MOVANTIK

Peripheral Mu Opioid Receptor Antagonists for Constipation
Peripheral Opioid Receptor Antagonists

Discontinue all maintenance laxative therapy prior to initiation of naloxegol. Laxative(s) can be used as needed if there is a suboptimal response to therapy after 3 days. 
Administer on an empty stomach at least 1 hour prior to the first meal of the day or 2 hours after the meal.
Avoid coadministration of grapefruit or grapefruit juice during treatment with naloxegol.
Discontinue naloxegol therapy if treatment with the opioid pain medication is also discontinued.

GI perforation / Delayed / Incidence not known
angioedema / Rapid / Incidence not known

abdominal pain / Early / 12.0-21.0
diarrhea / Early / 6.0-9.0
nausea / Early / 7.0-8.0
flatulence / Early / 3.0-6.0
vomiting / Early / 3.0-5.0
headache / Early / 4.0-4.0
hyperhidrosis / Delayed / 1.0-3.0
irritability / Delayed / Incidence not known
anxiety / Delayed / Incidence not known
chills / Rapid / Incidence not known
yawning / Early / Incidence not known
rash / Early / Incidence not known
urticaria / Rapid / Incidence not known

Movantik

Rx

Opioid antagonist indicated for the treatment of opioid-induced constipation (OIC) in adult patients with chronic non-cancer pain
At recommended doses, functions peripherally in GI tissues with limited CNS penetration
Metabolized via CYP3A isoenzymes; dose adjustments are recommended in patients taking CYP3A4 inhibitors/inducers

Avoid use of naloxegol 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. The effect of severe hepatic impairment (Child-Pugh Class C) on the pharmacokinetics of naloxegol has not been evaluated. 

For patients with CrCl less than 60 mL/minute (i.e., moderate, severe, or end-stage renal disease), initiate dose at 12.5 mg PO once daily. If dose is tolerated, however symptoms persist, the dose may be increased to 25 mg PO once daily. Monitor closely for adverse reactions.

Adagrasib: (Contraindicated) Concomitant use of naloxegol with adagrasib is contraindicated. Naloxegol is metabolized primarily by CYP3A. Strong CYP3A inhibitors, such as adagrasib, can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning.
Alvimopan: (Major) Avoid coadministration of alvimopan and other opiate antagonists, like naloxegol. There is a potential for additive effect of opioid receptor antagonism and increased risk of opioid withdrawal with concomitant use.
Amiodarone: (Major) Avoid concomitant administration of naloxegol and amiodarone due to the potential for increased naloxegol exposure. If coadministration cannot be avoided, decrease the naloxegol dosage to 12.5 mg once daily and monitor for adverse reactions including opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning. Naloxegol is a CYP3A4 substrate; amiodarone is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor increased naloxegol exposure by approximately 3.4-fold.
Amoxicillin; Clarithromycin; Omeprazole: (Contraindicated) Concomitant use of naloxegol with strong CYP3A4 inhibitors is contraindicated. Naloxegol is metabolized primarily by the CYP3A enzyme system. Strong CYP3A4 inhibitors, such as clarithromycin, can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning.
Apalutamide: (Major) Coadministration of naloxegol with apalutamide is not recommended due to the potential for decreased naloxegol efficacy. Naloxegol is a CYP3A4 substrate; apalutamide is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased naloxegol exposure by 89%.
Aprepitant, Fosaprepitant: (Major) Avoid concomitant administration of naloxegol and aprepitant, fosaprepitant due to the potential for increased naloxegol exposure. If coadministration cannot be avoided, decrease the naloxegol dosage to 12.5 mg once daily and monitor for adverse reactions including opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning. Naloxegol is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor. When administered as a single oral or single intravenous dose, the inhibitory effect of aprepitant on CYP3A4 is weak and did not result in a clinically significant increase in the AUC of a sensitive substrate. Coadministration with another moderate CYP3A4 inhibitor increased naloxegol exposure by approximately 3.4-fold.
Atazanavir: (Contraindicated) Concomitant use of naloxegol with atazanavir is contraindicated. Naloxegol is metabolized primarily by CYP3A. Strong CYP3A4 inhibitors, such as atazanavir, can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning.
Atazanavir; Cobicistat: (Contraindicated) Concomitant use of naloxegol with atazanavir is contraindicated. Naloxegol is metabolized primarily by CYP3A. Strong CYP3A4 inhibitors, such as atazanavir, can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning. (Contraindicated) Concomitant use of naloxegol with cobicistat is contraindicated. Naloxegol is metabolized primarily by CYP3A. Strong CYP3A4 inhibitors, such as cobicistat, can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning.
Berotralstat: (Major) Avoid concomitant administration of naloxegol and berotralstat due to the potential for increased naloxegol exposure. If coadministration cannot be avoided, decrease the naloxegol dosage to 12.5 mg once daily and monitor for adverse reactions including opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning. Naloxegol is a CYP3A4 substrate; berotralstat is a moderate CYP3A4 inhibitor. Coadministration of another moderate CYP3A4 inhibitor increased naloxegol exposure by approximately 3.4-fold.
Buprenorphine; Naloxone: (Major) Avoid concomitant use of naloxegol with other opioid antagonists because of the potential for additive effects of opioid receptor antagonism and increased risk of opioid withdrawal.
Bupropion; Naltrexone: (Major) Avoid concomitant use of naloxegol with other opioid antagonists because of the potential for additive effects of opioid receptor antagonism and increased risk of opioid withdrawal.
Carbamazepine: (Major) Coadministration of naloxegol with carbamazepine is not recommended due to the potential for decreased naloxegol efficacy. Naloxegol is a CYP3A4 substrate; carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased naloxegol exposure by 89%.
Ceritinib: (Contraindicated) Concomitant use of naloxegol with ceritinib is contraindicated. Naloxegol is metabolized primarily by CYP3A. Strong CYP3A4 inhibitors, such as ceritinib, can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning.
Chloramphenicol: (Contraindicated) Concomitant use of naloxegol with chloramphenicol is contraindicated. Naloxegol is metabolized primarily by CYP3A. Strong CYP3A4 inhibitors, such as chloramphenicol, can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning.
Cimetidine: (Minor) Although naloxegol is metabolized primarily by the CYP3A enzyme system, concomitant use with weak CYP3A4 inhibitors, such as cimetidine, is not expected to effect naloxegol concentrations in a clinically significant manner. No dosage adjustments are necessary.
Ciprofloxacin: (Major) Avoid concomitant administration of naloxegol and ciprofloxacin due to the potential for increased naloxegol exposure. If coadministration cannot be avoided, decrease the naloxegol dosage to 12.5 mg once daily and monitor for adverse reactions including opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning. Naloxegol is a CYP3A4 substrate; ciprofloxacin is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor increased naloxegol exposure by approximately 3.4-fold.
Clarithromycin: (Contraindicated) Concomitant use of naloxegol with strong CYP3A4 inhibitors is contraindicated. Naloxegol is metabolized primarily by the CYP3A enzyme system. Strong CYP3A4 inhibitors, such as clarithromycin, can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning.
Cobicistat: (Contraindicated) Concomitant use of naloxegol with cobicistat is contraindicated. Naloxegol is metabolized primarily by CYP3A. Strong CYP3A4 inhibitors, such as cobicistat, can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning.
Conivaptan: (Major) Avoid concomitant administration of naloxegol and conivaptan due to the potential for increased naloxegol exposure. If coadministration cannot be avoided, decrease the naloxegol dosage to 12.5 mg once daily and monitor for adverse reactions including opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning. Naloxegol is a CYP3A substrate; conivaptan is a moderate CYP3A inhibitor. Coadministration of another moderate CYP3A inhibitor increased naloxegol exposure by approximately 3.4-fold.
Crizotinib: (Major) Avoid concomitant administration of naloxegol and crizotinib due to the potential for increased naloxegol exposure. If coadministration cannot be avoided, decrease the naloxegol dosage to 12.5 mg once daily and monitor for adverse reactions including opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning. Naloxegol is a CYP3A4 substrate; crizotinib is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A4 inhibitor increased naloxegol exposure by approximately 3.4-fold.
Cyclosporine: (Major) Avoid concomitant administration of naloxegol and cyclosporine due to the potential for increased naloxegol exposure. If coadministration cannot be avoided, decrease the naloxegol dosage to 12.5 mg once daily and monitor for adverse reactions including opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning. Naloxegol is a CYP3A4 substrate; cyclosporine is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor increased naloxegol exposure by approximately 3.4-fold.
Dabrafenib: (Major) The concomitant use of dabrafenib and naloxegol may lead to decreased naloxegol concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents together is unavoidable, monitor patients for loss of naloxegol efficacy. Dabrafenib is a moderate CYP3A4 inducer and naloxegol is a sensitive CYP3A4 substrate. Concomitant use of dabrafenib with a single dose of another sensitive CYP3A4 substrate decreased the AUC value of the sensitive CYP3A4 substrate by 65%.
Danazol: (Major) Avoid concomitant administration of naloxegol and danazol due to the potential for increased naloxegol exposure. If coadministration cannot be avoided, decrease the naloxegol dosage to 12.5 mg once daily and monitor for adverse reactions including opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning. Naloxegol is a CYP3A4 substrate; danazol is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor increased naloxegol exposure by approximately 3.4-fold.
Darunavir: (Contraindicated) Concomitant use of naloxegol with darunavir is contraindicated. Naloxegol is metabolized primarily by CYP3A. Strong CYP3A4 inhibitors, such as darunavir, can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning.
Darunavir; Cobicistat: (Contraindicated) Concomitant use of naloxegol with cobicistat is contraindicated. Naloxegol is metabolized primarily by CYP3A. Strong CYP3A4 inhibitors, such as cobicistat, can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning. (Contraindicated) Concomitant use of naloxegol with darunavir is contraindicated. Naloxegol is metabolized primarily by CYP3A. Strong CYP3A4 inhibitors, such as darunavir, can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Contraindicated) Concomitant use of naloxegol with cobicistat is contraindicated. Naloxegol is metabolized primarily by CYP3A. Strong CYP3A4 inhibitors, such as cobicistat, can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning. (Contraindicated) Concomitant use of naloxegol with darunavir is contraindicated. Naloxegol is metabolized primarily by CYP3A. Strong CYP3A4 inhibitors, such as darunavir, can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning.
Delavirdine: (Contraindicated) Concomitant use of naloxegol with delavirdine is contraindicated. Naloxegol is metabolized primarily by CYP3A. Strong CYP3A4 inhibitors, such as delavirdine, can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning.
Diltiazem: (Major) Avoid concomitant administration of naloxegol and diltiazem due to the potential for increased naloxegol exposure. If coadministration cannot be avoided, decrease the naloxegol dosage to 12.5 mg once daily and monitor for adverse reactions including opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning. Naloxegol is a CYP3A4 substrate; diltiazem is a moderate CYP3A4 inhibitor. Coadministration with diltiazem increased naloxegol exposure by approximately 3.4-fold.
Dronedarone: (Major) Avoid concomitant administration of naloxegol and dronedarone due to the potential for increased naloxegol exposure. If coadministration cannot be avoided, decrease the naloxegol dosage to 12.5 mg once daily and monitor for adverse reactions including opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning. Naloxegol is a CYP3A4 substrate; dronedarone is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor increased naloxegol exposure by approximately 3.4-fold.
Duvelisib: (Major) Avoid concomitant administration of naloxegol and duvelisib due to the potential for increased naloxegol exposure. If coadministration cannot be avoided, decrease the naloxegol dosage to 12.5 mg once daily and monitor for adverse reactions including opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning. Naloxegol is a CYP3A4 substrate; duvelisib is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor increased naloxegol exposure by approximately 3.4-fold.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Contraindicated) Concomitant use of naloxegol with cobicistat is contraindicated. Naloxegol is metabolized primarily by CYP3A. Strong CYP3A4 inhibitors, such as cobicistat, can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Contraindicated) Concomitant use of naloxegol with cobicistat is contraindicated. Naloxegol is metabolized primarily by CYP3A. Strong CYP3A4 inhibitors, such as cobicistat, can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning.
Encorafenib: (Moderate) Coadministration of encorafenib with naloxegol may result in increased toxicity or decreased efficacy of naloxegol. Naloxegol is a sensitive CYP3A4 substrate. In vitro studies with encorafenib showed time-dependent inhibition of CYP3A4 and induction of CYP3A4. The clinical relevance of the in vivo effect of encorafenib on CYP3A4 is not established.
Enzalutamide: (Major) Coadministration of naloxegol with enzalutamide is not recommended due to the potential for decreased naloxegol efficacy. Naloxegol is a CYP3A4 substrate; enzalutamide is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased naloxegol exposure by 89%.
Erythromycin: (Major) Avoid concomitant administration of naloxegol and erythromycin due to the potential for increased naloxegol exposure. If coadministration cannot be avoided, decrease the naloxegol dosage to 12.5 mg once daily and monitor for adverse reactions including opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning. Naloxegol is a CYP3A4 substrate; erythromycin is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor increased naloxegol exposure by approximately 3.4-fold.
Fedratinib: (Major) Avoid concomitant administration of naloxegol and fedratinib due to the potential for increased naloxegol exposure. If coadministration cannot be avoided, decrease the naloxegol dosage to 12.5 mg once daily and monitor for adverse reactions including opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning. Naloxegol is a CYP3A4 substrate; fedratinib is a moderate CYP3A4 inhibitor. Coadministration of another moderate CYP3A4 inhibitor increased naloxegol exposure by approximately 3.4-fold.
Fluconazole: (Major) Avoid concomitant administration of naloxegol and fluconazole due to the potential for increased naloxegol exposure. If coadministration cannot be avoided, decrease the naloxegol dosage to 12.5 mg once daily and monitor for adverse reactions including opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning. Naloxegol is a CYP3A4 substrate; fluconazole is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor increased naloxegol exposure by approximately 3.4-fold.
Fluvoxamine: (Major) Avoid concomitant administration of naloxegol and fluvoxamine due to the potential for increased naloxegol exposure. If coadministration cannot be avoided, decrease the naloxegol dosage to 12.5 mg once daily and monitor for adverse reactions including opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning. Naloxegol is a CYP3A4 substrate; fluvoxamine is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor increased naloxegol exposure by approximately 3.4-fold.
Fosamprenavir: (Major) Avoid concomitant administration of naloxegol and fosamprenavir due to the potential for increased naloxegol exposure. If coadministration cannot be avoided, decrease the naloxegol dosage to 12.5 mg once daily and monitor for adverse reactions including opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning. Naloxegol is a CYP3A substrate; fosamprenavir is a moderate CYP3A inhibitor. Coadministration of another moderate CYP3A inhibitor increased naloxegol exposure by approximately 3.4-fold.
Fosphenytoin: (Major) Coadministration of naloxegol with fosphenytoin is not recommended due to the potential for decreased naloxegol efficacy. Naloxegol is a CYP3A4 substrate; fosphenytoin is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased naloxegol exposure by 89%.
Grapefruit juice: (Contraindicated) Patients should avoid grapefruit and grapefruit juice during naloxegol treatment. Concomitant use of naloxegol with grapefruit juice is contraindicated. Naloxegol is metabolized primarily by CYP3A. Strong CYP3A4 inhibitors, such as grapefruit juice, can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning.
Idelalisib: (Contraindicated) Concomitant use of naloxegol with idelalisib is contraindicated. Naloxegol is metabolized primarily by CYP3A. Strong CYP3A4 inhibitors, such as idelalisib, can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning.
Imatinib: (Major) Avoid concomitant administration of naloxegol and imatinib due to the potential for increased naloxegol exposure. If coadministration cannot be avoided, decrease the naloxegol dosage to 12.5 mg once daily and monitor for adverse reactions including opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning. Naloxegol is a CYP3A4 substrate; imatinib is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor increased naloxegol exposure by approximately 3.4-fold.
Indinavir: (Contraindicated) Concomitant use of naloxegol with indinavir is contraindicated. Naloxegol is metabolized primarily by CYP3A. Strong CYP3A4 inhibitors, such as indinavir, can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning.
Isavuconazonium: (Major) Avoid concomitant administration of naloxegol and isavuconazonium due to the potential for increased naloxegol exposure. If coadministration cannot be avoided, decrease the naloxegol dosage to 12.5 mg once daily and monitor for adverse reactions including opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning. Naloxegol is a CYP3A4 substrate; isavuconazonium is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor increased naloxegol exposure by approximately 3.4-fold.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Coadministration of naloxegol with rifampin is not recommended due to the potential for decreased naloxegol efficacy. Naloxegol is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased naloxegol exposure by 89%.
Isoniazid, INH; Rifampin: (Major) Coadministration of naloxegol with rifampin is not recommended due to the potential for decreased naloxegol efficacy. Naloxegol is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased naloxegol exposure by 89%.
Itraconazole: (Contraindicated) Concomitant use of naloxegol with itraconazole is contraindicated. Naloxegol is metabolized primarily by CYP3A. Strong CYP3A4 inhibitors, such as itraconazole, can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning.
Ivosidenib: (Moderate) Monitor for loss of efficacy of naloxegol during coadministration of ivosidenib; a naloxegol dose adjustment may be necessary. Naloxegol is a sensitive substrate of CYP3A4; ivosidenib induces CYP3A4 and may lead to decreased naloxegol concentrations.
Ketoconazole: (Contraindicated) Concomitant use of naloxegol with ketoconazole is contraindicated. Naloxegol is metabolized primarily by CYP3A. Strong CYP3A4 inhibitors, such as ketoconazole, can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning.
Lansoprazole; Amoxicillin; Clarithromycin: (Contraindicated) Concomitant use of naloxegol with strong CYP3A4 inhibitors is contraindicated. Naloxegol is metabolized primarily by the CYP3A enzyme system. Strong CYP3A4 inhibitors, such as clarithromycin, can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning.
Lefamulin: (Major) Avoid concomitant administration of naloxegol and oral lefamulin due to the potential for increased naloxegol exposure. If coadministration cannot be avoided, decrease the naloxegol dosage to 12.5 mg once daily and monitor for adverse reactions including opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning. Naloxegol is a CYP3A4 substrate; oral lefamulin is a moderate CYP3A4 inhibitor; an interaction is not expected with intravenous lefamulin. Coadministration of another moderate CYP3A4 inhibitor increased naloxegol exposure by approximately 3.4-fold.
Lenacapavir: (Major) Avoid concomitant administration of naloxegol and lenacapavir due to the potential for increased naloxegol exposure. If coadministration cannot be avoided, decrease the naloxegol dosage to 12.5 mg once daily and monitor for adverse reactions including opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning. Naloxegol is a CYP3A substrate; lenacapavir is a moderate CYP3A inhibitor. Coadministration of another moderate CYP3A inhibitor increased naloxegol exposure by approximately 3.4-fold.
Letermovir: (Major) Avoid concomitant administration of naloxegol and letermovir due to the potential for increased naloxegol exposure. If coadministration cannot be avoided, decrease the naloxegol dosage to 12.5 mg once daily and monitor for adverse reactions including opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning. Concurrent use is contraindicated if the patient is also receiving cyclosporine because the magnitude of the interaction may be amplified. Naloxegol is a CYP3A4 substrate; letermovir is a moderate CYP3A4 inhibitor. The combined effect of letermovir and cyclosporine on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor increased naloxegol exposure by approximately 3.4-fold. Coadministration of a strong CYP3A4 inhibitor increased naloxegol exposure by more than 12-fold.
Levoketoconazole: (Contraindicated) Concomitant use of naloxegol with ketoconazole is contraindicated. Naloxegol is metabolized primarily by CYP3A. Strong CYP3A4 inhibitors, such as ketoconazole, can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning.
Lonafarnib: (Contraindicated) Concomitant use of naloxegol with lonafarnib is contraindicated. Naloxegol is metabolized primarily by CYP3A4. Strong CYP3A4 inhibitors, such as lonafarnib, can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning.
Lopinavir; Ritonavir: (Contraindicated) Concomitant use of naloxegol with ritonavir is contraindicated. Naloxegol is metabolized primarily by CYP3A. Strong CYP3A4 inhibitors, such as ritonavir, can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning.
Lumacaftor; Ivacaftor: (Major) Coadministration of naloxegol with lumacaftor; ivacaftor is not recommended due to the potential for decreased naloxegol efficacy. Naloxegol is a CYP3A4 substrate; lumacaftor; ivacaftor is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased naloxegol exposure by 89%.
Lumacaftor; Ivacaftor: (Major) Coadministration of naloxegol with lumacaftor; ivacaftor is not recommended due to the potential for decreased naloxegol efficacy. Naloxegol is a CYP3A4 substrate; lumacaftor; ivacaftor is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased naloxegol exposure by 89%.
Methylnaltrexone: (Major) Avoid coadministration of methylnaltrexone and other opiate antagonists, like naloxegol. There is a potential for additive effect of opioid receptor antagonism and increased risk of opioid withdrawal with concomitant use.
Mifepristone: (Contraindicated) Concomitant use of naloxegol with chronic mifepristone therapy is contraindicated. Naloxegol is metabolized primarily by CYP3A. Strong CYP3A4 inhibitors, such as mifepristone, can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning. The clinical significance of this interaction when mifepristone is used for pregnancy termination is not established.
Mitotane: (Major) Coadministration of naloxegol with mitotane is not recommended due to the potential for decreased naloxegol efficacy. Naloxegol is a CYP3A4 substrate; mitotane is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased naloxegol exposure by 89%.
Naldemedine: (Major) Avoid concomitant use of naldemedine and naloxegol because of the potential for additive effects of opioid receptor antagonism and increased risk of opioid withdrawal.
Nalmefene: (Major) Avoid concomitant use of naloxegol with other opioid antagonists because of the potential for additive effects of opioid receptor antagonism and increased risk of opioid withdrawal.
Naloxone: (Major) Avoid concomitant use of naloxegol with other opioid antagonists because of the potential for additive effects of opioid receptor antagonism and increased risk of opioid withdrawal.
Naltrexone: (Major) Avoid concomitant use of naloxegol with other opioid antagonists because of the potential for additive effects of opioid receptor antagonism and increased risk of opioid withdrawal.
Nefazodone: (Contraindicated) Concomitant use of naloxegol with nefazodone is contraindicated. Naloxegol is metabolized primarily by CYP3A. Strong CYP3A4 inhibitors, such as nefazodone, can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning.
Nelfinavir: (Contraindicated) Concomitant use of naloxegol with nelfinavir is contraindicated. Naloxegol is metabolized primarily by CYP3A. Strong CYP3A4 inhibitors, such as nelfinavir, can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning.
Netupitant, Fosnetupitant; Palonosetron: (Major) Avoid concomitant administration of naloxegol and netupitant due to the potential for increased naloxegol exposure. If coadministration cannot be avoided, decrease the naloxegol dosage to 12.5 mg once daily and monitor for adverse reactions including opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning. Naloxegol is a CYP3A4 substrate; netupitant is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor increased naloxegol exposure by approximately 3.4-fold.
Nilotinib: (Major) Avoid concomitant administration of naloxegol and nilotinib due to the potential for increased naloxegol exposure. If coadministration cannot be avoided, decrease the naloxegol dosage to 12.5 mg once daily and monitor for adverse reactions including opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning. Naloxegol is a CYP3A4 substrate; nilotinib is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor increased naloxegol exposure by approximately 3.4-fold.
Nirmatrelvir; Ritonavir: (Contraindicated) Concomitant use of naloxegol with ritonavir is contraindicated. Naloxegol is metabolized primarily by CYP3A. Strong CYP3A4 inhibitors, such as ritonavir, can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning. (Contraindicated) Concomitant use of ritonavir-boosted nirmatrelvir and naloxegol is contraindicated due to the potential for opioid withdrawal symptoms; consider an alternative COVID-19 therapy. Coadministration can significantly increase naloxegol exposure which may precipitate opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning. Naloxegol is a CYP3A4 substrate and nirmatrelvir is a CYP3A inhibitor.
Olanzapine; Samidorphan: (Major) Avoid concomitant use of naloxegol with other opioid antagonists because of the potential for additive effects of opioid receptor antagonism and increased risk of opioid withdrawal.
Pentazocine; Naloxone: (Major) Avoid concomitant use of naloxegol with other opioid antagonists because of the potential for additive effects of opioid receptor antagonism and increased risk of opioid withdrawal.
Phenobarbital: (Major) Coadministration of naloxegol with phenobarbital is not recommended due to the potential for decreased naloxegol efficacy. Naloxegol is a CYP3A4 substrate; phenobarbital is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased naloxegol exposure by 89%.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Coadministration of naloxegol with phenobarbital is not recommended due to the potential for decreased naloxegol efficacy. Naloxegol is a CYP3A4 substrate; phenobarbital is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased naloxegol exposure by 89%.
Phenytoin: (Major) Coadministration of naloxegol with phenytoin is not recommended due to the potential for decreased naloxegol efficacy. Naloxegol is a CYP3A4 substrate; phenytoin is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased naloxegol exposure by 89%.
Posaconazole: (Contraindicated) Concomitant use of naloxegol with posaconazole is contraindicated. Naloxegol is metabolized primarily by CYP3A. Strong CYP3A4 inhibitors, such as posaconazole, can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning.
Primidone: (Major) Coadministration of naloxegol with primidone is not recommended due to the potential for decreased naloxegol efficacy. Naloxegol is a CYP3A4 substrate; phenobarbital, the active metabolite of primidone, is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased naloxegol exposure by 89%.
Quinine: (Major) Avoid concomitant administration of naloxegol and quinine due to the potential for increased naloxegol exposure. If coadministration cannot be avoided, decrease the naloxegol dosage to 12.5 mg once daily and monitor for adverse reactions including opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning. Naloxegol is a CYP3A4 substrate; quinine is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor increased naloxegol exposure by approximately 3.4-fold.
Ribociclib: (Major) Avoid concomitant administration of naloxegol and ribociclib due to the potential for increased naloxegol exposure. If coadministration cannot be avoided, decrease the naloxegol dosage to 12.5 mg once daily and monitor for adverse reactions including opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning. Naloxegol is a CYP3A4 substrate; ribociclib is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor increased naloxegol exposure by approximately 3.4-fold.
Ribociclib; Letrozole: (Major) Avoid concomitant administration of naloxegol and ribociclib due to the potential for increased naloxegol exposure. If coadministration cannot be avoided, decrease the naloxegol dosage to 12.5 mg once daily and monitor for adverse reactions including opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning. Naloxegol is a CYP3A4 substrate; ribociclib is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor increased naloxegol exposure by approximately 3.4-fold.
Rifampin: (Major) Coadministration of naloxegol with rifampin is not recommended due to the potential for decreased naloxegol efficacy. Naloxegol is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased naloxegol exposure by 89%.
Rifapentine: (Major) Coadministration of naloxegol with rifapentine is not recommended due to the potential for decreased naloxegol efficacy. Naloxegol is a CYP3A4 substrate; rifapentine is a strong CYP3A4 inducer. Coadministration of another strong CYP3A4 inducer decreased naloxegol exposure by 89%.
Ritlecitinib: (Major) Avoid concomitant administration of naloxegol and ritlecitinib due to the potential for increased naloxegol exposure. If coadministration cannot be avoided, decrease the naloxegol dosage to 12.5 mg once daily and monitor for adverse reactions including opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning. Naloxegol is a CYP3A substrate; ritlecitinib is a moderate CYP3A inhibitor. Coadministration of another moderate CYP3A inhibitor increased naloxegol exposure by approximately 3.4-fold.
Ritonavir: (Contraindicated) Concomitant use of naloxegol with ritonavir is contraindicated. Naloxegol is metabolized primarily by CYP3A. Strong CYP3A4 inhibitors, such as ritonavir, can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning.
Saquinavir: (Contraindicated) Concomitant use of naloxegol with saquinavir is contraindicated. Naloxegol is metabolized primarily by CYP3A. Strong CYP3A4 inhibitors, such as saquinavir, can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning.
St. John's Wort, Hypericum perforatum: (Major) Coadministration of naloxegol with St. John's Wort is not recommended due to the potential for decreased naloxegol efficacy. Naloxegol is a CYP3A4 substrate; St. John's Wort is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased naloxegol exposure by 89%.
Stiripentol: (Moderate) Consider a dose adjustment of naloxegol when coadministered with stiripentol. Coadministration may alter plasma concentrations of naloxegol resulting in an increased risk of adverse reactions and/or decreased efficacy. Naloxegol is a sensitive CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Tipranavir: (Contraindicated) Concomitant use of naloxegol with tipranavir is contraindicated. Naloxegol is metabolized primarily by CYP3A. Strong CYP3A4 inhibitors, such as tipranavir, can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning.
Trandolapril; Verapamil: (Major) Avoid concomitant administration of naloxegol and verapamil due to the potential for increased naloxegol exposure. If coadministration cannot be avoided, decrease the naloxegol dosage to 12.5 mg once daily and monitor for adverse reactions including opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning. Naloxegol is a CYP3A4 substrate; verapamil is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor increased naloxegol exposure by approximately 3.4-fold.
Tucatinib: (Contraindicated) Concomitant use of naloxegol with tucatinib is contraindicated. Naloxegol is metabolized primarily by CYP3A4. Strong CYP3A4 inhibitors, such as tucatinib, can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning.
Verapamil: (Major) Avoid concomitant administration of naloxegol and verapamil due to the potential for increased naloxegol exposure. If coadministration cannot be avoided, decrease the naloxegol dosage to 12.5 mg once daily and monitor for adverse reactions including opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning. Naloxegol is a CYP3A4 substrate; verapamil is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor increased naloxegol exposure by approximately 3.4-fold.
Vonoprazan; Amoxicillin; Clarithromycin: (Contraindicated) Concomitant use of naloxegol with strong CYP3A4 inhibitors is contraindicated. Naloxegol is metabolized primarily by the CYP3A enzyme system. Strong CYP3A4 inhibitors, such as clarithromycin, can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning.
Voriconazole: (Contraindicated) Concomitant use of naloxegol with voriconazole is contraindicated. Naloxegol is metabolized primarily by CYP3A. Strong CYP3A4 inhibitors, such as voriconazole, can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning.
Voxelotor: (Major) Avoid concomitant administration of naloxegol and voxelotor due to the potential for increased naloxegol exposure. If coadministration cannot be avoided, decrease the naloxegol dosage to 12.5 mg once daily and monitor for adverse reactions including opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning. Naloxegol is a CYP3A substrate; voxelotor is a moderate CYP3A inhibitor. Coadministration of another moderate CYP3A inhibitor increased naloxegol exposure by approximately 3.4-fold.

Movantik/Naloxegol Oral Tab: 12.5mg, 25mg

25 mg PO daily.

25 mg PO daily.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Naloxegol is an antagonist of opioid binding at the mu-opioid receptor and a PEGylated derivative of naloxone. Naloxegol is also a substrate of the P-glycoprotein transporter (P-gp). Its P-gp substrate properties, which increase efflux across the blood-brain barrier, coupled with the presence of the PEG moiety, reduce the CNS penetration of naloxegol compared to naloxone. When administered at the recommended dose levels, naloxegol functions as a peripherally-acting mu-opioid receptor antagonist in tissues such as the gastrointestinal tract, thereby decreasing the constipating effects of opioids. The potential for interference with centrally mediated opioid analgesia is limited with naloxegol use at recommended doses.

Naloxegol is administered orally. Plasma protein binding of naloxegol in humans is low (approximately 4.2%). In a mass balance study in humans, a total of 6 metabolites were identified in plasma, urine and feces. Naloxegol metabolism occurs via the cytochrome P450 isoenzyme system. Metabolites are formed via N-dealkylation, O-demethylation, oxidation and partial loss of the PEG chain. Human metabolism data suggests absence of major metabolites. The activity of the metabolites at the opioid receptor has not been determined. Following oral administration of radio-labelled naloxegol, 68% and 16% of total administered dose were recovered in the feces and urine, respectively. Parent naloxegol excreted in the urine accounted for less than 6% of the total administered dose. Approximately 16% of radioactivity in feces was noted to be unchanged naloxegol, while the remaining was attributed to metabolites. Thus, renal excretion is a minor clearance pathway for naloxegol. In a clinical pharmacology study, the half-life of naloxegol at therapeutic doses ranged from 6 to 11 hours.
 
Affected cytochrome P450 isoenzymes: CYP3A
Naloxegol is metabolized primarily by the CYP3A enzyme system.

Limited available data with naloxegol use in pregnant women are insufficient to inform a drug associated risk of adverse developmental outcomes. There are no well-controlled studies in pregnant women. The use of naloxegol during pregnancy may precipitate opioid withdrawal in a fetus due to the immature fetal blood brain barrier. In animal studies, no effects on embryo-fetal development were observed following administration of naloxegol in pregnant rats or rabbits during the period of organogenesis at doses up to 1452 and 409 times (respectively) the human AUC at the maximum recommended human dose. According to the manufacturer, naloxegol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

It is not known whether naloxegol is present in human milk; however, naloxegol is present in rat milk and is absorbed in nursing rat pups. Because of the potential for serious adverse reactions, including opioid withdrawal in breast-feeding infants, the manufacturer recommends that a decision be made to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.