RelistorTM Methylnaltrexone

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RelistorTM - Methylnaltrexone

• Manufacturer Wyeth
• FDA Approval Date June 2008

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Relistor - Methylnaltrexone Clinical Application

• Indications
• Opioid induced constipation in patients with
  advanced illnesses having an inadequate response
  to traditional laxatives
• Place in therapy
• Patients with advanced illnesses receiving
  palliative care experiencing an inadequate
  response to conventional laxative therapies

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Relistor - Methylnaltrexone Clinical Application

• Contraindications
• Mechanical bowel obstruction
• Warnings (and Black Box warnings)
• Stop methylnaltrexone if opioids are discontinued
  
• May cause dizziness
• Concomitant use with SSRIs, lithium,
  carbamazepine, or valproic acid may produce
  additive effects
• Precautions
• Use caution in patients with severe renal failure
  (lt30 ml/min use 50 of dose)

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Relistor - MethylnaltrexoneDrug Facts

• Pharmacology
• Antagonizes mu opioid receptors peripherally
  (unable to cross BBB), inhibits opioid induced
  decreased gastrointestinal motility and delay in
  gastrointestinal transit time

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Relistor - MethylnaltrexoneDrug Facts

• Pharmacokinetics
• A Rapid Cmax 0.5 hours
• D 1.1 L/Kg
• M Metabolized to methyl-6-naltrexol isomers,
  methylnaltrexone sulfate
• E Urine (50, primarily as unchanged drug),
  Feces (lt50, primarily as unchanged drug)

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Relistor - Methylnaltrexone Drug Interactions

• Methylnaltrexone is a weak inhibitor of CYP2D6
• No known drug interactions

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Relistor - Methylnaltrexone Adverse Effects
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RelistorTM - Methylnaltrexone Monitoring
Parameters

• Efficacy Monitoring
• Relief of constipation
• Toxicity Monitoring
• Discontinue if severe or persistent diarrhea
  occurs

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Relistor - Methylnaltrexone Prescription
Information

• Dosing
• Usually given as one dose every other day, as
  needed (Subcutaneous injection)
• lt38 kg 0.15 mg/kg (round up to nearest 0.1 ml of
  volume)
• 38 - lt62 kg 8 mg
• 62 114 kg 12 mg
• gt144 kg 0.15 mg/kg
• Max 1 dose / 24 hours
• Cost
• 12 mg vial 50

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Methylnaltrexone in Opioid-Induced Constipation

• Objective Study the safety and efficacy of
  methylnaltrexone for treatment of opioid-induced
  constipation in patients with advanced illness
• Study Design Double-blind placebo controlled
  trial

Thomas, J. et al. Methylnaltrexone for
Opioid-Induced Constipation in Advanced
Illness.NEJM. 20083582332-43
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Methylnaltrexone in Opioid-Induced Constipation

• Methods Patients were randomized to receive
  methylnaltrexone (0.15 mg/kg) or placebo every
  other day for 2 weeks
• Primary endpoints - rescue free laxation within 4
  hours after the first dose and laxation after 2
  or more hours of the first four doses

Thomas, J. et al. Methylnaltrexone for
Opioid-Induced Constipation in Advanced
Illness.NEJM. 20083582332-43
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Methylnaltrexone in Opioid-Induced Constipation
Thomas, J. et al. Methylnaltrexone for
Opioid-Induced Constipation in Advanced
Illness.NEJM. 20083582332-43
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Methylnaltrexone in Opioid-Induced Constipation
Thomas, J. et al. Methylnaltrexone for
Opioid-Induced Constipation in Advanced
Illness.NEJM. 20083582332-43
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Methylnaltrexone in Opioid-Induced Constipation

• Adverse Events
• The percentage of patients having at least one
  adverse event was similar between both groups
• Events occurring gt5 or more in both groups,
  abdominal pain, flatulence, nausea, increased
  body temperature, and dizziness occurred 3 more
  in the methylnaltrexone group than placebo

Thomas, J. et al. Methylnaltrexone for
Opioid-Induced Constipation in Advanced
Illness.NEJM. 20083582332-43
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RelistorTM - Methylnaltrexone Summary

• Methylnaltrexone is an alternative treatment
  option in opioid-induced constipation in patients
  with advanced illness
• It does not cross the BBB allowing patients to
  have relief of constipation while still receiving
  beneficial pain relief from opioids
• It is an effective, and relatively safe and well
  tolerated medication

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Relistor - Methylnaltrexone References

• http//www.wyeth.com/hcp/relistor/mechanism-of-act
  ion. Accessed Online 02/18/2009.
• Relistor package insert. Philadelphia, PA
  Wyeth April 2008
• Thomas, J. et al. Methylnaltrexone for
  Opioid-Induced Constipation in Advanced
  Illness.NEJM. 20083582332-43.