Xeomin (incobotulinumtoxinA)

Dosage of incobotulinumtoxinA is expressed in units of biologic activity; each unit is equivalent to the median intraperitoneal lethal dose (LD50) in mice. Assay methods used to determine potency of various botulinum toxin preparations are specific to each individual preparation; therefore, units of biologic activity of incobotulinumtoxinA cannot be compared with or converted to units of other botulinum toxin preparations.

Do not exceed the recommended maximum cumulative dose in a treatment session for any indication.

No dosing information is available for this tab.

No dosing information is available for this tab.

No dosing information is available for this tab.

No formal drug interaction studies have been conducted with incobotulinumtoxinA to date.

There are no contraindication interactions for this drug.

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Neuromuscular Blocking Agents/General Anesthetics (Inhl)

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: General anesthetics enhance the pharmacologic effects of nondepolarizing muscle relaxants.

CLINICAL EFFECTS: May see an increase in the neuromuscular blocking effects of the nondepolarizing muscle relaxant including respiratory depression, bradycardia, hypotension, flushing, or muscle weakness.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: It may be necessary to decrease the dose of the nondepolarizing muscle relaxant. Monitor neuromuscular function and adjust the dose of the nondepolarizing muscle relaxant accordingly.

DISCUSSION: Concomitant administration of general anesthetics and nondepolarizing muscle relaxants has been shown to produce synergistic neuromuscular blocking effects of nondepolarizing muscle relaxants.

Neuromuscular Blocking Agents/Misc Antibiotics

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Aminoglycosides, bacitracin, clindamycin, lincomycin, and polymyxins may enhance the pharmacologic effects of neuromuscular blocking agents.

CLINICAL EFFECTS: May see an increase in the pharmacologic effects of neuromuscular blocking agents, including prolonged respiratory depression and apnea.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: If it is necessary to administer these drugs concurrently, do so with extreme caution. Monitor neuromuscular function and adjust the dose of the neuromuscular blocking agent accordingly.

DISCUSSION: Concomitant administration of aminoglycosides, bacitracin, clindamycin, lincomycin, and polymixins with neuromuscular blocking agents has been shown to produce synergism of the effects on skeletal muscles. Concurrent administration of these drugs has been associated with prolonged respiratory depression, respiratory paralysis, and fatal apnea. The interaction usually occurs when the antibiotic is given prior to or concurrently with the neuromuscular blocking drug, but it may also occur when given after administration. Any antibiotic dosage or route of administration may produce respiratory depression.

Neuromuscular Blocking Agents/Quinine Derivatives

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Synergistic or additive pharmacologic activity.

CLINICAL EFFECTS: May see an increase in the neuromuscular blocking effects, including profound sedation, respiratory depression, coma, and/or death.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Avoid concurrent administration of neuromuscular blocking agents and quinine derivatives during the first several hours of postoperative period. If administered, respiratory support may be needed. If concurrent use is necessary, monitor patients for unusual dizziness or lightheadedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness.

DISCUSSION: Administration of quinidine during the immediate postoperative period has been associated with respiratory paralysis and apnea.

Moderate Interaction: Assess the risk to the patient and take action as needed.

Neuromuscular Blocking Agents/Lincosamides

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Lincosamides appear to augment the neuromuscular blocking effects of nondepolarizing muscle relaxants.

CLINICAL EFFECTS: The effects of nondepolarizing neuromuscular relaxants may be prolonged leading to profound sedation, respiratory depression, coma, and/or death.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Monitor respiratory function of the patient and provide the necessary support. In patients who have received nondepolarizing muscle relaxants, avoid use of lincosamides in the recovery room. If concurrent use is necessary, monitor patients for unusual dizziness or lightheadedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness.

DISCUSSION: Lincomycin has been reported to augment the neuromuscular blocking effect of pancuronium in seven anesthetized patients. The effect was readily antagonized by neostigmine administration. In a case report, clindamycin produced prolonged neuromuscular blockade in a patient who had received pancuronium. Neostigmine was ineffective in antagonizing the blockade.

Neuromuscular Blocking Agents/Polypeptide Antibiotics

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Synergistic pharmacologic activity. Polymyxin B affects neuromuscular transmission by blocking acetylcholine receptors. Its action is thus post-synaptic and the neuromuscular block has no antagonists. Polymyxin B causes neostigmine resistance to d-tubocurarine blockade and calcium resistance to the blockade evoked by aminoglycoside antibiotics (1,2,3,4). A pre-synaptic mechanism may also be involved with decreased release of acetylcholine.

CLINICAL EFFECTS: May see an increase in the neuromuscular blocking effects, including profound sedation, respiratory depression, coma, and/or death.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: If it is necessary to administer these drugs concurrently, do so with extreme caution. Monitor neuromuscular function and adjust the dose of the neuromuscular blocking agent accordingly. If concurrent use is necessary, monitor patients for unusual dizziness or lightheadedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness.

DISCUSSION: Concomitant administration of polypeptide antibiotics and neuromuscular blocking agents has been shown to produce synergism of the effects on skeletal muscles. Concurrent administration of these drugs has been associated with prolonged respiratory depression, respiratory paralysis, and apnea. This interaction has been documented with colistimethate, polymyxin B, bacitracin, and vancomycin.

Neuromuscular Blocking Agents/Trimethaphan

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Additive pharmacologic effects.

CLINICAL EFFECTS: May see an increase in the neuromuscular blocking effects, including profound sedation, respiratory depression, coma, and/or death.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: If it is necessary to administer these drugs concurrently, do so with extreme caution. Monitor neuromuscular function and adjust the dose of the neuromuscular blocking agent accordingly. If concurrent use is necessary, monitor patients for unusual dizziness or lightheadedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness.

DISCUSSION: Available data indicate that the neuromuscular blocking effects of tubocurarine and trimethaphan may be additive.

Select Neuromuscular Blocking Agents/Hydantoins

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: It has been suggested that phenytoin increases end-plate anticholinesterase activity, resulting in higher acetylcholine concentration at the neuromuscular junction.(1)

CLINICAL EFFECTS: A higher plasma concentration of the neuromuscular blocking agent was required to effect a given level of neuromuscular blockade in patients receiving phenytoin.(2,3)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Patients receiving hydantoin anticonvulsants should be monitored for a decreased response to the neuromuscular blocking agent. The dose of the neuromuscular blocking agent may need to be increased and/or given more frequently.(9)

DISCUSSION: In a study, patients receiving phenytoin were administered metocurine, attained 83% of maximum neuromuscular blockade compared with 98% in the control group.(1) In another study, patients maintained on phenytoin for more than one week had a significantly higher pancuronium requirement than those patients not receiving phenytoin.(1) In two separate case reports, patients maintained on phenytoin demonstrated a resistance to pancuronium and a decreased duration of neuromuscular blockade.(3,4) In a study, patients maintained on phenytoin and receiving vecuronium had a significantly shorter total duration and effect of neuromuscular blockade compared to those patients not receiving phenytoin.(5) In contrast, neither the effect nor duration of atracurium's neuromuscular blockade was affected by phenytoin.(5) Two in vitro studies showed that the neuromuscular blockade of curare and tubocurarine was potentiated by the use of phenytoin.(6,7) Ten children received a bolus dose of vecuronium 0.15mg/Kg while on phenytoin and showed a significantly increased clearance of vecuronium compared to the control group, 15.1 and 9.0 ml/Kg/min, respectively.(8) In a case report, a 58 year-old male previously stabilized on phenytoin (400 mg daily) was given an injection of vecuronium (8 mg) to induce muscle blockade during bowel surgery. While monitoring the effectiveness of vecuronium only 75% twitch height blockade was noted after seven minutes. The medication, due to its short duration and impaired effectiveness, had to be given more frequently throughout the surgery in order to maintain adequate muscle block.(9) A separate case report records a decreased response to pancuronium in a 15 year-old male, previously stabilized on phenytoin (350 mg daily), while undergoing surgery to remove a parietal tumor. Pancuronium (0.7 mg/kg) was given as a relaxant during the surgery and monitored using the train-of-four method. Intermittent doses of pancuronium (0.17 mg/kg) were given for the first hour of surgery without successful blockade apparent by the return of all four twitches within ten minutes of each dose. A second attempt at muscular blockade was made with continuous infusion atracurium (0.26-0.55 mg/kg/hour) for the duration of the surgery. Only 16 minutes after stopping the infusion, all four twitches were visible.(10)

*Known hypersensitivity (e.g., anaphylaxis, serum sickness, urticaria, soft tissue edema, dyspnea) to any botulinum toxin preparation or any ingredient (e.g., albumin, sucrose) in the formulation.

*Infection at injection site.

• Dyspnea
• Respiratory depression

• Amyotrophic lateral sclerosis
• Blepharoptosis
• Blurred vision
• Botulism
• Cerebral palsy-associated limb spasticity
• Dysarthria
• Dysphagia
• Eaton-lambert syndrome
• Muscle spasticity of cerebral origin
• Muscle spasticity of spinal origin
• Muscle weakness
• Myasthenia gravis
• Peripheral motor neuropathy
• Polyopia
• Urinary incontinence

• Predisposition to aspiration

The most common adverse effects occurring in at least 4% of adults with chronic sialorrhea receiving incobotulinumtoxinA were tooth extraction, dry mouth, diarrhea, and hypertension.

The most common adverse effects occurring in at least 1% of pediatric patients with chronic sialorrhea receiving incobotulinumtoxinA were bronchitis, headache, and nausea/vomiting.

The most common adverse effects occurring in at least 2% of adults with upper limb spasticity receiving incobotulinumtoxinA were seizure, nasopharyngitis, dry mouth, and upper respiratory tract infection.

The most common adverse effects occurring in at least 3% of pediatric patients with upper limb spasticity receiving incobotulinumtoxinA were nasopharyngitis and bronchitis.

The most common adverse effects occurring in at least 5% of patients with cervical dystonia receiving incobotulinumtoxinA were dysphagia, neck pain, muscle weakness, injection site pain, and musculoskeletal pain.

The most common adverse effects occurring in at least 10% of patients with blepharospasm receiving incobotulinumtoxinA were eyelid ptosis, dry eye, visual impairment, and dry mouth.

The most common adverse effect reported in more than 1% of individuals receiving incobotulinumtoxinA for cosmetic improvement of upper facial lines was injection site bruising.

More Frequent

• Dysphagia
• Dyspnea
• Hypertension
• Lagophthalmos
• Muscle weakness
• Seizure disorder

Less Frequent

• Accidental fall
• Diplopia
• Infection

Rare or Very Rare

• Acute respiratory distress syndrome
• Anaphylaxis
• Blinking decreased
• Botulism
• Dysarthria
• Ectropion
• General weakness
• Herpes zoster
• Hypersensitivity drug reaction
• Respiration changes
• Serum sickness
• Urinary incontinence

More Frequent

• Blepharoptosis
• Diarrhea
• Dry eye
• Headache disorder
• Injection site sequelae
• Neck pain
• Pharyngitis
• Upper respiratory infection
• Xerostomia

Less Frequent

• Allergic dermatitis
• Back pain
• Bronchitis
• Ecchymosis
• Eyelid edema
• Musculoskeletal pain
• Nausea
• Pruritus of skin
• Skin rash
• Visual changes
• Voice change
• Vomiting

Rare or Very Rare

• Blurred vision
• Edema
• Erythema
• Flu-like symptoms
• Muscle spasm
• Myalgia
• Urticaria

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Efficacy and safety of incobotulinumtoxinA have not been established in pediatric patients for the treatment of lower limb spasticity, cervical dystonia, and blepharospasm, or the temporary improvement in the appearance of upper facial lines.

Efficacy and safety of incobotulinumtoxinA for the treatment of chronic sialorrhea have not been established in pediatric patients <2 years of age. Use of incobotulinumtoxinA in pediatric patients 2 to 5 years of age is supported by evidence in pediatric patients >=6 years of age with chronic sialorrhea and by safety data in pediatric patients 2 to 5 years of age.

Efficacy and safety of incobotulinumtoxinA for the treatment of upper limb spasticity have not been established in pediatric patients <2 years of age.

There are no adequate and well-controlled clinical studies of incobotulinumtoxinA in pregnant women. In animal reproductive studies, an increased rate of abortion and embryotoxic effects (e.g., decreased fetal body weight, skeletal ossification) in relation to maternal toxicity were observed in rats and rabbits treated with incobotulinumtoxinA at dosages exceeding the maximum recommended human dose for cervical dystonia. IncobotulinumtoxinA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

It is not known whether incobotulinumtoxinA is distributed into human milk; its effects on the breastfed infant or on milk production are also unknown. Consider the developmental and health benefits of breastfeeding along with the mother's clinical need for incobotulinumtoxinA and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition.

In clinical studies of incobotulinumtoxinA in the treatment of chronic sialorrhea and upper limb spasticity, no differences in safety or effectiveness were observed between older and younger patients. Other clinical studies have not identified differences in responses between older and younger patients, but increased sensitivity in older patients cannot be ruled out.

In clinical studies of incobotulinumtoxinA for the treatment of cervical dystonia, the most common adverse events in patients 65 years of age and older were dysphagia and asthenia.

In clinical studies of incobotulinumtoxinA in the treatment of blepharospasm, no overall difference in effectiveness was observed between older and younger patients.

In clinical trials of incobotulinumtoxinA in the treatment of upper facial lines, the incidence of treatment-related adverse events was not increased in patients 65 years of age and older, but the trials did not include sufficient numbers of subjects 65 years of age and older to determine whether they respond differently from younger adults.