DRUG INTERACTIONS-(summary)

 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. 

 DRUG INTERACTIONS(details)

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.

• Aminoglycosides or other agents interfering with neuromuscular transmission

• Anticholinergic drugs

• Botulinum neurotoxin products • Muscle relaxants

U.S.  APPROVED DRUGS SURING 2022                                        

Serial No 19

Name-                        DAXXIFY

Active Ingredient -   Dabotulinumtoixna- [anm

Pharmacological Classification- To Treat moderate to severe glabellar lines                                                                      associated with corrugation and/or procerus                                                                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.

ADVERSE REACTIONS-

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

CONTRAINDICATIONS-

 • Known hypersensitivity to any botulinum toxin preparation, DAXXIFY or any of the components in the DAXXIFY formulation

 • Infection at the injection sites

WARNING AND PRECAUTIONS-

 • The potency Units of DAXXIFY are not interchangeable with other preparations of other botulinum toxin products.

 • Spread of toxin effects, swallowing and breathing difficulties can lead to death. Seek immediate medical attention if respiratory, speech or swallowing difficulties occur.

 • 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.

 • Concomitant neuromuscular disorder may exacerbate clinical effects of treatment.

 • Use with caution in patients with compromised respiratory function or dysphagia.

 • Potential serious adverse reactions after administration of DAXXIFY for unapproved use. 

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.

DOSAGE FORMS AND STRENGTHS-

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

17 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

 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. 

 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. PI761127-0.8

 CLINICAL PHARMACOLOGY

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.

2. Pharmacodynamics -                                                                                                 No formal pharmacodynamics studies have been conducted with DAXXIFY.

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

 USE IN SPECIFIC POPULATION

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.

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.

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

4. Pediatric Use Safety and effectiveness of DAXXIFY in patients less than 18 years of age have not been established.

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. 

 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.

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