incobotulinumtoxinA

Action and Spectrum

Actions and spectrum: 

incobotulinumtoxinA is a type of botulinum toxin used for therapeutic purposes, such as treating facial wrinkles, cervical dystonia, blepharospasm, and spasticity. It works by inhibiting the release of acetylcholine, which is a neurotransmitter that causes muscle contractions. 

More specifically, incobotulinumtoxinA selectively and reversibly binds to nerve terminals, where it blocks the release of acetylcholine from motor neurons.

This results in a temporary reduction in muscle activity and muscle relaxation, which can help alleviate symptoms associated with various conditions. The onset of action is typically within a few days of administration, and the effects can last for several months. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Cervical dystonia 

• Muscular weakness (7-11%) 
• Neck pain (7-15%) 
• Respiratory, mediastinal, and thoracic disorders (10-13%) 
• General disorders and administration site condition (11-16) 
• Infections and infestations (13-14%) 
• Dysphagia (13-18%) 
• Nervous system disorders (16-17%) 
• Musculoskeletal and connective tissue disorders (23-32%) 

Blepharospasm 

• Respiratory, thoracic, and mediastinal disorders (10-13%) 
• Visual impairment (12%) 
• Nervous system disorders (14%) 
• Dry eye (16%) 
• Xerostomia (16%) 
• Eyelid ptosis (19%) 

1-10% 

Chronic sialorrhea 

• Dry eye (3%) 
• Dysphonia (3%) 
• Fall (3%) 
• Back pain (3%) 
• Bronchitis (3%) 
• Hypertension (4%) 
• Dry mouth (4%) 
• Diarrhea (4%) 
• Tooth extraction (5%) 

Upper limb spasticity 

• Upper respiratory tract infection (2%) 
• Nasopharyngitis (2%) 
• Dry mouth (2%) 
• Seizure (3%) 

Cervical dystonia 

• Musculoskeletal pain (4-7%) 
• Neck pain (7%) 
• Muscular weakness (7%) 
• Injection site pain (9%) 

Blepharospasm 

• Respiratory tract infection (5%) 
• Dyspnea (5%) 
• Nasopharyngitis (5%) 
• Headache (7%) 
• Diarrhea (8%) 

Glabellar lines 

• Headache (5.4%) 

<1% 

• Injection site pain 
• Injection site swelling 
• Eye disorders 
• Blepharospasm 
• Injection site hematoma 
• Facial pain 
• Sensation of pressure 
• Eyelid edema 
• Eyelid ptosis 
• General disorders 

Post marketing Reports 

Allergic disorders: edema, Hypersensitivity, allergic dermatitis 

Gastroenterology: Nausea 

Local reactions:  injection site reaction, Injection site pain 

Musculoskeletal: muscle spasm, Muscular weakness, myalgia 

Infection: Herpes zoster 

Neurologic: dysphagia, Dysarthria 

Black Box Warning

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

incobotulinumtoxinA, like other botulinum toxin products, is contraindicated in patients with hypersensitivity to botulinum toxin or any of the components in the formulation. It is also contraindicated in patients with infection at the injection site(s) and in those with neuromuscular disorders i.e., myasthenia gravis. Additionally, it is contraindicated in individuals who are allergic to cow’s milk protein or human albumin. 

Caution: 

• Allergy or sensitivity: Individuals who have a known hypersensitivity to any botulinum toxin product or any of the excipients in incobotulinumtoxinA should not receive this medication. 
• Neuromuscular disorders: Caution should be taken in individuals with peripheral motor neuropathic diseases, such as Lambert-Eaton syndrome or myasthenia gravis. Patients with such conditions may have an increased risk of systemic effects. 
• Bleeding disorders: incobotulinumtoxinA should be used with caution in patients who have bleeding disorders, as this medication may increase the risk of bleeding at the injection site. 
• Pregnancy and breastfeeding: It is not known if incobotulinumtoxinA can harm a developing fetus or if it passes into breast milk, so caution should be taken in pregnant or breastfeeding individuals. 
• Medications: Caution should be taken when administering incobotulinumtoxinA to patients who are taking medications that interfere with neuromuscular transmission, such as aminoglycosides, spectinomycin, quinidine, and calcium channel blockers. 
• Injection site reactions: As with all injections, there is a risk of injection site reactions, such as swelling, bruising, pain, or redness. 

Comorbidities: 

• Muscle weakness or other conditions that affect muscle strength 
• Breathing difficulties or lung disease 
• Swallowing difficulties or problems with the gastrointestinal tract 
• Bleeding or clotting disorders 
• Infections or skin conditions at the injection site 
• Allergies or sensitivity to any of the ingredients in the medication 
• Pre-existing neurological or neuromuscular conditions such as Lambert-Eaton syndrome or myasthenia gravis 

Pregnancy / Lactation

Pregnancy consideration: pregnancy category C 

Lactation: safety and efficacy not established 

Pregnancy category: 

• Category A: Satisfactory and well-controlled studies show no risk to the fetus in the first or later trimester. 
• Category B: There is no evidence of risk to the fetus found in animal reproduction studies and there are not enough studies on pregnant women. 
• Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for an effect in humans, care must be taken for potential risks in pregnant women. 
• Category D: There is adequate data available with sufficient evidence of human fetal risk from various platforms, but despite potential risks may be used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh risks over benefits These category drugs should be prohibited for pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

incobotulinumtoxinA is a purified form of botulinum toxin type A, produced by the bacterium Clostridium botulinum. It acts by blocking the release of acetylcholine, a chemical neurotransmitter responsible for transmitting signals between nerves and muscles. By inhibiting acetylcholine release, incobotulinumtoxinA temporarily paralyzes the muscles at the injection site, leading to a reduction in muscle contractions and spasticity. 

incobotulinumtoxinA has a narrow therapeutic index, which means that the dose needed to produce the desired effect is very close to the dose that can cause toxic effects. Therefore, it is important to use this medication only as directed by a healthcare professional with expertise in its use.  

Pharmacodynamics: 

incobotulinumtoxinA is a neurotoxin that acts by blocking the release of neurotransmitter acetylcholine at the neuromuscular junction. This results in localized muscle paralysis and decreased muscle tone. The onset of action is typically within a few days, and the duration of effect can last up to several months. incobotulinumtoxinA has a dose-dependent effect, and its efficacy is influenced by the injection site, the amount of toxin injected, and the patient’s muscle tone. 

The specific mechanism of action of incobotulinumtoxinA involves its binding to receptors on the presynaptic nerve terminals, preventing the release of acetylcholine from the nerve endings. This leads to a reduction in the activity of the targeted muscles, resulting in a relaxation of the muscle fibers. 

incobotulinumtoxinA is used for both therapeutic and cosmetic purposes. Therapeutically, it is used to treat conditions such as cervical dystonia, blepharospasm, spasticity, and chronic migraine. Cosmetically, it is used to reduce the appearance of facial wrinkles, such as frown lines, forehead lines, and crow’s feet.  

Pharmacokinetics: 

Absorption 

After intramuscular injection, incobotulinumtoxinA is rapidly absorbed into the systemic circulation. The peak concentration is usually achieved within 1-2 weeks of injection. 

Distribution 

incobotulinumtoxinA is distributed to the peripheral neuromuscular junctions, where it exerts its pharmacological effect. 

Metabolism 

incobotulinumtoxinA is metabolized by proteases in the body, and the metabolites are eliminated through urine and feces. 

Elimination and excretion 

The elimination half-life of incobotulinumtoxinA is 3-4 months. It is eliminated through the kidneys as metabolites. 

Adminstartion

Administration: 

incobotulinumtoxinA is administered as an injection and acts locally at the injection site. The pharmacokinetics of incobotulinumtoxinA are dependent on the dose, injection technique, and site of injection.

Following intramuscular injection, the onset of action is observed within 2 to 3 days, with peak effect at 2 weeks and a duration of action ranging from 12 to 16 weeks. 

After injection, the toxin remains at the injection site and is taken up by nerve endings, where it inhibits the release of acetylcholine, resulting in muscle paralysis. The toxin is gradually degraded and eliminated by proteolytic enzymes. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: incobotulinumtoxinA 

Pronounced: [IN-koe-BOT-ue-LYE-num-TOX-in-A]  

Why do we use incobotulinumtoxinA? 

• Cervical dystonia: It is used to treat cervical dystonia, a condition which is characterized by the involuntary muscle contractions in the neck that causes abnormal movements and postures of the head and neck. 
• Blepharospasm: It is used to treat blepharospasm, a condition that causes involuntary spasms of the eyelid muscles. 
• Chronic migraine: It is used to prevent chronic migraine headaches. 
• Upper limb spasticity: It is used to treat upper limb spasticity in adults. 
• Strabismus: It is used to treat strabismus, a condition that causes misalignment of the eyes. 
• Hyperhidrosis: It is used to treat severe primary axillary hyperhidrosis (excessive sweating). 
• Facial wrinkles: It is used to treat forehead lines, frown lines, and crow’s feet. 
• Overactive bladder: It is used to treat overactive bladder, a condition characterized by urinary urgency, frequency, and incontinence.