Patient Information Leaflet

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

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

• Keep this leaflet, as you may need to read it again.
  If you have any questions, consult your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only, and you must not give it to others, even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor or pharmacist or nurse, even if they are not listed in this leaflet.See section 4.

1. What isUrapidil Accordand what it is used for

2. What you need to know before starting to useUrapidil Accord

3. How to useUrapidil Accord

4. Possible side effects

5. Storage ofUrapidil Accord

6. Contents of the pack and additional information

Urapidil Accord belongs to a group of medicines called alpha-adrenergic blockers (that is, they block alpha-adrenergic receptors responsible for the constriction of blood vessels and, therefore, the increase in blood pressure)andproduce 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 necessary maneuvers during anesthesia (intubation:insertion of a tube through the mouth to the trachea, to ensure breathing and extubation: removal of the same).

No use Urapidil Accord

• If you are allergic to urapidil or any of the other components of this medication (listed in section 6).
• If you have aortic isthmus stenosis (narrowing) or an arteriovenous shunt (except for an inactive hemodynamically dialysis shunt).

Warnings and Precautions

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

Special care is required when Urapidil Accord is used in:

• Patients with heart conditions.
• Children, as no studies have been conducted in this patient group.
• Patients with liver disease.
• Patients with kidney disease.
• Older patients.
• Patients being treated with cimetidine at the same time (see section “use of urapidil accord with other medications”).
• If you have previously taken or been given other anti-hypertensive medications.

Consult your doctor if any of the above circumstances have occurred at any time.

Use of Urapidil Accord with other medications

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

The anti-hypertensive effect of urapidil may increase if you are given other α-adrenergic receptor agonists and other anti-hypertensive medications, as well as in states of hypovolemia (decreased blood volume, for example, diarrhea or vomiting) or alcohol.

If you take or are given cimetidine at the same time as this medication, it may increase the levels of urapidil in the blood.

If you have taken or been given an angiotensin-converting enzyme inhibitor (anti-hypertensive medication, also called ACE inhibitors) you must inform your doctor, as the combination of urapidil with this type of medication is not recommended. Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication.

Pregnancy, breastfeeding, and fertility:

If you are pregnant or breastfeeding, or think you may be pregnant, consult your doctor or pharmacist before using this medication.

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

The excretion of urapidil in breast milk is unknown, therefore urapidil should not be used during breastfeeding.

Driving and operating machinery

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

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

Urapidil Accord contains propylene glycol and sodium

This medication 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 medication unless recommended by your doctor. Your doctor may perform additional checks while you are taking this medication.

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

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

This medication contains less than 23 mg (1 mmol) of sodium per ampoule, making it essentially “sodium-free”

Urapidil Accord will only be administered in the hospital by healthcare professionals. This medication will be administered intravenously.

Follow exactly the administration instructions of this medication indicated by your doctor, pharmacist or nurse. In case of doubt, consult your doctor, pharmacist or nurse again. The duration of treatment with urapidil will be, at most, seven days.

Adults

Emergency hypertension:

Intravenous injection:

Initial dose:

1/2 ampoule (25 mg) of urapidil will be administered, during 20 seconds. If after 5 minutes a sufficient decrease in blood pressure is produced, your doctor will pass to administer the maintenance dose. If the decrease in blood pressure has not been sufficient, 1/2 ampoule (25 mg) of urapidil will be administered again, during 20 seconds. If after 5 minutes the decrease in blood pressure is sufficient, your doctor will pass to administer the maintenance dose, and if, on the contrary, this decrease is insufficient, 1 ampoule (50 mg) of urapidil will be administered during 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).

Infusion or electric syringe:

Initial dose:

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

1/2 ampoule (25 mg) of urapidil will be administered during 20 seconds. If after 2 minutes a sufficient decrease in blood pressure is produced, your doctor will pass to administer the maintenance dose. If the decrease in blood pressure has not been sufficient, 1/2 ampoule (25 mg) of urapidil will be administered again during 20 seconds, and if after 2 minutes the reduction in blood pressure is sufficient, your doctor will pass to administer the maintenance dose. If, on the contrary, the decrease is insufficient, 1 ampoule (50 mg) of urapidil will be administered during 20 seconds and 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)

Infusion or electric syringe:

Initial dose:

• Infusion: 6 mg/min. (264 drops: 13.2 ml/min.) if a sufficient decrease in blood pressure is produced, your doctor will pass to administer the maintenance dose.
• Electric syringe: 6 mg/min. (3 ml/min.), if a sufficient decrease in blood pressure is produced, your doctor will pass 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 patients with kidney disease or in elderly patients:

Your doctor will evaluate the dose to be administered.

If they estimate that the action of urapidil is too strong or too weak, inform your doctor.

If you receive more Urapidil Accord than you should

This medication 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 received more urapidil than you should, inform your doctor immediately. In case of accidental overdose, consult the Toxicological Information Service (phone: 91-562.04.20), indicating the product and the amount administered. Bring this leaflet with you.

In case of overdose, the following symptoms may appear:

Circulatory symptoms: dizziness, orthostatic hypotension (sudden drop in blood pressure when standing up, with a brief sensation 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 decrease in blood pressure can be mitigated by placing the patient with their legs elevated and performing volume expansion. If these measures are not sufficient, a vasoconstrictor agent may be administered intravenously slowly, controlling blood pressure levels.

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

If treatment with Urapidil Accord is interrupted:

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

Like all medicines, this medicine may cause side effects, although not everyone will experience them.The majority of side effects listed below are due to a rapid decrease in blood pressure, which, according to experience, disappears in a few minutes, even during infusion.

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

Frequent (may affect up to 1 in 10 people)Less frequent: (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

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

Vascular disordersLess frequent: Decrease in blood pressure when changing position, for example, when standing up after being lying down (orthostatic hypotension).

Gastrointestinal disorders

Frequent: nausea

Less frequent: vomiting.

General disorders and administration site conditions

Less frequent: fatigue

Investigations

Less frequent: irregular heartbeats.

Very rare: In association with the 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

Frequent: dizziness, headache.

Mental and behavioral disorders

Very rare: agitation

Reproductive system and breast disorders

Rare: priapism (persistent erection, with pain)

Respiratory, thoracic and mediastinal disorders

Rare: nasal congestion.

Skin and subcutaneous tissue disorders

Unknown frequency: angioedema, urticaria.

Less frequent: excessive sweating

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

If you consider that any of the side effects you experience are severe or if you notice any side effect not mentioned in this leaflet, inform your doctor or pharmacist.

Reporting of side effectsIf you experience any type of side effect, consult your doctor or pharmacist or nurse, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use: www.notificaRAM.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the packaging and on the ampule after CAD. The expiration 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 must be used immediately for microbiological reasons. If the prepared solution is not used immediately, the user is responsible for the period and storage conditions.

Medicines should not be thrown into the drains or trash.Deposit the packaging and medicines that you no longer need at the SIGRE collection point of the pharmacy.In case of doubt, ask your pharmacist how to dispose of the packaging and medicines that you no longer need.This will help protect the environment.

Composition of Urapidil Accord

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

Appearance of the product and contents of the package

This medicine is presented in the form of a clear, transparent or slightly brownish injectable solution in ampoules. Each package contains 5 ampoules.

Holder of the marketing authorization and responsible for manufacturing:

Holder

Accord Healthcare, S.L.U.

World Trade Center

Moll de Barcelona s/n, Edifici Est,

6th floor 08039 Barcelona

Responsible for manufacturing

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

Last review date of this prospectus: February 2020

The detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/

-------------------------------------------------------------------------------------------------------------------

This information is intended solely for doctors or healthcare professionals:

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

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

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

The administration will be carried out according to the attached schedule. Taking into account the duration of the available toxicological studies, the duration of use of Urapidil Accord will be, at most, seven days.

PERIOPERATIVE USE

Intravenous injection:

Initial dose:

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

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

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)

Infusion or electric syringe:

Initial dose:

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

Preparation of solutions:

Infusions: add 5 ampoules of Urapidil Accord 5 mg/ml to 500 ml of solution

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

Recommended dosage for use before surgery

Children:

Initial dose: 2mg/Kg/h

Maintenance dose: 0.8 mg/Kg/h

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

URGENT HYPERTENSIVE EMERGENCIES

Intravenous injection:

Initial dose:

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

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)

Infusion or electric syringe:

Initial dose:

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

Preparation of solutions

Infusions: add 5 ampoules of Urapidil Accord 5 mg/ml to 500 ml of solution

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

Recommended dosage for the treatment of hypertensive episodes