Epinitril

PACKAGE LEAFLET: INFORMATION FOR THE USER

Epinitril 5 mg/24 hours transdermal patch, 10 mg/24 hours transdermal patch, 15 mg/24 hours transdermal patch

Nitroglycerin
Please read this leaflet carefully before using this medicine because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Never give it to others. This medicine could be dangerous for other people, even if their symptoms are the same as yours.
• If you experience any adverse reaction, inform your doctor or pharmacist. This includes any adverse reaction not listed in this leaflet. See section 4.

Contents of this leaflet:

1. What Epinitril is and what it is used for
2. What you need to know before using Epinitril
3. How to use Epinitril
4. Possible side effects
5. How to store Epinitril
6. Contents of the pack and other information

1. What Epinitril is and what it is used for

Epinitril patches contain the active substance nitroglycerin, a vasodilator used for cardiac conditions, which belongs to a group of medicines called organic nitrates.
Epinitril patches are applied to the skin, and the active substance passes through the skin and enters the body.
Epinitril is indicated for the prevention of angina attacks, taken either as monotherapy or in combination with other anti-anginal therapies.
Angina typically manifests as pain or a feeling of pressure in the chest, which may spread to the neck or arm. The pain occurs when the heart is inadequately oxygenated. Epinitril is not indicated for the treatment of acute angina episodes. Sublingual tablets or spray should be used for the treatment of acute attacks.
Epinitril patches are for external use only.

2. What you need to know before using Epinitril

Do not use Epinitril

• if you are allergic (hypersensitive) to nitroglycerin, to related organic nitrates, or to any of the excipients of Epinitril (listed in section 6);
• if you are currently experiencing or have recently experienced shock associated with very low blood pressure;
• if you have medical conditions such as headache, vomiting, or seizures associated with increased intracranial pressure, including that caused by head trauma;
• if you suffer from heart failure due to obstruction, such as narrowing of the aortic orifice or the atrioventricular orifice of the heart (aortic stenosis or mitral stenosis, respectively), or from fibrous thickening of the thin sac-like membrane surrounding the heart (constrictive pericarditis);
• if you are taking medicines for erectile dysfunction (e.g., sildenafil or other PDE-5 inhibitors). Nitrates must not be administered to patients treated with sildenafil or any other medicine for erectile dysfunction. Patients undergoing nitrate therapy must not take sildenafil or other medicines for the treatment of erectile dysfunction. The combination of a nitrate with sildenafil or any other PDE-5 inhibitor may cause a sudden and severe drop in blood pressure, which could lead to fainting, loss of consciousness, or even heart attack (see section “Other medicines and Epinitril”);
• if you are taking medicines containing riociguat, a soluble guanylate cyclase stimulator;
• if you suffer from severe hypotension (systolic blood pressure below 90 mm Hg);
• if you suffer from severe reduction in blood volume due to blood loss or loss of body fluids (severe hypovolemia);
• if you suffer from severe anemia;
• if you suffer from toxic fluid accumulation in the lungs (toxic pulmonary edema).

Warnings and precautions
Talk to your doctor or pharmacist before using Epinitril:

• if you are stopping treatment. Discontinuation of treatment with Epinitril should be done gradually, replacing the patch with decreasing oral doses of long-acting nitrates;
• if you need to undergo magnetic resonance imaging (MRI), electrical stimulation of the heart to restore normal heart rhythm (defibrillation or cardioversion), or prior to thermal therapy (diathermy). You must remove the Epinitril patch before undergoing these procedures;
• if you have had, or have recently had, a heart attack (myocardial infarction), or if you rapidly develop symptoms of heart failure (acute heart failure) such as shortness of breath, severe fatigue, or leg swelling. Your doctor may ask you to undergo laboratory tests to assess your cardiovascular function;
• if you develop severe hypotension during treatment with Epinitril, removal of the patch may be necessary. If you experience collapse or shock, the Epinitril patch must be removed;
• in case of chest pain (acute anginal attacks), if the heart does not receive enough blood and oxygen (unstable angina), or in case of heart attack (myocardial infarction). Epinitril must not be used as immediate treatment for these conditions;
• if you experience severe headache or if your blood pressure values are below normal (hypotension). This may occur with an initial dose that is too high. It is recommended to gradually increase the dose until the optimal effect is achieved;
• if you are taking other nitrates or sublingual nitroglycerin, as your body may develop resistance to the effects of these substances following repeated exposure (cross-tolerance);
• if you have experienced or previously experienced nitroglycerin-induced low blood pressure. In such cases, a slowing of the heart rate (paradoxical bradycardia) and worsening of angina may occur;
• if you have a disease of the optic nerve (closed-angle glaucoma);
• if your blood oxygen level is insufficient (hypoxemia) due to severe anemia, lung disease, or reduced blood supply to the heart (ischemic heart failure). Patients with these medical conditions frequently suffer from an imbalance in the ventilation/perfusion ratio, which is an indicator of respiratory function. In these patients, nitroglycerin may worsen the ventilation/perfusion imbalance and cause further reduction in blood oxygenation;
• if your angina is caused by thickening of the heart muscle (hypertrophic cardiomyopathy). Nitrates may worsen this type of angina;
• if you experience an increased frequency of anginal attacks during periods without the patch. Your doctor may consider whether additional antianginal therapy is appropriate;
• if you develop skin sensitization reactions (itching, burning, inflammation), stop treatment and consult your doctor.

Other medicines and Epinitril

Concomitant administration of medicines for erectile dysfunction (e.g., sildenafil or other PDE-5 inhibitors) enhances the hypotensive effects of nitrates and must therefore be avoided (see also section “Do not use Epinitril”).
Concomitant use with riociguat, a soluble guanylate cyclase stimulator, must be avoided, as it may cause hypotension (see also section “Do not use Epinitril”).
Concomitant use with the following medicines may enhance the hypotensive effects of Epinitril:

• medicines used to lower blood pressure, such as calcium channel blockers, ACE inhibitors (for treatment of congestive heart failure), beta-blockers (used to manage cardiac arrhythmias), diuretics (to increase fluid elimination from the body), and other antihypertensives;
• tricyclic antidepressants (medicines for the treatment of depressive disorders);
• neuroleptics (medicines used to manage psychoses);
• commonly used tranquilizers (sedatives);
• alcohol consumption;
• concomitant use of amifostine (a cytoprotective agent used in chemotherapy and radiotherapy);
• and concomitant use of acetylsalicylic acid (a NSAID).

Concomitant use with dihydroergotamine may reduce the effect of Epinitril.
Non-steroidal anti-inflammatory drugs (NSAIDs), except acetylsalicylic acid, may reduce the therapeutic response to Epinitril.
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicine.

Pregnancy, breastfeeding, and fertility
Epinitril must not be used during pregnancy, especially during the first three months, unless your doctor has specifically instructed you to do so.
Due to limited information on the presence of nitroglycerin in human breast milk, a risk to the breastfed infant cannot be excluded. Your doctor will assess whether to discontinue breastfeeding or Epinitril.
No data are available on the effect of Epinitril on male fertility.
If you are pregnant, suspect you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before taking this medicine.

Driving and using machines
Especially at the beginning of treatment or when dose adjustments are made, Epinitril may affect your ability to drive or operate machinery, as it may alter your reaction time or rarely cause low blood pressure in the upright position and dizziness, and, in exceptional cases, fainting following overdose.
If you experience these effects, you must avoid driving or operating machinery.

3. How to use Epinitril

Use Epinitril exactly as directed by your doctor. If you have any doubts, consult your doctor or pharmacist.
The recommended dose is one Epinitril patch once daily. Apply the patch carefully to the skin and leave it in place for 12–16 hours. Then, remove the patch and observe a patch-free interval of 8–12 hours for the remainder of the day.
You must replace the Epinitril patch according to the instructions provided by your doctor. Your doctor will inform you how long the patch should remain on the skin and the duration of the patch-free interval.

Use in children and adolescents
Epinitril must not be used in children and adolescents under 18 years of age.

Duration of treatment with Epinitril
Treatment with Epinitril may continue for several years; however, your doctor will want to examine you regularly to decide whether to continue treatment or modify the therapeutic regimen.

How to apply the patch
The patch must be applied to clean, dry skin and not on wounds, birthmarks, moles, or on an area where a cream, moisturizing lotion, or talcum powder has recently been applied. It is recommended to apply Epinitril transdermal patches to the skin of the chest (see Figure 1), or to the outer upper part of the arm, free from redness or irritation, and to rotate application sites. The application area may be shaved if necessary. Avoid areas that form folds or are subject to friction during movement.

Figure 1
Do not apply two patches consecutively to the same area.
The Epinitril patch should be applied to the skin immediately after removal from its pouch, as follows:
(I) Open the pouch by tearing at the marked notch.
Do not use scissors (see Figure 2).

Figure 2
(II) Hold the patch between your thumb and index finger at the smaller end of the protective liner marked by a notch (see Figure 3).

Figure 3
(III) With the other hand, remove the larger part of the protective liner and discard it (see Figure 4).
Do not touch the adhesive side of the patch, as this may impair proper adhesion.

Figure 4
(IV) Apply the patch to the skin, holding the part still covered by the protective liner between your thumb and index finger. Remove the remaining part of the protective liner and press firmly for approximately 10 seconds over the entire surface of the patch. Run your finger along the edges to ensure good adhesion.
Wash your hands before and after applying Epinitril.
To remove the patch, simply lift a corner and gently pull it off. After use, fold the patch in half with the adhesive sides facing inward and dispose of it in a waste container out of the reach of children.

What to do if the patch detaches
If Epinitril is applied correctly, it is highly unlikely that the patch will detach.
However, if the patch does come off, replace it with a new one and resume changing the patch as usual according to the original dosing schedule.

If you use more Epinitril than you should
If you are exposed to high doses of nitroglycerin, you may experience severe drop in blood pressure, increased heart rate, collapse, fainting, and alteration of hemoglobin (methemoglobinemia).
If you or someone else applies too many patches at the same time, remove them carefully and thoroughly wash the underlying skin to reduce absorption. If hypotension or collapse occurs, elevation of the legs or, if necessary, compressive bandaging is recommended.

If you forget to change the patch
If you forget to change the patch at the scheduled time, replace it as soon as possible, then continue with the original dosing schedule for the next patch application.

If you stop using Epinitril
When you stop treatment with Epinitril, you may experience a recurrence of anginal attacks.
If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, Epinitril can cause side effects, although not everyone experiences them.
The following side effects have been reported:

Very common side effects (affect more than 1 in 10 people):

• Nausea
• Vomiting

Common side effects (affect more than 1 and less than 10 in 100 people):

• Headache

Uncommon side effects (affect more than 1 and less than 10 in 1,000 people):

• Skin inflammation due to contact (contact dermatitis)
• Redness and irritation of the skin at the patch application site
• Itching
• Burning sensation

Rare side effects (affect more than 1 and less than 10 in 10,000 people):

• Fast heartbeat (tachycardia)
• Low blood pressure when standing (orthostatic hypotension), which may present as transient episodes of dizziness
• Flushing
• Increased heart rate during diagnostic tests

Very rare side effects (affect less than 1 in 10,000 people):

• Dizziness
• Fainting (syncope)

Side effects with unknown frequency:

• Irregular heartbeat (palpitations)
• Generalized skin rash (generalized rash)

If any of these side effects worsen or persist, inform your doctor or pharmacist.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, consult your doctor or pharmacist. You may also report side effects directly through the national reporting system at: http://www.agenziafarmaco.gov.it/content/come-segnalare-una-sospetta-reazione-avversa.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Epinitril

Keep this medicine out of the sight and reach of children.
Do not store above 25°C. Epinitril must be kept in its original foil pouch.
Do not use this medicine after the expiry date stated on the carton and on the pouches. The expiry date refers to the last day of the month.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package Contents and Other Information

What Epinitril Contains
Epinitril patches contain the active substance nitroglycerin and are available in three sizes:
Epinitril 5 mg/24 hours: contains 15.70 mg of the active substance nitroglycerin and releases
approximately 5 mg of nitroglycerin per day (0.2 mg/h); the release area of the patch is 6.38 cm². The identification code printed on the protective liner is NR5.
Epinitril 10 mg/24 hours: contains 31.37 mg of the active substance nitroglycerin and releases
approximately 10 mg of nitroglycerin per day (0.4 mg/h); the release area of the patch is 12.75 cm². The identification code printed on the protective liner is NR10.
Epinitril 15 mg/24 hours: contains 47.04 mg of the active substance nitroglycerin and releases
approximately 15 mg of nitroglycerin per day (0.6 mg/h); the release area of the patch is 19.12 cm². The identification code printed on the protective liner is NR15.
The excipients are an adhesive substance (acrylate-vinyl acetate copolymer), an adhesion promoter (hydroabietic phthalate), and a cross-linker (polybutyl titanate); this mixture of excipients and active substance is applied onto a support film (lacquered polypropylene sheet). The adhesive layer is covered with a double-sided siliconized and aluminiumized protective sheet, which is removed before use.

Description of the Appearance of Epinitril and Contents of the Pack
Epinitril patches are adhesive transdermal patches. Each patch is individually sealed in a protective pouch.
Pack sizes: 15 and 30 patches. It is possible that not all pack sizes are marketed.

Marketing Authorization Holder and Manufacturer
Viatris Healthcare Limited, Damastown Industrial Park, Mulhuddart, Dublin 15, DUBLIN, Ireland
Manufacturer
ROTTAPHARM Ltd.
Damastown Industrial Park, Mulhuddart
Dublin 15
Ireland
LTS Lohmann Therapie Systeme AG
Lohmannstraße 2
56626 Andernach
Germany

This medicinal product is authorized in the Member States of the European Economic Area under the following names:
Country Name
France Epinitril
Ireland Epinitril
Italy Epinitril
Portugal Epinitril
Spain Epinitril