Nitroglycerin ointment 0.4% is indicated for the treatment of moderate to severe pain associated with chronic anal fissure.

Apply 1 inch of ointment (375 mg of ointment equivalent to 1.5 mg of nitroglycerin) intra-anally every 12 hours for up to 3 weeks. A finger covering, such as plastic-wrap, disposable surgical glove or a finger cot, should be placed on the finger to apply the ointment. To obtain a 1.5 mg dose of nitroglycerin, the covered finger is laid alongside the 1 inch dosing line on the carton.

Refer to carton for accurate dosage guide.
The tube is gently squeezed until a line of ointment the length of the measuring line is expressed onto the covered finger. The ointment is gently inserted into the anal canal using the covered finger no further than to the first finger joint and the ointment is applied around the side of the anal canal. If this cannot be achieved due to pain, application of the ointment should be made directly to the outside of the anus. Treatment may be continued for up to three weeks.
Nitroglycerin ointment is not for oral, ophthalmic, or intravaginal use. Hands should be washed after application of the ointment [see Patient Instruction].

Ointment, 0.4% w/w (4 mg /1 g) in 30 g tubes.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The most common adverse reaction of nitroglycerin ointment applied to the anal canal is headache.

Headache may be recurrent following each dose. Headaches are typically of short duration and can be treated with an analgesic, e.g. acetaminophen, and are reversible upon discontinuation of treatment.

In Study REC-C-001, a double-blind, placebo-controlled trial in patients with a painful chronic anal fissure, the most frequent (>2%) adverse reactions reported were as follows (Table 1)

Table 1: Incidence of Adverse Reactions (> 2%) in Study REC-C-001

Hypotension

Transient episodes of light-headedness, occasionally related to blood pressure changes, also may occur. Hypotension (including orthostatic hypotension) occurs infrequently, but in some patients may be severe enough to warrant discontinuation of therapy.

Allergic Reactions
Flushing, allergic reactions, and application site reactions (including drug rash and exfoliative dermatitis) have been reported rarely.

Methemoglobinemia

In rare cases, therapeutic doses of organic nitrates have caused methemoglobinemia [see OVERDOSAGE (10)].

Nitroglycerin toxicity is generally mild. The estimated adult oral lethal dose of nitroglycerin is 200 mg to 1,200 mg. Infants may be more susceptible to toxicity from nitroglycerin. Consultation with a poison center should be considered.

Laboratory determinations of serum levels of nitroglycerin and its metabolites are not widely available, and such determinations have, in any event, no established role in the management of nitroglycerin overdose.

No data are available to suggest physiological maneuvers (e.g., maneuvers to change the pH of the urine) that might accelerate elimination of nitroglycerin and its active metabolites. Similarly, it is not known which, if any, of these substances can usefully be removed from the body by hemodialysis. No specific antagonist to the vasodilator effects of nitroglycerin is known, and no intervention has been subject to controlled study as a therapy of nitroglycerin overdose. Because the hypotension associated with nitroglycerin overdose is the result of venodilatation and arterial hypovolemia, prudent therapy in this situation should be directed toward increase in central fluid volume. Passive elevation of the patient's legs may be sufficient, but intravenous infusion of normal saline or similar fluid may also be necessary.

The use of epinephrine or other arterial vasoconstrictors in this setting is not recommended.

In patients with renal disease or congestive heart failure, therapy resulting in central volume expansion is not without hazard. Treatment of nitroglycerin ointment overdose in these patients may be subtle and difficult, and invasive monitoring may be required.

Methemoglobinemia
Methemoglobinemia has been rarely reported with organic nitrates. The diagnosis should be suspected in patients who exhibit signs of impaired oxygen delivery despite adequate arterial PO2. Classically, methemoglobinemic blood is described as chocolate brown, without color change on exposure to air.

If methemoglobinemia is present, intravenous administration of methylene blue, 1 to 2 mg/kg of body weight, may be required.

Nitroglycerin ointment, USP 0.4% is intended for intra-anal use. Nitroglycerin is 1,2,3,-propanetriol trinitrate, an organic nitrate vasodilator whose structural formula is as follows:

and whose molecular weight is 227.09. Nitroglycerin ointment, USP 0.4% contains 0.4% nitroglycerin w/w (4 mg nitroglycerin/1 g ointment), propylene glycol, lanolin, sorbitan sesquioleate, paraffin wax, and white petrolatum. Nitroglycerin ointment, USP 0.4% is available in tubes with a one-inch dosing line on the carton allowing the measurement of approximately 375 mg of nitroglycerin ointment, USP 0.4% (1.5 mg nitroglycerin) for application.

Nitroglycerin ointment was evaluated in a 3-week double-blind, randomized, multi-center, placebo- controlled study. Patients with a painful chronic anal fissure for at least 6 weeks and moderate or severe pain prior to treatment (≥ 50 mm on the 100mm visual analog scale, VAS) were randomized to receive 0.4% (1.5mg) nitroglycerin or placebo ointment applied to the anal canal every 12 hours. Pain as assessed by the change in VAS from baseline to Days 14-18 was lower in patients receiving 0.4% ointment compared to placebo. The mean change from baseline was 44mm for nitroglycerin ointment and 37mm for placebo. The difference in the mean change in pain between nitroglycerin ointment and placebo was -7.0mm (95% Confidence Interval: -13.6 to -0.4mm).

Nitroglycerin ointment, USP 0.4% is available in 30 g (NDC 21922-048-05) aluminum tubes with polyethylene screw caps.

Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F). [See USP Controlled Room Temperature].

Keep the tube tightly closed immediately after each use. Use within 8 weeks of first opening.

Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for
Use)

Interaction with PDE5 inhibitors

Advise patient not to use nitroglycerin ointment with medications for erectile dysfunction such as Viagra (sildenafil), Levitra (vardenafil), and Cialis (tadalafil). These products have been shown to increase the hypotensive effects of nitroglycerin ointment and other nitrate drugs [see Contraindications (4)].

Hypotension

Advise patients that treatment with nitroglycerin ointment may be associated with light-headedness on standing, especially just after rising from a lying or seated position. The effect may be more frequent in patients who have also consumed alcohol, since alcohol use contributes to hypotension. Advise patients to stand up from the supine or sitting position slowly.

Headaches

Advise patients that headaches sometimes accompany treatment with nitroglycerin ointment. For patients who get these headaches, the headaches may indicate the activity of the drug. Tolerance to headaches develops. Advise patients that if they experience headache they should not alter the schedule of their nitroglycerin ointment treatment to avoid the occurrence of headache. An analgesic, such as acetaminophen, may be used to prevent or relieve the headaches.

Dizziness

Advise patients that dizziness has been reported as a side-effect of treatment with nitroglycerin ointment. Advise patients not to drive or operate machinery immediately after applying nitroglycerin ointment.

Manufactured by:
Encube Ethicals Pvt. Ltd.
Plot No. C-1, Madkaim Industrial Estate,
Madkaim, Post: Mardol, Ponda,

Goa - 403 404, India.

Distributed by:
Encube Ethicals, Inc.
200 Meredith Drive, Suite 202

Durham, NC 27713 USA

Revised: 10/2024

 Nitroglycerin (nye" troe glis' er in) Ointment 0.4%

Read the Patient Information that comes with nitroglycerin ointment before you start using the product and each time you get a refill because there may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment. If you have any questions about nitroglycerin ointment, ask your healthcare provider.

What is nitroglycerin ointment?
Nitroglycerin ointment is a prescription medicine used to treat moderate to severe pain caused by chronic anal fissures. An anal fissure is a tear in the skin lining the anal canal.

Nitroglycerin ointment is not suitable for children and adolescents under the age of 18 years because it has not been assessed in people in this age group.

Who should not use nitroglycerin ointment?

Do not use nitroglycerin ointment if you:

• are taking a medicine for erectile dysfunction (male impotence), for example Viagra (sildenafil), Cialis (tadalafil) or Levitra (vardenafil).
• have been told by your doctor that you have severe anemia (low numbers of red blood cells in your blood)
• have increased intracranial pressure or high pressure within your skull e.g. following head trauma or bleeding in your brain
• are allergic to any of the ingredients in nitroglycerin ointment or if you have had allergic reactions to similar medicines in the past. See the end of this leaflet for a list of ingredients in nitroglycerin ointment.

What should I tell my healthcare provider before using nitroglycerin ointment?

Tell your healthcare provider about all your medical conditions, including if you:

• have low blood pressure
• have recently had a heart attack
• have heart or blood vessel disorders
• suffer from migraine or recurrent headaches
• are pregnant or plan to become pregnant. It is not known if nitroglycerin ointment will harm your unborn baby.
• are breast-feeding or plan to breast-feed. It is not known if the components of nitroglycerin ointment will harm your child if you breast-feed.

Nitroglycerin ointment may lower your blood pressure. When getting up from a lying or sitting position, you should get up slowly, otherwise you might feel faint.

Tell your healthcare provider about all the medicines you take, including prescription and non- prescription medicines, vitamins and herbal supplements. Other medicines may affect how nitroglycerin ointment works. Nitroglycerin ointment may also affect how other medicines work.

Specifically, tell your doctor if you are taking any of the following:

• other nitroglycerin containing products
• a medicine for erectile dysfunction (male impotence), for example sildenafil, tadalafil or vardenafil (see the section above ‘Who should not use nitroglycerin ointment’)
• medicines used to treat high blood pressure
• are taking aspirin, ergotamine (used to treat migraine) or are receiving tissue-type plasminogen activator (used to help dissolve blood clots formed in blood vessels in the heart, lungs and brain)
• are to be given heparin. If so, close monitoring of your blood will be required as your dose of heparin may need to be altered. Please discuss with your doctor before stopping nitroglycerin ointment.

How should nitroglycerin ointment be used? 

 Use nitroglycerin ointment exactly as prescribed. See detailed Patient Instructions for Applying nitroglycerin ointment at the end of this Patient Information leaflet.

Treatment may be continued for up to 3 weeks. If your anal pain does not get better after using nitroglycerin ointment you should talk to your doctor.

What should I avoid while using nitroglycerin ointment?
Do not drive or operate machinery immediately after applying nitroglycerin ointment. If you feel dizzy or light-headed after applying the ointment do not drive or operate machinery until the dizziness has stopped.

Avoid consuming alcohol while you are being treated with nitroglycerin ointment as your blood pressure is more likely to be affected if you consume alcoholic beverages.

What are the possible side effects of nitroglycerin ointment?

Nitroglycerin ointment can cause serious side-effects: Stop using the ointment and seek medical attention immediately if you have an allergic reaction. You may have swelling of the face, lips, tongue or throat, or difficulty breathing.

Common side-effects of nitroglycerin ointment are:

• Headaches, which can be severe. You could take painkillers for this (such as acetaminophen). If the headaches are unpleasant, you may need to ask your doctor whether you should stop using nitroglycerin ointment.
• Dizziness, faintness on standing, or light-headedness

These are not all the possible side effects of nitroglycerin ointment. Tell your healthcare provider if you have any side effect that bothers you or that does not go away. For more information, ask your healthcare provider or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800- FDA-1088.

How should I store nitroglycerin ointment?

• Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F). [See USP Controlled Room Temperature].
• Keep the tube tightly closed immediately after each use.
• Use within 8 weeks of first opening.

Keep nitroglycerin ointment out of the reach of children.

Do not use nitroglycerin ointment after the expiry date which is stated on the label and carton after ‘EXP.’ The expiry date refers to the last day of that month.

General information about nitroglycerin ointment

Medicines are sometimes prescribed for conditions that are not mentioned in Patient Information leaflets. Do not use nitroglycerin ointment for a condition for which it is not prescribed. Do not give nitroglycerin ointment to other people, even if they have the same symptoms you have. It may harm them.

This Patient Information leaflet summarizes the most important information about nitroglycerin ointment. If you would like more information, talk to your healthcare provider. You can ask your pharmacist or healthcare provider for information about nitroglycerin ointment that is written for health professionals.

For more information call 1-833-285-4151

Patient Instructions for Use When do I apply the ointment?
Apply the ointment every 12 hours exactly as your doctor has told you to.

How do I apply the ointment?

Cover your finger with plastic-wrap, a disposable surgical glove or a finger cot.

Lay the covered finger alongside the 1 inch dosing line marked on the side of the medicine box (see figure below) so that the tip of your finger is at one end of the dosing line. Starting at the tip of the finger, squeeze the ointment onto your finger for the same length marked on the box.

Refer to carton for accurate dosage guide.

Gently insert the finger with the ointment into the anal canal, up to the first finger joint. Carefully smear the ointment around the inner sides of the anal canal. If this cannot be achieved due to pain, application of the ointment should be made directly to the outside of the anus.

What do I do after I have applied the ointment?
Throw away the finger covering in the garbage, out of the reach of children and pets. Wash your hands.

What are the ingredients in nitroglycerin ointment?
Active ingredient: nitroglycerin
Inactive ingredients: propylene glycol, lanolin, sorbitan sesquioleate, paraffin wax and white petrolatum.

Manufactured by:
Encube Ethicals Pvt. Ltd.
Plot No. C-1, Madkaim Industrial Estate,
Madkaim, Post: Mardol, Ponda,
Goa - 403 404, India.

Distributed by:
Encube Ethicals, Inc.
200 Meredith Drive, Suite 202
Durham, NC 27713 USA

Revised: 10/2024

NDC 21922-048-05
Nitroglycerin Ointment, USP 0.4%
30 g
Rx only
Carton Label