CosMedics

Indications, Important Safety Information and Prescribing Information
BOTOX® Cosmetic (onabotulinumtoxinA) Important Information
Indications

BOTOX® Cosmetic (onabotulinumtoxinA) is indicated in adult patients for the temporary improvement in the appearance of:
– Moderate to severe glabellar lines associated with corrugator and/or procerus muscle activity
– Moderate to severe lateral canthal lines associated with orbicularis oculi activity

– Moderate to severe forehead lines associated with frontalis activity

IMPORTANT SAFETY INFORMATION, INCLUDING BOXED WARNING

WARNING: DISTANT SPREAD OF TOXIN EFFECT

Postmarketing reports indicate that the effects of BOTOX® Cosmetic 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 spasticity and at lower doses.

CONTRAINDICATIONS
BOTOX® Cosmetic is contraindicated in the presence of infection at the proposed injection site(s) and in individuals with known hypersensitivity to any botulinum toxin preparation or to any of the components in the formulation.

WARNINGS AND PRECAUTIONS
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.

Spread of Toxin Effect
Please refer to Boxed Warning for Distant Spread of Toxin Effect.
No definitive serious adverse event reports of distant spread of toxin effect associated with dermatologic use of BOTOX® Cosmetic at the labeled dose of 20 Units (for glabellar lines), 24 Units (for lateral canthal lines), 40 Units (for forehead lines with glabellar lines), 44 Units (for simultaneous treatment of lateral canthal lines and glabellar lines), and 64 Units (for simultaneous treatment of lateral canthal lines, glabellar lines, and forehead lines) have been reported. Patients or caregivers should be advised to seek immediate medical care if swallowing, speech, or respiratory disorders occur.

Serious Adverse Reactions With Unapproved Use
Serious adverse reactions, including excessive weakness, dysphagia, and aspiration pneumonia, with some adverse reactions associated with fatal outcomes, have been reported in patients who received BOTOX® injections for unapproved uses. In these cases, the adverse reactions were not necessarily related to distant spread of toxin, but may have resulted from the administration of BOTOX® to the site of injection and/or adjacent structures. In several of the cases, patients had pre-existing dysphagia or other significant disabilities. There is insufficient information to identify factors associated with an increased risk for adverse reactions associated with the unapproved uses of BOTOX®. The safety and effectiveness of BOTOX® for unapproved uses have not been established.

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 reactions occur, 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.

Increased Risk of Clinically Significant Effects With Pre-existing Neuromuscular Disorders
Individuals with peripheral motor neuropathic diseases, amyotrophic lateral sclerosis, or neuromuscular junction disorders (eg, myasthenia gravis or Lambert-Eaton syndrome) should be monitored when given botulinum toxin. Patients with neuromuscular disorders may be at increased risk of clinically significant effects including generalized muscle weakness, diplopia, ptosis, dysphonia, dysarthria, severe dysphagia, and respiratory compromise from onabotulinumtoxinA (see Warnings and Precautions).

Dysphagia and Breathing Difficulties
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 oropharyngeal muscles that control swallowing or breathing (see Boxed Warning).

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) or when excessive weakness or atrophy is present in the target muscle(s).

Dry Eye in Patients Treated With BOTOX® Cosmetic
There have been reports of dry eye associated with BOTOX® Cosmetic injection in or near the orbicularis oculi muscle. If symptoms of dry eye (eg, eye irritation, photophobia, or visual changes) persist, consider referring patients to an ophthalmologist.

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 and variant Creutzfeldt-Jakob disease (vCJD). There is a theoretical risk for transmission of Creutzfeldt-Jakob disease (CJD), but if that risk actually exists, the risk of transmission would also be considered extremely remote. No cases of transmission of viral diseases, CJD or vCJD have ever been identified for licensed albumin or albumin contained in other licensed products.

ADVERSE REACTIONS
The most frequently reported adverse reactions following injection of BOTOX® Cosmetic for glabellar lines were eyelid ptosis (3%), facial pain (1%), facial paresis (1%), and muscular weakness (1%).

The most frequently reported adverse reaction following injection of BOTOX® Cosmetic for lateral canthal lines was eyelid edema (1%).

The most frequently reported adverse reactions following injection of BOTOX® Cosmetic for forehead lines with glabellar lines were headache (9%), brow ptosis (2%) and eyelid ptosis (2%).

DRUG INTERACTIONS
Co-administration of BOTOX® Cosmetic and aminoglycosides or other agents interfering with neuromuscular transmission (eg, 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® Cosmetic 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® Cosmetic.

USE IN SPECIFIC POPULATIONS
There are no studies or adequate data from postmarketing surveillance on the developmental risk associated with use of BOTOX® Cosmetic in pregnant women. There are no data on the presence of BOTOX® Cosmetic in human or animal milk, the effects on the breastfed child, or the effects on milk production.

Please see BOTOX® Cosmetic full Prescribing Information including Boxed Warning and Medication Guide.

INDICATIONS

JUVÉDERM® VOLUMA™ XC injectable gel is indicated for deep (subcutaneous and/or supraperiosteal) injection for cheek augmentation to correct age-related volume deficit in the mid-face in adults over the age of 21.

JUVÉDERM® Ultra XC and JUVÉDERM® Ultra Plus XC injectable gels are indicated for injection into the mid-to-deep dermis for correction of moderate to severe facial wrinkles and folds (such as nasolabial folds).
JUVÉDERM® VOLLURE™ XC injectable gel is indicated for injection into the mid-to-deep dermis for correction of moderate to severe facial wrinkles and folds (such as nasolabial folds) in adults over the age of 21.
JUVÉDERM® Ultra XC injectable gel is indicated for injection into the lips and perioral area for lip augmentation in adults over the age of 21.

JUVÉDERM® VOLBELLA™ XC injectable gel is indicated for injection into the lips for lip augmentation and for correction of perioral rhytids in adults over the age of 21.
IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

These products should not be used in patients who have severe allergies, marked by a history of anaphylaxis or history or presence of multiple severe allergies, and should not be used in patients with a history of allergies to Gram-positive bacterial proteins or lidocaine contained in these products.

WARNINGS
Do not inject into blood vessels. Introduction of these products into the vasculature may lead to embolization, occlusion of the vessels, ischemia, or infarction. Take extra care when injecting soft-tissue fillers; for example, inject the product slowly and apply the least amount of pressure necessary. Rare, but serious, adverse events associated with the intravascular injection of soft-tissue fillers in the face have been reported and include temporary or permanent vision impairment, blindness, cerebral ischemia or cerebral hemorrhage leading to stroke, skin necrosis, and damage to underlying facial structures. Immediately stop the injection if a patient exhibits any of the following symptoms: changes in vision, signs of a stroke, blanching of the skin, unusual pain during or shortly after the procedure. Patients should receive prompt medical attention and, possibly, evaluation by an appropriate healthcare professional specialist should an intravascular injection occur
Product use at specific sites in which an active inflammatory process (skin eruptions such as cysts, pimples, rashes, or hives) or infection is present should be deferred until the underlying process has been controlled

PRECAUTIONS
In order to minimize the risk of potential complications, these products should only be used by healthcare professionals who have appropriate training, experience, and knowledge of facial anatomy
Healthcare professionals are encouraged to discuss the potential risks of soft-tissue injections with their patients prior to treatment and ensure that patients are aware of signs and symptoms of potential complications
The safety and effectiveness for the treatment of anatomic regions other than the mid-face with JUVÉDERM® VOLUMA™ XC; facial wrinkles and folds with JUVÉDERM® Ultra XC, JUVÉDERM® Ultra Plus XC, and JUVÉDERM® VOLLURE™ XC; and the lips and perioral area with JUVÉDERM® Ultra XC and JUVÉDERM® VOLBELLA™ XC have not been established in controlled clinical studies

As with all transcutaneous procedures, dermal filler implantation carries a risk of infection. Follow standard precautions associated with injectable materials

The safety for use during pregnancy, in breastfeeding females, and in patients with known susceptibility to keloid formation, hypertrophic scarring, and pigmentation disorders has not been studied
The safety for use of JUVÉDERM® VOLUMA™ XC in patients under 35 or over 65 years, JUVÉDERM® Ultra XC and JUVÉDERM® Ultra Plus XC in patients under 18 years, and JUVÉDERM® VOLLURE™ XC and

JUVÉDERM® VOLBELLA™ XC in patients under 22 years has not been established

Use with caution in patients on immunosuppressive therapy
Patients who are using products that can prolong bleeding (such as aspirin, nonsteroidal anti-inflammatory drugs, and warfarin) may experience increased bruising or bleeding at treatment sites
If laser treatment, chemical peel, or any other procedure based on active dermal response is considered after treatment, or if these products are administered before the skin has healed completely, there is a possible risk of an inflammatory reaction at the treatment site

Patients who experience skin injury near the site of implantation may be at a higher risk for adverse events
The safety of JUVÉDERM® VOLUMA™ XC injectable gel for use in patients with very thin skin in the mid-face has not been established

Patients may experience late onset nodules with use of dermal fillers, including JUVÉDERM® VOLUMA™ XC
Patients may experience late onset adverse events with use of dermal fillers

ADVERSE EVENTS
The most commonly reported side effects for JUVÉDERM® injectable gels were injection-site redness, swelling, pain, tenderness, firmness, lumps/bumps, bruising, discoloration, and itching. For
JUVÉDERM® VOLBELLA™ XC, dryness was also reported. For JUVÉDERM® VOLUMA™ XC, side effects were predominantly moderate in severity, with duration of 2 to 4 weeks; for JUVÉDERM® Ultra XC,
JUVÉDERM® Ultra Plus XC, or JUVÉDERM® VOLLURE™ XC, they were mostly mild or moderate in severity, with duration of 14 days or less; and for JUVÉDERM® VOLBELLA™ XC, they were predominantly mild or moderate, with duration of 30 days or less.

To report an adverse reaction with any product in the JUVÉDERM® Collection, please call Allergan at 1-800-433-8871. Please visit JuvedermDFU.com for more information.

Products in the JUVÉDERM® Collection are available by prescription only.

Indication

LATISSE^® (bimatoprost ophthalmic solution) 0.03% is indicated to treat hypotrichosis of the eyelashes by increasing their growth, including length, thickness, and darkness.

Important Safety Information

Contraindications: LATISSE^® is contraindicated in patients with hypersensitivity to bimatoprost or to any of the ingredients.

Warnings and Precautions: In patients using LUMIGAN^® (bimatoprost ophthalmic solution) or other prostaglandin analogs for the treatment of elevated intraocular pressure (IOP), the concomitant use of LATISSE^® may interfere with the desired reduction in IOP. Patients using prostaglandin analogs including LUMIGAN^® for IOP reduction should only use LATISSE^® after consulting with their physician and should be monitored for changes to their intraocular pressure.

Increased iris pigmentation has occurred when bimatoprost solution was administered. Patients should be advised about the potential for increased brown iris pigmentation, which is likely to be permanent.

Bimatoprost has been reported to cause pigment changes (darkening) to periorbital pigmented tissues and eyelashes. The pigmentation is expected to increase as long as bimatoprost is administered, but has been

reported to be reversible upon discontinuation of bimatoprost in most patients.

There is the potential for hair growth to occur in areas where LATISSE^® solution comes in repeated contact with skin surfaces. Apply LATISSE^® only to the skin of the upper eyelid margin at the base of the eyelashes.

LATISSE^® solution should be used with caution in patients with active intraocular inflammation (eg, uveitis) because the inflammation may be exacerbated. LATISSE^® should be used with caution in aphakic patients, in pseudophakic patients with a torn posterior lens capsule, or in patients with known risk factors for macular edema.

Adverse Reactions: The most frequently reported adverse events were eye pruritus, conjunctival hyperemia, skin hyperpigmentation, ocular irritation, dry eye symptoms, and periorbital erythema. These reactions occurred in less than 4% of patients.

Postmarketing Experience: The following adverse reactions have been identified during postapproval use of LATISSE^®: dry skin of the eyelid and/or periocular area, eye swelling, eyelid edema, hypersensitivity (local allergic reactions), lacrimation increased, madarosis and trichorrhexis (temporary loss of a few eyelashes to loss of sections of eyelashes, and temporary eyelash breakage, respectively), periorbital and lid changes associated with a deepening of the eyelid sulcus, rash (including macular and erythematous), skin discoloration (periorbital), and vision blurred.

Please see LATISSE® full Prescribing Information.