Opioid-induced constipation: Oral: 0.2 mg once daily. Discontinue treatment if opioid pain medication is discontinued.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
No dosage adjustment necessary.
Mild to moderate impairment (Child-Pugh classes A and B): No dosage adjustment necessary.
Severe impairment (Child-Pugh class C): Avoid use (has not been studied).
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Symproic: 0.2 mg
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Administer without regard to meals.
Opioid-induced constipation: Treatment of opioid-induced constipation (OIC) in adults with chronic noncancer pain, including patients with chronic pain related to prior cancer or its treatment who do not require frequent (eg, weekly) opioid dosage escalation.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Gastrointestinal: Abdominal pain (8%), diarrhea (7%)
1% to 10%:
Gastrointestinal: Nausea (4%), vomiting (3%), gastroenteritis (2%)
<1%, postmarketing, and/or case reports: Hypersensitivity reaction
Hypersensitivity to naldemedine or any component of the formulation; GI obstruction (known or suspected) or at increased risk of recurrent obstruction.
Concerns related to adverse effects:
• GI perforation: GI perforation has been reported with use of another peripherally acting opioid antagonist in patients with advanced illnesses associated with impaired structural integrity of the GI wall (eg, Ogilvie syndrome, peptic ulcer disease, diverticular disease, infiltrative GI tract malignancies, peritoneal metastases). Use with caution in these patients or in patients with other conditions that may result in impaired integrity of the GI wall (eg, Crohn disease). Monitor for development of severe, persistent or worsening abdominal pain; discontinue therapy if this occurs. Use is contraindicated in patients with known or suspected GI obstruction or in patients at increased risk of recurrent GI obstruction.
• Opioid withdrawal: May precipitate symptoms of opioid withdrawal (eg, abdominal pain, chills, diarrhea, hyperhidrosis, nausea, vomiting). Use with caution in patients with disruptions to the blood-brain barrier; may increase the risk for opioid withdrawal and/or reduced analgesia. Monitor for symptoms of opioid withdrawal in such patients.
• Hepatic impairment: Avoid use in severe impairment (Child-Pugh class C).
• Appropriate use: Efficacy has been established in patients who have taken opioids for ≥4 weeks; patients receiving opioids for <4 weeks may be less responsive to naldemedine.
Substrate of CYP3A4 (major), P-glycoprotein/ABCB1 (major), UGT1A3; Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of Naldemedine. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Naldemedine. Risk X: Avoid combination
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Naldemedine. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Naldemedine. Risk C: Monitor therapy
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Methylnaltrexone: May enhance the adverse/toxic effect of Opioid Antagonists. Specifically, the risk for opioid withdrawal may be increased. Risk X: Avoid combination
Naloxegol: Opioid Antagonists may enhance the adverse/toxic effect of Naloxegol. Specifically, the risk for opioid withdrawal may be increased. Risk X: Avoid combination
Opioid Antagonists: May enhance the adverse/toxic effect of Naldemedine. Specifically, the risk for opioid withdrawal may be increased. Risk X: Avoid combination
P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of Naldemedine. Risk C: Monitor therapy
Adverse events were observed in some animal reproduction studies. Based on animal data, naldemedine may cross the placenta and cause opioid withdrawal in the fetus if administered during pregnancy.
It is not known if naldemedine is present in breast milk. According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother. If naldemedine is discontinued to decrease exposure to the infant, breastfeeding may be resumed 3 days after the final dose.
Symptoms of GI perforation (eg, severe, persistent, or worsening abdominal pain); symptoms of opioid withdrawal.
Opioid antagonist that blocks opioid binding at the mu, delta, and kappa receptors; functions as a peripherally acting mu-opioid receptor antagonist, including actions on the GI tract to inhibit the delay in GI transit time, thereby decreasing the constipating effects of opioids.
Distribution: Vd: 155 L
Protein binding: 93% to 94%
Metabolism: CYP3A to nor-naldemedine (major); UGT1A3 to naldemedine 3-G (minor); also undergoes cleavage in the GI tract to form benzamidine and naldemedine carboxylic acid.
Half-life elimination: 11 hours
Time to peak: 0.75 hours; 2.5 hours (with food)
Excretion: Urine (57%; 16% to 18% as unchanged drug; 32% as benzamidine metabolite); feces (35%; 20% as benzamidine metabolite)
Tablets (Symproic Oral)
0.2 mg (per each): $16.63
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