The AGA published updated treatment guidelines for OIC in October of 2018 recommending the use of both lifestyle modifications as well as pharmacologic therapies.8 Prevention is a cornerstone of OIC management. Patient education focused on the potential constipating side effects of opioids at the onset of therapy can help to ensure that constipation is recognized and treated early in an effort to prevent treatment nonadherence, severe symptoms, and eventual fecal impaction or ileus. A bowel regimen can be initiated in patients who require opioids to prevent severe constipation before symptoms develop.12 In addition, clinicians should only prescribe opioids for the shortest timeframe needed to accomplish the clinician-patient agreed-upon goals of treatment.4
Once OIC is diagnosed, regardless of which treatment modality is chosen, it is essential to emphasize the importance of adherence to and consistency with the treatment. Understanding the patient’s baseline bowel movements prior to initiation of opioid therapy will help to identify the development of constipating side effects. This not only allows for easier recognition of OIC, but it also helps set goals for treatment.
Lifestyle modifications. The AGA guidelines recommend the use of nonpharmacologic lifestyle interventions in addition to pharmacologic agents when treating OIC. Lifestyle modifications include such behaviors as increasing fluid intake, implementation of a toilet schedule, taking in adequate fiber, and engaging in regular physical activity.8
Pharmacologic therapy. The AGA guidelines recommend the use of laxatives as first-line agents for OIC due to their general safety, availability, and low cost.8,14 For laxative-refractory OIC, which is defined as persistent constipation despite the scheduled use of 2 laxatives from 2 different classes for at least 2 weeks, the AGA recommends initiating targeted opioid antagonists.8 Four therapies are approved by the US Food and Drug Administration (FDA) for the treatment of mild to moderate OIC: lubiprostone, methylnaltrexone, naloxegol, and naldemedine (Table 1).
Laxatives. Two open-label studies have evaluated the efficacy of laxatives in OIC.15,16 Twycross et al demonstrated a 75% response rate to a stimulant laxative in cancer patients with constipation due to morphine therapy.15 Wirz et al compared the efficacy of polyethylene glycol (PEG), lactulose, and a stimulant laxative in treating OIC, with findings suggesting improvement in symptoms with the use of PEG or a stimulant laxative over lactulose.16 In a randomized control trial comparing the efficacy of PEG or lactulose to placebo for the treatment of OIC, a reduction in constipation symptoms was noted in patients who received either lactulose or PEG with no statistically significant difference between the 2 treatment arms.17
In addition to safety, availability, and cost, the AGA also considered that most OIC clinical trials offer laxatives as rescue agents to patients not responding to therapy and therefore recommends laxatives as first-line agents in OIC.8 Options for treatment include stimulant laxatives such as senna and bisacodyl, stool softeners such as docusate, and osmotic laxatives such as PEG, lactulose, sorbitol, milk of magnesia, and magnesium. Clinicians should use caution when considering magnesium-containing therapies for patients with renal disease.