Naldemedine

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.

• 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.ICD-10: K59.00

• 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.contraindicated

Administration ( 2.1 ) : 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 ( 2.2 ) : In adults, the recommended dosage is 0.2 mg once daily with or without food 2.1 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 [see Clinical Studies (14) ] . Discontinue SYMPROIC if treatment with the opioid pain medication is also discontinued. 2.2 Adult Dosage The recommended dosage of SYMPROIC is 0.2 mg orally once daily with or without food.

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 another peripherally acting opioid antagonist, including SYMPROIC. Postmarketing cases of GI perforation, including fatal cases, were reported when SYMPROIC was used in patients at risk of GI perforation (e.g., GI cancer, past GI surgery, diverticulitis, chemotherapy/radiation). SYMPROIC is contraindicated in patients with known or suspected gastrointestinal obstruction or in patients at risk of recurrent obstruction. Take into account the overall risk-benefit profile when using SYMPROIC in patients with these conditions or other conditions which might result in impaired integrity of the gastrointestinal tract wall (e.g., Crohn's disease). Monitor for the development of severe, persistent, or worsening abdominal pain; discontinue SYMPROIC in patients who develop this symptom. 5.2 Opioid Withdrawal Clusters of symptoms consistent with opioid withdrawal, including hyperhidrosis, chills, increased lacrimation, hot flush/flushing, pyrexia, sneezing, feeling cold, abdominal pain, diarrhea, nausea, and vomiting have occurred in patients treated with SYMPROIC [see Adverse Reactions (6.1) ] .

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 Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data described below reflect exposure to SYMPROIC in 1163 patients in clinical trials, including 487 patients with exposures greater than six months and 203 patients with exposures of 12 months. The following safety data are derived from three double-blind, placebo-controlled trials in patients with OIC and chronic non-cancer pain: two 12-week studies (Studies 1 and 2) and one 52-week study (Study 3) [see Clinical Studies (14) ]. In Studies 1 and 2, patients on laxatives were required to discontinue their use prior to study enrollment. All patients were restricted to bisacodyl rescue treatment during the study. In Study 3, approximately 60% of patients in both treatment groups were on a laxative regimen at baseline; patients were allowed to continue using their laxative regimen throughout the study duration.

Pregnancy : May precipitate opioid withdrawal in a fetus ( 8.1 ) Lactation : Discontinue drug or breastfeeding taking into consideration importance of drug to mother ( 8.2 ) Hepatic Impairment : Avoid in severe impairment ( 8.6 ) 8.1 Pregnancy Risk Summary There are no available data with naldemedine in pregnant women to inform a drug-associated risk of major birth defects and miscarriage. There is a potential for opioid withdrawal in a fetus when SYMPROIC is used in pregnant women [see Clinical Considerations ]. SYMPROIC should be used during pregnancy only if the potential benefit justifies the potential risk. In a rat embryo-fetal development study following oral administration of naldemedine during the period of organogenesis at doses resulting in systemic exposure approximately 23,000 times the human area under the plasma-concentration time curve (AUC) at the recommended human dose of 0.2 mg/day, no developmental abnormalities were observed. In rabbits, there were no adverse effects on embryo-fetal development following oral administration of naldemedine during the period of organogenesis at doses resulting in systemic exposure approximately 226 times the human AUC at the recommended human dose of 0.2 mg/day [see Data ]. No effects on pre- and postnatal development were observed in rats at exposures 12 times human exposures at the recommended human dose.

Metabolism

Absorption Following 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.

Single doses of naldemedine up to 100 mg (500 times the recommended dose) and multiple doses of up to 30 mg (150 times the recommended dose) for 10 days have been administered to healthy subjects in clinical studies. Dose-dependent increases in gastrointestinal-related adverse reactions, including abdominal pain, diarrhea, and nausea, were observed. Single doses of naldemedine up to 3 mg (15 times the recommended dose) and multiple doses of 0.4 mg (twice the recommended dose) for 28 days have been administered to patients with OIC in clinical studies. Dose-dependent increases in gastrointestinal-related adverse reactions, including abdominal pain, diarrhea, nausea, and vomiting, were observed. Also, chills, hyperhidrosis, and dizziness were reported more frequently at 1 and 3 mg doses and hyperhidrosis at the 0.4 mg dose. No antidote for naldemedine is known. Hemodialysis is not an effective means to remove naldemedine from the blood [see Clinical Pharmacology (12.3) ] .

• Mar 23, 2017NDANDA208854Bdsi

1. 1Diarrhoea18512%
2. 2Nausea1247.8%
3. 3Drug Ineffective1086.8%
4. 4Constipation1036.5%
5. 5Malignant Neoplasm Progression925.8%
6. 6Abdominal Pain875.5%
7. 7Interstitial Lung Disease774.9%
8. 8Decreased Appetite714.5%
9. 9Malaise674.2%
10. 10Anaemia644.0%
11. 11Pyrexia623.9%
12. 12Vomiting573.6%
13. 13Off Label Use503.2%
14. 14Hepatic Function Abnormal493.1%
15. 15Febrile Neutropenia473.0%

The 10 most recently updated of 12 ClinicalTrials.gov registrations naming Naldemedine as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Prophylactic Use of Naldemedine on Opioid-induced Nausea and Vomiting in Patients With Cancer: POSEIDON Study
  Completed · Phase 4 · Interventional · 120 enrolled · International University of Health and Welfare
  NCT07038551updated 2026-06-03
• Safety and Pharmacokinetics Study of Naldemedine in Paediatric Participants Receiving Opioids
  Recruiting · Phase 1 · Phase 2 · Interventional · 24 enrolled · Shionogi
  NCT05588323updated 2026-04-29
• Naldemedine in Clinical Practice in Cancer Patients With Opioid Induced CONstipation: Clinical Outcomes and Patient Experience
  Recruiting · Observational · 100 enrolled · Professor Monique A. H. Steegers
  NCT07231796updated 2026-01-02
• Risk of Major Adverse Cardiovascular Events for Naldemedine & Other Medications for Opioid Induced Constipation
  Recruiting · Observational · 34,532 enrolled · BioDelivery Sciences International
  NCT03720613updated 2025-02-12
• The Effect of Naldemedine on Opioid-induced Bowel Dysfunction
  Unknown · Phase 2 · Interventional · 20 enrolled · Asbjørn Mohr Drewes
  NCT06334198updated 2024-03-28
• Effects of a Peripherally Acting µ-opioid Receptor Antagonist on Recurrent Acute Pancreatitis
  Unknown · Phase 2 · Phase 3 · Interventional · 74 enrolled · Asbjørn Mohr Drewes
  NCT04966559updated 2024-03-21
• A Study of Naldemedine in Participants Undergoing Surgeries That Include a Bowel Resection or Bowel Transection
  Terminated · Phase 2 · Interventional · 2 enrolled · Shionogi
  NCT04355169updated 2022-01-18
• Long Term Safety of Naldemedine
  Completed · Phase 3 · Interventional · 1,246 enrolled · Shionogi
  NCT01965652updated 2018-04-18
• A Study of Naldemedine (S-297995) for the Treatment of Opioid-Induced Constipation in Adults With Non-Malignant Chronic Pain Receiving Opioid Therapy
  Completed · Phase 2 · Interventional · 244 enrolled · Shionogi
  NCT01443403updated 2017-06-26
• Efficacy and Safety of Naldemedine in Treating Opioid-induced Constipation
  Completed · Phase 3 · Interventional · 553 enrolled · Shionogi
  NCT01993940updated 2017-05-30

Frequently asked questions

How does Naldemedine work?

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.

What is Naldemedine used for?

According to FDA labeling, Naldemedine carries indications including: 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.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Naldemedine?

Naldemedine is classified as Peripheral opioid receptor antagonists, Opioid Antagonist, Opioid Antagonists, Opioid mu-Receptor Agonists, Increased Large Intestinal Motility.

What are the brand names for Naldemedine?

Naldemedine is marketed under brand names including Symproic.

What are the contraindications for Naldemedine?

Naldemedine labeling lists contraindications including: 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.. Always consult the full prescribing information and a clinician.