Hospital Pharmacy - July/August 2017 - 467

467

Baker
Patients having disruptions to the blood-brain barrier may
be at increased risk for opioid withdrawal or reduced analgesia. Take into account the overall risk-benefit profile when
using naldemedine in such patients. Monitor for symptoms
of opioid withdrawal in such patients.2
Methylnaltrexone and naloxegol have similar warnings
and precautions to naldemedine.10,11
Naldemedine does not cause QTc prolongation at therapeutic or supratherapeutic doses.2,27
The use of opioid antagonists during pregnancy may precipitate opioid withdrawal in a fetus.2,10,11
A decision should be made to discontinue breastfeeding or
use of naldemedine. If naldemedine is discontinued to minimize drug exposure to a breastfed infant, breastfeeding should
be delayed for 3 days after the final dose of naldemedine.2
The safety and effectiveness of naldemedine have not
been established in pediatric patients.2

Recommended Monitoring

Adverse Reactions

Product Availability

The most common adverse reactions with naldemedine (incidence of at least 5% and occurring at a greater frequency
than with placebo) in clinical trials were abdominal pain (ie,
abdominal discomfort, abdominal pain, lower abdominal
pain, upper abdominal pain, GI pain; 5.2%-11% vs 1.1%5%), diarrhea (6.6%-11% vs 1.8%-5.3%), nausea (4%-6% vs
2%-5%), vomiting (3% vs 2%), and gastroenteritis (2%-3%
vs 1%).2,18,19,25 Serious and important adverse reactions
include GI perforation and opioid withdrawal.2

The New Drug Application (NDA) for naldemedine was
accepted by the FDA in June 2016. The Prescription Drug
User Fee Act (PDUFA) target action date was March 23,
2017.28 Symproic was approved by the FDA on March 23,
2017.1
Naldemedine 0.2 mg is available as a film-coated tablet in
bottles of 90.2
Store naldemedine in a light-resistant container at 20°C to
25°C (68°F-77°F); excursions are permitted to 15°C to 30°C
(59°F-86°F).2

No special safety monitoring is recommended, with the
exception of monitoring for acute opiate withdrawal.

Dosing
The recommended dose is naldemedine 0.2 mg orally once
daily with or without food. There are no dosage adjustment
recommendations based on age or organ function; however, naldemedine therapy should be avoided in patients
with severe hepatic impairment. Alteration of analgesic
dosing is also not required; however, if the opioid pain
medication is discontinued, naldemedine therapy should
be discontinued.2
Patients receiving opioids for less than 4 weeks may be
less responsive to naldemedine therapy.2

Drug Interactions
Administration with strong CYP3A inducers (eg, carbamazepine, phenytoin, rifampin, St. John's wort) significantly
decreases plasma naldemedine concentrations and efficacy;
therefore, coadministration should be avoided.2
Administration with moderate (eg, aprepitant, atazanavir,
diltiazem, erythromycin, fluconazole) or strong (eg, clarithromycin, itraconazole, ketoconazole, ritonavir, saquinavir) CYP3A inhibitors significantly increases plasma
naldemedine concentrations, which increases the risk of
naldemedine-related adverse reactions.2
Administration with P-glycoprotein inhibitors (eg, amiodarone, captopril, cyclosporine, quercetin, quinidine, verapamil) may increase plasma naldemedine concentrations and
increase the risk of naldemedine-related adverse reactions.2
Coadministration with other opioid antagonists has the
potential for an additive effect on naldemedine's opioid receptor antagonism and increases the risk of opioid withdrawal.2
In in vitro studies, naldemedine at clinically relevant concentrations did not inhibit the major CYP enzymes (including CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4/5,
or 4A11 isozymes), inhibit transporters (including OATP1B1,
OATP1B3, OCT1, OCT2, OAT1, OAT3, BCRP, or P-gp), or
cause significant induction of CYP1A2, CYP2B6, CYP3A4,
UGT1A2, UGT1A6, or UGT2B7 isozymes.2

Drug Safety/REMS
No Risk Evaluation and Mitigation Strategy (REMS) is
required for naldemedine.

Conclusion
Naldemedine is an opioid antagonist approved for the treatment of OIC in adults with chronic noncancer pain. In clinical trials, naldemedine improved the frequency of SBMs and
did not affect opioid analgesic effects. Similar to naloxegol
and methylnaltrexone, naldemedine is available as oral tablets. There are no head-to-head studies comparing these
drugs, and none are intended for the treatment or management of OIC in cancer patients.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with
respect to the research, authorship, and/or publication of this
article.

Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.



Table of Contents for the Digital Edition of Hospital Pharmacy - July/August 2017

The Evolution of Drug Information Centers and Specialists
Letter: Sodium Phosphates Injection—Osmolarity Labeling Correction
ISMP Adverse Drug Reactions
Drug Monographs: Avelumab and Ribociclib
Formulary Drug Review: Naldemedine
Chimeric Antigen Receptor T-Cell Therapy for Lymphomas: A Review of a Drug Class or Therapeutic Class in a Late Stage of Clinical Development
International Mentoring Programs: Leadership Opportunities to Enhance Worldwide Pharmacy Practice
Compounded Apixaban Suspensions for Enteral Feeding Tubes
Impact of Developing Adult Ketamine Order Panels for the Emergency Department
Critical Appraisal of Biomedical Literature With a Succinct Journal Club Template: The ROOTs Format
Effect of a Rivaroxaban Patient Assistance Kit (R-PAK) for Patients Discharged With Rivaroxaban: A Randomized Controlled Trial
Examining the Use of Sodium Nitroprusside in Coronary Artery Bypass Grafting: Is the Benefit Worth the Cost?
Successful Implementation of an Antimicrobial Stewardship Program at an Academic Medical Center
Hospital Pharmacy - July/August 2017 - 445
Hospital Pharmacy - July/August 2017 - 446
Hospital Pharmacy - July/August 2017 - 447
Hospital Pharmacy - July/August 2017 - 448
Hospital Pharmacy - July/August 2017 - 449
Hospital Pharmacy - July/August 2017 - 450
Hospital Pharmacy - July/August 2017 - 451
Hospital Pharmacy - July/August 2017 - The Evolution of Drug Information Centers and Specialists
Hospital Pharmacy - July/August 2017 - 453
Hospital Pharmacy - July/August 2017 - Letter: Sodium Phosphates Injection—Osmolarity Labeling Correction
Hospital Pharmacy - July/August 2017 - ISMP Adverse Drug Reactions
Hospital Pharmacy - July/August 2017 - 456
Hospital Pharmacy - July/August 2017 - 457
Hospital Pharmacy - July/August 2017 - 458
Hospital Pharmacy - July/August 2017 - Drug Monographs: Avelumab and Ribociclib
Hospital Pharmacy - July/August 2017 - 460
Hospital Pharmacy - July/August 2017 - 461
Hospital Pharmacy - July/August 2017 - 462
Hospital Pharmacy - July/August 2017 - 463
Hospital Pharmacy - July/August 2017 - Formulary Drug Review: Naldemedine
Hospital Pharmacy - July/August 2017 - 465
Hospital Pharmacy - July/August 2017 - 466
Hospital Pharmacy - July/August 2017 - 467
Hospital Pharmacy - July/August 2017 - 468
Hospital Pharmacy - July/August 2017 - Chimeric Antigen Receptor T-Cell Therapy for Lymphomas: A Review of a Drug Class or Therapeutic Class in a Late Stage of Clinical Development
Hospital Pharmacy - July/August 2017 - 470
Hospital Pharmacy - July/August 2017 - International Mentoring Programs: Leadership Opportunities to Enhance Worldwide Pharmacy Practice
Hospital Pharmacy - July/August 2017 - 472
Hospital Pharmacy - July/August 2017 - 473
Hospital Pharmacy - July/August 2017 - 474
Hospital Pharmacy - July/August 2017 - 475
Hospital Pharmacy - July/August 2017 - 476
Hospital Pharmacy - July/August 2017 - 477
Hospital Pharmacy - July/August 2017 - Compounded Apixaban Suspensions for Enteral Feeding Tubes
Hospital Pharmacy - July/August 2017 - 479
Hospital Pharmacy - July/August 2017 - 480
Hospital Pharmacy - July/August 2017 - 481
Hospital Pharmacy - July/August 2017 - 482
Hospital Pharmacy - July/August 2017 - Impact of Developing Adult Ketamine Order Panels for the Emergency Department
Hospital Pharmacy - July/August 2017 - 484
Hospital Pharmacy - July/August 2017 - 485
Hospital Pharmacy - July/August 2017 - 486
Hospital Pharmacy - July/August 2017 - 487
Hospital Pharmacy - July/August 2017 - Critical Appraisal of Biomedical Literature With a Succinct Journal Club Template: The ROOTs Format
Hospital Pharmacy - July/August 2017 - 489
Hospital Pharmacy - July/August 2017 - 490
Hospital Pharmacy - July/August 2017 - 491
Hospital Pharmacy - July/August 2017 - 492
Hospital Pharmacy - July/August 2017 - 493
Hospital Pharmacy - July/August 2017 - 494
Hospital Pharmacy - July/August 2017 - 495
Hospital Pharmacy - July/August 2017 - Effect of a Rivaroxaban Patient Assistance Kit (R-PAK) for Patients Discharged With Rivaroxaban: A Randomized Controlled Trial
Hospital Pharmacy - July/August 2017 - 497
Hospital Pharmacy - July/August 2017 - 498
Hospital Pharmacy - July/August 2017 - 499
Hospital Pharmacy - July/August 2017 - 500
Hospital Pharmacy - July/August 2017 - 501
Hospital Pharmacy - July/August 2017 - Examining the Use of Sodium Nitroprusside in Coronary Artery Bypass Grafting: Is the Benefit Worth the Cost?
Hospital Pharmacy - July/August 2017 - 503
Hospital Pharmacy - July/August 2017 - 504
Hospital Pharmacy - July/August 2017 - 505
Hospital Pharmacy - July/August 2017 - 506
Hospital Pharmacy - July/August 2017 - 507
Hospital Pharmacy - July/August 2017 - Successful Implementation of an Antimicrobial Stewardship Program at an Academic Medical Center
Hospital Pharmacy - July/August 2017 - 509
Hospital Pharmacy - July/August 2017 - 510
Hospital Pharmacy - July/August 2017 - 511
Hospital Pharmacy - July/August 2017 - 512
Hospital Pharmacy - July/August 2017 - 513
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