General Information

Symproic (naldemedine) is an opioid antagonist.

Symproic is specifically indicated for the treatment of opioid-induced constipation (OIC) in adult patients with chronic non-cancer pain.

Mechanism of Action

Symproic (naldemedine) is an opioid antagonist with binding affinities for mu-, delta- and kappa-opioid receptors. Naldemedine functions as a peripherally-acting mu-opioid receptor antagonist in tissues such as the gastrointestinal tract, thereby decreasing the constipating effects of opioids. 

Side Effects

Adverse effects associated with the use of Symproic may include, but are not limited to, the following:

• abdominal pain
• diarrhea
• nausea

Dosing/Administration

Symproic is supplied as a tablet for oral administration. The recommended dosage is 0.2 mg once daily with or without food.

Clinical Trial Results

The FDA approval of Symproic was based on two replicate, 12-week, randomized, double-blind, placebo-controlled trials (study 1 and study 2) in which Symproic was used without laxatives in patients with OIC and chronic non-cancer pain. In both studies, OIC was confirmed through a two-week run-in period and was defined as no more than four spontaneous bowel movements (SBMs) total over 14 consecutive days and less than 3 SBMs in a given week with at least 25 percent of the SBMs associated with one or more of the following conditions: (1) straining; (2) hard or lumpy stools; (3) having a sensation of incomplete evacuation; and (4) having a sensation of anorectal obstruction/blockage. A total of 547 patients in study 1 and 553 patients in study 2 were randomized in a 1-to-1 ratio to receive Symproic 0.2 mg once daily or placebo for 12 weeks. Study medication was administered without regard to meals. The efficacy of Symproic was assessed in studies 1 and 2 using a responder analysis. A responder was defined as a patient who had at least three SBMs per week and a change from baseline of at least one SBM per week for at least nine out of the 12 weeks and three out of the last four weeks in studies 1 and 2. Study 1: Symproic arm: 130 subjects (48 percent) were responders versus placebo arm: 94 subjects (35 percent) (p=0.0020). Study 2: Symproic arm: 145 subjects (53 percent) were responders versus placebo arm: 92 subjects (34 percent) (p<0.0001).