Drug of the Month: Relistor® A Step-Therapy Approach to Opioid-Induced Constipation

by Alan Rook, PharmD, Clinical Pharmacist
Rachel Crow, PharmD candidate

1. What is Relistor®?

Relistor® (methylnaltrexone bromide), manufactured by Valeant Pharmaceuticals International, Inc., is FDA approved for opioid-induced constipation in patients with chronic non-cancer pain as well as opioid-induced constipation with advanced illness. Opioid analgesics are able to cross the blood brain barrier (BBB) and act on the mu opioid receptors in the brain, triggering pain relief. The mu opioid receptors are also seen in the gastrointestinal (GI) tract; when receptor binding occurs in the GI tract it causes the adverse effect of constipation. However, Relistor® does not cross the BBB, so the analgesic effects of the opioids remain and the constipation is relieved.

It is important for patients to discontinue all other laxative therapies prior to the initiation of Relistor®.

2. How is Relistor® administered?

Relistor® is available as a subcutaneous injection in 8 mg/0.4mL and 12 mg/0.6 mL dosages. Weight-based dosing is used to determine the once daily dose.

3. Step therapy approach:

A step therapy approach should be used when it comes to the relief of opioid-induced constipation. Starting with a generic laxative is appropriate for first-line treatment, partially because of its cost-effectiveness. Once a patient’s options have been exhausted with first-line therapies such as MiraLAX® or Senokot®, it would be appropriate to use the stepwise approach as described below. Each step down would provide a more costly option.

Step

      • Laxatives

      • Osmotic

• Osmotic laxatives are generally well tolerated and cause less cramping than stimulant laxatives. The patient may choose from MiraLAX® (polyethylene glycol) or lactulose. The usual dose for MiraLAX® is 17 g of powder dissolved in 4-8 ounces of a beverage, once daily. The maximum recommended duration of treatment is two weeks. Lactulose is dosed 10-20 g orally, once daily for 24-48 hours.

• Common side effects of osmotic laxatives include abdominal bloating, cramping, diarrhea, flatulence, and nausea.

     • Stimulant

• Stimulant laxatives increase the rate of gastrointestinal motility and secretions. The patient may choose from Dulcolax® (bisacodyl) or Senokot® (senna). The usual dose for Dulcolax® is 5-15 mg orally—once daily, or a 10 mg rectal suppository—once daily. Use of Dulcolax® for more than 7 days is not recommended. Senna should be dosed 17.2 mg sennosides (2 tablets) orally—once daily.

• Common side effects of stimulant laxatives include abdominal colic, abdominal discomfort, diarrhea, and proctitis (with suppository use).

     • Movantik®

• Movantik® (naloxegol) is an opioid antagonist that is also FDA approved for opioid-induced constipation in patients with chronic non-cancer related pain. Prior to administration, it is recommended that all laxatives be discontinued. If the patient has a suboptimal response to this drug, laxatives may be resumed after 3 days.

• The most common side effect of Movantik® is abdominal pain.

• For a 30-day supply with a daily dose of 25 mg of Movantik®, the AWP is $299.40. Amitiza®

• Amitiza® (lubiprostone), manufactured by Takeda Pharmaceuticals Inc., is FDA approved for opioid-induced constipation in patients with chronic non-cancer related pain. It promotes fluid secretion and assists with passing of the stool.

• The Average Wholesale Price (AWP) of Amitiza® is $6.29 per 8 mcg and $8.61 per 24 mcg capsules. The medication is dosed two times daily, requiring 60 tablets per month, making the AWP for a 30-day supply $377.40 and $516.60, respectively.

      • Linzess®

• Linzess® (linaclotide), manufactured by Actavis, is FDA approved for chronic idiopathic constipation and irritable bowel syndrome with constipation in adults. The AWP of Linzess® is $12.18 per 145 mcg capsule. Being dosed once daily requires 30 tablets per month, making the AWP for a 30-day supply $365.40.

• Since Linzess® is not FDA approved for opioid induced constipation, Movantik® and Amitiza® should be attempted first for the relief of opioid-induced constipation.

• Linzess® is available as an oral capsule as opposed to the more costly Relistor®

• Relistor ®

• The AWP of Relistor® is $299.99 for the 8 mg injection and $199.99 for the 12 mg injection. A patient would require 30 doses for one month, making the AWP for a 30-day supply $8,999.70 for the 8 mg injection and $5,999.70 for the 12 mg injection.

• Common side effects include abdominal pain, flatulence, and nausea.

• All other constipation relief options should be exhausted before a trial of Relistor® is attempted.

* AWP figures mentioned throughout the article are based on the unit cost at the time of this article’s publication and may vary slightly depending on the manufacturer.