Pharmacy Benefit Coverage Criteria

Effective Date ...... 10/1/2020 Next Review Date… ...... 5/1/2021 Coverage Policy Number ...... P0071

Skeletal Muscle Relaxants

Table of Contents Related Coverage Resources

Medical Necessity Criteria ...... 1 FDA Approved Indications ...... 2 Recommended Dosing ...... 3 Background ...... 3 References ...... 4

INSTRUCTIONS FOR USE The following Coverage Policy applies to health benefit plans administered by Cigna Companies. Certain Cigna Companies and/or lines of business only provide utilization review services to clients and do not make coverage determinations. References to standard benefit plan language and coverage determinations do not apply to those clients. Coverage Policies are intended to provide guidance in interpreting certain standard benefit plans administered by Cigna Companies. Please note, the terms of a customer’s particular benefit plan document [Group Service Agreement, Evidence of Coverage, Certificate of Coverage, Summary Plan Description (SPD) or similar plan document] may differ significantly from the standard benefit plans upon which these Coverage Policies are based. For example, a customer’s benefit plan document may contain a specific exclusion related to a topic addressed in a Coverage Policy. In the event of a conflict, a customer’s benefit plan document always supersedes the information in the Coverage Policies. In the absence of a controlling federal or state coverage mandate, benefits are ultimately determined by the terms of the applicable benefit plan document. Coverage determinations in each specific instance require consideration of 1) the terms of the applicable benefit plan document in effect on the date of service; 2) any applicable laws/regulations; 3) any relevant collateral source materials including Coverage Policies and; 4) the specific facts of the particular situation. Coverage Policies relate exclusively to the administration of health benefit plans. Coverage Policies are not recommendations for treatment and should never be used as treatment guidelines. In certain markets, delegated vendor guidelines may be used to support medical necessity and other coverage determinations.

Medical Necessity Criteria

This policy addresses coverage criteria for skeletal muscle relaxants.

Coverage for skeletal muscle relaxants varies across plans. Refer to the customer’s benefit plan document for coverage details. Where coverage requires the use of preferred products, the following criteria apply.

For Employer Group Plans: Non-Covered Standard / Value / Cigna Total Legacy Product Performance Advantage Savings Amrix® BOTH of the following: (cyclobenzaprine • Documented failure / inadequate response, intolerance or inability to use 15 mg and 30 mg cyclobenzaprine 5 mg, 7.5 mg, or 10 mg tablets extended release • Documented failure / inadequate response, contraindication per FDA label, intolerance capsules) or not a candidate for ALL of the following: carisoprodol, chlorzoxazone, methocarbamol, orphenadrine Chlorzoxazone BOTH of the following: 250 mg, 375 mg • Documented intolerance or inability to use chlorzoxazone 500 mg tablets and 750 mg

Page 1 of 4 Pharmacy Benefit Clinical Criteria: P0071 Non-Covered Standard / Value / Cigna Total Legacy Product Performance Advantage Savings • Documented failure / inadequate response, contraindication per FDA label, intolerance or not a candidate for ALL of the following: carisoprodol, cyclobenzaprine, methocarbamol, orphenadrine Lorzone® BOTH of the following: (chlorzoxazone • Documented intolerance or inability to use chlorzoxazone 500 mg tablets 375 mg and 750 • Documented failure / inadequate response, contraindication per FDA label, mg tablets) intolerance or not a candidate for ALL of the following: carisoprodol, cyclobenzaprine, methocarbamol, orphenadrine

Initial and reauthorization is up to 3 months.

When coverage is available and medically necessary, the dosage, frequency, duration of therapy, and site of care should be reasonable, clinically appropriate, and supported by evidence-based literature and adjusted based upon severity, alternative available treatments, and previous response to therapy.

Note: Receipt of sample product does not satisfy any criteria requirements for coverage.

*If you’re a Cigna provider, please log in to the Cigna for Health Care Professionals website and search for specific patients to view their covered medications.

FDA Approved Indications

Product FDA Approved Indications Amrix Amrix is indicated as an adjunct to rest and physical therapy for relief of muscle spasm (cyclobenzaprine) associated with acute, painful musculoskeletal conditions. Improvement is manifested by extended-release relief of muscle spasm and its associated signs and symptoms, namely, pain, capsule tenderness, and limitation of motion.

Limitations of Use • Amrix should be used only for short periods (up to two or three weeks) because adequate evidence of effectiveness for more prolonged use is not available and because muscle spasm associated with acute, painful musculoskeletal conditions is generally of short duration and specific therapy for longer periods is seldom warranted. • Amrix has not been found effective in the treatment of spasticity associated with cerebral or spinal cord disease or in children with cerebral palsy. Chlorzoxazone Chlorzoxazone is indicated as an adjunct to rest, physical therapy, and other measures 250 mg tablet for the relief of discomfort associated with acute, painful musculoskeletal conditions. The mode of action of this drug has not been clearly identified, but may be related to its sedative properties. Chlorzoxazone does not directly relax tense skeletal muscles in man. Lorzone Lorzone is indicated as an adjunct to rest, physical therapy, and other measures for the (chlorzoxazone) relief of discomfort associated with acute, painful musculoskeletal conditions. The mode tablet of action of this drug has not been clearly identified, but may be related to its sedative properties. Chlorzoxazone does not directly relax tense skeletal muscles in man.

Page 2 of 4 Pharmacy Benefit Clinical Criteria: P0071 Recommended Dosing

Product FDA Recommended Dosing Amrix The recommended adult dose for most patients is one (1) Amrix 15 mg capsule taken (cyclobenzaprine) once daily. Some patients may require up to 30 mg/day, given as one (1) Amrix 30 mg extended-release capsule taken once daily or as two (2) Amrix 15 mg capsules taken once daily. capsule The use of Amrix for periods longer than two or three weeks is not recommended. Chlorzoxazone Usual Adult Dosage 250 mg tablet 250 mg three or four times daily. Initial dosage for painful musculoskeletal conditions should be 500 mg three or four times daily. If adequate response is not obtained with this dose, it may be increased to 750 mg three or four times daily. As improvement occurs dosage can usually be reduced. Lorzone Usual Adult Dosage (chlorzoxazone) Lorzone Tablets (chlorzoxazone USP) 375 mg: tablet One (375 mg) tablet three or four times daily. If adequate response is not obtained with this dose, the 375 mg tablets may be increased to two tablets (750 mg) three or four times daily. As improvement occurs dosage can usually be reduced.

Lorzone Tablets (chlorzoxazone USP) 750 mg: 1/3 tablet (250 mg) three or four times daily. Initial dosage for painful musculoskeletal conditions should be 2/3 tablet (500 mg) three or four times daily. If adequate response is not obtained with this dose, it may be increased to one tablet (750 mg) three or four times daily. As improvement occurs dosage can usually be reduced.

Drug Availability Product Drug Availability Amrix Amrix is available as an extended-release capsule containing 15 mg or 30 mg of cyclobenzaprine. Lorzone Lorzone is available as a tablet containing 375 mg or 750 mg of chlorzoxazone.

Background

Therapeutic Alternatives Therapeutic alternatives to Amrix include the following skeletal muscle relaxants: carisoprodol, chlorzoxazone, methocarbamol and orphenadrine.

Therapeutic alternatives to Lorzone or chlorzoxazone include the following skeletal muscle relaxants: carisoprodol, cyclobenzaprine, methocarbamol and orphenadrine.

Professional Societies/Organizations American College of Physicians guidelines for the noninvasive treatment of acute, subacute and chronic low back pain state that most patients with acute or subacute low back pain improve over time regardless of treatment. For this reason, the guidelines recommend nonpharmacologic treatment with superficial heat, massage, acupuncture, or spinal manipulation as first line options. When pharmacologic treatment is chosen, nonsteroidal anti-inflammatory drugs or skeletal muscle relaxants should be chosen. The guidelines do not advocate the use of one product over another. (Qaseem, 2017)

Off Label Uses AHFS Drug Information 2019 Edition does not have a monograph for Amrix or Lorzone.

Comparative Studies There are no clinical studies comparing Amrix, chlorzoxazone or Lorzone with other therapeutic alternatives.

Page 3 of 4 Pharmacy Benefit Clinical Criteria: P0071 References

1. McEvoy GK, ed. 2019. AHFS Drug Information® - 60th Ed. Bethesda, MD. American Society of Health- System Pharmacists. 2. Qaseem A, Wilt TJ, McLean RM, et al. Noninvasive Treatments for Acute, Subacute, and Chronic Low Back Pain: A Clinical Practice Guideline From the American College of Physicians. Ann Intern Med. 2017 Apr 4; 166 (7): 514-530. 3. Teva Pharmaceuticals USA, Inc. Amrix (cyclobenzaprine) extended-release capsule [prescribing information]. North Wales, PA: Teva Pharmaceuticals USA, Inc. April 2019. 4. Vertical Pharmaceuticals LLC. Lorzone (chlorzoxazone) tablet [prescribing information]. Sayreville, NJ: Vertical Pharmaceuticals LLC; September 2014.

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Page 4 of 4 Pharmacy Benefit Clinical Criteria: P0071