Chemotherapy-, Antiemetic-, and Opioid-Induced Constipation

Written by: Brady Quinn and Britny Rogala, PharmD – University of Rhode Island College of Pharmacy
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The utilization of proper diet, over-the-counter medications, and alternative prescriptions can be helpful for patients suffering from multisource drug-induced constipation. Preventing this type of constipation requires less interventions than treating the symptoms once they occur.¹

Background:

Many chemotherapeutic medications, antiemetics, and pain regimens can commonly cause constipation. Drug-induced constipation, often characterized by infrequent, hard, or difficult to pass bowel movements, can significantly impair quality of life or cause severe pain, rectal fissures, or bowel obstruction.^1-3

Oral chemotherapy agents that commonly cause constipation(>30%): alectinib, crizotinib, ponatinib, ixazomib, lenalidomide, niraparib, pomalidomide, rucaparib, temozolomide, and thalidomide

Anti-emetics that commonly cause constipation: 5-HT₃ antagonists (e.g. ondansetron)

Diet/Exercise:

• Increase fiber intake; patients prone to small bowel obstruction (i.e. abdominal surgery) should avoid additional fiber intake
  • Whole grains, brown rice, raw fruits and vegetables, etc.
• Drink plenty of fluids
  • 8-10 glasses of water, fruit/vegetable juices, decaffeinated teas
• Try some sort of physical activity

Drug Therapy

Osmotic Laxative

• Polyethylene Glycol (OTC/RX)
  • Take 1 capful/packet/heaping tablespoon (17g) of powder dissolved in 4-8 ounces of any beverage daily.
  • Onset of action: 12-72 hours

Stool softener

• Docusate Sodium (OTC)
  • Take 1 softgel (100mg) up to 3 times per day in divided doses
  • Onset of action: 12-72 hours
  • Can take in combination with a stimulant laxative for best results

Stimulant laxatives

• Senna (OTC)
  • Take 2 tablets (17.2mg) as one dose once daily to start. If needed can take up to 4 tablets (34.4mg) twice daily
  • Onset of action: 6-12 hours
• Bisacodyl (OTC)
  • Take 1 tablet (5mg) once daily to start. If needed can take up to 3 tablets (15mg) once daily.
  • Onset of action: 6-12 hours

Prescription Options

• Methylnaltrexone (RX only)
  • Used to treat opioid-induced constipation
  • Rule out GI obstruction – contraindicated
  • Inject 1 prefilled syringe (dose may vary) subcutaneously up to every other day as needed
  • Rotate injection site between abdomen, thighs, and upper arms
  • Discontinue methylnaltrexone immediately if severe or persistent diarrhea or abdominal pain occurs
• Naloxegol (RX only)
  • Used to treat opioid-induced constipation
  • Rule out GI obstruction – contraindicated
  • Usual dose: take 1 tablet (25mg) daily at least 1 hour before the first meal of the day (dose may differ due to tolerability)
  • Concomitant use with strong CYP3A4 inhibitors is not recommended
  • Providers may request samples directly from the manufacturer

PQI Process:

Upon receipt of an oral chemotherapy agent with known constipation side effect

• Counsel patient on constipation management
• Provide information on foods to eat to prevent the onset of constipation
• Provide stool softener and stimulant laxative to patient if patient reports signs of constipation
• Keep stool softener and stimulant laxative well stocked if patient experiences intermittent constipation
• Consider scheduling a follow up phone call with patient within one week after initiation of therapy to assess if patient is experiencing constipation
  • Assess the cause of constipation (chemotherapy/antiemetic/opioid)
  • If opioid therapy is the cause of the constipation and significant effort to alleviate constipation has been made with no relief, consider prescription therapy (methylnaltrexone, naloxegol, etc.)
  • If antiemetic therapy is the cause of constipation provide a prescription for a different type of antiemetic for chemotherapy-induced nausea/vomiting (Refer to CINV PQI)

Patient Centered Activities:

Educate patients on different forms of laxatives (bulk forming, polyethylene glycol), if bowel movements do not become regular continue on to OTC agents.

Advise patient to:

• Try to find a diet and regimen that helps to keep bowel movements regular
• Attempt to treat to what their regular bowel movement schedule would normally be
• Keep track of how many bowel movements they make in a week
• Be sure to drink plenty of fluids while taking laxative and stool softening medications
• Contact clinic if they have not had a bowel movement in 2 or more days
• Notify your provider if you have been taking OTC medications continuously for 7 days.

References:

1. McQuade RM, Stojnovska V, Abalo R, Bomstein JC, Nurgali K. Chemotherapy-Induced Constipation and Diarrhea: Pathophysiology, Current and Emerging Treatments. Front Pharmacol. 2016;7:414.
2. Andrews CN, Storr M. The pathophysiology of chronic constipation. Can J Gastroenterol. 2011;25:16B-21B.
3. Kumar L, Barker C, Emmanuel A. Opioid-Induced Constipation: Pathophysiology, Clinical Consequences, and Management. Gastroenterology Research and Practice. 2014; https://doi.org/10.1155/2014/141737.

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