Constipation Agents

Preferred agents: linaclotide (LINZESS), naloxegol (MOVANTIK), naldemedine (SYMPROIC)

Non-Preferred Agents (step therapy): lubiprostone (AMITIZA), tenapanor (IBSRELA), prucalopride (MOTEGRITY), methylnaltrexone bromide tablets (RELISTOR), methylnaltrexone bromide subcutaneous injection (RELISTOR), plecanatide (TRULANCE), tegaserod (ZELNORM)

Indication for Prior Authorization:
  • Amitiza; lubiprostone authorized brand alternative (ABA)
    • Chronic Idiopathic Constipation (CIC) - Indicated for the treatment of CIC in adults.
    • Opioid-Induced Constipation (OIC) - Indicated for the treatment of OIC in adult patients with chronic non-cancer pain, including patients with chronic pain related to prior cancer or its treatment who do not require frequent (e.g., weekly) opioid dosage escalation. Limitations of Use: Effectiveness of Amitiza in the treatment of OIC in patients taking diphenylheptane opioids (e.g., methadone) has not been established.
    • Irritable Bowel Syndrome with Constipation (IBS-C) - Indicated for the treatment of IBS-C in women at least 18 years old.
  • Ibsrela
    • IBS-C - Indicated for the treatment of IBS-C.
  • Linzess
    • IBS-C - Indicated in adults for the treatment of IBS-C.
    • CIC - Indicated in adults for the treatment of CIC.
  • Motegrity
    • CIC - Indicated for the treatment of CIC in adults.
  • Movantik
    • OIC (chronic non-cancer pain, chronic pain related to prior cancer or its treatment) - Indicated for the treatment of OIC in adult patients with chronic non-cancer pain, including patients with chronic pain related to prior cancer or its treatment who do not require frequent (e.g., weekly) opioid dosage escalation.
  • Relistor Injection
    • OIC (advanced illness or pain caused by active cancer) - Indicated for the treatment of OIC in adult patients with advanced illness or pain caused by active cancer who require opioid dosage escalation for palliative care.
    • OIC (chronic non-cancer pain, chronic pain related to prior cancer or its treatment) - Indicated for the treatment of OIC in adult patients with chronic non-cancer pain, including patients with chronic pain related to prior cancer or its treatment who do not require frequent (e.g., weekly) opioid dosage escalation.
  • Relistor Tablet
    • OIC (chronic non-cancer pain, chronic pain related to prior cancer or its treatment) - Indicated for the treatment of OIC in adult patients with chronic non-cancer pain, including patients with chronic pain related to prior cancer or its treatment who do not require frequent (e.g., weekly) opioid dosage escalation.
  • Symproic
    • OIC (chronic non-cancer pain, chronic pain related to prior cancer or its treatment) - Indicated for the treatment of OIC in adult patients with chronic non-cancer pain, including patients with chronic pain related to prior cancer or its treatment who do not require frequent (e.g., weekly) opioid dosage escalation.
  • Trulance
    • CIC - Indicated in adults for the treatment of CIC.
    • IBS-C - Indicated in adults for the treatment of IBS-C.
  • Zelnorm
    • IBS-C - Indicated for the treatment of adult women less than 65 years of age with IBS-C.  Limitation of Use: The safety and effectiveness of Zelnorm in men with IBS-C have not been established.
Coverage Criteria:

Request for Motegrity, Trulance or Zelnorm:

  • Dose for an appropriate indication does not exceed the maximum approved by the FDA
    • Motegrity - up to 2 mg once daily for CIC.
    • Trulance - 3 mg once daily for CIC and IBS-C.
    • Zelnorm - 6 mg twice daily for IBS-C (females less than 65 years of age only); AND
  • Patient is 18 years of age or older; AND
  • Patient has experienced an inadequate response, contraindication, or intolerable side effect to Linzess.

Request for Relistor tablet or Relistor injection:

  • Dose for an appropriate indication does not exceed the maximum approved by FDA
    • Relistor tablet - up to 450 mg once daily for OIC (non-cancer pain).
    • Relistor injection - up to 12 mg once daily for OIC (non-cancer pain or advanced illness); AND
  • Patient is 18 years of age or older; AND
  • Patient has experienced an inadequate response, contraindication, or intolerable side effect to Symproic or Movantik.

Request for lubiprostone ABA or Amitiza:

  • Dose for an appropriate indication does not exceed the maximum approved by the FDA
    • lubiprostone (Amitiza) - up to 24 mcg twice daily for CIC and OIC.
    • lubiprostone (Amitiza) - 8 mcg twice daily for IBS-C (females only); AND
  • Patient is 18 years of age or older; AND
  • Patient has experienced an inadequate response, contraindication, or intolerable side effect to Linzess, Symproic, or Movantik.

Request for Ibsrela:

  • Dose for an appropriate indication does not exceed the maximum approved by the FDA
    • Ibsrela - up to 50 mg twice daily for IBS-C; AND
  • Patient is 18 years of age or older; AND
  • Patient has experienced an inadequate response, contraindication, or intolerable side effect to Linzess; AND
  • Patient has experienced an inadequate response, contraindication, or intolerable side effect to one of the following:
    o    Trulance
    o    Lubiprostone ABA 8 mcg twice daily (females only)
    o    Amitiza 8 mcg twice daily (females only)
Reauthorization Criteria:

Request for continuation of treatment:

  • Dose does not exceed FDA label maximum for an appropriate indication; AND
  • Patient has experienced a positive clinical response to therapy.
Coverage Duration:
  • Initial: 12/31/2099
  • Reauthorization: 12/31/2099
Authorization is not covered for the following:

The use of this drug for indications not listed in this policy does not meet the coverage criteria established by the Western Health Advantage (WHA) Pharmacy and Therapeutics (P&T) Committee.

Additional Information:
  • Linzess and Trulance carries a risk of serious dehydration in pediatric patients. The safety and effectiveness of Linzess and Trulance has not been established in patients less than 18 years.
  • Maintenance laxative therapy should be discontinued prior to initiating Relistor; may reintroduce laxatives as needed if suboptimal response to Relistor after 3 days.
  • Use of Relistor injections beyond 4 months has not been studied. Discontinue methylnaltrexone if opioids are discontinued.
  • Alteration in analgesic dosing regimen prior to initiating Movantik is not required.
  • Zelnorm should be discontinued in patients with an inadequate response after 4 to 6 weeks of treatment.
Policy Updates:
  • 10/19/2021 –Prior authorization policies for agents used to treat CIC, IBS-C, and OIC are combined into step therapy policy; Removed prior authorization from Linzess , Movantik, and Symproic; removed requirements for fiber therapy, osmotic agents, or laxative agents; added step therapy with Linzess, Symproic, or Movantik for coverage of lubiprostone ABA/Amitiza; added step therapy Linzess for coverage of Trulance/Motegrity; added step therapy with Movantik or Symproic for coverage of Relistor tabs or Relistor injection.
  • 08/16/2022 – Ibsrela: New policy approved by P&T.
References:
  1. Relistor Prescribing Information. Salix Pharmaceuticals. Bridgewater, NJ. April 2020.
  2. Per clinical consult with gastroenterologist, February 19, 2019.
  3. Crockett SD, Greer KB, Heidelbaugh JJ, et al. American Gastroenterological Association Institute Guideline on the Medical Management of Opioid-Induced Constipation. Gastroenterology. Gastroenterology. 2019;156:218-226.
  4. Movantik Prescribing Information. AstraZeneca Pharmaceuticals LP. Wilmington, DE. April 2020.
  5. Symproic Prescribing Information. Shionogi Inc. Florham Park, NJ. May 2020.
  6. Linzess Prescribing Information. Allergan USA, Inc. Madison, NJ. September 2020.
  7. Trulance Prescribing Information. Salix Pharmaceuticals Inc. Bridgewater, NJ. February 2021.
  8. Amitiza Prescribing Information. Takeda Pharmaceuticals America, Inc. Deerfield, IL. November 2020.
  9. Motegrity Prescribing Information. Takeda Pharmaceuticals America, Inc. Lexington, MA. November 2020.
  10. Ford AC, Moayyedi P, Chey WD, Harris LA, Lacy BE, Saito YA, Quigley EMM; ACG Task Force on Management of Irritable Bowel Syndrome. American College of Gastroenterology Monograph on Management of Irritable Bowel Syndrome. Am J Gastroenterol. 2018 Jun;113(Suppl 2):1-18.
  11. Ibsrela prescribing information. Ardelyx, Inc. Waltham, MA. May 2021. 
  12. UpToDate. Wald, A. Treatment of Irritable Bowel Syndrome in Adults. Available at https://www.uptodate.com/contents/treatment-of-irritable-bowel-syndrome-in-adults?search=irritable%20bowe%20syndrome%20with%20constipation&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1#H23037175. Accessed April 3, 2022. 
  13. Furnari, M., de Bortoli, N., et al. Optimal Management of Constipation Associated with Irritable Bowel Syndrome. Ther Clin Risk Manag. 2015;11:691-703. Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4425337/. Accessed April 3, 2022. 
  14. Lacy, Brian E. PhD, MD, FACG1; Pimentel, Mark MD, FACG2; Brenner, Darren M. MD, FACG3; Chey, William D. MD, FACG4; Keefer, Laurie A. PhD5; Long, Millie D. MDMPH, FACG (GRADE Methodologist)6; Moshiree, Baha MD, MSc, FACG7 ACG Clinical Guideline: Management of Irritable Bowel Syndrome, The American Journal of Gastroenterology: January 2021 - Volume 116 - Issue 1 - p 17-44 doi: 10.14309/ajg.0000000000001036
  15. Chang, L., Sultan, S., Lembo, A., Verne, G.N., Smalley, W., Heidelbaugh, J.J., AGA Clinical Practice Guideline on the Pharmacological Management of Irritable Bowel Syndrome With Constipation, Volume 163, Issue 1, P118-136, July 01, 2022., https://doi.org/10.1053/j.gastro.2022.04.016
  16. Black, C. J., Burr, N. E., Quigley, E., Moayyedi, P., Houghton, L. A., & Ford, A. C. (2018). Efficacy of Secretagogues in Patients With Irritable Bowel Syndrome With Constipation: Systematic Review and Network Meta-analysis. Gastroenterology, 155(6), 1753–1763. https://doi.org/10.1053/j.gastro.2018.08.021
  17. Shah, E. D., Lacy, B. E., Chey, W. D., Chang, L., & Brenner, D. M. (2021). Tegaserod for Irritable Bowel Syndrome With Constipation in Women Younger Than 65 Years Without Cardiovascular Disease: Pooled Analyses of 4 Controlled Trials. The American journal of gastroenterology, 116(8), 1601–1611. https://doi.org/10.14309/ajg.0000000000001313

Last review date: August 16, 2022