Methylnaltrexone Bromide

Pronunciation: METH-il-nal-TREX-one BROE-mide
Class: Antidote

Trade Names

Relistor
- Injection, solution 12 mg per 0.6 mL

Pharmacology

Methylnaltrexone is a selective antagonist of opioid binding at the mu-opioid receptor. It functions as a peripherally acting receptor antagonist in tissues such as the GI tract, decreasing the constipating effects of opioids.

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Pharmacokinetics

Absorption

Absorbed rapidly. T max is approximately 0.5 h. After a single 0.15 mg/kg dose, C max and AUC 24 are 117 ng/mL and 175 ng•h/mL, respectively.

Distribution

Vd at steady state is approximately 1.1 L/kg. Plasma protein binding is 11% to 15%.

Metabolism

Approximately 60% recovered as 5 distinct metabolites; none of the metabolites detected were in amounts exceeding 6%.

Elimination

Approximately 85% is eliminated unchanged (approximately 50% in the urine and somewhat less in the feces). The half-life is approximately 8 h.

Special Populations

Renal Function Impairment

Severe renal impairment decreases renal Cl of methylnaltrexone, resulting in a 2-fold increase in drug exposure. No studies were performed in patients with ESRD requiring dialysis.

Hepatic Function Impairment

No meaningful effect of hepatic impairment on the AUC or C max of methylnaltrexone. The effect of severe hepatic impairment has not been studied.

Indications and Usage

Treatment of opioid-induced constipation when response to laxative therapy has not been sufficient.

Contraindications

Known or suspected mechanical GI obstruction.

Dosage and Administration

Adults

Subcutaneous 8 mg (0.4 mL) for patients weighing 38 to less than 62 kg or 12 mg (0.6 mL) for patients weighing 62 to 114 kg every other day as needed, but no more frequently than 1 dose in a 24-h period. Patients whose weight falls outside these ranges should be dosed at 0.15 mg/kg. To determine the volume for these patients, multiply the patient's weight in kilograms by 0.0075 and round up the volume to the nearest 0.1 mL.

Renal Function Impairment
Adults

Subcutaneous In patients with severe renal impairment (CrCl less than 30 mL/min), administer 50% of the recommended dose.

General Advice

  • Inject subcutaneously in the upper arm, abdomen, or thigh.
  • Use beyond 4 mo has not been studied.
  • Inspect visually for particulate matter and discoloration prior to administration.

Storage/Stability

Store between 59° and 86°F. Do not freeze. Protect from light. Once drawn into the syringe, drug may be stored at room temperature and administered within 24 h.

Drug Interactions

None well documented.

Adverse Reactions

CNS

Dizziness (7%).

Dermatologic

Hyperhidrosis (7%).

GI

Abdominal pain (29%); flatulence (13%); nausea (12%); diarrhea (6%); GI perforations (postmarketing).

Precautions

Pregnancy

Category B .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Renal Function

Dosage reduction by half is recommended in patients with severe renal impairment (CrCl less than 30 mL/min).

Diarrhea

Severe or persistent diarrhea may occur during treatment.

Intestinal perforation

Rare cases of GI perforation have been reported in patients with advanced illness who have conditions that may be associated with localized or diffuse reduction of structural integrity in the wall of the GI tract (eg, cancer, peptic ulcer, Ogilvie syndrome). Use with caution in patients with known or suspected lesions of the GI tract.

Overdosage

Symptoms

Orthostatic hypotension was associated with a dose of 0.64 mg/kg as an IV bolus.

Patient Information

  • Inform patient that the usual dosage schedule is 1 dose every other day, but no more often than 1 dose in 24 h.
  • Advise patients to be within close proximity to toilet facilities once the drug is administered because approximately 30% of patients experience laxation within 30 min.
  • Instruct patients to discontinue the drug once they stop taking their opioid medication.
  • Advise patients to stop treatment and consult health care provider if they experience severe or persistent diarrhea and/or severe, persistent, and/or worsening abdominal symptoms.

Copyright © 2009 Wolters Kluwer Health.

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