Effective Date

Date of Origin   

10-01-2024           

Amitiza®*

(lubiprostone)

Capsule

Treatment of chronic idiopathic constipation (CIC) in adults

Treatment of opioid-induced constipation (OIC) in adults with chronic, non-cancer pain including patients with chronic pain related to prior cancer of its treatment who do not require frequent (e.g., weekly) opioid dosage escalation

Limitation of Use: Effectiveness of Amitiza in the treatment of OIC in patients taking diphenylheptane opioids (e.g., methadone) has not been established

Treatment of irritable bowel syndrome with constipation (IBS-C) in women greater than or equal to 18 years old

*generic available

1

Ibsrela®

(tenapanor)

Tablet

Treatment of irritable bowel syndrome with constipation (IBS-C) in adults

18

Linzess®

(linaclotide)

Capsule

Treatment of functional constipation (FC) in pediatric patients 6 to 17 years of age

Treatment of irritable bowel syndrome with constipation (IBS-C) in adults

Treatment of chronic idiopathic constipation (CIC) in adults

3

Motegrity®

(prucalopride)

Tablet

Treatment of chronic idiopathic constipation (CIC) in adults

11

Movantik®

(naloxegol)

Tablet

Treatment of opioid-induced constipation (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

14

Relistor®

(methylnaltrexone)

Subcutaneous injection (SC)

Tablet

Injection/Tablet:

Treatment of opioid-induced constipation (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

Injection:

Treatment of OIC in adult patients with advanced illness or pain caused by active cancer who require opioid dosage escalation for palliative care

13

Symproic®

(naldemedine)

Tablet

Treatment of opioid-induced constipation (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

15

Trulance®

(plecanatide)

Tablet

Treatment of chronic idiopathic constipation (CIC) in adults.

Treatment of irritable bowel syndrome with constipation (IBS-C) in adults

9

Irritable Bowel Syndrome with Constipation (IBS-C)

Irritable Bowel Syndrome (IBS) is a chronic functional disorder of the gastrointestinal system. Patients experience abdominal pain and altered bowel habit, with either predominantly diarrhea (IBS-D), constipation (IBS-C), or both (IBS-M). There is no definitive investigation as no biomarker has been found, so IBS is diagnosed clinically. The Rome criteria were developed by a panel of international experts in the field of functional gastrointestinal disorders. Although initially developed to guide researchers, these criteria have undergone several revisions with the intent of making them clinically useful whereas the criteria can be applied to diagnose IBS.(17)

Rome IV defines IBS as recurrent abdominal pain, on average, at least one day per week in the last three months associated with two or more of the following:(2,17)

• Related to defecation
• Associated with a change in stool frequency
• Associated with a change in stool form (appearance)

The goal of treatment of IBS-C is to improve symptoms such as abdominal bloating, discomfort, and constipation. The American College of Gastroenterology (ACG) updated (2021) guidelines suggest that soluble (e.g., psyllium, oat bran, barley, and beans), but not insoluble (e.g., wheat bran, whole grains, and some vegetables), fiber be used to treat IBS especially when the predominant symptom is constipation. Updated guidelines recommend against the use of polyethylene glycol (PEG), probiotics and antispasmodics. However, the authors do recognize that clinicians may use PEG as a first-line treatment for constipation in IBS, given its low cost and availability.(2)

Tricyclic antidepressants (TCAs) are also recommended for use with global symptoms of IBS, such as patients who report abnormal bowel habits of constipation, diarrhea, or both. TCAs are believed to improve visceral pain and central pain by acting on norepinephrine, and dopaminergic receptors, thus making them attractive candidates for the treatment of IBS-related abdominal pain. A recent systematic review and meta-analysis evaluated 7 RCTs that evaluated the effect of antidepressant therapy on abdominal pain. Antidepressants were more likely to improve symptoms of abdominal pain than placebo; however, the beneficial effects were due to TCA therapy, not serotonin reuptake inhibitors (SSRIs).(2,5,8)

The 2021 American Gastroenterological Association guidelines recommend lubiprostone with a strong recommendation, and with moderate quality of evidence; in addition to guanylate cyclase activators (linaclotide and plecanatide) with a strong recommendation, high quality of evidence to treat global IBS- C symptoms. Lubiprostone exhibits an appropriate safety profile and efficacy with the most common adverse events being gastrointestinal (i.e., nausea) in nature. Although there may be a delay in initial response, improvement in global symptoms is maintained or increases over time. Guanylate cyclase-C (GC-C) agonists, linaclotide 290 mcg and plecanatide 3 mg, target GC-C receptors residing in the apical membranes of intestinal epithelial cells. Recent comparative analyses suggest that both are comparably effective, safe, and well-tolerated. Responses develop quickly and are maintained over time. Diarrhea is the most common adverse event experienced, but discontinuation rates due to diarrhea are low and both are well-tolerated.(2,5,8)

Chronic Idiopathic Constipation (CIC)

Chronic idiopathic constipation (CIC) is a common functional bowel disorder characterized by difficult, infrequent, and/or incomplete defecation. Functional constipation Rome IV diagnostic criteria requires the presence of the following for at least 3 months:(12)

• Must include two or more of the following:
  • Straining during more than 25 percent of defecations
  • Lumpy or hard stools (Bristol Stool Scale Form 1-2) in more than 25 percent of defecations
  • Sensation of incomplete evacuation for more than 25 percent of defecations
  • Manual maneuvers to facilitate more than 25 percent of defecations (e.g., digital evacuation, support of the pelvic floor)
  • Fewer than three spontaneous bowel movements per week
• Loose stools are rarely present without the use of laxatives
• There are insufficient criteria for Irritable Bowel Syndrome (IBS)

According to 2021 American College of Gastroenterology (ACG) guidelines, polyethylene glycol (PEG) is a relatively inexpensive, widely available, nonprescription osmotic laxative that is US FDA-approved for occasional constipation based on several RCT studies. Four trials in chronic idiopathic have yielded improvement in stool frequency and stool consistency. American Gastroenterology Association recommends a gradual increase in fiber intake, as both foods included in the diet and as supplements and/or an inexpensive osmotic agent (e.g., milk of magnesia or polyethylene glycol (PEG)). Depending on stool consistency, the next step may be to supplement the osmotic agent with a stimulant laxative (e.g., bisacodyl or glycerol suppositories), preferably administered 30 minutes after a meal to synergize the pharmacologic agent with the gastrocolonic response. A newer agent (e.g., linaclotide, lubiprostone) should be considered when symptoms do not respond to other laxatives.10 Although linaclotide and lubiprostone are effective in CIC and are well tolerated, there have been no comparative studies. As both were evaluated in comparison with placebo rather than “standard therapy,” a recommendation regarding their precise position in a CIC treatment algorithm (i.e., for those who have failed fiber, osmotic, or stimulant laxatives, or as primary therapy) cannot be made at this time.(5)

Pediatric Functional Constipation

Rome IV defines functional constipation separately for infants and children greater than 4 years of age. For children greater than 4 years, must include 2 or more of the following occurring at least once per week for a minimum of 1 month with insufficient criteria for a diagnosis of irritable bowel syndrome:(19)

• 2 or fewer defecations in the toilet per week in a child of a developmental age of at least 4 years
• At least 1 episode of fecal incontinence per week
• History of retentive posturing or excessive volitional stool retention
• History of painful or hard bowel movements
• Presence of a large fecal mass in the rectum
• History of large diameter stools that can obstruct the toilet

Polyethylene glycol (PEG 3350) has become the first line treatment of functional constipation due to its efficacy, safety profile, and because it is well tolerated. There are variations in the amount of PEG 3350 recommended for the cleanout phase of the treatment regime, but a reasonable dose would be 1 to 1.5 grams per kilogram PEG 3350 mixed with 6 to 8 oz. water or juice. Significantly higher doses have been used, especially in the hospital setting. Patients should be encouraged to drink this over 3 hours, if possible. If there has not been a significant response to this treatment, the patient can repeat the dose the next day. If there is no response after two days of treatment or significant abdominal discomfort, persistent vomiting, or any other concerns, the family should present for follow-up and reevaluation.(19)

In the second phase of treatment, maintenance therapy, the goal is to keep the stool very soft, preventing reaccumulation of hard stool while the colon returns to normal size and function.(19)

Drugs in this phase are oral medications:(19)

• Osmotic laxatives: polyethylene glycol (PEG) 3350 at 0.2-0.8 g/kg/day, lactulose at 1- 3 mL /kg/day or magnesium hydroxide at 0.5-3 mL/kg/day
• Stool Softeners: docusate sodium at 5 mg/kg/day or mineral oil (lubricant) at 1-3 mL/kg/day
• Stimulant laxative for rescue therapy in addition or alone (duration less than 30 days): senna at 2.5-7.5 mL/day or bisacodyl at 5-10 mg/day

Normal fiber and fluid intake are recommended for children with constipation, along with an average amount of physical activity. There is no evidence to support the routine use of intensive behavioral protocolized therapy programs or biofeedback in addition to conventional treatment. There is no evidence to suggest the use of prebiotics or probiotics in the treatment of constipation. Among patients referred to pediatric gastroenterologists, 50 percent will recover as defined by 3 or more bowel movements per week without fecal incontinence and be without laxatives after 6 to 12 months. Approximately an additional 10 percent are well while taking laxatives, and 40 percent will still be symptomatic despite laxatives.(19)

Opioid-Induced Constipation (OIC)

In anticipation of potential OIC development with long-term opioid use, treatment guidelines recommend initiation of a prophylactic bowel regimen that may involve increased fluid and fiber intake, stool softeners, and/or laxatives. When a diagnosis of OIC is suspected despite prophylactic treatment, clinicians should confirm that initiation of opioid therapy has led to a change from baseline in the patient’s typical bowel habits, before consideration of further or alternative interventions. First line approaches to intervention also include dietary changes, OTC treatments, and exercise.(6)

National Comprehensive Cancer Network (NCCN) guidelines on adult cancer pain include the following recommendations on OIC. Preventative measures include prophylactic medications such as a stimulant laxative (e.g., senna and polyethylene glycol) in addition to maintaining adequate fluid intake, maintaining adequate dietary fiber, and exercise if feasible. Supplemental medicinal fiber (e.g., psyllium) is unlikely to control OIC and may worsen constipation. Docusate does not provide benefit. If constipation develops, pharmacological recommendations include titrating stool softeners/laxatives as needed to achieve one non-forced bowel movement every 1-2 days. Consider adjuvant analgesics to allow reduction of opioid dose. If constipation persists, pharmacological recommendations include the consideration of adding another agent (magnesium hydroxide, bisacodyl, rectal suppository, lactulose, sorbitol, magnesium citrate, or polyethylene glycol). When response to laxative therapy has not been sufficient for OIC in patients with advanced illness, then consider peripherally acting mu opioid receptor antagonists such as methylnaltrexone or naloxegol; other second line agents include lubiprostone and linaclotide.(4)

The American Gastroenterological Association Institute 2019 guideline for OIC recommends that patients with OIC, first line agents are traditional laxatives which include osmotic, stimulant, detergent/surfactant stool softener, and lubricant agents. In patients with laxative refractory OIC, naldemedine, naloxegol, and methylnaltrexone are recommended over no therapy. No recommendations are made on lubiprostone or prucalopride. Fiber or bulk-forming agents have limited role in OIC. Enemas may occasionally be prescribed as rescue therapy, but are not used regularly due to inconvenience, patient preference, and safety concerns.(16)

Safety

Amitiza carries the following contraindication:(1)

• Known or suspected mechanical gastrointestinal obstruction

Ibsrela carries the following contraindications:(18)

• Pediatric patients less than 6 years of age
• Patients with known of suspected mechanical gastrointestinal obstruction

Linzess carries the following contraindications:(3)

• Known or suspected mechanical gastrointestinal obstruction
• Patients under 6 years of age

Movantik carries the following contraindications:(14)

• Patients with known or suspected gastrointestinal obstruction and patients at increased risk of recurrent obstruction
• Concomitant use with strong CYP3A4 inhibitors (e.g., clarithromycin, ketoconazole)
• Known serious or severe hypersensitivity reaction to naloxegol or any of its excipients

Motegrity carries the following contraindications:(11)

• A history of hypersensitivity to Motegrity. Reactions including dyspnea, rash, pruritus, urticaria, and facial edema have been observed
• Intestinal perforation or obstruction due to structural or functional disorder of the gut wall, obstructive ileus, severe inflammatory conditions of the intestinal tract such as Crohn's disease, ulcerative colitis, and toxic megacolon/megarectum

Relistor carries the following contraindication:(13)

• Patients with known or suspected mechanical gastrointestinal obstruction and at increased risk of recurrent obstruction

Symproic carries the following contraindications:(15)

• Patients with known or suspected gastrointestinal obstruction at increased risk of recurrent obstruction
• Patients with a history of a hypersensitivity reaction to naldemedine

Trulance carries the following contraindications:(9)

• Patients less than 6 years of age due to the risk of serious dehydration.
• Patients with known or suspected mechanical gastrointestinal obstruction

1

Amitiza Prescribing Information. Sucampo Pharmaceuticals, Inc. November 2020.

2

Lacy, B, Chey WD, et al. ACG Clinical Guideline: Management of Irritable Bowel Syndrome. Am J Gastroenterol 2021;116:17–44. https://doi.org/10.14309/ajg.0000000000001036.

3

Linzess Prescribing Information. Forest Pharmaceuticals, Inc. June 2023.

4

National Comprehensive Cancer Network (NCCN) Clinical Practice guidelines in oncology. Adult Cancer Pain. Version 1.2023. 

5

Weinberg DS, Smalley W, et al. American Gastroenterological Association Institute Guideline on the Pharmacological Management of Irritable Bowel Syndrome. Gastroenterology. 2021;116:17-44.

6

Argoff C, Brennan M, Camilleri M, et al. Review Article: Consensus recommendations on initiating prescription therapies for opioid-induced constipation. Pain Med. 2015;16(12):2324-2337. DOI: 10.1111/pme.12937.

7

Chang, Lin, et al. American Gastroenterological Association-American College of Gastroenterology Clinical Practice Guideline: Pharmacological Management of Chronic Idiopathic Constipation. Gastroenterology, vol. 164, no. 7, 1 June 2023, pp. 1086–1106. https://doi.org/10.1053/j.gastro.2023.03.214.

8

World Gastroenterology Organization Global Guidelines. IBS: a Global Perspective Update September 2015. Available at: https://www.worldgastroenterology.org/guidelines/irritable-bowel-syndrome-ibs/irritable-bowel-syndrome-ibs-english

9

Trulance prescribing information. Synergy Pharms, Inc. April 2021.

10

American Gastroenterological Association Medical Position Statement on Constipation. Gastroenterology. 2013;144:211–217. https://www.gastrojournal.org/article/s0016-5085(12)01545-4/fulltext.

11

Motegrity prescribing information. Shire US, Inc. November 2020.

12

Crockett SD, Greer KB, Heidelbaugh JJ, et al. American Gastroenterological Association Institute guideline on the medical management of opioid-induced constipation. Gastroenterology 2019;156:218-226.

13

Relistor prescribing information. Salix Pharmaceuticals. April 2020.

14

Movantik prescribing information.  Astra Zeneca Pharmaceutical LP. March 2023.

15

Symproic prescribing information. Purdue Pharma LP. March 2020.

16

American College of Gastroenterology monograph on management of irritable bowel syndrome. American Journal of Gastroenterology. 2018; 113:1–18. https://journals.lww.com/ajg/fulltext/2018/06002/american_college_of_gastroenterology_monograph_on.1.aspx

17

Lacy BE, Patel NK. Rome Criteria and a Diagnostic Approach to Irritable Bowel Syndrome. Journal of Clinical Medicine. 2017; 6(11):99. https://doi.org/10.3390/jcm6110099.

18

Ibsrela prescribing information. Ardelyx, Inc. April 2022.

19

Allen P, Setya A, Lawrence VN. Pediatric Functional Constipation. Updated 2022 Aug 19. In: StatPearls. StatPearls Publishing; 2023 Jan. Available from: https://www.ncbi.nlm.nih.gov/books/NBK537037/.

Through Preferred

Symproic

naldemedine tosylate tab

0.2 MG

M ; N ; O ; Y

N

1. Preferred

Movantik

naloxegol oxalate tab

12.5 MG ; 25 MG

M ; N ; O ; Y

N

1. Preferred

Trulance

plecanatide tab

3 MG

M ; N ; O ; Y

N

1. Preferred

Linzess

linaclotide cap

145 MCG ; 290 MCG ; 72 MCG

M ; N ; O ; Y

N

2. Non-Preferred

Amitiza

lubiprostone cap

24 MCG ; 8 MCG

M ; N ; O ; Y

O ; Y

2. Non-Preferred

Relistor

methylnaltrexone bromide inj  ; methylnaltrexone bromide tab

12 MG/0.6ML ; 150 MG ; 8 MG/0.4ML

M ; N ; O ; Y

N

2. Non-Preferred

Motegrity

prucalopride succinate tab

1 MG ; 2 MG

M ; N ; O ; Y

N

2. Non-Preferred

Ibsrela

tenapanor hcl tab

50 MG

M ; N ; O ; Y

N

2. Non-Preferred

Through Preferred

Amitiza

Lubiprostone Cap 24 MCG

24 MCG

60

Capsules

30

DAYS

Amitiza

Lubiprostone Cap 8 MCG

8 MCG

120

Capsules

30

DAYS

Ibsrela

tenapanor hcl tab

50 MG

60

Tablets

30

DAYS

Linzess

linaclotide cap

145 MCG ; 290 MCG ; 72 MCG

30

Capsules

30

DAYS

Motegrity

prucalopride succinate tab

1 MG ; 2 MG

30

Tablets

30

DAYS

Movantik

naloxegol oxalate tab

12.5 MG ; 25 MG

30

Tablets

30

DAYS

Relistor

methylnaltrexone bromide inj

12 MG/0.6ML

60

Vials

30

DAYS

Quantity Limit allows for dosing for individuals at least 90th percentile weight

65649055102

Relistor

methylnaltrexone bromide inj

12 MG/0.6ML

30

Syringes

30

DAYS

65649055103 ; 65649055107

Relistor

Methylnaltrexone Bromide Inj 8 MG/0.4ML (20 MG/ML)

8 MG/0.4ML

30

Syringes

30

DAYS

Relistor

methylnaltrexone bromide tab

150 MG

90

Tablets

30

DAYS

Symproic

naldemedine tosylate tab

0.2 MG

30

Tablets

30

DAYS

Trulance

plecanatide tab

3 MG

30

Tablets

30

DAYS

Through Preferred

52580050102020

Relistor

methylnaltrexone bromide inj

12 MG/0.6ML

Quantity Limit allows for dosing for individuals at least 90th percentile weight

65649055102

Movantik

naloxegol oxalate tab

12.5 MG ; 25 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx

Symproic

naldemedine tosylate tab

0.2 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx

Trulance

plecanatide tab

3 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx

Amitiza

lubiprostone cap

24 MCG ; 8 MCG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx

Ibsrela

tenapanor hcl tab

50 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx

Linzess

linaclotide cap

145 MCG ; 290 MCG ; 72 MCG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx

Motegrity

prucalopride succinate tab

1 MG ; 2 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx

Relistor

methylnaltrexone bromide inj  ; methylnaltrexone bromide tab

12 MG/0.6ML ; 150 MG ; 8 MG/0.4ML

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx

Amitiza

Lubiprostone Cap 24 MCG

24 MCG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx

Amitiza

Lubiprostone Cap 8 MCG

8 MCG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx

Ibsrela

tenapanor hcl tab

50 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx

Linzess

linaclotide cap

145 MCG ; 290 MCG ; 72 MCG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx

Motegrity

prucalopride succinate tab

1 MG ; 2 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx

Movantik

naloxegol oxalate tab

12.5 MG ; 25 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx

Relistor

methylnaltrexone bromide inj

12 MG/0.6ML

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx

Relistor

methylnaltrexone bromide inj

12 MG/0.6ML

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx

Relistor

Methylnaltrexone Bromide Inj 8 MG/0.4ML (20 MG/ML)

8 MG/0.4ML

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx

Relistor

methylnaltrexone bromide tab

150 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx

Symproic

naldemedine tosylate tab

0.2 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx

Trulance

plecanatide tab

3 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx

Through Preferred

TARGET AGENT(S)

Preferred Agent(s)
Movantik (naloxegol)
Symproic (naldemedine)
Trulance (plecanatide)

Nonpreferred Agent(s)
Amitiza (lubiprostone)*
Ibsrela (tenapanor)
Linzess (linaclotide)
Motegrity (prucalopride)
Relistor (methylnaltrexone)
*-generic available

Initial Evaluation

Target Agent(s) will be approved when ALL of the following are met:

1. ONE of the following:
   1. The patient has a diagnosis of irritable bowel syndrome with constipation (IBS-C) AND ALL of the following:
      1. The patient has had IBS-C symptoms for greater than or equal to 3 months AND
      2. ONE of the following:
         1. The requested agent is Trulance (plecanatide), Linzess (linaclotide) OR Ibsrela (tenapanor) OR
         2. The requested agent is Amitiza (lubiprostone) AND ONE of the following:
            1. The patient’s sex is female OR
            2. The requested agent is medically appropriate for the patient’s sex and the intended diagnosis AND
      3. ONE of the following:
         1. The patient has tried and had an inadequate response to at least 2 standard laxative therapy classes (e.g., bulk-forming, stimulant, enema, osmotic, or stool softener) OR
         2. The patient has an intolerance or hypersensitivity to at least 2 standard laxative therapy classes OR
         3. The patient has an FDA labeled contraindication to ALL standard laxative therapy classes OR
   2. The patient has a diagnosis of chronic idiopathic constipation (CIC) AND ALL of the following:
      1. The patient has had CIC symptoms for greater than or equal to 3 months AND
      2. The requested agent is Amitiza (lubiprostone), Linzess (linaclotide), Motegrity (prucalopride), or Trulance (plecanatide) AND
      3. ONE of the following:
         1. The patient has tried and had an inadequate response to at least 2 standard laxative therapy classes (e.g., bulk-forming, stimulant, enema, osmotic, or stool softener) OR
         2. The patient has an intolerance or hypersensitivity to at least 2 standard laxative therapy classes OR
         3. The patient has an FDA labeled contraindication to ALL standard laxative therapy classes OR
   3. The patient has a diagnosis of opioid-induced constipation (OIC) AND ALL of the following:
      1. ONE of the following:
         1. BOTH of the following:
            1. ONE of the following:
               1. The requested agent is Symproic (naldemedine), Movantik (naloxegol), OR Relistor (methylnaltrexone) tablet OR
               2. The requested agent is Amitiza (lubiprostone) AND the patient is not currently receiving a diphenylheptane opioid (e.g., methadone) AND
            2. ONE of the following:
               1. The patient has chronic non-cancer pain OR
               2. The patient has chronic pain related to prior cancer or its treatment OR
               3. The patient has active cancer pain OR
         2. The requested agent is Linzess (linaclotide) AND the patient has active cancer pain OR
         3. The request is for Relistor (methylnaltrexone) injection and the patient is receiving palliative care AND ONE of the following:
            1. The patient has advanced illness OR
            2. The patient has pain caused by active cancer AND
      2. The patient has chronic use of an opioid agent in the past 30 days AND
      3. ONE of the following:
         1. The patient has tried and had an inadequate response to at least 2 standard laxative therapy classes (e.g., stimulant, enema, osmotic, or stool softener, but not including fiber or bulking agents) OR
         2. The patient has an intolerance or hypersensitivity to at least 2 standard laxative therapy classes OR
         3. The patient has an FDA labeled contraindication to ALL standard laxative therapy classes AND
   4. The patient has a diagnosis of pediatric functional constipation and ONE of the following:
      1. The patient has tried and had an inadequate response to at least 2 standard laxative therapy classes (e.g., bulk-forming, stimulant, enema, osmotic, or stool softener) OR
      2. The patient has an intolerance or hypersensitivity to at least 2 standard laxative therapy classes OR
      3. The patient has an FDA labeled contraindication to ALL standard laxative therapy classes AND
2. If the patient has an FDA labeled indication, then ONE of the following:
   1. The patient’s age is within FDA labeling for the requested indication for the requested agent OR
   2. There is support for using the requested agent for the patient’s age for the requested indication AND
3. If the request is for one of the following brand agents with an available generic equivalent (listed below), then ONE of the following:

3. The patient has an intolerance or hypersensitivity to the generic equivalent that is not expected to occur with the brand agent OR
4. The patient has an FDA labeled contraindication to the generic equivalent that is not expected to occur with the brand agent OR
5. There is support for the use of the requested brand agent over the generic equivalent AND
6. ONE of the following:
   1. The request is for Symproic (naldemedine), Trulance (plecanatide), Movantik (naloxegol), OR Relistor (methylnaltrexone) injection OR
   2. The request is for Linzess (linaclotide) for use in pediatric functional constipation OR
   3. The requested agent is for use in IBS-C or CIC AND ONE of the following:
      1. The patient has tried and had an inadequate response to Trulance (plecanatide) OR
      2. The patient has an intolerance or hypersensitivity to Trulance (plecanatide) that is not expected to occur with the requested agent OR
      3. The patient has an FDA labeled contraindication to Trulance (plecanatide) that is not expected to occur with the requested agent for the requested indication OR
   4. The requested agent is for use in OIC AND ONE of the following:
      1. The patient has tried and had an inadequate response to Symproic (naldemedine) and Movantik (naloxegol) OR
      2. The patient has an intolerance or hypersensitivity to Symproic (naldemedine) and Movantik (naloxegol) that is not expected to occur with the requested agent OR
      3. The patient has an FDA labeled contraindication to Symproic (naldemedine) and Movantik (naloxegol) that is not expected to occur with the requested agent AND
7. The patient will NOT be using the requested agent in combination with another constipation agent (i.e., Amitiza/lubiprostone, Ibsrela, Linzess, Motegrity, Movantik, Relistor, Symproic, Trulance) AND
8. The patient does NOT have any FDA labeled contraindications to the requested agent

Length of Approval: 12 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

*Step therapy requirement may not apply if a prior health plan paid for the medication - documentation of a paid claim may be required.

Renewal Evaluation

Target Agent(s) will be approved when ALL of the following are met:

1. The patient has been previously approved for the requested agent through the plan’s Prior Authorization process [Note: patients not previously approved for the requested agent will require initial evaluation review] AND
2. If the patient has an FDA labeled indication, then ONE of the following:
   1. The patient’s age is within FDA labeling for the requested indication for the requested agent OR
   2. There is support for using the requested agent for the patient’s age for the requested indication AND
3. The patient has had clinical benefit with the requested agent AND
4. The patient will NOT be using the requested agent in combination with another constipation agent (i.e., Amitiza/lubiprostone, Ibsrela, Linzess, Motegrity, Movantik, Relistor, Symproic, Trulance) AND
5. The patient does NOT have any FDA labeled contraindications to the requested agent

Length of Approval: 12 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

Quantity Limit for the Target Agent(s) will be approved when ONE of the following is met:

1. The requested quantity (dose) does NOT exceed the program quantity limit OR
2. The requested quantity (dose) exceeds the program quantity limit AND ONE of the following:
   1. BOTH of the following:
      1. The requested agent does NOT have a maximum FDA labeled dose for the requested indication AND
      2. There is support for therapy with a higher dose for the requested indication OR
   2. BOTH of the following:
      1. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication AND
      2. There is support for why the requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does NOT exceed the program quantity limit OR
   3. BOTH of the following:
      1. The requested quantity (dose) exceeds the maximum FDA labeled dose for the requested indication AND
      2. There is support for therapy with a higher dose for the requested indication

Length of Approval: up to 12 months