PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

Principal Display Panel - Carton Label

NDC 0713-0564-31

Rx only

Nitroglycerin Ointment, USP

0.4%

For Intra-anal Use Only

Do not discard the carton- Dosage Guide included on two sides of the carton

Use within 8 weeks of first opening.

30 g

Cosette Pharmaceuticals, Inc.

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DESCRIPTION SECTION

11 DESCRIPTION

Nitroglycerin ointment USP, 0.4% is intended for intra-anal use.Nitroglycerin is 1,2,3,-propanetriol trinitrate, an organic nitrate 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 0.4% (1.5 mg nitroglycerin) for application.

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INDICATIONS & USAGE SECTION

Highlight: Nitroglycerin ointment is a nitrate vasodilator indicated for the treatment of moderate to severe pain associated with chronic anal fissure ( 1).

1 INDICATIONS AND USAGE

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

DOSAGE & ADMINISTRATION SECTION

Highlight: 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 ( 2).

Nitroglycerin ointment is not for oral, ophthalmic, or intravaginal use ( 2)

2 DOSAGE AND ADMINISTRATION

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 Patients Instruction for Use.

DOSAGE FORMS & STRENGTHS SECTION

Highlight: Ointment 0.4% w/w (4 mg nitroglycerin/1 g ointment) ( 3)

3 DOSAGE FORMS AND STRENGTHS

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

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USE IN SPECIFIC POPULATIONS SECTION

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C

Animal reproduction and teratogenicity studies have not been conducted with nitroglycerin ointment. Nitroglycerin was not teratogenic when administered by topical or dietary route. There are no adequate and well-controlled studies in pregnant women. Nitroglycerin ointment should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Teratology studies in rats and rabbits were conducted with topically applied nitroglycerin ointment at doses up to 80 mg/kg/day and 240 mg/kg/day, respectively. No toxic effects on dams or fetuses were seen at any dose tested.

A teratogenicity study was conducted in rats with nitroglycerin administered in the diet at levels up to 1% content (approximately 430 mg/kg/day) on days 6 to 15 of gestation. In offspring of the high-dose group, an increased but not statistically significant incidence of diaphragmatic hernias was noted together with decreased hyoid bone ossification. The latter finding probably reflects delayed development, thus indicating no clear evidence of a potential teratogenic effect of nitroglycerin.

8.3 Nursing Mothers

It is not known whether nitroglycerin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when nitroglycerin ointment is administered to a nursing woman.

8.4 Pediatric Use

The safety and effectiveness of nitroglycerin ointment in pediatric patients under 18 years of age have not been established.

8.5 Geriatric Use

Clinical studies of nitroglycerin ointment did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Clinical data from the published literature indicate that the elderly demonstrate increased sensitivity to nitrates, which may be therapeutic but also manifest by more frequent or severe hypotension and related dizziness or fainting. Increased sensitivity may reflect the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

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CLINICAL STUDIES SECTION

14 CLINICAL STUDIES

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).

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SPL PATIENT PACKAGE INSERT SECTION

17.5 FDA-Approved Patient Labeling

Patient Information

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 Instructionsfor 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 from 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].
• Keep the tube tightly closed.
• 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 1-800-922-1038.

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HOW SUPPLIED SECTION

16 HOW SUPPLIED/STORAGE AND HANDLING

Nitroglycerin ointment USP, 0.4% is available in 30 g (NDC 0713-0564-31) aluminum tubes with polypropylene screw caps.

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

Keep the tube tightly closed. Use within 8 weeks of first opening.

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INSTRUCTIONS FOR USE SECTION

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.

Distributed by:
Cosette Pharmaceuticals, Inc.
South Plainfield, NJ 07080

8-0564CPLNC2
VC7724
Revised: April 2023

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