Ancillary Effects of Oral Naloxegol (Movantik)

Opioids are the gold standard for postoperative pain management, but they have been shown to
produce uncomfortable side effects such as urinary retention (an inability to completely
empty the bladder), constipation and nausea/vomiting. Clinical evidence demonstrates that
Naloxegol can safely and effectively block these undesirable side effects while maintaining
the painkilling effects of opioids in outpatients suffering from opioid-induced constipation.

Inclusion Criteria:

1. Provision of informed consent prior to any study specific procedures

2. Female or male aged at least 18 years

3. American Society of Anesthesiologists physical status 1-4;

4. Scheduled for elective primary hip or knee surgery under spinal anesthesia;

5. Expected to receive intravenous patient-controlled analgesia (IV PCA)

6. Expected to have significant postoperative pain

7. Negative pregnancy test

Exclusion Criteria:

1. Severe hepatic impairment, with/or twice the upper normal levels of liver enzymes

2. Severe renal impairment, or creatinine level > 2.0

3. History of bladder cancer

4. Patients receiving perioperative regional anesthesia blocks

5. Presence of a sacral nerve stimulator

6. Medications (anticholinergic agents such as antihistamines, phenothiazines,
antidepressants, antipsychotics), conditions or comorbidity causing urinary retention

7. Patient with requirement of urinary catheter insertion before or immediately
post-surgery due to immobility

8. Urinary Tract Infections and other urogenital comorbidity (incontinence,
cysto-ureteric reflux, known bladder retention) or conditions which can cause urinary
retention

9. Severe peptic ulcer disease, diverticular disease, infiltrative gastrointestinal tract
malignancies, or peritoneal metastases

10. Patients with known or suspected disruption of blood brain barrier, which may include
but not limited to: Alzheimer's disease, stroke, poliomyelitis, cerebral palsy,
multiple sclerosis, spinal lesions, and Parkinson's disease

11. Gastrointestinal obstruction/Gastrointestinal perforation

12. Strong CYP3A4 inhibitors (some antibiotics, antifungals, protease inhibitors, and
antidepressants), Strong CYP3A4 inducers, Other opioid antagonists

13. Hypersensitivity to MOVANTIK (naloxegol) or any of its excipients