Close this search box.


Medications have been shown to be effective in treating chronic constipation in multi-center, high quality clinical trials. These are prescription medications intended for specific use under a healthcare provider’s supervision.

Be sure to take any medication as directed. Always tell your health care providers about all the medicines you are taking, including over the counter and prescription medicines.

Secretagogues: These agents are a class of drugs which increase fluid secretion and movement in the GI tract. These drugs also can improve pain, discomfort, and bloating. There are three classes of secretagogues approved by the Food and Drug Administration (FDA) for the treatment of CC. These drugs include:

  • the chloride-channel activator (lubiprostone),
  • the guanylate cyclase C receptor activators (linaclotide and plecanatide), and
  • the sodium-hydrogen ion exchange inhibitor (tenapenor)

There are slight variations in the side-effects that can occur with these drugs. The most common side effect occurring in individuals taking linaclotide, plecanatide, and tenapenor is diarrhea. Mild nausea
is more commonly experienced by those taking lubiprostone.

Prokinetics: These drugs increase the frequency of contractions in the GI tract, which may improve gut
motility and stomach emptying. Two prokinetic drugs are currently FDA approved for the treatment
of CC:

  • Prucalopride for slow transit constipation (STC)
  • Tegaserod for constipation predominant irritable bowel syndrome (IBS-C).

The most commonly occurring side effects caused by these drugs include headaches, abdominal pain,
nausea, and diarrhea. In most cases, these develop early during treatment and do not last very long.
There were also initial concerns that these drugs increased the risk of cardiovascular (CV) or heart-related events. However, there has been no evidence to prove an increased CV risk with prucalopride. Tegaserod, originally approved in 2002 for the treatment of IBS, was voluntarily withdrawn from the market in 2007 after a small but significant increased risk of CV events were found. In 2019, tegaserod was reintroduced for use by female IBS-C sufferers under the age of 65 without a history of CV disease. Reevaluation of the
data showed no cases of major CV events in this limited population.

PAMORAs: Peripherally Acting Mu-Opioid Receptor Agonists (PAMORAs): PAMORAs are a special class
of drugs created to treat opioid induced constipation (OIC). These drugs were specifically designed to reverse the constipating effects of opioids in the GI tract while having little potential to penetrate the central nervous system (CNS). Opioids cause delayed gut motility, reduced fluid secretion, and increased fluid reabsorption. By entering the CNS (brain, spinal cord, nerves) these drugs could cause some pain relief and possibly help with opioid withdrawal. There are currently three FDA-approved drugs in the class:

  • methylnaltrexone bromide is available for the treatment of OIC in people with chronic non-cancer pain conditions.
  • naloxegol and naldemedine are only approved for the treatment of OIC in people with non-malignant pain syndromes. Non-malignant pain is pain that lasts far beyond a typical injury or
    illness and does not occur with cancers. Unlike methylnaltrexone, these drugs are metabolized
    by enzymes in the liver. You should speak with your healthcare provider about all medications
    you are taking to ensure they prescribe the proper dose of medication for you.

The most common adverse events associated with these medications are GI related (abdominal pain,
nausea, diarrhea). Evidence of opioid withdrawal is very rare.

Adapted from IFFGD Publication 281- “Constipation Overview” by By: Darren M. Brenner, M.D., AGAF, FACG, Associate Professor and Director of the Neurogastromotility Program, Division of Gastroenterology, Northwestern University Feinberg School of Medicine, Chicago, IL

Share this page
Topics of this article
Was this article helpful?

IFFGD is a nonprofit education and research organization. Our mission is to inform, assist, and support people affected by gastrointestinal disorders.

Our original content is authored specifically for IFFGD readers, in response to your questions and concerns.

If you found this article helpful, please consider supporting IFFGD with a small tax-deductible donation.

Related Information
Treatment of Constipation

Treatment help – Treatment of chronic constipation is best managed by first determining the underlying cause. While there may be several contributing factors, the 3

Read More »
Personal Stories
Treatment of Constipation

Treatment help – Treatment of chronic constipation is best managed by first determining the underlying cause. While there may be several contributing factors, the 3

Read More »
Skip to content