How often should nitroglycerin (glyceryl trinitrate) rectal ointment be applied for an anal fissure?

Nitroglycerin Rectal Ointment Application Frequency for Anal Fissure

Apply nitroglycerin rectal ointment twice daily (every 12 hours) for anal fissure treatment, continuing for at least 6–8 weeks to achieve optimal healing. 1, 2

Standard Dosing Protocol

• Apply 375 mg of 0.4% nitroglycerin ointment (delivering 1.5 mg nitroglycerin per dose) twice daily directly to the anoderm, which is the guideline-endorsed regimen for chronic anal fissure pain. 2

• The World Journal of Emergency Surgery recommends administration for at least 6 weeks, with pain relief typically occurring after 14 days of consistent use. 1

• Apply the ointment intra-anally using the applicator provided, ensuring direct contact with the anal canal tissue to maximize local sphincter relaxation. 2

Mechanism and Expected Outcomes

• Nitroglycerin acts as a nitric oxide donor that relaxes the hypertonic internal anal sphincter, reducing anal canal pressure and improving anodermal blood flow, which addresses the underlying pathophysiology of anal fissures. 1, 2

• Healing rates with twice-daily nitroglycerin range from 41–60% for chronic fissures, though this is significantly lower than calcium channel blockers like nifedipine (92% healing rate). 1, 3, 4

• The World Journal of Emergency Surgery notes that calcium channel blockers (diltiazem or nifedipine) are more effective than glyceryl trinitrate and carry less risk of headache and hypotension. 1

Critical Side Effects and Management

• Headache occurs in 75–100% of patients using nitroglycerin ointment, and is severe enough to cause treatment discontinuation in 20–25% of cases. 2, 3, 4

• The high incidence of headache is the primary limitation of nitroglycerin therapy, with one study concluding that "nitroglycerin more often causes a headache than treats the symptoms of anal fissure." 3

• If headache is intolerable, switch to topical 0.3% nifedipine with 1.5% lidocaine ointment applied every 12 hours for two weeks, which achieves 92% resolution without systemic side effects. 1

When to Consider Alternative Therapy

• If symptoms persist after 6–8 weeks of twice-daily nitroglycerin therapy, escalate to botulinum toxin injection or lateral internal sphincterotomy, as continued medical therapy beyond this point has diminishing returns. 1, 4, 5

• Botulinum toxin injection achieves 96% healing rates compared to 60% with nitroglycerin, with no headache side effects and no risk of fecal incontinence. 4

• Never perform manual anal dilatation, as it causes permanent sphincter injury with 52% incontinence rates at long-term follow-up. 1

Important Contraindications

• Avoid nitroglycerin in patients taking phosphodiesterase inhibitors (sildenafil within 24 hours, tadalafil within 48 hours) due to risk of life-threatening hypotension. 1

• Do not use if systolic blood pressure is <90 mmHg, as further vasodilation can compromise organ perfusion. 1