Side Effects of ISDN Cream for Anal Fissures
Headache is the most common side effect of topical isosorbide dinitrate (ISDN) for anal fissures, occurring in approximately 27% of patients, though it is typically mild, transient, and rarely requires discontinuation of therapy. 1, 2, 3
Primary Adverse Effects
Headache (Most Common)
- Headache is dose-related and may be severe or recurrent with each daily dose, particularly at higher doses 1
- All patients in one study experienced mild and transient headache shortly after beginning treatment, but this did not prevent continued therapy 3
- The headache side effect, combined with the frequent application requirement (4-6 times daily), leads to low compliance with ISDN therapy 2
Cardiovascular Effects
- Transient lightheadedness occasionally occurs, related to blood pressure changes 1
- Hypotension occurs infrequently but may be severe enough to warrant discontinuation in some patients 1
- Syncope, crescendo angina, and rebound hypertension have been reported but are uncommon 1
Rare but Serious Effects
- Methemoglobinemia can occur extremely rarely with ordinary doses of organic nitrates, even in normal-appearing patients, though this is so infrequent that it is not a major clinical concern 1
Clinical Context and Comparative Considerations
Efficacy vs. Side Effect Profile
- ISDN achieves 83% healing rates within 4 weeks when applied as 2.5 mg three times daily 4
- Despite its efficacy, ISDN is not commercially available in the United States and must be prepared by compounding pharmacies, limiting its practicality 4
Superior Alternatives
- Diltiazem 2% ointment should be considered as first-line treatment over ISDN because it requires only twice-daily application, has no reported systemic side effects, and demonstrates similar efficacy (48-75% healing rates) 4, 2
- Compounded 0.3% nifedipine with 1.5% lidocaine achieves 95% healing rates with minimal adverse effects, making it superior to ISDN 4
Important Clinical Pitfalls
- The 27% headache rate with ISDN is significantly higher than alternative calcium channel blockers like diltiazem, which have no reported systemic side effects 2
- The requirement for 4-6 times daily application creates a compliance barrier that undermines the theoretical efficacy of ISDN 2
- If headaches occur, they typically resolve within the first few days of treatment and rarely necessitate stopping therapy 3