--------DRUG INTERACTIONS---------------------- Aminoglycoside antibiotics, anticholinergic agents or any other agents that interfere with neuromuscular transmission may potentiate the effect of DAXXIFY; co-administer only with caution and close observation. (7) See 17 for PATIENT COUNSELING INFORMATION and Medication Guide

BRIEF SUMMARY-

DAXXIFY- (Sep 2022)

Indn- To Treat moderate to severe glabellar lines associated with Corrugator and /or process  muscular activity  

Comp-  For injection: 50 Units or 100 Units sterile lyophilized powder in a single-dose vial.   Glabellar Lines: 0.1 mL (8 Units) by intramuscular injection into each of five sites, for a total dose of 40 Units.

ADR- The most commonly observed adverse reactions (=1%) are headache (6%), eyelid ptosis (2%) and facial paresis (1%).

Ci-  Known hypersensitivity to any botulinum toxin preparation, DAXXIFY or any of the components in the DAXXIFY formulation (4.1) • Infection at the injection sites (4.2

Pat inform-

Swallowing, Speaking or Breathing Difficulties, or other Unusual Symptoms-Advise patients or caregivers to seek immediate medical care if swallowing, speech or respiratory disorders arise or existing symptoms worsen. 

Ability to Operate Machinery or Vehicles-                                                                        Advise patients if they develop any unusual symptoms such as loss of strength, muscle weakness, blurred vision, or drooping eyelids occur, they should avoid driving a car or engaging in other potentially hazardous activities.

Ophthalmic Adverse Reaction-                                                                               Inform patients that DAXXIFY injection may cause eye dryness. Advise patients to report symptoms of eye dryness (e.g., eye pain, eye irritation, photosensitivity, or changes in vision) to their doctor.

===================================================================

U.S.  APPROVED DRUGS SURING 2022                                        

Serial No 19

Name-                        DAXXIFY

Active Ingredient -   Daxibotulinumtoxina -lanm

Pharmacological Classification- To Treat moderate to severe glabellar lines                                                                   associated with Corrugator and /or process                                                                   muscular activity   

                                                                                                                                             Date of Approval-         9/7 /2022   

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use DAXXIFY safely and effectively. See full prescribing information for DAXXIFY. DAXXIFY™ (daxibotulinumtoxinA-lanm) for injection, for intramuscular use

Initial U.S. Approval: 2022

WARNING: DISTANT SPREAD OF TOXIN EFFECT See full prescribing information for complete boxed warning.

The effects of DAXXIFY 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. DAXXIFY is not approved for the treatment of spasticity or any conditions other than glabellar lines.

INDICATIONS AND USAGE

 DAXXIFY is an acetylcholine release inhibitor and neuromuscular blocking agent 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.

DOSAGE AND ADMINISTRATION

 Glabellar Lines: 0.1 mL (8 Units) by intramuscular injection into each of five sites, for a total dose of 40 Units. (2)

DOSAGE FORMS AND STRENGTHS

 For injection: 50 Units or 100 Units sterile lyophilized powder in a single-dose vial. (3) --

CONTRAINDICATIONS

 • Known hypersensitivity to any botulinum toxin preparation, DAXXIFY or any of the components in the DAXXIFY formulation (4.1) • Infection at the injection sites (4.2

ADVERSE REACTIONS

 The most commonly observed adverse reactions (=1%) are headache (6%), eyelid ptosis (2%) and facial paresis (1%).

---------------WARNING AND PRECAUTIONS--------------- • The potency Units of DAXXIFY are not interchangeable with other preparations of other botulinum toxin products. (5.2, 11) • Spread of toxin effects, swallowing and breathing difficulties can lead to death. Seek immediate medical attention if respiratory, speech or swallowing difficulties occur. (5.1) • Adverse event reports have been received involving the cardiovascular system with botulinum toxin products, some with fatal outcomes. Use caution when administering to patients with pre-existing cardiovascular disease. (5.5) • Concomitant neuromuscular disorder may exacerbate clinical effects of treatment. (5.6) • Use with caution in patients with compromised respiratory function or dysphagia. (5.7) • Potential serious adverse reactions after administration of DAXXIFY for unapproved use. (5.3)

--------------------ADVERSE REACTIONS---------------------- The most commonly observed adverse reactions (=1%) are headache (6%), eyelid ptosis (2%) and facial paresis (1%). (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Revance Therapeutics, Inc. at 1-877-373-8669 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. ------------

--------DRUG INTERACTIONS---------------------- Aminoglycoside antibiotics, anticholinergic agents or any other agents that interfere with neuromuscular transmission may potentiate the effect of DAXXIFY; co-administer only with caution and close observation. (7) See 17 for PATIENT COUNSELING INFORMATION and Medication Guide

PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Swallowing, Speaking or Breathing Difficulties, or other Unusual Symptoms-

Advise patients or caregivers to seek immediate medical care if swallowing, speech or respiratory disorders arise or existing symptoms worsen. [see Warnings and Precautions (5.7)]

Ability to Operate Machinery or Vehicles-

Advise patients if they develop any unusual symptoms such as loss of strength, muscle weakness, blurred vision, or drooping eyelids occur, they should avoid driving a car or engaging in other potentially hazardous activities.

Ophthalmic Adverse Reaction-

 Inform patients that DAXXIFY injection may cause eye dryness. Advise patients to report symptoms of eye dryness (e.g., eye pain, eye irritation, photosensitivity, or changes in vision) to their doctor. [see Warnings and Precautions (5.9)]

Manufactured by: Revance Therapeutics, Inc. Newark, CA 94560 U.S. License Number 2101 © 2022 Revance Therapeutics, Inc. DAXXIFY is a trademark of Revance Therapeutics, Inc.

CLINICAL PHARMACOLOGY 12.1 Mechanism of Action DAXXIFY blocks cholinergic transmission at the neuromuscular junction by inhibiting the release of acetylcholine. When injected into skeletal muscle, DAXXIFY is internalized into the nerve terminal, translocates into the neuronal cytosol where it cleaves SNAP25, a protein necessary for synaptic vesicle membrane docking and subsequent release of acetylcholine which produces a dose dependent decrease of muscle function. Recovery of activity is gradual and results from the degradation of neurotoxin light chain in the neurons with a contribution from the formation of axonal sprouts. Muscle reinnervation occurs, leading to a slow reversal of the pharmacological effects of DAXXIFY.

12.2 Pharmacodynamics No formal pharmacodynamics studies have been conducted with DAXXIFY. 12.3 Pharmacokinetics Using currently available analytical technology, it is not possible to detect DAXXIFY in the peripheral blood following intramuscular injection at the recommended dose. Reference ID: 5042005 13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term stud

DRUG INTERACTIONS No formal drug interaction studies have been conducted with DAXXIFY. However, the potential for certain drugs to potentiate the effects of DAXXIFY warrant consideration given the potential risks involved and should be used with caution. Reference ID: 5042005 • Aminoglycosides or other agents interfering with neuromuscular transmission • Anticholinergic drugs • Botulinum neurotoxin products • Muscle relaxants 8 USE IN SPECIFIC POPULATION 8.1 Pregnancy Risk Summary There are no available data on DAXXIFY use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies, intramuscular administration of DAXXIFY during pregnancy resulted in adverse effects on fetal growth (decreased fetal body weight and skeletal ossification) at maternally toxic doses approximately equivalent to 40 times the maximum recommended human dose (MRHD) (see Data). The background risk of major birth defects and miscarriage for the indicated population is unknown. 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. Data Animal Data Embryofetal development studies were conducted in rats and rabbits with DAXXIFY. For comparison of animal to human doses based on a body weight comparison, the MRHD is set at 40 Units/subject (0.67 Units/kg for an average 60 kg subject). Intramuscular administration of DAXXIFY (3, 10 or 30 Units/kg) to pregnant rats four times during the period of organogenesis (on gestation days 7, 10, 13, and 16) caused decreased fetal body weight and decreased fetal skeletal ossification at the highest dose, which was associated with maternal toxicity. No embryofetal developmental toxicity was noted at doses up to 10 Units/kg which is 15 times the MRHD. Intramuscular administration of DAXXIFY (0.02, 0.1, 0.48 or 2.4 Units/kg/day) to pregnant rabbits during the period of organogenesis (total of 13 doses) resulted in maternal lethality at 2.4 Units/kg/day and significant decreased maternal body weight at 0.48 Units/kg/day. No embryofetal developmental toxicity was noted at doses up to 0.48 Units/kg/day which is approximately equivalent to the MRHD. 8.2 Lactation Risk Summary There are no data on the presence of DAXXIFY 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 DAXXIFY and any potential adverse effects on the breastfed infant from DAXXIFY or from the underlying maternal condition. 8.4 Pediatric Use Safety and effectiveness of DAXXIFY in patients less than 18 years of age have not been established. 8.5 Geriatric Use Among the 406 subjects treated with DAXXIFY in the placebo-controlled clinical trials, 36 subjects were 65 years or older. There was no increase in the incidence of treatment-related adverse events in patients over 65 years treated with DAXXIFY. Clinical studies of DAXXIFY did not include sufficient numbers of subjects Reference ID: 5042005 aged 65 and older to determine whether they responded differently from younger subjects. [see Clinical Studies (14)] 10 OVERDOSAGE Excessive doses of DAXXIFY may be expected to produce neuromuscular weakness with a variety of symptoms. Respiratory support may be required where excessive doses cause paralysis of the respiratory muscles. In the event of overdose, the patient should be medically monitored for symptoms or excessive muscle weakness or muscle paralysis. [see Warnings and Precautions (5.6), (5.7)] Symptomatic treatment may be necessary. Symptoms of overdose are not likely 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 toxininduced 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 y

If you do not receive a response within 30 minutes, please contact the CDC directly at 1-770-488-7100.