What is the recommended treatment for a patient with anal fissures using diltiazem (calcium channel blocker) cream?

Diltiazem Cream for Anal Fissures

Apply compounded 2% diltiazem cream to the anal verge twice daily for 8 weeks as first-line pharmacologic therapy for chronic anal fissures, achieving healing rates of 48-75% without the headache side effects associated with nitroglycerin. 1, 2

Mechanism of Action and Rationale

Diltiazem blocks slow L-type calcium channels in vascular smooth muscle cells of the internal anal sphincter, reducing sphincter tone and increasing local blood flow to the ischemic ulcer, thereby facilitating healing. 3, 4 This addresses the underlying pathophysiology of anal fissures—internal anal sphincter hypertonia with decreased anodermal blood flow creating an ischemic environment. 2

Specific Treatment Protocol

Formulation and Application

• Standard formulation: 2% diltiazem cream applied to the anal verge 5, 6, 7
• Dosing: Apply approximately 2 cm (0.7 g) of cream twice daily 5
• Duration: Continue for 8 weeks minimum 5, 6
• Alternative enhanced formulation: 0.3% nifedipine with 1.5% lidocaine applied three times daily achieves 95% healing after 6 weeks 2, 3

Expected Timeline

• Pain relief typically occurs after 14 days of treatment 3
• Fissure healing assessed at 8 weeks, with most healing occurring within 2-3 months 5, 7
• Approximately 48-75% of chronic fissures heal with diltiazem therapy 5, 6, 7

Treatment Algorithm

First-Line Conservative Management (All Patients)

• Fiber supplementation of 25-30g daily to soften stools and minimize anal trauma 2, 3
• Adequate fluid intake to prevent constipation 2, 3
• Warm sitz baths to promote sphincter relaxation 2, 3
• Topical analgesics (lidocaine 5%) for pain control 1, 4

When to Initiate Diltiazem

• Start diltiazem if the fissure persists beyond 2 weeks despite conservative measures 4
• Diltiazem is particularly effective in patients who have failed glyceryl trinitrate (GTN) therapy, with 75% healing rate in this population 5, 6

Management of Non-Responders

• If no healing after 8 weeks: extend treatment for an additional 8 weeks, which heals an additional 47% of patients 7
• If symptomatic improvement occurs but fissure persists: 42% of patients may decline further treatment due to adequate symptom relief 5
• If treatment fails after extended therapy: consider botulinum toxin injection (75-95% cure rates) or lateral internal sphincterotomy 1

Advantages Over Alternative Therapies

Compared to Nitroglycerin (GTN)

• Similar efficacy: Diltiazem shows 48-75% healing rates versus GTN's 25-50% 1, 5, 6
• Superior side effect profile: Diltiazem causes minimal adverse effects, while GTN causes headaches in many patients requiring cessation 1, 6
• Lower recurrence rates: Diltiazem demonstrates better long-term outcomes than GTN 6

Compared to Surgery

• Avoids permanent sphincter damage: Chemical sphincterotomy with diltiazem avoids the small but permanent risk of minor incontinence associated with lateral internal sphincterotomy 1, 2
• Cost-effectiveness: Calcium channel blockers demonstrate remarkable cost-effectiveness compared to surgical interventions 3

Critical Pitfalls to Avoid

• Never use manual anal dilatation: This is absolutely contraindicated due to unacceptably high permanent incontinence rates of 10-30% 2, 4
• Do not perform surgery in acute phase: Surgical treatment is contraindicated in acute anal fissures and should only be considered after 6-8 weeks of failed medical therapy 1, 4
• Limit hydrocortisone use: Do not use hydrocortisone beyond 7 days due to risk of perianal skin thinning and atrophy, which can worsen the fissure 2, 3
• Rule out atypical pathology: Never proceed with any invasive treatment without excluding Crohn's disease, malignancy, or other atypical causes 2

Side Effects and Compliance

• Nearly 80% of patients report no adverse effects with diltiazem 8
• Most common side effect is perianal dermatitis (reported in 4 of 71 patients in one study) 7
• Headaches are rare with diltiazem (1 of 71 patients) compared to frequent occurrence with GTN 7
• Adverse effects rarely lead to reduced compliance 8

Long-Term Outcomes and Recurrence

• After successful healing, 66% of patients remain symptom-free at median 32 weeks follow-up 7
• Recurrences are common but usually amenable to repeat chemical sphincterotomy with diltiazem 7
• Overall, 59% of patients require further treatment (medical and/or surgical) over an average 2-year follow-up period 8
• Patients should be counseled that diltiazem may not be definitive treatment, and surgical options may eventually be needed 8

Special Considerations for Infected Fissures

If evidence of infection or poor genital hygiene exists, add topical metronidazole cream in combination with lidocaine 5%, applied 3 times daily, which demonstrates 86% healing rates compared to 56% with lidocaine alone. 4