A major reason patients visit their primary care providers is constipation. Often, the constipation is acute and prescribers can identify an underlying cause and correct it. Even more often, there is no underlying cause and the patient is diagnosed with chronic idiopathic constipation (CIC). Up to 40% of Americans have CIC, and people at greatest risk are women, people who have very low caloric intake, and older individuals. Its cost is significant, ranging from $1900 to $7500 per patient per year. At the 2019 Directions in Pharmacy conference, 1 session discussed constipation and recent findings that serotonin has a particular association with CIC.

Sneha Baxi Srivastava, PharmD, BCACP, CDE, Associate Professor from the Department of Pharmacy Practice at Rosalind Franklin University of Medicine and Science in North Chicago, Illinois, engaged the audience with a presentation on constipation. Dr. Srivastava began with diagnosis and potential causes. As most pharmacists already knew, many medications can be possible culprits, as can inactivity, poor diet, lack of hydration, and numerous other causes including physiologic alterations.

Dr. Srivastava noted the discrepancy between what providers think and what patients perceive. Providers tend to ask about stool frequency. Patients are more concerned about symptoms. When patients experience constipation, they may experience hard stools, incomplete bowel evacuations, abdominal discomfort, distension, or straining. Treatment goals seem simple—reduce symptoms, increase the rate of spontaneous bowel movement, enhance quality of life, and mitigate adverse effects—but are often elusive.

Dr. Srivastava discussed nonpharmacologic approaches, including increasing dietary fiber by 20 to 30 grams daily, increasing physical activity, ensuring the patient hydrates adequately, creating a bathroom routine, and using lower toilets or elevating the feet while defecating. (Patients often use nonprescription treatment options.) She educated participants about fiber and the differences between soluble and insoluble products; laxatives including polyethylene glycol, lactulose, sodium picosulfate, and bisacodyl; and probiotics (which have weak evidence supporting their use).

In terms of prescription therapy, most prescribers use polyethylene glycol 335 for adults and in children (with discretion). The FDA has approved 4 prescription medications for CIC, including lube lubiprostone, linaclotide, plecanatide, and prucalopride. Lubiprostone is a chloride channel activator. Linaclotide and plecanatide are both guanylate cyclase-C agonists. Prucalopride is a serotonin-4 receptor agonist approved in 2018.

Dr. Srivastava covered each FDA-approved agent, starting with lubiprostone. This drug enhances intestinal fluid secretion and increases motility in the intestine, which facilitates stool passage. Lubiprostone requires a dose reduction in hepatic impairment. Clinical studies demonstrated that lubiprostone significantly improves CIC, and its most common adverse effects (AEs) are nausea and headache. Long-term safety has been evaluated.

She next discussed linaclotide, which increases intra- and extracellular cyclic guanosine monophosphate and stimulates bicarbonate and chloride secretion into the intestinal lumen. This increases intestinal fluid and accelerates transit. Linaclotide’s dose depends on whether the patient has CIC or inflammatory bowel disease (IBD) with constipation, both of which are approved indications. Its most common AEs are diarrhea, abdominal pain, flatulence, abdominal distention, upper respiratory tract infection, and sinusitis.

Plecanatide’s mechanism of action is similar to that of linaclotide. It, too, is approved for CIC and IBD with constipation. Its most common AEs are severe diarrhea, sinusitis, upper respiratory tract infection, abdominal distention, flatulence, and abdominal tenderness. Five cases of increased liver function test have been reported.

Prucalopride stimulates colonic peristalsis and increases volatility. It is a prokinetic agent. It requires dose reductions in severe renal impairment (creatinine clearance < 30 mL/ min). Its most common AEs are headache, abdominal pain, nausea, diarrhea, abdominal distention, dizziness, vomiting, flatulence, and fatigue.

Dr. Srivastava provided a comparison chart that pharmacists could use to compare the 4 agents’ contraindications, warnings, precautions, and dosing considerations. She noted that all agents are contraindicated in patients who have known or suspected gastrointestinal obstructions. Of note, linaclotide and plecanatide are contraindicated in children younger than 6 years due to risk of severe dehydration. Lubiprostone must be taken with food. Prucalopride has been associated with suicidal ideation and behavior; pharmacists should monitor patients for worsening depression and suicidal thoughts.

Dr. Srivastava ended the session by reviewing a CIC management algorithm. She reminded participants that management begins with lifestyle modifications, should progress to osmotic laxatives, and if the patient is still not experiencing relief, clinicians need to consider prosecretory or prokinetic agents. After a trial of 8 to 12 weeks, clinicians need to reassess patients and make a decision about continuing the drug or referring the patient for specialist assessment. She reminded pharmacists that they can refer patients to the American College of Gastroenterology Patient and Education Resource Center at patients.gi.org/topics/constipation-and-defection-problems. She also made them aware of an online constipation symptom tracker (aboutibs.org/symptom-diary.html), and listed several apps for gastrointestinal health.