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Naloxegol: Drug information

Naloxegol: Drug information
(For additional information see "Naloxegol: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Movantik
Brand Names: Canada
  • Movantik
Pharmacologic Category
  • Gastrointestinal Agent, Miscellaneous;
  • Opioid Antagonist, Peripherally-Acting
Dosing: Adult

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. Patients receiving opioids for less than 4 weeks may be less responsive.

Opioid-induced constipation

Opioid-induced constipation: Oral: 25 mg once daily in the morning. Reduce dose to 12.5 mg once daily if patient develops intolerance (eg, abdominal pain or diarrhea). Severe intolerance may require discontinuation (Chey 2014); consider restarting at 12.5 mg daily once symptoms resolve. Discontinue treatment if opioid pain medication is discontinued.

Opioid-induced constipation; cancer pain related

Opioid-induced constipation; cancer pain related (adjunctive therapy) (off-label use): Oral: 12.5 to 25 mg once daily (Cobo Dols 2021; Davies 2022; Lemaire 2021).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

CrCl ≥60 mL/minute: No dosage adjustment necessary.

CrCl <60 mL/minute: Initial dose: 12.5 mg once daily; if well tolerated but opioid-induced constipation symptoms continue, may increase to 25 mg once daily, taking into consideration the potential for markedly increased exposures in some patients with renal impairment and the increased risk of adverse reactions with higher exposures.

Hemodialysis, intermittent (thrice weekly): Not readily dialyzed (ineffective).

Dosing: Hepatic Impairment: Adult

Mild to moderate impairment (Child-Pugh class A and B): No dosage adjustment necessary.

Severe impairment (Child-Pugh class C): Avoid use (has not been studied).

Dosing: Older Adult

No dosage adjustment necessary. Refer to adult dosing.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Movantik: 12.5 mg, 25 mg

Generic Equivalent Available: US

No

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Movantik: 12.5 mg, 25 mg

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:

Movantik: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/204760s009lbl.pdf#page=16

Administration: Adult

Oral: Administer on an empty stomach at least 1 hour prior to or 2 hours after the first meal of the day. 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.

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.

Use: Off-Label: Adult

Opioid-induced constipation; cancer pain related

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%: Gastrointestinal: Abdominal pain (12% to 21%; including severe abdominal pain)

1% to 10%:

Dermatologic: Hyperhidrosis (3%)

Gastrointestinal: Diarrhea (6% to 9%; including severe diarrhea), flatulence (6%), nausea (7% to 8%), vomiting (5%)

Nervous system: Headache (4%), opioid withdrawal syndrome (1% to 3%)

Postmarketing:

Dermatologic: Skin rash, urticaria

Gastrointestinal: Gastrointestinal perforation

Hypersensitivity: Angioedema

Contraindications

Known 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).

Warnings/Precautions

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.

• 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).

• Opioid withdrawal: Symptoms consistent with opioid withdrawal (eg, hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, yawning) have occurred. Use with caution in patients with disruptions to the blood-brain barrier; may increase the risk for opioid withdrawal or reduced analgesia.

Other warnings/precautions:

• Appropriate use: Patients receiving opioids for less than 4 weeks may be less responsive.

Metabolism/Transport Effects

Substrate of CYP3A4 (major), P-glycoprotein/ABCB1 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Bevacizumab: May enhance the adverse/toxic effect of Naloxegol. Specifically, the risk for gastrointestinal perforation may be increased. Risk C: Monitor therapy

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CYP3A4 Inducers (Moderate): May decrease the serum concentration of Naloxegol. Risk C: Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of Naloxegol. Risk X: Avoid combination

CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Naloxegol. Management: The use of naloxegol and moderate CYP3A4 inhibitors should be avoided. If concurrent use is unavoidable, reduce naloxegol dose to 12.5 mg once daily and monitor for signs of opiate withdrawal (eg, hyperhidrosis, chills, diarrhea, anxiety, irritability). Risk D: Consider therapy modification

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Naloxegol. Risk X: Avoid combination

Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Grapefruit Juice: May increase the serum concentration of Naloxegol. Risk X: Avoid combination

Methylnaltrexone: May enhance the adverse/toxic effect of Opioid Antagonists. Specifically, the risk for opioid withdrawal may be increased. Risk X: Avoid combination

Naldemedine: Opioid Antagonists may enhance the adverse/toxic effect of Naldemedine. Specifically, the risk for opioid withdrawal may be increased. Risk X: Avoid combination

Opioid Antagonists: May enhance the adverse/toxic effect of Naloxegol. Specifically, the risk for opioid withdrawal may be increased. Risk X: Avoid combination

P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of Naloxegol. Risk C: Monitor therapy

St John's Wort: May decrease the serum concentration of Naloxegol. Risk X: Avoid combination

Food Interactions

Naloxegol serum concentrations may be increased when taken with grapefruit or grapefruit juice. Management: Avoid concurrent use.

Pregnancy Considerations

Adverse events were not observed in animal reproduction studies. However, exposure during pregnancy may potentiate opioid withdrawal in the fetus.

Breastfeeding Considerations

It is not known if naloxegol is present in breast milk. Due to the potential for serious adverse reactions (which could include opioid withdrawal in the breastfeeding infant), breastfeeding is not recommended by the manufacturer.

Dietary Considerations

Avoid grapefruit or grapefruit juice.

Monitoring Parameters

Monitor for symptoms of GI obstruction (eg, severe, persistent, or worsening abdominal pain) and for symptoms of opioid withdrawal (eg, chills, diaphoresis, anxiety, irritability, changes in blood pressure or heart rate). Monitor for development of severe, persistent, or worsening abdominal pain and/or diarrhea.

Mechanism of Action

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).

Pharmacokinetics

Absorption: Rapid. With a high-fat meal, Cmax and AUC increased by 30% and 45%, respectively.

Distribution: Vd: 968 to 2,140 L

Protein binding: ~4.2%

Metabolism: 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.

Half-life elimination: 6 to 11 hours

Time to peak: <2 hours; in majority of subjects, a secondary Cmax occurs ~0.4 to 3 hours after the first Cmax

Excretion: Feces (68%; ~16% as unchanged drug); Urine (16%; <6% as unchanged drug)

Pharmacokinetics: Additional Considerations

Altered kidney function: Some patients with renal impairment demonstrated higher naloxegol exposures (up to 10-fold) compared with the control group when administered a 25 mg single oral dose; reason for these high exposures is unknown. Patients with ESRD on hemodialysis had similar plasma concentrations to those with normal renal function, when naloxegol was given either pre- or posthemodialysis (Bui 2014).

Hepatic function impairment: After administration of a single 25 mg oral dose, slight decreases in AUC of naloxegol were observed in subjects with mild and moderate hepatic impairment (Child-Pugh classes A and B) compared with subjects with normal hepatic function.

Older adult: The mean Cmax,ss and AUCtau,ss values seen in elderly healthy Japanese subjects were approximately 45% and 54% greater than those obtained in young healthy subjects following multiple daily doses of naloxegol (25 mg).

Race/ethnicity: AUC was approximately 20% lower in blacks and Cmax was approximately 10% lower and 30% higher in blacks and Asians, respectively.

Pricing: US

Tablets (Movantik Oral)

12.5 mg (per each): $15.37

25 mg (per each): $15.37

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Moventig (BE, CH, CZ, DE, DK, EE, ES, FI, GB, GR, HR, IE, IL, LT, MT, NL, NO, PL, PT, SE, SK)


For country abbreviations used in Lexicomp (show table)
  1. Bui K, She F, Sostek M. The effects of renal impairment on the pharmacokinetics, safety, and tolerability of naloxegol [published online ahead of print June 19 2014]. J Clin Pharmacol. 2014. doi: 10.1002/jcph.349. [PubMed 24946021]
  2. Chey WD, Webster L, Sostek M, Lappalainen J, Barker PN, Tack J. Naloxegol for opioid-induced constipation in patients with noncancer pain. N Engl J Med. 2014;370(25):2387-2396. doi:10.1056/NEJMoa1310246 [PubMed 24896818]
  3. Cobo Dols M, Beato Zambrano C, Cabezón Gutiérrez L, et al. Efficacy of naloxegol on symptoms and quality of life related to opioid-induced constipation in patients with cancer: a 3-month follow-up analysis. BMJ Support Palliat Care. 2021;11(1):25-31. doi:10.1136/bmjspcare-2020-002249 [PubMed 32376758]
  4. Davies A, Cinieri S, Dupoiron D, et al, on behalf of the Nacasy Study Group. A prospective, real-world, multinational study of naloxegol for patients with cancer pain diagnosed with opioid-induced constipation-the NACASY study. Cancers (Basel). 2022;14(5):1128. doi:10.3390/cancers14051128 [PubMed 35267436]
  5. Davies A, Leach C, Caponero R, et al. MASCC recommendations on the management of constipation in patients with advanced cancer. Support Care Cancer. 2020;28(1):23-33. doi:10.1007/s00520-019-05016-4 [PubMed 31396746]
  6. Lemaire A, Pointreau Y, Narciso B, Piloquet FX, Braniste V, Sabaté JM. Effectiveness of naloxegol in patients with cancer pain suffering from opioid-induced constipation. Support Care Cancer. 2021;29(12):7577-7586. doi:10.1007/s00520-021-06299-2 [PubMed 34120247]
  7. Movantik (naloxegol) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; April 2020.
  8. Sarrió RG, Calsina-Berna A, García AG, Esparza-Miñana JM, Ferrer EF; Working Group ActEIO Project, Porta-Sales J. Delphi consensus on strategies in the management of opioid-induced constipation in cancer patients. BMC Palliat Care. 2021;20(1):1. doi:10.1186/s12904-020-00693-z [PubMed 33388041]
  9. Webster L, Dhar S, Eldon M, Masuoka L, Lappalainen J, Sostek M. A phase 2, double-blind, randomized, placebo-controlled, dose-escalation study to evaluate the efficacy, safety, and tolerability of naloxegol in patients with opioid-induced constipation. Pain. 2013;154(9):1542-1550. [PubMed 23726675]
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