Onabotulinumtoxina
FDA Drug Information • Also known as: Botox, Botox Cosmetic
- Brand Names
- Botox, Botox Cosmetic
- Drug Class
- Acetylcholine Release Inhibitor [EPC], Neuromuscular Blocker [EPC]
- Route
- INTRAMUSCULAR
- Dosage Form
- INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION
- Product Type
- HUMAN PRESCRIPTION DRUG
⚠ Boxed Warning (Black Box)
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 the se symptoms. In unapproved uses and in approved indications, cases of spread of effect have been reported at doses comparable to those used to treat cervical dystonia an d spasticity and at lower doses [ see Warnings and Precautions ( 5.1 )] . 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 )
Description
11 DESCRIPTION OnabotulinumtoxinA 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 AbbVie’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. Each vial of BOTOX (onabotulinumtoxinA) for injection contains either 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.
What Is Onabotulinumtoxina Used For?
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 cervical dystonia in adult patients, to reduce the severity of abnormal head position and neck pain ( 1.5 ) Treatment of severe axillary hyperhidrosis that is inadequately managed by topical agents in adult patients ( 1.6 ) Treatment of blepharospasm associated with dystonia in patients 12 years of age and older ( 1.7 ) Treatment of strabismus in patients 12 years of age and older ( 1.7 ) Limitations of Use Safety and effectiveness of BOTOX have not been established for: Prophylaxis of episodic migraine (14 headache days or fewer per month) ( 1.3 ) Treatment of hyperhidrosis in body areas other than axillary ( 1.6 ) 1.1 Adult Bladder Dysfunction 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. 1.2 Pediatric Detrusor Overactivity A ssociated with a Neurologic Condition 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. 1. 3 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). 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. 1. 4 Spasticity BOTOX is indicated for the treatment of spasticity in patients 2 years of age and older. Limitations of Use...
Dosage and Administration
2 DOSAGE AND ADMINISTRATION Follow indication-specific dosage and administration recommendations. In a 3 month interval, do not exceed a total dose of:
Side Effects (Adverse Reactions)
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 ( 5.1 )] Serious Adverse Reactions with Unapproved Use [see Warnings and Precautions ( 5.3 )] Hypersensitivity Reactions [see Contraindications ( 4 ) a nd Warnings and Precautions ( 5.4 )] Increased Risk of Clinically Significant Effects with Pre-Existing Neuromuscular Disorders [see Warnings and Precautions ( 5.5 )] Dysphagia and Breathing Difficulties [see Warnings and Precautions ( 5.6 )] Pulmonary Effects of BOTOX in Patients with Compromised Respiratory Status Treated for Spasticity or for Detrusor Overactivity Associated with a Neurologic Condition [see Warnings and Precautions ( 5.7 )] Corneal Exposure and Ulceration in Patients Treated with BOTOX for Blepharospasm [see Warnings and Precautions ( 5.8 )] Retrobulbar Hemorrhages in Patients Treated with BOTOX for Strabismus [see Warnings and Precautions ( 5.9 )] Bronchitis and Upper Respiratory Tract Infections in Patients Treated for Spasticity [se e Warnings and Precautions ( 5.10 )] Autonomic Dysreflexia in Patients Treated for Detrusor Overactivity Associated with a Neurologic Condition [see Warnings and Precautions ( 5.11 )] Urinary Tract Infections in Patients with Overactive Bladder [see Warnings and Precautions ( 5.12 )] Urinary Retention in Patients Treated for Bladder Dysfunction [see Warnings and Precautions ( 5.13 )] The most common adverse reactions (≥5% and >placebo, if applicable) are ( 6.1 ): OAB: urinary tract infection, dysuria, urinary retention Adult Detrusor Overactivity associated with a neurologic condition: urinary tract infection, urinary retention Pediatric Detrusor Overactivity associated with a neurologic condition: urinary tract infection, leukocyturia, bacteriuria Chronic Migraine: neck pain, headache Adult Spasticity: pain in extremity Pediatric Spasticity: upper respiratory tract infection 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 AbbVie at 1-800-678-1605 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 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. Symptoms associated with flu-like symptoms (e.g., nausea, fever, myalgia) have been reported after treatment. Needle-related pain and/or anxiety may result in vasovagal responses (including 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 ( 5.1 )] . Overactive Bladder Table 14 presents the most frequently reported adverse reactions in double-blind, placebo-controlled clinical trials for overactive bladder occurring within 12 weeks of the first BOTOX treatment. Table 14: Adverse Reactions Reported...
Drug Interactions
7 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 ( 7.1 , 7.4 ) 7.1 Aminoglycosides and Other Agents Interfering with Neuromuscular Transmission 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. 7.2 Anticholinergic Drugs Use of anticholinergic drugs after administration of BOTOX may potentiate systemic anticholinergic effects. 7.3 Other Botulinum Neurotoxin Products 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. 7.4 Muscle Relaxants Excessive weakness may also be exaggerated by administration of a muscle relaxant before or after administration of BOTOX.
Contraindications
4 CONTRAINDICATIONS 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 )] . Hypersensitivity to any botulinum toxin preparation or to any of the components in the formulation ( 4 , 5.4 , 6 ) Infection at the proposed injection site ( 4 ) Intradetrusor Injections: Urinary tract infection or urinary retention ( 4 )
Pregnancy and Breastfeeding
8.1 Pregnancy 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,...
Overdosage
10 OVERDOSAGE Excessive doses of BOTOX (onabotulinumtoxinA) for injection may be expected to produce neuromuscular weakness with a variety of symptoms. Symptoms of overdose are likely not to be present immediately following injection. Should accidental injection or oral ingestion occur or overdose be suspected, the person should be medically supervised for several weeks for signs and symptoms of systemic muscular weakness which could be local, or distant from the site of injection [see Boxed Warning and Wa rnings and Precautions ( 5.1 , 5.6 )] . These patients should be considered for further medical evaluation and appropriate medical therapy immediately instituted, which may include hospitalization. If the musculature of the oropharynx and esophagus are affected, aspiration may occur which may lead to development of aspiration pneumonia. If the respiratory muscles become paralyzed or sufficiently weakened, intubation and assisted respiration may be necessary until recovery takes place. Supportive care could involve the need for a tracheostomy and/or prolonged mechanical ventilation, in addition to other general supportive care. In the event of overdose, antitoxin raised against botulinum toxin is available from the Centers for Disease Control and Prevention (CDC) in Atlanta, GA. 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.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING 16 .1 How Supplied 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. 16.2 Storage and Handling 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 )] . 16 .1 How Supplied 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.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.