Pharmacologic class: Opioid antagonist (peripheral)
Active ingredient: Methylnaltrexone bromide 12 mg/0.6 mL; solution for subcutaneous (SC) injection
Indication: Opioid-induced constipation
Pharmacology: The use of opioid analgesics can lead to constipation due to their effect on intestinal smooth muscle and their interference with the bowel’s normal elimination function. Methylnaltrexone bro-mide is a µ-opioid receptor antagonist that has limited ability to cross the blood-brain barrier. It blocks the effects of opioids in peripheral tissues, including the GI tract, mitigating their constipating effects without interfering with their centrally-mediated analgesia.
Clinical trials: The results of two placebo-controlled studies demonstrated the efficacy and safety of Relistor in treating opioid-induced constipation. The studies involved 287 patients with advanced illness (e.g., incurable cancer, end-stage chronic obstructive pulmonary disease, heart failure, Alzheimer’s disease, and AIDS). Before screening, patients had been receiving palliative opioid therapy and had opioid-induced constipation. They were on a stable opioid regimen for at least three days before randomization. The first study compared single
doses of the study drug (0.15 mg/kg or 0.3 mg/kg) with placebo in a double-blind phase that was followed by an open-label four-week period in which Relistor was used as needed. The primary end point was the proportion of patients with rescue-free laxation within four hours of the double-blind dose of the study drug. Patients given either dose of Relistor had a significantly higher rate of laxation than those given placebo.
In the second trial, either the study drug or placebo was given every other day for two weeks. During the first week, patients received either Relistor 0.15 mg/kg or placebo. In the second week, the dose could be increased to 0.3 mg/kg if needed (two or fewer rescue-free laxations up to Day 8). Patients given the study drug had a higher rate of laxation within four hours of the first dose than those given placebo, and they had significantly higher rates of laxation within four hours after at least two of the first four doses. The laxation response rate was shown to be consistent from the first dose to the seventh dose over the two-week period.There was no relationship seen between baseline opioid doses and the laxation response in patients given Relistor. Daily opioid use did not change substantially in either the patients given the study drug or those given placebo, and there were no relevant changes in pain scores from baseline between the groups. Open-label extension studies indicate that the drug maintains its effectiveness for up to four months of treatment.
Adults: Give by SC injection in upper arm, abdomen, or thigh once every other day as needed (maximum one dose/24 hours); rotate injection sites. <38 kg or >114 kg: 0.15 mg/kg. 38-62 kg: 8 mg. 62-114 kg: 12 mg. Severe renal impairment (creatinine clearance <30 mL/min): reduce dose by half.
Children: Not recommended.
Contraindications: Mechanical GI obstruction (known or suspected).
Precautions: Re-evaluate if severe or persistent diarrhea occurs. Peritoneal catheterization. Bowel movement may occur within 30 minutes of dosing. Pregnancy (Cat. B). Nursing mothers.
Adverse reactions: Abdominal pain, flatulence, nausea, dizziness, diarrhea.
How supplied: Single-use vial—1 Kit (with seven vials, syringes, needles, supplies)—1
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