Prabotulinum Toxin Type A

FDA Drug Information • Also known as: Jeuveau

Brand Names: Jeuveau
Drug Class: Acetylcholine Release Inhibitor [EPC], Neuromuscular Blocker [EPC]
Route: INTRAMUSCULAR
Dosage Form: POWDER
Product Type: HUMAN PRESCRIPTION DRUG

⚠ Boxed Warning (Black Box)

WARNING: DISTANT SPREAD OF TOXIN EFFECT The effects of all botulinum toxin products, including JEUVEAU, 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. JEUVEAU is not approved for the treatment of spasticity or any conditions other than glabellar lines. [ See Warnings and Precautions ( 5.1 ) ] WARNING: DISTANT SPREAD OF TOXIN EFFECT See full prescribing information for complete boxed warning. The effects of all botulinum toxin products, including JEUVEAU, 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. JEUVEAU is not approved for the treatment of spasticity or any conditions other than glabellar lines. ( 5.1 )

Description

11 DESCRIPTION PrabotulinumtoxinA-xvfs is an acetylcholine release inhibitor and a neuromuscular blocking agent. PrabotulinumtoxinA-xvfs is supplied as a sterile, vacuum-dried powder in a single-dose vial intended for intramuscular use after reconstitution. PrabotulinumtoxinA-xvfs is a 900 kDa botulinum toxin type A, produced from fermentation of Clostridium botulinum . The primary release procedure for JEUVEAU uses an animal based potency assay to determine the potency relative to a reference standard. The assay is specific to Evolus’ product, JEUVEAU. One Unit of JEUVEAU corresponds to the calculated median intraperitoneal lethal dose (LD 50 ) in mice. Due to specific details of this assay, Units of biological activity of JEUVEAU cannot be converted into Units of any other botulinum toxin or any toxin assessed with any other specific assay method. Each vial of JEUVEAU (prabotulinumtoxinA-xvfs) for injection contains 100 Units of botulinum toxin type A neurotoxin complex, human serum albumin (0.5 mg), and sodium chloride (0.9 mg) in a sterile, vacuum-dried form without a preservative.

What Is Prabotulinum Toxin Type A Used For?

1 INDICATIONS AND USAGE JEUVEAU 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. JEUVEAU is an acetylcholine release inhibitor and a 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 ( 1 )

Dosage and Administration

2 DOSAGE AND ADMINISTRATION Glabellar Lines Administration: 0.1 mL (4 Units) by intramuscular injection into each of five sites, for a total dose of 20 Units ( 2.2 , 2.3 ) 2.1 Instructions for Safe Use The potency Units of JEUVEAU (prabotulinumtoxinA-xvfs) 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 JEUVEAU cannot be compared to nor converted into units of any other botulinum toxin products assessed with any other specific assay method [ see Warnings and Precautions ( 5.2 ) and Description ( 11 ) ]. Retreatment of JEUVEAU should be administered no more frequently than every three months. Consideration of the cumulative dose is necessary when treating adult patients with JEUVEAU for glabellar lines if other botulinum toxin products are or have been used to treat other indications approved for those products. The safe and effective use of JEUVEAU depends upon proper storage of the product, selection of the correct dose, and proper reconstitution and administration techniques. Physicians administering JEUVEAU 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 ( 5.4 ) ]. 2.2 Preparation and Dilution Technique JEUVEAU is supplied in a single-dose 100 Unit vial. Prior to intramuscular injection, reconstitute each vacuum-dried vial of JEUVEAU with only sterile, preservative-free 0.9% Sodium Chloride Injection, USP 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 (see Table 1 ). Slowly inject the diluent into the vial. Discard the vial if a vacuum does not pull the diluent into the vial. Dispose of any unused saline. Gently mix JEUVEAU with 0.9% Sodium Chloride Injection USP by rotating the vial. JEUVEAU should be administered within 24 hours after reconstitution. During this time period, unused reconstituted JEUVEAU should be stored in a refrigerator between 2° to 8°C (36°F to 46°F) in the original carton to protect from light for up to 24 hours until time of use. Do not freeze reconstituted JEUVEAU. JEUVEAU vials are for single-dose only. After reconstitution, JEUVEAU should be used for only one injection session and for only one patient. Discard any remaining solution after administration. Table 1. Dilution Instructions for JEUVEAU Vials (100 Units) Diluent Preservative-free 0.9% Sodium Chloride Injection, USP Added to 100 Unit Vial Resulting Dose Units per 0.1 mL 2.5 mL 4 Units Reconstituted JEUVEAU should be clear, colorless, and free of particulate matter otherwise it should not be injected. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. 2.3 Administration Glabellar facial lines arise from the activity of the...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following serious adverse reactions are discussed in greater detail in other sections of the labeling:

Spread of Toxin Effects [ see Warnings and Precautions ( 5.1 ) ]

Hypersensitivity [ see Contraindications ( 4.1 ) and Warnings and Precautions ( 5.4 ) ]

Dysphagia and Breathing Difficulties [ See Warnings and Precautions ( 5.7 ) ] The most common adverse reactions are headache (12%), eyelid ptosis (2%), upper respiratory tract infection (3%), and increased white blood cell count (1%) ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Evolus at [1-877-386-5871] 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. In general, most adverse reactions occur within the first week following injection of JEUVEAU 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 syncope and 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 effect [ see Warnings and Precautions ( 5.1 ) ]. Glabellar Lines The adverse reactions below reflect exposure to JEUVEAU in the treatment of glabellar lines in placebo-controlled trials [ See Clinical Studies ( 14 ) ]. Table 2. Adverse Reactions Reported at Higher Frequency (≥1%) in the JEUVEAU Group Compared to the Placebo Group JEUVEAU EV-001, EV-002 N=492 n (%) PLACEBO EV-001, EV-002, N=162 n (%) Headache 57 (12%) 21 (13%) Eyelid Ptosis 8 (2%) 0 (0%) Upper Respiratory Tract Infection 13 (3%) 1 (1%) White blood cell count increase 6 (1%) 0 (0%) Two multi-center, open label, 1-year repeat dose safety trials, EV-004 [NCT02184988] and EV-006 [NCT02428608], were also conducted with JEUVEAU. Both trials evaluated repeat treatments of 20 units of JEUVEAU, up to a maximum total of 80 units, for the treatment of moderate to severe glabellar lines in adult subjects. Of the 922 subjects enrolled, the median number of treatments was three. The adverse events profile was similar to that reported in single dose trials. 6.2 Immunogenicity As with all therapeutic proteins, there is a potential for immunogenicity. The detection of antibody formation is 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 prabotulinumtoxinA-xvfs in the studies described below, with the incidence of antibodies in other studies, or to other products may be misleading. Treatment with botulinum toxins may result in the formation of antibodies that may reduce the effectiveness of subsequent treatments by inactivating biological activity of the toxin. Among 1,414 subjects treated with prabotulinumtoxinA-xvfs, 2 subjects were found to have pre-existing antibodies and 2 subjects had treatment-emergent antibodies.

Drug Interactions

7 DRUG INTERACTIONS No formal drug interaction studies have been conducted with JEUVEAU (prabotulinumtoxinA-xvfs) for injection. However, the potential for certain drugs to potentiate the effects of JEUVEAU 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 relaxant Closely observe patients receiving concomitant treatment of JEUVEAU and aminoglycosides or other agents interfering with neuromuscular transmission (e.g., curare-like agents), or muscle relaxants because JEUVEAU’s effect may be potentiated ( 7 )

Contraindications

4 CONTRAINDICATIONS

Hypersensitivity to any botulinum toxin preparation or to any of the components in the formulation ( 4.1 )

Infection at the injection site ( 4.2 ) 4.1 Known Hypersensitivity to Botulinum Toxin JEUVEAU 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 ( 5.4 ) ]. 4.2 Infection at the Injection Site(s) JEUVEAU is contraindicated in the presence of infection at the proposed injection site(s).

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary The limited available data on JEUVEAU use in pregnant women are insufficient to inform a drug associated risk of adverse developmental outcomes. An embryofetal developmental study conducted with JEUVEAU in pregnant rats revealed no treatment-related effects to the developing fetus when JEUVEAU was administered intramuscularly during organogenesis at doses up to 12 times the maximum recommended human dose (MRHD) ( see Data ). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In an embryofetal developmental study, intramuscular doses up to 4 Unit/kg JEUVEAU were administered to pregnant rats once daily during organogenesis (gestation days 6 to 16). No maternal or embryofetal toxicities were observed at doses up to 4 Unit/kg (12 times the MRHD of 20 Units, based on Unit/kg comparison).

Overdosage

10 OVERDOSAGE There is no information regarding overdose from clinical studies of JEUVEAU. Excessive doses of JEUVEAU (prabotulinumtoxinA-xvfs) 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 ( 5.1 ) ]. 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/ncidod/srp/drugs/formulary.html#1a.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING JEUVEAU (prabotulinumtoxinA-xvfs) for injection is a vacuum-dried powder supplied in a single-dose vial in the following size: 100 Units (NDC 72301-595-10) Storage Unopened vials of JEUVEAU should be stored in a refrigerator between 2° to 8°C (36° to 46° F) in the original carton to protect from light.

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.