Naloxegol
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Dosing in kidney impairment
Dosage in Adult Patients with Renal Impairment The starting dosage for patients with creatinine clearance (CLcr) <60 mL/min (i.e., patients with moderate, severe, or end-stage renal impairment) is 12.5 mg once daily. If this dosage is well tolerated but OIC symptoms continue, the dosage may be increased 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 [see Use in Specific Populations and Clinical Pharmacology ] .
Dosing in liver impairment
Hepatic Impairment The effect of severe hepatic impairment (Child-Pugh Class C) on the pharmacokinetics of naloxegol has not been evaluated. Avoid use of MOVANTIK in patients with severe hepatic impairment, as the dosage in these patients has not been determined. No dosage adjustment is required for patients with mild or moderate hepatic impairment [see Clinical Pharmacology ] .
Preparation and administration
Administration Instructions Discontinue all maintenance laxative therapy prior to initiation of MOVANTIK. Laxative(s) can be used as needed if there is a suboptimal response to MOVANTIK after three days. Alteration in analgesic dosing regimen prior to initiating MOVANTIK is not required. Patients receiving opioids for less than 4 weeks may be less responsive to MOVANTIK [see Clinical Studies ] .
Take MOVANTIK on an empty stomach at least 1 hour prior to the first meal of the day or 2 hours after the meal. For patients who are unable to swallow the MOVANTIK tablet whole, the tablet can be crushed to a powder, mixed with 4 ounces (120 mL) of water, and drunk immediately. The glass should be refilled with 4 ounces (120 mL) of water, stirred and the contents drunk.
MOVANTIK can also be administered via a nasogastric (NG) tube, as follows: 1. Flush the NG tube with 1 ounce (30 mL) of water using a 60 mL syringe. 2. Crush the tablet to a powder in a container and mix with approximately 2 ounces (60 mL) of water. 3. Draw up the mixture using the 60 mL syringe and administer the syringe contents through the NG tube. 4.
Add approximately 2 ounces (60 mL) of water to the same container used to prepare the dose of MOVANTIK. 5. 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. Avoid consumption of grapefruit or grapefruit juice during treatment with MOVANTIK.
Discontinue MOVANTIK if treatment with the opioid pain medication is also discontinued.
Drug interactions
Check naloxegol against a medication listLabel text (5 paragraphs)
Moderate CYP3A4 inhibitors (e.g., diltiazem, erythromycin, verapamil) : Increased naloxegol concentrations; avoid concomitant use; if unavoidable, reduce dosage to 12.5 mg once daily and monitor for adverse reactions. (2.4 , 7.1) Strong CYP3A4 inducers (e.g., rifampin) : Decreased concentrations of naloxegol; concomitant use is not recommended. (7.1) Other opioid antagonists : Potential for additive effect and increased risk of opioid withdrawal; avoid concomitant use. (7.1)
7.1 Effects of Other Drugs on MOVANTIK Table 2 displays the effects of other drugs on MOVANTIK. Table 2. Effects of Other Drugs on MOVANTIK Concomitant Agent Mechanism of Action Clinical Recommendation CYP3A4 Inhibitors •Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin) •Increase plasma naloxegol concentrations and may increase the risk of adverse reactions [see Clinical Pharmacology (12.3) ]. •Use with strong CYP3A4 inhibitors is contraindicated [see Contraindications (4) ] .
•Moderate CYP3A4 inhibitors (e.g., diltiazem, erythromycin, verapamil) •Avoid use with moderate CYP3A4 inhibitors; if unavoidable, decrease the dosage of MOVANTIK to 12.5 mg once daily and monitor for adverse reactions [see Dosage and Administration (2.4) ] . •Weak CYP3A4 inhibitors (e.g., quinidine, cimetidine) •Clinically significant increases in naloxegol concentrations are not expected. •No dosage adjustments are necessary. •Grapefruit or grapefruit juice The effect of grapefruit juice varies widely among brands and is concentration-, dose-, and preparation-dependent.
Studies have shown that it can be classified as a “strong CYP3A inhibitor” when a certain preparation was used (e.g., high dose, double strength) or as a “moderate CYP3A inhibitor” when another preparation was used (e.g., low dose, single strength). •Can increase plasma naloxegol concentrations. •Avoid consumption of grapefruit or grapefruit juice during treatment with MOVANTIK [see Dosage and Administration (2.1) ] . CYP3A4 Inducers •Strong CYP3A4 inducers (e.g., rifampin, carbamazepine, St. John’s Wort) •Significantly decrease plasma naloxegol concentrations and may decrease the efficacy of MOVANTIK [see Clinical Pharmacology (12.3) ] .
•Use with strong CYP3A4 inducers is not recommended . Other Drug Interactions •Other opioid antagonists •Potential for additive effect of opioid receptor antagonism and increased risk of opioid withdrawal. •Avoid use of MOVANTIK with another opioid antagonist.
Contraindications
4 CONTRAINDICATIONS MOVANTIK is contraindicated in: Patients with known or suspected gastrointestinal obstruction and patients at risk of recurrent obstruction, due to the potential for gastrointestinal perforation [see Warnings and Precautions (5.3) ] . Patients concomitantly using strong CYP3A4 inhibitors (e.g., clarithromycin, ketoconazole) because these medications can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning [see Drug Interactions (7.1) and Clinical Pharmacology (12.3) ] .
Patients who have had a known serious or severe hypersensitivity reaction to MOVANTIK or any of its excipients [see Adverse Reactions (6.2) ] . Patients with known or suspected gastrointestinal obstruction and at risk of recurrent obstruction. (4 , 5.3 ) Concomitant use with strong CYP3A4 inhibitors (e.g., clarithromycin, ketoconazole). (4 , 7.1) Known serious or severe hypersensitivity reaction to MOVANTIK or any of its excipients. (4)
Safety data
Reported adverse events (FAERS)
Liver injury (LiverTox)
ELikelihood score E: Unlikely cause of clinically apparent liver injury.
Naloxegol is a peripherally acting opioid antagonist which is used to treat constipation caused by chronic opioid use for noncancer pain. Naloxegol has not been linked to serum enzyme elevations during therapy or to clinically apparent liver injury.
ABCDEA: well known cause; E: unlikely cause. [HD]: high doses only.
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary Limited available data with MOVANTIK use in pregnant women are insufficient to inform a drug associated risk of adverse developmental outcomes. MOVANTIK may precipitate opioid withdrawal in the pregnant women and the fetus (see Clinical Considerations ) . In animal development studies, no effects on embryo-fetal development were observed following administration of naloxegol in pregnant rats during the period of organogenesis at doses up to 1452 times the human AUC (area under the plasma concentration-time curve) at the maximum recommended human dose.
No effects on embryo-fetal development were observed following administration of naloxegol in pregnant rabbits during the period of organogenesis at doses up to 409 times the human AUC at the maximum recommended human dose. The estimated background risk of major birth defects and miscarriage for the indicated populations are unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically-recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Clinical Considerations Maternal and Fetal/Neonatal adverse reactions The use of MOVANTIK may be associated with opioid withdrawal in the pregnant woman and the fetus. Data Animal Data Oral administration of up to 750 mg/kg/day naloxegol in rats (1452 times the human AUC at the maximum recommended human dose) and 450 mg/kg/day naloxegol in rabbits (409 times the human AUC at the maximum recommended human dose) during the period of organogenesis produced no adverse effects on embryo-fetal development.
Oral administration of up to 500 mg/kg/day in rats (195 times the maximum recommended human dose based on body surface area) during the period of organogenesis through lactation produced no adverse effects on parturition or the offspring.
Breastfeeding (LactMed)
No information is available on the excretion of naloxegol into breastmilk. Because of the possibility of inducing opioid withdrawal in the breastfed infant, the manufacturer states that breastfeeding is not recommended during treatment with naloxegol. If it is used, observe breastfed infants who have been exposed to opioids during pregnancy or postpartum for signs of opioid withdrawal, especially diarrhea. An alternate drug may be preferable.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
Price ladder
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