Naloxegol

Uses

Naloxegol is a peripherally-selective opioid antagonist used to treat opioid-induced constipation (OIC) in adult patients with chronic non-cancer pain.

Indicated for the treatment of opioid-induced constipation (OIC) in adult patients with chronic non-cancer pain.

Naloxegol is also used to associated treatment for these conditions: Opioid Induced Constipation (OIC)

How Naloxegol works

Naloxegol is an antagonist of opioid binding at the mu-opioid receptor. When administered at the recommended dose levels, naloxegol functions as a peripherally-acting mu-opioid receptor antagonist in tissues such as the gastrointestinal tract, thereby decreasing the constipating effects of opioids. Naloxegol has shown more than 6000 fold selectivity for the peripheral mu receptors, and its PEGylated form restricts its action only to the periphery, not affecting the pain-relieving mechanism of opioids in the central nervous system.

Food Interaction

• Take on an empty stomach. High-fat food increases drug absorption. Take naloxegol at least 1 hour prior to the first meal of the day or 2 hours after the meal.

[Major] GENERALLY AVOID: Grapefruit juice may significantly increase the plasma concentrations of naloxegol.

The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit.

In pharmacokinetic studies, naloxegol systemic exposure (AUC) was increased approximately 3.5-fold by the moderate CYP450 3A4 inhibitor diltiazem and nearly 13-fold by the potent inhibitor ketoconazole.

The interaction has not been studied with grapefruit juice.

In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands.

Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition.

Increased exposure to naloxegol may precipitate opioid withdrawal symptoms such as hyperhidrosis, lacrimation, rhinorrhea, chills, diarrhea, abdominal pain, anxiety, insomnia, irritability, restlessness, and yawning.

ADJUST DOSING INTERVAL: Food may increase the rate and extent of naloxegol absorption.

When administered with a high-fat meal, naloxegol peak plasma concentration (Cmax) and systemic exposure (AUC) increased by approximately 30% and 45%, respectively.

In clinical trials, naloxegol was given on an empty stomach approximately 1 hour prior to the first meal in the morning.

MANAGEMENT: Patients treated with naloxegol should avoid consumption of grapefruit and grapefruit juice.

Naloxegol should be taken on an empty stomach at least 1 hour prior to the first meal of the day or 2 hours after the meal.

Naloxegol Drug Interaction

Unknown: zolpidem, lubiprostone, aspirin, aspirin, mupirocin topical, duloxetine, fentanyl, ibuprofen, lidocaine topical, linaclotide, pregabalin, morphine, morphine, oxycodone, promethazine, albuterol, bifidobacterium infantis / lactobacillus acidophilus, dulaglutide, cyanocobalamin, cholecalciferol

Naloxegol Disease Interaction

Major: hepatic impairment, intestinal obstructionModerate: renal impairment

Volume of Distribution

968 to 2140 L.

Elimination Route

Following oral administration, naloxegol is absorbed with peak concentrations (Cmax) achieved in less than 2 hours.

Half Life

6-11 hours.

Clearance

Feces (68%), urine (16%).

Elimination Route

Feces: 68% after oral administration. Urine: 16% after oral administration.

Innovators Monograph

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