(meth il nal TREKS one)
Opioid-induced constipation with advanced illness: Treatment of opioid-induced constipation in adult patients with advanced illness (receiving palliative care) who have an inadequate response to conventional laxative regimens.
Opioid-induced constipation with chronic non-cancer pain: Treatment of opioid-induced constipation in adult patients with chronic non-cancer pain.
Known or suspected gastrointestinal obstruction; patients at increased risk of recurrent obstruction due to the potential for gastrointestinal perforation.
Canadian labeling: Additional contraindications (not in U.S. labeling): Hypersensitivity to methylnaltrexone or any component of the formulation
Opioid-induced constipation with chronic non-cancer pain: SubQ: 12 mg once daily. Note: Discontinue all laxatives prior to use; if response is not optimal after 3 days, laxative therapy may be reinitiated.
Opioid-induced constipation with advanced illness: SubQ: Dosing is according to body weight: Administer 1 dose every other day as needed; maximum: 1 dose/24 hours
<38 kg: 0.15 mg/kg (round dose up to nearest 0.1 mL of volume)
38 to <62 kg: 8 mg
62 to 114 kg: 12 mg
>114 kg: 0.15 mg/kg (round dose up to nearest 0.1 mL of volume)
Refer to adult dosing.
Mild-to-moderate impairment: No dosage adjustment necessary.
Severe impairment (CrCl <30 mL/minute): Administer 50% of normal dose.
End-stage renal impairment (dialysis-dependent): There are no dosing adjustments provided in the manufacturer 's labeling (has not been studied).
Mild-to-moderate impairment (Child-Pugh class A or B): No dosage adjustment necessary.
Severe impairment: There are no dosing adjustments provided in the manufacturer 's labeling (has not been studied).
Administer by subcutaneous injection into the upper arm, abdomen, or thigh. Rotate injection sites at each dose. Toilet facilities should be nearby immediately following administration. Discard any unused medication that remains in the vial.
Store intact vials and prefilled syringes between 20 ‚ °C and 25 ‚ °C (68 ‚ °F and 77 ‚ °F); excursions are permitted between 15 ‚ °C and 30 ‚ °C (59 ‚ °F and 86 ‚ °F). Do not freeze. Protect from light. Solution withdrawn from the single use vial is stable in a syringe for 24 hours at room temperature. Do not remove the prefilled syringe from the tray until ready to administer.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Kit, Subcutaneous:
Relistor: 12 mg/0.6 mL [contains edetate calcium disodium]
Solution, Subcutaneous:
Relistor: 8 mg/0.4 mL (0.4 mL); 12 mg/0.6 mL (0.6 mL) [contains edetate calcium disodium]
Naloxegol: Opioid Antagonists may enhance the adverse/toxic effect of Naloxegol. Specifically, the risk for opioid withdrawal may be increased. Avoid combination
Opioid Antagonists: Methylnaltrexone may enhance the adverse/toxic effect of Opioid Antagonists. Specifically, the risk for opioid withdrawal may be increased. Avoid combination
Severe, persistent, or worsening abdominal pain; symptoms of opioid withdrawal; adequate analgesia; signs or symptoms of orthostatic hypotension.
>10%: Gastrointestinal: Abdominal pain (21% to 29%), flatulence (13%), nausea (9% to 12%)
1% to 10%:
Central nervous system: Dizziness (7%), chills (1%)
Dermatologic: Hyperhidrosis (6%)
Endocrine & metabolic: Hot flash (3%)
Gastrointestinal: Diarrhea (6%)
Neuromuscular & skeletal: Tremor (1%)
<1% (Limited to important or life-threatening): Abdominal cramps, gastrointestinal perforation, increased body temperature, muscle spasm, opioid withdrawal syndrome, piloerection, syncope
Severe renal impairment decreases renal clearance of methylnaltrexone, resulting in a 2-fold increase in drug exposure. No studies were performed in patients with ESRD requiring dialysis.
Concerns related to adverse effects:
- Diarrhea: Discontinue treatment for severe or persistent diarrhea.
- Gastrointestinal perforation: Gastrointestinal perforations have been reported in patients with advanced illnesses associated with impaired structural integrity of the GI wall (eg, Ogilvie 's syndrome, peptic ulcer disease, diverticular disease, infiltrative GI tract malignancies, or 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 at increased risk of recurrent obstruction.
- Opioid withdrawal: May precipitate symptoms of opioid withdrawal (eg, abdominal pain, anxiety, chills, diarrhea, hyperhidrosis, and yawning). Use with caution in patients with disruptions to the blood-brain barrier; may increase the risk for withdrawal and/or reduced analgesia. Monitor for symptoms of opioid withdrawal in such patients.
Disease-related concerns:
- Renal impairment: Use with caution in patients with renal impairment; dosage adjustment recommended for severe renal impairment (CrCl <30 mL/minute). Has not been studied in patients with end-stage renal impairment requiring dialysis.
Other warnings/precautions:
- Appropriate use: Use beyond 4 months has not been studied. Discontinue methylnaltrexone if opioids are discontinued.
- Opioid-induced constipation with chronic non-cancer pain: Appropriate use: Efficacy has been established in patients who have taken opioids for ≥4 weeks; sustained exposure to opioids prior to initiation of methylnaltrexone may increase sensitivity to effects. All laxative maintenance therapy should be discontinued prior to initiation of therapy; laxative therapy may be added if a suboptimal response to therapy is noted after 3 days. When the opioid regimen has been changed, the patient should be re-evaluated for the need to continue methylnaltrexone therapy.
C
Adverse effects were not observed in animal reproduction studies. Maternal use of methylnaltrexone during pregnancy may precipitate opioid withdrawal effects in newborn.
An opioid receptor antagonist which blocks opioid binding at the mu receptor, methylnaltrexone is a quaternary derivative of naltrexone with restricted ability to cross the blood-brain barrier. It therefore functions as a peripheral acting opioid antagonist, including actions on the gastrointestinal tract to inhibit opioid-induced decreased gastrointestinal motility and delay in gastrointestinal transit time, thereby decreasing opioid-induced constipation. Does not affect opioid analgesic effects.
SubQ: Rapid
Vdss: ~1.1 L/kg
Metabolized to methyl-6-naltrexol isomers, methylnaltrexone sulfate, and other minor metabolites
Urine (~54%, primarily as unchanged drug); feces (~17%, primarily as unchanged drug)
Usually within 30-60 minutes (in responding patients)
SubQ: 30 minutes
Terminal: ~8 hours
11% to 15%
- Discuss specific use of drug and side effects with patient as it relates to treatment. HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience dizziness, flushing, flatulence, or sweating a lot. Have patient report immediately to prescriber severe diarrhea; chills; severe abdominal pain; severe abdominal edema; tremors; vomiting blood; nausea; vomiting; or black, tarry, or bloody stools (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.