BOTOX is prepared by drawing into an appropriately sized sterile syringe an amount of the properly reconstituted
toxin slightly greater than the intended dose. Air bubbles in the syringe barrel are expelled and the syringe is attached to an
appropriate injection needle. Patency of the needle should be confirmed. A new, sterile, needle and syringe should be used to enter the
vial on each occasion for removal of BOTOX.
Reconstituted BOTOX should be clear, colorless, and free of particulate matter. Parenteral drug products should be inspected visually
for particulate matter and discoloration prior to administration and whenever the solution and the container permit.
Reconstitute a 200 Unit vial of BOTOX with 6 mL of 0.9% non-preserved saline solution and mix the vial gently. Draw 2 mL from
the vial into each of three 10 mL syringes. Complete the reconstitution by adding 8 mL of 0.9% non-preserved saline solution into
each of the 10 mL syringes, and mix gently. This will result in three 10 mL syringes each containing 10 mL (~67 Units in each), for a
total of 200 Units of reconstituted BOTOX. Use immediately after reconstitution in the syringe. Dispose of any unused saline.
2.3 Detrusor Overactivity associated with a Neurologic Condition
Patients should not have an acute urinary tract infection prior to treatment. Prophylactic antibiotics (except aminoglycosides, see Drug
Interactions (7)) should be administered 1-3 days pre-treatment, on the treatment day, and 1-3 days post-treatment.
Patients should discontinue anti-platelet therapy at least 3 days before the injection procedure. Patients on anti-coagulant therapy need
to be managed appropriately to decrease the risk of bleeding.
Appropriate caution should be exercised when performing a cystoscopy.
An intravesical instillation of diluted local anesthetic with or without sedation, or general anesthesia may be used prior to injection,
per local site practice. If a local anesthetic instillation is performed, the bladder should be drained and irrigated with sterile saline
before injection.
The recommended dose is 200 Units of BOTOX per treatment, and should not be exceeded.
Alternatively, reconstitute two 100 Unit vials of BOTOX, each with 6 mL of 0.9% non-preserved saline solution and mix the vials
gently. Draw 4 mL from each vial into each of two 10 mL syringes. Draw the remaining 2 mL from each vial into a third 10 mL
syringe. Complete the reconstitution by adding 6 mL of 0.9% non-preserved saline solution into each of the 10 mL syringes, and mix
gently. This will result in three 10 mL syringes each containing 10 mL (~67 Units in each), for a total of 200 Units of reconstituted
BOTOX. Use immediately after reconstitution in the syringe. Dispose of any unused saline.
This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda
Reconstituted BOTOX (200 Units/30 mL) is injected into the detrusor muscle via a flexible or rigid cystoscope, avoiding the trigone.
The bladder should be instilled with enough saline to achieve adequate visualization for the injections, but over-distension should be
avoided.
The injection needle should be filled (primed) with approximately 1 mL of reconstituted BOTOX prior to the start of injections
(depending on the needle length) to remove any air.
The needle should be inserted approximately 2 mm into the detrusor, and 30 injections of 1 mL (~6.7 Units) each (total volume of
30 mL) should be spaced approximately 1 cm apart (see Figure 1). For the final injection, approximately 1 mL of sterile normal saline
should be injected so the full dose is delivered. After the injections are given, the saline used for bladder wall visualization should be
drained. The patient should be observed for at least 30 minutes post-injection.
Patients should be considered for re-injection when the clinical effect of the previous injection diminishes (median time to
qualification for re-treatment in the double-blind, placebo-controlled clinical studies was 295-337 days [42-48 weeks] for BOTOX
200 Units), but no sooner than 12 weeks from the prior bladder injection.
Figure 1: Injection Pattern for Detrusor Overactivity associated with a Neurologic Condition
2.4 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 (see Table 1). The
recommended dose for treating chronic migraine is 155 Units administered intramuscularly (IM) using a sterile 30-gauge, 0.5 inch
needle as 0.1 mL (5 Units) injections per each site. Injections should be divided across 7 specific head/neck muscle areas as specified
in the diagrams and Table 2 below. A one inch needle may be needed in the neck region for patients with thick neck muscles. With the
exception of the procerus muscle, which should be injected at one site (midline), all muscles should be injected bilaterally with half
the number of injection sites administered to the left, and half to the right side of the head and neck. The recommended re-treatment
schedule is every 12 weeks.
Diagrams 1-4: Recommended Injection Sites (A thru G) for Chronic Migraine
1 2 3 4
This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda
Table 2: BOTOX Dosing by Muscle for Chronic Migraine
Head/Neck Area Recommended Dose (Number of Sites
a
)
Frontalis
b
20 Units divided in 4 sites
Corrugator
b
10 Units divided in 2 sites
Procerus 5 Units in 1 site
Occipitalis
b
30 Units divided in 6 sites
Temporalis
b
40 Units divided in 8 sites
Trapezius
b
30 Units divided in 6 sites
Cervical Paraspinal
Muscle Group
b
20 Units divided in 4 sites
Total Dose:
155 Units divided in 31 sites
a
Each IM injection site = 0.1 mL = 5 Units BOTOX
b
Dose distributed bilaterally
2.5 Upper Limb Spasticity
Dosing in initial and sequential treatment sessions should be tailored to the individual based on the size, number and location of
muscles involved, severity of spasticity, the presence of local muscle weakness, the patient’s response to previous treatment, or
adverse event history with BOTOX. In clinical trials, doses ranging from 75 Units to 360 Units were divided among selected muscles
at a given treatment session.
T
able 3: BOTOX Dosing by Muscle for Upper Limb Spasticity
Muscle Recommended Dose
Total Dosage (Number of Sites)
Biceps Brachii 100 Units-200 Units divided in 4 sites
Flexor Carpi Radialis 12.5 Units-50 Units in 1 site
Flexor Carpi Ulnaris 12.5 Units-50 Units in 1 site
Flexor Digitorum Profundus 30 Units-50 Units in 1 site
Flexor Digitorum Sublimis 30 Units-50 Units in 1 site
The recommended dilution is 200 Units/4 mL or 100 Units/2 mL with 0.9% non-preserved sterile saline (see Table 1). The lowest
recommended starting dose should be used, and no more than 50 Units per site should generally be administered. An appropriately
sized needle (e.g., 25-30 gauge) may be used for superficial muscles, and a longer 22 gauge needle may be used for deeper
musculature. Localization of the involved muscles with electromyographic guidance or nerve stimulation techniques is recommended.
Repeat BOTOX treatment may be administered when the effect of a previous injection has diminished, but generally no sooner than
12 weeks after the previous injection. The degree and pattern of muscle spasticity at the time of re-injection may necessitate
alterations in the dose of BOTOX and muscles to be injected.
2.6 Cervical Dystonia
A double-blind, placebo-controlled study enrolled patients who had extended histories of receiving and tolerating BOTOX injections,
with prior individualized adjustment of dose. The mean BOTOX dose administered to patients in this study was 236 Units (25th to
75th percentile range of 198 Units to 300 Units). The BOTOX dose was divided among the affected muscles [see Clinical Studies
(14.3)].
Dosing in initial and sequential treatment sessions should be tailored to the individual patient based on the patient’s head and neck
position, localization of pain, muscle hypertrophy, patient response, and adverse event history. The initial dose for a patient without
prior use of BOTOX should be at a lower dose, with subsequent dosing adjusted based on individual response. Limiting the total dose
injected into the sternocleidomastoid muscle to 100 Units or less may decrease the occurrence of dysphagia [see Warnings and
Precautions (5.2, 5.4, 5.5)].
The recommended dilution is 200 Units/2 mL, 200 Units/4 mL, 100 Units/1 mL, or 100 Units/2 mL with 0.9% non-preserved sterile
saline, depending on volume and number of injection sites desired to achieve treatment objectives (see Table 1). In general, no more
than 50 Units per site should be administered. An appropriately sized needle (e.g., 25-30 gauge) may be used for superficial muscles,
This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda
and a longer 22 gauge needle may be used for deeper musculature. Localization of the involved muscles with electromyographic
guidance may be useful.
Clinical improvement generally begins within the first two weeks after injection with maximum clinical benefit at approximately six
weeks post-injection. In the double-blind, placebo-controlled study most subjects were observed to have returned to pre-treatment
status by 3 months post-treatment.
Patients should shave underarms and abstain from use of over-the-counter deodorants or antiperspirants for 24 hours prior to the test.
Patient should be resting comfortably without exercise, hot drinks for approximately 30 minutes prior to the test. Dry the underarm
area and then immediately paint it with iodine solution. Allow the area to dry, then lightly sprinkle the area with starch powder. Gently
blow off any excess starch powder. The hyperhidrotic area will develop a deep blue-black color over approximately 10 minutes.
2.7 Primary Axillary Hyperhidrosis
The recommended dose is 50 Units per axilla. The hyperhidrotic area to be injected should be defined using standard staining
techniques, e.g., Minor’s Iodine-Starch Test. The recommended dilution is 100 Units/4 mL with 0.9% preservative-free sterile saline
(see Dilution Table). Using a 30 gauge needle, 50 Units of BOTOX (2 mL) is injected intradermally in 0.1 to 0.2 mL aliquots to each
axilla evenly distributed in multiple sites (10-15) approximately 1-2 cm apart.
Repeat injections for hyperhidrosis should be administered when the clinical effect of a previous injection diminishes.
Instructions for the Minor’s Iodine-Starch Test Procedure:
Each injection site has a ring of effect of up to approximately 2 cm in diameter. To minimize the area of no effect, the injection sites
should be evenly spaced as shown in Figure 2.
Figure 2: Injection Pattern for Primary Axillary Hyperhidrosis
Each dose is injected to a depth of approximately 2 mm and at a 45° angle to the skin surface, with the bevel side up to minimize
leakage and to ensure the injections remain intradermal. If injection sites are marked in ink, do not inject BOTOX directly through the
ink mark to avoid a permanent tattoo effect.
2.8 Blepharospasm
For blepharospasm, reconstituted BOTOX is injected using a sterile, 27-30 gauge needle without electromyographic guidance. The
initial recommended dose is 1.25 Units-2.5 Units (0.05 mL to 0.1 mL volume at each site) injected into the medial and lateral pre-
tarsal orbicularis oculi of the upper lid and into the lateral pre-tarsal orbicularis oculi of the lower lid. Avoiding injection near the
levator palpebrae superioris may reduce the complication of ptosis. Avoiding medial lower lid injections, and thereby reducing
diffusion into the inferior oblique, may reduce the complication of diplopia. Ecchymosis occurs easily in the soft eyelid tissues. This
can be prevented by applying pressure at the injection site immediately after the injection.
The recommended dilution to achieve 1.25 Units is 50 Units/4 mL or 100 Units/8 mL; for 2.5 Units it is 50 Units/2 mL or 100 Units/4
mL (see Table 1).
In general, the initial effect of the injections is seen within three days and reaches a peak at one to two weeks post-treatment. Each
treatment lasts approximately three months, following which the procedure can be repeated. At repeat treatment sessions, the dose
may be increased up to two-fold if the response from the initial treatment is considered insufficient, usually defined as an effect that
does not last longer than two months. However, there appears to be little benefit obtainable from injecting more than 5 Units per site.
Some tolerance may be found when BOTOX is used in treating blepharospasm if treatments are given any more frequently than every
three months, and is rare to have the effect be permanent.
The cumulative dose of BOTOX treatment for blepharospasm in a 30-day period should not exceed 200 Units.
2.9 Strabismus
BOTOX is intended for injection into extraocular muscles utilizing the electrical activity recorded from the tip of the injection needle
as a guide to placement within the target muscle. Injection without surgical exposure or electromyographic guidance should not be
attempted. Physicians should be familiar with electromyographic technique.
This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda
To prepare the eye for BOTOX injection, it is recommended that several drops of a local anesthetic and an ocular decongestant be
given several minutes prior to injection.
The volume of BOTOX injected for treatment of strabismus should be between 0.05-0.15 mL per muscle.
The initial listed doses of the reconstituted BOTOX [see Dosage and Administration (2.1)] typically create paralysis of the injected
muscles beginning one to two days after injection and increasing in intensity during the first week. The paralysis lasts for 2-6 weeks
and gradually resolves over a similar time period. Overcorrections lasting over six months have been rare. About one half of patients
will require subsequent doses because of inadequate paralytic response of the muscle to the initial dose, or because of mechanical
factors such as large deviations or restrictions, or because of the lack of binocular motor fusion to stabilize the alignment.
Initial doses in Units
Use the lower listed doses for treatment of small deviations. Use the larger doses only for large deviations.
• For vertical muscles, and for horizontal strabismus of less than 20 prism diopters: 1.25 Units-2.5 Units in any one muscle.
• For horizontal strabismus of 20 prism diopters to 50 prism diopters: 2.5 Units-5 Units in any one muscle.
• For persistent VI nerve palsy of one month or longer duration: 1.25 Units-2.5 Units in the medial rectus muscle.
Subsequent doses for residual or recurrent strabismus
• It is recommended that patients be re-examined 7-14 days after each injection to assess the effect of that dose.
• Patients experiencing adequate paralysis of the target muscle that require subsequent injections should receive a dose
comparable to the initial dose.
• Subsequent doses for patients experiencing incomplete paralysis of the target muscle may be increased up to two-fold
compared to the previously administered dose.
• Subsequent injections should not be administered until the effects of the previous dose have dissipated as evidenced by
substantial function in the injected and adjacent muscles.
• he maximum recommended dose as a single injection for any one muscle is 25 Units.
The recommended dilution to achieve 1.25 Units is 50 Units/4 mL or 100 Units/8 mL; for 2.5 Units it is 50 Units/2 mL or 100 Units/4
mL (see Table 1).
3 DOSAGE FORMS AND STRENGTHS
Single-use, sterile 50 Units, 100 Units, or 200 Units vacuum-dried powder for reconstitution only with sterile, non-preserved 0.9%
Sodium Chloride Injection USP prior to injection.
4 CONTRAINDICATIONS
4.1 Known Hypersensitivity to Botulinum Toxin
BOTOX is contraindicated in patients who are hypersensitive to any botulinum toxin preparation or to any of the components in the
formulation [see Warnings and Precautions (5.3)].
4.2 Infection at the Injection Site(s)
Intradetrusor injection of BOTOX is contraindicated in patients with detrusor overactivity associated with a neurologic condition who
have acute urinary tract infection, and in patients with acute urinary retention who are not routinely performing clean intermittent self-
catheterization (CIC).
BOTOX is contraindicated in the presence of infection at the proposed injection site(s).
4.3 Acute Urinary Tract Infection and/or Acute Urinary Retention
The potency Units of BOTOX are specific to the preparation and assay method utilized. They are not interchangeable with
other preparations of botulinum toxin products and, therefore, units of biological activity of BOTOX cannot be compared to
nor converted into units of any other botulinum toxin products assessed with any other specific assay method [see Dosage and
Administration (2.1), Description (11)].
5 WARNINGS AND PRECAUTIONS
5.1 Lack of Interchangeability between Botulinum Toxin Products
5.2 Spread of Toxin Effect
Postmarketing safety data from BOTOX and other approved botulinum toxins suggest that 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. These symptoms have been reported hours to weeks after injection. Swallowing and breathing difficulties can be
life threatening and there have been reports of death related to spread of toxin effects. The risk of symptoms is probably greatest in
This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda
children treated for spasticity but symptoms can also occur in adults treated for spasticity and other conditions, and particularly in
those patients who have an underlying condition that would predispose them to these symptoms. In unapproved uses, including
spasticity in children, and in approved indications, symptoms consistent with spread of toxin effect have been reported at doses
comparable to or lower than doses used to treat cervical dystonia. Patients or caregivers should be advised to seek immediate medical
care if swallowing, speech or respiratory disorders occur.
No definitive serious adverse event reports of distant spread of toxin effect associated with dermatologic use of BOTOX/BOTOX
Cosmetic
at the labeled dose of 20 Units (for glabellar lines) or 100 Units (for severe primary axillary hyperhidrosis) have been
reported.
No definitive serious adverse event reports of distant spread of toxin effect associated with BOTOX for blepharospasm at the
recommended dose (30 Units and below), strabismus, or for chronic migraine at the labeled doses have been reported.
5.3 Hypersensitivity Reactions
Serious and/or immediate hypersensitivity reactions have been reported. These reactions include anaphylaxis, serum sickness,
urticaria, soft tissue edema, and dyspnea. If such a reaction occurs, further injection of BOTOX should be discontinued and
appropriate medical therapy immediately instituted. One fatal case of anaphylaxis has been reported in which lidocaine was used as
the diluent, and consequently the causal agent cannot be reliably determined.
5.4 Dysphagia and Breathing Difficulties in Treatment of Cervical Dystonia
Treatment with BOTOX and other botulinum toxin products can result in swallowing or breathing difficulties. Patients with pre-
existing swallowing or breathing difficulties may be more susceptible to these complications. In most cases, this is a consequence of
weakening of muscles in the area of injection that are involved in breathing or swallowing. When distant effects occur, additional
respiratory muscles may be involved [see Warnings and Precautions (5.2)].
Deaths as a complication of severe dysphagia have been reported after treatment with botulinum toxin. Dysphagia may persist for
several months, and require use of a feeding tube to maintain adequate nutrition and hydration. Aspiration may result from severe
dysphagia and is a particular risk when treating patients in whom swallowing or respiratory function is already compromised.
Treatment of cervical dystonia with botulinum toxins may weaken neck muscles that serve as accessory muscles of ventilation. This
may result in a critical loss of breathing capacity in patients with respiratory disorders who may have become dependent upon these
accessory muscles. There have been postmarketing reports of serious breathing difficulties, including respiratory failure, in cervical
dystonia patients.
Patients with smaller neck muscle mass and patients who require bilateral injections into the sternocleidomastoid muscle have been
reported to be at greater risk for dysphagia. Limiting the dose injected into the sternocleidomastoid muscle may reduce the occurrence
of dysphagia. Injections into the levator scapulae may be associated with an increased risk of upper respiratory infection and
dysphagia.
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 [see Warnings and
Precautions (5.2) and Adverse Reactions (6.1)].
5.5 Pre-Existing Neuromuscular Disorders
Individuals with peripheral motor neuropathic diseases, amyotrophic lateral sclerosis or neuromuscular junction disorders (e.g.,
myasthenia gravis or Lambert-Eaton syndrome) should be monitored particularly closely when given botulinum toxin. Patients with
neuromuscular disorders may be at increased risk of clinically significant effects including severe dysphagia and respiratory
compromise from therapeutic doses of BOTOX [see Adverse Reactions (6.1)].
5.6 Pulmonary Effects of BOTOX in Patients with Compromised Respiratory Status Treated for Spasticity or for
Detrusor Overactivity associated with a Neurologic Condition
Patients with compromised respiratory status treated with BOTOX for upper limb spasticity should be monitored closely. In a double-
blind, placebo-controlled, parallel group study in patients with stable reduced pulmonary function (defined as FEV
1
40-80% of
predicted value and FEV
1
/FVC ≤ 0.75), the event rate in change of Forced Vital Capacity ≥15% or ≥20% was generally greater in
patients treated with BOTOX than in patients treated with placebo (see Table 4).
This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda
Table 4: Event rate per patient treatment cycle among patients with reduced lung function who experienced at least a 15% or
20% decrease in forced vital capacity from baseline at Week 1, 6, 12 post-injection with up to two treatment cycles with
BOTOX or placebo
BOTOX
360 Units
BOTOX
240 Units
Placebo
>
15% >20% >15% >20% >15% >20%
Week 1 4% 0% 3% 0% 7% 3%
Week 6 7% 4% 4% 2% 2% 2%
Week 12 10% 5% 2% 1% 4% 1%
Differences from placebo were not statistically significant
In patients with reduced lung function, upper respiratory tract infections were also reported more frequently as adverse reactions in
patients treated with BOTOX than in patients treated with placebo [see Warnings and Precautions (5.9)].
In an ongoing double-blind, placebo-controlled, parallel group study in adult patients with detrusor overactivity associated with a
neurologic condition and restrictive lung disease of neuromuscular etiology [defined as FVC 50-80% of predicted value in patients
with spinal cord injury between C5 and C8, or MS] the event rate in change of Forced Vital Capacity ≥15% or ≥20% was generally
greater in patients treated with BOTOX than in patients treated with placebo (see Table 5).
Table 5. Number and percent of patients experiencing at least a 15% or 20% decrease in FVC from baseline at Week 2, 6, 12
post-injection with BOTOX or placebo
BOTOX
200 Units
Placebo
>
15% >20% >15% >20%
Week 2 0/12 (0%) 0/12 (0%) 1/11 (9%) 0/11 (0%)
Week 6 2/11 (18%) 1/11 (9%) 0/11 (0%) 0/11 (0%)
Week 12 0/11 (0%) 0/11 (0%) 0/6 (0%) 0/6 (0%)
5.7 Corneal Exposure and Ulceration in Patients Treated with BOTOX for Blepharospasm
Reduced blinking from BOTOX
injection of the orbicularis muscle can lead to corneal exposure, persistent epithelial defect, and
corneal ulceration, especially in patients with VII nerve disorders. Vigorous treatment of any epithelial defect should be employed.
This may require protective drops, ointment, therapeutic soft contact lenses, or closure of the eye by patching or other means.
5.8 Retrobulbar Hemorrhages in Patients Treated with BOTOX for Strabismus
During the administration of BOTOX for the treatment of strabismus, retrobulbar hemorrhages sufficient to compromise retinal
circulation have occurred. It is recommended that appropriate instruments to decompress the orbit be accessible.
5.9 Bronchitis and Upper Respiratory Tract Infections in Patients Treated for Spasticity
Bronchitis was reported more frequently as an adverse reaction in patients treated for upper limb spasticity with BOTOX (3% at 251
Units-360 Units total dose), compared to placebo (1%). In patients with reduced lung function treated for upper limb spasticity, upper
respiratory tract infections were also reported more frequently as adverse reactions in patients treated with BOTOX
(11% at 360 Units
total dose; 8% at 240 Units total dose) compared to placebo (6%).
5.10 Autonomic Dysreflexia and Urinary Retention 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).
In double-blind, placebo-controlled trials, the proportion of subjects who were not using clean intermittent catheterization (CIC) prior
to injection and who subsequently required catheterization for urinary retention following treatment with BOTOX or placebo is shown
in Table 6. The duration of post-injection catheterization is also shown.
This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda
Table 6. Proportion of Patients not using CIC at baseline and then Catheterizing for Urinary Retention and Duration of
Catheterization following injection in double-blind, placebo-controlled clinical trials
Timepoint
BOTOX 200 Unit
(N=108)
Placebo
(N=104)
Proportion of Patients Catheterizing for Urinary Retention
At any time during complete treatment cycle
33 (30.6%) 7 (6.7%)
Duration of Catheterization for Urinary Retention (Days)
Median 289 358
Min, Max 1, 530 2, 379
Among patients not using CIC at baseline, those with MS were more likely to require CIC post-injection than those with SCI (see
Table 7).
Table 7. Proportion of Patients by Etiology (MS and SCI) not using CIC at baseline and then Catheterizing for Urinary
Retention following injection in double-blind, placebo-controlled clinical trials
MS SCI
Timepoint
BOTOX
200 Unit
(N=86)
Placebo
(N=88)
BOTOX
200 Unit
(N=22)
Placebo
(N=16)
At any time during
complete treatment cycle
27 (31%) 4 (5%) 6 (27%) 3 (19%)
In patients who are not catheterizing, post-void residual (PVR) urine volume should be assessed within 2 weeks post-treatment and
periodically as medically appropriate up to 12 weeks. Catheterization should be instituted if PVR urine volume exceeds 200 mL and
continued until PVR falls below 200 mL. Patients should be instructed to contact their physician if they experience difficulty in
voiding as catheterization may be required.
5.11 Human Albumin and Transmission of Viral Diseases
This 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. A theoretical risk for transmission of Creutzfeldt-Jakob disease
(CJD) is also considered extremely remote. No cases of transmission of viral diseases or CJD have ever been reported for albumin.
6 ADVERSE REACTIONS
The following adverse reactions to BOTOX (onabotulinumtoxinA) for injection are discussed in greater detail in other sections of the
labeling:
• Spread of Toxin Effects [see Warnings and Precautions (5.2)]
• Hypersensitivity [see Contraindications (4.1) and Warnings and Precautions (5.3)]
• Dysphagia and Breathing Difficulties in Treatment of Cervical Dystonia [see Warnings and Precautions (5.4)]
• Bronchitis and Upper Respiratory Tract Infections in Patients Treated for Spasticity [see Warnings and Precautions (5.9)]
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed in the clinical trials of a
drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical
practice.
BOTOX and BOTOX Cosmetic contain the same active ingredient in the same formulation, but with different labeled Indications and
Usage. Therefore, adverse reactions observed with the use of BOTOX
Cosmetic also have the potential to be observed with the use of
BOTOX.
In general, adverse reactions occur within the first week following injection of BOTOX and while generally transient, may have a
duration of several months or longer. Localized pain, infection, inflammation, tenderness, swelling, erythema, and/or
bleeding/bruising may be associated with the injection. Needle-related pain and/or anxiety may result in vasovagal responses
(including e.g., syncope, hypotension), which may require appropriate medical therapy.
Local weakness of the injected muscle(s) represents the expected pharmacological action of botulinum toxin. However, weakness of
nearby muscles may also occur due to spread of toxin [see Warnings and Precautions (5.2)].
This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda
Detrusor Overactivity associated with a Neurologic Condition
Table 8 presents the most frequently reported adverse reactions in double-blind, placebo-controlled studies within 12 weeks of
injection for detrusor overactivity associated with a neurologic condition.
Table 8: Adverse Reactions Reported by >
2% of BOTOX treated Patients and More Frequent than in Placebo-treated
Patients Within the First 12 Weeks after Intradetrusor Injection in Double-blind, Placebo-controlled Clinical Trials
Adverse Reactions by Body System
BOTOX
200 Unit
(N=262)
Placebo
(N=272)
Infections and infestations
Urinary tract infection
64 (24%)
47 (17%)
Renal and urinary disorders
Urinary retention
Hematuria
45 (17%)
10 (4%)
8 (3%)
8 (3%)
General disorders and administration site
conditions
Fatigue
10 (4%)
3 (1%)
Psychiatric disorders
Insomnia
4 (2%)
0 (0%)
No change was observed in the overall safety profile with repeat dosing.
The following adverse event rates with BOTOX 200 Units were reported at any time following initial injection and prior to re-
injection or study exit (median duration of 44 weeks of exposure): urinary tract infections (49%), urinary retention (17%), fatigue
(6%), constipation (4%), muscular weakness (4%), dysuria (4%), fall (3%), gait disturbance (3%), insomnia (3%), and muscle spasm
(2%).
In the MS patients enrolled in the double-blind, placebo-controlled trials, the MS exacerbation annualized rate (i.e., number of MS
exacerbation events per patient-year) was 0.23 for BOTOX and 0.20 for placebo.
Chronic Migraine
In double-blind, placebo-controlled chronic migraine efficacy trials (Study 1 and Study 2), the discontinuation rate was 12% in the
BOTOX-treated group and 10% in the placebo-treated group. Discontinuations due to an adverse event were 4% in the BOTOX group
and 1% in the placebo group. The most frequent adverse events leading to discontinuation in the BOTOX group were neck pain,
headache, worsening migraine, muscular weakness and eyelid ptosis.
The most frequently reported adverse reactions following injection of BOTOX for chronic migraine appear in Table 9.
This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda
Table 9: Adverse Reactions Reported by >
2% of BOTOX treated Patients and More Frequent than in Placebo-treated
Patients in Two Chronic Migraine Double-blind, Placebo-controlled Clinical Trials
Adverse Reactions by Body Systems
BOTOX
155 Units-195 Units
(N=687)
Placebo
(N=692)
Nervous system disorders
Headache
Migraine
Facial paresis
32 (5%)
26 (4%)
15 (2%)
22 (3%)
18 (3%)
0 (0%)
Eye disorders
Eyelid ptosis
25 (4%)
2 (<1%)
Infections & Infestations
Bronchitis
17 (3%)
11 (2%)
Musculoskeletal and connective tissue disorders
Neck pain
Musculoskeletal stiffness
Muscular weakness
Myalgia
Musculoskeletal pain
Muscle spasms
60 (9%)
25 (4%)
24 (4%)
21 (3%)
18 (3%)
13 (2%)
19 (3%)
6 (1%)
2 (<1%)
6 (1%)
10 (1%)
6 (1%)
General disorders and administration site
conditions
Injection site pain
23 (3%)
14 (2%)
Vascular Disorders
Hypertension
11 (2%)
7 (1%)
Other adverse reactions that occurred more frequently in the BOTOX group compared to the placebo group at a frequency less than
1% and potentially BOTOX related include: vertigo, dry eye, eyelid edema, dysphagia, eye infection, and jaw pain. Severe worsening
of migraine requiring hospitalization occurred in approximately 1% of BOTOX-treated patients in Study 1 and Study 2, usually within
the first week after treatment, compared to 0.3% of placebo-treated patients.
Upper Limb Spasticity
The most frequently reported adverse reactions following injection of BOTOX for adult spasticity appear in Table 10.
Table 10: Adverse Reactions Reported by ≥2% of BOTOX treated Patients and More Frequent than in Placebo-treated
Patients in Adult Spasticity Double-blind, Placebo-controlled Clinical Trials
Adverse Reactions by Body
System
BOTOX
251 Units-
360 Units
(N=115)
BOTOX
150 Units-
250 Units
(N=188)
BOTOX
<150 Units
(N=54)
Placebo
(N=182)
Gastrointestinal disorder
Nausea
3 (3%)
3 (2%)
1 (2%)
1 (1%)
General disorders and
administration site conditions
Fatigue
4 (3%)
4 (2%)
1 (2%)
0
Infections and infestations
Bronchitis
4 (3%)
4 (2%)
0
2 (1%)
Musculoskeletal and
connective tissue disorders
Pain in extremity
Muscular weakness
7 (6%)
0
10 (5%)
7 (4%)
5 (9%)
1 (2%)
8 (4%)
2 (1%)
Cervical Dystonia
In cervical dystonia patients evaluated for safety in double-blind and open-label studies following injection of BOTOX, the most
frequently reported adverse reactions were dysphagia (19%), upper respiratory infection (12%), neck pain (11%), and headache
(11%).
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For current labeling information, please visit https://www.fda.gov/drugsatfda
Other events reported in 2-10% of patients in any one study in decreasing order of incidence include: increased cough, flu syndrome,
back pain, rhinitis, dizziness, hypertonia, soreness at injection site, asthenia, oral dryness, speech disorder, fever, nausea, and
drowsiness. Stiffness, numbness, diplopia, ptosis, and dyspnea have been reported.
Dysphagia and symptomatic general weakness may be attributable to an extension of the pharmacology of BOTOX resulting from the
spread of the toxin outside the injected muscles [see Warnings and Precautions (5.2, 5.4)].
The most common severe adverse reaction associated with the use of BOTOX injection in patients with cervical dystonia is dysphagia
with about 20% of these cases also reporting dyspnea [see Warnings and Precautions (5.2, 5.4)]. Most dysphagia is reported as mild
or moderate in severity. However, it may be associated with more severe signs and symptoms [see Warnings and Precautions (5.4)].
Additionally, reports in the literature include a case of a female patient who developed brachial plexopathy two days after injection of
120 Units of BOTOX for the treatment of cervical dystonia, and reports of dysphonia in patients who have been treated for cervical
dystonia.
Primary Axillary Hyperhidrosis
The most frequently reported adverse reactions (3-10% of adult patients) following injection of BOTOX in double-blind studies
included injection site pain and hemorrhage, non-axillary sweating, infection, pharyngitis, flu syndrome, headache, fever, neck or back
pain, pruritus, and anxiety.
The data reflect 346 patients exposed to BOTOX 50 Units and 110 patients exposed to BOTOX 75 Units in each axilla.
Primary Axillary Hyperhidrosis
The most frequently reported adverse reactions (3-10% of adult patients) following injection of BOTOX in double-blind studies
included injection site pain and hemorrhage, non-axillary sweating, infection, pharyngitis, flu syndrome, headache, fever, neck or back
pain, pruritus, and anxiety.
The data reflect 346 patients exposed to BOTOX 50 Units and 110 patients exposed to BOTOX 75 Units in each axilla.
Blepharospasm
In a study of blepharospasm patients who received an average dose per eye of 33 Units (injected at 3 to 5 sites) of the currently
manufactured BOTOX, the most frequently reported adverse reactions were ptosis (21%), superficial punctate keratitis (6%), and eye
dryness (6%).
Other events reported in prior clinical studies in decreasing order of incidence include: irritation, tearing, lagophthalmos, photophobia,
ectropion, keratitis, diplopia, entropion, diffuse skin rash, and local swelling of the eyelid skin lasting for several days following eyelid
injection.
In two cases of VII nerve disorder, reduced blinking from BOTOX injection of the orbicularis muscle led to serious corneal exposure,
persistent epithelial defect, corneal ulceration and a case of corneal perforation. Focal facial paralysis, syncope, and exacerbation of
myasthenia gravis have also been reported after treatment of blepharospasm.
Strabismus
Extraocular muscles adjacent to the injection site can be affected, causing vertical deviation, especially with higher doses of BOTOX.
The incidence rates of these adverse effects in 2058 adults who received a total of 3650 injections for horizontal strabismus was 17%.
The incidence of ptosis has been reported to be dependent on the location of the injected muscles, 1% after inferior rectus injections,
16% after horizontal rectus injections and 38% after superior rectus injections.
In a series of 5587 injections, retrobulbar hemorrhage occurred in 0.3% of cases.
6.2 Immunogenicity
As with all therapeutic proteins, there is a potential for immunogenicity. Formation of neutralizing antibodies to botulinum toxin type
A may reduce the effectiveness of BOTOX treatment by inactivating the biological activity of the toxin.
In a long term, open-label study evaluating 326 cervical dystonia patients treated for an average of 9 treatment sessions with the
current formulation of BOTOX, 4 (1.2%) patients had positive antibody tests. All 4 of these patients responded to BOTOX therapy at
the time of the positive antibody test. However, 3 of these patients developed clinical resistance after subsequent treatment, while the
fourth patient continued to respond to BOTOX therapy for the remainder of the study.
This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda
One patient among the 445 hyperhidrosis patients (0.2%), two patients among the 380 adult upper limb spasticity patients (0.5%), no
patients among 406 migraine patients, and no patients among 475 detrusor overactivity associated with a neurologic condition patients
with analyzed specimens developed the presence of neutralizing antibodies.
The data reflect the patients whose test results were considered positive or negative for neutralizing activity to BOTOX in a mouse
protection assay. The results of these tests are highly dependent on the sensitivity and specificity of the assay. For these reasons,
comparison of the incidence of neutralizing activity to BOTOX with the incidence reported to other products may be misleading.
The critical factors for neutralizing antibody formation have not been well characterized. The results from some studies suggest that
BOTOX injections at more frequent intervals or at higher doses may lead to greater incidence of antibody formation. The potential for
antibody formation may be minimized by injecting with the lowest effective dose given at the longest feasible intervals between
injections.
Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their
frequency or establish a causal relationship to drug exposure.
6.3 Post-Marketing Experience
There have been spontaneous reports of death, sometimes associated with dysphagia, pneumonia, and/or other significant debility or
anaphylaxis, after treatment with botulinum toxin [see Warnings and Precautions (5.3, 5.4)].
There have also been reports of adverse events involving the cardiovascular system, including arrhythmia and myocardial infarction,
some with fatal outcomes. Some of these patients had risk factors including cardiovascular disease. The exact relationship of these
events to the botulinum toxin injection has not been established.
New onset or recurrent seizures have also been reported, typically in patients who are predisposed to experiencing these events. The
exact relationship of these events to the botulinum toxin injection has not been established.
The following adverse events have been identified during postapproval use of BOTOX: abdominal pain; anorexia; brachial
plexopathy; diarrhea; dyspnea; facial palsy; facial paresis; hyperhidrosis; hypoacusis; hypoaesthesia; localized numbness; malaise;
muscle weakness; myalgia; paresthesia; pyrexia; radiculopathy; skin rash (including erythema multiforme, and psoriasiform eruption);
tinnitus; vertigo; visual disturbances; and vomiting.
7 DRUG INTERACTIONS
No formal drug interaction studies have been conducted with BOTOX (onabotulinumtoxinA) for injection.
Co-administration of BOTOX and aminoglycosides or other agents interfering with neuromuscular transmission (e.g., curare-like
compounds) should only be performed with caution as the effect of the toxin may be potentiated.
Use of anticholinergic drugs after administration of BOTOX may potentiate systemic anticholinergic effects.
The effect of administering different botulinum neurotoxin products at the same time 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.
Excessive weakness may also be exaggerated by administration of a muscle relaxant before or after administration of BOTOX.
This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
It is not known whether BOTOX is excreted in human milk. Because many drugs are excreted in human milk, caution should be
exercised when BOTOX is administered to a nursing woman.
Pregnancy Category C.
There are no adequate and well-controlled studies in pregnant women. BOTOX should be used during pregnancy only if the potential
benefit justifies the potential risk to the fetus.
When BOTOX (4, 8, or 16 Units/kg) was administered intramuscularly to pregnant mice or rats two times during the period of
organogenesis (on gestation days 5 and 13), reductions in fetal body weight and decreased fetal skeletal ossification were observed at
the two highest doses. The no-effect dose for developmental toxicity in these studies (4 Units/kg) is approximately 1½ times the
average high human dose for upper limb spasticity of 360 Units on a body weight basis (Units/kg).
When BOTOX was administered intramuscularly to pregnant rats (0.125, 0.25, 0.5, 1, 4, or 8 Units/kg) or rabbits (0.063, 0.125, 0.25,
or 0.5 Units/kg) daily during the period of organogenesis (total of 12 doses in rats, 13 doses in rabbits), reduced fetal body weights and
decreased fetal skeletal ossification were observed at the two highest doses in rats and at the highest dose in rabbits. These doses were
also associated with significant maternal toxicity, including abortions, early deliveries, and maternal death. The developmental no-
effect doses in these studies of 1 Unit/kg in rats and 0.25 Units/kg in rabbits are less than the average high human dose based on
Units/kg.
When pregnant rats received single intramuscular injections (1, 4, or 16 Units/kg) at three different periods of development (prior to
implantation, implantation, or organogenesis), no adverse effects on fetal development were observed. The developmental no-effect
level for a single maternal dose in rats (16 Units/kg) is approximately 3 times the average high human dose based on Units/kg.
8.3 Nursing Mothers
8.4 Pediatric Use
Urinary Incontinence due to Detrusor Overactivity associated with a Neurologic Condition
Safety and effectiveness in patients below the age of 18 years have not been established.
Prophylaxis of Headaches in Chronic Migraine
Safety and effectiveness in patients below the age of 18 years have not been established.
Spasticity
Safety and effectiveness in patients below the age of 18 years have not been established.
Axillary Hyperhidrosis
Safety and effectiveness in patients below the age of 18 years have not been established.
Cervical Dystonia
Safety and effectiveness in pediatric patients below the age of 16 years have not been established.
Blepharospasm and Strabismus
Safety and effectiveness in pediatric patients below the age of 12 years have not been established.
8.5 Geriatric Use
Clinical studies of BOTOX did not include sufficient numbers of subjects aged 65 and over to determine whether they respond
differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly
and younger patients. There were too few patients over the age of 75 to enable any comparisons. In general, dose selection for an
elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased
hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
10 OVERDOSAGE
Excessive doses of BOTOX (onabotulinumtoxinA) for injection may be expected to produce neuromuscular weakness with a variety
of symptoms. Respiratory support may be required where excessive doses cause paralysis of respiratory muscles. In the event of
overdose, the patient should be medically monitored for symptoms of excessive muscle weakness or muscle paralysis [see Boxed
Warning and Warnings and Precautions (5.2, 5.4)]. Symptomatic treatment may be necessary.
This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda
Symptoms of overdose are likely not to be present immediately following injection. Should accidental injection or oral ingestion
occur, the person should be medically supervised for several weeks for signs and symptoms of excessive muscle weakness or
paralysis.
In the event of overdose, antitoxin raised against botulinum toxin is available from the Centers for Disease Control and Prevention
(CDC) in Atlanta, GA. However, the antitoxin will not reverse any botulinum toxin-induced effects already apparent by the time of
antitoxin administration. 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. More information can be obtained at
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5232a8.htm.
Each vial of BOTOX contains either 50 Units of Clostridium botulinum type A neurotoxin complex, 0.25 mg of Albumin Human, and
0.45 mg of sodium chloride; 100 Units of Clostridium botulinum type A neurotoxin complex, 0.5 mg of Albumin Human, and 0.9 mg
of sodium chloride; or 200 Units of Clostridium botulinum type A neurotoxin complex, 1 mg of Albumin Human, and 1.8 mg of
sodium chloride in a sterile, vacuum-dried form without a preservative.
11 DESCRIPTION
BOTOX (onabotulinumtoxinA) for injection is a sterile, vacuum-dried purified botulinum toxin type A, produced from fermentation
of Hall strain Clostridium botulinum type A, and intended for intramuscular, intradetrusor and intradermal use. It is purified from the
culture solution by dialysis and a series of acid precipitations to a complex consisting of the neurotoxin, and several accessory
proteins. The complex is dissolved in sterile sodium chloride solution containing Albumin Human and is sterile filtered (0.2 microns)
prior to filling and vacuum-drying.
The primary release procedure for BOTOX uses a cell-based potency assay to determine the potency relative to a reference standard.
The assay is specific to Allergan’s products BOTOX and BOTOX
Cosmetic. One Unit of BOTOX corresponds to the calculated
median intraperitoneal lethal dose (LD
50
) in mice. Due to specific details of this assay such as the vehicle, dilution scheme, and
laboratory protocols, Units of biological activity of BOTOX cannot be compared to nor converted into Units of any other botulinum
toxin or any toxin assessed with any other specific assay method. The specific activity of BOTOX is approximately 20
Units/nanogram of neurotoxin protein complex.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
BOTOX blocks neuromuscular transmission by binding to acceptor sites on motor or sympathetic 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 injection, BOTOX affects the efferent pathways of detrusor activity via inhibition of acetylcholine release. In
addition, BOTOX is believed to inhibit afferent neurotransmitters and sensory pathways.
12.3 Pharmacokinetics
Using currently available analytical technology, it is not possible to detect BOTOX in the peripheral blood following intramuscular
injection at the recommended doses.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenesis
Long term studies in animals have not been performed to evaluate the carcinogenic potential of BOTOX.
Mutagenesis
BOTOX was negative in a battery of in vitro (microbial reverse mutation assay, mammalian cell mutation assay, and chromosomal
aberration assay) and in vivo (micronucleus assay) genetic toxicologic assays.
This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda
Impairment of Fertility
In fertility studies of BOTOX (4, 8, or 16 Units/kg) in which either male or female rats were injected intramuscularly prior to mating
and on the day of mating (3 doses, 2 weeks apart for males, 2 doses, 2 weeks apart for females) to untreated animals, reduced fertility
was observed in males at the intermediate and high doses and in females at the high dose. The no-effect doses for reproductive toxicity
(4 Units/kg in males, 8 Units/kg in females) are approximately equal to the average high human dose for upper limb spasticity of 360
Units on a body weight basis (Units/kg).
13.2 Animal toxicology
In a study to evaluate inadvertent peribladder administration, bladder stones were observed in 1 of 4 male monkeys that were injected
with a total of 6.8 Units/kg divided into the prostatic urethra and proximal rectum (single administration). No bladder stones were
observed in male or female monkeys following injection of up to 36 Units/kg (~12X the human dose) directly to the bladder as either
single or 4 repeat dose injections or in female rats for single injections up to 100 Units/kg (~33X the human dose).
14 CLINICAL STUDIES
14.1 Detrusor Overactivity associated with a Neurologic Condition
Two double-blind, placebo-controlled, randomized, multi-center clinical studies were conducted in patients with urinary incontinence
due to detrusor overactivity associated with a neurologic condition who were either spontaneously voiding or using catheterization. A
total of 691 spinal cord injury (T1 or below) or multiple sclerosis patients, who had an inadequate response to or were intolerant of at
least one anticholinergic medication, were enrolled. These patients were randomized to receive either 200 Units of BOTOX (n=227),
300 Units of BOTOX (n=223), or placebo (n=241).
In both studies, significant improvements compared to placebo in the primary efficacy variable of change from baseline in weekly
frequency of incontinence episodes were observed for BOTOX (200 Units) at the primary efficacy time point at week 6. Increases in
maximum cystometric capacity and reductions in maximum detrusor pressure during the first involuntary detrusor contraction were
also observed. These primary and secondary endpoints are shown in Tables 11 and 12, and Figures 3 and 4.
No additional benefit of BOTOX 300 Units over 200 Units was demonstrated.
** Primary Timepoint
Table 11: Key Primary and Secondary Endpoints at Baseline and Change from Baseline in Study 1
BOTOX
200 Units
Placebo Treatment
Difference*
p-value*
Weekly Frequency of Urinary Incontinence
Episodes
a
N
Mean Baseline
Mean Change* at Week 2
Mean Change* at Week 6**
Mean Change* at Week 12
134
32.3
-15.3
-19.9
-19.8
146
28.3
-10.0
-10.6
-8.8
-5.3
-9.2
(-13.1, -5.3)
-11.0
─
p<0.001
─
Maximum Cystometric Capacity
b
(mL)
N
Mean Baseline
Mean Change* at Week 6**
123
253.8
135.9
129
259.1
12.1
123.9
(89.1, 158.7)
p<0.001
Maximum Detrusor Pressure during First
Involuntary Detrusor Contraction
b
(cmH
2
0)
N
Mean Baseline
Mean Change* at Week 6**
41
63.1
-28.1
103
57.4
-3.7
-24.4
─
* Mean change, treatment difference and p-value are based on a LOCF analysis using an ANCOVA model with baseline weekly
endpoint as covariate and treatment group, etiology at study entry (spinal cord injury or multiple sclerosis), concurrent anticholinergic
therapy at screening, and investigator as factors.
This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda
a
Primary endpoint
** Primary Timepoint
b
Secondary endpoint
Table 12: Key Primary and Secondary Endpoints at Baseline and Change from Baseline in Study 2
BOTOX
200 Units
Placebo
Treatment
Difference*
p-value*
Weekly Frequency of Urinary Incontinence
Episodes
a
N
Mean Baseline
Mean Change* at Week 2
Mean Change* at Week 6**
Mean Change* at Week 12
91
32.7
-18.0
-19.6
-19.6
91
36.8
-7.9
-10.8
-10.7
-10.1
-8.8
(-14.5, -3.0)
-8.9
─
p=0.003
─
Maximum Cystometric Capacity
b
(mL)
N
Mean Baseline
Mean Change* at Week 6**
88
239.6
150.8
85
253.8
2.8
148.0
(101.8, 194.2)
p<0.001
Maximum Detrusor Pressure during First
Involuntary Detrusor Contraction
b
(cmH
2
0)
N
Mean Baseline
Mean Change* at Week 6**
29
65.6
-28.7
68
43.7
2.1
-30.7
─
* Mean change, treatment difference and p-value are based on a LOCF analysis using an ANCOVA model with baseline weekly
endpoint as covariate and treatment group, etiology at study entry (spinal cord injury or multiple sclerosis), concurrent anticholinergic
therapy at screening, and investigator as factors.
a
Primary endpoint
b
Secondary endpoint
Figure 3: Mean Change from Baseline in Weekly Frequency of Urinary Incontinence Episodes During Treatment Cycle 1 in
Study 1
This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda
Figure 4: Mean Change from Baseline in Weekly Frequency of Urinary Incontinence Episodes During Treatment Cycle 1 in
Study 2
The median duration of response in the two pivotal studies, based on patient qualification for re-treatment was 295-337 days (42-48
weeks) for the 200 Unit dose group compared to 96-127 days (13-18 weeks) for placebo. Re-treatment was based on loss of effect on
incontinence episode frequency (50% of effect in study 1; 70% of effect in study 2).
14.2 Chronic Migraine
BOTOX was evaluated in two randomized, multi-center, 24-week, 2 injection cycle, placebo-controlled double-blind studies. Study 1
and Study 2 included chronic migraine adults who were not using any concurrent headache prophylaxis, and during a 28-day baseline
period had >
15 headache days lasting 4 hours or more, with >50% being migraine/probable migraine. In both studies, patients were
randomized to receive placebo or 155 Units to 195 Units BOTOX injections every 12 weeks for the 2-cycle, double-blind phase.
Patients were allowed to use acute headache treatments during the study. BOTOX treatment demonstrated statistically significant and
clinically meaningful improvements from baseline compared to placebo for key efficacy variables (see Table 13).
Table 13: Week 24 Key Efficacy Variables for Study 1 and Study 2
Study 1 Study 2
Efficacy per 28 days
BOTOX
(N=341)
Placebo
(N=338)
BOTOX
(N=347)
Placebo
(N=358)
Change from baseline in
frequency of headache days
-7.8* -6.4 -9.2* -6.9
Change from baseline in
total cumulative hours of
headache on headache days
-107* -70 -134* -95
*
Significantly different from placebo (p<0.05)
Patients treated with BOTOX had a significantly greater mean decrease from baseline in the frequency of headache days at most
timepoints from Week 4 to Week 24 in Study 1 (Figure 5), and all timepoints from Week 4 to Week 24 in Study 2 (Figure 6),
compared to placebo-treated patients.
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Figure 5: Mean Change from Baseline in Number of Headache Days for Study 1
Figure 6: Mean Change from Baseline in Number of Headache Days for Study 2
14.3 Upper Limb Spasticity
The efficacy and safety of BOTOX for the treatment of upper limb spasticity were evaluated in three randomized, multi-center,
double-blind, placebo-controlled studies.
Study 1 included 126 patients (64 BOTOX and 62 placebo) with upper limb spasticity (Ashworth score of at least 3 for wrist flexor
tone and at least 2 for finger flexor tone) who were at least 6 months post-stroke. BOTOX (a total dose of 200 Units to 240 Units) and
placebo were injected intramuscularly (IM) into the flexor digitorum profundus, flexor digitorum sublimis, flexor carpi radialis, flexor
carpi ulnaris, and if necessary into the adductor pollicis and flexor pollicis longus (see Table 14). Use of an EMG/nerve stimulator was
recommended to assist in proper muscle localization for injection. Patients were followed for 12 weeks.
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Table 14: Study Medication Dose and Injection Sites in Study 1
Muscles Injected
Volume (mL) BOTOX
(Units)
Number of
Injection Sites
Wrist
Flexor Carpi Radialis
1
50
1
Flexor Carpi Ulnaris 1 50 1
Finger
Flexor Digitorum Profundus
1
50
1
Flexor Digitorum Sublimis 1 50 1
Thumb
Adductor Pollicis
a
0.4
20
1
Flexor Pollicis Longus
a
0.4 20 1
a
injected only if spasticity is present in this muscle
The primary efficacy variable was wrist flexors muscle tone at week 6, as measured by the Ashworth score. The Ashworth Scale is a
clinical measure of the force required to move an extremity around a joint, with a reduction in score clinically representing a reduction
in the force needed to move a joint (i.e., improvement in spasticity).
Possible scores range from 0 to 4:
0 = No increase in muscle tone (none)
1 = Slight increase in muscle tone, giving a 'catch' when the limb was moved in flexion or extension (mild)
2 = More marked increase in muscle tone but affected limb is easily flexed (moderate)
3 = Considerable increase in muscle tone - passive movement difficult (severe)
4 = Limb rigid in flexion or extension (very severe).
Key secondary endpoints included Physician Global Assessment, finger flexors muscle tone, and thumb flexors tone at Week 6. The
Physician Global Assessment evaluated the response to treatment in terms of how the patient was doing in his/her life using a scale
from -4 = very marked worsening to +4 = very marked improvement. Study 1 results on the primary endpoint and the key secondary
endpoints are shown in Table 15.
Table 15: Primary and Key Secondary Endpoints by Muscle Group at Week 6 in Study 1
BOTOX
(N=64)
Placebo
(N=62)
Median Change from Baseline in Wrist Flexor
Muscle Tone on the Ashworth Scale
†a
-2.0
*
0.0
Median Change from Baseline in Finger
Flexor Muscle Tone on the Ashworth Scale
††b
-1.0
*
0.0
Median Change from Baseline in Thumb
Flexor Muscle Tone on the Ashworth Scale
††c
-1.0
-1.0
Median Physician Global Assessment of
Response to Treatment
††
2.0
*
0.0
†
Primary endpoint at Week 6
††
Secondary endpoints at Week 6
*
Significantly different from placebo (p<0.05)
a
BOTOX injected into both the flexor carpi radialis and ulnaris muscles
b
BOTOX
injected into the flexor digitorum profundus and flexor digitorum sublimis muscles
c
BOTOX injected into the adductor pollicis and flexor pollicis longus muscles
Study 2 compared 3 doses of BOTOX with placebo and included 91 patients [BOTOX 360 Units (N=21), BOTOX 180 Units (N=23),
BOTOX 90 Units (N=21), and placebo (N=26)] with upper limb spasticity (expanded Ashworth score of at least 2 for elbow flexor
tone and at least 3 for wrist flexor tone) who were at least 6 weeks post-stroke. BOTOX and placebo were injected with EMG
guidance into the flexor digitorum profundus, flexor digitorum sublimis, flexor carpi radialis, flexor carpi ulnaris, and biceps brachii
(see Table 16).
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Table 16: Study Medication Dose and Injection Sites in Study 2 and Study 3
Total Dose
Muscles Injected
BOTOX
low dose
(90 Units)
BOTOX
mid dose
(180 Units)
BOTOX
high dose
(360 Units)
Volume
(mL)
per site
Injection
Sites
(n)
Wrist
Flexor Carpi Ulnaris
10 Units
20 Units
40 Units
0.4
1
Flexor Carpi Radialis 15 Units 30 Units 60 Units 0.6 1
Finger
Flexor Digitorum
Profundus
7.5 Units
15 Units
30 Units
0.3
1
Flexor Digitorum
Sublimis
7.5 Units
15 Units
30 Units
0.3
1
Elbow
Biceps Brachii
50 Units
100 Units
200 Units
0.5
4
The primary efficacy variable in Study 2 was the wrist flexor tone at Week 6 as measured by the expanded Ashworth Scale. The
expanded Ashworth Scale uses the same scoring system as the Ashworth Scale, but allows for half-point increments.
Key secondary endpoints in Study 2 included Physician Global Assessment, finger flexors muscle tone, and elbow flexors muscle tone
at Week 6. Study 2 results on the primary endpoint and the key secondary endpoints at Week 6 are shown in Table 17.
Table 17: Primary and Key Secondary Endpoints by Muscle Group and BOTOX Dose at Week 6 in Study 2
†
Primary endpoint at Week 6
BOTOX
low dose
(90 Units)
(N=21)
BOTOX
mid dose
(180 Units)
(N=23)
BOTOX
high dose
(360 Units)
(N=21)
Placebo
(N=26)
Median Change from Baseline in Wrist
Flexor Muscle Tone on the Ashworth
Scale
†b
-1.5
*
-1.0
*
-1.5
*
-1.0
Median Change from Baseline in Finger
Flexor Muscle Tone on the Ashworth
Scale
††c
-0.5
-0.5
-1.0
-0.5
Median Change from Baseline in Elbow
Flexor Muscle Tone on the Ashworth
Scale
††d
-0.5
-1.0
*
-0.5
a
-0.5
Median Physician Global Assessment of
Response to Treatment
1.0*
1.0*
1.0*
0.0
††
Secondary endpoints at Week 6
*
Significantly different from placebo (p<0.05)
a
p=0.053
b
Total dose of BOTOX
injected into both the flexor carpi radialis and ulnaris muscles
c
Total dose of BOTOX
injected into the flexor digitorum profundus and flexor digitorum sublimis muscles
d
Dose of BOTOX
injected into biceps brachii muscle
Study 3 compared 3 doses of BOTOX with placebo and enrolled 88 patients [BOTOX 360 Units (N=23), BOTOX 180 Units (N=23),
BOTOX 90 Units (N=23), and placebo (N=19)] with upper limb spasticity (expanded Ashworth score of at least 2 for elbow flexor
tone and at least 3 for wrist flexor tone and/or finger flexor tone) who were at least 6 weeks post-stroke. BOTOX and placebo were
injected with EMG guidance into the flexor digitorum profundus, flexor digitorum sublimis, flexor carpi radialis, flexor carpi ulnaris,
and biceps brachii (see Table 16).
The primary efficacy variable in Study 3 was wrist and elbow flexor tone as measured by the expanded Ashworth score. A key
secondary endpoint was assessment of finger flexors muscle tone. Study 3 results on the primary endpoint at Week 4 are shown in
Table 18.
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Table 18: Primary and Key Secondary Endpoints by Muscle Group and BOTOX Dose at Week 4 in Study 3
BOTOX
low dose
(90 Units)
(N=23)
BOTOX
mid dose
(180 Units)
(N=21)
BOTOX
high dose
(360 Units)
(N=22)
Placebo
(N=19)
Median Change from Baseline in Wrist
Flexor Muscle Tone on the Ashworth
Scale
†b
-1.0
-1.0
-1.5
*
-0.5
Median Change from Baseline in Finger
Flexor Muscle Tone on the Ashworth
Scale
††c
-1.0
-1.0
-1.0
*
-0.5
Median Change from Baseline in Elbow
Flexor Muscle Tone on the Ashworth
Scale
†d
-0.5
-0.5
-1.0
*
-0.5
d
Dose of BOTOX
injected into biceps brachii muscle
†
Primary endpoint at Week 4
††
Secondary endpoints at Week 4
*
Significantly different from placebo (p<0.05)
b
Total dose of BOTOX
injected into both the flexor carpi radialis and ulnaris muscles
c
Total dose of BOTOX
injected into the flexor digitorum profundus and flexor digitorum sublimis muscles
14.4 Cervical Dystonia
A randomized, multi-center, double-blind, placebo-controlled study of the treatment of cervical dystonia was conducted. This study
enrolled adult patients with cervical dystonia and a history of having received BOTOX in an open label manner with perceived good
response and tolerable side effects. Patients were excluded if they had previously received surgical or other denervation treatment for
their symptoms or had a known history of neuromuscular disorder. Subjects participated in an open label enrichment period where
they received their previously employed dose of BOTOX. Only patients who were again perceived as showing a response were
advanced to the randomized evaluation period. The muscles in which the blinded study agent injections were to be administered were
determined on an individual patient basis.
There were 214 subjects evaluated for the open label period, of which 170 progressed into the randomized, blinded treatment period
(88 in the BOTOX group, 82 in the placebo group). Patient evaluations continued for at least 10 weeks post-injection. The primary
outcome for the study was a dual endpoint, requiring evidence of both a change in the Cervical Dystonia Severity Scale (CDSS) and
an increase in the percentage of patients showing any improvement on the Physician Global Assessment Scale at 6 weeks after the
injection session. The CDSS quantifies the severity of abnormal head positioning and was newly devised for this study. CDSS allots 1
point for each 5 degrees (or part thereof) of head deviation in each of the three planes of head movement (range of scores up to
theoretical maximum of 54). The Physician Global Assessment Scale is a 9 category scale scoring the physician’s evaluation of the
patients’ status compared to baseline, ranging from –4 to +4 (very marked worsening to complete improvement), with 0 indicating no
change from baseline and +1 slight improvement. Pain is also an important symptom of cervical dystonia and was evaluated by
separate assessments of pain frequency and severity on scales of 0 (no pain) to 4 (constant in frequency or extremely severe in
intensity). Study results on the primary endpoints and the pain-related secondary endpoints are shown in Table 19.
Table 19: Efficacy Outcomes of the Phase 3 Cervical Dystonia Study (Group Means)
Placebo
(N=82)
BOTOX
(N=88)
95% CI on
Difference
Baseline CDSS
9.3 9.2
Change in CDSS
at Week 6
-0.3 -1.3 (-2.3, 0.3)
[a,b]
% Patients with Any
Improvement on Physician
Global Assessment
31% 51% (5%, 34%)
[a]
Pain Intensity Baseline
1.8 1.8
Change in Pain Intensity
at Week 6
-0.1 -0.4 (-0.7, -0.2)
[c]
Pain Frequency Baseline
1.9 1.8
Change in Pain Frequency
at Week 6
-0.0 -0.3 (-0.5, -0.0)
[c]
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[a]
Confidence intervals are constructed from the analysis of covariance table with treatment and investigational site as main effects,
and baseline CDSS as a covariate.
[b]
These values represent the prospectively planned method for missing data imputation and statistical test. Sensitivity analyses
indicated that the 95% confidence interval excluded the value of no difference between groups and the p-value was less than 0.05.
These analyses included several alternative missing data imputation methods and non-parametric statistical tests.
[c]
Confidence intervals are based on the t-distribution.
Exploratory analyses of this study suggested that the majority of patients who had shown a beneficial response by week 6 had returned
to their baseline status by 3 months after treatment. Exploratory analyses of subsets by patient sex and age suggest that both sexes
receive benefit, although female patients may receive somewhat greater amounts than male patients. There is a consistent treatment-
associated effect between subsets greater than and less than age 65. There were too few non-Caucasian patients enrolled to draw any
conclusions regarding relative efficacy in racial subsets.
In this study the median total BOTOX dose in patients randomized to receive BOTOX (N=88) was 236 Units, with 25th to 75th
percentile ranges of 198 Units to 300 Units. Of these 88 patients, most received injections to 3 or 4 muscles; 38 received injections to
3 muscles, 28 to 4 muscles, 5 to 5 muscles, and 5 to 2 muscles. The dose was divided amongst the affected muscles in quantities
shown in Table 20. The total dose and muscles selected were tailored to meet individual patient needs.
Table 20: Number of Patients Treated per Muscle and Fraction of Total Dose Injected into Involved Muscles
Muscle
Number of
Patients Treated
in this Muscle
(N=88)
Mean % Dose
per Muscle
Mid-Range of %
Dose per Muscle*
Splenius capitis/cervicis
83 38 25-50
Sternocleidomastoid
77 25 17-31
Levator scapulae
52 20 16-25
Trapezius
49 29 18-33
Semispinalis
16 21 13-25
Scalene
15 15 6-21
Longissimus
8 29 17-41
*The mid-range of dose is calculated as the 25th to 75th percentiles.
There were several randomized studies conducted prior to the double-blind, placebo-controlled study, which were supportive but not
adequately designed to assess or quantitatively estimate the efficacy of BOTOX.
14.5 Primary Axillary Hyperhidrosis
The efficacy and safety of BOTOX for the treatment of primary axillary hyperhidrosis were evaluated in two randomized, multi-
center, double-blind, placebo-controlled studies. Study 1 included adult patients with persistent primary axillary hyperhidrosis who
scored 3 or 4 on a Hyperhidrosis Disease Severity Scale (HDSS) and who produced at least 50 mg of sweat in each axilla at rest over 5
minutes. HDSS is a 4-point scale with 1 = “underarm sweating is never noticeable and never interferes with my daily activities”; to 4
= “underarm sweating is intolerable and always interferes with my daily activities”. A total of 322 patients were randomized in a 1:1:1
ratio to treatment in both axillae with either 50 Units of BOTOX, 75 Units of BOTOX, or placebo. Patients were evaluated at 4-week
intervals. Patients who responded to the first injection were re-injected when they reported a re-increase in HDSS score to 3 or 4 and
produced at least 50 mg sweat in each axilla by gravimetric measurement, but no sooner than 8 weeks after the initial injection.
Study responders were defined as patients who showed at least a 2-grade improvement from baseline value on the HDSS 4 weeks after
both of the first two treatment sessions or had a sustained response after their first treatment session and did not receive re-treatment
during the study. Spontaneous resting axillary sweat production was assessed by weighing a filter paper held in the axilla over a period
of 5 minutes (gravimetric measurement). Sweat production responders were those patients who demonstrated a reduction in axillary
sweating from baseline of at least 50% at week 4.
In the three study groups the percentage of patients with baseline HDSS score of 3 ranged from 50% to 54% and from 46% to 50% for
a score of 4. The median amount of sweat production (averaged for each axilla) was 102 mg, 123 mg, and 114 mg for the placebo, 50
Units and 75 Units groups respectively.
The percentage of responders based on at least a 2-grade decrease from baseline in HDSS or based on a >50% decrease from baseline
in axillary sweat production was greater in both BOTOX groups than in the placebo group (p<0.001), but was not significantly
different between the two BOTOX doses (see Table 21).
This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda
Duration of response was calculated as the number of days between injection and the date of the first visit at which patients returned to
3 or 4 on the HDSS scale. The median duration of response following the first treatment in BOTOX-treated patients with either dose
was 201 days. Among those who received a second BOTOX injection, the median duration of response was similar to that observed
after the first treatment.
In study 2, 320 adults with bilateral axillary primary hyperhidrosis were randomized to receive either 50 Units of BOTOX (n=242) or
placebo (n=78). Treatment responders were defined as subjects showing at least a 50% reduction from baseline in axillary sweating
measured by gravimetric measurement at 4 weeks. At week 4 post-injection, the percentages of responders were 91% (219/242) in the
BOTOX group and 36% (28/78) in the placebo group, p<0.001. The difference in percentage of responders between BOTOX and
placebo was 55% (95% CI=43.3, 65.9).
Table 21: Study 1 - Study Outcomes
Treatment Response
BOTOX
50 Units
(N=104)
BOTOX
75 Units
(N=110)
Placebo
(N=108)
BOTOX
50-placebo
(95% CI)
BOTOX
75-placebo
(95% CI)
HDSS Score change >2
(n)
a
55% (57) 49% (54) 6% (6)
49.3%
(38.8, 59.7)
43%
(33.2, 53.8)
>50% decrease in axillary
sweat production % (n)
81% (84) 86% (94) 41% (44) 40%
(28.1, 52.0)
45%
(33.3, 56.1)
14.6 Blepharospasm
a
Patients who showed at least a 2-grade improvement from baseline value on the HDSS 4 weeks after both of the first two treatment
sessions or had a sustained response after their first treatment session and did not receive re-treatment during the study.
Botulinum toxin has been investigated for use in patients with blepharospasm in several studies. In an open label, historically
controlled study, 27 patients with essential blepharospasm were injected with 2 Units of BOTOX
at each of six sites on each side.
Twenty-five of the 27 patients treated with botulinum toxin reported improvement within 48 hours. One patient was controlled with a
higher dosage at 13 weeks post initial injection and one patient reported mild improvement but remained functionally impaired.
In another study, 12 patients with blepharospasm were evaluated in a double-blind, placebo-controlled study. Patients receiving
botulinum toxin (n=8) improved compared with the placebo group (n=4). The effects of the treatment lasted a mean of 12 weeks.
One thousand six hundred eighty-four patients with blepharospasm who were evaluated in an open label trial showed clinical
improvement as evaluated by measured eyelid force and clinically observed intensity of lid spasm, lasting an average of 12 weeks
prior to the need for re-treatment.
14.7 Strabismus
Six hundred seventy-seven patients with strabismus treated with one or more injections of BOTOX were evaluated in an open label
trial. Fifty-five percent of these patients improved to an alignment of 10 prism diopters or less when evaluated six months or more
following injection.
16 HOW SUPPLIED/STORAGE AND HANDLING
BOTOX is supplied in a single-use vial in the following sizes:
50 Units NDC 0023-3920-50
100 Units NDC 0023-1145-01
200 Units NDC 0023-3921-02
Vials of BOTOX have a holographic film on the vial label that contains the name “Allergan” within horizontal lines of rainbow color.
In order to see the hologram, rotate the vial back and forth between your fingers under a desk lamp or fluorescent light source. (Note:
the holographic film on the label is absent in the date/lot area.) If you do not see the lines of rainbow color or the name “Allergan”, do
not use the product and contact Allergan for additional information at 1-800-890-4345 from 7:00 AM to 3:00 PM Pacific Time.
Storage
Unopened vials of BOTOX should be stored in a refrigerator (2° to 8°C) for up to 36 months for the 100 Units vial or up to 24 months
for the 50 Units and 200 Units vial. Do not use after the expiration date on the vial. Administer BOTOX within 24 hours of
reconstitution; during this period reconstituted BOTOX should be stored in a refrigerator (2° to 8°C). Reconstituted BOTOX should
be clear, colorless, and free of particulate matter.
This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda
17 PATIENT COUNSELING INFORMATION
“See FDA-approved patient labeling (Medication Guide)”
Provide a copy of the Medication Guide and review the contents with the patient.
17.1 Swallowing, Speaking or Breathing Difficulties, or Other Unusual Symptoms
Patients should be advised to inform their doctor or pharmacist if they develop any unusual symptoms (including difficulty with
swallowing, speaking, or breathing), or if any existing symptom worsens [see Boxed Warning and Warnings and Precautions (5.2,
5.4)].
17.2 Ability to Operate Machinery or Vehicles
Patients should be counseled that if loss of strength, muscle weakness, blurred vision, or drooping eyelids occur, they should avoid
driving a car or engaging in other potentially hazardous activities.
17.3 Voiding Difficulties after Bladder Injections
After bladder injections for urinary incontinence, patients should be instructed to contact their physician if they experience difficulties
in voiding.
This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda
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, or strabismus, or when BOTOX Cosmetic
has been used at the recommended dose to treat frown lines.
MEDICATION GUIDE
BOTOX
®
BOTOX
®
Cosmetic
(Boe-tox)
(onabotulinumtoxinA)
for Injection
Read the Medication Guide that comes with BOTOX or BOTOX
Cosmetic before you start using it and each time it is given to you.
There may be new information. This information does not take the place of talking with your doctor about your medical condition or
your treatment. You should share this information with your family members and caregivers.
What is the most important information I should know about BOTOX
and BOTOX Cosmetic?
BOTOX and BOTOX Cosmetic may cause serious side effects that can be life threatening, including
:
• Problems breathing or swallowing
• Spread of toxin effects
These problems can happen hours, days, to weeks after an injection of BOTOX or BOTOX Cosmetic. Call your doctor or get
medical help right away if you have any of these problems after treatment with BOTOX
or BOTOX
Cosmetic:
1. Problems swallowing, speaking, or breathing. These problems can happen hours, days, to weeks after an injection of
BOTOX or BOTOX Cosmetic usually because the muscles that you use to breathe and swallow can become weak after the injection.
Death can happen as a complication if you have severe problems with swallowing or breathing after treatment with BOTOX
or
BOTOX Cosmetic.
• People with certain breathing problems may need to use muscles in their neck to help them breathe. These people may be at
greater risk for serious breathing problems with BOTOX or BOTOX Cosmetic.
• Swallowing problems may last for several months. People who cannot swallow well may need a feeding tube to receive food and
water. If swallowing problems are severe, food or liquids may go into your lungs. People who already have swallowing or
breathing problems before receiving BOTOX or BOTOX
Cosmetic have the highest risk of getting these problems.
2. Spread of toxin effects. In some cases, the effect of botulinum toxin may affect areas of the body away from the injection site
and cause symptoms of a serious condition called botulism. The symptoms of botulism include:
• loss of strength and muscle weakness all over the body
• 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
These symptoms can happen hours, days to weeks after you receive an injection of BOTOX
or BOTOX
Cosmetic.
These problems could make it unsafe for you to drive a car or do other dangerous activities. See "What should I avoid while receiving
BOTOX or BOTOX Cosmetic?"
What are BOTOX and BOTOX Cosmetic?
BOTOX
is a prescription medicine that is injected into muscles and used:
• to treat leakage of urine (incontinence) in adults with overactive bladder due to neurologic disease.
• 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 elbow, wrist, and finger muscles in adults with upper limb 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
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.
This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda
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
is safe or effective in people younger than:
• 18 years of age for treatment of urinary incontinence
• 18 years of age for treatment of chronic migraine
• 18 years of age for treatment of spasticity
• 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
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 or effective to prevent headaches in people with migraine who have
14 or fewer headache days each month (episodic migraine).
It is not known whether BOTOX and BOTOX Cosmetic are safe or effective for other types of muscle spasms or for severe sweating
anywhere other than your armpits.
• 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)
Who should not take BOTOX
or BOTOX Cosmetic?
Do not take BOTOX or BOTOX Cosmetic if you:
• are allergic to any of the ingredients in BOTOX
or BOTOX
Cosmetic. See the end of this Medication Guide for a 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)
What should I tell my doctor before taking BOTOX or BOTOX Cosmetic?
Tell your doctor about all your medical conditions, including if you :
• have a disease that affects your muscles and nerves (such as amyotrophic lateral sclerosis [ALS or Lou Gehrig's disease],
myasthenia gravis or Lambert-Eaton syndrome). See "What is the most important information I should know about BOTOX
and BOTOX Cosmetic?"
• have allergies to any botulinum toxin product
• had any side effect from any botulinum toxin product in the past
• have or have had a breathing problem, such as asthma or emphysema
• have or have had swallowing problems
• have or have had bleeding problems
• have plans to have surgery
• had surgery on your face
• have weakness of your forehead muscles, such as trouble raising your eyebrows
• have drooping eyelids
• have any other change in the way your face normally looks
• 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 breast-feeding or plan to breastfeed. It is not known if BOTOX or BOTOX Cosmetic passes into breast milk.
This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda
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 four months
• have received injections of botulinum toxin, such as Myobloc
®
(rimabotulinumtoxinB), Dysport
®
(abobotulinumtoxinA), or
Xeomin
®
(incobotulinumtoxinA) 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) and/or anti-coagulants (blood thinners)
Ask your doctor if you are not sure if your medicine is one that is listed above.
Know the medicines you take. Keep a list of your medicines with you to show your doctor and pharmacist each time you get a new
medicine.
How should I take BOTOX or BOTOX Cosmetic?
• 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 should I avoid while taking BOTOX or BOTOX Cosmetic?
BOTOX
and BOTOX Cosmetic may cause loss of strength or general muscle weakness, or vision problems within hours to weeks of
taking BOTOX or BOTOX Cosmetic. If this happens, do not drive a car, operate machinery, or do other dangerous activities.
See "What is the most important information I should know about BOTOX and BOTOX Cosmetic?"
This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda
Xeomin
®
is a registered trademark of Merz Pharma GmbH & Co KGaA.
What are the possible side effects of BOTOX and BOTOX Cosmetic?
BOTOX
and BOTOX Cosmetic can cause serious side effects. See "What is the most important information I should know about
BOTOX and BOTOX Cosmetic?"
Other side effects of BOTOX and BOTOX Cosmetic 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.
• urinary tract infection in people 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. Tell your doctor or get medical help right away if you are
wheezing or have asthma symptoms, or if you become dizzy or faint.
Tell your doctor if you have any side effect that bothers you or that does not go away.
These are not all the possible side effects of BOTOX and BOTOX Cosmetic. For more information, ask your doctor or pharmacist.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
General information about BOTOX and BOTOX Cosmetic:
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide.
This Medication Guide summarizes the most important information about BOTOX and BOTOX Cosmetic. If you would like more
information, talk with your doctor. You can ask your doctor or pharmacist for information about BOTOX and BOTOX Cosmetic that
is written for healthcare professionals. For more information about BOTOX and BOTOX Cosmetic call Allergan at 1-800-433-8871
or go to www.BOTOX.com.
What are the ingredients in BOTOX and BOTOX Cosmetic?
Active ingredient: botulinum toxin type A
Inactive ingredients: human albumin and sodium chloride
Issued: 08/2011
This Medication Guide has been approved by the U.S. Food and Drug Administration.
Manufactured by: Allergan Pharmaceuticals Ireland
a subsidiary of: Allergan, Inc.
2525 Dupont Dr.
Irvine, CA 92612
© 2011 Allergan, Inc.
®
mark owned by Allergan, Inc.
U.S. Patents 6,974,578; 6,683,049; and 6,896,886
Myobloc
®
is a registered trademark of Solstice Neurosciences, Inc.
Dysport
®
is a registered trademark of Ipsen Biopharm Limited Company.
This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda
