URAPIDIL ACCORD 5 mg/ml INJECTABLE SOLUTION AND PERFUSION SOLUTION

Introduction

Package Leaflet: Information for the Patient

Urapidil Accord 5 mg / ml Solution for Injection and Infusion EFG

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again. If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the Package Leaflet

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

1. What is Urapidil Accord and what is it used for

Urapidil Accord belongs to a group of medicines called alpha-adrenergic blockers (i.e., they block alpha-adrenergic receptors that are responsible for the constriction of blood vessels and, therefore, the increase in blood pressure) and produce a balanced decrease in blood pressure.

This medicine is indicated for the treatment of hypertensive crises (sudden high blood pressure in the periods before and after surgery, especially in neurology and cardiac surgery in adults and children) and for protection before and after surgery against increases in blood pressure caused by indispensable maneuvers during anesthesia (intubation: introduction of a tube through the mouth to the trachea, to ensure breathing, and extubation: removal of the same).

2. What you need to know before you start using Urapidil Accord

Do not use Urapidil Accord

• If you are allergic to urapidil or any of the other components of this medicine (listed in section 6).
• If you have a narrowing (stenosis) of the aortic isthmus or an arteriovenous shunt (with the exception of inactive hemodynamic dialysis shunt).

Warnings and precautions

Consult your doctor or pharmacist or nurse before starting to use Urapidil Accord.

Special care is required when Urapidil Accord is used in:

• Patients with heart problems.
• Children, as no studies have been conducted in this patient group.
• Patients with liver disease.
• Patients with kidney disease.
• Older adults.
• Patients being treated with cimetidine at the same time (see section "Use of Urapidil Accord with other medicines").
• If you have previously taken or been administered other antihypertensive medicines.

Consult your doctor if any of the above circumstances have ever occurred to you.

Use of Urapidil Accord with other medicines

Urapidil, at high doses, may prolong the duration of action of barbiturates.

The antihypertensive action of urapidil may increase if other alpha-adrenergic receptor medicines and other antihypertensive medicines are administered at the same time, as well as in cases of hypovolemia (decrease in blood volume, e.g., diarrhea or vomiting) or alcohol consumption.

In case you are taking or being administered cimetidine at the same time as this medicine, urapidil levels in the blood may increase.

In case you have taken or been administered an angiotensin-converting enzyme inhibitor (a type of antihypertensive medicine, also called ACE inhibitors), you should inform your doctor, as the combination of urapidil with this type of medicine is not recommended. Inform your doctor or pharmacist if you are using, have recently used, or may need to use any other medicine.

Pregnancy, breastfeeding, and fertility:

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

The use of urapidil is not recommended during pregnancy, unless the potential benefit to the mother outweighs the potential risk to the fetus.

It is not known if urapidil is excreted in breast milk; therefore, urapidil should not be used during breastfeeding.

Driving and using machines

Do not drive because this medicine may alter your ability to drive.

Do not operate tools or machines. This medicine may alter your ability to use machinery or work without firm support, especially at the start of treatment, when changing treatment, and in combination with alcohol.

Urapidil Accord contains propylene glycol and sodium

This medicine contains 1000 mg of propylene glycol in 10 ml, which is equivalent to 100 mg/ml.

If you are pregnant or breastfeeding, do not take this medicine unless it is recommended by your doctor. Your doctor may perform additional checks while you are taking this medicine.

If you have liver or kidney failure, do not take this medicine unless it is recommended by your doctor. Your doctor may perform additional checks while you are taking this medicine.

If the child is under 5 years of age, consult your doctor or pharmacist, especially if other medicines containing propylene glycol or alcohol have been administered.

This medicine contains less than 23 mg (1 mmol) of sodium per ampoule, so it is considered essentially "sodium-free".

3. How to use Urapidil Accord

Urapidil Accord will only be administered in a hospital by healthcare professionals. This medicine will be administered intravenously.

Follow exactly the administration instructions of this medicine indicated by your doctor, pharmacist, or nurse. If in doubt, consult your doctor, pharmacist, or nurse again. The duration of treatment with urapidil will be a maximum of seven days.

Adults

Hypertensive emergencies:

Intravenous injection:

Initial dose:

Half an ampoule (25 mg) of urapidil will be administered over 20 seconds. If after 5 minutes there is a sufficient decrease in blood pressure, your doctor will proceed to administer the maintenance dose. If the decrease in blood pressure is not sufficient, half an ampoule (25 mg) of urapidil will be administered again over 20 seconds. If after 5 minutes the decrease in blood pressure is sufficient, your doctor will proceed to administer the maintenance dose, and if the decrease is insufficient, one ampoule (50 mg) of urapidil will be administered over 20 seconds, and then the maintenance dose will be administered if the reduction in blood pressure after 5 minutes is sufficient.

Maintenance dose:

• Infusion: 9 to 30 mg/h (average 15) (7 to 22 drops/min) (average 11).
• Electric syringe: 9 to 30 mg/h (average 15) (4.5 to 15 ml/h) (average 7.5).

Intravenous infusion or electric syringe:

Initial dose:

• Infusion: 2 mg/min (88 drops: 4.4 ml/min), if the decrease in blood pressure is sufficient, your doctor will proceed to administer the maintenance dose.
• Electric syringe: 2 mg/min (1 ml/min), if the decrease in blood pressure is sufficient, your doctor will proceed to administer the maintenance dose.

Maintenance dose:

• Infusion: 9 to 30 mg/h (average 15) (7 to 22 drops/min) (average 11).
• Electric syringe: 9 to 30 mg/h (average 15) (4.5 to 15 ml/h) (average 7.5).

Perioperative use:

Intravenous injection:

Initial dose:

Half an ampoule (25 mg) of urapidil over 20 seconds. If after 2 minutes there is a sufficient decrease in blood pressure, your doctor will proceed to administer the maintenance dose. If the decrease in blood pressure is not sufficient, half an ampoule (25 mg) of urapidil will be administered again over 20 seconds, and if after 2 minutes the decrease in blood pressure is sufficient, your doctor will proceed to administer the maintenance dose. If the decrease is insufficient, one ampoule (50 mg) of urapidil will be administered over 20 seconds, and then the maintenance dose will be administered if the decrease in blood pressure after 2 minutes is sufficient.

Maintenance dose:

• Infusion: 60 to 180 mg/h (average 120) (44 to 132 drops/min) (average 88)
• Electric syringe: 60 to 180 mg/h (average 120) (30 to 90 ml/h) (average 60)

Intravenous infusion or electric syringe:

Initial dose:

• Infusion: 6 mg/min (264 drops: 13.2 ml/min), if the decrease in blood pressure is sufficient, your doctor will proceed to administer the maintenance dose.
• Electric syringe: 6 mg/min (3 ml/min), if the decrease in blood pressure is sufficient, your doctor will proceed to administer the maintenance dose.

Maintenance dose:

• Infusion: 60 to 180 mg/h (average 120) (44 to 132 drops/min) (average 88)
• Electric syringe: 60 to 180 mg/h (average 120) (30 to 90 ml/h) (average 60).

Children:Initial dose: 2 mg/kg/h Maintenance dose: 0.8 mg/kg/h.

In case of patients with renal disease or older adults:

Your doctor will assess the dose to be administered.

If you think the action of urapidil is too strong or too weak, inform your doctor.

If you receive more Urapidil Accord than you should

This medicine will only be administered in a hospital by healthcare professionals, so it is unlikely that you will receive more urapidil than you should. However, if you think you have been administered more urapidil than you should, inform your doctor immediately. In case of accidental overdose, consult the Toxicology Information Service (telephone: 91-562.04.20), indicating the product and the amount administered. Carry this leaflet with you.

In case of overdose, the following symptoms may occur:

Circulatory symptoms: dizziness, orthostatic hypotension (sudden drop in blood pressure when standing up, with a fleeting feeling of dizziness), collapse (sudden failure of the circulatory system).

Central nervous system symptoms: fatigue and alteration of reaction speed.

Information for the doctor:

An excessive reduction in blood pressure can be mitigated by placing the patient with their legs elevated and performing volume expansion. If these measures are not adequate, a vasoconstrictor agent can be administered by slow intravenous injection, controlling blood pressure levels.

Intravenous injection of catecholamines (such as adrenaline, 0.5-1.0 mg in 10 ml of isotonic saline solution) is necessary in very rare cases.

If you stop treatment with Urapidil Accord:

This medicine will only be administered in a hospital by healthcare professionals, so it is unlikely that you will not receive the dose of urapidil that you should; however, if you think you have missed a dose of this medicine, inform your doctor immediately.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. Most of the side effects listed below are due to a rapid decrease in blood pressure, which, according to experience, disappears within a few minutes, even during infusion.

The following side effects have been observed, which are related to organs and systems and frequencies. Frequencies are defined as:

Common (may affect up to 1 in 10 people)

Uncommon: (may affect up to 1 in 100 people)

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

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

Cardiac disorders

Uncommon: palpitations, tachycardia (increased heart rate), bradycardia (reduced heart rate), feeling of precordial oppression (in front of the heart).

Vascular disorders

Uncommon: orthostatic hypotension (decrease in blood pressure when changing posture, e.g., when standing up after being lying down).

Gastrointestinal disorders

Common: nausea

Uncommon: vomiting.

General disorders and administration site conditions

Uncommon: fatigue

Investigations

Uncommon: irregular heartbeats.

Very rare: In temporal association with oral administration of urapidil, a decrease in platelet count has been observed, although a causal relationship with urapidil treatment has not been established.

Nervous system disorders

Common: dizziness, headache.

Psychiatric disorders

Very rare: agitation

Reproductive system and breast disorders

Rare: priapism (persistent and painful erection)

Respiratory, thoracic, and mediastinal disorders

Rare: nasal congestion.

Skin and subcutaneous tissue disorders

Frequency not known: angioedema, urticaria.

Uncommon: excessive sweating

Very rare: allergic reactions such as pruritus (itching), skin redness, and exanthema (skin rash with redness).

If you think any of the side effects you are experiencing is serious or if you notice any side effects not mentioned in this leaflet, inform your doctor or pharmacist.

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if it is a possible side effect not listed in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Urapidil Accord

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the packaging and on the ampoule after EXP. The expiry date is the last day of the month indicated.

After dilution with NaCl 0.9%, glucose 5%, or glucose 10%, the prepared solution is physically and chemically stable for 50 hours at 15-25°C. The prepared solution should be used immediately for microbiological reasons. If the prepared solution is not used immediately, the user is responsible for the storage period and conditions.

Medicines should not be disposed of via wastewater or household waste. Dispose of the packaging and any unused medicine in the pharmacy's SIGRE collection point. If in doubt, ask your pharmacist how to dispose of the packaging and any unused medicine. This will help protect the environment.

6. Container contents and additional information

Composition of Urapidil Accord

• The active ingredient is urapidil. A 10 ml ampoule contains 50 mg of urapidil
• The other components are propylene glycol, sodium dihydrogen phosphate dihydrate, sodium hydrogen phosphate dihydrate, hydrochloric acid, sodium hydroxide, and water for injectables.

Appearance of the product and container contents

This medication is presented in the form of a clear, transparent, or slightly brown injectable solution, in ampoules. Each container contains 5 ampoules.

Marketing authorization holder and manufacturer:

Holder

Accord Healthcare, S.L.U.

World Trade Center

Moll de Barcelona s/n, Edifici Est,

6th floor 08039 Barcelona

Manufacturer

Combino Pharm S.L.

Fructuós Gelabert, 6 – 8

08970 Sant Joan Despí - Barcelona

Spain

or

CENEXI

52, rue Marcel et Jacques Gaucher

94120 Fontenay Sous Bois

France

Date of the last revision of thisleaflet: February 2020

Detailed and updated information on this medication is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/

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This information is intended only for doctors or healthcare professionals:

Incompatibilities:Urapidil Accord should not be mixed with alkaline solutions for injection or infusion, as it may cause clouding or flocculation due to the acidic properties of the injection solution.

Instructions for use and handling:The chemical and physical stability of the prepared formulation has been demonstrated for 50 hours at 15-25°C. From a microbiological point of view, the prepared formulation for use should be used immediately.

If it is not used immediately, the storage within the time and conditions of use are the responsibility of the handler.

Administration will be carried out according to the attached scheme. Taking into account the duration of the available toxicological studies, the duration of use of Urapidil Accord will be a maximum of seven days.

PERIOPERATIVE USE

Intravenous injection:

Initial dose:

25 mg of Urapidil in 20 seconds. If a sufficient reduction in blood pressure occurs after 2 minutes, your doctor will proceed to administer the maintenance dose.

If the reduction in blood pressure has not been sufficient after 5 minutes, 25 mg of Urapidil will be administered again in 20 seconds, and if the reduction in blood pressure is sufficient after 2 minutes, your doctor will proceed to administer the maintenance dose. If, on the other hand, the reduction in blood pressure is insufficient after 5 minutes, 50 mg of Urapidil will be administered in 20 seconds, and the maintenance dose will be administered if the reduction in blood pressure is sufficient after 2 minutes.

Maintenance dose:

• Perfusion: 60 to 180 mg/h (average 120) (44 to 132 drops/min.) (average 88)
• Electric syringe: 60 to 180 mg/h (average 120) (30 to 90 ml/h) (average 60)

Intravenous perfusion or electric syringe:

Initial dose:

• Perfusion: 6 mg/min. (264 drops = 13.2 ml/min.) if the reduction in blood pressure is sufficient, your doctor will proceed to administer the maintenance dose.
• Electric syringe: 6 mg/min. (3 ml/min.), if the reduction in blood pressure is sufficient, your doctor will proceed to administer the maintenance dose.

Preparation of solutions:

Perfusions: add 5 ampoules of Urapidil Accord 5 mg/ml in 500 ml of solution

Electric syringe: 2 ampoules of Urapidil Accord 5 mg/ml in 50 ml of solution

Posological recommendation for preoperative use

Children:

Initial dose: 2 mg/Kg/h

Maintenance dose: 0.8 mg/Kg/h

Urapidil Accord injectable ampoules can be used for a maximum of 7 days

HYPERTENSIVE EMERGENCIES

Intravenous injection:

Initial dose:

25 mg of Urapidil will be administered in 20 seconds. If a sufficient reduction in blood pressure occurs after 5 minutes, your doctor will proceed to administer the maintenance dose. If the reduction in blood pressure has not been sufficient after 5 minutes, 25 mg of Urapidil will be administered again in 20 seconds. If the reduction in blood pressure is sufficient after 5 minutes, your doctor will proceed to administer the maintenance dose, and if, on the other hand, this reduction in blood pressure is insufficient after 5 minutes, 50 mg of Urapidil will be administered in 20 seconds, and the maintenance dose will be administered if the reduction in blood pressure is sufficient after 5 minutes.

Maintenance dose:

• Perfusion: 9 to 30 mg/h (average 15) (7 to 22 drops/min.) (average 11)
• Electric syringe: 9 to 30 mg/h (average 15) (4.5 to 15 ml/h) (average 7.5)

Intravenous perfusion or electric syringe:

Initial dose:

• Perfusion: 2 mg/min. (88 drops: 4.4 ml/min.), if the reduction in blood pressure is sufficient, your doctor will proceed to administer the maintenance dose.
• Electric syringe: 2 mg/min. (1 ml/min.), if the reduction in blood pressure is sufficient, your doctor will proceed to administer the maintenance dose.

Preparation of solutions

Perfusions: add 5 ampoules of Urapidil Accord 5 mg/ml in 500 ml of solution

Electric syringe: 2 ampoules of Urapidil Accord 5 mg/ml in 50 ml of solution

Posological recommendation for the treatment of hypertensive episodes