53
Treating Opioid Induced Constipation:Integral to Cancer Pain Management
Charles E. Argoff, MD Professor of NeurologyAlbany Medical College
Director, Comprehensive Pain ProgramAlbany Medical Center
Albany, New York
Overview
• Cancer-related pain (CRP) is a burdensome symptom with the potential to negatively impact quality-
of-life (QoL) for patients and their families.
• While effective, opioids are commonly associated with opioid-induced constipation (OIC), an adverse
event that is well-known to physicians and especially, to oncology advanced practitioners.
• OIC is often unrecognized, under assessed, and ineffectively managed, and may compromise the
effectiveness of the patient’s comprehensive treatment plan, and has been reported to interfere with
pain management, increase healthcare costs, decrease work productivity and daily activities, and
significantly affect QoL.
• The National Comprehensive Cancer Network (NCCN) recognizes the burden of OIC to the patient
and advises in their Adult Cancer Pain guidelines that “patients taking daily opioids almost always
require agents for the management of constipation” and that “prevention of expected analgesic
effects, especially constipation in the setting of opioid use, is key for effective pain management”.
• Thus, clinicians, physicians and oncology advanced practitioners, need to be aware that the
appropriate use of opioids, as well as assessment and management of OIC, are important strategies
for pain management and establishing maximum function for cancer patients.
• This CME/CNE symposium features a multi-disciplinary faculty presenting insights and experience to
guide clinicians collaboratively through the challenges and opportunities of managing OIC in cancer
patients.
Learning Objectives
• Summarize current NCCN guidelines for opiate use in chronic
malignant pain
• Identify how opioid analgesia affects the GI tract and creates risk for
OIC
• Review the epidemiology, evaluation & clinical impact of OIC
• Make recommendations for pharmacologic and nonpharmacologic
strategies to managing OIC
• Assess current pharmacologic treatment in managing OIC
• Provide care and collaborative decision making, as part of a multi-
disciplinary team, including oncology advanced practitioners and
clinical nurse specialists, in managing patients with OIC employing a
multimodal range of non-pharmacological and pharmacological
approaches
Sources: Fine PG, et al. J Support Oncol. 2004;2(suppl 4):5-22. Portenoy RK, et al. In: Lowinson JH, et al, eds. Substance Abuse: A Comprehensive Textbook. 4th ed. Philadelphia, PA: Lippincott, Williams & Wilkins; 2005:863-903.
Multimodal Therapeutic
Strategies for Pain and
Associated Disability
Pharmaco-therapy
Opioids, Nonopioids,
Adjuvant analgesicsPhysical
Medicine and Rehabilitation
Assistive devices, Electrotherapy
Goal: Define Most Appropriate Treatment Regimen
For Each Person With Cancer Pain, Which Could
Include Opioids
Interventional Approaches
Injections, Neurostimulation
Lifestyle Change
Exercise, Weight Loss
Psychological Support
Psychotherapy, Group Support
Complementary Alternative
Medicine
Massage, Supplements
Starting Opioids — Patient Education and Informed Consent
Chou R, et al. J Pain. 2009;10:113-130.
BEFORE starting a trial of
opioid therapy, benefits/risks,
alternatives to opioid therapy and
patient concerns should be
discussed with the patient and
informed consent obtained.
Hyperalgesia
Endocrine effects
Constipation
Nausea
Vomiting
Sweating
Pruritus
Respiratory depression &
death
Opioid
Adverse
Effects
NCCN Principles of Management of Opioid AEs
• AEs to opioids are common, should be anticipated, and should be
managed aggressively
• Patient and family/caregiver education is essential for successful
anticipation and management of pain and opioid AEs
• Recognize that pain is rarely treated in isolation in cancer and AEs
also may be from other treatments or the cancer itself
• Opioid AEs generally improve over time, except with constipation.
Maximize non-opioid and nonpharmacologic interventions to limit
opioid dose and treat AEs. If AEs persist, consider opioid rotation
• Multisystem assessment is necessary
• Information from patient and family/caregiver about AEs is essential for
appropriate opioid dose adjustment and treatment of AEs
Shaw et al. NCCN Clinical Practice Guidelines in Adult Cancer Pain. V1. 2018.
• Constipation is common among patients taking opioids1
– 40%–90% have constipation and other gastrointestinal adverse effects,
which can adversely affect adherence to pain medication regimens and
quality of life1-5
• Unlike other opioid-related adverse effects, OIC is not dose-dependent
nor does it resolve over time1,5
• Many patients fail to respond to conventional stool softeners and
laxatives1
• FDA-approved therapies for OIC include PAMORAs (methylnaltrexone,
naloxegol and naldemedine) and lubiprostone, a chloride channel
agonist6
– Naloxone is included with oxycodone in a combination product to block
OIC6,7
Opioid-Induced Constipation
Abbreviations: OIC, opioid-induced constipation; PAMORA, peripherally acting mu-opioid receptor antagonist.
1. Bell TJ, et al. Pain Med. 2009;10:35-42. 2. Chey WD, et al. N Engl J Med. 2014;370:2387-2396. 3. Holzer P. Therapy. 2008; 5:531–543. 4. Kalso
E, et al. Pain. 2004;112:372-380. 5. Tuteja AK, et al. Neurogastroenterol Motil. 2010;22:424-430. 6. Nelson AD, et al. Therap Adv Gastroenterol.
2015;8:206-220. 7. Smith K, et al. Expert Opin Investig Drugs. 2011;20:427-439.
Reproduced with permission. Kalso E et al. Pain. 2004;112:372-380.
The “Cost” of OIC
• 32% loss of productivity per week
• Decreased QOL
• Increased patient anxiety
• Reduction of opioids
• Fear of “the discussion”
Pergolizzi, J. Pain Medicine New. Opioid Induced Constipation: Treating the Patient Holistically. Dec 2015. 25-35.
Personal Definition of Constipation
• Fewer bowel movements from “the norm”
• Discomfort or difficulty with defecation
• 80 year old’s definition vs 40 year old’s
definition
ROME Criteria For Constipation >/2 for 3 months
– Straining >/25% of the time
– Hard stools >/25% of the time
– Incomplete evacuation >/25% of the time
– <3 bowel movements per week
Bristol Stool Chart
Opioid-induced Constipation
• Pathophysiology of constipation
• Main types of opioid receptors and their
main actions
• Pharmacological effects of µ-opioid
agonists on motility and secretion
Opioids: Visceral Anti-Nociception and Gastrointestinal Effects
CNS
PNS
PAIN ,
Analgesia
Respiratory
depression
Dependence
Constipation
MOTILITY: ,
SECRETION:
All 3 classes
decrease release
of excitatory
neurotransmitters
such as Ach and
substance P
through inhibition
of calcium
channels and
decreased cAMP
and protein kinase
A (PKA) activity
[Galligan et al.,
2014].
Reproduced with permission. De Schepper HU, Cremonini F, Park M-I, Camilleri M: Opioids and the gut: pharmacology and current clinical experience. Neurogastroenterology and Motility 16:383-394, 2004
Pharmacological GI Effects of µ-Opioids
Reproduced with permission. De Schepper et al Neurogastroenterol Motil (2004) 16, 1–12.
Site Pharmacological Effect Clinical Effect
Lower esophageal
sphincter
Inhibition LES relaxation, “achalasia”
motility pattern
achalasia-like picture
Gastroduodenum Inhibition gastric emptying
Increased pyloric tone
Increased gastric acid secretion
Increased duodenal motility (MMC) followed
by quiescence
Anorexia
Nausea, Emesis
Gall Bladder Contraction,
Spasm sphincter of Oddi
Decreased secretion
Biliary pain
Delayed digestion
Small Bowel Increased tone/segmentation
Prolonged transit time
Increased absorption, decreased secretion
Delayed digestion;
Hard stool, Constipation
Colon Hard stool, Constipation
Bloating, Distension
Spasm, Cramps, Pain
Anorectum Decrease rectal sensitivity
Increased resting (IAS) sphincter tone
Incomplete evacuation,
Straining constipation
Kaufman PN. Krevsky B. et al . Gastro 94:1351-6, 1988
Retardation of Colonic Transit by Morphine
Common OTC OptionsNonspecific for the underlying cause
• Stool softeners
• Stimulant laxatives
• Enemas
• Suppositories
Laxatives: Emollient and Bulk Emollient Laxatives Bulk Forming Laxatives
MOA Stool softener
Allow water and fat to penetrate the fecal
mass
Interesting chemical pearl: Docusate
sodium causes foaming and spreading of
water. Assists in putting out fires by water.
Slow onset of action (24 to 48 hours)
Preferred agents (effective with few AEs)
General Concepts
- Not absorbed by the intestines
- Attracts large amounts of water into the colon
• Increasing viscosity
• Softer stool
• Bulkier stool
• Stimulates the constriction
of intestinal smooth muscles
Recommended fluid intake
- Use with >1.5 liters/day non-caffeinated fluid
Precautions Docusate enhances intestinal mineral oil
absorption
Do not use docusate with mineral oil
preparations
May also increase absorption of other
medications
Adverse effects
-Poorly tolerated in atonic colon (e.g. Megacolon)
-Bloating is common in larger doses initially
-Reduced by slowly increasing fiber intake
-Bloating
Drug interactions
-May interfere with absorption of medications
-Do not take medications at the same time as
psyllium
Examples: Carbamazepine, Lithium
Gastroenterology: Pharmacology Chapter in Family Practice Notebook. Constipation Chapter.
http://www.fpnotebook.com/gi/Constipation/index.htm.
Laxatives: Emollient and Bulk (cont.)
Emollient Laxatives Bulk Forming Laxatives
Dosing Docusate Sodium:
Adult (200-400mg per day)
Pediatric
Age <3 years: 10-40 mg per dose
Age 3-6 years: 20-60 mg per dose
Docusate Calcium:
Adult: 240mg PO daily
Child: 50-150mg PO daily
Mineral Oil
Oral:
Administer in juice
Co-administer multivitamin daily if used
chronically
Adult: 5-45mL PO QHS
Suppository:
One suppository (adult or pediatric) PR prn
Indicated for constipation in infants
Psyllium (Metamucil): 10 grams per day
-Dose: 1-2 tsp in 8 ounces of water or juice PO
TID
Methylcellulose (Citrucel): 6 grams per day
-Dose: 2 grams in 8 ounces liquid PO TID
Calcium polycarbophil (Fibercon)
-Synthetic bulk agent containing polyacrylic acid
- Dose: Two 625 mg tablets PO TID
Dietary sources with as much fiber (lower cost)
Wheat bran, oat bran or all-bran cereal, beans
(lima, navy, kidney and baked)
Gastroenterology: Pharmacology Chapter in Family Practice Notebook. Constipation Chapter.
http://www.fpnotebook.com/gi/Constipation/index.htm.
Osmotic LaxativesPoorly absorbed
saccharides
(Lactulose,
Sorbitol)
Magnesium
Laxatives
Sodium
bisphosphate
(Phospho-Soda)
Polyethylene
glycol lavage
solution
(GoLytely)
General Converts ammonia
to unabsorbed
ammonium
Poorly absorbed
(may be used in
renal failure)
Saline osmotic
Relieves
occasional
constipation by
drawing water into
the intestine,
leading to a bowel
movement
Monobasic sodium
phosphate
monohydrate and
dibasic sodium
phosphate
heptahydrate
Draws fluid into
bowel
PEG osmotic
Attracts water into
the colon to ease,
hydrate, and soften
stool to increase
the frequency of
bowel movements
Indications Hepatic
encephalopathy
Constipation
Constipation Constipation Constipation
Precautions/
Complications
Produces diarrhea
Alters bowel flora
Complications
-Hypermagnesemia
(in patients with
renal failure)
-Hypocalcemia
(phosphate
overdose)
Complications
Acute phosphate
nephropathy
-calcium-phosphate
crystals in the renal
tubules
- permanent kidney
dysfunction
When using PEG
as laxative, do not
give for >1 week
Gastroenterology: Pharmacology Chapter in Family Practice Notebook. Constipation Chapter.
http://www.fpnotebook.com/gi/Constipation/index.htm.
Osmotic Laxatives (cont.)Poorly absorbed
saccharides (Lactulose,
Sorbitol)
Magnesium
Laxatives
Sodium
bisphosphate
(Phospho-Soda)
Polyethylene
glycol lavage
solution
(GoLytely)
Notes Lactulose is easier to
administer to young children
-May cause abdominal
cramping and flatus
-Onset of action within 24-48
hours
Sorbitol 70% less expensive
than lactulose , sweet taste
Contraindicated in
renal failure
Magnesium hydroxide
generally produces a
bowel movement in ½
to 6 hours
<2 years: PR safety &
efficacy not
established
<5 years: PO safety &
efficacy not
established
Does not cause harsh
side effects such as
gas, bloating,
cramping, and sudden
urgency
Generally produces a
bowel movement in 1-
3 days. Many get relief
in 1 day
Dosing for
constipation
Lactulose
-Adults: 15-60mL PO daily
-Child (10 mg/15 mL): 1-3
cc/Kg/day divided QD-BID
Sorbitol
-Adult: 15-60 mL PO daily
-Child: 1-3 mL/Kg/day divided
twice daily
Magnesium hydroxide
(400 mg/5 mL): 30-60
mL/day PO at bedtime
or in divided doses
Magnesium hydroxide
(800 mg/5 mL): 15-30
mL/day PO at bedtime
or in divided doses
Chewable tablet: 8
tablets/day PO at
bedtime or in divided
doses
PR: Administer
contents of 4.5 oz
enema rectally as
single dose
PO: Administer 15 mL
as single dose daily
not to exceed 45
mL/day
17 g in 4-8 oz water
PO once daily for ≤1
week
Gastroenterology: Pharmacology Chapter in Family Practice Notebook. Constipation Chapter.
http://www.fpnotebook.com/gi/Constipation/index.htm.
Stimulant Laxatives• Abuse potential• Least favorable for chronic use• Other laxative types preferred over these
Anthraquinone Laxative Diphenylmethane Laxative
Examples Cascara sagrada extract (Casanthranol)
Senna extract (Senokot)
Bisacodyl (Dulcolax)
Phenolphthalein (OTC, Correctol, Ex-Lax)
-High risk of overuse (removed from OTC
market)
-Associated with Stevens-Johnson Syndrome
Onset of
Action
6-12 hrs 6-12 hrs (PO); 1 hr (PR)
Dosing Cascara (casanthranol) extract
Dose: 325mg PO QHS
Previous branded Peri-Colace (DOSS +
cascara)
Senna extract
Two to four 8.6mg tablets PO bid
Child: Senna Syrup (8.6 grams per 5mL)
Age 2-6 years: 2.5 to 7.5mL per day divided
bid
Age 6-12 years: 5 to 15mL per day divided bid
Combo: docusate-S (Senokot-S)
Bisacodyl (Dulcolax)
-Adult: 5-10 mg PO/PR per day (PO may be
repeated)
-Child (6-12 years old): 5 mg PO/PR
Phenolphthalein (OTC Preparations:
Correctol, Ex-Lax): 100 mg tablets, 1-2 PO
q8H
Gastroenterology: Pharmacology Chapter in Family Practice Notebook. Constipation Chapter.
http://www.fpnotebook.com/gi/Constipation/index.htm.
Long-term OTC Laxative Use
• Colonic denervation and atony (cathartic colon)
– Associated with anthraquinone laxatives
• Decreased motility of right colon
• Results from myenteric plexus injury
• Electrolyte and nutritional disturbance
– Hypokalemia
– Sodium overload
– Protein-losing enteropathy
• Melanosis coli
– Benign darkening of colonic mucosa
– Macrophage deposition in lamina propria
Gastroenterology: Pharmacology Chapter in Family Practice Notebook. Constipation Chapter.
http://www.fpnotebook.com/gi/Constipation/index.htm.
Newer Laxation Therapies
• OIC has a specific cause and effect
• Targeted reversal avoids issues associated with OTCs
• Newer laxation therapies
– ClC2 (Chloride Channel Protein 2)
• ClC2 is involved with chloride ion transport
– Lubiprostone
» FDA approved for OIC in CNCP and Chronic Idiopathic
Constipation
– PAMORAs
• Peripherally acting mu opioid receptor antagonists
Gudin J, Fudin J, Laitman A, Kominek C. Opioid-Induced Constipation: New and Emerging Therapies.
Practical Pain Management. 2015 Dec; 15(10); 38-45.
For access to the OIC Consensus Recommendations on Initiating Prescription Therapies featured in Pain Medicine, please visit:
http://onlinelibrary.wiley.com/doi/10.1111/pme.12937/full
New Consensus Guidelines
• The consensus guidelines are intended NOT to provide specific treatment recommendations for a specific patient BUT to consider what factors can be considered to help select whether or not OIC prescription medication is warranted
• Prior treatment guidelines have emphasized the potential of OIC development with long-term opioid use
• Prior treatment guidelines have emphasized initiation of a prophylactic bowel regimen that may involve increased fluid and fiber intake, stool softeners and/or laxatives- these recommendations ARE NOT based upon the results of randomized, placebo-controlled studies of these treatments
Argoff et al Consensus recommendations on initiating prescription therapies for opioid-induced constipation
Pain Medicine 2015;16:2324-2337
New Consensus Guidelines (cont’d.)
• The use of enemas/rectal suppositories and/or manual evacuation, modalities not infrequently recommended are associated with invasiveness, discomfort, embarrassment as well as increased health care burden
• Complications of the above include pain, rectal bleeding, and bowel perforation
• One study completed in a palliative care setting demonstrated that the total health care staff time spent on these procedures was greater than time spent on most other tasks related to constipation management , e.g., oral laxatives, discussions of bowel care
Argoff et al Consensus recommendations on initiating prescription therapies for opioid-induced constipation
Pain Medicine 2015;16:2324-2337
Making the Decision to Use A Prescription Medication for OIC
• The consensus panel preferred the use of a simple and easy-to-use method to make the diagnosis of OIC- practicality was very important to the panel
• After reviewing several tools including the Bowel Function Index (BFI), the PAC-SYM and the PAC-QOL, the panel came to the consensus that the BFI captures the most relevant symptoms for OIC
• The panel recognized that other options could be considered; however, these would require validation studies and might be too cumbersome for universal clinical application
Argoff et al Consensus recommendations on initiating prescription therapies for opioid-induced constipation
Pain Medicine 2015;16:2324-2337
Reproduced with permission. Argoff et al Consensus recommendations on initiating prescription therapies for
opioid-induced constipation Pain Medicine 2015;16:2324-2337
Making the Decision to Use A Prescription Medication for OIC (cont’d)
• A score of ≥ 30 points on the BFI was selected by the panel on the basis of a study conducted by Uberall et al. that identified a reference range of 0-28.8 for most (95%) non-constipated patients with chronic pain
• The selected threshold was also chosen based upon the belief that people experiencing OIC should NOT be denied consideration for further therapy if their BFI score surpasses the range of non-constipation and if they have shown inadequate response(s) to first-line options
Argoff et al Consensus recommendations on initiating prescription therapies for opioid-induced constipation Pain Medicine 2015;16:2324-
2337.
Uberall MA, et al. The Bowel Function Index for evaluating constipation in pain patients: Definition of a reference range for a non-
constipated population of pain patients J Int Med Res 2011;39:41-50.
Sites of Action of Novel Pharmacotherapies
Credit: Yang H and Ma T. Front. Pharmacol., 30 June 2017 | https://doi.org/10.3389/fphar.2017.00418
Summary of FDA-Approved Agents for OICLubiprostone Methylnaltrexone Naldemedine Naloxegol
Class Chloride
channel
activator
PAMORA PAMORA PAMORA
Indication OIC in CNCP
Chronic
idiopathic
constipation in
adults and
treatment of IBS
with
constipation in
women ≥ 18
years of age
Original Indication:
treatment of OIC in pts
with advanced illness
receiving palliative
care, when response to
laxative therapy has not
been sufficient. Also
available as oral
formulation.
Available as SC where
dosing is dependent on
indication & weight as
well as oral preparation,
indication: to treat OIC
in CNCP pts
OIC in patients
with CNCP
including
patients with
chronic pain
related to prior
cancer or its
treatment who
do not require
frequent opioid
dosage
escalation
OIC in patients
with CNCP
including patients
with chronic pain
related to prior
cancer or its
treatment who do
not require
frequent opioid
dosage
escalation
Route of
Administration
Oral capsule Subcutaneous injection Oral tablet Oral tablet
https://general.takedapharm.com/amitizapi; http://www.relistor.com/hcp; http://www.movantikhcp.com; https://symproic.com/hcp
Summary of FDA-Approved Agents for OIC (cont.)Lubiprostone Methylnaltrexone Naldemedine Naloxegol
Dosage in OIC 24 μg BID with food
and water
Chronic noncancer pain: 12
mg QD
Advanced illness: 8 mg every
other day (patients 38 to <62
kg); 12 mg every other day
(patients 62–114 kg); 0.15
mg/kg every other day for
patients outside these weight
ranges
0.2 mg QD 25 mg QD
12.5 mg QD in
patients intolerant to
25 mg
12.5 mg QD in patients
with renal impairment
(creatinine clearance
<60 mL/min); can be
increased to 25 mg
once daily if tolerated;
monitor for adverse
reactions
Time to
Laxation
24 to ≥ 48 h 4 - ≥24 h Within 24 h 6-12 h (25 mg)
20 h (12.5 mg)
Adverse Effects >4% incidence in
OIC are nausea
and diarrhea
≥5% in clinical trials and at
an incidence greater than
placebo are abdominal
pain, flatulence, nausea,
dizziness , and diarrhea
≥5% of patients in
clinical trials and an
incidence greater
than placebo:
abdominal pain,
diarrhea
≥3% of patients in
clinical trials and a
an incidence greater
than placebo:
abdominal pain,
diarrhea, nausea,
flatulence, vomiting,
headache, and
hyperhidrosis
https://general.takedapharm.com/amitizapi; http://www.relistor.com/hcp; http://www.movantikhcp.com; https://symproic.com/hcp
Summary: OIC in Cancer Patients
• OIC is a common occurrence in opioid‐treated cancer patients
• OIC imposes a substantial burden by:
– Decreasing QOL
– Reducing work productivity
– Impairing effectiveness of pain management
– Leading to clinically significant physical sequelae such as those related to bowel
obstruction and fecal impaction
• OIC in cancer patients should be anticipated and managed aggressively
• BFI is a simple assessment tool with a validated threshold of clinically
significant constipation
• Prescription treatments for opioid‐induced constipation should be
considered for patients who have a BFI score of ≥30 points and an
inadequate response to first‐line interventions
Argoff et al. Pain Medicine. 2015;16:2324-2337.
Shaw et al. NCCN Clinical Practice Guidelines in Adult Cancer Pain. V1. 2018.
Clinical Challenges in Multidisciplinary Management of Opioid-Induced Constipation
in Cancer-Related Pain
Barton T. Bobb, NPMassey’s Thomas Palliative Care Services
Department of Internal Medicine
Virginia Commonwealth University Health System
Richmond, Virginia
Learning Objectives
• Recognize the need for oncology advanced practitioners in the multidisciplinary treatment approach to managing OIC
• Define clinical impact of OIC
• Incorporate the guidelines for management of OIC in chronic pain related to prior cancer or its treatment
• Assess the potential need for prescription medication management
• Apply learning gains to real-life cases of OIC
Clinical Overview of OIC
• Definition – change in baseline bowel habits after starting
opioids:
– Decreased frequency, increased straining, sensation of incomplete
evacuation, and harder consistency
• Reported to occur in 50% to 95% of cancer populations,
especially those taking opioids [Cimprich 1985; McShane
and McLane 1985; Smith 2001]
• Potential burden
• Reduced QOL - as opioid dose is missed/decreased analgesia
and QOL are therefore reduced
Prichard D and Bharucha A. Int J Palliat Nurs. 2015;21(6):272,274-80.
Challenges to Management: Multifactorial Causes to Constipation in Cancer Patients
• Constipation is common in cancer patients undergoing palliative care
• Common causes include:
– Opioid use
– The cancer itself, which can obstruct the bowel, affect the autonomic
nervous system, or cause spinal cord compression
– Disease effects from illness such as dehydration, spinal cord compression,
immobility, electrolyte abnormalities (i.e., hypercalcemia) or changes in
normal bowel habits
– Previous laxative abuse
– Cancer therapies such as the vinca alkaloids, thalidomide
– Other interventions for symptom management such as TCAs, 5-HT3
antagonists
Woolery M et al. Clin J of Onc Nursing. 2008;12(2):317-337.
Wilkes G, Barton-Burke M. Oncology Drug Nursing Handbook. 2006.
OIC Management Requires Multidisciplinary Approach
• Multidisciplinary team approach is important in preventing
and managing OIC
– Physicians, nurses, oncology advanced practitioners, physician assistants,
pharmacists
• Interdisciplinary collaborative approach is integral to
effectively managing pain and OIC
• Oncology advanced practice nurses have an important role
in identifying and treating OIC since they are in regular
contact with patients and are also ideally positioned to
identify patients at high risk for OIC, ruling out other causes
of chronic constipation.
OIC Management Requires Multidisciplinary Approach (cont.)
• A detailed patient history should be obtained that includes diet, physical
activity, and a review of all medications the patient is currently taking. A
thorough patient examination should be conducted and accompanying
signs and symptoms such nausea, vomiting or abdominal pain/distention
should be noted. Patient bowel habits as well as the quantity and quality
of stools should be monitored.
• Clinicians should also provide patient education to ensure that lifestyle
changes such as increased fluid intake and physical activity are
implemented. Laxatives should be prescribed prophylactically in
patients at high risk for OIC.
• Important to ensuring patient compliance with treatments designed to
alleviate OIC as well as monitoring the effectiveness of such therapies
once they are instituted.
QoL Becomes Paramount Concern in Palliative Care or End-of-life Care
• In a study of 178 hospice patients with cancer, a stronger negative
relationship was found between constipation and quality of life (r =
−0.38; P = .000) than between pain and quality of life (r = −0.20; P =
.01) [McMillan and Small 2002]
• In a study of 502 hospice and palliative care nurses, 109 end-stage
cancer pts, and 200 caregivers [Lentz and McMillan 2010]:
– 82% of patients reported experiencing pain on a daily basis
– Up to 25% of patients reported OIC as a challenge to maintaining QoL
– Better control of OIC is important to pain relief (patients-80%, nurses-95%)
McMillan SC, Small B. Oncol Nurs Forum. 2002;29(10):1421-1428.
Lentz J, McMillan SC. J Hosp & Pall Nursing. 2010;12(1):29-39.
Zdanowicz M. Adv Practice Nurs 1:118.
Guidelines for Basic Management of OIC in Cancer Patients
• NCCN Guideline on Adult Cancer Pain,
section on Management of Opioid Adverse
Effects – Constipation
• Opioid-Induced Constipation and Bowel
Dysfunction: A Clinical Guideline (Mueller-
Lissner et al, Pain Medicine, 2017)
Shaw et al. NCCN Clinical Practice Guidelines in Adult Cancer Pain. V1. 2018.
Mueller-Lissner et al. Pain Med. 2017;18(10):1837-1863.
Basic Principles Derived from NCCN Guideline
Patients taking daily opioids almost always require agents for management
of constipation
• Prophylaxis: patient/family education, non-pharmacologic (e.g., fluid &
fiber intake, exercise), stimulant laxatives
• Initial onset of OIC: Assess, r/o obstruction, laxative titration as needed
• Persistent OIC: Re-evaluate (e.g., BFI), r/o obstruction/impaction,
consider other laxative agent(s) & possibly Rx
– Oral methylnaltrexone
– Naloxegol
Shaw et al. NCCN Clinical Practice Guidelines in Adult Cancer Pain. V1. 2018
Assessment of Potential Need For Prescription Medication Management
• Evaluate prior/concurrent bowel prophylaxis
treatment regimen
• BFI, Bowel Function Index, tool w/ 3 items,
each rated 0-100:
– Ease of defecation, sensation of incomplete
bowel evacuation, overall rating of constipation
– Average of 3 items = final score, consideration
of prescription therapy is at ≥ 30 Argoff C et al. Consensus recommendations on initiating prescription therapies for opioid-induced constipation Pain
Medicine 2015;16:2324-2337.
Challenges in the Management of OIC
• Cost of medications (e.g., Rx co-pay and OTC)
• Patient compliance
• Non-physiologic factors can impact pain
perception and lead to higher opioid use - e.g.,
chemical coping, psychological/existential
distress, or substance abuse
• Lack of insurance coverage/unavailability on
formulary
Case Study #1: Metastatic Colon Cancer, Chronic OIC With Post-op Ileus
• 54 yo man with met colon CA, chronic abdominal
pain and chronic OIC (on polyethylene glycol,
dandelion tea, senna)
• Hx of anxiety, OCD, situational depression
• OR: R hemi-colectomy, unable to resect liver
• Epidural placement ineffective – removed POD
#2, pt refused replacement
• Develops post-op ileus – requires NG tube
Case Study #1 (cont.)
• Opioid rotations ineffective, no response to
methylnaltrexone 12 mg SQ x2 on POD #5
• Methadone (20 mg PO q8 after self-escalation)
stopped due to QTc prolongation (520 ms)
• Other complications include urinary retention, R
hydronephrosis, R flank pain w/ severe exac
• 1st small BM on POD #9, NG tube removed POD
#11
• Challenges as consultants
Case Study #2: Metastatic Pseudomyogenic Hemangioendothelioma
• 29 yo man with metastatic pseudomyogenic
hemangioendothelioma, chronic back pain
• Inconsistent compliance with F/U
• Self-escalates oxycodone IR regularly (60
mg instead of 30 mg q6h prn, occ. 90 mg),
even methadone (10 mg PO q8h) added
• Admitted w/ new onset abd pain, distension,
emesis x1, BM “pellets” day prior to admit
Case Study #2 (cont.): Metastatic Pseudomyogenic Hemangioendothelioma
• Home bowel regimen: polyethylene glycol
17gm daily prn, 2 senna bid, compliant?
• KUB shows significant stool burden, prior
abd CT done 3 weeks ago had also shown
some stool burden
• Pt receives 12 mg SQ methylnaltrexone
then 300 ml mag citrate a few hours later
during the night after admission – BM x 2
