Trinitrina

Package leaflet: Information for the patient

TRINITRINA 0.3 mg film-coated tablets

nitroglycerin
Please read this leaflet carefully before taking 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 others, even if their symptoms are the same as yours, as it could be harmful.
• If you experience any adverse reactions, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What TRINITRINA is and what it is used for

TRINITRINA contains the active substance nitroglycerin, which belongs to a group of medicines called vasodilators, used in the treatment of certain heart diseases. This medicine works by dilating the blood vessels and improving blood circulation.
TRINITRINA is indicated for the treatment of sudden and severe chest pain caused by reduced oxygen supply to the heart (angina pectoris).

2. What you need to know before using TRINITRINA

Do not use TRINITRINA

• if you are allergic to nitroglycerin, to similar medicines (organic nitrates), or to any of the other ingredients of this medicine (listed in section 6);
• if you suffer from severe circulatory disorders due to reduced heart function (shock, cardiogenic shock);
• if you have an acute heart attack characterized by low blood pressure;
• if you have very low blood pressure (severe hypotension, systolic blood pressure <90 mmHg);
• if you have a significant reduction in circulating blood volume (severe hypovolemia);
• if you have increased intracranial pressure, or head injuries such as head trauma or cerebral hemorrhage;
• if you suffer from severe heart problems (myocardial failure due to obstruction, obstructive hypertrophic cardiomyopathy);
• if you have a severe condition characterized by fluid accumulation in the lungs (toxic pulmonary edema);
• if you have a severe reduction in the number of red blood cells in the blood (severe anemia);
• if you suffer from a disease affecting the eye that may cause serious damage to the optic nerve (closed-angle glaucoma);
• if you are pregnant or breastfeeding (See section “Pregnancy and breastfeeding”);
• if the person taking this medicine is a child or adolescent;
• if you are taking a medicine called sildenafil for the treatment of male impotence (See section “Other medicines and TRINITRINA”).

Warnings and precautions
Talk to your doctor or pharmacist before taking TRINITRINA.
TRINITRINA tablets must not be swallowed but placed under the tongue (sublingual route), as only in this way is the medicine effective.
Take only the lowest necessary dose of the medicine and for short periods of time, as headaches (severe headache) and allergic reactions may occur.
Take this medicine with extreme caution:

• if your heart functions less than normal (heart failure). In this case, your doctor should perform periodic examinations and blood tests, as low blood pressure (hypotension) and increased heart rate (tachycardia) may occur;
• if you have a reduced circulating blood volume (hypovolemia) or suffer from low blood pressure (hypotension). In such cases, your symptoms may worsen (severe hypotension), and you may experience dizziness upon standing due to low blood pressure (orthostatic hypotension). Occasionally, a decrease in heart rate (paradoxical bradycardia) and increased chest pain (anginal pain) may occur;
• if you experience dizziness upon standing due to low blood pressure (orthostatic hypotension). Occasionally, a decrease in heart rate (paradoxical bradycardia) and increased chest pain (anginal pain) may occur;
• if you suffer from a disease characterized by thickening of the heart walls (hypertrophic cardiomyopathy), as chest pain (angina) may worsen;
• if you have reduced oxygen levels in the blood (hypoxemia) caused by a severe reduction in the number of red blood cells (severe anemia).

Stop treatment with this medicine and consult your doctor if you experience visual disturbances (blurred vision) or a sensation of dry mouth (dryness of the mouth).
Other medicines and TRINITRINA
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Use particular caution and inform your doctor if you are taking the following medicines:

• α-adrenergic blockers, calcium channel blockers (antihypertensives) used to lower blood pressure;
• aspirin and indomethacin, used to relieve pain and inflammation;
• phenothiazines, used to treat severe mental illnesses (antipsychotics);
• amitriptiline, desipramine, doxepine, used to treat depression;
• anticholinergics, used to treat certain nervous system disorders;
• long-acting nitrates similar to TRINITRINA, used to treat certain heart conditions.

Do not use TRINITRINA together with:

• sildenafil, used to treat male impotence, as excessive lowering of blood pressure may occur;
• ergotamine-containing medicines, used to treat headache (cephalalgia), as a condition called ergotism may develop, characterized by circulatory and brain problems (seizures, hallucinations). If your doctor considers it necessary to take both medicines, you must be closely monitored.
  Inform your doctor if you are scheduled for blood tests to check cholesterol levels (Zlatkis/Zak colorimetric assay), as nitroglycerin may alter the results.
  TRINITRINA and alcohol
  Consumption of ethanol may cause excessive lowering of blood pressure (hypotension); therefore, avoid drinking alcoholic beverages during treatment with TRINITRINA.
  Pregnancy, breastfeeding and fertility
  If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, ask your doctor or pharmacist for advice before taking this medicine.
  If you are in the first 3 months of pregnancy or are breastfeeding, take TRINITRINA only when absolutely necessary and under direct medical supervision.
  Driving and using machines
  This medicine may cause dizziness upon standing due to low blood pressure (orthostatic hypotension), nausea, and dizziness. Therefore, if you experience these symptoms, avoid driving vehicles or operating machinery.
  TRINITRINA contains glucose, lactose, sucrose and para-hydroxybenzoates
  This medicine contains glucose, sucrose and lactose, three types of sugars. If your doctor has diagnosed you with an intolerance to certain sugars, contact your doctor before taking this medicine.
  This medicine contains para-hydroxybenzoates which may cause allergic reactions (including delayed reactions).

3. How to use TRINITRINA

Use this medicine exactly as directed by your doctor or pharmacist. If you have
any doubts, consult your doctor or pharmacist.
Crush the tablets with your teeth and allow them to dissolve under the tongue.
Do not swallow the tablets, as the medicine will lose its effectiveness.
The recommended dose is 1 tablet taken at the onset of a painful chest attack.
If necessary, your doctor may advise you to take a second tablet after a few minutes.

If you use more TRINITRINA than you should
If you think you have taken an excessive dose of nitroglycerin, inform your doctor or pharmacist immediately, as this may cause an excessive drop in blood pressure (hypotension) accompanied by an accelerated heart rate (reflex tachycardia). These symptoms can be managed by reducing or stopping administration of this medicine, or by taking medicines to raise blood pressure (alpha-adrenergic agents) such as methoxamine or phenylephrine.
Other symptoms of overdose may include cold skin and pallor, headache, dizziness, confusion, visual disturbances, nausea and vomiting with abdominal pain, diarrhoea, increased awareness of heartbeats (palpitations), loss of consciousness (syncope), and serious heart and circulation problems (cardiocirculatory collapse). Rarely, an abnormality in the structure of haemoglobin in the blood (methaemoglobinaemia) may occur, which can be resolved by reducing the rate of nitroglycerin infusion and administering a medicine called methylene blue (see section “Possible side effects”).
In case of accidental ingestion/overdose of TRINITRINA, contact your doctor immediately or go to the nearest hospital.

If you forget to use TRINITRINA
Do not take a double dose to make up for the missed tablet.

If you stop using TRINITRINA
If you have any questions about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Below are the side effects associated with nitroglycerin.

Frequency not known (frequency cannot be estimated from the available data)

• abnormal structure of hemoglobin in the blood (methemoglobinemia), which resolves upon administration of methylene blue;
• dizziness, headache (also immediately after administration);
• increased vagus nerve activity leading to slowing of the heartbeat (hypervagotonia), confusion, agitation;
• blurred vision;
• accelerated or slowed heartbeat (tachycardia or bradycardia), increased awareness of heartbeat (palpitations), and temporary loss of consciousness (syncope);
• decrease in blood pressure upon changing posture (postural hypotension);
• nausea, vomiting, digestive disturbances, pallor, sweating;
• painful muscle contractions (cramps), abdominal and sternal pain;
• skin damage such as skin rash, erythema, and exfoliative dermatitis (especially if you are taking other medicines containing nitrates);
• burning sensation, erythema;
• bluish-purple discoloration of the body (cyanosis).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist.
You may also report side effects directly via the national reporting system at: 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 TRINITRINA

Keep this medicine out of the 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.
The expiry date refers to the medicine kept in its original, undamaged packaging and stored correctly.
Store the medicine at a temperature not exceeding 25°C.
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 TRINITRINA contains
TRINITRINA 0.3 mg coated tablets

• The active substance is nitroglycerin. Each tablet contains 0.3 mg of nitroglycerin.
• The other components are: sucrose, maize starch, lactose monohydrate, mannitol, talc, microcrystalline cellulose, silica, titanium dioxide, anhydrous glucose, acacia gum, potato starch, magnesium carbonate, magnesium stearate, calcium stearate, gelatin, polyvinyl alcohol, vanillin, methyl p-hydroxybenzoate.

Description of the appearance of TRINITRINA and contents of the pack
TRINITRINA 0.3 mg coated tablets
Pack containing 35 coated tablets in PVC/PVDC/aluminum blisters.
Marketing Authorization Holder
ACARPIA FARMACEUTICI S.r.l.
Viale L. Majno, 18 – 20129 Milan (Italy)
Manufacturers
KLEVA S.A. - Parnithos Avenue 189, Acharnai Attiki, 13675 – Greece
Complete production, control and release
CIT S.r.l.
Via Primo Villa, 17
20875 Burago Molgora (MB)
Secondary packaging and release

Patient Information Leaflet: Information for the User

TRINITRINA 5mg/1.5 ml concentrate for solution for infusion

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 nurse.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor or nurse. See section 4.

Contents of this leaflet:

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

1. What TRINITRINA is and what it is used for

TRINITRINA contains the active substance nitroglycerin, which belongs to a group of medicines called vasodilators, used in the treatment of certain heart diseases. This medicine works by dilating blood vessels and improving blood circulation.

TRINITRINA is indicated for the treatment of:

• chest pain caused by heart problems, such as unstable angina, variant angina, and Prinzmetal's angina;
• impaired heart function, such as acute left ventricular failure due to various causes and characterized by high blood pressure;
• swelling due to fluid accumulation around the lungs (pulmonary edema and pre-pulmonary edema);
• rapid increase in blood pressure (hypertensive crisis).

2. What you need to know before using TRINITRINA

Do not use TRINITRINA

• if you are allergic to nitroglycerin, to similar medicines (organic nitrates), or to any of the other ingredients of this medicine (listed in section 6);
• if you suffer from severe circulatory disorders due to reduced heart function (shock, cardiogenic shock);
• if you have acute heart attack, characterized by low blood pressure;
• if you have very low blood pressure (severe hypotension, <90 mmHg systolic pressure);
• if you have a significant decrease in circulating blood volume (severe hypovolemia);
• if you have increased intracranial pressure, or head injuries such as head trauma or cerebral hemorrhage;
• if you suffer from severe heart problems (myocardial failure due to obstruction, constrictive pericarditis, obstructive hypertrophic cardiomyopathy);
• if you have a serious condition characterized by fluid accumulation in the lungs (toxic pulmonary edema);
• if you have a severe reduction in the number of red blood cells in the blood (severe anemia);
• if you suffer from a disease affecting the eye that may cause serious damage to the optic nerve (closed-angle glaucoma);
• if you are pregnant or breastfeeding (See section “Pregnancy and breastfeeding”);
• if the person using this medicine is a child or adolescent;
• if you are taking a medicine called sildenafil for the treatment of male impotence (See section “Other medicines and TRINITRINA”).

Warnings and precautions
Talk to your doctor or nurse before TRINITRINA is administered to you.
This medicine will only be administered in a hospital setting and by specialized medical staff, who will monitor your blood pressure, heart rate (cardiac frequency), and your general health status during the treatment period.
TRINITRINA will be administered with extreme caution if you suffer from head problems such as head trauma or cerebral hemorrhage.
For individuals engaged in sports, the use of medicines containing ethyl alcohol may lead to a positive result in anti-doping tests, depending on the alcohol concentration limits specified by certain sports federations.

Other medicines and TRINITRINA
Inform your doctor or nurse if you are using, have recently used, or might use any other medicine.
This medicine will be administered with particular caution if you are taking the following medicines, as they may increase the effectiveness of nitroglycerin:

• medicines used to dilate blood vessels (vasodilators);
• medicines used to lower blood pressure (antihypertensives);
• medicines used to increase urine excretion (diuretics).

Inform your doctor if you are taking:

• indomethacin, a medicine used to relieve inflammation, as it may reduce the effectiveness of nitroglycerin;
• alteplase or heparin, medicines used for blood coagulation disorders.

Do not use TRINITRINA together with medicines used to treat male impotence, such as sildenafil, as this may cause excessive lowering of blood pressure.
Inform your doctor if you need to undergo blood tests to monitor cholesterol levels (Zlatkis/Zak colorimetric assay), as nitroglycerin may alter the results.

TRINITRINA and alcohol
Consumption of ethanol may increase the effect of this medicine; therefore, avoid drinking alcoholic beverages during treatment with TRINITRINA.

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding, consult your doctor, pharmacist, or nurse before using this medicine.
Use TRINITRINA with caution during the first three months of pregnancy or while breastfeeding, only in cases of absolute necessity and under direct medical supervision.

Driving and using machines
This medicine may cause dizziness upon standing due to lowering of blood pressure (orthostatic hypotension), nausea, and dizziness. If you experience these symptoms, avoid driving vehicles or operating machinery.

TRINITRINA contains alcohol
This medicine contains 43.13% vol ethanol (alcohol), e.g., up to 647 mg per dose (1.5 ml), equivalent to 16.4 ml of beer or 6.8 ml of wine per dose.
It may be harmful for alcoholics.
This should be taken into account in pregnant or breastfeeding women, children, and high-risk groups such as patients with liver disease or epilepsy.

3. How to use TRINITRINA FIALE

This medicine will be administered to you by a doctor or a nurse. If you have any doubts, please consult your doctor or nurse.
The recommended dose ranges from 0.5 to 6 mg/hour, depending on the patient's condition and needs, and must be administered by continuous drop-by-drop intravenous infusion or using an automatic infusion device.
The doctor will determine the dose and method of administration.
If you use more TRINITRINA FIALE than you should
If you think you have been given an excessive dose of nitroglycerin, inform the doctor or nurse immediately, as this may cause excessive lowering of blood pressure (hypotension) accompanied by increased heart rate (reflex tachycardia). These symptoms can be managed by reducing or stopping the administration of this medicine or by giving medicines to raise blood pressure (alpha-adrenergic agents) such as methoxamine or phenylephrine.
Other symptoms of overdose may include cold skin and pallor, headache, dizziness, confusion, visual disturbances, nausea and vomiting with abdominal pain, diarrhea, increased awareness of heartbeats (palpitations), loss of consciousness (syncope), serious heart and circulation problems (cardiocirculatory collapse). Rarely, an abnormality in the structure of hemoglobin in the blood (methemoglobinemia) may occur, which can be resolved by reducing the infusion rate of nitroglycerin and administering a medicine called methylene blue (see section “Possible side effects”).
In case of accidental ingestion/intake of an excessive dose of TRINITRINA, inform your doctor immediately or go to the nearest hospital.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The following are side effects associated with nitroglycerin.
Frequency not known (frequency cannot be estimated from the available data)

• abnormal structure of hemoglobin in the blood (methemoglobinemia), which resolves upon administration of methylene blue;
• dizziness, headache (also immediately after administration);
• increased vagus nerve activity leading to slowing of the heartbeat (hypervagotonia), confusion, agitation;
• blurred vision;
• increased or slowed heartbeat (tachycardia or bradycardia), increased awareness of heartbeat (palpitations), and temporary loss of consciousness (syncope);
• decrease in blood pressure upon postural changes (postural hypotension);
• nausea, vomiting, digestive disturbances, pallor, sweating;
• painful muscle contractions (cramps), abdominal and sternal pain;
• skin reactions such as rash, erythema, and exfoliative dermatitis (especially if you are taking other medicines containing nitrates);
• burning sensation at the injection site, erythema;
• bluish-purple discoloration of the body (cyanosis).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please consult your doctor or pharmacist. You may also report side effects directly through the national reporting system at: 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 TRINITRINA

Keep this medicine out of the 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.
The expiry date applies to the medicine in its original, unopened packaging, correctly stored.
No special storage conditions regarding temperature are required.
Do not dispose of any medicine 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 TRINITRINA contains
TRINITRINA 5mg/1.5ml concentrate for solution for infusion

• The active substance is nitroglycerin. Each vial contains 5 mg of nitroglycerin.
• The other components are: alcohol, water for injections.

Description of the appearance of TRINITRINA and contents of the pack
TRINITRINA 5mg/1.5ml concentrate for solution for infusion
Box containing 10 glass vials of 5 mg/1.5 ml.
Marketing Authorization Holder
ACARPIA FARMACEUTICI S.r.l. - Viale L. Majno, 18 - 20129 Milan (Italy)
Manufacturer
FISIOPHARMA S.r.l. - Industrial Area - 84020 Palomonte (SA) - Italy

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Package leaflet: information for the physician

TRINITRINA 5mg/1.5 ml concentrate for solution for infusion

nitroglycerin
Therapeutic indications
Unstable angina, variant angina, Prinzmetal's angina. Acute left ventricular failure, with or without antecedent acute myocardial infarction, particularly when associated with elevated filling pressure and reduced cardiac output. Acute pulmonary edema and pre-pulmonary edema. Hypertensive crisis.
Dosage and administration
Dosage should be adjusted according to the individual needs of each patient and in response to monitored parameters. Based on reported experience, the dosage ranges between 0.5–6 mg/hour of nitroglycerin administered by continuous intravenous infusion.
These dosage levels are rarely exceeded, even up to 6 mg/hour. The intravenous infusion solution is prepared by appropriately diluting nitroglycerin according to the table below and administered either via an automated device or drop by drop, following the infusion table (1 ml corresponds to approximately 20 drops from a standard infusion set).
Dilution table

Infusion table

Incompatibilities
Nitroglycerin is compatible with infusion solutions commonly used in clinical practice, such as isotonic saline solution, 4-30% glucose solution, Ringer's solution, and protein-containing solutions. No incompatibilities with other infusion solutions are currently known. Dilution must be performed only in glass infusion bottles.

Nitroglycerin tends to rapidly migrate into many plastic materials. Therefore, dilution of injectable nitroglycerin to obtain intravenous infusion solution must be carried out exclusively in glass infusion containers.

The nitroglycerin contained in the final infusion solution may be absorbed by the PVC material commonly used in standard administration sets, with losses ranging from 40% to 80% of the total amount. The rate of absorption is inversely proportional to the infusion rate. For this reason, administration sets made of polyethylene are recommended, as they result in minimal loss of nitroglycerin.

Instructions for use and handling
The product must always be diluted prior to intravenous infusion. Dilutions must be prepared in glass infusion bottles, using polyethylene administration sets.

Package leaflet: Information for the user

TRINITRINA 50mg/50ml concentrate for solution for infusion

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 nurse.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or nurse. See section 4.

Contents of this leaflet:

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

1. What TRINITRINA is and what it is used for

TRINITRINA contains the active substance nitroglycerin, which belongs to a group of medicines called vasodilators, used in the treatment of certain heart diseases. This medicine works by dilating blood vessels and improving blood circulation.

TRINITRINA is indicated for the treatment of:

• chest pain caused by heart problems, such as unstable angina, variant angina, and Prinzmetal's angina;
• conditions involving reduced heart function, such as acute left ventricular failure due to various causes and characterized by high blood pressure;
• swelling due to fluid accumulation around the lungs (pulmonary edema and pre-pulmonary edema);
• rapid increase in blood pressure (hypertensive crisis).

2. What you need to know before using TRINITRINA

Do not use TRINITRINA

• if you are allergic to nitroglycerin, to similar medicines (organic nitrates), or to any of the other ingredients of this medicine (listed in section 6);
• if you have severe circulatory problems due to reduced heart function (shock, cardiogenic shock);
• if you have acute myocardial infarction associated with low blood pressure;
• if you have very low blood pressure (severe hypotension, systolic blood pressure <90 mmHg);
• if you have a significant decrease in blood volume (severe hypovolemia);
• if you have increased intracranial pressure, or head injuries such as head trauma or cerebral hemorrhage;
• if you suffer from severe heart conditions (myocardial insufficiency due to obstruction, constrictive pericarditis, obstructive hypertrophic cardiomyopathy);
• if you have a severe condition characterized by fluid accumulation in the lungs (toxic pulmonary edema);
• if you have a severe reduction in red blood cells (severe anemia);
• if you suffer from a disease affecting the eye that may cause serious damage to the optic nerve (closed-angle glaucoma);
• if you are pregnant or breastfeeding (See section “Pregnancy and breastfeeding”);
• if the person who is to take this medicine is a child or adolescent;
• if you are taking a medicine called sildenafil for the treatment of male impotence (See section “Other medicines and TRINITRINA”).

Warnings and precautions
Talk to your doctor or nurse before TRINITRINA is administered to you.
This medicine will only be administered in a hospital setting and by specialized medical staff, who will monitor your blood pressure, heart rate (cardiac frequency), and your general health status during the treatment period.
TRINITRINA will be administered with extreme caution if you have head problems such as head trauma or cerebral hemorrhage.

Other medicines and TRINITRINA
Inform your doctor or nurse if you are taking, have recently taken, or might take any other medicines.
This medicine will be administered with particular caution if you are taking the following medicines, as they may increase the effect of nitroglycerin:

• medicines used to dilate blood vessels (vasodilators);
• medicines used to lower blood pressure (antihypertensives);
• medicines used to increase urine elimination (diuretics).

Inform your doctor if you are taking:

• indomethacin, a medicine used to relieve inflammation, as it may reduce the effectiveness of nitroglycerin;
• alteplase or heparin, medicines used for blood coagulation disorders.

Do not use TRINITRINA together with medicines used to treat male impotence, such as sildenafil, as they may enhance the blood pressure-lowering effect.
Inform your doctor if you are due to undergo blood tests to monitor cholesterol levels (Zlatkis/Zak colorimetric assay), as nitroglycerin may alter the test results.

TRINITRINA and alcohol
Consumption of ethanol may enhance the effect of this medicine; therefore, avoid drinking alcoholic beverages during treatment with TRINITRINA.

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or are breastfeeding, consult your doctor or nurse before using this medicine.
If you are in the first three months of pregnancy or are breastfeeding, use TRINITRINA with caution, only in cases of absolute necessity and under direct medical supervision.

Driving and use of machines
This medicine may cause dizziness upon standing due to a drop in blood pressure (orthostatic hypotension), nausea, and dizziness. If you experience these symptoms, avoid driving vehicles or operating machinery.

TRINITRINA contains propylene glycol
This medicine contains 50 mg of propylene glycol per vial, which may lead to lactic acidosis; therefore, it is recommended not to use the medicine for more than three consecutive days. Additionally, it may cause symptoms similar to those caused by alcohol.

3. How to use TRINITRINA

This medicine will be administered to you by a doctor or nurse. If you have any doubts, consult your doctor or nurse.

The recommended dose ranges from 0.5 to 6 mg/hour, depending on the patient's condition and needs, and must be administered by continuous drop-by-drop infusion or by using an automatic device.

The doctor will determine the dose and route of administration.

If you use more TRINITRINA than you should

If you think you have been given too high a dose of nitroglycerin, inform your doctor or nurse immediately, as this may cause excessive lowering of blood pressure (hypotension) with increased heart rate (reflex tachycardia). These symptoms can be managed by reducing or stopping the administration of this medicine, or by giving medicines to raise blood pressure (alpha-adrenergic agents) such as methoxamine or phenylephrine.

Other symptoms of overdose may include cold skin and pallor, headache, dizziness, confusion, visual disturbances, nausea and vomiting with abdominal pain, diarrhoea, increased awareness of heartbeats (palpitations), loss of consciousness (syncope), and serious heart and circulation problems (cardiocirculatory collapse). Rarely, an abnormality in the structure of haemoglobin in the blood (methaemoglobinaemia) may occur, which can be resolved by reducing the infusion rate of nitroglycerin and administering a medicine called methylene blue (see section “Possible side effects”).

In case of accidental ingestion/overdose of TRINITRINA, contact your doctor immediately or go to the nearest hospital.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The following are effects of nitroglycerin.
Frequency not known (frequency cannot be estimated from the available data)

• abnormal structure of hemoglobin in the blood (methemoglobinemia), which resolves after administration of methylene blue;
• dizziness, headache (also immediately after administration);
• increased vagus nerve activity leading to slowing of the heartbeat (hypervagotonia), confusion, agitation;
• blurred vision;
• rapid or slow heartbeat (tachycardia or bradycardia), increased awareness of heartbeat (palpitations), and temporary loss of consciousness (syncope);
• decrease in blood pressure upon postural change (postural hypotension);
• nausea, vomiting, digestive disturbances, pallor, sweating, painful muscle contractions (cramps), abdominal and sternal pain;
• skin damage such as skin rash, erythema, and exfoliative dermatitis (especially if taking other medicines containing nitrates);
• burning sensation at the injection site, erythema;
• bluish-purple discoloration of the body (cyanosis).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist.
You may also report side effects directly via the national reporting system at: 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 TRINITRINA

Keep this medicine out of the 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.
The expiry date applies to the medicine in its original, unopened packaging, correctly stored.
No special temperature storage conditions are required.
Do not dispose of any medicine 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 TRINITRINA contains
TRINITRINA 50mg/50ml concentrate for solution for infusion

• The active substance is nitroglycerin. Each vial contains 50 mg of nitroglycerin.
• The other components are: propylene glycol, anhydrous dextrose, water for injections, pH adjusters (hydrochloric acid or sodium hydroxide).

Description of the appearance of TRINITRINA and contents of the package
TRINITRINA 50mg/50ml concentrate for solution for infusion
Box containing 5 glass vials of 50 mg/50 ml.
Marketing Authorization Holder
ACARPIA FARMACEUTICI S.r.l. - Viale L. Majno, 18 – 20129 Milano (Italy)
Manufacturers
A) KLEVA S.A. Parnithos Avenue 189, Acharnai Attiki, 13675 – Greece
B) FISIOPHARMA S.r.l. - Industrial Area - 84020 Palomonte (SA) - Italy
The product is manufactured and controlled in facility A or B, respectively, depending on whether the letter A or B appears on the packaging before the batch number.

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Package leaflet: information for the physician
TRINITRINA 50mg/50ml concentrate for solution for infusion
nitroglycerin
Therapeutic indications
Unstable angina, variant angina, Prinzmetal's angina. Acute left ventricular failure, with or without preceding acute myocardial infarction, particularly when associated with elevated filling pressure and reduced cardiac output. Acute pulmonary edema and pre-pulmonary edema. Hypertensive crisis.

Dosage and method of administration
Dosage should be adjusted according to the individual needs of each patient and in response to monitored parameters. Based on reported experience, the dosage ranges between 0.5–6 mg/hour of nitroglycerin by continuous intravenous infusion.
These doses are rarely exceeded, even up to 6 mg/hour. The intravenous infusion solution is prepared by appropriately diluting nitroglycerin according to the table below, and administered via an automatic infusion device or drop-by-drop, following the infusion table recommendations (1 ml corresponds to approximately 20 drops of a standard infusion).

Dilution table
| Number of vials | 1 | 2 | 3 |
|-----------------|----|-----|------|
| (Amount of active substance) | (50 mg) | (100 mg) | (150 mg) |
| Vial solution volume | 50 ml | 100 ml | 150 ml |
| Required diluent volume (ml) | | | |
| Dilution 1:10 | 500 | 1000 | 1500 |
| Dilution 1:20 | 1000 | 2000 | 3000 |
| Dilution 1:40 | 2000 | 4000 | 6000 |
| Final volume of ready solution (ml) | | | |
| Dilution 1:10 | 550 | 1100 | 1650 |
| Dilution 1:20 | 1050 | 2100 | 3150 |
| Dilution 1:40 | 2050 | 4100 | 6150 |
| Final nitroglycerin concentration (mg/ml) | | | |
| Dilution 1:10 | 0.09 | | |
| Dilution 1:20 | 0.05 | | |
| Dilution 1:40 | 0.02 | | |

Infusion table
| Desired NTG dose per hour | Dilution 1:10 | | Dilution 1:20 | | Dilution 1:40 | |
|---------------------------|---------------|----|---------------|----|---------------|----|
| | ml/h | gtt/min | ml/h | gtt/min | ml/h | gtt/min |
| 0.50 mg | 5.50 | 2 | 10.50 | 3–4 | 20.50 | 6–7 |
| 0.75 mg | 8.25 | 3 | 15.75 | 5 | 30.75 | 10 |
| 1.00 mg | 11.00 | 3–4 | 21.00 | 7 | 41.00 | 13–14 |
| 1.25 mg | 13.75 | 4–5 | 26.25 | 8–9 | 51.25 | 17 |
| 1.50 mg | 16.50 | 5–6 | 31.50 | 10–11 | 61.50 | 20–21 |
| 2.00 mg | 22.00 | 6–7 | 42.00 | 14 | 82.00 | 26–27 |
| 2.50 mg | 27.50 | 9 | 52.50 | 17 | 105.00 | 34 |
| 3.00 mg | 33.00 | 11 | 63.00 | 21 | 123.00 | 41 |
| 3.50 mg | 38.50 | 13 | 73.50 | 24–25 | 143.50 | 47–48 |
| 4.00 mg | 44.00 | 12–13 | 84.00 | 28 | 164.00 | 53 |
| 4.50 mg | 49.50 | 14–15 | 94.50 | 31–32 | 184.50 | 59–60 |
| 5.00 mg | 55.00 | 18 | 105.00 | 35 | 205.00 | 68 |
| 5.50 mg | 60.50 | 20 | 115.50 | 38–39 | 225.50 | 74–75 |
| 6.00 mg | 66.00 | 22 | 126.00 | 42 | 246.00 | 82 |

Overdose
Signs and symptoms are primarily due to marked vasodilation and methemoglobinemia. Manifestations include: hypotension and reflex tachycardia, cold and pale skin, headache, dizziness, mental confusion, visual disturbances, nausea and vomiting with colicky abdominal pain, possibly associated with watery diarrhea. Palpitations, syncope, and cardiovascular collapse. Treatment of symptoms due to severe and generalized hypotension requires immediate reduction of the infusion rate and placing the patient in Trendelenburg position (lying down with passive limb movements), along with intravenous fluid administration. If necessary, administer alpha-adrenergic agonists (e.g., methoxamine or phenylephrine). Adrenaline and similar substances are ineffective against severe hypotension caused by overdose.

Treatment of cyanosis due to methemoglobinemia: when methemoglobin levels reach 0.8 g/100 ml, treatment consists of intravenous administration of 1% methylene blue (1–2 mg/kg). In less severe cases, an oral dose of 50 mg/kg should be administered. Treatment in a specialized center is recommended.

Incompatibilities
Nitroglycerin is compatible with clinically used infusion solutions such as isotonic saline solution, 4–30% glucose solution, Ringer's solution, protein-containing solutions. No incompatibilities with other infusion solutions are currently known. Dilution must only be performed in glass infusion containers.

Nitroglycerin tends to rapidly migrate into many plastic materials. The dilution of injectable nitroglycerin to obtain the final intravenous infusion solution must be carried out exclusively in glass infusion containers.

Nitroglycerin in the final infusion solution may be absorbed by the PVC commonly used in standard infusion sets, with losses ranging from 40% to 80% of the total amount; the absorption rate is inversely proportional to the infusion rate. Therefore, polyethylene tubing, which results in minimal loss of nitroglycerin, is recommended.

Instructions for use and handling
The product must always be diluted before intravenous infusion. Dilutions should be performed in glass infusion containers using polyethylene administration sets.