SYMPROIC (naldemedine tosylate)

AbsorptionFollowing oral administration, naldemedine is absorbed with a time to achieve peak concentrations (T max ) of approximately 0.75 hours in a fasted state. Across the range of doses evaluated, the maximum plasma concentration (C max ) and area under the plasma concentration-time curve (AUC) increased in a dose-proportional or almost dose-proportional manner. Accumulation was minimal following multiple daily doses of naldemedine. Food Effect A high-fat meal decreased the rate but not the...

SYMPROIC was evaluated in 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. Patients receiving a stable opioid morphine equivalent daily dose of at least 30 mg for at least 4 weeks before enrollment and self-reported OIC were eligible for clinical trial participation. Patients with evidence of significant structural abnormalities of the GI tract were not enrolled in these trials. In Studies 1 and 2, patients had to either be not using laxatives or willi...

Serious and important adverse reactions described elsewhere in labeling include: Gastrointestinal perforation [see Warnings and Precautions (5.1) ] Opioid withdrawal [see Warnings and Precautions (5.2) ] Most common adverse reactions (≥2%) are: abdominal pain, diarrhea, nausea and gastroenteritis ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact BioDelivery Sciences International, Inc. at 1-800-469-0261 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Becaus...

SYMPROIC is contraindicated in: Patients with known or suspected gastrointestinal obstruction and patients at increased risk of recurrent obstruction, due to the potential for gastrointestinal perforation [see Warnings and Precautions (5.1) ]. Patients with a history of a hypersensitivity reaction to naldemedine. Reactions have included bronchospasm and rash [see Adverse Reactions (6.1) ] . Patien...

Gastrointestinal perforation : Consider the overall risk benefit in patients with known or suspected lesions of the GI tract. Monitor for severe, persistent, or worsening abdominal pain; discontinue if development of symptoms ( 5.1 ) Opioid withdrawal : Consider the overall risk benefit in patients with disruptions to the blood-brain barrier. Monitor symptoms of opioid withdrawal ( 5.2 ) 5.1 Gastrointestinal Perforation Cases of gastrointestinal (GI) perforation have been reported with use of an...

7 DRUG INTERACTIONS Table 3 includes drugs with clinically important drug interactions with SYMPROIC and instructions for preventing or managing the interaction.

Table 3Clinically Relevant Interactions Affecting Naldemedine When Co-Administered with Other Drugs Strong CYP3A Inducers (e.g., rifampin, carbamazepine, phenytoin, St. John's Wort) Clinical Impact Significant decrease in plasma naldeme...