Clinical Review & Education
Teachable Moment
Preventing Opioid-Induced Constipation
A Teachable Moment
Srishti Saha, MD; Piyush Nathani, MD; Arjun Gupta, MD
Story From the Front Lines
A man in his 70s with advanced prostate cancer diagnosed 6 months
previously presented with progressive disease, as demonstrated by an
increasing prostate-specific antigen level and worsening restaging
scans,todiscussnewtreatmentoptions.Hereportedgeneralizedbone
pain (6 out of 10 in intensity, worse with activity). His Eastern Coop-
erative Oncology Group performance status was 1 (scale, 0-5, with
0 = fully active and 5 = dead). Prior imaging showed no fractures. His
oncologist discussed initiating therapy with oral abiraterone (CYP17A1
inhibitor, reducing androgen production). The oncologist also pre-
scribed as-needed oxycodone instant-release 5-mg tablets, which he
started taking 1 to 2 times a day.
Ten days later, the patient presented to the emergency
department with abdominal pain. He reported no bowel move-
ments for 6 days (baseline 1-2 times/d). The abdominal pain was
diffuse, intermittent, and crampy. Abdominal examination noted
mild, nonfocal tenderness, and rectal examination noted hard,
brownish stool without blood or mucus. Laboratory testing
revealed no metabolic derangements, and abdominal radiogra-
phy demonstrated significant stool burden. He was admitted for
treatment of constipation and treated aggressively with hydra-
tion, disimpaction, stimulant laxatives, and a water enema. He
was discharged 3 days later, with scheduled sennosides. At a clinic
appointment 3 weeks later, he was doing well and was having 1 to
2 soft bowel movements daily.
Teachable Moment
Opioid-induced constipation (OIC) is the most common adverse ef-
fect of opioid therapy and occurs in 40% to 80% of patients receiv-
ing opioids.1 Approximately 9 million to 12 million people in the US
(4%-5% of the adult population) receive long-term opioid therapy for
chronic pain, placing a substantial population at risk for OIC. Impor-
tantly, even otherwise healthy individuals who receive short-term
low-dose opioid therapy can develop OIC, because OIC development
is somewhat independent of opioid dose/route, and recipients do not
develop tolerance. Opioid-induced constipation manifests as harden-
ing of stool, decreased stool frequency, straining during defecation, or
incomplete evacuation. Although opioids directly cause constipa-
tion, associated patient factors tied to opioid use (eg, pain and immo-
bility with injury, metabolic abnormalities and bowel obstruction with
cancer) compound OIC risk.
Opioid-induced constipation is beyond an inconvenience and
significantly affects quality of life and health care resource utiliza-
tion. In one study, researchers surveyed 322 patients receiving daily
opioid treatment for predominantly musculoskeletal conditions using
the Patient Reports of Opioid-Related Bothersome Effects (PROBE)-1
survey.2 Common symptoms were constipation (81%) and strain-
ing (58%), and OIC was associated with worse well-being. One-
third of patients decreased opioid use to counter OIC, and almost
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all such patients reported worsening pain. In another retrospective
study of patients with cancer and OIC, 10% had 1 or more emer-
gency department visits, and 35% had 1 or more clinic visits related
to OIC in the first year of opioid therapy.3
Opioid-induced constipation is preventable, and the best treat-
ment remains prevention. All patients initiating opioid therapy should
be counseled regarding the risk of OIC, preventive lifestyle mea-
sures (hydration, physical activity, and scheduled toileting), and the
use of laxatives.4 In one Japanese multi-institutional retrospective
study of inpatients with cancer receiving opioids, OIC developed in
34% of patients who received sennosides or magnesium-based pro-
phylaxis, vs 55% of patients without prophylaxis (hazard ratio, 0.43;
95% CI, 0.30-0.62).4 National Comprehensive Cancer Network
guidelines5 recommend OIC prophylaxis, with either a stimulant (bi-
sacodyl, senna) or osmotic (lactulose, polyethylene glycol) laxa-
tive, for almost all patients initiating opioid therapy. Docusate has
equivocal efficacy and should not be used; when a combination of
sennosides and docusate is effective, sennosides are the active agent.
We recommend prescribing sennosides or polyethylene glycol for
Box. Rules of Thumb to Prevent Opioid-Induced Constipation
(OIC) in Patients Receiving Opioidsa
Step 1
• Counsel all patients regarding OIC.
• Symptoms of OIC include:
• Hard stools
• Straining during defecation
• Incomplete evacuation
• Reduced stool volume and/or frequency
• General nonpharmacologic measures:
• Maintain hydration.
• Engage in physical activity.
• Practice regular toileting habits.
Step 2
• If no preexisting loose stools or diarrhea and plan for opioid
therapy beyond a few days:
• Prescribe pharmacologic prophylaxis: a stimulant or osmotic
laxative (sennosides 8.6 mg, 2 tablets daily, or polyethylene
glycol 17 g once daily).
• Educate patients on laxative use and dose titration.
Step 3
• Monitor symptoms and tailor therapy.
• Goal is to have regular, soft, nonforced bowel movements
(maintain baseline bowel movements, no “one-target-for-all”
approach).
• Increase dose or add another laxative agent if needed.
• Down-titrate or stop laxatives if diarrhea develops. Be mindful
of laxative use when evaluating diarrhea.
a
Specific evidence for these interventions is poor, and it may be challenging
for ill patients to follow these recommendations.
(Reprinted) JAMA Internal Medicine October 2020 Volume 180, Number 10 1371
 Clinical Review & Education Teachable Moment

almost all patients initiating opioid therapy (Box). Laxative dosing
must be titrated, and prescription must be coupled with patient
education.
Rates of prophylactic laxative prescription are unfortunately
low. In a study of more than 100 000 veterans with lung cancer
initiating opioid therapy, 75% received no prophylaxis, and 12%
received only docusate.1 In a national analysis of more than 20 mil-
lion emergency department visits, only 1% of patients discharged
with an opioid prescription received a laxative prescription.6 Intui-
tively, laxative prophylaxis seems more appropriate in patients
with chronic pain (and thus, long-term opioid use) vs acute pain.
We recognize that polypharmacy and an overtreatment cascade
are potential harms of a one-size-fits-all, scheduled, laxative pro-
phylaxis regimen. However, constipation is not just decreased fre-
quency of stools, but also straining and incomplete evacuation. By
the time decreased stool frequency (the usual trigger for reporting
constipation) sets in, most patients have well-established consti-
pation, for which as-needed laxative prophylaxis is less effective.
Established constipation often requires treatment with more inva-
sive rectal-based interventions or newer, more expensive OIC
treatments. Thus, patient education on recognizing OIC (including
early symptoms) and titrating laxatives must accompany opioid
prescriptions, along with strong consideration of prescribing
scheduled laxatives. The patient in this scenario received no edu-
cation or laxative prophylaxis and experienced a preventable
hospitalization.
A first step in engaging clinicians about preventing OIC is this
memorable dictum: The hand that writes the opioid prescription
should be the hand that writes the bowel regimen. Otherwise, that
same hand should be responsible for disimpaction.

ARTICLE INFORMATION
Author Affiliations: Department of Internal
Medicine, University of Texas Southwestern
Medical Center, Dallas (Saha, Nathani); Sidney
Kimmel Comprehensive Cancer Center, Johns
Hopkins University, Baltimore, Maryland (Gupta).
Corresponding Author: Arjun Gupta, MD, Medical
Oncology, Sidney Kimmel Comprehensive Cancer
Center, Johns Hopkins University, Baltimore, MD
21231 (guptaarjun90@gmail.com).
for reviewing earlier versions of the manuscript.
They were not compensated for their work.
REFERENCES
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appropriate laxative prophylaxis for opioid-induced
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Support Care Cancer. 2019;27(2):687-696. doi:10.
1007/s00520-018-4366-z
4. Ishihara M, Ikesue H, Matsunaga H, et al;
Japanese Study Group for the Relief of
Opioid-induced Gastrointestinal Dysfunction.
A multi-institutional study analyzing effect of
prophylactic medication for prevention of
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0b013e318237d626

Published Online: August 24, 2020.
doi:10.1001/jamainternmed.2020.3285
Conflict of Interest Disclosures: Dr Gupta is
supported by a Conquer Cancer, the ASCO
Foundation Young Investigator Award (YIA).
No other disclosures were reported.
Additional Contributions: We thank the patient for
granting permission to publish this information. We
also thank Rab Razzak, MD, Thomas J. Smith, MD,
Sahil Khanna, MBBS, MS, and Deepak Agrawal, MD,
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5. National Comprehensive Cancer Network. NCCN
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Accessed July 22, 2020. https://www.nccn.org/
professionals/physician_gls/pdf/palliative.pdf
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