A pegylated derivative of the opioid antagonist naloxone for oral treatment of opioid induced constipation in adults with chronic noncancer pain.
Presently the only oral opioid antagonist approved for this indication.
Laxatives and stool softeners are commonly used for initial treatment of opioid induced constipation, but their efficacy is limited.
Methylmalonaltrexone , a subcutaneous injected opioid antagonist, and lubiprostone and oral chloride channel activator are effective in increasing the frequency of bowel movements in opioid induced constipation.
In a dose of 25 mg/day increases the number of spontaneous bowel movements and improve quality-of-life at the expense of a higher risk of abdominal pain in adults with opioid induced constipation.
A peripheral mu-opioid receptor antagonist.
Pegylation reduces the ability of this agent to cross the blood brain barrier and makes it a substrate of the efflux transporter P-glycoprotein, minimizing it’s interference with the opioid analgesic effects in the CNS
Adverse effects are dose related.
Most common adverse effects are GI related and include:abdominal pain, diarrhea, nausea, flatulence, and vomiting.
Contraindicated in patients with GI obstruction or at increased risk of recurrent obstruction.
Category C in pregnancy.
May be associated with opioid withdrawal with hyperhidrosis, chills, anxiety, or irritatability which occurs in 3% of patients taking 25 mg dose and 1% of patients taking 12.5 mg dose compared with less than 1% of patients taking placebo.
Doses:25 mg, 12.5 mg.
The recommended dosage is 25 mg once daily in the morning at least one hour before or two hours after a meal.
The daily dose can be reduced to 12.5 mg in patients who cannot tolerate the higher dose and starting doses for patients with a creatinine clearance less than 60 mLper minute is 12.5 mg once daily.
Coadministration with a strong CYP3A4 inhibitor ketoconazole results in a 12.85 fold increase in naloxegol exposure, and could result in opioid withdrawal.
Concomitant use with any strong CYP3A4 inhibitor is contrindicated.
Diltiazem in moderate CYP3A4 inhibitor increases naloxegol concentration by about 3 fold.
Patients on this drug should avoid consuming a grapefruit or grapefruit juice which inhibit CYP3A4.
Strong CYP3A4 inhibitors such as rifampin can significantly lower serum concentration of this drug and possibly reduce its efficacy.
Should not be taken with another opioid antagonist because it may have additional effects and increased risk of opioid withdrawal.
Maintenance laxatives should be stopped before initiating treatment with this drug, and can be restarted after three days if symptoms persist.