What is the use of ISDN (Isosorbide Dinitrate) cream in adults with anal fissures?

ISDN Cream for Anal Fissures

ISDN (isosorbide dinitrate) cream is an effective first-line topical treatment for chronic anal fissures, achieving 93% primary healing rates within 8 weeks, though it has been largely superseded by calcium channel blockers like nifedipine and diltiazem due to their superior efficacy and fewer side effects. 1, 2

Mechanism of Action

• ISDN works as a nitric oxide donor that reduces internal anal sphincter pressure at rest and increases anodermal blood flow to the ischemic ulcer, promoting healing of the fissure 3, 4
• The medication addresses the underlying pathophysiology of chronic anal fissures: internal anal sphincter hypertonia with decreased blood flow creating an ischemic environment 5

Application Protocol

• Apply ISDN 1% ointment intra-anally every 3 hours during waking hours (4-6 times daily), excluding nighttime application 4, 2
• Treatment duration should be at least 6-8 weeks, with many patients requiring continuation beyond 6 weeks for complete healing 3, 6
• Pain relief typically occurs within 3 weeks, though complete fissure healing takes longer 4

Expected Outcomes

• Primary healing rates of 93% within 8 weeks have been demonstrated in prospective studies 1
• Healing progression: 56% healed at 6 weeks, 69% at 9 weeks, and 94% at 12 weeks 4
• For recurrent fissures after initial ISDN healing, 54% can be successfully retreated with ISDN 1
• Recurrence rates after successful healing are approximately 4.8% at 12 months 7

Side Effects and Compliance Issues

• Headache is the most common side effect, occurring in 27-100% of patients, though typically mild and transient 1, 2, 4
• Headaches usually respond well to paracetamol and resolve as treatment continues 7
• The high application frequency (4-6 times daily) combined with headache side effects leads to poor compliance compared to alternatives 2

Mandatory Adjunctive Measures

• All patients must receive fiber supplementation of 25-30g daily to soften stools and minimize anal trauma 5, 6
• Adequate fluid intake is essential to prevent constipation 5
• Warm sitz baths promote sphincter relaxation and should be used as adjunctive therapy 5
• Topical analgesics like lidocaine 5% can be added for pain control 5

Comparison with Alternative Treatments

• Compounded 0.3% nifedipine with 1.5% lidocaine achieves superior 95% healing rates compared to ISDN's 60-70% rates, with significantly fewer headaches 6, 8
• Diltiazem 2% ointment shows similar efficacy to ISDN (48-75% healing) but requires only twice-daily application with no systemic side effects, making it preferable as first-line therapy 5, 2
• Lateral internal sphincterotomy (LIS) demonstrates 92-97% healing rates by 6 months versus 77% with ISDN, though surgery carries a small risk of minor incontinence 7, 5

Treatment Failure and Next Steps

• If no healing occurs after 6-8 weeks of ISDN therapy, classify as treatment failure and consider alternative treatments or surgical referral 6
• Approximately 7% of patients show no response to ISDN and require surgery 1
• Botulinum toxin injection (75-95% cure rates) or LIS (>95% healing rates) should be considered for refractory cases 5

Critical Pitfalls to Avoid

• Never perform manual anal dilatation—it is absolutely contraindicated due to unacceptably high permanent incontinence rates of 10-30% 5
• Do not use hydrocortisone beyond 7 days due to risk of perianal skin thinning and atrophy that can worsen the fissure 5
• Atypical fissure locations (lateral or multiple fissures) require urgent evaluation for IBD, cancer, HIV, syphilis, or other underlying conditions before initiating ISDN therapy 5
• Do not rush to surgery for acute fissures, as 50% heal with conservative management alone within 10-14 days 5

Current Clinical Position

• While ISDN remains effective, calcium channel blockers (nifedipine or diltiazem) should be preferred as first-line pharmacologic therapy due to better efficacy, fewer side effects, and improved compliance 2, 5
• ISDN can still be offered to selected patients, particularly those who cannot access compounded formulations or have contraindications to calcium channel blockers 7