naloxegol

REMS

Opioid-induced constipation in patients with chronic noncancer pain, including those with chronic pain related to prior cancer or its treatment who do not require frequent (e.g., weekly) opioid dose escalation.

Action ⬆ ⬇

Acts peripherally as a mu receptor antagonist, blocking opioid receptors in the GI tract.

Therapeutic effects:

Blocks constipating effects of opioids on the GI tract without loss of analgesia.

Pharmacokinetics ⬆ ⬇

Absorption: Systemic absorption follows oral administration. High-fat meals ↑ absorption.

Distribution: Does not cross the blood-brain barrier.

Metabolism/Excretion: Primarily metabolized by the liver via the CYP3A4 isoenzyme; 68% excreted in feces, 16% in urine mostly as metabolites.

Half-Life: 6–11 hr.

Time/Action Profile ⬆ ⬇

(spontaneous bowel movement)

ROUTE	ONSET	PEAK	DURATION
PO	within 24 hr	unknown	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Known/suspected/history of GI obstruction;
Severe hepatic impairment;
Concurrent use of strong CYP3A4 inhibitors, strong CYP3A4 inducers, or other opioid antagonists;
Severe hepatic impairment;
Lactation: Lactation.

Use Cautiously in:

Infiltrative GI tract malignancy, recent GI tract surgery, diverticular disease, ischemic colitis, or concurrent use of bevacizumab (↑ risk of GI perforation);
Patients with disruption of the blood-brain barrier (may precipitate opioid withdrawal);
OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
Pedi: Safety and effectiveness not established in children;
Geri: Levels are ↑ in older Japanese patients.

Adv. Reactions/Side Effects ⬆ ⬇

Derm: ↑sweating

GI: abdominal pain, diarrhea, flatulence, GI PERFORATION, nausea, vomiting

Neuro: headache

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANGIOEDEMA), opioid withdrawal

Interactions ⬆ ⬇

Drug-drug:

Strong CYP3A4 inhibitors, including clarithromycin and ketoconazole, may significantly ↑ levels and risk of toxicity; concurrent use contraindicated.
Strong CYP3A4 inducers, including rifampin, may significantly ↓ levels and effectiveness; concurrent use contraindicated.
Other opioid antagonists may precipitate opioid withdrawal; concurrent use contraindicated.
Moderate CYP3A4 inhibitors, including diltiazem, erythromycin, and verapamil, may ↑ levels and risk of toxicity; ↓ naloxegol dose.
Methadone for pain ↑ risk of stomach pain and diarrhea.
Bevacizumab may ↑ risk of GI perforation.

Drug-Food:

Grapefruit/grapefruit juice may ↑ levels and risk of toxicity; avoid concurrent use.

Route/Dosage ⬆ ⬇

PO (Adults ): 25 mg once daily; if poorly tolerated, ↓ dose to 12.5 mg once daily; Concurrent use of moderate CYP3A4 inhibitors: 12.5 mg once daily (careful monitoring recommended).

Renal Impairment

PO (Adults ): CCr <60 mL/min: 12.5 mg once daily initially; may cautiously ↑ to 25 mg once daily, if necessary, with careful monitoring.

Availability ⬆ ⬇

Tablets: 12.5 mg; 25 mg

Assessment ⬆ ⬇

Assess bowel sounds and frequency, quantity, and consistency of stools periodically during therapy.
Monitor for signs of opioid withdrawal in patients with disruptions to the blood-brain barrier and assess for ↓ analgesic effects in patients using concurrent opioids.
Monitor for signs and symptoms of GI perforation (severe, persistent, or worsening abdominal pain) and diarrhea periodically during therapy. If symptoms of GI perforation occur, discontinue naloxegol.

Implementation ⬆ ⬇

Discontinue all maintenance laxative therapy before starting naloxegol. If a suboptimal response occurs with naloxegol, laxatives may be used after 3 days.
PO: Administer on an empty stomach ≥1 hr before 1st meal in morning or 2 hr after meal. Tablet may be crushed to a powder and mixed with 4 ounces of water (120 mL). Drink mixture immediately; refill glass with 120 mL water, stir, and drink contents.
- May be administered by nasogastric (NG) tube. Flush the NG tube with 1 ounce (30 mL) of water using a 60 mL syringe. Crush tablet to a powder and mix with 2 ounces (60 mL) of water. Draw up mixture using the 60 mL syringe and administer through the NG tube. Add 2 ounces (60 mL) of water to rinse container and administer to flush NG tube and any remaining medicine from NG tube into stomach.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication. Advise patient to read Patient Information before starting therapy.
Caution patient to avoid grapefruit and grapefruit juice during therapy.
Advise patient to notify health care provider immediately if stomach pain or diarrhea that does not go away occurs.
Advise patient to notify health care provider if signs and symptoms of opioid withdrawal (sweating, chills, diarrhea, stomach pain, anxiety, irritability, yawning) occur. Patients taking methadone for pain are at ↑ risk for stomach pain and diarrhea.
Instruct patient to stop taking naloxegol if they stop taking opioid medications.
Instruct patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care provider before taking any new medications.
Rep: Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected and to avoid breastfeeding during therapy. May cause opioid withdrawal in infant.

Evaluation/Desired Outcomes ⬆ ⬇

Relief of opioid-induced constipation, especially if opioid therapy has been for ≥4 wk.

US Brand Names ⬆ ⬇

Code ⬆

NDC Code

24584- Piramal Healthcare UK Limited
- 24584-1115-
  - 24584-1115-1- 54644 TABLET, FILM COATED in 1 DRUM (24584-1115-1)

24584- Piramal Healthcare UK Limited
- 24584-1116-
  - 24584-1116-1- 27397 TABLET, FILM COATED in 1 DRUM (24584-1116-1)

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇