to surround [60:<60 mL/minute. 1 (See Renal Impairment under Dosage and Administration.) Common Adverse Effects Abdominal pain, 1 2 diarrhea, 1 2 nausea, 1 2 flatulence, 1 2 vomiting, 1 2 headache, 1 2 hyperhidrosis. 1 Interactions for Naloxegol Oxalate Principally metabolized by CYP3A isoenzymes. 1 Did not inhibit CYP1A2, 2C9, 2C19, 2D6, or 3A4 nor substantially induce CYP 1A2, 2B6, or 3A4 at clinically relevant concentrations in vitro; not expected to alter metabolic clearance of drugs metabolized by these enzymes. 1 Substrate, but not clinically important inhibitor, of P-glycoprotein (P-gp). 1 Does not substantially inhibit breast cancer resistance protein (BCRP), organic anion transporter (OAT) 1 or 3, organic cation transporter (OCT) 2, or organic anion transport protein (OATP) 1B1 or 1B3. 1 Drugs Affecting Hepatic Microsomal Enzymes Potent CYP3A4 inhibitors: Increased plasma naloxegol concentrations and increased risk of adverse effects. 1 Concomitant use contraindicated. 1 Moderate CYP3A4 inhibitors: Increased plasma naloxegol concentrations and increased risk of adverse effects. 1 Avoid concomitant use; if concomitant use cannot be avoided, reduce naloxegol dosage to 12.5 mg once daily and monitor for adverse effects. 1 4 Weak CYP3A4 inhibitors: Clinically important interaction not expected. 1 No dosage adjustment required. 1 Potent CYP3A4 inducers: Decreased plasma naloxegol concentrations and possible decreased naloxegol efficacy. 1 Concomitant use not recommended. 1 Specific Drugs and Foods Drug or Food Interaction Comments Carbamazepine Decreased plasma naloxegol concentrations; possible decreased efficacy 1 Concomitant use not recommended 1 Cimetidine Clinically important pharmacokinetic interaction unlikely 1 Dosage adjustment not needed 1 Clarithromycin Increased plasma naloxegol concentrations; possible increased risk of adverse effects 1 Concomitant use contraindicated 1 Diltiazem Peak plasma concentration and AUC of naloxegol increased by 2.9- and 3.4-fold, respectively; possible increased risk of adverse effects 1 4 Avoid concomitant use; if such use cannot be avoided, reduce naloxegol dosage to 12.5 mg once daily and monitor for adverse effects 1 4 Efavirenz Pharmacokinetic simulations suggest a 50% reduction in naloxegol exposure 1 4 Erythromycin Increased plasma naloxegol concentrations; possible increased risk of adverse effects 1 4 Avoid concomitant use; if such use cannot be avoided, reduce naloxegol dosage to 12.5 mg once daily and monitor for adverse effects 1 Grapefruit or grapefruit juice Increased plasma naloxegol concentrations; possible increased risk of adverse effects 1 Avoid concomitant use 1 Itraconazole Increased plasma naloxegol concentrations; possible increased risk of adverse effects 1 Concomitant use contraindicated 1 Ketoconazole Peak plasma concentration and AUC of naloxegol increased by 9.6- and 12.9-fold, respectively; possible increased risk of adverse effects 1 Concomitant use contraindicated 1 Morphine No meaningful effect on systemic exposure to morphine or its major circulating metabolites 1 4 Opiate antagonists Possible additive opiate receptor antagonism and increased risk of opiate withdrawal 1 Avoid concomitant use 1 Quinidine Peak plasma concentration and AUC of naloxegol increased by 2.5- and 1.4-fold, respectively 1 4 6 No dosage adjustment necessary 1 Rifampin Peak plasma concentration and AUC of naloxegol decreased by 76 and 89%, respectively; possible decreased efficacy 1 4 Concomitant use not recommended 1 4 St. John's wort ( Hypericum perforatum ) Decreased plasma naloxegol concentrations; possible decreased efficacy 1 Concomitant use not recommended 1 Verapamil Increased plasma naloxegol concentrations; possible increased risk of adverse effects 1 4 Avoid concomitant use; if such use cannot be avoided, reduce dosage of naloxegol to 12.5 mg once daily and monitor for adverse effects 1 Naloxegol Oxalate Pharmacokinetics Absorption Bioavailability Rapidly absorbed from GI tract, with peak concentration attained less than 2 hours after oral administration. 1 9 10 Secondary peak generally observed approximately 0.4 3 hours after the first peak, suggesting enterohepatic circulation. 1 9 10 Peak plasma concentration and AUC increase in dose-proportional or almost dose-proportional manner. 1 Food High-fat meal increases extent and rate of absorption (peak plasma concentration and AUC increased by approximately 30 and 45%, respectively). 1 Special Populations Hepatic impairment: AUC decreased slightly in patients with mild or moderate hepatic impairment (Child-Pugh class A or B). 1 7 Renal impairment with Cl cr> <60 mL/minute (moderate or severe renal impairment, ESRD not requiring dialysis): Pharmacokinetic profile in most patients similar to that in healthy individuals. 1 8 However, marked (up to tenfold) increase in exposure observed in some patients with moderate or severe renal impairment or ESRD; reason for increased exposure unknown. 1 8 ESRD requiring dialysis: Plasma concentrations similar to concentrations in healthy individuals whether drug administered before or after hemodialysis. 1 8 Age: Peak concentration and AUC increased approximately 45 and 54%, respectively, in healthy geriatric Japanese individuals compared with younger individuals. 1 Race: AUC increased by approximately 20% in Caucasian patients compared with patients of other races. 1 Distribution Extent Distributed into milk in rats; not known whether distributed into human milk. 1 CNS penetration expected to be negligible at recommended dosage. 1 5 10 11 Plasma Protein Binding Approximately 4%. 1 Elimination Metabolism Extensively metabolized, principally via CYP3A isoenzymes; undergoes N -dealkylation, O -demethylation, oxidation, and shortening of the polyethylene glycol (PEG) chain. 1 9 Elimination Route Excreted principally in feces (68%, approximately 16% of which is unchanged drug) and to lesser extent in urine (16%). 1 Half-life 6 11 hours. 1 Stability Storage Oral Tablets 20 25 C (may be exposed to 15 30 C). 1 Actions Peripherally acting μ-opiate receptor antagonist; covalent conjugate of naloxone and PEG. 1 2 3 5 11 Blocks μ-opiate receptors in the GI tract, thereby reversing opiate-induced constipating effects (e.g., slowing of GI motility and transit). 1 3 5 10 Conjugation with PEG decreases passive permeability of the drug across the blood-brain barrier and renders naloxegol a substrate for P-gp, which results in increased efflux across the blood-brain barrier. 1 2 3 5 10 11 CNS penetration expected to be negligible at recommended dosages, limiting the potential for interference with centrally mediated opiate analgesia. 1 5 10 11 Exhibits antagonist effects at μ- and δ-opiate receptors and weak partial agonist activity at κ-opiate receptors, but has highest affinity for μ-receptors; 13 affinity for μ-receptors is approximately 20-fold lower than that of naloxone. 13 Advice to Patients Importance of reading the manufacturer's medication guide before beginning treatment and each time the prescription is refilled. 1 Importance of discontinuing all maintenance laxative therapy prior to initiation of naloxegol. 1 Laxatives may be used as needed if response to naloxegol is suboptimal after 3 days. 1 Importance of taking naloxegol on an empty stomach 1 hour before or 2 hours after the first meal of the day. 1 Importance of swallowing naloxegol tablets intact and not crushing or chewing the tablets. 1 Importance of informing clinician if therapy is not tolerated, as dosage adjustment may be appropriate. 1 Importance of informing clinician if opiate analgesics are discontinued, since naloxegol should be discontinued if opiates are discontinued. 1 Possible risk of GI perforation. 1 Importance of discontinuing naloxegol and promptly seeking medical attention if unusually severe, persistent, or worsening abdominal pain occurs. 1 Potential for symptoms consistent with opiate withdrawal (e.g., sweating, chills, diarrhea, abdominal pain, anxiety, irritability, yawning) to occur. 1 Inform methadone-treated patients that they may be more likely than patients receiving other opiates to experience adverse GI effects that may be related to opiate withdrawal. 1 Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed. 1 Advise women that naloxegol use during pregnancy may precipitate fetal opiate withdrawal because the fetal blood-brain barrier is immature. 1 Advise women not to breast-feed while receiving the drug because of the potential for opiate withdrawal in nursing infants. 1 Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs (especially those that alter CYP3A4 activity), as well as any concomitant illnesses. 1 Advise patients to avoid consumption of grapefruit or grapefruit juice and to inform their clinician when they initiate or discontinue any concomitant drug therapy. 1 Importance of informing patients of other important precautionary information. 1 (See Cautions.) Preparations Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details. Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations. Naloxegol Oxalate Routes Dosage Forms Strengths Brand Names Manufacturer Oral Tablets, film-coated 12.5 mg (of naloxegol) Movantik AstraZeneca 25 mg (of naloxegol) Movantik AstraZeneca AHFS DI Essentials. Copyright 2017, Selected Revisions February 25, 2016. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814. References 1. AstraZeneca Pharmaceuticals. Movantik (naloxegol) tablets prescribing information. Wilmington, DE; 2015 Jan. 2. Chey WD, Webster L, Sostek M et al. Naloxegol for opioid-induced constipation in patients with noncancer pain. N Engl J Med . 2014; 370:2387-96. [PubMed 24896818] 3. Leonard J, Baker DE. Naloxegol: treatment for opioid-induced constipation in chronic non-cancer pain. Ann Pharmacother . 2015; 49:360-5. [PubMed 25471070] 4. US Food and Drug Administration. Center for Drug Evaluation and Research. Application number204760Orig1s000: Clinical pharmacology and biopharmaceutics review(s). From FDA website. 5. Bruner HC, Atayee RS, Edmonds KP et al. Clinical utility of naloxegol in the treatment of opioid-induced constipation. J Pain Res . 2015; 8:289-94. [PubMed 26109876] 6. Bui K, She F, Zhou D et al. The effect of quinidine, a strong P-glycoprotein inhibitor, on the pharmacokinetics and central nervous system distribution of naloxegol. J Clin Pharmacol . 2015; :. 7. Bui K, She F, Sostek M. The effects of mild or moderate hepatic impairment on the pharmacokinetics, safety, and tolerability of naloxegol. J Clin Pharmacol . 2014; 54:1368-74. [PubMed 24945932] 8. Bui K, She F, Sostek M. The effects of renal impairment on the pharmacokinetics, safety, and tolerability of naloxegol. J Clin Pharmacol . 2014; 54:1375-82. [PubMed 24946021] 9. Bui K, She F, Hutchison M et al. Absorption, distribution, metabolism, and excretion of [14C]-labeled naloxegol in healthy subjects. Int J Clin Pharmacol Ther . 2015; :. [PubMed 26329350] 10. Garnock-Jones KP. Naloxegol: a review of its use in patients with opioid-induced constipation. Drugs . 2015; 75:419-25. [PubMed 25666542] 11. Jones R, Prommer E, Backstedt D. Naloxegol: A Novel Therapy in the Management of Opioid-Induced Constipation. Am J Hosp Palliat Care . 2015; :. [PubMed 26150678] 12. Salix. Relistor (methylnaltrexone bromide) subcutaneous injection prescribing information. Raleigh, NC; 2014 Sep. 13. US Food and Drug Administration. Center for Drug Evaluation and Research. Application number204760Orig1s000: Pharmacology review(s). From FDA website. Next Interactions Print this page Add to My Med List More about naloxegol Side Effects During Pregnancy Dosage Information Drug Interactions Support Group En Español 153 Reviews Add your own review/rating Drug class: peripheral opioid receptor antagonists Consumer resources Naloxegol Naloxegol (Advanced Reading) Professional resources Naloxegol (Wolters Kluwer) Other brands: Movantik Related treatment guides Opioid-Induced Constipation Constipation, Chronic Constipation, Drug Induced> ]} FEATURED: CAR-T Cell Therapy Overview Mechanism of Action KTE-C19 Studies KTE-C19 Cancer Targets Adverse Events Manufacturing Drug Status Rx Availability Prescription only C Pregnancy Category Risk cannot be ruled out N/A CSA Schedule Not a controlled drug Approval History Drug history at FDA Drug Class Peripheral opioid receptor antagonists Related Drugs Opioid-Induced Constipation Amitiza , Movantik , lubiprostone , Relistor , naloxegol , methylnaltrexone , Symproic , naldemedine , More... Constipation, Chronic Amitiza , Linzess , lactulose , Movantik , linaclotide , GoLYTELY , MoviPrep , lubiprostone , More... Constipation, Drug Induced Amitiza , Movantik , lubiprostone , Relistor , naloxegol , methylnaltrexone , More... Naloxegol Rating 153 User Reviews 4.7 /10 153 User Reviews 4.7 Rate it!} } disregarded
do away with Naloxegol Oxalate train
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