Drug: Botox Cosmetic

BOTOX Cosmetic (onabotulinumtoxinA) for injection, is a sterile, vacuum-dried purified botulinum toxin type A, produced from fermentation of Hall strain Clostridium botulinum type A intended for intramuscular 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 Cosmetic 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 Cosmetic corresponds to the calculated median intraperitoneal lethal dose (LD50) in mice. Due to specific details of this assay such as the vehicle, dilution scheme and laboratory protocols, Units of biological activity of BOTOX Cosmetic 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 Cosmetic is approximately 20 Units/nanogram of neurotoxin complex. Each vial of BOTOX Cosmetic contains either 50 Units of Clostridium botulinum type A neurotoxin complex, 0.25 mg of Albumin Human, and 0.45 mg of sodium chloride; or 100 Units of Clostridium botulinum type A neurotoxin complex, 0.5 mg of Albumin Human, and 0.9 mg of sodium chloride in a sterile, vacuum-dried form without a preservative.

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The following adverse reactions to BOTOX Cosmetic (onabotulinumtoxinA) for injection are discussed in greater detail in other sections of the labeling:
  • Spread of Toxin Effects [see WARNINGS AND PRECAUTIONS]
  • Hypersensitivity [see CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS]
  • Dysphagia and Breathing Difficulties in Treatment of Cervical Dystonia [see WARNINGS AND PRECAUTIONS]
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 have different labeled Indications and Usage. Therefore, adverse events observed with the use of BOTOX also have the potential to be observed with the use of BOTOX Cosmetic. In general, adverse reactions occur within the first week following injection of BOTOX Cosmetic 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]. Glabellar Lines Table 2 lists selected adverse reactions reported by ≥ 1% of BOTOX Cosmetic treated subjects (N=405) aged 18 to 75 who were evaluated in the randomized, placebo-controlled clinical studies to assess the use of BOTOX Cosmetic in the improvement of the appearance of glabellar lines. Table 2: Adverse Reactions Reported by ≥ 1% of the BOTOX Cosmetic treated Patients and More Frequent than in Placebo-treated Patients in Double-blind, Placebo-controlled Clinical Studies of Treatment of Glabellar Lines
Adverse Reactions by System Organ Class BOTOX Cosmetic
(N=405) Placebo
(N=130) General Disorders and Administration Site Conditions Facial pain 6 (1%) 0 (0%) Nervous System Disorders Facial paresis 5 (1%) 0 (0%) Eye Disorders Eyelid ptosis 13 (3%) 0 (0%) Musculoskeletal and Connective Tissue Disorders Muscular Weakness 6 (1%) 0 (0%) Lateral Canthal Lines Table 3 lists selected adverse reactions reported within 90 days following injection by ≥ 1% of BOTOX Cosmetic treated subjects (N=526) aged 18 to 75 who were evaluated in two randomized, double-blind, placebo-controlled clinical studies to assess the use of BOTOX Cosmetic in the improvement of the appearance of lateral canthal lines alone. Table 3: Adverse Reaction Reported by ≥ 1% of BOTOX Cosmetic treated Patients and More Frequent than in Placebo-treated Patients Within 90 Days, in Double-blind, Placebo-controlled Clinical Studies of Treatment of Lateral Cantal Lines
Adverse Reactions by System Organ Class BOTOX Cosmetic 24 Units
(N=526) Placebo
(N=530) Eye disorders Eyelid edema 5 (1%) 0 (0%) Immunogenicity As with all therapeutic proteins, there is a potential for immunogenicity. Treatment with botulinum toxins may result in the formation of neutralizing antibodies that may reduce the effectiveness of subsequent treatments by inactivating biological activity of the toxin. In three Lateral Canthal Line trials, 916 subjects (517 subjects at 24 Units and 399 subjects at 44 Units) treated with BOTOX Cosmetic had specimens analyzed for antibody formation. Among the 916 BOTOX Cosmetic treated subjects, 14 subjects (1.5%) developed binding antibodies and no subjects (0%) developed the presence of neutralizing antibodies. The data reflect the subjects whose test results were considered positive or negative for neutralizing activity to BOTOX Cosmetic in a mouse protection assay. The results of these tests are highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to BOTOX Cosmetic with the incidence of antibodies 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 botulinum toxin 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. Post-marketing Experience Because these reactions 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. 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]. 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. New onset or recurrent seizures have also been reported, typically in patients who are predisposed to experiencing these events. The following adverse reactions by System Organ Class have been identified during post-approval use of BOTOX/BOTOX Cosmetic: Ear and labyrinth disorders Hypoacusis; tinnitus; vertigo Eye disorders Diplopia; strabismus; visual disturbances; vision blurred Gastrointestinal disorders Abdominal pain; diarrhea; dry mouth; nausea; vomiting General disorders and administration site conditions Denervation; malaise; pyrexia Metabolism and nutrition disorders Anorexia Musculoskeletal and connective tissue disorders Muscle atrophy; myalgia Nervous system disorders Brachial plexopathy; dysarthria; facial palsy; hypoaesthesia; localized numbness; myasthenia gravis; paresthesia; peripheral neuropathy; radiculopathy; syncope Respiratory, thoracic and mediastinal disorders Aspiration pneumonia; dyspnea; respiratory depression and/or respiratory failure Skin and subcutaneous tissue disorders Alopecia, including madarosis; hyperhidrosis; pruritus; skin rash (including erythema multiforme, dermatitis psoriasiform, and psoriasiform eruption) Read the Botox Cosmetic (onabotulinumtoxina for injection) Side Effects Center for a complete guide to possible side effectsLearn More »

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Instructions for Use The potency Units of BOTOX Cosmetic (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 Cosmetic cannot be compared to nor converted into units of any other botulinum toxin products assessed with any other specific assay method [see DESCRIPTION]. Indication specific dosage and administration recommendations should be followed. In treating adult patients for one or more indications with BOTOX and BOTOX Cosmetic, the maximum cumulative dose should generally not exceed 360 Units, in a 3 month interval. The safe and effective use of BOTOX Cosmetic depends upon proper storage of the product, selection of the correct dose, and proper reconstitution and administration techniques. Physicians administering BOTOX Cosmetic must understand the relevant neuromuscular and/or orbital anatomy of the area involved and any alterations to the anatomy due to prior surgical procedures [see WARNINGS AND PRECAUTIONS]. Preparation and Dilution Technique BOTOX Cosmetic is supplied in single-use 50 Units and 100 Units per vial. Prior to intramuscular injection, reconstitute each vacuum-dried vial of BOTOX Cosmetic with sterile, preservative-free 0.9% Sodium Chloride Injection USP. Draw up the proper amount of diluent in the appropriate size needle and syringe to obtain a reconstituted solution at a concentration of 4 Units/0.1 mL and a total treatment dose of 20 Units in 0.5 mL for glabellar lines and 24 Units in 0.6 ml for lateral canthal lines (see Table 1). Then slowly inject the diluent into the vial. Discard the vial if a vacuum does not pull the diluent into the vial. Gently mix BOTOX Cosmetic with the saline by rotating the vial. Record the date and time of reconstitution on the space on the label. BOTOX Cosmetic should be administered within 24 hours after reconstitution. During this time period, reconstituted BOTOX Cosmetic should be stored in a refrigerator (2° to 8°C). BOTOX Cosmetic vials are for single-use only. Discard any remaining solution. Table 1: Dilution Instructions for BOTOX Cosmetic Vials (100 Units and 50 Units)
Diluent* Added to 100 Unit Vial Resulting Dose Units per 0.1 mL Diluent* Added to 50 Unit Vial Resulting Dose Units per 0.1 mL 2.5 mL 4 Units 1.25 mL 4 Units *Preservative-free 0.9% Sodium Chloride Injection, USP Only Reconstituted BOTOX Cosmetic 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. Do not freeze reconstituted BOTOX Cosmetic. Administration Draw at least 0.5 mL (for glabellar lines) or 0.6 mL (for lateral canthal lines) of the properly reconstituted toxin into the sterile syringe, preferably a tuberculin syringe and expel any air bubbles in the syringe barrel. Remove the needle used to reconstitute the product and attach a 30-33 gauge needle. Confirm the patency of the needle. Glabellar Lines Glabellar facial lines arise from the activity of the corrugator and orbicularis oculi muscles. These muscles move the brow medially, and the procerus and depressor supercilii pull the brow inferiorly. This creates a frown or “furrowed brow”. The location, size, and use of the muscles vary markedly among individuals. Lines induced by facial expression occur perpendicular to the direction of action of contracting facial muscles. An effective dose for facial lines is determined by gross observation of the patient's ability to activate the superficial muscles injected. In order to reduce the complication of ptosis the following steps should be taken:
  • Avoid injection near the levator palpebrae superioris, particularly in patients with larger brow depressor complexes.
  • Lateral corrugator injections should be placed at least 1 cm above the bony supraorbital ridge.
  • Ensure the injected volume/dose is accurate and where feasible kept to a minimum.
  • Do not inject toxin closer than 1 cm above the central eyebrow.
Inject 4 Units/0.1 mL of reconstituted BOTOX Cosmetic intramuscularly into each of 5 sites, 2 in each corrugator muscle and 1 in the procerus muscle for a total dose of 20 Units (see Figure 1). Typically the initial doses of reconstituted BOTOX Cosmetic induce chemical denervation of the injected muscles one to two days after injection, increasing in intensity during the first week. The duration of effect of BOTOX Cosmetic for glabellar lines is approximately 3-4 months. The safety and effectiveness of dosing with BOTOX Cosmetic more frequently than every 3 months have not been clinically evaluated. Figure 1
Lateral Canthal Lines Lateral canthal lines arise largely from the activity of the orbicularis oculi muscles around the eye responsible for blinking and eyelid closure. Forceful contraction of the orbicularis oculi results in lateral and radially oriented folds (crow's feet lines) which originate from the lateral canthus. The distribution of these radial lines differs among patients. Injections should be given with the needle bevel tip up and oriented away from the eye. Inject 4 Units/0.1 mL of reconstituted BOTOX Cosmetic into 3 sites per side (6 total injection points) in the lateral orbicularis oculi muscle for a total of 24 Units/0.6 mL (12 Units per side). The first injection (A) should be approximately 1.5-2.0 cm temporal to the lateral canthus and just temporal to the orbital rim. If the lines in the lateral canthal region are above and below the lateral canthus, inject per Figure 2. Alternatively, if the lines in the lateral canthal region are primarily below the lateral canthus, inject per Figure 3. Figure 2
Figure 3
For simultaneous treatment with glabellar lines, the dose is 24 Units for lateral canthal lines and 20 Units for glabellar lines (see Glabellar Lines Administration and Figure 1), with a total dose of 44 Units. The safety and effectiveness of dosing with BOTOX Cosmetic more frequently than every 3 months have not been clinically evaluated.

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No formal drug interaction studies have been conducted with BOTOX Cosmetic (onabotulinumtoxinA) for injection. Aminoglycosides and Other Agents Interfering with Neuromuscular Transmission Co-administration of BOTOX Cosmetic 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. Anticholinergic Drugs Use of anticholinergic drugs after administration of BOTOX Cosmetic may potentiate systemic anticholinergic effects. 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. Muscle Relaxants Excessive weakness may also be exaggerated by administration of a muscle relaxant before or after administration of BOTOX Cosmetic. Read the Botox Cosmetic Drug Interactions Center for a complete guide to possible interactions Learn More »

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Glabellar Lines BOTOX Cosmetic (onabotulinumtoxinA) for injection is indicated for the temporary improvement in the appearance of moderate to severe glabellar lines associated with corrugator and/or procerus muscle activity in adult patients. Lateral Canthal Lines BOTOX Cosmetic is indicated for the temporary improvement in the appearance of moderate to severe lateral canthal lines associated with orbicularis oculi activity in adult patients.

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Known Hypersensitivity to Botulinum Toxin BOTOX Cosmetic is contraindicated in individuals with known hypersensitivity to any botulinum toxin preparation or to any of the components in the formulation [see WARNINGS AND PRECAUTIONS]. Infection at the Injection Site(s) BOTOX Cosmetic is contraindicated in the presence of infection at the proposed injection site(s). Last reviewed on RxList: 9/26/2013
This monograph has been modified to include the generic and brand name in many instances.

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Excessive doses of BOTOX Cosmetic (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, these patients should be considered for further medical evaluation and appropriate medical therapy immediately instituted, which may include hospitalization. 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 WARNINGS AND PRECAUTIONS]. 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.

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Dosage Forms And Strengths
  • For injection: 50 Units, vacuum-dried powder in a single-use vial for reconstitution
  • For injection: 100 Units, vacuum-dried powder in a single-use vial for reconstitution
Storage And Handling BOTOX Cosmetic is supplied in a single-use vial in the following sizes: 50 Units: NDC 0023-3919-50
100 Units: NDC 0023-9232-01 Vials of BOTOX Cosmetic 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 Cosmetic should be stored in a refrigerator 2° to 8°C (36° to 46°F). Do not use after the expiration date on the vial. Reconstituted BOTOX Cosmetic should be stored in a refrigerator 2° to 8°C (36° to 46°F) and administered within 24 hours. Manufactured by: Allergan Pharmaceuticals Ireland a subsidiary of: Allergan, Inc. 2525 Dupont Dr. Irvine, CA 92612 . 2013 Allergan, Inc. ® marks owned by Allergan, Inc. Revised: Sep 2013 Last reviewed on RxList: 9/26/2013
This monograph has been modified to include the generic and brand name in many instances.

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Lack of Interchangeability between Botulinum Toxin Products The potency Units of BOTOX Cosmetic 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 Cosmetic cannot be compared to nor converted into units of any other botulinum toxin products assessed with any other specific assay method [see DESCRIPTION]. Spread of Toxin Effect Postmarketing safety data from BOTOX Cosmetic 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 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 difficulties 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), 24 Units (for lateral canthal lines), 44 Units (for simultaneous treatment of lateral canthal lines and 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 chronic migraine at the labeled doses have been reported. Injections In or Near Vulnerable Anatomic Structures Care should be taken when injecting in or near vulnerable anatomic structures. Serious adverse events including fatal outcomes have been reported in patients who had received BOTOX injected directly into salivary glands, the oro-lingual-pharyngeal region, esophagus and stomach. Safety and effectiveness have not been established for indications pertaining to these injection sites. Some patients had pre-existing dysphagia or significant debility. Pneumothorax associated with injection procedure has been reported following the administration of BOTOX near the thorax. Caution is warranted when injecting in proximity to the lung, particularly the apices. 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 Cosmetic 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. Cardiovascular System There have been reports following administration of BOTOX of adverse events involving the cardiovascular system, including arrhythmia and myocardial infarction, some with fatal outcomes. Some of these patients had risk factors including pre-existing cardiovascular disease. Use caution when administering to patients with pre-existing cardiovascular disease. 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 typical doses of BOTOX Cosmetic. 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 preexisting 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. 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. Pre-existing Conditions at the Injection Site Caution should be used when BOTOX Cosmetic treatment is used in the presence of inflammation at the proposed injection site(s), ptosis, or when excessive weakness or atrophy is present in the targeted muscle(s). Corneal Exposure and Ulceration in Patients Treated with BOTOX for Blepharospasm Reduced blinking from BOTOX Cosmetic 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. Spatial Disorientation, Double Vision or Past-pointing in Patients Treated for Strabismus Inducing paralysis in one or more extraocular muscles may produce spatial disorientation, double vision or past pointing. Covering the affected eye may alleviate these symptoms. 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. Patient Counseling Information See FDA-approved patient labeling (Medication Guide) Provide a copy of the Medication Guide and review the contents with the patient. 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]. 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. Nonclinical Toxicology Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Long term studies in animals have not been performed to evaluate carcinogenic potential of BOTOX Cosmetic. Mutagenesis BOTOX Cosmetic 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. Impairment of Fertility In fertility studies of BOTOX Cosmetic (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 5-10 times the average high human dose for glabellar lines and lateral canthal lines of 44 Units on a body weight basis (Units/kg). Use In Specific Populations Pregnancy Teratogenic Effects - Pregnancy Category C There are no adequate and well-controlled studies in pregnant women. BOTOX Cosmetic should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. When BOTOX Cosmetic (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 5 times the average high human dose for glabellar lines and lateral canthal lines of 44 Units on a body weight basis (Units/kg). When BOTOX Cosmetic 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 is approximately 1.4 times the average human dose based on Units/kg, and the developmental no-effect dose of 0.25 Units/kg in rabbits is 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 22 times the average high human dose based on Units/kg. Nursing Mothers It is not known whether BOTOX Cosmetic is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when BOTOX Cosmetic is administered to a nursing woman. Pediatric Use Safety and effectiveness in patients below the age of 18 years have not been established. Geriatric Use Glabellar Lines In the two initial glabellar lines clinical studies of BOTOX Cosmetic, the responder rates appeared to be higher for subjects younger than age 65 than for subjects 65 years or older [see Clinical Studies]. Lateral Canthal Lines In the two lateral canthal lines clinical studies of BOTOX Cosmetic, the responder rates appeared to be higher for subjects younger than age 65 than for subjects 65 years or older. Last reviewed on RxList: 9/26/2013
This monograph has been modified to include the generic and brand name in many instances.

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