Drug type

• A peripheral acting narcotic antagonist, opioid reversing agent

Indications

• Treatment of constipation caused by narcotic (opiate-type) medication for patients with advanced illness who have had poor responses to conventional laxative regimens. 

Mechanism of action

• Peripheral mu-opioid receptor antagonist

• Limited ability to cross the blood brain barrier (BBB)

• Methylnaltrexone reduces opioid-induced constipation without abolishing opioid-induced analgesia.

Dosage and administration

• Subcutaneous injectable solution

—   12mg/0.6mL vial

• Opioid-induced constipation (after failure of laxatives)

—   Weight-based dosing:

38-62 kg: 8 mg/dose SC every other day

62-114kg: 12 mg/dose SC every other day

<38 kg or >114 kg: 0.15 mg/kg/dose SC every other day

–   Not to exceed one dose/24 h

• Renal impairment, severe (creatinine clearance [CrCl] <30 mL/min)

—   Give half-dose

—   Has not been studied in end stage renal impairment (dialysis dependent)

Pregnancy and lactation

• Pregnancy Category: B

• Lactation: not known if distributed in breast milk

—   Use caution

Cautions

• Severe renal impairment

• Discontinue if severe/persistent diarrhea develops

• Rare cases of GI perforation have been reported

—   With advanced illness in conditions that may be associated with localized or diffuse reduction of structural integrity in GI tract wall (ie, cancer, peptic ulcer, Ogilvie syndrome)

Adverse effects

• More than 10% of patients

—   Abdominal pain (28.5%)

—   Flatulence (13.5%)

—   Nausea (11.5%)

• 1% to 10% of patients

—   Dizziness (7.3%)

—   Diarrhea (5.5%)

• Frequency not defined

—   Hyperhidrosis

—   Gastrointestinal perforation