Adesitrin

Patient Information Leaflet

Adesitrin 5 mg/24 h Transdermal Patches, 10 mg/24 h Transdermal Patches, 15 mg/24 h Transdermal Patches

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. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Adesitrin is and what it is used for

Adesitrin contains the active substance nitroglycerin and belongs to a group of medicines called organic nitrates.
Organic nitrates work by dilating both peripheral venous and arterial vessels, thereby reducing the workload of the heart. They also act by dilating the blood vessels of the heart, thus increasing blood supply to the area in need.
Adesitrin is used to prevent and treat angina pectoris at rest and on exertion, either as monotherapy or in combination with other medicines such as beta-blockers, calcium antagonists, etc., both during stable and unstable phases resulting from or associated with coronary insufficiency, coronary artery disease, coronary sub-occlusion, and subacute myocardial infarction.
Angina usually presents as a pressing, constricting pain in the chest, neck, and/or left arm, caused by reduced blood flow to the walls of the heart.

2. What you need to know before using Adesitrin

Do not use Adesitrin

• If you are allergic to nitroglycerin, other nitrates, or any of the other ingredients of this medicine (listed in section 6).
• If you have a disease that severely impairs the heart's ability to pump blood adequately into the vessels, such as cardiogenic shock (severe impairment of heart function), narrowing of heart valves (aortic or mitral stenosis), obstructive hypertrophic cardiomyopathy (increased thickness of the heart walls leading to reduced ability to contract and pump blood), constrictive pericarditis (inflammation of the pericardium, the sac surrounding the heart), or cardiac tamponade (fluid accumulation in the pericardium that prevents the heart from functioning properly).
• If you have any condition in which blood pressure is very low (systolic pressure < 90 mmHg).
• Acute circulatory failure associated with very low blood pressure (shock, collapse).
• If you have conditions associated with increased pressure in the head (increased intracranial pressure), have experienced bleeding in the brain (cerebral hemorrhage), any head injury or trauma (cranial trauma), or suffer from increased pressure inside the eye (closed-angle glaucoma).
• If you have severe anemia (reduced red blood cells in the blood).
• If you have reduced blood volume (hypovolemia).
• If you are taking any other medicine used for erectile dysfunction (phosphodiesterase inhibitors such as sildenafil (Viagra), tadalafil, vardenafil); see section "Warnings and precautions" and "Other medicines and Adesitrin".
• If you are taking medicines used for pulmonary hypertension (such as riociguat, a soluble guanylate cyclase stimulator); see section "Other medicines and Adesitrin".
• If you are experiencing an acute angina attack.

Warnings and precautions
Talk to your doctor or pharmacist before using Adesitrin.
Particular caution is required under the following conditions:

• If you have a heart condition with severe impairment of the heart's pumping function (myocardial infarction with left ventricular failure).
• If you have recently had a heart attack (myocardial infarction) or have heart failure.
• If you suffer from anemia (reduced red blood cells in the blood).
• If you have orthostatic dysfunction, in which blood pressure drops when standing up.
• If you suffer from arterial hypoxia and ventilation/perfusion imbalance due to lung disease or ischemic heart failure. Inform your doctor if you are using products containing phosphodiesterase inhibitors (e.g., sildenafil, tadalafil, vardenafil). The Adesitrin patch does not contain aluminum or other metals and therefore does not need to be removed if undergoing magnetic resonance imaging (MRI). Children and adolescents The safety and efficacy of Adesitrin in children have not yet been established.

Other medicines and Adesitrin
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicine.
Do not use Adesitrin with:

• Phosphodiesterase inhibitors such as sildenafil, vardenafil, and tadalafil, used for erectile dysfunction. Using Adesitrin with these medicines may cause blood pressure to drop to dangerously low levels. Do not stop or interrupt treatment with Adesitrin to take phosphodiesterase inhibitors, as this increases the risk of experiencing an angina attack.
• Soluble guanylate cyclase stimulators such as riociguat, used for pulmonary hypertension. Using Adesitrin with this medicine may cause a drop in blood pressure. Inform your doctor if you are taking:
• Medicines used to lower blood pressure (e.g., beta-blockers, calcium antagonists, ACE inhibitors, monoamine oxidase inhibitors, diuretics), as they may cause a further drop in blood pressure.
• Medicines used to treat depression (tricyclic antidepressants) or other mental illnesses (such as neuroleptics and major tranquilizers). These medicines may also cause a further drop in blood pressure.
• Medicines used to treat migraine (dihydroergotamine). If taken together, excessive increase in blood pressure may occur.
• Aspirin, as it may cause a further drop in blood pressure.
• Anti-inflammatory medicines (except aspirin), which may reduce the effectiveness of Adesitrin.
• Medicines used, for example, to reduce side effects of certain cancer treatments or radiotherapy (amifostine).
• Medicines containing sapropterin (used, for example, in the treatment of a disease called phenylketonuria).

Adesitrin with food, drinks, and alcohol
Alcohol may enhance the blood pressure-lowering effect. Do not consume alcohol during treatment with Adesitrin.
Pregnancy, breastfeeding, and fertility
If you are pregnant, think you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor or pharmacist before using this medicine.
Pregnancy
Adesitrin should be used during pregnancy only if strictly necessary and under medical prescription and continuous medical supervision.
Breastfeeding
Since the active ingredient of Adesitrin is excreted in breast milk and may cause problems in the newborn, inform your doctor if you are breastfeeding.
Fertility
There are no data available on the effect of Adesitrin on male fertility.
Driving and using machines
Adesitrin may affect your reaction ability or rarely cause a drop in blood pressure (orthostatic hypotension), nausea, dizziness, and lightheadedness, to the extent of impairing your ability to drive or operate machinery. This effect is enhanced by alcohol (see section "Adesitrin with food, drinks, and alcohol"). Do not drive or operate machinery until you have determined whether this medicine affects your ability to perform these activities.

3. How to use Adesitrin

Use this medicine exactly as directed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
You will normally start treatment with a low dose, which your doctor may adjust, if necessary, until the appropriate dose is reached.
You must change the Adesitrin patch once daily. To achieve the required dose, different Adesitrin patches are available, each releasing a different amount of active substance per day: 5 mg/24 h, 10 mg/24 h, and 15 mg/24 h.

Adults
The recommended starting dose is one 5 mg patch per day. If necessary, based on your doctor's judgment, the dose may be increased in the following days. Two patches may be used simultaneously. The maximum recommended daily dose is 15 mg. For the management of acute angina attacks, concomitant administration of fast-acting nitroglycerin is recommended.

Elderly
There is no evidence suggesting the need for dose adjustment in elderly patients.

Use in children
This medicine is not suitable for children. If you have further questions about using this medicine, consult your doctor.

Instructions for using Adesitrin:
The Adesitrin patch is effective when applied anywhere on the body, provided it is not placed on areas of thick skin (e.g., feet) or areas with poor circulation. To avoid skin irritation, the patch should be applied daily to a different site. A previous application site should not be reused for at least 2–3 days. The best areas for application are easily accessible, relatively static areas on the front or side of the chest. However, the patch may also be applied to the upper arm, thigh, abdomen, or shoulder. (Figure 1)

Figure 1
Skin at the application site
The skin at the application site must be healthy, intact, relatively smooth, and hair-free.

• Do not apply the patch to damaged or diseased skin.
• The patch will adhere better if applied to an area of skin that does not undergo significant movement when the patient moves.
• Do not apply the patch to heavily hairy skin. Shaving the area or cutting the hair with scissors is not recommended, as regrowing hair may lift the patch from the skin. The application site must be cleaned and dried before applying the patch.
• Before applying the patch, wash the skin with soap in the usual way. There is no need to use strong detergents such as alcohol.
• Do not apply the patch immediately after a shower or bath, until the body has returned to normal temperature and the skin is completely dry. If the patch has already been applied before taking a shower, bath, or swimming, it generally adheres firmly and continues to work. However, to be safe, avoid prolonged immersion in water. Skin care products must not be used before applying the patch.
• Products containing oils, creams, or lotions must not be used on the application site before using the patch, as the patch does not adhere well to oily skin. The invisible layer of natural fat that protects the skin does not affect patch adhesion.

Application of the Adesitrin patch: Each patch is individually packaged in a sealed pouch and should remain in the pouch until ready for use. The sealed pouch can be easily opened using one of the notches along its edge. (Figure 2)

Figure 2
Remove the patch from the pouch and hold it with both hands, protective liner facing upward.
Bend the patch so that the central S-shaped opening line opens up. (Figure 3)

Figure 3
Peel off one half of the protective liner, taking care not to touch the adhesive surface with your fingers.
Apply the patch to the prepared skin area and then remove the other half of the protective liner. (Figure 4)

Figure 4
Press the patch firmly with the palm of your hand to ensure that the entire adhesive surface is securely attached to the skin. (Figure 5)

Figure 5
Do not cut the patch into pieces.
To avoid the development of tolerance, the patch should remain on the skin for approximately 10–14 hours only, ensuring a nitrate-free interval of 10–12 hours. During the nitrate-free interval, your doctor may prescribe additional antianginal therapy with non-nitrate medications.

If you use more Adesitrin than you should
Possible symptoms of Adesitrin overdose include: a drastic drop in blood pressure, pallor, sweating, weak pulse, rapid heartbeat, collapse, fainting (syncope), dizziness when standing, headache, weakness, nausea, vomiting, and diarrhea.
An increase in pressure within the head (intracranial pressure) may also occur, leading to symptoms of brain distress.
Cases of hemoglobin alteration (methemoglobinemia) have also been reported, resulting in bluish discoloration of the lips, nails, and skin (cyanosis), increased respiratory rate (tachypnea), anxiety, loss of consciousness, and cardiac arrest.
If you have any doubts about using this medicine, consult your doctor or pharmacist.
However, in case of low blood pressure, it is important to lie down with your head slightly lowered and your legs slightly raised.

If you forget to replace the patch at the usual time
If you forget to replace the patch at the usual time, remove the old patch and inform your doctor.

If you stop using Adesitrin
Do not stop using Adesitrin suddenly, even if you feel better. Stopping the medicine may worsen your condition. Continue using Adesitrin until your doctor tells you to stop. If your doctor decides that you should discontinue treatment with Adesitrin, your dose will be gradually reduced.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Very common (may affect more than 1 in 10 people)

• Headache (especially at the beginning of treatment)
• Nausea
• Vomiting

Common (may affect up to 1 in 10 people)

• Dizziness (including dizziness upon standing)
• Drowsiness
• Increased heart rate (tachycardia)
• Sudden drop in blood pressure upon standing from a sitting or lying position (orthostatic hypotension)
• Feeling weak (asthenia)

Uncommon (may affect up to 1 in 100 people)

• Worsening of angina symptoms (e.g. chest pain)
• Circulatory collapse, sometimes with slowed heart rate and fainting (syncope)
• Allergic skin reactions (e.g. rash)
• At the application site: redness, itching, burning, irritation. After removal of the transdermal patch, mild skin redness, itching or burning usually disappear within a few hours. The application site should be changed regularly to prevent local irritation.

Rare (may affect up to 1 in 1,000 people)

• Flushing
• Increased heart rate

Very rare (may affect up to 1 in 10,000 people)

• Heartburn (pyrosis)

Not known (frequency cannot be estimated from the available data)

• Palpitations
• Decrease in blood pressure (hypotension)
• Thickening of the skin surface with peeling (exfoliative dermatitis)

During treatment with Adesitrin, a reduction in blood oxygen levels (hypoxaemia) may occur. Like other nitrate-containing preparations, ADESITRIN commonly causes dose-dependent headaches, which usually disappear after a few days without discontinuing treatment.

Reporting of side effects

If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Adesitrin

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after: Exp.
The expiry date refers to the last day of that month.
Do not store above 25°C. Store in the original packaging.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of
medicines no longer in use. This will help protect the environment.

6. Package contents and other information

What Adesitrin contains

• The active substance is glyceryl trinitrate. Each Adesitrin 5 mg/24 h patch releases 5 mg of glyceryl trinitrate over 24 hours. Each 9 cm patch contains 18.7 mg of glyceryl trinitrate. Each Adesitrin 10 mg/24 h patch releases 10 mg of glyceryl trinitrate over 24 hours. Each 18 cm patch contains 37.4 mg of glyceryl trinitrate. Each Adesitrin 15 mg/24 h patch releases 15 mg of glyceryl trinitrate over 24 hours. Each 27 cm patch contains 56.2 mg of glyceryl trinitrate.
• The other components are: acrylic-vinyl acetate copolymer (adhesive matrix). Support layer: BOPP (biaxially oriented polypropylene) film.

Description of the appearance of Adesitrin and pack contents
Adesitrin is a transdermal patch. The patches are individually packaged in pouches and placed in cardboard boxes containing:
5 mg/24 h: 15 patches
10 mg/24 h: 15 patches
15 mg/24 h: 15 patches

Marketing Authorization Holder
MERUS LABS LUXCO II S.A.R.L, 26-28 Rue Edward Steichen, L2540 Luxembourg (Luxembourg)

Manufacturer
Aesica Pharmaceuticals GmbH, Alfred-Nobel-Strasse 10, Monheim, Germany