Drug information of Naloxegol
Naloxegol reduces constipation caused by opioid (narcotic) pain medicine used to treat severe chronic pain. Naloxegol works by treating constipation without reducing the pain-relieving effects of the narcotic.
Naloxegol is used in people who have been taking narcotic pain medicine for at least 4 weeks, to treat chronic pain that is not caused by cancer.
Mechanism of effect
Naloxegol is a mu-opioid receptor antagonist. It is composed of naloxone conjugated with a polyethylene glycol polymer, which limits its ability to cross the blood-brain barrier. When administered at the recommended dose, naloxegol functions peripherally in tissues such as the GI tract, thereby decreasing the constipation associated with opioids (Webster, 2013).
Gastrointestinal Agent, Miscellaneous
Opioid Antagonist, Peripherally-Acting
Rapid. With a high-fat meal, Cmax and AUC increased by 30% and 45%, respectively
Vd: 968 to 2,140 L
Hepatic via CYP3A (primarily). Data suggests no major metabolites. Minor metabolites formed via N-dealkylation, O-demethylation, oxidation and partial loss of the PEG chain.
Feces (68%; ~16% as unchanged drug); Urine (16%; <6% as unchanged drug)
Time to Peak
<2 hours; in majority of subjects, a secondary Cmax occurs ~0.4 to 3 hours after the first Cmax
6 to 11 hours
Use: Labeled Indications
Opioid-induced constipation: Treatment of opioid-induced constipation (OIC) in adults with chronic noncancer pain, including patients with chronic pain related to prior cancer or its treatment who do not require frequent (eg, weekly) opioid dosage escalation.
Note: Discontinue all maintenance laxative therapy prior to use; may reintroduce laxatives as needed if suboptimal response to naloxegol after 3 days. Alteration in analgesic dosing regimen prior to initiating naloxegol is not required.
Opioid-induced constipation: Oral: 25 mg once daily. If not tolerated, reduce dose to 12.5 mg once daily. Discontinue treatment if opioid pain medication is discontinued.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions
database for more information.
database for more information.
Refer to adult dosing.
Serious or severe hypersensitivity reaction to naloxegol or any component of the formulation; GI obstruction (known or suspected) or at risk of recurrent obstruction; concomitant use with strong CYP3A4 inhibitors (eg, clarithromycin, ketoconazole).
Check with your doctor immediately if any of the following side effects occur while taking naloxegol:
Incidence not known
Bloody, black or tarry stools
severe abdominal or stomach pain, cramping, or burning
vomiting of material that looks like coffee grounds, severe and continuous
Side effects not requiring immediate medical attention
Some side effects of naloxegol may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.
Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:
excess air or gas in the stomach or bowels
passing of gas
InteractionsCarbamazepine , Mibefradil , cobicistat , Delavirdine , Letermovir , Alvimopan , Apalutamide , Crizotinib , Naldemedine , oleandomycin , Naltrexone and Bupropion , nafcillin , tucatinib , Abametapir
st. john's wort
Concerns related to adverse reactions:
• GI effects: Severe abdominal pain and/or diarrhea have been reported; may result in hospitalization. Most cases of severe abdominal pain were due to the 25 mg dosage and generally occurred within a few days of initiation of therapy. Monitor for development of abdominal pain and/or diarrhea; discontinue therapy if this occurs. May consider restarting at lower dose.
• GI perforation: GI perforation has been reported, including fatalities. Most cases occurred in patients at risk for GI perforation (eg, concurrent treatment with bevacizumab, diverticular disease including diverticulitis, infiltrative GI tract malignancies, ischemic colitis, recent GI tract surgery). Use with caution in these patients or in patients with other conditions that might result in impaired integrity of the GI tract wall (eg, Crohn disease). Monitor for development of severe, persistent, or worsening abdominal pain; discontinue therapy if this occurs. Use is contraindicated in patients with GI obstruction (known or suspected) or at risk of recurrent GI obstruction.
Points of recommendation
Avoid consumption of grapefruit or grapefruit juice during treatment.
Oral: Administer on an empty stomach at least 1 hour prior to or 2 hours after the first meal of the day. Swallow tablets whole, do not chew. For patients unable to swallow tablet whole, may crush the tablet into a powder and mix with 120 mL of water, and drink immediately; refill glass with 120 mL water, stir and drink.
Nasogastric (NG) feeding tube: Flush the NG tube with 30 mL water using a 60 mL syringe. Crush tablet into a powder and mix with ~60 mL of water; draw up the mixture using the 60 mL syringe and administer through the NG tube. Rinse the same container used to prepare the dose with ~60 mL of water; draw up the water using the same syringe and use all of the water to flush the NG tube and any remaining medicine
AU TGA pregnancy category: B1
US FDA pregnancy category: C
Breast feeding warningNo information is available on the excretion of naloxegol into breastmilk. Because of the possibility of inducing opioid withdrawal in the breastfed infant, the manufacturer recommends that breastfeeding is not recommended during treatment with naloxegol
Related drugsAlvimopan , Naldemedine
polyethylene glycol electrolyte solution