Constipation Treatment Options

Introduction to Constipation Medications

The American Gastroenterological Association recommends newer medications, including peripherally acting μ-opioid receptor antagonists, secretagogues, and selective 5-HT4 receptor agonists, for effective treatment of constipation in various patient populations 1, 2, 3

Plecanatide, a pH-dependent guanylate cyclase-C agonist, is approved for chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C) at a dose of 3 mg daily, and may improve stool consistency based on the Bristol Stool Form Scale compared with placebo 4
Lubiprostone, an orally active prostaglandin analog, is FDA-approved for treatment of CIC in adults, opioid-induced constipation (OIC) in adult patients with chronic non-cancer pain, and IBS-C in women, and can be used in combination with peripherally acting μ-opioid receptor antagonists such as methylnaltrexone 1, 3, 5

Methylnaltrexone provides effective relief of opioid-induced constipation (OIC) while preserving opioid-mediated analgesia, with a recommended dose of 0.15 mg per kilogram of body weight every other day, and should not be used in patients with postoperative ileus or mechanical bowel obstruction 1, 2, 6
Naloxegol is a peripherally-acting μ-opioid receptor antagonist for treating OIC in patients receiving chronic opioids for noncancer pain, and is FDA-approved for OIC in adults with chronic noncancer pain, including those with chronic pain related to previous cancer or treatment 1, 3, 6

Prucalopride is a selective, high-affinity 5-HT4 agonist that promotes neurotransmission by enteric neurons, stimulating peristaltic reflex, intestinal secretions, and GI motility, and is FDA-approved for treatment of chronic idiopathic constipation (CIC) in adults, with a recommended dose of 2 mg daily 4

The American Gastroenterological Association recommends a treatment algorithm for constipation, starting with first-line treatments such as traditional laxatives and stimulant laxatives, and progressing to second-line treatments such as secretagogues and peripherally acting μ-opioid receptor antagonists for patients who do not respond to first-line treatments 7, 8, 9

Before initiating newer medications, assess for and treat other causes of constipation, such as hypercalcemia, hypokalemia, hypothyroidism, and diabetes mellitus, and rule out impaction or obstruction before starting treatment 1, 3
Monitor for diarrhea with secretagogues, which can lead to dehydration in some patients, particularly with linaclotide and plecanatide, and consider combination therapy for patients with refractory constipation 1, 3, 4, 5