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Although it's difficult to determine exactly how many patients experience opioid-induced constipation, the large quantities of prescribed opioids in circulation create widespread potential for this bothersome adverse effect.
Although it’s difficult to determine exactly how many patients experience opioid-induced constipation (OIC), the large quantities of prescribed opioids in circulation create widespread potential for this bothersome adverse effect.
OIC is preventable and manageable, but prescribing clinicians often fail to anticipate, identify, or treat it. For that reason, pharmacists should know the following things about OIC:
1. OIC Isn’t the Same as Regular Constipation
Many clinicians are surprised to learn that OIC is physiologically different than functional constipation. Regular constipation usually occurs subsequent to poor dietary choices, inactivity, or dehydration, while OIC follows interrupted receptor activity.
OIC develops when exogenous opioids create several changes—slower motility, altered fluid balance, sluggish mental status (leading to hampered mobility), and increased luminal fluid absorption—when opioid agonists bind to mu-opioid receptors in the enteric nervous system. Notably, this may cause abdominal pain that can rival the pain caused by the conditions for which opioids are prescribed.
2. Certain OTC Products Can Serve as OIC Prophylaxis
At PAINWeek 2016, pain expert Jeffrey Gudin, MD, advised that an OTC stool softener and a stimulant laxative— particularly docusate sodium and a senna product—should always be coprescribed or codispensed with an opioid to help prevent OIC.
“If someone comes to the pharmacy to fill their opioid prescription, the pharmacist should reflexively say, ‘What are you taking for stool softener and laxative?’ ” Dr. Gudin said. “…The pharmacist can play a role to make sure that at least there’s a regimen in place to address the constipation that comes from opioids.”
In addition to recommending a concomitant stool softener and laxative as prophylaxis, pharmacists can suggest lifestyle interventions, such as increasing fluid intake and dietary fiber consumption. Although bulk-forming laxatives are considered a cornerstone for managing chronic constipation, these fiber supplements should generally be avoided in OIC patients because they’re “not only likely to be ineffective, but they also can result in bowel obstruction,” according to Mary M. Bridgeman, PharmD.
3. If Prophylaxis Doesn’t Work, There Are Pharmacologic Options Available
When traditional laxatives are inadequate, clinicians should consider adding a prescriptive-strength agent specifically indicated for treating OIC. Available agents include the chloride channel activator lubiprostone, the subcutaneously administered methylnaltrexone bromide, and the orally administered naloxogol, which can reverse OIC symptoms in the gut without affecting analgesia or causing withdrawal.
“There aren’t too many places in medicine where we have an antidote or antivenom for a problem, but this is one of them,” Dr. Gudin explained. “This is…a novel class of drug to change an age-old problem of OIC.”
There are also some new agents on the horizon, including serotonin receptor agonists and other formulations of methylnaltrexone.
4. OIC Treatment Options Have Some Drug Interactions and Contraindications
Pharmacists should know that methadone is thought to interfere with the chloride channel receptor that lubiprostone serves to activate, so “it’s not likely that patients with OIC related to methadone use would respond to that particular therapy,” Dr. Bridgeman explained. For that reason, lubiprostone hasn’t been studied in patients on methadone and its effectiveness in this population hasn’t been established.
Meanwhile, naloxogol is contraindicated when strong CYP34A inhibitors are used, and all 3 previously described agents are contraindicated in patients with known or suspected mechanical gastrointestinal obstruction.