Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Movantik: 12.5 mg, 25 mg
Pharmacology
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/Pharmacodynamics
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%
Use in Specific Populations
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 increased risk of recurrent obstruction; concomitant use with strong CYP3A4 inhibitors (eg, clarithromycin, ketoconazole)
Dosage and Administration
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.
Dosing adjustment with concomitant medications:
Moderate CYP3A4 Inhibitors (eg, diltiazem, erythromycin, verapamil): Avoid concomitant use. If concurrent use is unavoidable, reduce dose of naloxegol to 12.5 mg once daily and monitor for adverse reactions.
Strong CYP3A4 inhibitors (eg, clarithromycin, ketoconazole): Concomitant use is contraindicated.
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
Bosentan: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). 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 CYP3A4 Substrates (High risk with Inducers). Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Naloxegol. Avoid combination
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Naloxegol. Avoid combination
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. 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. Avoid combination
Lorlatinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences. Consider therapy modification
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
Ranolazine: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. 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:
- Gastrointestinal 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 with use of another peripherally acting opioid antagonist (ie, methylnaltrexone) in patients with localized or diffuse reduction of structural wall integrity of the GI tract (eg, peptic ulcer disease, Ogilvie syndrome, diverticular disease, infiltrative GI tract malignancies, peritoneal metastases). 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 increased 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.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
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
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.
Frequently reported side effects of this drug
- Passing gas
- Headache
Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:
- Severe or persistent diarrhea
- Severe abdominal swelling
- Severe abdominal pain
- Vomiting blood
- Nausea
- Vomiting
- Black, tarry, or bloody tools
- Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of 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 brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.
