Adjusting Laxative Therapy for Inadequate Response to PEG and Senna
For patients with constipation not adequately controlled on polyethylene glycol (PEG) and senna, the most effective approach is to increase the PEG dose first, as it has the strongest evidence for efficacy and safety in chronic constipation with no clear maximum dose limit. 1
Assessment of Current Regimen
Before making adjustments:
- Verify current doses being used (PEG 17g daily is standard starting dose)
- Ensure adequate hydration (2-3 liters daily unless contraindicated)
- Check for signs of fecal impaction which may require manual disimpaction
Step-by-Step Adjustment Algorithm
Step 1: Optimize PEG Dosing
- Increase PEG dose by 50-100% (up to 34g daily) 1, 2
- PEG has no clear maximum dose and has demonstrated durable efficacy over 6 months 1
- Reassess response after 2-3 days
Step 2: If Inadequate Response to Increased PEG
- Increase senna dose (up to 4 tablets twice daily) 1
- Senna works by stimulating colonic motility and reducing colonic water absorption
Step 3: If Still Inadequate
- Add magnesium oxide (400-500mg daily) 1
- Caution: Avoid in renal impairment 1
- OR add lactulose (15g daily) 1
- Note: Lactulose may cause more bloating and flatulence than PEG
Step 4: For Persistent Constipation
- Consider adding bisacodyl (5-10mg daily) for short-term rescue therapy 1
- For opioid-induced constipation specifically, consider peripheral opioid antagonists like naldemedine or naloxegol 1
Evidence for Combination Therapy
The combination of PEG and senna has shown synergistic effects:
- Studies show that adding senna to PEG improves bowel cleansing efficacy compared to PEG alone 3, 4
- Low-volume PEG plus senna has demonstrated similar efficacy to high-volume PEG alone with fewer side effects 3
Important Considerations
- Avoid adding bulk-forming laxatives like psyllium, especially in opioid-induced constipation 1, 2
- For opioid-induced constipation specifically, prophylactic bowel regimens are recommended, with stimulant laxatives plus PEG being more effective than stool softeners 1
- Rectal interventions (suppositories, enemas) should be considered if oral medications fail and the rectum is full 1, 2
Monitoring Response
- Goal: One non-forced bowel movement every 1-2 days 1
- Assess for adverse effects such as bloating, abdominal discomfort, and cramping
- If diarrhea develops, reduce the dose of the most recently added or increased agent
Special Situations
For opioid-induced constipation that remains refractory:
- Consider peripheral opioid antagonists (methylnaltrexone, naloxegol, or naldemedine) 1
- Opioid rotation to fentanyl or methadone may be beneficial 1
By systematically adjusting laxative therapy following this algorithm, most cases of constipation can be effectively managed without needing to immediately add new agents like lactulose.