BOTOX- onabotulinumtoxina injection, powder, lyophilized, for solution

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

BOTULINUM TOXIN TYPE A (UNII: E211KPY694) (BOTULINUM TOXIN TYPE A - UNII:E211KPY694)

Available from:

Allergan, Inc.

INN (International Name):

botulinum toxin type A

Composition:

botulinum toxin type A 100 [USP'U]

Administration route:

INTRADERMAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Overactive Bladder BOTOX  for injection is indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency, in adults who have an inadequate response to or are intolerant of an anticholinergic medication. Detrusor Overactivity associated with a Neurologic Condition BOTOX  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. BOTOX is indicated for the treatment of neurogenic detrusor overactivity (NDO) in pediatric patients 5 years of age and older who have an inadequate response to or are intolerant of anticholinergic medication. 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). Limitations of Use 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. BOTOX is indicated for the treatment of spasticity in patients 2 years of age and older. Limitations of Use   BOTOX has not been shown to improve upper extremity functional abilities, or range of motion at a joint affected by a fixed contracture. 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. BOTOX is indicated for the treatment of severe primary axillary hyperhidrosis that is inadequately managed with topical agents. Limitations of Use 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. 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 older. BOTOX is contraindicated: - In patients who are hypersensitive to any botulinum toxin product or to any of the components in the formulation [see Warnings and Precautions ( 5.4 )] .  - In the presence of infection at the proposed injection site(s). - For intradetrusor injection in patients with a urinary tract infection; or in patients with urinary retention or post-void residual (PVR) urine volume >200 mL who are not routinely performing clean intermittent self-catheterization (CIC) [see Warnings and Precautions ( 5.12 , 5.13 )] . Risk Summary There are no studies or adequate data from postmarketing surveillance on the developmental risk associated with use of BOTOX in pregnant women. In animal studies, administration of BOTOX during pregnancy resulted in adverse effects on fetal growth (decreased fetal weight and skeletal ossification) at clinically relevant doses, which were associated with maternal toxicity [see Data ]. In the U.S. general population, the estimated background risk of major birth defects and miscarriages in clinically recognized pregnancies is 2-4% and 15-20%, respectively. The background risk of major birth defects and miscarriage for the indicated populations is unknown. Data Animal Data 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 equal to the human dose of 400 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 human dose of 400 Units, 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 2 times the human dose of 400 Units, based on Units/kg. Risk Summary There are no data on the presence of BOTOX in human or animal milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for BOTOX and any potential adverse effects on the breastfed infant from BOTOX or from the underlying maternal conditions. Detrusor Overactivity associated with a Neurologic Condition The safety and effectiveness of BOTOX for detrusor overactivity associated with a neurologic condition have been established in pediatric patients 5 years of age and older who have an inadequate response to or are intolerant of anticholinergic medication. Use of BOTOX in this patient population is based on the results of a randomized, double-blind, parallel group trial in 113 pediatric patients 5 to 17 years of age (inclusive) with detrusor overactivity associated with a neurologic condition (Study 191622-120) and a long-term, multicenter, double-blind, long-term extension trial (Study 191622-121) [see Clinical Studies ( 14.3 )]. The most common adverse reactions in this population were urinary tract infection, bacteriuria, hematuria, and leukocyturia [see Adverse Reactions   ( 6.1 ) ] . The safety and effectiveness of BOTOX have not been established in patients with NDO younger than 5 years of age. Overactive Bladder The safety and effectiveness of BOTOX for the treatment of overactive bladder have not been established in pediatric patients. Efficacy was not demonstrated in a multicenter, randomized, double-blind, parallel-group, multiple-dose clinical study which was conducted to evaluate the efficacy and safety of BOTOX in pediatric patients aged 12 to 17 years with overactive bladder. Fifty-five patients who had an inadequate response to or were intolerant of at least one anticholinergic medication were treated with BOTOX. There was not a statistically significant difference in the mean change from baseline in the daily average frequency of daytime urinary incontinence episodes (primary efficacy endpoint) at week 12 post-treatment when a medium and high dose were each compared to a low dose of BOTOX. The adverse reactions in pediatric patients treated with BOTOX were comparable with the known safety profile in adults with overactive bladder.  Prophylaxis of Headaches in Chronic Migraine Safety and effectiveness in patients below the age of 18 years have not been established. In a 12-week, multicenter, double-blind, placebo-controlled clinical trial, 123 adolescent patients (ages 12 to below 18 years) with chronic migraine were randomized to receive BOTOX 74 Units, BOTOX 155 Units, or placebo, for one injection cycle. This trial did not establish the efficacy of BOTOX, compared with placebo, for the prophylaxis of headaches in adolescents with chronic migraine. Spasticity Safety and effectiveness have been established in pediatric patients 2 to 17 years of age [see Warnings and Precautions ( 5.1 ), Adverse Reactions ( 6.1 ) , and Clinical Studies ( 14.6 )] . The safety and effectiveness of BOTOX have been established by evidence from adequate and well-controlled studies of BOTOX in patients 2 to 17 years of age with upper and lower limb spasticity. Safety and effectiveness in pediatric patients below the age of 2 years have not been established [see Boxed Warning and Warnings and Precautions ( 5.1 )]. 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. Juvenile Animal Data In a study in which juvenile rats received intramuscular injection of BOTOX (0, 8, 16, or 24 Units/kg) every other week from postnatal day 21 for 12 weeks, changes in bone size/geometry associated with decreased bone density and bone mass were observed at all doses, in association with limb disuse, decreased muscle contraction, and decreased body weight gain. Impairment of fertility and male reproductive organ histopathology (degeneration of seminiferous tubules of the testis) were observed at the mid and high doses. Bone and male reproductive organ effects showed evidence of reversibility after dosing cessation. The no-effect dose for adverse developmental effects in juvenile animals (8 Units/kg) is similar to the human dose (400 Units) on a body weight (kg) basis. Of the 2145 adult patients in placebo-controlled clinical studies of BOTOX for the treatment of spasticity, 33.5% were 65 or older, and 7.7% were 75 years of age or older. No overall differences in safety were observed between elderly patients and adult patients younger than 65 years of age.  In clinical studies of BOTOX across other indications, no overall differences in safety were observed between elderly patients and younger adult patients, with the exception of Overactive Bladder (see below). Other reported clinical experience has not identified differences in responses between the elderly and younger adult patients, but greater sensitivity of some older individuals cannot be ruled out. Overactive Bladder Of 1242 overactive bladder patients in placebo-controlled clinical studies of BOTOX, 41.4% were 65 years of age or older, and 14.7% were 75 years of age or older. Adverse reactions of UTI and urinary retention were more common in patients 65 years of age or older in both placebo and BOTOX groups compared to younger patients (see Table 24). Otherwise, there were no overall differences in the safety profile following BOTOX treatment between patients aged 65 years and older compared to adult patients younger than 65 years of age in these studies. Observed effectiveness was comparable between these age groups in placebo-controlled clinical studies.

Product summary:

BOTOX (onabotulinumtoxinA) for injection is a sterile, vacuum-dried powder supplied in a single-dose vial in the following sizes: 100 Units NDC 0023-1145-01 200 Units NDC 0023-3921-02 BOTOX cartons have features to alert users if contents may have been compromised. Each BOTOX vial label and carton also contains the U.S. License number: 1889 [see Dosage and Administration ( 2.1 )] . Do not use the product and contact AbbVie for additional information at 1-800-678-1605 if the labeling is not described as above. Unopened vials of BOTOX should be stored in a refrigerator between 2° to 8°C (36º to 46ºF) for up to 36 months. Do not use after the expiration date on the vial. Reconstituted BOTOX may be stored in a refrigerator (2° to 8°C) for up to 24 hours until time of use [see Dosage   and  Administ r ation ( 2.2 )] .  

Authorization status:

Biologic Licensing Application

Patient Information leaflet

Allergan, Inc.
----------
MEDICATION GUIDE
BOTOX®
BOTOX® Cosmetic
(Boe-tox)
(onabotulinumtoxinA)
for injection, for intramuscular, intradetrusor,
or intradermal use
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:
•
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.
•
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
○ t

Summary of Product characteristics

BOTOX- ONABOTULINUMTOXINA INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION
ALLERGAN, INC.
----------
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
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.
(5.1)
INDICATIONS AND USAGE
BOTOX is an acetylcholine release inhibitor and a neuromuscular
blocking agent indicated for:
Treatment of overactive bladder (OAB) with symptoms of urge urinary
incontinence, urgency, and
frequency, in adults who have an inadequate response to or are
intolerant of an anticholinergic
medication (1.1)
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)
Treatment of neurogenic detrusor overactivity (NDO) in pediatric
patients 5 years of age and older who
have an inadequate response to or are intolerant of anticholinergic
medication. (1.2)
Prophylaxis of headaches in adult patients with chronic migraine
(≥15 days per month with headache
lasting 4 hours a day or longer) (1.3)
Treatment of spasticity in patients 2 years of age and older (1.4)
Treatment of c