Naldemedine, sold under the 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 who have previously been treated with a laxative in the European Union, or to treat opioid induced constipation in adults with chronic non-cancer pain in the US.

Examples include itraconazole (which increased naldemedine exposure 2.9-fold in a study), ketoconazole, clarithromycin and grapefruit juice.

[1][5] Strong inhibitors of the pump P-glycoprotein such as ciclosporin may increase naldemedine concentrations in the blood plasma.

[1][5] Naldemedine is a derivative of naltrexone and, like this substance, blocks opioid receptors of the types μ (mu), δ (delta) and κ (kappa).

While naltrexone is able to cross the blood–brain barrier and can therefore be used to treat opioid dependence, the large hydrophilic side chain of naldemedine and its affinity to P-glycoprotein result in negligible concentrations in the central nervous system when recommended doses are applied.

Minor metabolites are the 6-glucuronide, the 7-(R/S)-hydroxy-derivates, and two products formed by enterobacteria through cleaving the oxadiazole ring: naldemedine carboxylic acid and benzamidine.

The part of the molecule "left" of the cleavage line (the sum of original substance, nor-naldemedine, glucuronides, hydroxy-derivative, and carboxylic acid) is found to 20.4% in the urine and to 64.3% in the faeces, while the part "right" to the line (the sum of original substance, nor-naldemedine, glucuronides, hydroxy-derivative, and benzamidine) is found to 57.3% in the urine and to 34.8% in the faeces.

[8] Purdue Pharma LP is a privately held pharmaceutical company based in the United States that specializes in chronic pain disorders.

[9] Purdue Pharma appealed to remove the Class II scheduling of Symproic as accordant to the Controlled Substances Act.

COMPOSE-I and COMPOSE-II were 12-week double blind randomized controlled trials comparing the use of naldemedine to placebo in the patient population.

[16] COMPOSE-III was a 52-week clinical trial examining the long term safety with naldemedine in patients with non cancer chronic pain.

Results from this trial showed statistical significance for increased weekly bowel movements and no opioid withdrawal symptoms.