Management of Constipation After First-Line Agents Fail

Stepwise Approach

The National Comprehensive Cancer Network recommends adding bisacodyl 10-15 mg daily to three times daily for constipation that persists after MiraLAX and senna, with a goal of one non-forced bowel movement every 1-2 days 1
For opioid-induced constipation that doesn't respond to traditional laxatives, peripheral opioid antagonists such as naldemedine, naloxegol, or methylnaltrexone are recommended, as suggested by the European Society for Medical Oncology and the American Gastroenterological Association 2, 3
Magnesium-based laxatives, such as magnesium hydroxide 30-60 mL daily-BID or magnesium citrate 8 oz daily, can be effective but should be used cautiously in patients with renal impairment due to risk of hypermagnesemia, according to the National Comprehensive Cancer Network and the European Society for Medical Oncology 1, 4
Lactulose 30-60 mL BID-QID can be added if other measures fail, as recommended by the National Comprehensive Cancer Network 1

The National Comprehensive Cancer Network suggests ruling out impaction, especially if diarrhea accompanies constipation, and ruling out obstruction through physical examination and considering abdominal x-ray or GI consultation if suspected 1
Discontinuing any non-essential constipating medications and treating other causes of constipation, such as hypercalcemia, hypokalemia, hypothyroidism, or diabetes mellitus, is recommended by the National Comprehensive Cancer Network 1

For impaction, administering glycerine suppository with or without mineral oil retention enema is recommended by the National Comprehensive Cancer Network 1
Considering bisacodyl suppository (one rectally daily-BID) for more direct stimulation of the rectum is suggested by the National Comprehensive Cancer Network 1
For opioid-induced constipation, considering methylnaltrexone 0.15 mg/kg subcutaneously every other day (no more than once daily) except in cases of post-operative ileus or mechanical bowel obstruction is recommended by the National Comprehensive Cancer Network 1
Tap water enemas until clear may be necessary for severe impaction, as recommended by the National Comprehensive Cancer Network 1
Considering use of a prokinetic agent such as metoclopramide 10-20 mg PO QID is suggested by the National Comprehensive Cancer Network 1

Avoiding bulk laxatives like psyllium in opioid-induced constipation is recommended by the European Society for Medical Oncology 3
For patients with advanced disease and limited life expectancy, considering increasing the dose of stimulant laxatives with stool softeners (senna with docusate, 2-3 tablets BID-TID) is suggested by the National Comprehensive Cancer Network 1
Enemas are contraindicated for patients with neutropenia, thrombocytopenia, paralytic ileus, intestinal obstruction, recent colorectal or gynecological surgery, recent anal or rectal trauma, severe colitis, or undiagnosed abdominal pain, as recommended by the European Society for Medical Oncology 3

The American Society of Clinical Oncology recommends performing digital rectal examination to identify distal rectal impaction versus proximal sigmoid/colonic impaction 5, 6
If the rectum is empty on exam but clinical suspicion remains high, consider abdominal imaging as proximal impactions will not be detected by digital exam 6
Digital fragmentation and manual extraction of the impacted stool mass should be performed, followed by oil retention enema or osmotic micro-enemas, then oral polyethylene glycol (PEG) to prevent recurrence 5, 6

The ESMO guidelines provide specific enema choices based on mechanism, including oil retention enemas, osmotic micro-enemas, docusate sodium enema, and normal saline enemas 7
Oil retention enemas, such as cottonseed, olive, or arachis oil, lubricate and soften stool, and must be retained for at least 30 minutes for maximum effect 7

The American Society of Clinical Oncology recommends avoiding enemas in patients with neutropenia, thrombocytopenia, paralytic ileus, intestinal obstruction, recent colorectal/gynecological surgery, anal/rectal trauma, severe colitis, abdominal inflammation/infection, toxic megacolon, undiagnosed abdominal pain, or recent pelvic radiotherapy 5, 6, 7

Giving oral laxatives alone without addressing the physical impaction can be ineffective, as the mass must be mechanically disrupted first; oral agents cannot penetrate a hard, impacted fecal ball 5, 6
Using tap water enemas initially can be harmful, and gentler oil retention or osmotic enemas should be used first 7, 8
Failing to premedicate with analgesia and anxiolysis can make manual disimpaction painful and distressing 8
Not establishing maintenance therapy with a prophylactic bowel regimen can lead to re-impaction 5, 6