How should Carafate (sucralfate) be dosed and administered for duodenal ulcer, and what are its contraindications, side effects, and drug interactions?

Carafate (Sucralfate) for Duodenal Ulcer

Dosing and Administration

For active duodenal ulcer, administer sucralfate 1 gram four times daily on an empty stomach (30 minutes before meals and at bedtime) for 4-8 weeks, or alternatively 2 grams twice daily (upon waking and at bedtime) which offers comparable efficacy with better convenience. 1

Standard Dosing Regimen

• Active duodenal ulcer: 1 gram four times daily, taken 30 minutes before meals and at bedtime 1
• Treatment duration: Continue for 4-8 weeks unless healing is demonstrated earlier by endoscopy or x-ray 1
• Maintenance therapy: 1 gram twice daily after acute ulcer healing 1

Alternative Dosing

• 2 grams twice daily (upon waking and at bedtime) is equally effective as the four-times-daily regimen, with healing rates of 79% at 4 weeks and 85% at 8 weeks 2, 3
• This simplified regimen may improve compliance while maintaining therapeutic efficacy 2, 3

Administration Considerations

• Must be taken on an empty stomach for optimal efficacy 1
• Separate from antacids by at least 30 minutes, as antacids may be used for pain relief but should not be taken within one-half hour before or after sucralfate 1
• Separate from acid-suppressive agents (PPIs or H2-blockers) by at least 2 hours to avoid interaction 4
• Elderly patients: Start at the low end of the dosing range due to potential decreased organ function 1

---

Mechanism of Action

Sucralfate works through multiple local mechanisms at the ulcer site rather than systemic absorption 5, 6:

• Forms a protective barrier by binding to proteinaceous material at the ulcer crater 5, 6
• Inhibits pepsin activity and hydrogen ion diffusion 5, 6
• Adsorbs bile salts 5
• Remains at gastric ulcer sites for up to 6 hours 5
• Only 3-5% is systemically absorbed; over 90% is excreted unchanged in feces 5

---

Contraindications

The only absolute contraindication is known hypersensitivity to sucralfate or any excipients. 1

---

Side Effects

Sucralfate is remarkably well-tolerated due to minimal systemic absorption 5, 6:

• Constipation: Most common side effect, occurring in 2-4% of patients 5, 6
• Dry mouth (xerostomia): Occurs in approximately 1% of patients 5
• Skin eruptions: Rare, occurring in 0.6% of patients 5
• Diarrhea or constipation: Depending on formulation 7

---

Drug Interactions

• Minimal drug-drug interactions have been reported due to lack of systemic absorption 5
• May interfere with absorption of other medications when taken concurrently 7
• Must be separated from acid-suppressive agents (PPIs, H2-blockers) by at least 2 hours 4
• Antacids should be separated by at least 30 minutes 1

---

Clinical Context and Limitations

Efficacy Profile

• Effective for duodenal ulcers: Healing rates of 91.7% at 4 weeks compared to 58.1% with placebo 8
• Comparable to cimetidine in duodenal ulcer healing 5, 6
• Less effective for gastric ulcers: Healing rates are less impressive than for duodenal ulcers 5

Important Clinical Caveats

Sucralfate is NOT recommended as first-line therapy for gastric ulcers or NSAID-related gastric injury due to the availability of far superior alternatives (PPIs). 9, 7

• PPIs are the preferred first-line agents for both treatment and prophylaxis of NSAID- and aspirin-associated GI injury 9, 7
• Sucralfate is effective for NSAID-associated duodenal ulcers only when the NSAID is discontinued, but is not effective for gastric ulcers 9
• Not effective for prevention or treatment of radiation-induced oral mucositis 9
• Oral sucralfate is not recommended for radiation-induced gastrointestinal mucositis in patients receiving radiation therapy for solid tumors 9, 10

When to Consider Sucralfate

• Second-line agent when PPIs or H2-blockers cannot be used 7, 10
• Stress ulcer prophylaxis in critically ill patients, particularly those at high risk for ventilator-associated pneumonia (sucralfate may have lower pneumonia risk than acid-suppressive therapies) 7, 4, 10
• Duodenal ulcers specifically where it has proven efficacy 1, 8

Critical Pitfall to Avoid

Do not confuse oral sucralfate with sucralfate enemas—they have completely different evidence bases and indications. Sucralfate enemas (not oral) are effective for radiation proctitis with rectal bleeding, while oral sucralfate is ineffective and potentially harmful for radiation injury 4, 10.