Antitussives

Pharmacy Benefit Coverage Criteria

Effective Date ...... 9/1/2021 Next Review Date… ...... 9/1/2022 Coverage Policy Number ...... P0083

Antitussives

Table of Contents Related Coverage Resources

Medical Necessity Criteria ...... 1 Opioid Therapy FDA Approved Indications ...... 3 Recommended Dosing ...... 5 Background ...... 6 References ...... 7

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 the following antitussive products: • Benzonatate 150 mg capsules • Opioid-containing cough suppressant regimens • TussiCapsTM (hydrocodone polistirex/chlorpheniramine polistirex) capsules

Standard / Performance Plans Value / Advantage Plans Cigna Total Savings Plans Legacy Plans Hycodan Individual is 18 years of age or older AND day supply is greater than or equal to 21 (hydrocodone- days, then ALL of the following: homatropine) • Documented symptomatic relief of cough • Documented failure/inadequate response, contraindication per FDA label, Hydrocodone- intolerance, or not a candidate for nonopioid pharmacologic therapies intended to Chlorpheniramine- treat cough (for example, benzonatate*, dextromethorphan) Pseudoephedrine *May be subject to prior authorization.

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Hydrocodone bitrate- Chlorpheniramine maleate

Hydrocodone polistirex- Chlorpheniramine polistirex

Hydrocodone- Guaifenesin

Hydrocodone- Homatropine

Promethazine- Codeine

Promethazine- Phenylepherine- Codeine

Tuxarin ER (chlorpheniramine maleate-codeine phosphate)

Tuzistra XR (chlorpheniramine polistirex-codeine polistirex)

Coverage for the following products varies across plans: • Benzonatate 150 mg capsules • TussiCapsTM (hydrocodone polistirex/chlorpheniramine polistirex) capsules

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: Standard / Performance Plans Value / Advantage Plans Cigna Total Savings Plans Legacy Plan Benzonatate 150 All of the following mg • Documented intolerance to BOTH of the following: o Benzonatate 100 mg capsule o Benzonatate 200 mg capsule

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Standard / Performance Plans Value / Advantage Plans Cigna Total Savings Plans Legacy Plan TussiCapsTM ALL of the following: (hydrocodone • Individual is 18 years of age or older polistirex / • Documented symptomatic relief of cough chlorpheniramine • Documented failure/inadequate response, contraindication per FDA label, polistirex) intolerance, or not a candidate for nonopioid pharmacologic therapies intended to treat cough (for example, benzonatate*, dextromethorphan) • Documented failure/inadequate response, contraindication per FDA label, intolerance, not a candidate for, or inability to use to ONE of the following: o chlorpheniramine/hydrocodone extended release suspension* o promethazine/codeine syrup* o Tuzistra XR (codeine/chlorpheniramine polistirex) extended release suspension* *May be subject to prior authorization

Use of opioid-containing cough suppressants is considered not medically necessary if under the age of 18.

Initial and reauthorization is up to 3 months unless otherwise stated.

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.

Opioid-containing cough suppressant regimens are considered experimental, investigational or unproven for ANY other use.

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

FDA Approved Indication

FDA Safety Communication In January 2018, the FDA issued a drug safety communication restricting the use of prescription codeine and hydrocodone pain and cough medicines in children. The FDA required safety labeling changes for all cough and cold medicines containing codeine or hydrocodone to limit the use of these products to adults 18 years and older stating the risks of these medicines outweigh their benefits in children younger than eighteen. FDA gave an additional directive that all products are required to have a Boxed Warning regarding the risks of misuse, abuse, addiction, overdose, death , and slowed or difficult breathing (FDA website, 2018). Tussicaps’ product label has not yet been updated to reflect these FDA requirements.

Brand Name Approved Indication Benzonatate Indicated for the symptomatic relief of cough. Hydrocodone- Indicated for the temporary relief of cough and upper respiratory symptoms, including Chlorpheniramine- nasal congestion, associated with allergy or the common cold in patients 18 years of Pseudoephedrine age and older.

Limitations of Use:

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Brand Name Approved Indication • Not indicated for pediatric patients under 18 years of age • Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, reserve hydrocodone-CPM-pseudoephedrine for use in adult patients for whom the benefits of cough suppression are expected to outweigh the risks, and in whom an adequate assessment of the etiology of the cough has been made Hydrocodone Indicated for the temporary relief of cough and upper respiratory symptoms associated polistirex- with allergy or the common cold in patients 18 years of age and older. Chlorpheniramine polistirex Limitations of Use: • Not indicated for pediatric patients under 18 years of age • Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, reserve hydrocodone-chlorpheniramine extended-release for use in adult patients for whom the benefits of cough suppression are expected to outweigh the risks, and in whom an adequate assessment of the etiology of the cough has been made Hydrocodone Indicated for the temporary relief of cough and upper respiratory symptoms associated bitrate- with allergy or the common cold in patients 18 years of age and older. Chlorpheniramine maleate Limitations of Use: • Not indicated for pediatric patients under 18 years of age • Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, reserve hydrocodone-chlorpheniramine for use in adult patients for whom the benefits of cough suppression are expected to outweigh the risks, and in whom an adequate assessment of the etiology of the cough has been made Hydrocodone- Indicated for the symptomatic relief of cough and to loosen mucus associated with the Guaifenesin common cold in patients 18 years of age and older.

Limitations of Use: • Not indicated for pediatric patients under 18 years of age • Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, reserve hydrocodone-guaifenesin for use in adult patients for whom the benefits of cough suppression are expected to outweigh the risks, and in whom an adequate assessment of the etiology of the cough has been made Hydrocodone- Indicated for the symptomatic relief of cough in patients 18 years of age and older. Homatropine Limitations of Use: • Not indicated for pediatric patients under 18 years of age • Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, reserve hydrocodone-homatropine for use in adult patients for whom the benefits of cough suppression are expected to outweigh the risks, and in whom an adequate assessment of the etiology of the cough has been made Promethazine- Indicated for the temporary relief of coughs and upper respiratory symptoms associated Codeine with allergy or the common cold in patients 18 years of age and older.

Limitations of Use: • Not indicated for pediatric patients under 18 years of age • Because of the risks of addiction, abuse, and misuse with opioids, even a recommended doses, reserve promethazine-codeine for use in adult patients for whom the benefits of cough suppression are expected to outweigh the risks, and in whom an adequate assessment of the etiology of the cough has been made

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Brand Name Approved Indication Promethazine- Indicated for the temporary relief of coughs and upper respiratory symptoms, including Phenylephrine- nasal congestion, associated with allergy or the common cold in patients 18 years of Codeine age and older.

Limitations of Use: • Not indicated for pediatric patients under 18 years of age • Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, reserve promethazine HCl, phenylephrine HCl and codeine phosphate oral solution for use in adult patients for whom the benefits of cough suppression are expected to outweigh the risks, and in whom an adequate assessment of the etiology of the cough has been made TussiCapsTM Tussicaps extended-release capsules are indicated for relief of cough and upper (hydrocodone respiratory symptoms associated with allergy or a cold in adults. polistirex / chlorpheniramine polistirex) Tuxarin ERTM Tuxarin ER is indicated for the temporary relief of cough and upper respiratory (codeine- symptoms associated with allergy or the common cold in patients 18 years of age and chlorpheniramine) older.

Limitations of Use: • Not indicated for pediatric patients under 18 years of age. • Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, reserve Tuzistra XR for use in adult patients for whom the benefits of cough suppression are expected to outweigh the risks, and in whom an adequate assessment of the etiology of the cough has been made. Tuzistra XR® Tuzistra XR® is indicated for the temporary relief of cough and upper respiratory (codeine- symptoms associated with allergy or the common cold in patients 18 years of age and chlorpheniramine) older.

Recommended Dosing

FDA Recommended Dosing Brand Name Recommended Dosing Benzonatate Adults and Children over 10 years of age: • Usual dose is one 100 mg, 150 mg, or 200 mg capsule three times a day as needed for cough. If necessary to control cough, up to 600 mg daily in three divided doses may be given. • Benzonatate should be swallowed whole. Benzonatate capsules are not to be broken, chewed, dissolved, cut or crushed Hydrocodone- Adults 18 years of age and older: Chlorpheniramine- • 5 mL every 4 to 6 hours as needed, not to exceed 4 doses (20 mL) in 24 hours Pseudoephedrine Hydrocodone Adults 18 years of age and older: polistirex- • 5 mL every 12 hours as needed, not to exceed 2 doses (10 mL) in 24 hours

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Brand Name Recommended Dosing Chlorpheniramine polistirex Hydrocodone Adults 18 years of age and older: bitrate- • 5 mL every 4 to 6 hours as needed, not to exceed 4 doses (20 mL) in 24 hours Chlorpheniramine maleate Hydrocodone- Adults 18 years of age and older: Guaifenesin • 10 mL every 4 to 6 hours as needed, not to exceed 6 doses (60 mL) in 24 hours Hydrocodone- Adults 18 years of age and older: homatropine • One (1) tablet or 5 mL of the oral solution every 4 to 6 hours as needed; not to exceed six (6) tablets or 30 mL in 24 hours Promethazine- Adults 18 years of age and older: Codeine • 5 mL every 4 to 6 hours as needed, not to exceed 6 doses (30 mL) in 24 hours Promethazine- Adults 18 years of age and older: Phenylephrine- • 5 mL every 4 to 6 hours as needed, not to exceed 6 doses (30 mL) in 24 hours Codeine TussiCapsTM Adults (hydrocodone • One (1) full-strength TussiCaps® extended-release capsule every 12 hours, not polistirex / exceed 2 capsules in 24 hours chlorpheniramine polistirex) Tuxarin ERTM Adults 18 years of age and older: (codeine- • One (1) tablet every 12 hours as needed, not to exceed 2 tablets in 24 hour chlorpheniramine) Tuzistra XR® Adults 18 years of age and older: (codeine- • 10 mL every 12 hours as needed, not to exceed 2 doses (20 mL) in 24 hours chlorpheniramine)

Background

Professional Societies/Organizations American Academy of Family Physicians (AAFP) The AAFP guidelines on the treatment of the common cold in children and adults recommend against the use opioids in the treatment of cough, citing there are no clinical differences between treatment and placebo (Fashner, 2012).

American College of Chest Physicians (ACCP) The ACCP classifies cough based on duration of the symptom. An acute cough is one that last less than three weeks and is typically a symptom of common cold, acute bronchitis, allergic rhinitis, or community-acquired pneumonia. A cough duration between 3 weeks and 8 weeks is classified as subacute is typically attributed to pertussis or of postinfectious process. A cough lasting greater than 8 weeks is classified as chronic and can be a symptom of several conditions such as asthma, gastroesophageal reflux, drug-induced, or occupational. In the 2017 update of the guideline for the treatment of acute cough associated with common cold, the ACCP recommends avoiding the use of codeine-containing medications in those less than 18 years old for cough due to the common cold. ACCP noted the potential for serious side effects including respiratory distress as support for this recommendation (Maleskar, 2017; Irwin, 2014, 2006).

Published guidelines do address benzonatate’s place in therapy (Fashner et al, 2012; Maleskar, 2017).

Off-label uses AHFS Drug Information 2019 Edition supports no off-label uses for either benzonatate or TussiCapsTM.

Generics

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The FDA’s generic drug approval process does not require the drug sponsor to repeat costly animal and clinical research on ingredients or dosage forms already approved for safety and effectiveness. Generic drugs must establish the following for approval: • contain the same active ingredients as the innovator drug(inactive ingredients may vary) • be identical in strength, dosage form, and route of administration • have the same use indications • be bioequivalent • meet the same batch requirements for identity, strength, purity, and quality • be manufactured under the same strict standards of FDA's good manufacturing practice regulations required for innovator products

A generic drug is the same as a brand-name drug in dosage, safety, strength, quality, the way it works, the way it is taken and the way it should be used. FDA requires generic drugs have the same high quality, strength, purity and stability as brand-name drugs. Not every brand-name drug has a generic drug. When new drugs are first made they have drug patents. Most drug patents are protected for 20 years. The patent, which protects the company that made the drug first, doesn't allow anyone else to make and sell the drug. When the patent expires, other drug companies can start selling a generic version of the drug. But, first, they must test the drug and the FDA must approve it.

References

1. Benzonatate [prescribing information], Montvale, NJ: Ascend Laboratories, LLC.; October 2014. 2. Croughan-Minihane MS, Petitti DB, Rodnick JE, et al. Clinical trial examining effectiveness of three cough syrups. J Am Board Fam Pract. 1993;6(2):109-115. 3. Fashner J, Ericson K, Werner S. Treatment of the common cold in children and adults. Am Fam Physician. 2012;86(2):153-159. 4. FDA Safety Communication: FDA requires labeling changes for prescription opioid couch and cold medicine to limit their use to adults 18 years and older. January 11, 2018. FDA website. https://www.fda.gov/Drugs/DrugSafety/ucm590435.htm. Accessed January 7, 2019. 5. Hydrocodone bitrate-chlorpheniramine maleate [package insert], Morristown, NJ: Hawthorn Pharmaceuticals, Inc.; June 2018. 6. Hydrocodone-chlorpheniramine-pseudoephedrine [package insert], Morristown, NJ: Hawthorn Pharmaceuticals, Inc.; June 2018. 7. Hydrocodone-Guaifenesin [package insert], Wilmington, DE: BBK Pharmaceuticals, LLC; June 2018. 8. Hydrocodone-homatropine [package insert], Malver, PA: Endo Pharmaceuticals Inc.; June 2018. 9. Hydrocodone polistirex-Chlorpheniramine polistirex [package insert], Smyrna, GA: UCB Inc.; June 2018. 10. Irwin RS, Baumann MH, Bolser DC, et al. Diagnosis and management of cough executive summary: ACCP evidence-based clinical practice guidelines. Chest. 2006;129(1 Suppl):1S. 11. Irwin RS, French CT, Lewis SZ, et al. Overview of the Management of Cough: CHEST Guideline and Expert Panel Report. CHEST2014; 146( 4): 885 – 889. 12. Malesker MM; and CHEST Expert Cough Panel, Pharmacologic and nonpharmacologic treatment of acute cough associated with the common cold. Chest. 2017;152(5):1021-1037. doi: 10.1016/j.chest.2017.08.009. 13. Promethazine with codeine oral solution [package insert], Morton Grove, IL: Morton Grove Pharmaceuticals, Inc.; November 2018. 14. Promethazine-phenylephrine-codeine [package insert], Lincolnton, NC: Actavis Mid Atlantic LLC; February 2013. 15. TussiCapsTM [prescribing information], St. Louis, MI: Mallinckrodt Inc.; January 2007. 16. Tuxarin ER [package insert], Louisville, KY: MainPointe Pharmaceuticals, LLC; August 2018. 17. Tuzistra XR [package insert], Berwyn, PA: Vernalis Pharmaceuticals, Inc.; August 2018.

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