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Botulinum toxin is a potent neurotoxin produced by the bacterium Clostridium botulinum. There are seven distinct serotypes of botulinum toxin; types A and B have been developed for clinical use. The potency units of botulinum toxin products are specific to the preparation and assay method utilized. They are not interchangeable and, therefore, units of biological activity of one botulinum toxin product cannot be compared or converted into units of any other botulinum toxin products. Botulinum toxin injections cause muscle paralysis by acting at the peripheral nerve endings to block release of the neurotransmitter acetylcholine.

Four botulinum toxin agents are commercially available in the United States. Three of these, onabotulinum toxin A (Botox®, Botox® Cosmetic), abobotulinum toxin A (Dysport®), and incobotulinum toxin A (Xeomin®), are serotype A agents. One agent, rimabotulinum toxin B (Myobloc®) is a serotype B preparation.

Onabotulinum toxin A (Botox®) is FDA-approved for the following indications:

• Treatment of cervical dystonia in adult patients, to reduce the severity of abnormal head position and neck pain.
• Treatment of strabismus and blepharospasm associated with dystonia, including benign essential blepharospasm or VII (facial) nerve disorders in patients 12 years of age and above.
• Treatment of upper limb spasticity in adult patients, to decrease the severity of increased muscle tone in elbow, wrist, finger, and thumb flexors.
• Treatment of lower limb spasticity in adult patients, to decrease the severity of increased muscle tone in ankle and toe flexors.
• Prophylaxis of headaches in adult patients with chronic migraine (>15 days per month with headache lasting 4 hours a day or longer).
• Treatment of severe primary axillary hyperhidrosis that is inadequately managed with topical agents in adult patients.
• Treatment of urinary incontinence due to detrusor overactivity associated with a neurologic condition [e.g., spinal cord injury (SCI), multiple sclerosis (MS)] in adults who have an inadequate response to or are intolerant of an anticholinergic medication.
• Treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency, in adults who have an inadequate response to or are intolerant of an anticholinergic medication.

Onabotulinum toxin A (Botox® Cosmetic) is FDA-approved for the following indications:

• Temporary improvement in the appearance of moderate to severe glabellar lines associated with corrugator and/or procerus muscle activity in adult patients.
• Temporary improvement in the appearance of moderate to severe lateral canthal lines associated with orbicularis oculi activity in adult patients.
• Temporary improvement in the appearance of moderate to severe forehead lines associated with frontalis muscle activity in adult patients.

Abobotulinum toxin A (Dysport®) is FDA-approved for the following indications:

• Treatment of cervical dystonia in adults.
• Treatment of spasticity in adult patients.
• Treatment of lower limb spasticity in pediatric patients 2 years of age and older.
• Temporary improvement in the appearance of moderate to severe glabellar lines associated with procerus and corrugator muscle activity in adult patients less than 65 years of age.

Incobotulinum toxin A (Xeomin®) is FDA-approved for the following indications:

• Treatment of cervical dystonia in adults, in both botulinum toxin-naïve and previously treated patients.
• Treatment of blepharospasm in adult patients.
• Treatment of upper limb spasticity in adult patients.
• Temporary improvement in the appearance of moderate to severe glabellar lines associated with corrugator and/or procerus muscle activity in adult patients.
• Treatment of chronic sialorrhea in adult patients.

Rimabotulinum toxin B (Myobloc®) is FDA-approved for treatment of cervical dystonia in adult patients, to reduce the severity of abnormal head position and neck pain.

I.   Abobotulinum Toxin A (Dysport®) Initial Review

Abobotulinum toxin A (Dysport^®) may be considered MEDICALLY NECESSARY AND APPROPRIATE when ALL of the following criteria are met: 

• Diagnosis of ONE of the following:
  • Blepharospasm associated with dystonia, including benign essential blepharospasm or VII (facial) nerve disorders, in a patient 12 years of age or older; OR
  • Cervical dystonia (spasmodic torticollis; applicable whether congenital, due to child birth injury, or traumatic injury) AND BOTH of the following:
    1. Cervical dystonia must be associated with sustained head tilt or abnormal posturing with limited range of motion in the neck; AND
    2. History of recurrent involuntary contraction(s) of one or more of the muscles of the neck (e.g., sternocleidomastoid, splenius, trapezius, or posterior cervical muscles); OR
  • Hemifacial spasm; OR
  • Spasticity associated with ONE of the following conditions:
    1. Cerebral palsy; OR
    2. Stroke; OR
  • Spasticity of the lower limb; OR
  • Spasticity of the upper limb;

AND

• No FDA labeled contraindications to therapy (see table 1 below); AND
• Dose is within the FDA labeled dose for labeled indications or supported in literature for additional indications (see table 2 below). 

II.   Abobotulinum Toxin A (Dysport®) Renewal Review

Abobotulinum toxin A (Dysport^®) may be considered MEDICALLY NECESSARY AND APPROPRIATE when ALL of the following criteria are met:

• Previously approved for therapy through the initial review process; AND
• Abobotulinum toxin A treatment has resulted in a reduction of symptom severity and/or frequency from baseline (prior to therapy); AND
• No FDA labeled contraindications to therapy (see table 1 below); AND
• Dose is within FDA labeled dose for labeled indications or supported in literature for additional indications (see table 2 below). 

III.  Incobotulinum Toxin A (Xeomin®) Initial Review

Incobotulinum toxin A (Xeomin^®) may be considered MEDICALLY NECESSARY AND APPROPRIATE when ALL of the following criteria are met:

• Diagnosis of ONE of the following:
  • Blepharospasm associated with dystonia, including benign essential blepharospasm or VII (facial) nerve disorders, in a patient 18 years of age or older ; OR

1. Cervical dystonia must be associated with sustained head tilt or abnormal posturing with limited range of motion in the neck; AND
2. History of recurrent involuntary contraction(s) of one or more of the muscles of the neck (e.g., sternocleidomastoid, splenius, trapezius, or posterior cervical muscles); OR
   • Spasticity of the upper limb; OR
   • Chronic sialorrhea AND ONE of the following:
     1. Failed one conventional agent prerequisite (e.g., oral hyoscine, atropine drops, glycoprrolate, or amitriptyline); OR
     2. Documented intolerance, FDA labeled contraindication, or hypersensitivity to at least one conventional agent;

AND

• No FDA labeled contraindications to therapy (see table 1 below); AND

• Dose is within the FDA labeled dose for labeled indications (see table 2 below; AND
• For commercial health plan members only, step therapy supplement criteria may apply for select conditions (see policy II-242: Step Therapy Supplement).

IV.  Incobotulinum Toxin A (Xeomin®) Renewal Review

Incobotulinum toxin A (Xeomin^®) may be considered MEDICALLY NECESSARY AND APPROPRIATE when ALL of the following criteria are met:

• Previously approved for therapy through the initial review process; AND
• Incobotulinum toxin A treatment has resulted in a reduction of symptom severity and/or frequency from baseline (prior to therapy); AND
• No FDA labeled contraindications to therapy (see table 1 below); AND
• Dose is within the FDA labeled dose for labeled indications (see table 2 below). 

V.   Onabotulinum Toxin A (Botox®) Initial Review

Onabotulinum toxin A (Botox^®) may be considered MEDICALLY NECESSARY AND APPROPRIATE when ALL of the following criteria are met: 

• Diagnosis of ONE of the following:
  • Blepharospasm associated with dystonia, including benign essential blepharospasm or VII (facial) nerve disorders, in a patient 12 years of age or older; OR
  • Cervical dystonia (spasmodic torticollis; applicable whether congenital, due to child birth injury, or traumatic injury) AND BOTH of the following:
    1. Cervical dystonia must be associated with sustained head tilt or abnormal posturing with limited range of motion in the neck; AND
    2. History of recurrent involuntary contraction(s) of one or more of the muscles of the neck (e.g., sternocleidomastoid, splenius, trapezius, or posterior cervical muscles); OR
  • Chronic anal fissures AND the following:
    1. Failed one conventional therapy (e.g., bulking agents, sitz baths, laxatives, dietary changes, or 0.4% intra-anal nitroglycerin); OR
  • Chronic migraine headache in a patient 18 years of age or older AND ALL of the following:
    1. 15 or more headache days (headaches last 4 hours or more per day) per month for at least 3 months, with ≥50% of headaches being migraine/probable migraine; AND
    2. Evaluated for and does not have medication overuse headache; AND
    3. ONE of the following:
       • Failed one conventional agent prerequisite from at least two of the following classes; antidepressants (e.g., amitriptyline, venlafaxine), calcium channel or beta blockers (e.g., propranolol, metoprolol, bisoprolol, verapamil), antiepileptics (e.g., topiramate, valproic acid), and calcitonin gene-related peptides (CGRPs) (e.g. erenumab, fremanezumab, galcanezumab); OR
       • Documented intolerance, FDA labeled contraindication, or hypersensitivity to conventional agents from at least two of the following classes; antidepressants (e.g., amitriptyline, venlafaxine), calcium channel or beta blockers (e.g., propranolol, metoprolol, bisoprolol, verapamil), antiepileptics (e.g., topiramate, valproic acid), and calcitonin gene-related peptites (CGRPs) (e.g. erenumab, fremanezumab, galcanezumab); OR
  • Dystonia associated with ONE of the following conditions:
    1. Focal upper limb dystonia (e.g., organic writer's cramp); OR
    2. Oromandibular dystonia (e.g., orofacial dyskinesia, jaw-closing dystonia, Meige syndrome); OR
    3. Laryngeal dystonia (adductor spasmodic dysphonia); OR
    4. Idiopathic (primary or genetic) torsion dystonia; OR
    5. Symptomatic (acquired) torsion dystonia; OR
  • Esophageal achalasia AND ONE of the following:
    1. Failed to respond to pneumatic dilation or myotomy; OR
    2. Not a good candidate for pneumatic dilation or myotomy; OR
  • Facial synkinesis; OR
  • Hemifacial spasm; OR
  • Overactive bladder AND ALL of the following:
    1. Symptoms of urge urinary incontinence, urgency, and frequency; AND
    2. Conservative therapies including bladder training, pelvic floor muscle exercises, and fluid management have been inadequate; AND
    3. ONE of the following:
       • Failed two conventional agent prerequisites, including one anticholinergic agent (e.g., oxybutynin, tolterodine, trospium, darifenacin, solifenacin, or fesoterodine) AND mirabegron; OR
       • Documented intolerance, FDA labeled contraindication, or hypersensitivity to at least one anticholinergic agent AND mirabegron. OR
  • Palmar or axillary hyperhidrosis AND ONE of the following:
    1. Failed aluminum chloride 20% solution; OR
    2. Documented intolerance, FDA labeled contraindication, or hypersensitivity to aluminum chloride 20% solution; OR
  • Sialorrhea AND ONE of the following:
    1. Failed one conventional agent prerequisite (e.g., oral hyoscine, atropine drops, glycoprrolate, or amitriptyline); OR
    2. Documented intolerance, FDA labeled contraindication, or hypersensitivity to at least one conventional agent; OR
  • Spasticity associated with ONE of the following conditions:
    1. Cerebral palsy; OR
    2. Stroke; OR
    3. Acquired spinal cord or traumatic brain injury; OR
    4. Hereditary spastic paraplegia; OR
    5. Spastic hemiplegia; OR
    6. Neuromyelitis optica; OR
    7. Multiple sclerosis; OR
    8. Schilder's disease; OR
  • Spasticity of the lower limb; OR
  • Spasticity of the upper limb; OR
  • Strabismus, including persistent cranial VI nerve palsy of one month or longer, in a patient 12 years of age or older AND ALL of the following:
    1. Inadequate response to corrective lenses; AND
    2. Inadequate response to any other additional, patient appropriate, conservative corrective therapies (e.g., exercises); AND
    3. Good vision in both eyes; AND
    4. Eye movements are not restricted; AND
    5. Small to moderate angle of esotropia; AND
    6. Potential for the patient to experience binocular vision; OR
  • Urinary incontinence due to detrusor overactivity associated with a neurologic condition (e.g., spinal cord injury, multiple sclerosis) AND ONE of the following:
    1. Failed two conventional agent prerequisites, including one anticholinergic agent (e.g., oxybutynin, tolterodine, trospium, darifenacin, solifenacin, or fesoterodine) AND mirabegron; OR
    2. Documented intolerance, FDA labeled contraindication, or hypersensitivity to at least one anticholinergic agent AND mirabegron;

AND

• No FDA labeled contraindications to therapy (see table 1 below); AND

• Dose is within the FDA labeled dose for labeled indications or supported in literature for additional indications (see table 2 below); AND
• For commercial health plan members only, step therapy supplement criteria may apply for select conditions (see policy II-242: Step Therapy Supplement).

VI.  Onabotulinum Toxin A (Botox®) Renewal Review

Onabotulinum toxin A (Botox^®) may be considered MEDICALLY NECESSARY AND APPROPRIATE when ALL of the following criteria are met:

• Previously approved for therapy through the initial review process; AND
• ONE of the following:
  • Diagnosis of chronic migraine headache AND ONE of the following:
    1. Onabotulinum toxin A treatment has resulted in a reduction of 7 or more headache days per month from baseline (prior to therapy); OR
    2. Onabotulinum toxin A treatment has resulted in a reduction of 100 or more headache hours per month from baseline (prior to therapy); OR
  • Another diagnosis AND onabotulinum toxin A treatment has resulted in a reduction of symptom severity and/or frequency from baseline (prior to therapy);

AND

• No FDA labeled contraindications to therapy (see table 1 below); AND
• Dose is within the FDA labeled dose for labeled indications or supported in literature for additional indication (see table 2 below).

VII. Rimabotulinum Toxin B (Myobloc®) Initial Review

Rimabotulinum toxin B (Myobloc®) may be considered MEDICALLY NECESSARY AND APPROPRIATE when ALL of the following criteria are met:

• Diagnosis of ONE of the following:
  • Cervical dystonia (spasmodic torticollis; applicable whether congenital, due to child birth injury, or traumatic injury) AND BOTH of the following:
    1. Cervical dystonia must be associated with sustained head tilt or abnormal posturing with limited range of motion in the neck; AND
    2. History of recurrent involuntary contraction(s) of one or more of the muscles of the neck (e.g., sternocleidomastoid, splenius, trapezius, or posterior cervical muscles); OR
  • Chronic Sialorrhea AND ONE of the following:
    1. Failed one conventional agent prerequisite (e.g., oral hyoscine, atropine drops, glycoprrolate, or amitriptyline); OR
    2. Documented intolerance, FDA labeled contraindication, or hypersensitivity to at least one conventional agent;

AND

• No FDA labeled contraindications to therapy (see table 1 below); AND
• Dose is within the FDA labeled dose for labeled indications or supported in literature for additional indications (see table 2 below); AND
• For commercial health plan members only, step therapy supplement criteria may apply for select conditions (see policy II-242: Step Therapy Supplement).
  

VIII. Rimabotulinum Toxin B (Myobloc®) Renewal Review

Rimabotulinum toxin B (Myobloc^®) may be considered MEDICALLY NECESSARY AND APPROPRIATE when ALL of the following criteria are met:

• Previously approved for therapy through the initial review process; AND
• Rimabotulinum toxin B treatment has resulted in a reduction of symptom severity and/or frequency from baseline (prior to therapy); AND
• No FDA labeled contraindications to therapy (see table 1 below); AND
• Dose is within the FDA labeled dose for labeled indications or supported in literature for additional indications (see table 2 below).

IX.  Cosmetic Indications

The use of abobotulinum toxin A, incobotulinum toxin A, onabotulinum toxin A, or rimabotulinum toxin B is considered COSMETIC for the treatment of glabellar lines or wrinkles and other indications solely to improve appearance.

X.   Experimental/Investigative Indications  

All other uses of abobotulinum toxin A, incobotulinum toxin A, onabotulinum toxin A, or rimabotulinum toxin B are considered EXPERIMENTAL/INVESTIGATIVE, including but not limited to the following conditions, due to the lack of clinical evidence demonstrating an impact on improved health outcomes:

• Bell's palsy
• Benign prostatic hyperplasia
• Chronic low back pain
• Chronic motor tic disorder, and tics associated with Tourette syndrome (motor tics)
• Depressive disorders
• Detrusor sphincteric dyssynergia
• Essential tremor
• Facial wound healing
• Gastroparesis
• Headaches, except as noted above for chronic migraine headache
• Hirschsprung's disease
• Internal anal sphincter (IAS) achalasia
• Interstitial cystitis
• Joint pain
• Lateral epicondylitis
• Mechanical neck disorders
• Myofascial pain syndrome
• Neuropathic pain after neck dissection
• Pain after hemorrhoidectomy or lumpectomy
• Prevention of pain associated with breast reconstruction after mastectomy
• Raynaud's disease/Raynaud's phenomenon
• Tinnitus
• Trigeminal neuralgia

Table 1.  FDA Labeled Contraindications

Table 2.  Dosing

Onabotulinum Toxin A (Botox) Dosing (1 unit = 1 billable unit)

For one or more indications, unless otherwise stated below, the maximum cumulative dose for onabotulinum toxin A (Botox®) is 400 units every 12 weeks.

Abobotulinum Toxin A (Dysport) Dosing (5 units = 1 billable unit)

For one or more indications, unless otherwise stated below, the maximum cumulative dose for abobotulinum toxin A (Dysport®) is 1,000 units every 12 weeks.

Rimabotulinum Toxin B (Myobloc) Dosing (100 units = 1 billable unit)

For one or more indications, unless otherwise stated below, the maximum cumulative dose for rimabotulinum toxin B (Myobloc®) is 10,000 every 12 weeks.

Incobotulinum Toxin A (Xeomin) Dosing (1 unit = 1 billable unit)

For one or more indications, unless otherwise stated below, the maximum cumulative dose for incobotulinum toxin A (Xeomin®) is 400 units every 12 weeks.

Documentation Submission

Documentation supporting the medical necessity criteria described in the policy must be included in the prior authorization. In addition, the following documentation must also be submitted:

Initial Review

1. Clinical notes describing the diagnosis and clinical features of the diagnosis.
2. Clinical notes describing current and past treatments for the diagnosis, including response to the treatments. For onabotulinum toxin A (Botox^®) requests to treat chronic migraine headache, clinical notes should include evaluation for potential medication overuse headache.
3. The dose being requested, including the patient's weight if the requested botulinum toxin agent and diagnosis require weight-based dosing. If the requested dose is higher or more frequent than the dosing guidelines provided above, a clear explanation for the medical necessity of the requested dose MUST be submitted, including prior dosing (strength and frequency) associated with inadequate response.
4. For commercial health plan members only, when step therapy requirements apply for the requested indication, documentation for one or more of the step therapy supplement criteria MUST be provided (see policy II-242).
   

Renewal Review

1. Documentation of prior approval for the requested botulinum toxin agent through the initial review process.
2. Documentation supporting reduction of symptom severity and/or frequency from baseline. For onabotulinum toxin A (Botox^®) requests to treat chronic migraine headache, include information from the medical record and/or headache diary/log entries quantifying a reduction in migraine frequency or duration compared to baseline.
3. Clinical notes describing current and past treatments for the diagnosis, including response to the treatments.
4. The dose being requested, including the patient's weight if the requested botulinum toxin agent and diagnosis require weight-based dosing. If the requested dose is higher or more frequent than the dosing guidelines provided above, a clear explanation for the medical necessity of the requested dose MUST be submitted, including prior dosing (strength and frequency) associated with inadequate response.

Link to Pre-Authorization Form:  https://www.bluecrossmn.com/sites/default/files/DAM/2020-01/X21916R02_Botulinum%2BToxin_Pre-Auth_Request_Form.pdf