Oscar Botulinum Toxin (CG033) Form

Botulinum toxins are a class of injectable medications that block the nerves responsible for controlling muscle function.

The paralysis of targeted muscles typically occurs within 2 to 5 days after administration and can last for 2 to 3 months. There are seven different types (A-G) of Botulinum toxin, but only types A and B are approved for clinical use:

• There are currently five botulinum toxin preparations available in the US, including:
  • four type A preparations (abobotulinumtoxinA [Dysport®], daxibotulinumtoxinA-lanm [Daxxify®], incobotulinumtoxinA [Xeomin®], and onabotulinumtoxinA [Botox®, Botox® Cosmetic])
  • one type B preparation (rimabotulinumtoxinB [Myobloc®])
• Botulinum toxin preparations must be prescribed and administered by a licensed physician or medical provider.

Botulinum toxins have pharmacological uses in the treatment of various medical conditions characterized by muscle spasms or overactivity, such as cerebral palsy, stroke, and spinal cord disorders. In these conditions, Botulinum toxins are used to reduce muscle tone, relieve pain, and improve functional1ability. Botulinum toxins are also used to treat other conditions, such as chronic migraine, hyperhidrosis, and strabismus.

Botulinum toxins can also be used for cosmetic purposes, such as decreasing wrinkles, but such use is not considered medically necessary by the Plan. In cosmetic applications, Botulinum toxins are used to reduce the appearance of wrinkles by relaxing the muscles responsible for facial expressions. The effects of cosmetic Botulinum toxin injections typically last for 3 to 4 months.

NOTE: The Plan may require the use of preferred medications as the first-line treatment. Please refer to the following applicable Plan Clinical Guideline for a comprehensive list of our preferred and non- preferred drugs on the medical benefit:

1. Commercial Preferred Physician-Administered Specialty Drugs (CG052).
2. Botulinum Toxins - Medical Benefit Preferred Physician-Administered Drug Exceptions Criteria (CG088).

Definitions

Achalasia is a failed relaxation of the lower esophageal sphincter resulting in painful spasms and/or regurgitation of food.

Blepharospasm refers to uncontrolled blinking or spasms of the eyelids.

Botulinum Toxins refer to the seven serologically distinct neurotoxins derived from the bacterium Clostridium botulinum. These agents differ in their synthesis and the specific bacterium strain from which they are isolated. Botulinum toxins function by inhibiting acetylcholine release at the neuromuscular junction to cause flaccid paralysis of muscles.

Cervical Dystonia (also known as Spasmodic Torticollis) refers to painful contraction of the neck muscles causing twisting or tilting of the head to one side.

Chronic anal fissure is a tear in the skin of the anus that persists for more than 8 weeks.

Chronic migraine is a type of migraine headache that occurs at least 15 days per month for more than three months.

Detrusor Hyperactivity (also known as Bladder Overactivity) refers to spasms of the bladder muscles resulting in pain or incontinence.

Detrusor sphincter dyssynergia (DSD) is a medical condition that affects the coordination between the bladder and the muscles around the urethra, which is called the external urinary sphincter.

Essential tremors is a neurological disorder characterized by involuntary shaking or trembling movements, usually affecting the arms and hands but sometimes involving the head and other parts of the body.

Hyperhidrosis refers to inappropriate, excessive sweating.

Hemifacial spasms is a neurological disorder characterized by involuntary contractions of the facial muscles on one side of the face.

Hyperhidrosis Disease Severity Scale (HDSS) is a tool used to assess the severity of hyperhidrosis, a condition characterized by excessive sweating beyond what is necessary for regulating body temperature. The HDSS is a simple and quick questionnaire that consists of only one question and is rated on a scale from 1 to 4:

1. No interference with daily activities
2. Noticeable but not causing interference with daily activities
3. Some interference with daily activities
4. Severe interference with daily activities

The HDSS is used by healthcare professionals to determine the impact of hyperhidrosis on a patient's quality of life and to guide treatment decisions. Patients with HDSS scores of 3 or 4 are considered to have severe hyperhidrosis and may require more aggressive treatment options, such as prescription antiperspirants, oral medications, or minimally invasive procedures like botulinum toxin injections or iontophoresis. Patients with HDSS scores of 1 or 2 may benefit from less invasive treatments like topical antiperspirants or lifestyle modifications.

Lower extremity Refers to the leg, knee, ankle, and foot.

Muscle Spasms refer to the involuntary contractions of one or more muscles.

Neurogenic refers to a condition or disorder that is caused by or related to problems with the nervous system.

Oromandibular dystonias (OMD) refer to a group of neurological movement disorders that affect the muscles of the jaw, mouth, and face. OMD can cause involuntary muscle contractions that result in abnormal movements and postures, such as jaw clenching, teeth grinding, lip pursing, or tongue protrusion.

Oromandibular dystonias (OMD) can be classified into several types based on the location and pattern of muscle contractions, including jaw-opening, jaw-closing, or mixed OMD.

"Overactive bladder" is a condition in which the muscles in the bladder contract involuntarily and cause a sudden urge to urinate.

"Prophylaxis" is a preventative treatment intended to stop or reduce the recurrence of a disease or condition.

"Sialorrhea" (also known as "Ptyalism") refers to excess salivation or drooling.

"Spasmodic dysphonia" is a neurological disorder that affects the muscles of the voice box, causing spasms and interruptions in speech.

"Spasticity" is a condition characterized by increased muscle tone, which can cause stiffness, spasms, or involuntary movements.

"Strabismus" is a vision disorder in which the eyes are not properly aligned and point in different directions.

"Temporomandibular disorders (TMD)" refer to a group of conditions that affect the temporomandibular joint (TMJ) and the muscles of the jaw and face.

"Upper extremity" refers to the arm, shoulder, and hand.

"Urge incontinence" is a type of urinary incontinence characterized by the sudden, strong urge to urinate that is followed by an involuntary loss of urine.

"Urinary incontinence" is a condition in which a person cannot control their bladder, leading to the involuntary loss of urine.

"Urodynamic testing" is a medical diagnostic procedure that evaluates how well the lower urinary tract (including the bladder and urethra) is functioning. The test measures various parameters, such as bladder pressure, urine flow rate, and capacity, to help diagnose conditions that affect the urinary system, such as incontinence, urinary tract obstruction, or nerve or muscle problems.

Clinical Indications

Medical Necessity Criteria for Initial Authorization

OnabotulinumtoxinA (Botox) (J0585)

The Plan deems OnabotulinumtoxinA (Botox) medically necessary for the following indications if the disease-specific criteria for initial requests are met (refer to Continued Care for reauthorization criteria or Table 1 for standard initial/retreatment authorization durations):

1. Achalasia, when BOTH of the following are met:
   • The request is by a provider specialist who will administer botulinum toxin (e.g., gastroenterologist, endoscopist, ENT); and
   • Documented evidence of ALL of the following
     • Confirmed diagnosis with esophageal manometry; and
     • Alternative causes of the symptoms (e.g., esophageal stricture, carcinoma, schatzki's ring, or extrinsic compression), have been ruled out by upper endoscopy and/or adequately treated; and
     • Presence of progressive dysphagia to solids and liquids; and
     • ONE of the following:
       1. Pneumatic dilation or surgical myotomy (i.e., laparoscopic Heller myotomy, or peroral endoscopic myotomy (POEM)) has been attempted but was unsuccessful; or
       2. The member was not a good candidate for the procedure; or
       3. The member refused treatment/surgery.
2. Axillary hyperhidrosis or palmar hyperhidrosis, when ALL of the following are met:
   • The request is by a provider specialist who will administer botulinum toxin (e.g., dermatologist, neurologist); and
   • The member is 18 years of age or older; and
   • Documented evidence of ALL of the following
     • Severe hyperhidrosis, defined as ONE of the following:
       1. a score of 3 or 4 on the Hyperhidrosis Disease Severity Scale; or
       2. The impact of excessive sweating on quality of life has been significant, causing interference with daily activities (e.g., social, professional) and leading to feelings of anxiety and embarrassment; and
     • Alternative causes of the symptoms (e.g., hyperthyroidism, lifestyle factors), have been ruled out or adequately treated; and
     • The member is unable to use, or has tried and failed first-line management with BOTH of the following:
       1. lifestyle measures such as avoiding known triggers and tight clothing; and
       2. using antiperspirants (e.g., aluminum chloride hexahydrate).
3. Blepharospasm, when ALL of the following are met:
   • The request is by a provider specialist who will administer botulinum toxin (e.g., ophthalmologist, movement disorder specialist); and
   • Member is 12 years of age or older; and
   • Documented evidence of BOTH of the following
     • Diagnosis of ONE or more of the following:
       1. Benign essential blepharospasm; or
       2. Blepharospasm associated with dystonia; or
       3. Blepharospasm associated with facial nerve disorders such as Bell palsy; and
     • Alternative causes of the symptoms have been ruled out or adequately treated, including but not limited to neuromuscular diseases (e.g., myasthenia gravis).

topical calcium channel blockers (e.g., Diltiazem 2% rectal ointment, nifedipine 0.2% or 0.5% rectal ointment); and

1. The member does NOT have documented evidence of ANY of the following:
   • Anal fistula; or
   • Hemorrhoids; or
   • HIV; or
   • Inflammatory bowel disease; or
   • Perianal abscess; or
   • Perianal cancer; or
   • Prior perianal surgical intervention.

F. Chronic migraine prophylaxis, when ALL of the following are met:

1. The request is by a provider specialist who will administer botulinum toxin (e.g., neurologist, headache specialist); and
2. Member is 18 years of age or older; and
3. Documented evidence of ALL of the following:
   • Diagnosis of migraine headache (with or without aura) per International Classification of Headache Disorders criteria, defined as meeting ALL of the following criteria:
     1. Headache is characterized by at least TWO of the following:
        • Pulsating quality; and/or
        • Unilateral location; and/or
        • Moderate to severe pain/intensity; and/or
        • Aggravation by physical activity; and
     2. Symptoms are associated with at least ONE of the following:
        • Nausea and/or vomiting; or
        • Photophobia (sensitivity to light) and phonophobia (sensitivity to sound); and
     3. Other potential causes of headache have been ruled out; and
   • The member has chronic migraines, defined as frequent headaches that occur on at least 15 days per month for more than three months, and at least eight of these headaches (per month) must have the features of a migraine;
   • The member is unable to use ALL, or has adequately tried and failed an 8-week trial of at least TWO (2) preventative therapies, from at least TWO (2) of the following drug classes:
     1. Anticonvulsants (such as topiramate, divalproex, sodium valproate); and/or
     2. Antidepressants (such as amitriptyline, nortriptyline, venlafaxine); and/or
     3. Beta blockers (such as propranolol, metoprolol); AND
   • The member does NOT have documented evidence of ANY of the following:
     • Neuromuscular disease (e.g., myasthenia gravis); or
     • Botox (onabotulinumtoxinA) will be used concomitantly with a preventative calcitonin gene-related peptide (CGRP) antagonist for migraine headache prophylaxis.
       • i.e. the following products when used for preventive treatment of migraine: Aimovig (erenumab), Ajovy (fremanezumab), Emgality (galcanezumab), Nurtec (rimegepant), Qulipta (atogepant), Vyepti (eptinezumab).
       • i.e. no restriction for Botox (onabotulinumtoxinA) used concurrently with the following products when used for acute/abortive treatment: Emgality (galcanezumab), Nurtec (rimegepant), Ubrelvy (ubrogepant).
   • NOTE: Please refer to the Plan's pharmacy benefit and Plan Clinical Guideline Anti-migraine Agents/ Calcitonin Gene-Related Peptide (CGRP) Antagonists and Serotonin Receptor 5-HT1F Agonists (PG008).

G. Essential tremors, when BOTH of the following criteria are met:

1. The request is by a provider specialist who will administer botulinum toxin (e.g., neurologist, movement disorder specialist, otolaryngology); and
2. Documented evidence of BOTH of the following:
   • ONE of the following diagnosis:
     1. disabling head and neck tremor; or
     2. disabling essential hand tremor; and
   • The member is unable to use ALL, or has tried and failed TWO (2) of the following:
     1. Propranolol (immediate-release or extended-release); and/or
     2. Primidone; and/or
     3. Topiramate;

H. Hemifacial spasm, when ALL of the following are met:

1. The request is by a provider specialist who will administer botulinum toxin (e.g., neurologist, movement disorder specialist); and
2. Member is 12 years of age or older; and
3. Documented evidence of BOTH of the following:
   • Diagnosis of hemifacial spasm in muscles innervated by the facial nerve (cranial nerve VII); and
   • Alternative causes of the symptoms have been ruled out or adequately treated, including but not limited to neuromuscular diseases (e.g. myasthenia gravis).

I. Oromandibular dystonias (i.e., cranial dystonia), when BOTH of the following are met:

1. The request is by a provider specialist who will administer botulinum toxin (e.g., neurologist, movement disorder specialist, orofacial pain specialist, otolaryngologist); and
2. Documented evidence of BOTH of the following:
   • characterized by continuous, bilateral, asynchronous muscle spasms in the face, jaw, pharynx, and tongue; and
   • causing difficulty in jaw closing or opening and interfering with fluid and food intake and speech.

J. Overactive bladder with urge incontinence, when ALL of the following are met:

1. The request is by a provider specialist who will administer botulinum toxin (e.g., urologist); and
2. Member is 18 years of age or older; and
3. Documented evidence of BOTH of the following:
   • Urodynamic testing confirms urinary incontinence with urgency; and
   • Symptoms had not been adequately managed with BOTH of the following:
     1. Behavioral therapies (such as bladder training and pelvic floor muscle therapy), for at least 8 weeks; and
     2. A minimum of three pharmacologic therapies, with either inadequate response or intolerable side effects, each tried for at least 4 weeks:
        • Anticholinergic (i.e., antimuscarinics) therapy, such as darifenacin (Enablex), fesoterodine (Toviaz), oxybutynin (Ditropan XL), solifenacin (Vesicare), tolterodine (Detrol/Detrol LA), or trospium (Sanctura/Sanctura XR); and/or
        • Beta-3 Adrenergic Agonists, such as Gemtesa (vibegron) or Myrbetriq (miraberon); and
4. The member does NOT have documented evidence of ANY of the following:
   • acute urinary retention; or
   • acute urinary tract infection; and

K. Sialorrhea, when BOTH of the following are met:

1. The request is by a provider specialist who will administer botulinum toxin (e.g., neurologist, PM&R, or ENT); and
2. Documented evidence of ALL of the following:
   • Chronic sialorrhea resulting from a neurological condition (e.g., Parkinson's disease, atypical parkinsonism, stroke, or traumatic brain injury); and
   3. Complications such as recurrent infection or chronic skin breakdown that have failed treatment with topical agents or lifestyle modifications; and
   4. The member is unable to use ALL, or has adequately tried and failed TWO (2) months of pharmacotherapy with ONE (1) of the following:
      1. Benztropine; and/or
      2. Glycopyrrolate; and/or
      3. Scopolamine.

   L. Spasmodic dysphonia (i.e., laryngeal dystonia), when BOTH of the following are met:

   1. The request is by a provider specialist who will administer botulinum toxin (e.g., gastroenterologist, endoscopist, ENT); and
   2. Documented evidence of BOTH of the following:
      1. Adductor-type spasmodic dysphonia confirmed by fiberoptic laryngoscopy; and
      2. Moderate to severe phonation difficulties.

   M. Spasticity of the upper and/or lower extremity, when ALL of the following criteria are met:

   1. The request is by a provider specialist who will administer botulinum toxin (e.g., neurologist, physical medicine and rehabilitation); and
   2. The member is characterized by ONE of the following:
      1. Members greater than the age of 2 with spasticity due to cerebral palsy who are receiving ongoing rehabilitation; or
      2. Members 18 years of age or older with ONE of the following:
         1. Spasticity secondary to multiple sclerosis or other demyelinating diseases of the central nervous system; or
         2. Spasticity secondary to spinal cord injury; or
         3. Post-stroke spasticity; and
   3. Documentation of ALL of the following:
      1. Joint is not affected by fixed contracture; and
      2. Abnormal muscle tone that interferes with daily functioning or is expected to result in joint contracture with further growth; and
      3. Treatment is expected to improve functioning and/or allow for further therapeutic rehabilitation; and
      4. Surgical intervention is the only alternative option; and
      5. If the request is for the treatment of lower limb spasticity, the member has tried and failed appropriate non-surgical medical treatments (e.g., pharmacologic and physical therapies).

   N. Strabismus, when ALL of the following are met:

   1. The request is by a provider specialist who will administer botulinum toxin (e.g., ophthalmologist); and
   2. The member is 12 years of age or older; and
   3. The member does NOT have documented evidence of ANY of the following:
      1. Duane’s syndrome with lateral rectus weakness; or
      2. Likely to have a spontaneous recovery; or
      3. Ocular deviations exceeding 50 prism diopters; or
      4. Restrictive strabismus; or
      5. Strabismus secondary to prior surgical overrecession of the ocular antagonist muscle.

   O. Upper extremity focal dystonia (e.g., writer’s cramp), when ALL of the following are met:

   1. The request is by a provider specialist who will administer botulinum toxin (e.g., neurologist, movement disorder specialist); and
   2. The member is 16 years of age or older; and
   3. Documented evidence of ALL of the following:
      1. Significant pain and/or abnormal hand or forearm positioning that adversely affects daily functioning; and
      2. No prior surgical intervention; and
      3. Failure of at least two months of conservative therapy and/or lifestyle modification.

   P. Urinary incontinence due to detrusor overactivity (i.e., detrusor instability or detrusor hyperreflexia) or detrusor-sphincter dyssynergia, when ALL of the following are met:

   1. The request is by a provider specialist who will administer botulinum toxin (e.g., urologist); and
   2. The member is 5 years of age or older; and
   3. Documented evidence of ALL of the following:
      1. The condition is associated with a neurologic condition (e.g., spinal cord injury, multiple sclerosis, Parkinson's disease, cerebral palsy, stroke); and
      2. Symptoms had not been adequately managed with ALL of the following:
         1. Behavioral therapies (such as bladder training and pelvic floor muscle therapy) for 8 to 12 weeks; and
         2. At least one anticholinergic (i.e. antimuscarinics) therapy such as darifenacin (Enablex), fesoterodine (Toviaz), oxybutynin (Ditropan XL), solifenacin (Vesicare), tolterodine (Detrol/Detrol LA), or trospium (Sanctura/Sanctura XR) for 4 to 8 weeks (inadequate response or intolerable adverse effects); and
         3. ONE of the following:
            1. Balloon sphincter dilation or surgical treatment has been attempted but was unsuccessful; or
            2. The member was not a candidate due to comorbidities; or
            3. The member refused surgery.
      3. The member does NOT have documented evidence of ANY of the following:
         1. urinary tract infection (UTI); or
         2. urinary retention or postvoid residuals (PVR) greater than 200 mL unless the patient is receiving intermittent catheterization as part of the overall treatment plan.

   The request is by a provider specialist who will administer botulinum toxin (e.g., ophthalmologist, neurologist, movement disorder specialist); and
   b. Member is 18 years of age or older; and
   c. Documented evidence of BOTH of the following:

   • Diagnosis of ONE or more of the following:
     1. Benign essential blepharospasm; or
     2. Blepharospasm associated with dystonia; or
     3. Hemifacial spasm involving the orbicularis oculi muscle; and
   • Alternative causes of the symptoms have been ruled out or adequately treated, including but not limited to neuromuscular diseases (e.g., myasthenia gravis).

   C. Cervical dystonia (i.e., spasmodic torticollis), when ALL of the following are met:

   1. The request is by a provider specialist who will administer botulinum toxin (e.g., neurologist, movement disorder specialist); and
   2. Member is 16 years of age or older; and
   3. Documented evidence of ALL of the following:
      1. Symptoms (e.g., abnormal head positioning, neck pain, limited range of motion, muscle spasms) have been present for at least 6 months; and
      2. Neck pain and abnormal head tilt/torsion adversely affects range of motion and daily functioning; and
      3. Sustained involuntary contractions in the neck muscles (e.g splenius, trapezius, posterior cervical, or sternocleidomastoid); and
      4. Alternative causes of the symptoms have been ruled out or adequately treated,including but not limited to:
         1. Neuromuscular disease (e.g., myasthenia gravis); or
         2. Chronic neuroleptic treatment; or
         3. Fixed muscle contractures;

   D. Chronic anal fissure, when ALL of the following are met:

   1. The request is by a provider specialist who will administer botulinum toxin (e.g., gastroenterologist, colon or rectal surgeon); and
   2. Documented evidence of ALL of the following:
      1. At least 2 months of symptoms, including ONE or more of the following:
         1. Nocturnal pain and bleeding; or
         2. Post-defecation pain; and
      2. The member is unable to use ALL, or has tried and failed ONE of the following:
         1. topical nitrates (e.g., Nitroglycerin 0.2% or 0.4% rectal ointment); or
         2. topical calcium channel blockers (e.g., Diltiazem 2% rectal ointment, nifedipine 0.2% or 0.5% rectal ointment); and
      3. The member does NOT have documented evidence of ANY of the following:
         • Anal fistula; or
         • Hemorrhoids; or
         • HIV; or
         • Inflammatory bowel disease; or
         • Perianal abscess; or
         • Perianal cancer; or
         • Prior perianal surgical intervention.

   E. Sialorrhea, when BOTH of the following are met:

   1. The request is by a provider specialist who will administer botulinum toxin (e.g., neurologist, PM&R, or ENT); and
   2. Documented evidence of ALL of the following:
      1. Chronic sialorrhea resulting from a neurological condition (e.g., Parkinson's disease, atypical parkinsonism, stroke, or traumatic brain injury); and
      2. Complications such as recurrent infection or chronic skin breakdown that have failed treatment with topical agents or lifestyle modifications; and
      3. The member is unable to use ALL, or has adequately tried and failed TWO (2) months of pharmacotherapy with ONE (1) of the following:
         1. Benztropine; or
         2. Glycopyrrolate; or
         3. Scopolamine.

   F. Spasticity of the upper and/or lower extremity, when ALL of the following criteria are met:

   1. The request is by a provider specialist who will administer botulinum toxin (e.g., neurologist, physical medicine and rehabilitation); and
   2. The member is characterized by ONE of the following:
      1. Members greater than the age of 2 with spasticity due to cerebral palsy who are receiving ongoing rehabilitation; or
      2. Members 18 years of age or older with ONE of the following:
         1. Spasticity secondary to multiple sclerosis or other demyelinating diseases of the central nervous system; or
         2. Spasticity secondary to spinal cord injury; or
         3. Post-stroke spasticity; and
   3. Documentation of ALL of the following:
      • Joint is not affected by fixed contracture; and
      • Abnormal muscle tone that interferes with daily functioning or is expected to result in joint contracture with further growth; and
      • Treatment is expected to improve functioning and/or allow for further therapeutic rehabilitation; and
      • Surgical intervention is the only alternative option; and
      • If the request is for the treatment of lower limb spasticity, the member has tried and failed appropriate non-surgical medical treatments (e.g., pharmacologic and physical therapies).

   G. Upper extremity focal dystonia (e.g., writer’s cramp), when ALL of the following are met:

   1. The request is by a provider specialist who will administer botulinum toxin (e.g., neurologist, movement disorder specialist); and
   2. The member is 16 years of age or older; and
   3. Documented evidence of ALL of the following:
      • Significant pain and/or abnormal hand or forearm positioning that adversely affects daily functioning; and
      • No prior surgical intervention; and
      • Failure of at least two months of conservative therapy and/or lifestyle modification.

   RimabotulinumtoxinB (Myobloc) (J0587)

   The Plan deems RimabotulinumtoxinB (Myobloc) medically necessary for the following indications if the disease-specific criteria for initial requests are met (refer to Continued Care for reauthorization criteria or Table 1 for standard initial/retreatment authorization durations):

   A. Cervical dystonia (i.e., spasmodic torticollis), when ALL of the following are met:

   1. The request is by a provider specialist who will administer botulinum toxin (e.g., neurologist, movement disorder specialist); and
   2. Member is 18 years of age or older; and
   3. Documented evidence of ALL of the following:
      1. Symptoms (e.g., abnormal head positioning, neck pain, limited range of motion, muscle spasms) have been present for at least 6 months; and
      2. Neck pain and abnormal head tilt/torsion adversely affects range of motion and daily functioning; and
      3. Sustained involuntary contractions in the neck muscles (e.g splenius, trapezius, posterior cervical, or sternocleidomastoid);

   Alternative causes of the symptoms have been ruled out or adequately treated, including but not limited to:

   1. Neuromuscular disease (e.g., myasthenia gravis); or
   2. Chronic neuroleptic treatment; or
   3. Fixed muscle contractures; and

   B. Sialorrhea, when ALL of the following are met:

   1. The request is by a provider specialist who will administer botulinum toxin (e.g., neurologist, PM&R, or ENT); and
   2. Member is 18 years of age or older; and
   3. Documented evidence of ALL of the following:
      1. Chronic sialorrhea resulting from a neurological condition (e.g., Parkinson's disease, atypical parkinsonism, stroke, or traumatic brain injury); and
      2. Complications such as recurrent infection or chronic skin breakdown that have failed treatment with topical agents or lifestyle modifications; and
      3. The member is unable to use ALL, or has adequately tried and failed TWO (2) months of pharmacotherapy with ONE (1) of the following:
         1. Benztropine; or
         2. Glycopyrrolate; or
         3. Scopolamine.

   IncobotulinumtoxinA (Xeomin) (J0588)

   The Plan deems IncobotulinumtoxinA (Xeomin) medically necessary for the following indications if the disease-specific criteria for initial requests are met (refer to Continued Care for reauthorization criteria or Table 1 for standard initial/retreatment authorization durations):

   A. Blepharospasm or hemifacial spasms, when ALL of the following are met:

   1. The request is by a provider specialist who will administer botulinum toxin (e.g., ophthalmologist, neurologist, movement disorder specialist); and
   2. Member is 18 years of age or older; and
   3. Documented evidence of BOTH of the following:
      1. Diagnosis of ONE or more of the following:
         1. Benign essential blepharospasm; or
         2. Blepharospasm associated with dystonia; or
         3. Hemifacial spasm involving the orbicularis oculi muscle; and
      2. Alternative causes of the symptoms have been ruled out or adequately treated,including but not limited to neuromuscular diseases (e.g., myasthenia gravis).

   B. Cervical dystonia (i.e., spasmodic torticollis), when ALL of the following are met:

   1. The request is by a provider specialist who will administer botulinum toxin (e.g., neurologist, movement disorder specialist); and
   2. Member is 18 years of age or older; and
   3. Documented evidence of ALL of the following:
      1. Symptoms (e.g., abnormal head positioning, neck pain, limited range of motion, muscle spasms) have been present for at least 6 months; and
      2. Neck pain and abnormal head tilt/torsion adversely affects range of motion and daily functioning; and
      3. Sustained involuntary contractions in the neck muscles (e.g splenius, trapezius, posterior cervical, or sternocleidomastoid); and
      4. Alternative causes of the symptoms have been ruled out or adequately treated, including but not limited to:
         1. Neuromuscular disease (e.g., myasthenia gravis); or
         2. Chronic neuroleptic treatment; or
         3. Fixed muscle contractures.

   C. Sialorrhea, when ALL of the following are met:

   1. The request is by a provider specialist who will administer botulinum toxin (e.g., neurologist, PM&R, or ENT); and
   2. Member is 2 years of age or older; and
   3. Documented evidence of ALL of the following:
      1. Chronic sialorrhea resulting from a neurological condition (e.g., Parkinson's disease, atypical parkinsonism, stroke, or traumatic brain injury); and
      2. Complications such as recurrent infection or chronic skin breakdown that have failed treatment with topical agents or lifestyle modifications; and
      3. The member is unable to use ALL, or has adequately tried and failed TWO (2) months of pharmacotherapy with ONE (1) of the following:
         1. Benztropine; or
         2. Glycopyrrolate; or
         3. Scopolamine.

   D. Spasticity of the upper limb, when ALL of the following criteria are met:

   1. The request is by a provider specialist who will administer botulinum toxin (e.g., neurologist, physical medicine and rehabilitation); and
   2. The member is characterized by ONE of the following:
      1. Members 2 to 17 years of age and ONE of the following:
         1. the spasticity is not caused by cerebral palsy; or
         2. with spasticity due to cerebral palsy who are receiving ongoing rehabilitation; or
      2. Members 18 years of age or older:
         1. Spasticity secondary to multiple sclerosis or other demyelinating diseases of the central nervous system; or
         2. Spasticity secondary to spinal cord injury; or
         3. Post-stroke spasticity; and
   3. Documentation of ALL of the following:
      1. Joint is not affected by fixed contracture; and
      2. Abnormal muscle tone that interferes with daily functioning or is expected to result in joint contracture with further growth; and
      3. Treatment is expected to improve functioning and/or allow for further therapeutic rehabilitation; and
      4. Surgical intervention is the only alternative option.

   DaxibotulinumtoxinA-lanm (Daxxify) (C9399, J3590)

   The Plan deems DaxibotulinumtoxinA-lanm (Daxxify) medically necessary for the following indications if the disease-specific criteria for initial requests are met (refer to Continued Care for reauthorization criteria or Table 1 for standard initial/retreatment authorization durations):

   A. Cervical dystonia (i.e., spasmodic torticollis), when ALL of the following are met:

   1. The request is by a provider specialist who will administer botulinum toxin (e.g., neurologist, movement disorder specialist); and
   2. Member is 18 years of age or older; and
   3. Documented evidence of ALL of the following:
      1. Symptoms (e.g., abnormal head positioning, neck pain, limited range of motion, muscle spasms) have been present for at least 6 months; and
      2. Neck pain and abnormal head tilt/torsion adversely affects range of motion anddaily functioning; and
      3. Sustained involuntary contractions in the neck muscles (e.g splenius, trapezius, posterior cervical, or sternocleidomastoid); and
      4. Alternative causes of the symptoms have been ruled out or adequately treated, including but not limited to:
         1. Neuromuscular disease (e.g., myasthenia gravis); or
         2. Chronic neuroleptic treatment; or
         3. Fixed muscle contractures.

   Fixed muscle contractures.18Continued Care

   Medical Necessity Criteria for Reauthorization

   Except for specific conditions outlined elsewhere, the Plan considers continuing botulinum toxin treatment medically necessary if, at the end of the initial trial period:

   1. A positive response is documented in the medical record, which should typically last for 3 months; and
   2. The member would continue to meet the clinical criteria for the specific botulinum toxin agent in the absence of further treatment; and
   3. The prescribing clinician provides an expected duration and frequency of ongoing treatment, which may require ongoing approval.

   NOTE: Treatment with botulinum toxin more frequently than every 3 months for a covered condition, regardless of diagnosis, is generally not considered medically necessary.

   D. For chronic migraine prophylaxis with OnabotulinumtoxinA (Botox), after the initial trial period, which is defined as 6 months or a maximum of 2 treatments, the Plan considers continuing treatment medically necessary if the member experiences any of the following:

   • a reduction of greater than 30% in the frequency of migraine headaches; or
   • at least 2 fewer migraine days per month; or
   • at least a reduction of 7 headache days over a one-month period compared to the pre- treatment average.

   Criteria for Discontinuing Treatment

   Botulinum toxin treatment is generally no longer considered medically necessary and should be discontinued, except as outlined for specific conditions elsewhere, when the following criteria are met:

   1. Lack of documented clinical response after initial trial; or
   2. In cases where the initial trial was successful, lack of documented clinical response to two consecutive treatments precludes treatment at that site for a period of at least one year; or
   3. For chronic migraine prophylaxis using OnabotulinumtoxinA (Botox), if the patient does not respond adequately (less than 30% reduction in headache days per month) after the initial trial period, defined as six months or a maximum of two treatments.

   General Recommendations for Time to Retreatment and Dosing

   Table 1 provides general recommendations for:

   1. the time to retreatment with botulinum toxin agents, assuming that all other clinical criteria remain met. These recommendations may differ for individual members but should not occur more frequently than every three months. If requests for more frequent injection frequency are made, documentation of medical necessity should be provided.
   2. the doses (in units) of botulinum toxin agents, assuming that all other clinical criteria are met. Although the recommended doses may vary by individual member and condition, they should not be exceeded regardless of indication. If injection dosages exceeding the recommended amounts are requested, further review and documentation of medical necessity may be required.

   Table 1: Dosage and retreatment information for botulinum toxin regimens by indication

   Botox (onabotulinumtoxinA)

   Indication	Initial dose	Subsequent Dose	Retreatment	Additional Considerations
   Achalasia	80-100 units		3 months	inject into four quadrants in the lower esophageal sphincter
   Blepharospasm	1.25-2.5 units per injection site Typically, 4-6 injection per affected eye.	maximum dose per site: 5 units	3 months	Dose during subsequent treatment sessions may be increased by up to twofold if initial response is insufficient (e.g., the duration of effect is <2 months) Cumulative dose: <200 units in 30- day period (i.e., maximum dose of 100 units per eye in a three-month period)
   Cervical dystonia	50-200 units total	50-360 units total	3 months	Dose should be divided across injected sites; Max 50 units/site
   Chronic anal fissure	25-50 units		2-4 months	Generally injected into the internal anal sphincter, with half on the right and the remainder into the left

   ● In pediatric patients below 18 years, the maximum cumulative dose is 10 units/kg or 340 units, whichever is less.

   ● In adolescents & adults ≥18 years treated for 1 or more indications, the maximum cumulative dose should not exceed 400 units (i.e., ≤400 units per 3 months).

   Chronic migraine prophylaxis	155 units total	Dose Per Muscle	No. of Injection Sites per Muscle
   Head/Neck Area Muscle(s)
   Frontalis		20 units	4 sites
   Corrugator		10 units	2 sites
   Procerus	5 units	1 site
   Occipitalis		30 units	6 sites
   Temporalis	40 units	8 sites
   Trapezius		30 units	6 sites
   Cervical paraspinal muscle group		20 units	4 sites
   Total dose per treatment session	155 units	31 sites

   Essential tremor of the hands and arms

   Dose

   150-100 units

   Retreatment

   3-4 months

   Injected into the affected hand, divided among multiple injection sites

   Essential tremor of the head and neck

   Dose

   100-200 units

   Retreatment

   3-4 months

   Injected into the affected muscles in the neck and/or head, divided among multiple injection sites

   Hemifacial spasm

   Dose	12-25 units administered into the inferior and superior orbicularis oculi, buccolabial, and/or platysma muscles.

   Typically, 20-30 injection sites are used on the affected side of the face, with a starting dosage of 2.5-5 units per injection site.

   3 months

   Cumulative dose: <200 units in 30-day period (i.e., maximum dose of 200 units per treatment session)

   Hyperhidrosis:
   Axillary: 50 units/axilla
   Injections should be evenly distributed into multiple sites (10 to15)
   Retreatment: 4 months

   Hyperhidrosis:
   Palmar: 100–120 units
   Inject among multiple (e.g., 50–60) sites in the hyperhidrotic area
   Retreatment: 3 months

   Laryngeal dysphonia	1-5 units/muscle	3 months
   Oromandibular dystonias (i.e., cranial dystonia)	10-50 units injected into each affected muscle	3-4 months	Total dose not to exceed 100 units per treatment session
   Overactive bladder	100 units per treatment	3 months	Dose should be divided across 20 injection sites
   Sialorrhea	10-40 units/side	3 months	Total dose should be divided across parotid and submandibular glands if injecting both
   Spasticity, Adult Upper Limb	75 Units to 400 Units divided among selected muscles; <50 units per site		3 months	Dose listed is total dose administered as divided separate intramuscular injections

   For stroke-related upper limb spasticity including Adductor pollicis, Biceps brachii, Flexor digitorum profundus, Flexor digitorum sublimis, Flexor carpi radialis, Flexor carpi ulnaris, use the following doses:

   • Adductor pollicis: 20 units (1 to 2 sites)
   • Biceps brachii: 100 to 200 units (up to 4 sites)
   • Flexor digitorum profundus: 15 to 50 units (1 to 2 sites)
   • Flexor digitorum sublimis: 15 to 50 units (1 to 2 sites)
   • Flexor carpi radialis: 15 to 60 units (1 to 2 sites)
   • Flexor carpi ulnaris: 10 to 50 units (1 to 2 sites)
   • Flexor pollicis longus: 20 units (1 to 2 sites)

   Retreatment: 3 months
   Total Dose: 300 Units to 400 Units divided among 5 muscles; ≤50 units per site

   Spasticity, Adult Lower Limb	Gastrocnemius lateral head: 75 units (divided into 3 sites) Gastrocnemius medial head: 75 units (divided into 3 sites) Soleus: 75 units (divided into 3 sites) Tibialis posterior: 75 units (divided into 3 sites)	3 months	Maximum dose per treatment session: 3-6 units/kg for large muscles , 1-2 units/kg for small muscles; max dose of 50 units per injection site Upper extremity: 3 to 6 units/kg total Lower extremity: 4 to 8 units/kg total
   Strabismus	Horizontal strabismus <20 prism diopters: 1.25 to 2.5 units in any one muscle Horizontal strabismus of 20 to 50 prism diopters: 2.5 to 5 units in any one muscle Persistent VI nerve palsy =>1 month: 1.25 to 2.5 units in the medial rectus muscle	3 months	Max dose for any one muscle: 25 units. Subsequent doses may be increased up to twice the previous administered dose.
   Upper extremity focal dystonia	20-80 units/limb	3 months	Total dose should be injected across affected muscles
   Urinary incontinence due to	Adults: 200 units per treatment given as 30 separate injections of approximately 6.7 units each

   the detrusor muscle (avoiding the trigone)
   detrusor overactivity secondary to neurologic condition	Children ≥5 years and <18 years, weight ≥34 kg: 200 units per treatment		3 months	administered as 20 injections
   	Children ≥5 years and <18 years, weight <34 kg: 6 units/kg per treatment			administered as 20 injections

   Dysport (abobotulinumtoxinA)

   Indication	Initial dose	Subsequent Dose	Retreatment	Additional Considerations
   Axillary hyperhidrosis	100-200 units/axilla	100-500 units/axilla	3 months	injections should be evenly distributed into multiple sites 1 to 2 cm apart (10 to 20 injections)
   Blepharospasm or hemifacial spasm	40-80 units	40-120 units	3 months	Cumulative dose: <60 units/eye or 120 units/both eyes per 3 month period
   Cervical dystonia	250-500 units	250-1000 units	3 months	Dose should be divided among all treated muscles, retreatment should be no greater than 250 units more than prior treatment dose
   Chronic anal fissure	90 to 150 units in 2 divided doses		2-4 months	injected into the internal anal sphincter on each side of the anterior midline

   Sialorrhea

   15 to 75 units injected per gland (submandibular, parotid or both) either unilaterally or bilaterally
   Retreatment: 4-6 months
   Injection should be into parotid and/or submandibular gland

   Spasticity of upper/lower extremity (Adult)

   Maximum recommended total dose (upper and lower limbs combined) is 1,500 units e upper limb spasticity, total doses of 500 and 1,000 units divided among selected muscles e lower limb spasticity, total doses of 1,000 and 1,500 units divided among selected muscles Upper limbs:

   • Brachialis: 200 to 400 units (1 to 2 injections per muscle).
   • Brachioradialis: 100 to 200 units (1 to 2 injections per muscle).
   • Biceps brachii: 200 to 400 units (1 to 2 injections per muscle).
   • Flexor carpi radialis: 100 to 200 units (1 to 2 injections per muscle).
   • Flexor carpi ulnaris: 100 to 200 units (1 to 2 injections per muscle).
   • Flexor digitorum profundus: 100 to 200 units (1 to 2 injections per muscle).
   • Flexor digitorum superficialis: 100 to 200 units (1 to 2 injections per muscle).
   • Pronator teres: 100 to 200 units (1 injection per muscle).

   Lower limbs:

   • Flexor digitorum longus: 130 to 200 (1 to 2 injections per muscle).
   • Flexor hallucis longus: 70 to 200 units (1 injection per muscle).
   • Gastrocnemius, medial head: 100 to 150 units (1 injection per muscle).
   • Gastrocnemius, lateral head: 100 to 150 units (1 injection per muscle).
   • Soleus: 330 to 500 units (3 injections per muscle).
   • Tibialis posterior: 200 to 300 units (2 injections per muscle).

   Upper Limb Spasticity (Pediatric, Children ≥2 years and Adolescents <18 years)

   8 Units/kg to 16 Units/kg per limb
   Maximum total dose per treatment session = 16 Units/kg or 640 Units, whichever is lower
   Lower Limb: 10 Units/kg to 15 Units/kg per limb
   Maximum total dose per treatment session for unilateral limb injections = 15 Units/kg or 1000 Units, whichever is lower
   Maximum total dose per session for bilateral injections = 30 Units/kg or 1000 Units, whichever is lower
   Total dose for Gastrocnemius: 6 to 9 units/kg (1 to 4 sites per muscle)
   Total dose for Soleus: 4 to 6 units/kg (1 to 4 sites per muscle)
   Total dose combined for both muscles: 10 to 15 units/kg (1 to 6 sites per muscle)

   Oromandibular dystonia

   15-150 units
   Total dose should be injected across affected muscles
   Retreatment: 3 months

   Myobloc (rimabotulinumtoxinB)

   Upper extremity focal dystonia

   Cervical dystonia: 2,500 to 5,000 units divided among the affected muscles in patients previously treated with botulinum toxin

   Myobloc (rimabotulinumtoxinB)

   Indication	Initial dose	Subsequent Dose	Retreatment	Additional Considerations
   Sialorrhea	1,500 to 3,500 units divided among the parotid (500 to 1,500 units/gland) and submandibular (250 units/gland) glands (1 injection per side of face)	4-6 months	Injection should be into parotid and/or submandibular gland
   Upper extremity focal dystonia	Toxin treatment-naive patients: Use a lower initial dose.	3-4 months

   Xeomin (incobotulinumtoxinA)

   Indication	Initial dose	Subsequent Dose	Retreatment	Additional Considerations
   Blepharospasm or a hemifacial spasm	25 units per eye (50 units per treatment session)	Maximum dose: 50 units per eye (100 units per treatment session)	3 months
   Cervical dystonia	120 units	120-400 units	3 months	Maximum cumulative dose per treatment session: 400 units. Initial doses >120 units not shown to provide additional efficacy and may be associated with increased incidence of adverse effects.
   Sialorrhea	100 units divided between the parotid and submandibular glands on both sides (ie, 4 injection sites per treatment session)	4 months	Divide dose with a ratio of 3:2 between parotid and submandibular glands.
   Spasticity of the upper limb	See the below table for specific muscle group dose.	Maximum cumulative dose per treatment session: 400 units.	3 months

   Dosing of IncobotulinumtoxinA for Upper Limb Spasticity in Adults

   Clinical Pattern/Muscle	Recommended Dose per Muscle	Recommended No. of Injection Sites per Muscle
   Clenched fist; flexor digitorum superficialis	25-100 units	2 sites
   Clenched fist; flexor digitorum profundus	25-100 units	2 sites
   Flexed wrist; flexor carpi radialis	25-100 units	1-2 sites
   Flexed wrist; flexor carpi ulnaris	20-100 units	1-2 sites
   Flexed elbow; brachioradialis	25-100 units	1-3 sites
   Flexed elbow; biceps	50-200 units	1-4 sites

   Dosing of IncobotulinumtoxinA for Upper Limb Spasticity in Children ≥2 years and Adolescents ≤17 years

   Muscle	Dosage Range	Maximum Dose (units)	Number of Injection Sites Per Muscle
   Adductor pollicis	0.5 units/kg	12.5	1
   Biceps	2 to 3 units/kg	75	1 to 3
   Brachialis	1 to 2 units/kg	50	1 to 2
   Brachioradialis	1 to 2 units/kg	50	1 to 2
   Flexor carpi radialis	1 unit/kg	25	1
   Flexor carpi ulnaris	1 unit/kg	25	1
   Flexor digitorum profundus	1 unit/kg	25	1
   Flexor digitorum superficialis	1 unit/kg	25	1
   Flexor pollicis brevis/Opponens pollicis	0.5 unit/kg	12.5	1
   Flexor pollicis longus	1 unit/kg	25	1
   Pronator quadratus	0.5 units/kg	12.5	1
   Pronator teres	1 to 2 units/kg	50	1 to 2

   Daxxify (daxibotulinumtoxinA-lanm)

   Indication	Initial dose	Subsequent Dose	Retreatment	Additional Considerations
   Cervical dystonia	125 to 250 units divided among affected muscles	3 months	Total recommended dosage for a single treatment session: 125 to 250 units. Dose and number of injection sites should be personalized considering previous treatment, response, duration of effect, and any adverse events. The dosage can be modified by increments of 50 to 75 units depending on the individual's response.

   Experimental or Investigational / Not Medically Necessary

   1. All botulinum toxin preparations (regardless of type) are considered contraindicated, experimental, investigational, or unproven in the following cases:
      • Infection at the proposed injection site; or
      • Known hypersensitivity to any botulinum toxin preparation or the components in the formulation; or
      • Retreatment of a condition with the same or different agent after a failed initial trial, regardless of if the member continues to meet clinical criteria; orNOTE: If the member initially failed therapy due to an agent-specific intolerance or reaction, rather than a clinical feature, then this statement may not apply.
   2. The Plan deems the use of botulinum toxin for ALL cosmetic purposes as not medically necessary. Such cosmetic purposes include, but are not limited to:
      • Chin dimpling; or

   Experimental or Investigational / Not Medically Necessary

   1. All botulinum toxin preparations (regardless of type) are considered contraindicated, experimental, investigational, or unproven in the following cases:
      • Infection at the proposed injection site; or
      • Known hypersensitivity to any botulinum toxin preparation or the components in the formulation; or
      • Retreatment of a condition with the same or different agent after a failed initial trial, regardless of if the member continues to meet clinical criteria; orNOTE: If the member initially failed therapy due to an agent-specific intolerance or reaction, rather than a clinical feature, then this statement may not apply.
   2. The Plan deems the use of botulinum toxin for ALL cosmetic purposes as not medically necessary. Such cosmetic purposes include, but are not limited to:
      • Chin dimpling; or

   eyebrow elevation/shaping (“brow lift”); or
   c. flaring nostrils (nasal flare); or
   d. forehead lines; or
   e. glabellar facial (“frown”) lines; or
   f. labiomandibular grooves; or
   g. lateral brow lift; or
   h. lateral canthal lines (“crow’s feet”); or
   i. lip lines; or
   j. radial lines on the dorsum of the nose (bunny lines); or
   k. to treat prominent platysma muscle bands (age-related neck degeneration).

   OnabotulinumtoxinA (Botox) (J0585)

   The use of OnabotulinumtoxinA (Botox) for any other indication not listed above is considered experimental, investigational, or unproven; these excluded indications include, but are not limited to, the following:

   • A. Acute and chronic back pain
   • B. Acute and chronic shoulder pain
   • C. Anal sphincter achalasia
     • Rationale: A 2012 meta-analysis on 16 nonrandomized studies examining Botox for internal anal sphincter achalasia revealed significantly higher rates of non-response and adverse outcomes when compared to myectomy. Further evidence is required to determine a potential benefit of Botox therapy in this patient population.
   • D. benign prostatic hyperplasia (BPH, benign prostatic hypertrophy) with lower urinary tract symptoms (LUTS)
     • Rationale: There is insufficient evidence to support the use of OnabotulinumtoxinA for men with lower urinary tract symptoms caused by benign prostatic hyperplasia. Currently, no guidelines in the field endorse OnabotulinumtoxinA as a potential treatment option. To fully evaluate the short- and long-term efficacy, including the need for repeated injections in patients with LUTS due to BPH, large-scale, placebo-controlled randomized trials are necessary. Furthermore, given the availability of several effective treatments for BPH, the potential role of BoNT-A should be examined in further randomized trials that compare it to α-blockers, 5-α reductase inhibitors, minimally invasive treatments, and even traditional surgery.
   • E. Carpal tunnel syndrome
   • F. Chronic idiopathic constipation (CIC)
   • G. Chronic pain, including, but not limited to: myofascial pain syndrome, inflammatory pain, knee osteoarthritis, musculoskeletal pain (including acute shoulder and back pain), neuropathic pain, postoperative pain, post-herpetic neuralgia, gynecologic pain syndromes, fibromyalgia.
     • Rationale: Multiple systematic reviews and meta-analyses have concluded that the current evidence is inadequate to support the use of Botox in chronic pain syndromes.
   • H. Chronic paralytic strabismus, except when used in conjunction with surgical repair to reduce ocular antagonist muscle contracture.
   • I. Club foot (e.g. talipes equinovarus)
     • Rationale: The existing evidence consists of a small (n=20) randomized trial showing no benefit with Botox in reducing cast time, need for further procedural intervention, or risk for relapse. A separate, larger study with 239 patients found some evidence of efficacy for Botox, however the study was designed as a retrospective case series. Further randomized, prospective evidence is needed to determine a potential benefit of Botox for this indication.
   • J. Cosmetic strabismus, defined as adults with congenital strabismus without binocular fusion.
   • K. Depression
   • L. First-bite syndrome, with or without pain that has failed traditional analgesics
   • M. Frey Syndrome (i.e. Gustatory sweating)
     • Rationale: A 2013 evidence-based review concluded that the lack of randomized clinical evidence for Botox in Frey's syndrome limits the support for clinical use.
   • N. Gastroparesis
     • Rationale: There is limited evidence to support the use of OnabotulinumtoxinA for gastroparesis. Some small studies have suggested potential benefit in reducing symptoms and improving gastric emptying, but larger randomized controlled trials are needed to further evaluate its efficacy and safety for this condition. Therefore, more research is needed before making a definitive conclusion about the effectiveness of OnabotulinumtoxinA for gastroparesis.
   • O. Hyperhidrosis of the face/neck
     • Rationale: more high-quality studies are needed to further evaluate the safety and efficacy of Botox in the treatment of craniofacial hyperhidrosis.
   • P. Migraines or other headaches (e.g. tension, cluster, chronic daily) that do not meet the above criteria
     • Rationale: OnabotulinumtoxinA has been used with varying degrees of success in a small number of patients suffering from headaches other than chronic migraine, including post-whiplash (cervicogenic) headache, tension-type headache, and cluster headache. The manufacturer cautions that the safety and effectiveness of onabotulinumtoxinA for prophylaxis of episodic migraine (less than or equal to 14 headache days per month) have not been established. The American Academy of Neurology (AAN) does not endorse the use of onabotulinumtoxinA as a treatment for headaches other than chronic migraine.
   • Q. Motor tics / Tourette Syndrome
     • Rationale:The American Academy of Neurology provides level C rating in 2019 practice guideline for prescribing botulinum toxin injections for the treatment of adolescents and adults with localized and bothersome simple motor tics when the benefits of treatment outweigh the risks. Furthermore, AAN provide level C rating for prescribing botulinum toxin injections for the treatment of older adolescents and adults with severely disabling or aggressive vocal tics when the benefits of treatment outweigh the risks. Therefore, Botox for Tourette Syndrome will be considered experimental or investigational. 
     • A 2018 Cochrane Database analysis looked at the use of Botox in the treatment of motor tics. They found only a single randomized trial that met their selection criteria, and only 20 patients enrolled in the study, and that the quality of the evidence was “low-quality”.

   Botulinum toxin antibody assays are considered experimental or investigational and are therefore not covered by the Plan.

   In conclusion, the authors stated that they were “uncertain about botulinum toxin effects in the treatment of focal motor and phonic tics in select cases, as we assessed the quality of the evidence as very low. Additional randomised controlled studies are needed to demonstrate the benefits and harms of botulinum toxin therapy for the treatment of motor and phonic tics in patients with Tourette's syndrome.”

   • Obesity
   • S&S CHYS
   • Painful bruxism
   • Palatal myoclonus
   • Phonic tics
   • Plantar fasciitis
   • Postnatal brachial plexus injury
   • Post-radiation myokymia, including facial myokymia and trismus
   • Raynaud’s Phenomenon

   Rationale: Limited studies, including small non-controlled trials, case series, and retrospective reviews, have suggested some potential benefits of using onabotulinumtoxinA (botulinum toxin A) for severe symptoms associated with primary or secondary Raynaud phenomenon (RP). While a small randomized, double-blind, placebo-controlled trial in patients with scleroderma-associated RP also showed some positive effect in patient-reported clinical measures, it did not demonstrate significant improvements in blood flow as measured by laser Doppler imaging, which was the primary outcome. A systemic review found insufficient evidence to assess the efficacy of onabotulinumtoxinA in severe RP, and experts recommend reserving its use for patients who have not tolerated or have failed initial conventional therapy. Further trials may be necessary to determine the role of onabotulinumtoxinA in this condition.

   • Refractory interstitial cystitis
   • Tardive dyskinesia
   • Temporomandibular Disorders (TMD)
   • Thoracic outlet syndrome
   • Trigeminal neuralgia

   Rationale: The current evidence is either uncontrolled or nonrandomized with small patient samples. Review articles have suggested there may be some efficacy for Botox in trigeminal neuralgia but indicate that further study is needed.

   AbobotulinumtoxinA (Dysport) (J0586)

   The use of AbobotulinumtoxinA (Dysport) for any other indication not listed above is considered experimental, investigational, or unproven; these excluded indications include, but are not limited to, the following:

   • AbobotulinumtoxinA (Dysport) is contraindicated in members with allergy to cow’s milk protein, per FDA guidelines
   • Achalasia or upper esophageal sphincter dysfunction
   • Benign prostatic hypertrophy (BPH)

   Rationale: A 2011 review article on abobotulinumtoxinA for lower urinary tract symptoms related to BPH concluded that the level of evidence is low and further randomized controlled trials are necessary.

   • Carpal tunnel syndrome
   • Charcot-Marie-Tooth disease
   • Chronic musculoskeletal and myofascial pain

   Rationale: A systematic review of the available randomized trials found lack of efficacy for Dysport in myofascial pain syndromes.

   • Gastroparesis

   Rationale: There is currently insufficient evidence to support the use of AbobotulinumtoxinA (Dysport) for gastroparesis. While botulinum toxin type A has been studied in the treatment of gastroparesis, most studies have focused on the use of onabotulinumtoxinA (Botox) and there is limited research on the efficacy of abobotulinumtoxinA for this indication. More research is needed to determine the safety and effectiveness of abobotulinumtoxinA in the treatment of gastroparesis.

   • Headaches, including migraines, tension headaches, or headaches secondary to cranial neuralgia

   Rationale: A prospective, multi-center, randomized, double-blind placebo-controlled trial found no significant difference between placebo and Dysport in headache free days (primary outcome) among patients suffering from chronic migraine.

   • Hyperhidrosis, other than axillary hyperhidrosis

   Rationale: An expert review by the American Academy of Neurology concluded that the evidence for Dysport in palmar hyperhidrosis was inadequate to guide clinical decision making.

   • Lateral epicondylitis
   • Obesity
   • Plantar fasciitis
   • Postnatal brachial plexus injury
   • Raynaud’s Phenomenon
   • Refractory interstitial cystitis
   • Shoulder pain
   • Strabismus
   • Tardive dyskinesia
   • Temporomandibular Disorders (TMD)

   T. Tourette Syndrome

   Rationale: There is currently insufficient evidence to support the use of Dysport (abobotulinumtoxinA) in the treatment of Tourette Syndrome. While some small studies and case reports have shown promise, larger, well-designed clinical trials are needed to fully evaluate the safety and efficacy of this treatment approach. The American Academy of Neurology's clinical practice guidelines currently do not recommend the use of botulinum toxin for the treatment of tics in Tourette Syndrome.

   U. Trigeminal neuralgia

   RimabotulinumtoxinB (Myobloc) (J0587)

   The use of RimabotulinumtoxinB (Myobloc) for any other indication not listed above is considered experimental, investigational, or unproven; these excluded indications include, but are not limited to, the following:

   • A. Bladder dysfunction (e.g. overactive bladder, detrusor hyperreflexia)

     Rationale: The evidence has been contradictory or inconclusive, with some studies showing RimabotulinumtoxinB efficacy while others have demonstrated a lack of benefit. A 2011 Cochrane review (updating the previous 2007 review) identified 19 studies meeting inclusion criteria, and found that the efficacy of RimabotulinumtoxinB was inferior to that of type A toxins with a substantially shorter duration of benefit across randomized trials for bladder dysfunction.

   • B. Blepharospasm and Associated Facial Nerve Disorders (e.g., hemifacial spasm)

     Rationale: RimabotulinumtoxinB is limited in efficacy and experience, but has been used for blepharospasm or hemifacial spasm, mainly in patients who have responded to onabotulinumtoxinA. The American Academy of Neurology recommends onabotulinumtoxinA and incobotulinumtoxinA as treatment options, and abobotulinumtoxinA may be considered for blepharospasm, but does not make a recommendation for rimabotulinumtoxinB due to insufficient data.

   • C. Disabling headaches (e.g., migraine, cluster headache)
   • D. Gastroparesis

     Rationale: There is limited evidence to support the use of RimabotulinumtoxinB (Myobloc) in the treatment of gastroparesis. Some small studies have suggested potential benefit in improving symptoms such as nausea and vomiting, but more research is needed to establish the safety and effectiveness of this treatment for gastroparesis.

   • E. Hyperhidrosis (including primary axillary hyperhidrosis and focal palmar hyperhidrosis)

     Rationale: Although RimabotulinumtoxinB has been utilized for symptomatic management of primary axillary and focal palmar hyperhidrosis characterized by excessive glandular secretion, its efficacy evidence and experience are less extensive when compared to OnabotulinumtoxinA.

   • F. Incontinence after spinal cord injury
   • G. Involuntary (smooth) muscle overactivity (e.g., neurogenic voiding dysfunction, anal sphincter disorders)
   • H. Musculoskeletal pain disorders (e.g., myofascial pain syndrome, chronic low back pain, pain associated with brachial plexopathy)
   • I. Raynaud’s Phenomenon

     Rationale: There is currently insufficient evidence to support the use of RimabotulinumtoxinB (Myobloc) in the treatment of Raynaud's Phenomenon.

   • J. Spasmodic dysphonia
   • K. Spasticity in adults, including post-stroke spasticity and spasticity of the upper and/or lower extremities associated with other neurological disorders

     Rationale: The clinical evidence for RimabotulinumtoxinB (type b agent) is substantially limited compared to type A agents. A single randomized trial on 24 patients showed possible improvements with RimabotulinumtoxinB but concluded that larger studies with long-term follow up were needed for further evidence. The US Pharmacopeial Convention has stated that off-label use of RimabotulinumtoxinB for spasticity secondary to stroke or brain injury may be indicated, however updated data has failed to demonstrate the statistically significant benefit seen in earlier studies. The American Academy of Neurology currently states (per 2016 guidelines), that the data is insufficient to determine the efficacy of Myobloc in lower limb spasticity, and the evidence is limited to a single Class I study for upper limb spasticity.

   • L. Spasticity in children with cerebral palsy (CP)

     Rationale: A review by the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society concluded that the evidence was limited in children with CP, and that the existing evidence on RimabotulinumtoxinB showed inferior efficacy compared to type A toxins.

   • M. Temporomandibular Disorders (TMD)

     Rationale: There is currently insufficient evidence to support the use of RimabotulinumtoxinB (Myobloc) in the treatment of Temporomandibular Disorders (TMD). While there are some studies investigating the use of botulinum toxin in TMD, the evidence is limited and conflicting, with some studies reporting positive outcomes and others reporting no significant benefit. Further research is needed to determine the efficacy of RimabotulinumtoxinB in the treatment of TMD.

   • N. Tourette Syndrome

     Rationale: There is currently limited evidence on the use of RimabotulinumtoxinB (Myobloc) in the treatment of Tourette Syndrome. While some small studies have shown potential benefit, further research is needed to determine its efficacy and safety for this indication.

   • O. Upper esophageal dysfunction or achalasia

   RimabotulinumtoxinB (Myobloc) (J0587)

   Rationale: A 2014 Cochrane review revealed no randomized clinical trials on RimabotulinumtoxinB for upper esophageal dysfunction.

   IncobotulinumtoxinA (Xeomin) (J0588)

   The use of IncobotulinumtoxinA (Xeomin) for any other indication not listed above is considered experimental, investigational, or unproven; these excluded indications include, but are not limited to, the following:

   • Atrial fibrillation
   • Detrusor hyperactivity (e.g. bladder overactivity)
     • Rationale: There is limited evidence on Xeomin in patients with overactive bladder. Preliminary results on 95 patients from a double-blinded study on Xeomin and Botox in bladder overactivity were presented at the 27th Annual Congress of the European Association of Urology. However, further peer-reviewed randomized evidence is currently lacking, limiting guidance for clinical application.
   • Hyperhidrosis, including axillary, palmar, and craniofacial
     • Rationale: Xeomin and Botox were compared in a double-blind trial in treating palmar hyperhidrosis. There were no significant differences in short- or long-term efficacy outcomes, however only 25 patients were included in the study. Given the small sample size and lack of confirmatory studies, further evidence is required. Similar limitations are present in comparable studies on axillary hyperhidrosis. Further evidence is needed to determine a potential benefit of Xeomin for this indication.
   • Gastroparesis
     • Rationale: There is currently insufficient evidence to support the use of IncobotulinumtoxinA (Xeomin) for gastroparesis. While some small studies have shown promising results, larger randomized controlled trials are needed to establish its efficacy and safety in this condition. The use of botulinum toxin for gastroparesis is still considered investigational and not recommended for routine clinical use.
   • Migraine prophylaxis
     • Rationale: The evidence for Xeomin in migraine prophylaxis comes from small, retrospective case series and poster presentations, indicating further prospective, randomized evidence is required to guide any potential clinical application.
   • Parkinson disease with tremor
     • Rationale: There is insufficient, conflicting, or poor evidence regarding the use of incobotulinumtoxinA for Parkinson disease with tremor, and more research is needed.
   • Plantar fasciitis
     • Rationale: There is a lack of sufficient, conflicting, or poor evidence regarding the use of incobotulinumtoxinA for plantar fasciitis.
   • Post-stroke lower limb spasticity
     • Rationale: A prospective, open label study on 71 patients demonstrated safety and efficacy of Xeomin in post-stroke lower limb spasticity, however further randomized studies are required to establish clinical use. Furthermore, the 2016 American Academy of Neurology Guidelines state that there 'is insufficient evidence to support or refute the use of incoBoNT-A for the treatment of lower limb spasticity.'
   • Raynaud’s Phenomenon
     • Rationale: There is currently insufficient evidence to support the use of IncobotulinumtoxinA (Xeomin) for Raynaud's Phenomenon.
   • Temporomandibular Disorders (TMD)
     • Rationale: There is limited evidence to support the use of IncobotulinumtoxinA for the treatment of Temporomandibular Disorders (TMD). While some studies have shown potential benefits, more research is needed to establish its efficacy and safety in this context.
   • Tourette Syndrome
     • Rationale: There is insufficient evidence to support the use of IncobotulinumtoxinA (Xeomin) for Tourette Syndrome.

   DaxibotulinumtoxinA-lanm (Daxxify) (C9399, J3590)

   The use of DaxibotulinumtoxinA-lanm (Daxxify) for any other indication not listed above is considered experimental, investigational, or unproven; these excluded indications include, but are not limited to, the following:

   • Pancreatic Carcinoma
   • Plantar fascial fibromatosis
   • Spasmodic Dysphonia