(nal OX ee gol)
- Naloxegol Oxalate
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Movantik: 12.5 mg, 25 mg
Brand Names: U.S.
- Gastrointestinal Agent, Miscellaneous
- Opioid Antagonist, Peripherally-Acting
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).
Rapid. With a high-fat meal, Cmax and AUC increased by 30% and 45%, respectively
Vd: 968 to 2,140 L
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.
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
6 to 11 hours
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 adult patients with chronic noncancer pain.
Serious or severe hypersensitivity reaction to naloxegol or any component of the formulation; known or suspected GI obstruction or at increased risk of recurrent obstruction; concomitant use with strong CYP3A4 inhibitors (eg, clarithromycin, ketoconazole)
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 in the morning on an empty stomach. If not tolerated, reduce dose to 12.5 mg once daily. Discontinue treatment if opioid pain medication is discontinued.
Dosing adjustment with concomitant medications:
Weak CYP3A4 inhibitors (eg, quinidine, cimetidine):
US labeling: No dosage adjustment necessary
Canadian labeling: Initial: 12.5 mg once daily
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.
Refer to adult dosing.
Dosing: Renal Impairment
CrCl ≥60 mL/minute: No dosage adjustment necessary.
CrCl <60 mL/minute and end-stage renal disease (ESRD): 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.
Dialysis: Not readily dialyzed (ineffective).
Dosing: Hepatic Impairment
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).
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.
Take on an empty stomach. Avoid grapefruit or grapefruit juice.
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).
Bosentan: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Avoid combination
CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates. 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. 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
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates. Avoid combination
Grapefruit Juice: May increase the serum concentration of Naloxegol. Avoid combination
Idelalisib: May increase the serum concentration of CYP3A4 Substrates. Avoid combination
Ivacaftor: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Luliconazole: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Methylnaltrexone: May enhance the adverse/toxic effect of Opioid Antagonists. 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. 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
Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Simeprevir: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
St John's Wort: May decrease the serum concentration of Naloxegol. Avoid combination
Stiripentol: May increase the serum concentration of CYP3A4 Substrates. 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. Monitor therapy
>10%: Gastrointestinal: Abdominal pain (12% to 21%)
1% to 10%:
Central nervous system: Headache (4%)
Dermatologic: Hyperhidrosis (≤3%)
Gastrointestinal: Diarrhea (6% to 9%), nausea (7% to 8%), flatulence (3% to 6%), vomiting (5%)
<1% (Limited to important or life-threatening):Anxiety, arthritis, back pain, chills, gastrointestinal perforation, irritability, joint pain, yawning
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 naloxegol if this occurs; may consider restarting at lower dose.
• Gastrointestinal perforation: Gastrointestinal (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 gastrointestinal tract malignancies, peritoneal metastases). Consider the overall risk-benefit profile when using naloxegol in patients with these conditions or other conditions which might result in impaired integrity of the GI tract wall (eg, Crohn disease). Monitor for development of severe, persistent or worsening abdominal pain; discontinue naloxegol if this occurs. Use is contraindicated in patients with known or suspected GI obstruction or at increased risk of recurrent obstruction.
• Withdrawal: Symptoms consistent with opioid withdrawal (eg, hyperhidrosis, chills, abdominal pain, anxiety, irritability) have occurred. In clinical trials, patients receiving methadone for pain management were observed to have a higher frequency of GI adverse reactions that may have been related to opioid withdrawal than patients receiving other opioids. Patients having disruptions to the blood-brain barrier may be at increased risk for opioid withdrawal or reduced analgesia. Consider the overall risk-benefit profile when using naloxegol in such patients. Monitor for symptoms of opioid withdrawal in such patients.
• Hepatic impairment: Avoid use in patients with severe hepatic impairment.
• Renal impairment: Dosage reduction 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.
• Appropriate use: Discontinue naloxegol if opioids are discontinued.
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 Risk Factor
Adverse events were not observed in animal reproduction studies. However, exposure during pregnancy may potentiate opioid withdrawal in the fetus.
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience flatulence or headache. Have patient report immediately to prescriber severe diarrhea; severe abdominal edema; severe abdominal pain; vomiting blood; nausea; vomiting; or black, tarry, or bloody stools (HCAHPS).
• Educate patient about signs of a significant reaction (eg, 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. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
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- Other brands: Movantik