FDA approves subcutaneous injection for opioid-induced constipation in chronic non-cancer pain

FDA approved methylnaltrexone bromide (Relistor, Salix Pharmaceuticals and Progenics Pharmaceuticals) subcutaneous injection, 12 mg/0.6 mL, for the treatment of opioid-induced constipation (OIC) in patients taking opioids for chronic non-cancer pain.

Relistor is currently the only available peripherally acting mu opioid receptor antagonist that is approved for treating OIC at the cause without interfering with the centrally acting analgesic properties of the opioid.

“Opioid-induced constipation is a very common problem in patients receiving high-dose opioids for pain control as a results of malignancy or other pain syndromes [sickle cell disease etc.],” said FormularyWatch advisor James M. Wooten, PharmD, associate professor, department of medicine, University of Missouri-Kansas City School of Medicine. “This particular drug may help treat this very common side effect of opioid administration. Unfortunately, patients do not become tolerant to the constipating effects of opioids so as opioid doses are increased for better pain control the greater the constipation.”

This new drug may offer patients on chronic opioids quite a bit of relief, according to Dr Wooten.

“Traditional laxative treatments are often ineffective for many chronic pain patients suffering with opioid-induced constipation,” he explained.

Approximately 80% of chronic pain patients with OIC that were taking laxative therapy continued to report difficulties dealing with their constipation symptoms, as documented by a large patient survey published in 2008 in Pain Medicine, as cited by Dr Wooten. One-third of these chronic pain patients reported stopping or lowering their opioid dose in order to relieve their opioid-induced constipation, resulting in increased pain levels.

The approval was based on a phase 3 randomized, double blind, placebo-controlled trial was conducted to evaluate the efficacy and safety of Relistor 12 mg once daily for the treatment of OIC in patients with chronic non-cancer pain.

A total of 312 patients with a history of non-cancer pain and taking opioids for at least 1 month prior to study entry were eligible for enrollment. Patients also had confirmed OIC defined at <3 spontaneous bowel movements per week during the screening period. Constipation due to opioid use had to be associated with 1 or more of the following: A Bristol Stool Form Scale score of 1 or 2 for at least 25% of the bowel movements (BM), straining during at least 25% of the BMs or a sensation of incomplete evacuation after at least 25% of the BMs. The median duration of opioid-induced constipation at baseline was 59 months. The median daily baseline oral morphine equivalent dose was 161 mg. Patients were randomly assigned to receive Relistor 12 mg or placebo once daily for 4 weeks followed by an 8-week open-label phase when patients could take medications as needed.

In the study a significantly greater portion of patients taking Relistor 12 mg daily reported having 3 or more spontaneous bowel movements (SBM) per week during the 4-week double blind period compared to placebo (59% vs. 38%). Following the first dose, 33% of patients in the Relistor 12 mg once daily treatment group had a SBM within 4 hours and approximately half of patients had a SBM prior to the second dose of Relistor.

Commonly reported side effects included: abdominal pain (21%), diarrhea (6%), nausea (9%) and hyperhidrosis (6%).

An estimated 27 million patients in the United States take opioids for chronic pain. Constipation is one of the most common and distressing side effects in patients receiving chronic opioid therapy. Approximately 40% of chronic pain patients, or nearly 11 million patients, on opioid therapy will experience OIC.

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New drug approved by FDA for treatment of opioid-induced constipation