Naldemedine

SYMPROIC is indicated for the treatment of opioid-induced constipation (OIC) in adult patients with chronic non-cancer pain, including patients with chronic pain related to prior cancer or its treatment who do not require frequent (e.g., weekly) opioid dosage escalation. SYMPROIC is an opioid antagonist indicated for the treatment of opioid-induced constipation (OIC) in adult patients with chronic non-cancer pain, including patients with chronic pain related to prior cancer or its treatment who do not require frequent (e.g., weekly) opioid dosage escalation

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. Naldemedine is a derivative of naltrexone to which a side chain has been added that increases the molecular weight and the polar surface area, thereby reducing its ability to cross the blood-brain barrier (BBB). Naldemedine is also a substrate of the P-glycoprotein (P-gp) efflux transporter. Based on these properties, the CNS penetration of naldemedine is expected to be negligible at the recommended dose levels, limiting the potential for interference with centrally-mediated opioid analgesia.

Administration: Alteration of analgesic dosing regimen prior to initiating SYMPROIC is not required Patients receiving opioids for less than 4 weeks may be less responsive to SYMPROIC Discontinue SYMPROIC if treatment with the opioid pain medication is also discontinued Dosage: In adults, the recommended dosage is 0.2 mg once daily with or without food

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. Patients with a history of a hypersensitivity reaction to naldemedine. Reactions have included bronchospasm and rash. Patients with known or suspected gastrointestinal obstruction or at increased risk of recurrent obstruction.

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. Opioid withdrawal: Consider the overall risk benefit in patients with disruptions to the blood-brain barrier. Monitor symptoms of opioid withdrawal

Serious and important adverse reactions described elsewhere in labeling include: Gastrointestinal perforation Opioid withdrawal Most common adverse reactions (≥2%) are: abdominal pain, diarrhea, nausea and gastroenteritis

Table 3 includes drugs with clinically important drug interactions with SYMPROIC and instructions for preventing or managing the interaction. Table 3: Clinically 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 naldemedine concentrations, which may reduce efficacy Intervention Avoid use of SYMPROIC with strong CYP3A inducers. Other Opioid Antagonists Clinical Impact Potential for additive effect of opioid receptor antagonism and increased risk of opioid withdrawal. Intervention Avoid use of SYMPROIC with another opioid antagonist.

Store SYMPROIC in a light resistant container at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (59°F and 86°F).