Methylnaltrexone

Methylnaltrexone is a selective antagonist of opioid binding at the mu-opioid receptor. As a quaternary amine, the ability of methylnaltrexone to cross the blood-brain barrier is restricted.

• • RELISTOR is an opioid antagonist. RELISTOR tablets and RELISTOR injection are indicated for the treatment of opioid-induced constipation (OIC) in adults 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

• RELISTOR 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 known or suspected mechanical gastrointestinal obstruction and at increased risk of recurrent obstruction.contraindicated

Administration Instructions ( 2.1 ) • Be within close proximity to toilet facilities once administered. • Discontinue if treatment with opioid pain medication is also discontinued. • In adult patients with chronic non-cancer pain and OIC: o Patients receiving opioids for less than 4 weeks may be less responsive to RELISTOR. o Discontinue all maintenance laxative therapy before starting RELISTOR; may resume laxatives if there is a suboptimal response to RELISTOR after 3 days. o Re-evaluate the continued need for RELISTOR when opioid regimen is changed to avoid adverse reactions. • In patients with chronic non-cancer pain and OIC, take RELISTOR tablets with water on an empty stomach at least 30 minutes before the first meal of the day. Dosing • For OIC in adult patients with chronic non-cancer pain ( 2.2 ): o RELISTOR tablets: The recommended dosage is 450 mg once daily in the morning. o RELISTOR injection: The recommended dosage is 12 mg subcutaneously once daily. • For OIC in adult patients with advanced illness ( 2.3 ): o The pre-filled syringe is only for patients who require a RELISTOR injection dose of 8 mg or 12 mg. Use the vial for patients who require other doses of RELISTOR injection. o RELISTOR injection: See Table 1 in the full prescribing information for the recommended dosage; administer one dose every other day, as needed, but no more frequently than one dose in a 24-hour period. Dosage Adjustment • See full prescribing information dosage adjustment in renal or hepatic impairment by indication.

• 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 ) • Severe or Persistent Diarrhea : Discontinue if severe or persistent diarrhea occurs during treatment. ( 5.2 ) • Opioid Withdrawal : Consider the overall risk benefit in patients with disruptions to the blood-brain barrier. Monitor closely for symptoms of opioid withdrawal. ( 5.3 ) 5.1 Gastrointestinal Perforation Cases of gastrointestinal perforation have been reported in adult patients with OIC and advanced illness with conditions that may be associated with localized or diffuse reduction of structural integrity in the wall of the gastrointestinal tract (e.g., peptic ulcer disease, Ogilvie’s syndrome, diverticular disease, infiltrative gastrointestinal tract malignancies or peritoneal metastases). Take into account the overall risk-benefit profile when using RELISTOR 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 RELISTOR in patients who develop this symptom [see Contraindications ( 4 )]. 5.2 Severe or Persistent Diarrhea If severe or persistent diarrhea occurs during treatment, advise patients to discontinue therapy with RELISTOR and consult their healthcare provider.

Serious and important adverse reactions described elsewhere in the labeling include: • Gastrointestinal perforation [see Warnings and Precautions ( 5.1 )] • Severe or persistent diarrhea [see Warnings and Precautions ( 5.2 )] • Opioid withdrawal [see Warnings and Precautions ( 5.3 )] The most common adverse reactions are: OIC in adult patients with chronic non-cancer pain ( 6.1 ) • RELISTOR tablets (≥ 2%): abdominal pain, diarrhea, headache, abdominal distention, vomiting, hyperhidrosis, anxiety, muscle spasms, rhinorrhea, and chills. • RELISTOR injection (≥ 1%): abdominal pain, nausea, diarrhea, hyperhidrosis, hot flush, tremor, and chills. OIC in adult patients with advanced illness ( 6.1 ) • RELISTOR injection (≥ 5%): abdominal pain, flatulence, nausea, dizziness, and diarrhea. To report SUSPECTED ADVERSE REACTIONS, contact Salix Pharmaceuticals at 1-800-321-4576 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 clinical practice. Opioid-Induced Constipation in Adult Patients with Chronic Non-Cancer Pain The safety of RELISTOR tablets was evaluated in a double-blind, placebo-controlled trial in adult patients with OIC and chronic non-cancer pain receiving opioid analgesia.

• Pregnancy : May precipitate opioid withdrawal in a fetus ( 8.1 ) • Lactation : Breastfeeding not recommended. ( 8.2 ) 8.1 Pregnancy Risk Summary The limited available data with RELISTOR in pregnant women are not sufficient to inform a drug-associated risk for major birth defects and miscarriages. There are clinical considerations when RELISTOR is used by pregnant women [see Clinical Considerations]. In animal reproduction studies, no effects on embryofetal development were observed with the administration of intravenous methylnaltrexone bromide during organogenesis in rats and rabbits at doses up to 20 times and 26 times, respectively, the subcutaneous maximum recommended human dose (MRHD) of 12 mg RELISTOR injection per day. The intravenous doses in rats and rabbits are about 0.5 times and 0.7 times, respectively, the oral MRHD of 450 mg/day [see Data]. Advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. 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. Clinical Considerations Fetal/Neonatal Adverse Reactions The use of RELISTOR during pregnancy may precipitate opioid withdrawal in a fetus due to the immature fetal blood-brain barrier.

Metabolism

Between the oral dosage range of 150 mg to 450 mg for RELISTOR tablets and the subcutaneous dosage range of 0.15 mg/kg to 0.50 mg/kg for RELISTOR injection, the mean C max and area under the plasma concentration-time curve (AUC) of methylnaltrexone increased in a dose-proportional manner. There was no significant accumulation of methylnaltrexone following once-daily oral dosing of 450 mg RELISTOR tablets or subcutaneous dosing of 12 mg RELISTOR injection for seven consecutive days in healthy subjects.

During clinical trials of RELISTOR administered orally and subcutaneously, one accidental case of methylnaltrexone bromide overdose was reported and no adverse events were reported as a result of the overdosage. A study of healthy subjects noted orthostatic hypotension associated with a dose of 0.64 mg/kg administered as an intravenous bolus. Monitor for signs or symptoms of orthostatic hypotension and initiate treatment as appropriate. If a patient on opioid therapy receives an overdose of RELISTOR, 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.

• Apr 24, 2008NDANDA021964Salix Pharms
• Jul 19, 2016NDANDA208271Salix

1. 1Death23916%
2. 2Drug Ineffective20514%
3. 3Nausea1177.9%
4. 4Constipation1107.4%
5. 5Abdominal Pain1057.1%
6. 6Pain845.7%
7. 7Diarrhoea785.3%
8. 8Vomiting755.1%
9. 9Fatigue644.3%
10. 10Abdominal Pain Upper563.8%
11. 11Headache563.8%
12. 12Off Label Use503.4%
13. 13Weight Decreased443.0%
14. 14Abdominal Distension422.8%
15. 15Dyspnoea422.8%

The 10 most recently updated of 59 ClinicalTrials.gov registrations naming Methylnaltrexone as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Methylnatrexone In Resectable Head and Neck Squamous Cell Carcinoma (MINK). A "Window of Opportunity" Pilot Study.
  Recruiting · Phase 4 · Interventional · 25 enrolled · M.D. Anderson Cancer Center
  NCT06162377updated 2026-06-10
• RELISTOR's Effects on Opioid-Induced Constipation
  Withdrawn · Observational · 0 enrolled · Methodist Health System
  NCT04930237updated 2026-03-23
• Chronic Widespread Pain in HIV: Novel Mechanisms and Therapeutics
  Recruiting · Interventional · 200 enrolled · Florida International University
  NCT04787848updated 2026-01-14
• Methylnaltrexone vs Naloxegol in the Treatment of Opioid-Induced Constipation
  Completed · Phase 4 · Interventional · 15 enrolled · University of Missouri-Columbia
  NCT03523520updated 2024-09-19
• Effects of Peripherally Acting µ-opioid Receptor Antagonists on Acute Pancreatitis
  Completed · Phase 2 · Phase 3 · Interventional · 105 enrolled · Asbjørn Mohr Drewes
  NCT04743570updated 2023-04-21
• Naloxone and Intravenous Methylnaltrexone Effects on Bladder Function
  Completed · Phase 1 · Interventional · 15 enrolled · Bausch Health Americas, Inc.
  NCT01367561updated 2023-04-12
• Naloxegol to Prevent Lower Gastrointestinal Paralysis in Critically Ill Adults Administered Opioids
  Terminated · Phase 4 · Interventional · 12 enrolled · Tufts Medical Center
  NCT02977286updated 2023-02-16
• Dasatinib, Bevacizumab, Paclitaxel in Patients With Advanced Malignancies
  Completed · Phase 1 · Interventional · 122 enrolled · M.D. Anderson Cancer Center
  NCT01015222updated 2022-11-23
• Subcutaneous Methylnaltrexone Versus Placebo for Postoperative Ileus Prevention
  Completed · Phase 2 · Interventional · 82 enrolled · Ohio State University
  NCT03852524updated 2021-10-27
• An Extension Study of Methylnaltrexone Bromide (MNTX) in Participants With Advanced Pancreatic Cancer
  Withdrawn · Phase 3 · Interventional · 0 enrolled · Bausch Health Americas, Inc.
  NCT04151719updated 2021-05-07

Frequently asked questions

How does Methylnaltrexone work?

Methylnaltrexone is a selective antagonist of opioid binding at the mu-opioid receptor. As a quaternary amine, the ability of methylnaltrexone to cross the blood-brain barrier is restricted.

What is Methylnaltrexone used for?

According to FDA labeling, Methylnaltrexone carries indications including: • RELISTOR is an opioid antagonist. RELISTOR tablets and RELISTOR injection are indicated for the treatment of opioid-induced constipation (OIC) in adults 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 Methylnaltrexone?

Methylnaltrexone is classified as Opioid Antagonist, Opioid Antagonists, Increased Gastric Motility.

What are the brand names for Methylnaltrexone?

Methylnaltrexone is marketed under brand names including Relistor.

What are the contraindications for Methylnaltrexone?

Methylnaltrexone labeling lists contraindications including: RELISTOR 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 known or suspected mechanical gastrointestinal obstruction and at increased risk of recurrent obstruction.. Always consult the full prescribing information and a clinician.