A clinical review published in the Journal of Clinical Gastroenterology outlined the safety profiles of over-the-counter (OTC) and prescription laxatives in patients who are pregnant or planning to become pregnant.
The safety of OTC and prescription laxatives for both patient and fetus is not well-established due to the frequent exclusion of pregnant patients from clinical trials. To inform this gap, investigators performed a review of all laxatives currently approved by the Food and Drug Administration (FDA) for the treatment of chronic constipation. Known safety concerns were examined for all major OTC and prescription laxatives; results were presented separately for each treatment type.
While first-line treatment for constipation often involves lifestyle changes, certain cases may require the use of OTC agents. OTC treatments examined in this review include bulk fibers, stool softeners, osmotic laxatives, stimulant laxatives, and rectal therapy.
1. Bulk fibers – Increased dietary fiber intake is often a first-line treatment for constipation. A 2015 review and meta-analysis examining constipation interventions during pregnancy found that an added 10 g of fiber daily was associated with improved stool frequency and consistency. Consumption of OTC bulk fibers such as psyllium, polycarbophil, and methylcellulose can also improve regularity, though they do not provide immediate relief. Side effects include abdominal bloating and cramping; titrating bulk fibers from 3 g daily up to 10 to 20 mg daily, depending on tolerance, is recommended.
2. Stool softeners – Docusate sodium is used frequently to treat constipation in pregnant women due to its favorable safety profile. However, it appears to be less effective than other treatments, such as psyllium. Docusate use is not associated with fetal safety concerns, though it may cause electrolyte abnormalities in the patient.
3. Osmotic laxatives – Osmotic laxatives treat constipation by retaining water in the intestinal tract, which improves stool frequency. The major classes of these laxatives are polyethylene glycol (PEG), lactulose, and osmotic salts. While PEG has not been extensively studied in pregnancy, it is minimally absorbed and thus unlikely to cause fetal malformation. Lactulose is considered safe for use during pregnancy but is prescribed less frequently than PEG and may cause nausea, abdominal cramping, and flatulence. As with PEG, it has low bioavailability when consumed, meaning risk to the fetus is minimal. Osmotic salts have been studied the least of the 3 osmotic laxative types, but are considered safe for short-term use. However, long-term use is associated with sodium retention and hypermagnesemia.
4. Stimulant laxatives – Stimulant laxatives increase colonic motor activity and are highly effective for the treatment of constipation. However, they are infrequently prescribed during pregnancy and may cause inadvertent diarrhea, which can lead to dehydration and electrolyte imbalance. Due to their minimal systemic absorption, they are considered to have low teratogenic potential. However, certain types, such as senna, are excreted in breast milk. The effects of senna metabolites on infants are not well understood. As such, this class of laxatives is only recommended when bulk fibers and osmotic laxatives have failed to resolve constipation.
5. Rectal therapy – Enemas, sodium phosphate, and other rectal therapies are generally not recommended due to the risk of inducing labor. Further, rectal therapies are often less effective than other OTC treatments for constipation.
Prescription treatment options for chronic constipation include secretagogues and serotonin receptor type 4 (5-HT4) agonists. These medications are often only used as a second-line treatment, such as when dietary changes and OTC remedies have failed. Secretagogues of interest include chloride channel activators and guanylate cyclase-C receptor activators.
1. Chloride channel (ClC-2) activators – These medications work by increasing chloride secretion, which subsequently improves passive transport of water into the intestinal lumen. Lubiprostone, a CIC-2 activator, was FDA-approved for the treatment of chronic constipation in 2006. Initially, due to fetal safety concerns, the FDA recommended that women have a negative pregnancy test prior to beginning lubiprostone. While this guideline was retracted in 2012, CIC-2 activators are still not recommended during pregnancy unless the benefits of their use outweigh potential risks to the fetus. Additionally, lubiprostone is known to cause nausea, which may be intolerable during pregnancy.
2. Guanylate cyclase-C receptor activators – Little is known about the safety of these drugs in pregnancy. One drug, linaclotide, was FDA-approved for the treatment of chronic constipation in 2012. However, due to the lack of data on fetal safety, it is not currently recommended for use during pregnancy. Plecanatide, another guanylate cyclase-C receptor agonist, is minimally systemically absorbed and is thought to present little risk to the fetus. However, the lack of clinical trial data means the FDA recommends against its use in pregnancy and during breastfeeding.
3. Serotonin agonists – Prucalopride is a selective 5-HTA receptor agonist that was approved for the treatment of constipation in 2018. Prucalopride works by increasing colonic transit and motility. Its side effects include abdominal pain, nausea, diarrhea, and headache. It is not thought to have adverse effects on embryofetal development, though it is not recommended for use during pregnancy due to a lack of safety data. Prucalopride can also be secreted in breast milk, though its effects on the breastfeeding infant are not known.
Constipation is estimated to affect 11% to 38% of pregnant patients. Even so, few studies have explored the safety of OTC and prescription laxatives in pregnant individuals. First-line therapies include an increase in dietary fiber, following which PEG and docusate may be employed. Prescription options are only recommended in patients with constipation refractory to OTC methods.
“This update serves as a tool to aid the physician in a risk-benefit discussion with patients about which laxatives should be started, continued, or stopped during pregnancy and during lactation,” the clinical review authors wrote. “Further studies are needed regarding the safety of both OTC but especially prescription laxatives during pregnancy and the post-partum period.”
Brigstocke S, Yu V, Nee J. Review of the safety profiles of laxatives in pregnant women. J Clin Gastroenterol. 2022;56(3):197-203. doi:10.1097/MCG.0000000000001660