Nitroglycerin ointment for anal fissure: does it work, and can you live with the headache?

How does nitroglycerin ointment help an anal fissure heal?

Nitroglycerin, also called glyceryl trinitrate or GTN, is the same molecule people with angina put under the tongue. In the body it releases nitric oxide, the natural signal that tells smooth muscle to relax. The internal anal sphincter is smooth muscle, and in a chronic fissure it is stuck in a state of high resting tone.

That tone is the whole problem. The tight sphincter squeezes the small arteries that feed the back of the anal canal, the tear gets too little blood, and it cannot heal. Each bowel movement then reopens it, the pain triggers more spasm, and the cycle continues. A nitroglycerin ointment applied at the anal opening lowers the resting pressure for several hours, blood flow improves, and the tear finally has a chance to close. Surgeons sometimes call this a "chemical sphincterotomy": the effect of cutting part of the muscle, but reversible and without a knife.

The catch is that nitric oxide does not stay in the anus. It reaches the bloodstream and widens blood vessels everywhere, including those around the brain. That is where the headache comes from, and it is the same reason the ointment can make you lightheaded when you stand up.

How well does nitroglycerin ointment actually work?

Honestly: it works, but less than its reputation suggests. The numbers from the sources we trust most:

• Against placebo: the Cochrane review of non-surgical therapy found that nitroglycerin healed 48.9 % of chronic fissures compared with 35.5 % for placebo. That gap is real but modest, and the review noted that about half of the fissures that healed with nitroglycerin came back later.
• Against diltiazem: a systematic review of seven randomized trials with 481 patients found the same healing rate for both ointments, but diltiazem caused fewer headaches (risk ratio 0.39) and fewer recurrences (risk ratio 0.68).
• Against botulinum toxin: in a trial published in the New England Journal of Medicine, 96 % of fissures had healed at two months with botulinum toxin against 60 % with nitroglycerin. A later meta-analysis of six trials found no significant difference in healing or recurrence, but far fewer adverse effects with the toxin (odds ratio 0.12), at the cost of more temporary incontinence.

So why do guidelines still list it as first line? Because it is cheap, widely available as a licensed product, avoids a procedure, and for the patients who tolerate it, it does the job. The American (ASCRS 2023) and British (ACPGBI 2023) guidelines both accept topical nitrates or calcium channel blockers as the first treatment for a chronic fissure. The practical difference between them is tolerance, not healing.

Why does nitroglycerin cause headaches, and how common are they?

Headache is the defining side effect of nitroglycerin ointment. It affects up to half of patients, and in many it is the reason they quit. The mechanism is the same widening of blood vessels that relaxes the sphincter: the vessels around the brain dilate, and the result is a throbbing, pressure-type headache, often at the front or the temples.

What patients describe in clinic follows a fairly typical pattern:

• The headache starts within minutes to an hour after an application and fades over the next hours.
• It is usually worst in the first days of treatment. Many people notice it becomes milder as the body gets used to the drug, which is the same tolerance that cardiologists see in angina patients.
• It can come with flushing of the face, lightheadedness when standing up, or a pounding heartbeat.
• People who already have migraines tend to have a harder time.

The real cost of the headache is not the discomfort itself but what it does to adherence. A fissure needs 6 to 8 weeks of steady treatment. Someone who skips the evening dose because of the headache, then the morning one, ends up with a few weeks of partial treatment, a fissure that has not closed, and the conclusion that "creams do not work". If that sounds like your story, read Four weeks on fissure cream and no better: what to check and what comes next before you give up on medical treatment.

How can you reduce the headache and still finish the treatment?

You do not have to choose between a headache and an open fissure. These are the measures we give patients who start nitroglycerin:

1. Use the measured amount, not more. Each product has its own dosing guide (a line on the box or a measured strip). More ointment does not heal the tear sooner; it only means more nitroglycerin in your blood and a worse headache.
2. Protect your finger. Nitroglycerin crosses intact skin. Apply it with a finger cot or a disposable glove, or wash your hands well right away, so you are not absorbing a second dose through the fingertip.
3. Sit or lie down after applying. Rest for a while after each dose and stand up slowly. This limits the dizziness and lets the worst of the headache pass while you are still.
4. Time the evening dose for bedtime. Many people sleep through most of the headache from the second dose.
5. Ask about a simple painkiller. Acetaminophen (paracetamol) usually controls the headache. Check with your doctor or pharmacist first, especially if you take other medicines.
6. Avoid alcohol in the hours after applying it: it adds to the drop in blood pressure.

If the headache is severe, comes with every dose after the first week, or makes you faint, do not simply stop. Ask your doctor to switch you to a calcium channel blocker ointment. Diltiazem 2% cream for anal fissure: who it is for, how to use it and what to expect and Nifedipine cream for anal fissure: dose, application, side effects and the 8-week plan explain the two alternatives, which heal about as often with far fewer headaches. Other side effects and how to handle them are covered in Side effects of anal fissure creams and how to manage them.

Who should not use nitroglycerin ointment?

Because nitroglycerin acts on blood vessels throughout the body, it is not for everyone. Tell your doctor before starting it if any of these apply:

• You take erectile dysfunction pills such as sildenafil, tadalafil or vardenafil, or the lung drug riociguat. The combination can cause a severe fall in blood pressure. This is an absolute no.
• You have low blood pressure, faint easily, or are dehydrated.
• You have certain heart conditions, such as a narrowed aortic or mitral valve or hypertrophic cardiomyopathy, where a sudden drop in blood pressure is dangerous.
• You have had a recent head injury, bleeding in the brain or raised pressure inside the skull.
• You have severe anemia or frequent migraines.
• You are pregnant or breastfeeding. Treatment choices are different; we explain them in Which anal fissure cream is safe in pregnancy and while breastfeeding?.

One more safety point that matters in practice: the 2 % nitroglycerin ointment sold for angina is several times stronger than the anal products and must never be used on a fissure. If a pharmacy offers you "nitroglycerin ointment" without saying the strength, ask.

Rectiv, Rectogesic or a pharmacy-made ointment: what can you get where you live?

Nitroglycerin ointment for anal fissure needs a prescription in every country we cover. What changes is the product:

If you are weighing Rectogesic against its alternatives, we compare them point by point in Rectogesic or an alternative? What surgeons weigh before choosing your fissure ointment. For a broader head-to-head with nifedipine and diltiazem, see Nifedipine, diltiazem or nitroglycerin: which fissure ointment should you choose?, and for the basics of each drug, our nitroglycerin page.

How long should you use it, and what if the fissure does not close?

Use nitroglycerin ointment twice a day for 6 to 8 weeks, together with fiber, water and sitz baths. Pain usually falls in the first two weeks; the tear needs the full course to close. Stopping when it stops hurting is the most common reason for a fissure to reopen, and with nitroglycerin, where recurrence is already high, that matters even more. How to apply any fissure ointment correctly is covered in How to apply anal fissure cream correctly: where, how much and when.

If the fissure is still open after 8 weeks of correct use, more nitroglycerin is not the answer. The next steps are a botulinum toxin injection or a lateral internal sphincterotomy, decided with a colorectal surgeon; see All guides and our treatment overview.

And some symptoms mean the problem may not be a simple fissure at all. See a doctor without delay if you have:

Where does FISURIN fit?

FISURIN does not contain nitroglycerin. It is the cream our surgeons at Clínica Proctológica de Lima prescribe for chronic and post-operative fissures, combining nifedipine (a calcium channel blocker, the class that heals about as often as nitroglycerin with fewer headaches) and lidocaine in a water-based hydrogel, with a written 6-week protocol. It is a reasonable option for patients who cannot tolerate nitroglycerin, but it still needs soft stools and the full course, and it cannot promise closure in every case. Today FISURIN is a magistral formula prepared under prescription in Peru and is not shipped abroad; FISURIN Hydrogel and FISURIN Relief are in preparation with a waiting list by country. See what is inside FISURIN or how to get it where you live.