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Naloxegol

Medically reviewed by Drugs.com. Last updated on Sep 4, 2020.

Pronunciation

(nal OX ee gol)

Index Terms

  • Naloxegol Oxalate
  • NKTR-118

Dosage Forms

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

Tablet, Oral:

Movantik: 12.5 mg, 25 mg

Brand Names: U.S.

  • Movantik

Pharmacologic Category

  • Gastrointestinal Agent, Miscellaneous
  • Opioid Antagonist, Peripherally-Acting

Pharmacology

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).

Absorption

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

Distribution

Vd: 968 to 2,140 L

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.

Excretion

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

Half-Life Elimination

6 to 11 hours

Protein Binding

~4.2%

Special Populations: Renal Function Impairment

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)

Special Populations: 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.

Special Populations: Elderly

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).

Special Populations: Race

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

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.

Contraindications

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).

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.

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.

Dosing: Geriatric

Refer to adult dosing.

Administration

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.

Dietary Considerations

Avoid grapefruit or grapefruit juice.

Storage

Store at 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F).

Drug Interactions

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

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

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

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

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

CYP3A4 Inducers (Strong): May decrease the serum concentration of Naloxegol. 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). Consider therapy modification

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

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

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

Erdafitinib: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors). Monitor therapy

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

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

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

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

Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

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

Lasmiditan: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors). Avoid combination

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

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

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

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

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

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

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

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

Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Adverse Reactions

>10%: Gastrointestinal: Abdominal pain (12% to 21%)

1% to 10%:

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

Dermatologic: Hyperhidrosis (3%)

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

<1%, postmarketing, and/or case reports: Angioedema, skin rash, urticaria

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. 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.

• 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. Monitor for symptoms of opioid withdrawal in such patients.

Disease-related concerns:

• Hepatic impairment: Avoid use in patients with severe hepatic impairment.

• Renal impairment: Dosage adjustment recommended in patients with CrCl <60 mL/minute.

Other warnings/precautions:

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

Monitoring Parameters

Symptoms of GI obstruction (eg, severe, persistent, or worsening abdominal pain); symptoms of opioid withdrawal (eg, chills, diaphoresis, anxiety, irritability, changes in blood pressure or heart rate).

Pregnancy Considerations

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

Patient Education

What is this drug used for?

• It is used to treat constipation caused by some pain drugs.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Passing gas

• Headache

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Severe or persistent diarrhea

• Severe abdominal swelling

• Severe abdominal pain

• Vomiting blood

• Nausea

• Vomiting

• Black, tarry, or bloody tools

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine’s uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

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