Recommended Bowel Regimen for Clozapine (Clozaril)
All patients starting clozapine must receive prophylactic laxatives from day one, as clozapine causes severe constipation that can progress to life-threatening bowel obstruction and death. 1, 2
Prophylactic Regimen (Start Immediately with Clozapine)
First-line prophylaxis should include:
- Stimulant laxative: Senna (sennosides) 2 tablets twice daily, or bisacodyl 10 mg daily 1, 3
- Osmotic laxative: Polyethylene glycol (PEG) 3350 - one heaping tablespoon (17 grams) mixed in 8 oz water twice daily 1, 3
- Adequate fluid intake throughout the day (not just water with medications) 1
- Encourage physical activity when appropriate 1
- Dietary fiber only if patient maintains adequate fluid intake 1
The FDA label explicitly warns about gastrointestinal hypomotility with severe complications and advises close monitoring and prompt treatment of constipation 2. This prophylactic approach is critical because clozapine causes multi-regional gastrointestinal dysfunction in 82% of patients, affecting the stomach, small bowel, and colon 4.
Treatment Goal
Aim for one non-forced bowel movement every 1-2 days 1, 3. This is the objective measure of adequate bowel function on clozapine.
Management of Established Constipation
If constipation develops despite prophylaxis:
- Titrate stimulant laxatives: Increase senna to 3 tablets two to three times daily (maximum 8-12 tablets per day), or bisacodyl 10-15 mg two to three times daily 1, 3
- Ensure adequate hydration and physical activity 1
- Continue or optimize PEG 3350 at 17 grams twice daily 3
- Assess response after 2-4 days of dose adjustment 3
For persistent constipation:
- Add magnesium-based products: Magnesium hydroxide 30-60 mL daily or magnesium citrate 8 oz daily 3
- Consider bisacodyl suppositories 10 mg rectally if oral agents insufficient 3
- Consider prokinetic agents: Metoclopramide 10-20 mg orally four times daily for severe or refractory cases 1
For severe refractory constipation:
- Peripherally acting μ-opioid receptor antagonists: Methylnaltrexone 0.15 mg/kg subcutaneously every other day may be considered 1
Critical Pitfalls to Avoid
Do NOT use docusate (stool softener) alone or as primary therapy - it has no proven benefit and is explicitly not recommended by NCCN guidelines 1, 5. Adding docusate to senna is less effective than senna alone 6.
Do NOT add psyllium or fiber supplements for clozapine-induced constipation - they are ineffective and may worsen symptoms 3. Supplemental medicinal fiber can actually exacerbate constipation 6.
Do NOT wait for patient complaints - subjective reporting of constipation has low sensitivity (only 18% of patients with documented dysmotility had normal studies) 4. Constipation must be actively monitored, not passively reported.
Do NOT assume male patients are adequately treated - laxative use is more common in female patients (49%) than male patients (29%), suggesting males may be undertreated 7.
Do NOT assume dose-related risk - constipation occurs at any clozapine dose or plasma concentration 7. Even patients on stable, lower doses require prophylaxis.
Monitoring Strategy
- Proactively ask about bowel movements at every visit, targeting one non-forced movement every 1-2 days 1, 3
- Rule out bowel obstruction if constipation worsens despite treatment 6
- Discontinue non-essential constipating medications when possible 3
- Recognize that patients do not develop tolerance to clozapine-induced constipation, requiring ongoing prophylactic treatment 3
Why This Matters
Clozapine causes delayed gastric emptying in 41%, delayed small bowel transit in 71%, and delayed colon transit in 50% of patients 4. This multi-regional dysfunction can progress to intestinal pseudo-obstruction, bowel perforation, and death 2, 8. The morbidity from gastrointestinal hypomotility exceeds that of agranulocytosis 4. Prophylactic treatment is not optional - it is mandatory for patient safety.