Dosing and uses of Movantik (naloxegol)
Adult dosage forms and strengths
tablet
- 12.5mg
- 25mg
Opioid-Induced Constipation
Peripherally acting mu-opioid receptor antagonist (PAMORA) indicated for opioid-induced constipation in adults with chronic noncancer pain
25 mg PO qDay in morning; give at least1 hr ac or 2 hr pc
Decrease dose to 12.5 mg/day if patient unable to tolerate 25 mg/day
Also see Administration
Dosage modifications
Coadministration with strong CYP3A4 inducers: Not recommended
Coadministration with CYP3A4 inhibitors
- Strong CYP3A4 inhibitors: Contraindicated
- Moderate CYP3A4 inhibitors: Avoid coadministration; if unavoidable, reduce dose to 12.5 mg qDay
Renal impairment
- Mild: No dosage adjustment required
- CrCl <60 mL/min (ie, moderate, severe, or end-stage renal disease): Decrease starting dose to 12.5 mg/day; if this dose is well tolerated, but OIC symptoms continue, may increase to 25 mg/day (monitor for potential adverse effects associated with higher exposure)
Hepatic impairment
- Mild-to-moderate: No dosage adjustment required
- Severe: Avoid use
Pediatric dosage forms and strengths
Safety and efficacy not established
Movantik (naloxegol) adverse (side) effects
>10%
Abdominal pain (12-21%)
GI effects
- Patients receiving methadone as therapy for their pain condition have a higher frequency of GI adverse reactions than patients receiving other opioids
- 12.5 mg/day of naloxegol: 39% (methadone) vs 26% (other opioid)
- 25 mg/day of naloxegol: 75% (methadone) vs 34% (other opioid)
1-10%
Diarrhea (6-9%)
Nausea (7-8%)
Flatulence (3-6%)
Vomiting (3-5%)
Headache (4%)
Opioid withdrawal (1-3%)
Hyperhidrosis (<1-3%)
Postmarketing Reports
Severe diarrhea
Warnings
Contraindications
Known serious or severe hypersensitivity reaction
Known or suspected GI obstruction and patients at increased risk of recurrent obstruction; increases risk for GI perforation
Coadministration with strong CYP3A4 inhibitors; can significantly increase naloxegol systemic exposure, which may precipitate opioid withdrawal symptoms
Cautions
GI perforation reported with other PAMORA in patients with conditions associated with reduced structural integrity in the wall of the GI tract (eg, PUD, Ogilvie syndrome, diverticular disease, infiltrative GI malignancies, peritoneal metastases, Crohn disease); monitor for development of severe, persistent, or worsening abdominal pain; discontinue naloxegol in patients who develop these symptoms
Monitor for development of severe abdominal pain and /or diarrhea symptoms after initiating treatment and discontinue if severe symptoms develop; consider restarting therapy at 12.5 mg once daily if appropriate
Symptoms consistent with opioid withdrawal (eg, hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, yawning) reported
Higher frequency of GI adverse effects related to opioid withdrawal reported in patients receiving methadone than other opioid analgesics
Patients with disruption to the blood-brain barrier may be at increased risk for opioid withdrawal or reduced analgesia; consider overall risk benefit in patients with disruptions to blood-brain barrier; monitor for symptoms of opioid withdrawaL
Avoid coadministration with other opioid antagonists
Severe abdominal pain and/or diarrhea
- Severe abdominal pain and/or diarrhea reported, some of which resulted in hospitalization
- Most cases were with the 25 mg dose
- Symptoms generally occurred within a few days after initiating naloxegol
- Monitor and discontinue therapy if severe symptoms occur
- Consider restarting at 12.5 mg qDay, if appropriate
Pregnancy and lactation
Pregnancy category: C
Lactation: Unknown if distributed in human breast milk; patient should be advised against breast feeding during treatment; a decision should be made to discontinue nursing or discontinue the drug taking into account the importance of the drug to the patient
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Movantik (naloxegol)
Mechanism of action
Peripherally acting mu-opioid receptor antagonist (PAMORA); contains naloxegol oxalate (pegylated derivative of naloxone)
Antagonism of gastrointestinal mu-opioid receptors by naloxegol inhibits the opioid-induced delay of GI transit time
Absorption
Peak plasma time: <2 hr; secondary peak occurs in most patients 0.4-3 hr after the first peak
High-fat meal increases extent and rate of absorption; Cmax and AUC increased by ~30% and 45%, respectively
Distribution
Protein bound: Low (~4.2%)
Vd: 968-2140 L
Metabolism
Substrate of CYP3A and P-gp
Elimination
Excretion: 68% feces (~16% unchanged); 16% urine (<6% unchanged)
Administration
Oral Administration
Discontinue all maintenance laxative therapy prior to initiating naloxegoL
Laxatives can be used PRN if there is suboptimal response to naloxegol after 3 days
Alteration in analgesic dosing regimen prior to initiating is not required
Naloxegol is efficacious in patients who have taken opioids for at least 4 wk; sustained opioid exposure prior to starting may increase sensitivity to naloxegol effects
Take on empty stomach at least 1 hr before first meal of the day or 2 hr after the meaL
For patients who are unable to swallow tablet whole, tablet can be crushed and given orally or administered via nasogastric tube
Avoid grapefruit or grapefruit juice during treatment with naloxegoL
Discontinue if treatment with opioid pain medication is also discontinued
If unable to swallow tablet whole
- Tablet can be crushed to a powder, mixed with 120 mL of water and drunk immediately; refill the glass with 120 mL of water, stir, and drink contents to assure whole tablet is consumed
- Administer by NG-tube
- Flush the NG tube with 30 mL of water using a 60 mL syringe
- Crush the tablet to a powder in a container and mix with ~60 mL of water
- Draw up the mixture using the 60 mL syringe and administer the syringe contents through the NG tube
- Add ~60 mL of water to the same container used to prepare the dose
- Draw up the water using the same 60 mL syringe and use all the water to flush the NG tube and any remaining medicine from the NG tube into the stomach
