LetibotulinumtoxinA-Wlbg - An Overview

Drug Overview

LetibotulinumtoxinA-wlbg is a medication used to treat glabellar lines, which are the vertical frown lines that appear between the eyebrows. The effects of LetibotulinumtoxinA-wlbg typically last for several months, with most patients experiencing visible improvement for up to three to four months following treatment.

Common side effects may include temporary injection site reactions such as pain, redness, swelling, or bruising. More serious adverse effects are rare but may include muscle weakness or drooping eyelids. The FDA (U.S. Food and Drug Administration) approved it as a treatment drug for glabellar lines in 2024.

For Patients:

What Are the Clinical Indications for LetibotulinumtoxinA-Wlbg?

LetibotulinumtoxinA-Wlbg, akin to other formulations of botulinum toxin type A, is mainly prescribed to temporarily enhance the appearance of moderate to severe frown lines between the eyebrows.

What Is the Dosage of LetibotulinumtoxinA-Wlbg?

The dosage is 0.1 milliliters (ml), equivalent to 4 units, to be administered via intramuscular injection.

What Are the Things to Inform the Doctor Before Taking LetibotulinumtoxinA-Wlbg?

The patient must inform the doctor if they are on other medications before starting this drug. They should also inform them about the below-mentioned conditions:

• Pregnancy.

• Heart disease.

• Liver disease.

• Migraines.

• Seizures.

• Kidney diseases.

• Stroke.

• Cancer.

• Depression.

• Diabetes.

How Is LetibotulinumtoxinA-Wlbg Administered?

LetibotulinumtoxinA-wlbg is administered via intramuscular injection. The medication is typically reconstituted according to the manufacturer's instructions using a sterile, preservative-free saline solution. The injection is administered directly into the muscles that cause the formation of glabellar lines, typically at precise locations within these muscles, to achieve the best possible outcomes while reducing the chances of negative side effects.

What Are the Side Effects of LetibotulinumtoxinA-Wlbg?

Side effects of LetibotulinumtoxinA-wlbg may include:

• Injection site reactions (pain, redness, swelling).

• Headache.

• Eyelid drooping (ptosis).

• Muscle weakness.

• Dry mouth.

• Flu-like symptoms.

Missed Dose: It is advised to speak with the healthcare provider if a person has missed more than one dose or is unsure what to do. Healthcare workers can advise and suggest the best course of action.

Overdose: Too much LetibotulinumtoxinA-wlbg is administered, leading to neuromuscular weakness, causing various symptoms. Respiratory assistance may be necessary if excessive doses result in paralysis of the respiratory muscles. Signs of an overdose may not appear immediately after the injection. If an accidental injection or ingestion happens, or if an overdose is suspected, medical supervision is needed for several weeks to monitor for signs of systemic muscle weakness or paralysis.

Storage: Store unopened LetibotulinumtoxinA-wlbg vials in their original carton in a refrigerator at temperatures between two and eight degrees Celsius to shield them from light. Avoid freezing the vials.

For Doctors:

Indication:

LetibotulinumtoxinA-wlbg is a medication that inhibits the release of acetylcholine and blocks neuromuscular activity. It is used to temporarily enhance the appearance of moderate to severe glabellar lines caused by the activity of the corrugator and/or procerus muscles in adult patients.

Dose:

The dosage is 20 units per treatment session, distributed across five equal intramuscular injections of four units each. These injections typically involve two injections into each corrugator muscle and one injection into the procerus muscle.

Dosing Considerations:

• The potency units of LetibotulinumtoxinA-wlbg are unique to the preparation and assay used. They cannot be compared or converted into units of other botulinum toxin products assessed with different assays.

• LetibotulinumtoxinA-wlbg should be administered at most every three months.

• When treating adult patients with LetibotulinumtoxinA-wlbg for glabellar lines, the cumulative dose should be considered, especially if other botulinum toxin products have been used or are being used to treat other approved indications for those products.

Pharmacological Aspects of LetibotulinumtoxinA-Wlbg

Mechanism Of Action

• Inhibition of Acetylcholine Release: LetibotulinumtoxinA-wlbg contains botulinum toxin type A, a potent neurotoxin. Once bound, it impedes the release of acetylcholine, a neurotransmitter responsible for transmitting signals from nerve cells to muscle cells at the neuromuscular junction.

• Disruption of Nerve-Muscle Communication: LetibotulinumtoxinA-wlbg disrupts communication between nerves and muscles by inhibiting acetylcholine release. Normally, acetylcholine would bind to receptors on muscle cells, triggering muscle contraction. However, with its release inhibited, this signaling cascade is interrupted, preventing the muscle from receiving the message to contract.

• Temporary Muscle Paralysis: This interruption causes the targeted muscles to experience temporary paralysis. Without the ability to contract, the muscle activity responsible for causing wrinkles, such as glabellar lines (frown lines between the eyebrows), is significantly reduced or halted altogether.

• Reduction of Wrinkle Appearance: The temporary paralysis of targeted muscles relaxes the overlying skin, smoothing out wrinkles and lines caused by repetitive muscle contractions during facial expressions. In the case of glabellar lines, the diminished muscle activity results in a softening or disappearance of the frown lines between the eyebrows.

• Gradual Restoration of Muscle Function: While LetibotulinumtoxinA-wlbg induces temporary muscle paralysis, the effects are not permanent. Over several months, new nerve terminals develop, and the neuromuscular junctions regenerate, restoring muscle function. As a result, repeat injections may be necessary to maintain the desired cosmetic improvements.

Pharmacodynamics:

• Selective Action on Facial Muscles: LetibotulinumtoxinA-wlbg targets specific facial muscles, notably the corrugator and procerus muscles, which play crucial roles in facial expression dynamics. These muscles are particularly implicated in forming glabellar lines, the vertical wrinkles between the eyebrows associated with frowning or squinting.

• Blocking Muscle Contraction: LetibotulinumtoxinA-wlbg interacts with nerve terminals within the targeted muscles upon injection. It binds to specific proteins involved in neurotransmitter release, specifically acetylcholine, which is vital for initiating muscle contraction.

• Interference with Neuromuscular Communication: By interfering with the release of acetylcholine at the neuromuscular junction, LetibotulinumtoxinA-wlbg disrupts the normal signaling process between nerves and muscles. This disruption prevents the transmission of nerve impulses to the muscle, effectively blocking muscle contraction.

• Temporary Muscle Relaxation: LetibotulinumtoxinA-wlbg inhibits muscle contraction, resulting in temporary muscle relaxation. Consequently, the overlying skin in the treated area experiences reduced tension and movement, which contributes to smoothing out wrinkles and lines caused by repetitive muscle contractions.

• Reduction of Glabellar Lines: Specifically, in the case of glabellar lines, the temporary relaxation of the corrugator and procerus muscles leads to a visible reduction in the prominence of the vertical frown lines between the eyebrows. By preventing these muscles from contracting forcefully, LetibotulinumtoxinA-wlbg effectively diminishes the appearance of glabellar lines.

• Gradual Reversal of Effects: While the effects of LetibotulinumtoxinA-wlbg are temporary, typically lasting several months, muscle function gradually returns as the neuromuscular junctions regenerate and new nerve terminals form. Consequently, repeat treatments may be necessary to sustain the desired cosmetic improvements.

Pharmacokinetics:

• Absorption and Distribution: LetibotulinumtoxinA-Wlbg is taken up into the bloodstream from the injection site after injection into the muscle. From there, it is distributed throughout the body, reaching its target muscles, including the corrugator and procerus muscles responsible for glabellar lines.

• Onset of Action: The onset of LetibotulinumtoxinA-wlbg's action typically occurs within a few days to a week after injection. At first, there might be slight or subtle changes that are not very noticeable. However, during this period, the neurotoxin starts to block the release of acetylcholine at the neuromuscular junction, resulting in muscle relaxation.

• Peak Effects: The maximum effects of LetibotulinumtoxinA-wlbg are usually reached within two to four weeks after injection. During this time, the targeted muscles experience a significant reduction in activity, resulting in the visible smoothing of wrinkles and lines.

• Metabolism: LetibotulinumtoxinA-wlbg is metabolized locally within the injected muscles. The neurotoxin undergoes enzymatic degradation, breaking down its molecular structure and rendering it inactive.

• Elimination: After metabolism, the remnants of LetibotulinumtoxinA-wlbg are cleared from the body through normal physiological processes. The breakdown products are eventually eliminated via renal and hepatic pathways.

• Duration of Action: LetibotulinumtoxinA-wlbg's action varies among individuals but generally lasts several months. During this time, muscle relaxation and wrinkle reduction effects are sustained. However, as the neurotoxin gradually wears off and muscle activity resumes, the cosmetic improvements become less pronounced.

• Need for Repeat Injections: Due to the temporary nature of LetibotulinumtoxinA-wlbg's effects, repeat injections are often necessary to maintain the desired cosmetic outcomes. The timing of repeat treatments typically aligns with the gradual return of muscle function and the reappearance of wrinkles.

Clinical Studies and Efficacy:

Because clinical trials are conducted under different circumstances, the rates of adverse reactions observed in one drug's trials cannot be directly compared to those of another drug or reflect the rates observed in real-world clinical practice.

In the three Phase 3 clinical trials (BLESS I, II, and III) evaluating LetibotulinumtoxinA-wlbg for temporary improvement in moderate to severe glabellar lines, safety analyses included 911 out of 955 subjects who received a single 20 units dose of LetibotulinumtoxinA-wlbg and 310 out of 317 subjects who received a single dose of placebo.

What Are the Contraindications of LetibotulinumtoxinA-Wlbg?

LetibotulinumtoxinA-wlbg is contraindicated in the following cases:

• Individuals with a confirmed hypersensitivity to any botulinum toxin formulation or any constituents present in the LetibotulinumtoxinA-wlbg formulation.

• Patients who have an ongoing infection at the intended sites of injection.

Warnings and Precautions:

Spread of Toxin Effects:

• Postmarketing data from other botulinum toxin products suggests potential effects beyond the injection site, including symptoms like double vision, drooping eyelids, difficulty swallowing, changes in voice, speech difficulties, loss of bladder control, unclear vision, and respiratory problems.

• These symptoms, consistent with the mechanism of botulinum toxin action, may manifest hours to weeks after injection and could be life-threatening, with reports of fatalities related to toxin spread. Immediate medical attention should be sought if swallowing, speech, or breathing difficulties arise.

Lack of Interchangeability:

• LetibotulinumtoxinA-wlbg's potency units are specific to its formulation and assay method and cannot be compared or converted to those of other botulinum toxin products assessed using different assays.

Serious Adverse Reactions with Unapproved Use:

• Severe adverse effects, such as extreme weakness, difficulty swallowing, and pneumonia caused by inhaling food or liquid into the lungs, have been documented in patients who received botulinum toxin injections for purposes not approved by regulatory agencies. In some cases, these complications led to fatalities.

Hypersensitivity Reactions:

• Serious hypersensitivity reactions, such as anaphylaxis and serum sickness, have been reported for botulinum toxin products. Immediate medical therapy should be initiated if such reactions occur.

Cardiovascular System Adverse Reactions:

• Adverse conditions have been reported following botulinum toxin administration, some with fatal outcomes.

Dysphagia and Dyspnea:

• Treatment with LetibotulinumtoxinA-wlbg may lead to dysphagia, dyspnea, and respiratory failure, which can manifest within hours to weeks post-injection. Individuals with preexisting dysphagia and dyspnea may be at increased risk. Most of these complications are due to muscle weakening in the injected area or affecting oropharyngeal muscles controlling swallowing or breathing.

Severe dysphagia-related deaths have been reported post-botulinum toxin treatment, with dysphagia potentially lasting several months. Patients receiving LetibotulinumtoxinA-wlbg should promptly seek medical attention if they encounter swallowing, speech, or breathing difficulties within hours to weeks following the injection.

Pre-existing Conditions at the Injection Site:

• Exercise caution when administering LetibotulinumtoxinA-wlbg in the presence of inflammation at the intended injection sites or when excessive weakness or atrophy is evident in the targeted muscles.

Factors to Consider for Special Patient Populations:

• Special care is advised when treating patients with marked facial asymmetry, previous surgical modifications to facial anatomy, pre-existing eyelid or eyebrow ptosis, excessive weakness or atrophy in the target muscles, excessive dermatochalasis, deep dermal scarring, or thick sebaceous skin. These factors may affect treatment outcomes or pose increased risks.

Ophthalmic Adverse Reactions:

• Adverse ophthalmic reactions reported with LetibotulinumtoxinA-wlbg treatment include dry eye, reduced tear production, decreased blinking, and corneal disorders. Patients experiencing persistent dry eye symptoms such as eye irritation, photophobia, or visual changes should be referred to an ophthalmologist for evaluation.

Risk of Transmission of Viral Diseases:

• LetibotulinumtoxinA-wlbg contains albumin derived from human blood, posing a remote risk of viral disease transmission or variant Creutzfeldt-Jakob disease (CJD). While effective donor screening and product manufacturing processes mitigate this risk, no such transmissions have been identified with licensed albumin or albumin-containing products.

Specific Considerations

Pregnancy:

There is insufficient evidence from a limited number of case reports involving the use of LetibotulinumtoxinA-wlbg during pregnancy to ascertain the associated risk of significant birth defects, miscarriage, or other adverse outcomes for both the mother and the fetus. The systemic exposure following the intramuscular injection of LetibotulinumtoxinA-wlbg was not evaluated. Animal reproduction studies demonstrated adverse effects on fetal growth, including decreased fetal body weight and skeletal ossification, at maternally toxic doses equivalent to three times the maximum recommended human dose (MRHD).

Lactation:

There is no available data on the presence of LetibotulinumtoxinA-wlbg in human or animal milk, its effects on the breastfed infant, or its impact on milk production. Systemic exposure following intramuscular injection of LetibotulinumtoxinA-wlbg has not been evaluated. Healthcare providers should assess the clinical need for LetibotulinumtoxinA-wlbg in lactating mothers against potential risks to the breastfed infant or the underlying maternal condition.

Pediatric Use:

The safety and efficacy of LetibotulinumtoxinA-wlbg in pediatric patients have not been established.

Geriatric Use:

While clinical trials of LetibotulinumtoxinA-wlbg included a subset of subjects aged 65 and older, no clinically significant differences in safety or efficacy were noted between older and younger subjects. However, the number of older subjects enrolled in these trials needed to be increased to determine whether they responded differently from younger subjects.