LetibotulinumtoxinA-wlbg (Monograph)

Drug class: Botulinum toxins

Introduction

LetibotulinumtoxinA-wlbg is an acetylcholine release inhibitor and a neuromuscular blocking agent.

Uses for LetibotulinumtoxinA-wlbg

LetibotulinumtoxinA-wlbg has the following uses:

LetibotulinumtoxinA-wlbg 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.

LetibotulinumtoxinA-wlbg Dosage and Administration

General

LetibotulinumtoxinA-wlbg is available in the following dosage form(s) and strength(s):

For Injection: 50 Units or 100 Units freeze-dried powder in a single-dose vial for reconstitution.

Dosage

Adults

Dosage and Administration

• The potency units of letibotulinumtoxinA-wlbg for injection are specific to the preparation and assay utilized. They are not interchangeable with other preparations of botulinum toxin products and, therefore, units of biological activity of letibotulinumtoxinA-wlbg cannot be compared to nor converted into units of any other botulinum toxin products assessed with any other specific assay.

• Prior to IM injection, reconstitute each freeze-dried vial of the drug with the required amount of sterile, preservative-free 0.9% Sodium Chloride Injection, USP to achieve a reconstituted solution at a concentration of 4 Units/0.1 mL. Administer within 24 hours of reconstitution.

• The total recommended dose of letibotulinumtoxinA-wlbg is 20 Units per treatment session divided into five equal IM injections of 4 Units each (two injections in each corrugator muscle and one injection in the procerus muscle).

• LetibotulinumtoxinA-wlbg should be administered no more frequently than every 3 months. Consideration of the cumulative dose is necessary when treating adult patients with letibotulinumtoxinA-wlbg 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 letibotulinumtoxinA-wlbg depends upon proper storage of the product, selection of the correct dose, and proper reconstitution and administration techniques.

• See Full Prescribing Information for additional instructions on preparation and administration.

Cautions for LetibotulinumtoxinA-wlbg

Contraindications

• Patients with known hypersensitivity to any botulinum toxin preparation or to any of the components in the letibotulinumtoxinA-wlbg formulation.

• The presence of infection at the proposed injection site(s).

Warnings/Precautions

Warnings

Spread of Toxin Effects

Postmarketing safety data from other approved botulinum toxins suggest that botulinum toxin effects may 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, blurred vision 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. In unapproved uses and approved indications, symptoms consistent with spread of toxin effects have been reported at doses comparable to or lower than the maximum recommended total dose. LetibotulinumtoxinA-wlbg is not approved for any conditions other than glabellar lines. Patients or caregivers should be advised to seek immediate medical care if swallowing, speech or respiratory difficulties occur.

Lack of Interchangeability between Botulinum Toxin Products

The potency units of letibotulinumtoxinA-wlbg 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 letibotulinumtoxinA-wlbg cannot be compared to or converted into units of any other botulinum toxin products assessed with any other specific assay method.

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 botulinum toxin injections for unapproved uses. In these cases, the adverse reactions may have resulted from the administration of botulinum toxin products to the site of injection and/or adjacent structures. In several of the cases, patients had preexisting 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 botulinum toxin products.

Hypersensitivity Reactions

Serious and/or immediate hypersensitivity reactions have been reported for botulinum toxin products. These reactions include anaphylaxis, serum sickness, urticaria, soft tissue edema, and dyspnea. If such a reaction occurs, discontinue further injection of letibotulinumtoxinA-wlbg and immediately institute appropriate medical therapy.

Cardiovascular System Adverse Reactions

There have been reports following administration of botulinum toxins 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

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 typical doses of letibotulinumtoxinA-wlbg. Monitor patients with peripheral motor neuropathic diseases, amyotrophic lateral sclerosis, or neuromuscular junction disorders (e.g., myasthenia gravis or Lambert-Eaton syndrome) for increased neuromuscular compromise following botulinum toxin treatment.

Dysphagia and Dyspnea

Treatment with botulinum toxin products, including letibotulinumtoxinA-wlbg, can result in dysphagia and dyspnea including respiratory failure. These reactions can occur within hours to weeks after injection with botulinum toxin. Patients with preexisting dysphagia and dyspnea may be more susceptible to these complications. In most cases, this has been a consequence of weakening of muscles in the area of injection that are involved in breathing or oropharyngeal muscles that control swallowing or breathing.

Deaths as a complication of severe dysphagia have been reported after treatment with botulinum toxin products. Dysphagia may persist for several months. Patients treated with botulinum toxin products, including letibotulinumtoxinA-wlbg, may require immediate medical attention should they develop problems with swallowing, speech, or breathing. These reactions can occur within hours to weeks after injection with botulinum toxin.

Pre-existing Conditions at the Injection Site

Use caution when letibotulinumtoxinA-wlbg 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).

Use caution when letibotulinumtoxinA-wlbg treatment is used in patients who have marked facial asymmetry, with surgical alterations to the facial anatomy, pre-existing eyelid or eyebrow ptosis, when excessive weakness or atrophy is present in the target muscles, excessive dermatochalasis, deep dermal scarring, thick sebaceous skin (e.g., the inability to substantially lessen glabellar lines even by physically spreading them apart).

Ophthalmic Adverse Reactions in Patients Treated with Botulinum Toxin Products

Dry eye has been reported with the use of botulinum toxin products in the treatment of glabellar lines. Reduced tear production, reduced blinking, and corneal disorders may occur with use of botulinum toxins, including letibotulinumtoxinA-wlbg. If symptoms of dry eye (e.g., eye irritation, photophobia or visual changes) persist, consider referring patient 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 a remote risk for transmission of viral diseases and variant Creutzfeldt-Jakob disease (CJD). There is a theoretical risk for transmission of CJD, which would also be considered remote. No cases of transmission of viral diseases or CJD or vCJD have ever been identified for licensed albumin or albumin contained in other licensed products.

Specific Populations

Pregnancy

Available data from case reports with letibotulinumtoxinA-wlbg use in pregnant women are insufficient to identify a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Systemic exposure following intramuscular injection of letibotulinumtoxinA-wlbg was not assessed. In an animal reproduction study, intramuscular administration of letibotulinumtoxinA-wlbg to rats during pregnancy resulted in adverse effects on fetal growth (decreased fetal body weight and skeletal ossification) at maternally toxic doses 3 times the maximum recommended human dose (MRHD).

The 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.

Lactation

There are no data regarding the presence of letibotulinumtoxinA-wlbg in human or animal milk, its effects on the breastfed infant, or the effects on milk production. Systemic exposure following intramuscular injection of letibotulinumtoxinA-wlbg was not assessed. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for letibotulinumtoxinA-wlbg and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition.

Pediatric Use

The safety and effectiveness of letibotulinumtoxinA-wlbg in pediatric patients have not been established.

Geriatric Use

The 3 clinical trials of letibotulinumtoxinA-wlbg included 148 subjects 65 years of age and older. Although no clinically meaningful differences in safety or efficacy were observed between older and younger subjects, clinical studies of letibotulinumtoxinA-wlbg did not include sufficient numbers of subjects 65 years of age or older to determine whether they respond differently from younger subjects.

Common Adverse Effects

The most common adverse reaction is headache (2%).

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

No drug interaction studies have been conducted with letibotulinumtoxinA-wlbg. Certain drugs may potentiate the effects of letibotulinumtoxinA-wlbg which may result in excessive neuromuscular weakness and heighten systemic anticholinergic effects. Use caution with concurrent use of letibotulinumtoxinA-wlbg with the following products and monitor closely for excessive neuromuscular weakness:

• Aminoglycosides or other agents interfering with neuromuscular transmission

• Anticholinergic drugs

• Botulinum neurotoxin products administered as the same time or within several months of letibotulinumtoxinA-wlbg

• Muscle relaxants administered before or after administration of letibotulinumtoxinA-wlbg

Actions

LetibotulinumtoxinA-wlbg blocks cholinergic transmission at the neuromuscular junction by inhibiting the release of acetylcholine. When injected intramuscularly at therapeutic doses, letibotulinumtoxinA-wlbg is internalized into the nerve terminal, translocates into the neuronal cytosol where it cleaves SNAP25, a protein necessary for synaptic membrane docking and subsequent release of acetylcholine which produces a dose dependent decrease of muscle function. Recovery of muscle function is gradual due to degradation of the neurotoxin and formation of axonal sprouts. Muscle reinnervation occurs, leading to a slow reversal of the pharmacological effects of letibotulinumtoxinA-wlbg.

Advice to Patients

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

• Advise patients or caregivers to seek immediate medical care if swallowing, speech, or respiratory disorders arise or existing symptoms worsen.

• Advise patients 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.

• Inform patients that letibotulinumtoxinA-wlbg 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 healthcare provider.

Additional Information

AHFSfirstRelease™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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Frequently asked questions

• What is botulinum toxin used to treat?

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