Methylnaltrexone Bromide (2 brand names, 2 dosage forms, 2 routes)
Available dosage forms: SOLUTION, TABLET.
Routes of administration: SUBCUTANEOUS, ORAL.
Brand Names
- METHYLNALTREXONE BROMIDE
- RELISTOR
Dosage and Administration
•Be within close proximity to toilet facilities once RELISTOR is administered. •Discontinue RELISTOR if treatment with the opioid pain medication is also discontinued. •In adult patients with chronic non-cancer pain and OIC: oPatients receiving opioids for less than 4 weeks may be less responsive to RELISTOR [see Clinical Studies (14.1)]. oDiscontinue all maintenance laxative therapy prior to initiation of RELISTOR. Laxative(s) can be used as needed if there is a suboptimal response to RELISTOR after three days. oRe-evaluate the continued need for RELISTOR when the opioid regimen is changed to avoid adverse reactions. oIn 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.
Contraindications
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)].
Warnings and Precautions
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 )].
Adverse Reactions
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)]
Drug Interactions
Avoid concomitant use of RELISTOR with other opioid antagonists because of the potential for additive effects of opioid receptor antagonism and increased risk of opioid withdrawal.
Mechanism of Action
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. This allows methylnaltrexone to function as a peripherally-acting mu-opioid receptor antagonist in tissues such as the gastrointestinal tract, thereby decreasing the constipating effects of opioids without impacting opioid-mediated analgesic effects on the central nervous system (CNS).
Overdosage
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.