Naldemedine (brand name Symproic in the US and Rizmoic in the European Union) is a medication that is used for the treatment of opioid-induced constipation in adults with chronic non-cancer pain. It is a peripherally acting μ-opioid receptor antagonist and was developed by Shionogi. Clinical studies have found it to possess statistically significant effectiveness for these indications and to be generally well tolerated, with predominantly mild to moderate gastrointestinal side effects. Effects indicative of central opioid withdrawal or impact on the analgesic or miotic effects of co-administered opioids have only been observed in a small number of patients. Medical uses
In the US, naldemedine is approved for the treatment of opioid induced constipation in adults with chronic non-cancer pain, including those who have chronic pain related to prior cancer or its treatment and do not need frequent opioid dosage escalation.In the European Union, naldemedine is also approved for the treatment of opioid induced constipation in adults, but as a second-line therapy after treatment with a laxative. Contraindications
The drug is contraindicated in patients with gastrointestinal obstruction or perforation, or those at risk for these problems. Side effects
Side effects in studies were abdominal pain (8–11% of patients as compared to 2–5% under placebo, depending on the study), diarrhea (7% versus 2–3%), nausea (4–6% versus 2–5%), vomiting (3% versus 2%), gastroenteritis (2–3% versus 1%), and opioid withdrawal syndrome (1.5–3.2% versus 0.5–1.5%). The latter was severe but manageable in one patient, and otherwise mild to moderate. Hypersensitivity reactions were rare; they occurred in two patients.
Purdue Pharma has begun advertising for the medication to be available by October 2017. Intellectual property
There are currently three patents issued for naldemedine tosylate by the United States Patent and Trademark Office. All patents are owned by Shionogi Inc. and will expire from 2026 to 2031. Naldemedine tosylate has 46 other patents in 18 different countries. Clinical trials
The approval of naldemedine came from the results of the COMPOSE program, a phase three clinical studies program conducted in adults 18–80 years of age with chronic non-cancer pain opioid induced constipation. COMPOSE-I and COMPOSE-II were 12-week double blind randomized controlled trials comparing the use of naldemedine to placebo in the patient population. COMPOSE-I began in August 2013 until January 2015 in 68 outpatient clinic in seven countries. COMPOSE-II began in November 2013 until June 2015 taking place in 69 outpatient clinics in six countries. In both trials, patients were randomly assigned to receive either naldemedine 0.2 mg or placebo once daily for 12 weeks. A responder had at least three spontaneous bowel movements per week with an increase of one spontaneous bowel movement for nine of the 12 weeks, including three of the final four weeks of the study. In COMPOSE-I and COMPOSE-II, the proportion of responders were significantly higher in the naldemedine group than the placebo group. Adverse events were similar in both trials, however, patients in the naldemedine group had slightly higher rates of adverse events.COMPOSE-III was a 52-week clinical trial examining the long term safety with naldemedine in patients with non cancer chronic pain.