Opioid-induced Constipation Is More Than a Tolerability Issue

Though constipation as a side effect of opioid therapy is generally considered a tolerability issue that can be treated with over-the-counter laxatives, opioid-induced constipation (OIC) may still lead to serious gastrointestinal (GI) complications. Nevertheless, the incidence and risk of GI events among opioid users with constipation remain unknown.

At the American Pain Society 33rd Annual Scientific Meeting, held April 30, 2014, to May 3, 2014, in Tampa, FL, Laura Wallace, MPH, Rayna K. Matsuno, and Venkatesh Harikrishnan of Purdue Pharma, LP, presented a poster that detailed their efforts to estimate the cumulative frequency and relative risk of GI complications associated with constipation in opioid-treated and non-opioid-treated patients.

For their retrospective cohort study, Wallace and her colleagues relied on healthcare claims data from a database of inpatient and outpatient diagnostic and prescription information on more than 60 million commercially-insured and Medicare patients in the United States. From that population, the researchers included 7.3 million opioid-treated patients and 4.3 million non-opioid-treated patients.

The poster authors stratified the patients by age, sex, and opioid use, and then further grouped the opioid-treated subjects by dose in morphine equivalents and duration of drug use <90 days or ≥90 days. Among those with a diagnosis of constipation that was captured in the healthcare insurance claims data, the investigators looked for serious GI complications, such as intestinal obstruction, rectal prolapse, rectal perforation, rectocle, fecal impaction, hemorrhoids, anal fissure, stercoral ulcer, diverticulosis, and colonic stenosis.

At the conclusion of their study, Wallace, Matsuno, and Harikrishnan determined that “with the exception of hemorrhoids and diverticulosis, GI complications were uncommon, occurring in <1% of patients, but they occurred more often in those with diagnosed constipation.” Additionally, the researchers found “GI complications were more common in patients treated (with opioids) for ≥90 days than in those treated for <90 days; however, these patients also had a higher prevalence of preexisting GI comorbidity at baseline,” such as irritable bowel syndrome (IBS), Crohn’s disease, and ulcerative colitis.

While estimating the occurrence of constipation based on morphine-equivalent opioid dose, the poster authors discovered “the incidence of most complications increased only slightly by dose.”

Irrespective of opioid treatment in general, “patients with diagnosed constipation had higher risk of GI complications than those without this diagnosis,” Wallace and her co-authors wrote. Still, they noted the relative risk and incidence of GI events was higher among opioid-treated patients, although those subjects were also “older, sicker, and on polypharmacy.”

“These data suggest that the incidence of most GI complications is low in the general population, but is substantially higher among patients with diagnosed constipation,” the study authors concluded. However, diagnosed constipation is also infrequent, though they inferred the condition’s scarcity may be related to how it is recorded in claims data, since “it is possible that only more serious cases that require prescription treatments or medical procedures are being captured.”

Regardless of the true prevalence of OIC, Wallace, Matsuno, and Harikrishnan emphasized that their findings suggest “constipation is more than a tolerability issue and needs to be prevented or treated to avoid more serious problems.”