Methylnaltrexone (Relistor), an opioid-receptor antagonist with peripheral action, is used to treat persistent constipation (in cancer patients and those with a terminal illness).

Methylnaltrexone (Relistor) Uses:

• Advanced sickness and opioid-induced constipation (injection only):

  • Used to treat opioid-induced constipation in individuals who need opioid dose escalation for palliative care due to advanced illness or pain from aggressive cancer.

• Constipation brought on by opiate use (from pills and injections) and ongoing non-cancer pain:

  • Used to treat patients with chronic non-cancer pain, including those who continue to have pain after receiving therapy for cancer in the past and do not require frequent (weekly, for example) opioid dosage escalation.

Read: Naltrexone (Revia, Vivitrol); Uses, Dose, Side effects Read: Naloxone (Narcan); Uses, Dose, Side effects, Indication

Methylnaltrexone (Relistor) Dose in Adults:

Methylnaltrexone (Relistor) Dose in the treatment of Opioid-induced constipation with advanced illness:

• SubQ: The dosage is determined by body weight: As needed, take 1 dosage every other day; at most, take 1 dose every 24 hours.
  • >114 kg:
    • 0.15 mg per kg (round dose up to closest 0.1 mL of volume)
  • 38 to <62 kg:
    • 8 mg
  • <38 kg:
    • 0.15 mg per kg (round dose up to closest 0.1 mL of volume)
  • 62 to 114 kg:
    • 12 mg

Methylnaltrexone (Relistor) Dose for Chronic Non-Cancer Pain with Opioid-Induced Constipation:

Note: Stop using all laxatives for maintenance before beginning therapy; if the reaction is not ideal after three days, laxative therapy may be started again. 

• 450 mg orally, one day. 
• 12 mg SubQ once a day.

Use in Children:

Not indicated.

Methylnaltrexone (Relistor) Pregnancy Risk Category: B1

• Animal reproduction studies have not allowed for adverse events to be monitored.
• Pregnancy and maternal use of methylnaltrexone may lead to opioid withdrawal symptoms in newborns.

Methylnaltrexone use during breastfeeding:

• It is unknown if breast milk contains methylnaltrexone.
• The manufacturer does not recommend breastfeeding because of the risk of serious adverse reactions.

Methylnaltrexone (Relistor) Dose in Kidney Disease:

• CrCl ≥60 mL/minute:
  • No dosage adjustment is required.
• CrCl <60 mL/minute:

  • Constipation brought on by opioids and a serious illness: SubQ:

    • >114 kg:
      • 0.075 mg per kg every other day (round dose up to nearest 0.1 mL of volume)
    • 38 to <62 kg:
      • 4 mg every other day
    • <38 kg:
      • 075 mg per kg every other day (round dose up to nearest 0.1 mL of volume)
    • 62 to 114 kg:
      • 6 mg every other day

  • Constipation brought on by opioids and ongoing non-cancer pain:

    • 150 mg orally, once daily
    • 6 mg once a day in SubQ
• End-stage renal impairment (dialysis-dependent):
  • The manufacturer’s labeling doesn't provide any dosage adjustments (has not been studied).

Methylnaltrexone (Relistor) Dose in Liver disease:

• Constipation brought on by opioids and a serious illness:

  • The manufacturer's labeling doesn't provide any dosage adjustments.
    • If a patient has a significant impairment and continuous non-cancer pain, consider providing the injection in accordance with the recommendations for subcutaneous dosage for opioid-induced constipation (Child-Pugh class C).

• Constipation brought on by opioids and ongoing non-cancer pain:

  • Oral:
    • Mild impairment (Child-Pugh class A):
      • No dosage adjustment is required.
    • Moderate or severe impairment (Child-Pugh class B and C):
      • 150 mg once a day.
  • SubQ:
    • In cases of mild or moderate impairment (Child-Pugh class A or B), there is no need to change the dose.
    • Extreme impairment (Child-Pugh class C):
      • 38 to <62 kg:
        • 4 mg once a day.
      • >114 kg:
        • 0.075 mg/kg once a day (round dose up to nearest 0.1 mL of volume)
      • 62 to 114 kg:
        • 6 mg once a day
      • <38 kg:
        • 0.075 mg per kg once a day (round dose up to nearest 0.1 mL of volume)

Typical Side Impacts of Methylnaltrexone (Relistor):

• Gastrointestinal:

  • Abdominal pain
  • Flatulence
  • Nausea

Less Common Side Effects of Methylnaltrexone (Relistor):

• Dermatologic:

  • Hyperhidrosis

• Neuromuscular & skeletal:

  • Muscle spasm
  • Tremor

• Endocrine & metabolic:

  • Hot flash

• Central nervous system:

  • Dizziness
  • Headache
  • Anxiety
  • Chills

• Respiratory:

  • Rhinorrhea

• Gastrointestinal:

  • Diarrhea
  • Abdominal distension
  • Vomiting

Contraindications to Methylnaltrexone (Relistor):

• Obstructive GI (known or suspected);
• Patients are at higher risk for recurrent GI obstruction.

Canadian labeling: US labeling omits further contraindications. 

• Hypersensitivity to any ingredient in the formulation, including methylnaltrexone

Warnings and precautions

• Diarrhea:

  • Stop treating severe or persistent diarrhea.

• Gastrointestinal perforation:

  • Gastrointestinal perforations have occurred in patients with severe disorders such as Ogilvie's syndrome, diverticular disease, peptic ulcer, Ogilvie's syndrome, infiltrative conditions, GI tract cancers, or peritoneal metastases.
  • Take care when treating these patients, or patients suffering from other conditions that could compromise the integrity of their GI walls (eg Crohn's disease).
  • If severe symptoms develop, discontinue therapy immediately.
  • It is not recommended for individuals with known or suspected GI blockage or those who are more susceptible to recurrent GI dysfunction to take this product.

• Withdrawal of Opioids:

  • This may lead to symptoms such as nausea, vomiting, stomach pain, hyperhidrosis, and anxiety.
  • Patients with blood-brain barrier disruptions should be treated with caution. This could increase withdrawal risk and/or reduce analgesia.
  • If you notice signs of withdrawal, be sure to monitor.

• Hepatic impairment

  • Patients with severe or moderate hepatic impairment should be cautious when using it.

• Renal impairment

  • Patients with severe renal impairment took it with caution.
  • Dosage adjustment is necessary for patients with moderate to severe renal impairment (CrCl lower than 60 mL/minute).

Methylnaltrexone: Drug Interaction

Monitoring parameters:

Abdominal pain that is severe, ongoing, or getting worse; signs of opiate withdrawal; and sufficient analgesia.

How to administer Methylnaltrexone (Relistor)?

SubQ:

• Subcutaneous injections into the upper arm, belly, or thigh should be used to administer.
• With each dose, switch up the injection sites.

Tablet: Oral:

• Take with water on an empty stomach at least 30 minutes before the first meal of the day.

Mechanism of action of Methylnaltrexone (Relistor):

• Additionally to inhibiting opioid-induced reduced intestinal motility and prolonged gastrointestinal transit time, it functions as a peripheral opioid antagonist.
• It is an opioid receptor antagonist.
• This decreases opioid-induced constipation. It doesn't affect the opioid analgesic effects.
• Methylnaltrexone, a quaternary derivative, prevents opioids from attaching to mu receptors and is an antagonist of this process.

Half-life elimination:

• Terminal: ~15 hours (oral)

Protein binding:

• 11 percent to 15 percent

Time to peak, plasma:

• SubQ: 30 minutes;
• Oral: ~1.5 hours (postponed by 2 hours with a fat-rich meal)

Metabolism:

• Metabolized into methyl-6-naltrexol isomers, methylnaltrexone sulphate, and other insignificant metabolites

Excretion:

• Urine (~44 percent to 54 percent, primarily as an unchanged drug);
• feces (~17%, primarily as unchanged drug)

International Brand Names of Methylnaltrexone:

• Relistor

Methylnaltrexone Brand Names in Pakistan:

There is no brand available in Pakistan