What is the use of nitroglycerin (glyceryl trinitrate) rectal ointment?

From the Guidelines

Nitroglycerin rectal ointment is not the first-line treatment for anal fissures due to its variable healing rates and potential side effects, such as headaches, and instead, topical calcium channel blockers like diltiazem or nifedipine are recommended as a more effective and safer alternative 1.

Treatment Overview

The primary goals of anal fissure therapy are to achieve internal anal sphincter (IAS) relaxation, reduce pain, and facilitate the healing process.

• Stool softeners, such as increased intake of oral fluids, high-fiber diet, or fiber supplements, and bulk-forming laxatives, are recommended to minimize anal trauma and increase blood flow.
• Sphincter muscle relaxers, including warm sitz baths, local application of calcium channel blockers like diltiazem or nifedipine, and botulinum injection, can help achieve IAS relaxation.

Nitroglycerin Rectal Ointment

Nitroglycerin rectal ointment is a medication that releases nitric oxide, causing smooth muscle relaxation in the internal anal sphincter, reducing pressure and pain, and increasing blood flow to promote healing.

• The typical prescription is 0.2% or 0.4% nitroglycerin ointment applied to the anal canal with a finger or applicator, usually a pea-sized amount, 2-3 times daily for 6-8 weeks.
• However, according to a recent systematic review and meta-analysis, calcium channel blockers (diltiazem or nifedipine) are more effective than glyceryl trinitrate, with healing rates ranging from 65 to 95%, and have fewer side effects, such as headaches and hypotension 1.

Side Effects and Precautions

• Headaches are the most common side effect of nitroglycerin rectal ointment, occurring in up to 50% of patients, and can be managed by taking acetaminophen 30 minutes before application or by temporarily reducing the dose.
• Other possible side effects include dizziness and light-headedness, especially when standing up quickly.
• Patients should avoid using this medication if they take medications for erectile dysfunction, have severe anemia, glaucoma, or recent head trauma.

Alternative Treatments

• Topical calcium channel blockers, such as diltiazem or nifedipine, are recommended as a more effective and safer alternative to nitroglycerin rectal ointment for the treatment of anal fissures 1.
• Botulinum injection can also be used to achieve temporary paralysis of the anal sphincter muscle for 2-3 months.
• Controlled anal dilatation, including balloon dilatation and staged dilatation, may be considered as a non-operative management option, but more studies are needed to confirm its effectiveness in the acute setting.

From the Research

Nitroglycerine Rectal Ointment

• Nitroglycerine rectal ointment is used to treat chronic anal fissure pain, with a mechanism of action involving the donation of nitric oxide, which mediates relaxation of the internal anal sphincter 2.
• The dosage and administration of 0.4% nitroglycerin rectal ointment is 375 mg, applied twice daily, delivering a daily nitroglycerin dose of 3mg 2.
• Common adverse events associated with nitroglycerine rectal ointment include headache, which can be severe in up to 25% of patients 2, 3.
• Studies have shown that nitroglycerine rectal ointment can be effective in treating anal fissures, with one study reporting a 56% success rate in acute fissures and 41% in chronic fissures 3.
• However, another study found that nitroglycerine ointment was only effective in approximately half of patients with anal fissure, with a high incidence of adverse reactions 3.
• A systematic review and meta-analysis of treatments for anal fissure found that glyceryl trinitrate (GTN) was more effective than control in achieving sustained cure, but the quality of evidence was very poor due to heterogeneity and risk of bias 4.
• Other treatment options for anal fissures include topical calcium channel blockers, botulinum toxin injection, and surgical interventions such as partial lateral internal sphincterotomy (LIS) 4, 5.
• The choice of treatment for anal fissure depends on the severity and persistence of the fissure, as well as the presence of any underlying conditions 5.