For a pregnant woman with ondansetron‑induced constipation, is lactulose (Nutalact) or sodium picosulfate (Picofit) the safer first‑line treatment?

Lactulose (Nutalact) is the safer first-line choice for ondansetron-induced constipation in pregnancy

For a pregnant woman experiencing constipation as a side effect of ondansetron, lactulose (Nutalact) should be preferred over sodium picosulfate (Picofit) as the initial laxative therapy. This recommendation is based on current guidelines that explicitly endorse osmotic laxatives as first-line agents, while stimulant laxatives like sodium picosulfate are reserved for second-line or short-term use.

Evidence-Based Treatment Algorithm

First-Line Therapy: Osmotic Laxatives

• Lactulose is specifically recommended by the 2024 AGA guidelines as a safe first-line treatment option for constipation in pregnancy 1
• Lactulose has been studied extensively in pregnant women and is the only osmotic agent with dedicated pregnancy safety data 1
• A multicenter study of 62 pregnant women demonstrated that lactulose significantly increased defecation frequency from 2.5 to 4.0 stools per week after just 1 week, with normalization to 6 stools per week by week 2 2
• Lactulose is not absorbed in the small intestine and does not appear in breast milk, making it safe for both the developing fetus and for continuation during nursing 2
• The main limitation is that lactulose may cause more bloating and flatulence compared to polyethylene glycol, particularly at higher doses 1

Alternative First-Line Option: Polyethylene Glycol

• Polyethylene glycol (PEG) 17g daily is also endorsed as a preferred first-line agent by the 2024 AGA guidelines 3, 4
• A randomized controlled trial comparing PEG 4000 to lactulose in 113 pregnant women found both were effective and safe, though PEG demonstrated faster therapeutic effect at weeks 1 and 2 (P=0.029) 5
• PEG causes less bloating than lactulose and may be better tolerated 1, 5

Why Sodium Picosulfate (Picofit) Should NOT Be First-Line

• Stimulant laxatives like sodium picosulfate are recommended only as second-line therapy during the second and third trimesters, not as initial treatment 6
• The 2024 AGA/ACG guidelines on chronic constipation explicitly state that stimulant laxatives (including bisacodyl and picosulfate) are "recommended for short-term use or rescue therapy" with unknown long-term safety and efficacy 1
• The primary concern with stimulant laxatives in pregnancy is tenesmus (painful straining), which is associated with increased risk of preterm labor 6
• Stimulant laxatives can cause cramping, abdominal discomfort, and with prolonged or excessive use may lead to diarrhea and electrolyte imbalances 1
• While sodium picosulfate has been studied in pregnancy and appears safe regarding teratogenicity, it lacks the extensive safety profile of osmotic laxatives 6, 7

Clinical Implementation Strategy

Step 1: Initiate Lactulose or PEG

• Start with lactulose 15g daily (can be given as 15 mL twice daily if needed) 1, 2
• Alternatively, use PEG 17g daily if bloating is a major concern 3, 4
• Ensure adequate hydration (water intake) to optimize laxative efficacy 3, 4

Step 2: Titrate Based on Response

• Assess bowel movement frequency and stool consistency after 1 week 2, 5
• Titrate dose upward based on symptom response and tolerability 1
• Goal is soft, formed stools every 1-2 days 4

Step 3: Consider Second-Line Agents Only If First-Line Fails

• If lactulose or PEG are ineffective after adequate trial (2-3 weeks at optimal dose), then consider sodium picosulfate as second-line therapy 6
• Use stimulant laxatives cautiously and only for short-term relief 1, 6
• Avoid stimulant laxatives in the first trimester when possible 6

Important Clinical Caveats

Ondansetron-Specific Considerations

• Ondansetron itself is associated with constipation as a known side effect, making laxative therapy particularly important 1
• Consider whether ondansetron can be discontinued or dose-reduced if nausea/vomiting has improved, as this may resolve the constipation without additional medication 1
• Metoclopramide causes less constipation than ondansetron and could be considered as an alternative antiemetic if appropriate 1

Safety Monitoring

• Avoid prolonged use of stimulant laxatives due to risk of electrolyte imbalances and unknown long-term safety 1, 7
• Osmotic laxatives should also be used cautiously long-term to avoid dehydration, though they are safer than stimulants 7
• Monitor for signs of dehydration (decreased urine output, orthostatic hypotension) particularly if diarrhea develops 8

When to Escalate Care

• If constipation persists despite optimal laxative therapy, evaluate for other contributing factors (iron supplementation, other medications, anatomic obstruction) 1
• Severe abdominal pain, inability to pass gas, or vomiting may indicate bowel obstruction and requires urgent evaluation 4

The evidence strongly supports osmotic laxatives (lactulose or PEG) as the safest and most appropriate first-line therapy for ondansetron-induced constipation in pregnancy, with stimulant laxatives like sodium picosulfate reserved for refractory cases only.