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.
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).
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).
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Movantik: 12.5 mg, 25 mg
No
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Movantik: 12.5 mg, 25 mg
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
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.
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.
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
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).
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.
Substrate of CYP3A4 (major), P-glycoprotein/ABCB1 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Asciminib: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
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
Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy
Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Erdafitinib: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
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
Gilteritinib: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Grapefruit Juice: May increase the serum concentration of Naloxegol. Risk X: Avoid combination
Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy
Lasmiditan: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors). 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
Mitapivat: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
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
Naloxegol serum concentrations may be increased when taken with grapefruit or grapefruit juice. Management: Avoid concurrent use.
Adverse events were not observed in animal reproduction studies. However, exposure during pregnancy may potentiate opioid withdrawal in the fetus.
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.
Avoid grapefruit or grapefruit juice.
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).
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
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)
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).
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.
Geriatric: 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: AUC was approximately 20% lower in blacks and Cmax was approximately 10% lower and 30% higher in blacks and Asians, respectively.
Tablets (Movantik Oral)
12.5 mg (per each): $15.37
25 mg (per each): $15.37
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