Naloxegol

Naloxegol is an antagonist of opioid binding at the mu-opioid receptor. When administered at the recommended dose levels, naloxegol functions as a peripherally-acting mu-opioid receptor antagonist in tissues, such as the gastrointestinal tract, thereby decreasing the constipating effects of opioids.

• MOVANTIK ® 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. MOVANTIK 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.ICD-10: K59.00

• MOVANTIK is contraindicated in: Patients with known or suspected gastrointestinal obstruction and patients at risk of recurrent obstruction, due to the potential for gastrointestinal perforation [see Warnings and Precautions (5.3) ] . Patients concomitantly using strong CYP3A4 inhibitors (e.g., clarithromycin, ketoconazole) because these medications can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning [see Drug Interactions (7.1) and Clinical Pharmacology (12.3) ] .contraindicated

Administration : Discontinue maintenance laxative therapy before starting MOVANTIK; may resume laxatives if patients have OIC symptoms after taking MOVANTIK for 3 days. (2.1) Alteration in analgesic dosing regimen prior to starting MOVANTIK is not required. (2.1) Patients receiving opioids for less than 4 weeks may be less responsive to MOVANTIK. (2.1) Take on an empty stomach at least 1 hour prior to the first meal of the day or 2 hours after the meal. (2.1) For patients who are unable to swallow the MOVANTIK tablet whole, the tablet can be crushed and given orally or administered via nasogastric tube, see full prescribing information. (2.1) Avoid consumption of grapefruit or grapefruit juice. (2.1 , 7.1) Discontinue if treatment with the opioid pain medication is also discontinued. (2.1) Recommended dosage : 25 mg once daily; if not tolerated, reduce to 12.5 mg once daily. (2.2) Renal Impairment (CLcr < 60 mL/min): 12.5 mg once daily; increase to 25 mg once daily if tolerated and monitor for adverse reactions. (2.3 , 8.6) 2.1 Administration Instructions Discontinue all maintenance laxative therapy prior to initiation of MOVANTIK. Laxative(s) can be used as needed if there is a suboptimal response to MOVANTIK after three days. Alteration in analgesic dosing regimen prior to initiating MOVANTIK is not required. Patients receiving opioids for less than 4 weeks may be less responsive to MOVANTIK [see Clinical Studies (14) ] . Take MOVANTIK on an empty stomach at least 1 hour prior to the first meal of the day or 2 hours after the meal.

Opioid withdrawal : Consider the overall risk benefit in patients with disruptions to the blood-brain barrier. Monitor for symptoms of opioid withdrawal. (5.1) Severe abdominal pain and/or diarrhea : Monitor for the development of symptoms after initiating treatment with MOVANTIK and discontinue if severe symptoms develop. Consider restarting MOVANTIK at 12.5 mg once daily if appropriate. (5.2) 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. (5.3) 5.1 Opioid Withdrawal Clusters of symptoms consistent with opioid withdrawal, including hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning have occurred in patients treated with MOVANTIK [see Adverse Reactions (6.1 )] . In addition, patients receiving methadone as therapy for their pain condition were observed in clinical trials to have a higher frequency of gastrointestinal adverse reactions that may have been related to opioid withdrawal than patients receiving other opioids [see Adverse Reactions (6.1) ] . Patients having disruptions to the blood-brain barrier may be at increased risk for opioid withdrawal or reduced analgesia. Take into account the overall risk-benefit profile when using MOVANTIK in such patients. Monitor for symptoms of opioid withdrawal in such patients.

Serious and important adverse reactions described elsewhere in labeling include: Opioid withdrawal [see Warnings and Precautions (5.1) ] Severe abdominal pain and/or diarrhea [see Warnings and Precautions (5.2) ] Gastrointestinal perforation [see Warnings and Precautions (5.3) ] The most common adverse reactions in clinical trials (≥3%) are: abdominal pain, diarrhea, nausea, flatulence, vomiting, and headache. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Valinor at 1-877-592-2337 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 MOVANTIK in 1497 patients in clinical trials, including 537 patients exposed for greater than six months, and 320 patients exposed for 12 months. The safety data described in Table 1 are derived from two double-blind, placebo-controlled trials (Studies 1 and 2) in patients with OIC and non-cancer related pain [see Clinical Studies (14) ] . Study 3 (n=302) was a safety extension study that allowed patients from Study 1 to continue the same blinded treatment for an additional 12 weeks. Safety data for patients in Study 3 are similar to those listed in Table 1.

Pregnancy : May precipitate opioid withdrawal in pregnant women and the fetus. (8.1) Lactation : Breastfeeding not recommended. (8.2) Hepatic Impairment : Avoid in severe impairment. (8.7) 8.1 Pregnancy Risk Summary Limited available data with MOVANTIK use in pregnant women are insufficient to inform a drug associated risk of adverse developmental outcomes. MOVANTIK may precipitate opioid withdrawal in the pregnant women and the fetus (see Clinical Considerations ) . In animal development studies, no effects on embryo-fetal development were observed following administration of naloxegol in pregnant rats during the period of organogenesis at doses up to 1452 times the human AUC (area under the plasma concentration-time curve) at the maximum recommended human dose. No effects on embryo-fetal development were observed following administration of naloxegol in pregnant rabbits during the period of organogenesis at doses up to 409 times the human AUC at the maximum recommended human dose. The estimated background risk of major birth defects and miscarriage for the indicated populations are unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically-recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Metabolism

Absorption Following oral administration, MOVANTIK is absorbed with peak concentrations (C max ) achieved at less than 2 hours. In a majority of subjects, a secondary plasma concentration peak of naloxegol was observed approximately 0.4 to 3 hours after the first peak.

In a clinical study of patients with OIC a daily dose of 50 mg (twice the recommended dosage), administered over 4 weeks, was associated with an increased incidence of GI adverse reactions, such as abdominal pain, diarrhea, and nausea. These adverse reactions frequently occurred within 1-2 days after dosing. No antidote is known for naloxegol. Dialysis was noted to be ineffective as a means of elimination in a clinical study in patients with renal failure. If a patient on opioid therapy receives an overdose of naloxegol, the patient should be monitored closely for potential evidence of opioid withdrawal symptoms such as chills, rhinorrhea, diaphoresis, or reversal of central analgesic effect. Base treatment on the degree of opioid withdrawal symptoms, including changes in blood pressure and heart rate, and on the need for analgesia.

• Sep 16, 2014NDANDA204760Averitas

1. 1Diarrhoea3749.7%
2. 2Constipation3719.7%
3. 3Drug Ineffective3669.5%
4. 4Pain3599.4%
5. 5Nausea3248.4%
6. 6Off Label Use2687.0%
7. 7Abdominal Pain2566.7%
8. 8Abdominal Pain Upper2245.8%
9. 9Intentional Product Misuse2225.8%
10. 10Vomiting2065.4%
11. 11Hyperhidrosis1854.8%
12. 12Death1844.8%
13. 13Headache1824.7%
14. 14Fatigue1794.7%
15. 15Malaise1704.4%

The 10 most recently updated of 43 ClinicalTrials.gov registrations naming Naloxegol as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Effect of Naloxegol on Postoperative Ileus in Patients Undergoing Cardiac Surgery
  Completed · Phase 3 · Interventional · 305 enrolled · CMC Ambroise Paré
  NCT04433390updated 2026-05-20
• The NIPA Study Naloxegol Administration to Prevent Opioids Induced Gastrointestinal Motility Disturbance in Brain Injured PAtients
  Recruiting · Phase 3 · Interventional · 370 enrolled · University Hospital, Brest
  NCT05008926updated 2025-11-21
• Naloxegol in Treating Patients With Stage IIIB-IV Non-small Cell Lung Cancer
  Terminated · Phase 2 · Interventional · 50 enrolled · Alliance for Clinical Trials in Oncology
  NCT03087708updated 2025-07-17
• 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
• Methylnaltrexone vs Naloxegol in the Treatment of Opioid-Induced Constipation
  Completed · Phase 4 · Interventional · 15 enrolled · University of Missouri-Columbia
  NCT03523520updated 2024-09-19
• Naloxegol Drug Utilization Post Authorisation Safety Study
  Completed · Observational · 17,254 enrolled · Kyowa Kirin Pharmaceutical Development Ltd
  NCT02813148updated 2024-07-23
• Naloxegol Health Outcome Post Authorisation Safety Study
  Terminated · Observational · 10,000 enrolled · Kyowa Kirin Pharmaceutical Development Ltd
  NCT02813369updated 2024-07-23
• Real World Observational Study of Naloxegol for Patients With Cancer Pain Diagnosed With OIC.
  Completed · Observational · 183 enrolled · Kyowa Kirin Pharmaceutical Development Ltd
  NCT03638440updated 2024-06-17
• Phase I Pharmacokinetics and Safety Study of Naloxegol in Paediatric OIC Patients
  Completed · Phase 1 · Interventional · 61 enrolled · Kyowa Kirin Pharmaceutical Development Ltd
  NCT02099591updated 2024-06-17
• Ancillary Effects of Oral Naloxegol (Movantik)
  Completed · Phase 4 · Interventional · 136 enrolled · The Cleveland Clinic
  NCT03235739updated 2023-09-05

Frequently asked questions

How does Naloxegol work?

Naloxegol is an antagonist of opioid binding at the mu-opioid receptor. When administered at the recommended dose levels, naloxegol 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 Naloxegol used for?

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

What class of drug is Naloxegol?

Naloxegol is classified as Peripheral opioid receptor antagonists, Opioid Antagonist, Cytochrome P450 3A4 Inhibitors, Opioid Antagonists, Increased Gastric Motility.

What are the brand names for Naloxegol?

Naloxegol is marketed under brand names including Movantik.

What are the contraindications for Naloxegol?

Naloxegol labeling lists contraindications including: MOVANTIK is contraindicated in: Patients with known or suspected gastrointestinal obstruction and patients at risk of recurrent obstruction, due to the potential for gastrointestinal perforation [see Warnings and Precautions (5.3) ] . Patients concomitantly using strong CYP3A4 inhibitors (e.g., clarithromycin, ketoconazole) because these medications can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning [see Drug Interactions (7.1) and Clinical Pharmacology (12.3) ] .. Always consult the full prescribing information and a clinician.