Usual Adult Dose for Sialorrhea

Total dose per treatment session: 100 Units via intra-salivary gland injection as follows:

• Parotid gland: 30 Units per side
• Submandibular gland 20 Units per side

Total of 4 injections per treatment session

Comments:

• Injection should be into the parotid and submandibular glands on both sides. The dose is divided with a ratio of 3 to 2 between the parotid and submandibular glands.
• Product labeling provides an illustration and directions for locating salivary glands using anatomic landmarks.
• A cumulative dose for any indication should not exceed 400 Units in a treatment session.
• Repeat treatment should be individualized, but no sooner than every 16 weeks.

Use: For the treatment of chronic sialorrhea.

Usual Adult Dose for Upper Limb Spasticity

Individualize dose based on size, number, and location of muscles to be treated, severity of spasticity, presence of local muscle weakness and patient's response to prior treatment.

• For botulinum toxin-naive patients: Initial dosing should begin at the low end of the dosing range and titrated as necessary

Suggested Dosing Ranges:
CLENCHED FIST:

• Flexor digitorum superficialis: 25 to 100 Units; (2 injection sites per muscle)
• Flexor digitorum profundus: 25 to 100 Units; (2 injection sites per muscle)

FLEXED WRIST:

• Flexor carpi radialis: 25 to 100 Units; (1 to 2 injection sites per muscle)
• Flexor carpi ulnaris: 20 to 100 Units; (1 to 2 injection sites per muscle)

FLEXED ELBOW:

• Brachioradialis: 25 to 100 Units; (1 to 3 injection sites per muscle)
• Biceps: 50 to 200 Units; (1 to 4 injection sites per muscle)
• Brachialis: 25 to 100 Units; (1 to 2 injection sites per muscle)

PRONATED FOREARM:

• Pronator quadratus: 10 to 50 Units; (1 injection site per muscle)
• Pronator teres: 25 to 75 Units; (1 to 2 injection sites per muscle)

THUMB-IN-PALM:

• Flexor pollicis longus: 10 to 50 Units; (1 injection site per muscle)
• Adductor pollicis: 5 to 30 Units; (1 injection site per muscle)
• Flexor pollicis brevis/Opponens pollicis: 5 to 30 Units; (1 injection site per muscle)

Comments:

• Maximum total recommended dose: Up to 400 Units per treatment session
• Repeat treatment should be no more frequent than every 12 weeks; most patients in clinical trials were retreated between 12 and 14 weeks.

Use: For the treatment of upper limb spasticity

Usual Adult Dose for Cervical Dystonia

Initial total dose: 120 Units

• Injections are usually into the sternocleidomastoid, levator scapulae, splenius capitis, scalenus, and/or the trapezius muscle(s); however, any of the muscles responsible for controlling head position may require treatment

Subsequent doses: Individualize dose based on number and location of muscles to be treated, degree of spasticity/dystonia, muscle mass, body weight, and response to any previous treatment

Comments:

• In a study of initial doses of 120 or 240 Units, no meaningful difference in effectiveness was demonstrated between the doses.
• Frequency of repeat treatments should be determined by clinical response, but should generally be no more frequent than every 12 weeks.

Use: For the treatment of adults with cervical dystonia.

Usual Adult Dose for Blepharospasm

Initial dose (treatment-naive): 50 Units (25 Units per eye)
Initial dose (previously treated with a botulinum toxinA): Use past dose, response to treatment, duration of effect, and adverse event history to determine dose

TOTAL dose should not exceed 100 Units (50 Units/eye)

• Frequency of repeat treatments should be determined by clinical response, but generally no more frequent than every 12 weeks

Comments:

• Injections are into the lateral and medial orbicularis oculi muscle of the upper lid; lateral canthus and the lateral orbicularis oculi muscle of the lower lid; and the corrugator muscle, if needed.
• The number and location of injections may be changed in response to adverse reactions or based on response to treatment.
• See product labeling for diagram of injection sites.

Use: For the treatment of blepharospasm.

Usual Adult Dose for Glabellar Lines

20 Units per treatment session divided into 5 equal IM injections of 4 Units each:

• Two injections in each corrugator muscle
• One injection in the procerus muscle

Retreatment should be no more frequently than every 3 months

Comments:

• See product labeling for diagram of injection sites.

Use: For temporary improvement in the appearance of moderate to severe glabellar lines associated with corrugator and/or procerus muscle activity.

Usual Pediatric Dose for Upper Limb Spasticity

2 years and older:

• Individualize dose based on the size, number and localization of muscles involved, severity of spasticity, and presence of local muscle weakness.
• Maximum recommended total dose: 8 Units/kg divided among affected muscles, up to a maximum dose of 200 Units per single upper limb, or 16 Units/kg up to a maximum of 400 Units if both upper limbs are treated

Suggested Dosing Ranges:
FLEXED ELBOW:

• Brachioradialis: 1 to 2 Units/kg; Maximum: 50 Units (1 to 2 injection sites per muscle)
• Biceps: 2 to 3 Units/kg; Maximum: 75 Units (1 to 3 injection sites per muscle)
• Brachialis: 1 to 2 Units/kg; Maximum 50 Units; (1 to 2 injection sites per muscle)

FLEXED WRIST:

• Flexor carpi radialis: 1 Unit/kg; Maximum: 25 Units (1 injection site per muscle)
• Flexor carpi ulnaris: 1 Unit/kg; Maximum: 25 Units (1 injection site per muscle)

PRONATED FOREARM:

• Pronator quadratus: 0.5 Units/kg; Maximum: 12.5 Units (1 injection site per muscle)
• Pronator teres: 1 to 2 Units/kg; Maximum: 50 Units (1 to 2 injection site per muscle)

CLENCHED FIST:

• Flexor digitorum superficialis: 1 Unit/kg; Maximum: 25 Units (1 injection site per muscle)
• Flexor digitorum profundus: 1 Unit/kg; Maximum: 25 Units (1 injection site per muscle)

THUMB-IN-PALM:

• Flexor pollicis longus: 1 Unit/kg; Maximum: 25 Units (1 injection site per muscle)
• Adductor pollicis: 0.5 Units/kg; Maximum: 12.5 Units (1 injection site per muscle)
• Flexor pollicis brevis/Opponens pollicis: 0.5 Units/kg; Maximum: 12.5 Units (1 injection site per muscle)

Comments:

• Localization of the involved muscles with techniques such as electromyographic guidance, nerve stimulation, or ultrasound is recommended.
• Frequency of repeat treatments should be determined by clinical response, but generally no more frequent than every 12 weeks

Use: For the treatment of upper limb spasticity in pediatric patients 2 years or older, excluding spasticity caused by cerebral palsy.

Usual Pediatric Dose for Sialorrhea

2 years or older: A total of 4 injections per treatment session; ultrasound imaging is recommended to guide needle placement into the salivary glands; dosed by body weight with a ratio of 3 to 2 between the parotid and submandibular glands:

• Weight: 12 to less than 15 kg: Total dose 20 units (parotid gland: 6 Units per side; submandibular gland 4 Units per side)
• Weight: 15 to less than 19 kg: Total dose 30 units (parotid gland: 9 Units per side; submandibular gland 6 Units per side)
• Weight: 19 to less than 23 kg: Total dose 40 units (parotid gland: 12 Units per side; submandibular gland 8 Units per side)
• Weight: 23 to less than 27 kg: Total dose 50 units (parotid gland: 15 Units per side; submandibular gland 10 Units per side)
• Weight: 27 to less than 30 kg: Total dose 60 units (parotid gland: 18 Units per side; submandibular gland 12 Units per side)
• Weight: 30 kg or more: Total dose 75 units (parotid gland: 22.5 Units per side; submandibular gland 15 Units per side)

Comments:

• This drug has not been studied in children weighing less than 12 kg.
• Product labeling provides an illustration and directions for locating salivary glands using anatomic landmarks.
• A cumulative dose for any indication should not exceed 400 Units in a treatment session.
• Repeat treatment should be individualized, but no sooner than every 16 weeks.

Use: For the treatment of chronic sialorrhea in pediatric patients 2 years or older.

Renal Dose Adjustments

No adjustment recommended

Liver Dose Adjustments

No adjustment recommended

Precautions

US BOXED WARNINGS: DISTANT SPREAD OF TOXIN EFFECT

• Postmarketing reports indicate the effects of this drug and all botulinum toxin effects may spread from the area of injection to produce symptoms consistent with botulinum toxin effects. These may include asthenia, generalized muscle weakness, diplopia, blurred vision, ptosis, dysphagia, dysphonia, dysarthria, urinary incontinence, 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. The risk is probably greatest in children treated for spasticity but symptoms can occur in adults treated for spasticity and other conditions, particularly those patients who have underlying conditions that would predispose them to these symptoms. In unapproved uses, including spasticity in children, and in approved indications, cases of spread of effect have been reported at doses comparable to those used to treat cervical dystonia and at lower doses.

CONTRAINDICATIONS:

• Hypersensitivity to any botulinum toxin product or any product excipients
• Infection at the proposed injection sites

Safety and effectiveness have not been established in pediatric patients younger than 18 years for lower limb spasticity, cervical dystonia, blepharospasm, or glabellar frown lines. Safety and effectiveness have not been established in pediatric patients younger than 2 years for any indication.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• For intramuscular or intra-salivary gland injection only
• Maximum cumulative dose for any indication should not exceed 400 Units in a treatment session
• Safe and effective use depends upon selection of the correct dose, dilution, and proper administration techniques; see product labeling for indication specific administration recommendations
• Prior to administration the physician should be familiar with the anatomy and any alterations to the anatomy due to prior surgical procedures of the patient
• If injection sites are marked with a pen, the product should not be injected through the pen marks; otherwise a permanent tattooing effect may occur
• Care should be exercised when injecting at sites close to sensitive structures, such as the carotid artery, lung apices and esophagus
• Care should be taken to ensure that the product is not injected into a blood vessel
• This drug should be used with caution if bleeding disorders occur in patients receiving anticoagulant therapy or taking other substances in anticoagulant doses
• Localization of the involved muscles with electromyographic guidance or nerve stimulation techniques may be useful.

Storage requirements:

• Unopened vials: May be stored at room temperature, refrigerated, or in freezer; do not use after expiration date on label
• Once reconstituted, store in refrigerator at 2 to 8 degrees C (36 to 46 degrees F) and use within 24 hours; discard unused portion
• Vials should be used for 1 injection session and 1 patient only

General:

• Potency Units of incobotulinumtoxinA are specific to preparation and assay method utilized; botulinum toxins are not interchangeable.
• When initiating treatment, the lowest recommended dose should be used.
• Standard electromyographic techniques are required for treatment of strabismus, upper or lower limb spasticity, and may be useful for the treatment of cervical dystonia.
• Median onset of effect occurs within 7 days of injection; typical duration is up to 12 to 16 weeks, although the duration of effect may vary in individual patients.

Monitoring:

• Monitor for distant spread of toxin

Patient advice:

• Read the US FDA-approved patient labeling (Medication Guide).
• Patients and caregivers should be instructed to inform their healthcare provider if they develop any unusual symptoms or if any existing symptoms worsen; they should be instructed to seek immediate medical attention if they have trouble swallowing, speaking, or breathing; patients should understand the risk of aspiration.
• Patients experiencing loss of strength, muscle weakness, blurred vision, dizziness, or drooping eyelids should avoid engaging in potentially hazardous activities including driving.
• Patients should understand that this drug may cause reduced blinking and they should consult with their healthcare provider if eye pain or irritation develops following treatment.

Frequently asked questions

• What is botulinum toxin used to treat?