Leaflet: Information for the User

Urapidil Kalceks 5 mg/ml injectable solution and for infusion EFG

urapidil

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 or nurse.
• If you experience any side effects, consult your doctor or nurse, even if they are not listed in this leaflet. See section 4.

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

2. What you need to know before starting to use Urapidil Kalceks

3. How to use Urapidil Kalceks

4. Possible side effects

5. Storage of Urapidil Kalceks

6. Contents of the pack and additional information

Urapidil Kalceks contains the active ingredient urapidil. Urapidil is a medication that lowers blood pressure (antihypertensive) and belongs to a group of medications called alpha-adrenergic blockers. This medication exerts its effects on blood vessels (i.e., arteries and veins). It reduces blood pressure by relaxing the walls of blood vessels.

This medication is used in adults:

• in cases of emergency due to increased blood pressure (such as a sudden and significant increase in blood pressure called "hypertensive crisis");
• to treat severe or extremely severe high blood pressure or high blood pressure that does not respond to treatment;

to reduce high blood pressure during and/or after a surgical intervention.

No useUrapidil Kalceks

• If you are allergic to urapidil or any of the other components of this medication (listed in section6);
• If you have a narrowing of the main artery (aortic stenosis) or a blood vessel anomaly calledshunt(arteriovenous shunt) (except for arteriovenous shunt for inactive hemodynamically hemodialysis);
• Lactation

Warnings and precautions

A rapid decrease in blood pressure may cause a decrease in heart rate or cardiac arrest.

Consult your doctor or nurse before starting to use this medication if any of the following situations apply to you, as in that case special precautions are required:

• You have had diarrhea or vomiting (or any other cause of fluid reduction in your body);
• Patients with heart failure caused by mechanical obstruction, for example, a narrowing of the heart valve (aortic or mitral stenosis);
• Patients with a blockage of an artery in the lungs (pulmonary embolism);
• Patients with heart failure caused by inflammation of the tissue surrounding the heart (pericarditis);

• Patients with liver problems;
• Patients with moderate or severe kidney problems;
• Older adults;
• Patients using cimetidine simultaneously (medication to reduce stomach acid).

If you are unsure whether any of the above situations apply to you, speak with your doctor or nurse.

Before undergoing eye surgery due to cataract (opacity of the crystalline lens), inform your ophthalmologist before the operation that you are using or have used urapidil previously. This is because urapidil may cause complications during the operation that can be managed if your specialist is prepared in advance.

If you have been administered another medication to lower blood pressure before urapidil, your doctor will wait long enough for the previously administered medication to take effect. Your doctor will reduce the dose of urapidil. A rapid decrease in blood pressure may cause a decrease in heart rate or cardiac arrest.

Children

This medication should not be used in children or adolescents.

Other medications and Urapidil Kalceks

Inform your doctor or nurse if you are taking, have taken recently, or may need to take any other medication.

Inform your doctor or nurse before administering this medication if you are taking any of the following medications, as they may interact with Urapidil Kalceks, altering the effects of the medications or increasing the likelihood of side effects:

• Alpha-adrenergic blockers (medications used to treat urinary tract disorders associated with prostate disease);
• Any medication to reduce blood pressure;
• Cimetidine (used to inhibit stomach acid production);
• Barbiturates (medications used to treat epilepsy).

Use of Urapidil Kalceks with alcohol

Alcohol may increase the effect of this medication.

Pregnancy, lactation, and fertility

If you are pregnant or breastfeeding, or if you think you may be pregnant, ask your doctor for advice before this medication is administered.

There is insufficient data on the safety of urapidil in pregnant women. This medication should not be used during pregnancy unless the woman's clinical condition requires treatment. If high blood pressure develops during pregnancy and you need to be treated with this medication, blood pressure reduction should be gradual and always monitored by a doctor.

The excretion of this medication in breast milk is unknown, so, for safety reasons, this medication should not be used during lactation.

This medication is not recommended for women who may become pregnant and do not use a contraceptive method.

Studies in animals have shown that urapidil affects fertility. However, its influence on humans is unknown.

Driving and operating machinery

This medication may affect your ability to drive or operate machinery, especially at the beginning of treatment, with an increase in dose, or with a change in medication, and in combination with alcohol.

Urapidil Kalceks contains propylene glycol (E1520) and sodium

Propylene glycol:

• This medication contains 1,000mg of propylene glycol per 10ml of solution, which is equivalent to 100mg/ml.
• If you are pregnant or breastfeeding, you should not receive this medication unless your doctor recommends it. Your doctor may perform additional checks while you are receiving this medication.
• If you have liver or kidney disease, you should not receive this medication unless your doctor recommends it. Your doctor may perform additional checks while you are receiving this medication.
• The propylene glycol in this medication may have the same effects as alcohol and increase the likelihood of side effects.

Sodium:

This medication contains less than 1mmol of sodium (23mg) per ml of solution; it is essentially “sodium-free”.

How to use this medication

• This medication will be administered by a healthcare professional.

• This medication will be administered as an injection or infusion through a vein. It can be administered as a single injection or repeated injections, or as prolonged infusions. Injections can be combined with (subsequent) prolonged infusions.
• You should be in a supine position while this medication is being administered to you.
• Your blood pressure will be constantly monitored during treatment.

Dose

The doctor will decide on the appropriate dose based on your clinical condition.

Hypertensive crises and severe or extremely severe forms of high blood pressure or unresponsive high blood pressure

Through injection into a vein

As an injection, 10‑50mg of urapidil are administered intravenously at a slow rate, with continuous monitoring of blood pressure. A decrease in blood pressure is expected within 5minutes following the injection. The urapidil injection can be repeated based on the response of the blood pressure.

Through infusion into a vein (by intravenous drip or with a syringe pump)

For intravenous drip, 250mg of urapidil are added to 500ml of a compatible infusion solution (0.9% sodium chloride or 5% or 10% glucose solution).

When using a syringe pump, 100mg of urapidil are extracted in a syringe pump and diluted to a volume of 50ml with a compatible infusion solution (see above) (maximum 4mg of urapidil per ml of infusion solution).

The initial administration rate is 2mg/min. The maintenance dose is approximately 9mg/hour. The magnitude of blood pressure reduction will be determined by the dose infused within the first 15minutes. Subsequently, the established blood pressure can be maintained with much lower doses.

Reduction of high blood pressure during and/or after surgical intervention

To maintain the blood pressure values achieved with the injection, continuous infusion is used via syringe pump or intravenous drip.

Through injection into a vein

Initially, 25mg of urapidil are administered. This dose will be repeated if there is not a sufficient decrease in blood pressure after 2 minutes. If, within the 2 minutes following the second dose, the blood pressure decrease remains insufficient, 50mg of urapidil will be administered.

Once the blood pressure has decreased sufficiently 2minutes after the dose administered, you will be switched to the maintenance dose.

Through infusion into a vein (by intravenous drip or with a syringe pump)

Initially, up to 6mg will be administered over 1‑2minutes. The dose will then be reduced.

Special patient groups

It may be necessary to reduce the dose in patients with liver and/or kidney dysfunction.

In elderly patients, this medication should be administered with caution. At the beginning of treatment, smaller doses will be administered, as sensitivity to these medications is often altered in these patients.

Duration of treatment

The duration of treatment with this medication should not exceed 7days.

If you receive more Urapidil Kalceks than you should

If you receive an excessive amount of this medication, you may experience dizziness, slight drowsiness, or fainting upon standing, fatigue, and slower reaction time. In this case, lie down with your legs elevated. If symptoms persist, immediately inform your doctor or nurse.

If you have any other doubts about the use of this medication, ask your doctor or nurse.

Like all medications, this medication may produce adverse effects, although not all people may experience them.

The adverse effects described below are generally a consequence of a sudden drop in blood pressure.

However, based on experience, they disappear in a few minutes, even during prolonged infusions. The doctor will decide whether to interrupt or not the treatment based on the severity of the adverse effects.

Frequent(may affect up to 1 in 10people)

Dizziness, headache, nausea.

Occasional(may affect up to 1 in 100people)

Sleep disturbances, palpitations, increased or decreased heart rate, sensation of pressure or pain in the chest (like angina pectoris), difficulty breathing, decrease in blood pressure when standing up from a seated or lying position (orthostatic desregulation), vomiting, diarrhea, dry mouth, sweating, fatigue, irregular heartbeats.

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

Nasal congestion, allergic reactions (itching, skin redness, rash), prolonged and painful erection.

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

Restlessness, increased urgency to urinate, increased urinary incontinence, decrease in platelet count (blood cells that help the body form clots to stop bleeding).

Unknown frequency(the frequency cannot be estimated from available data)

Thrombi, severe allergic reaction with swelling of the face, lips, tongue, and throat.

Reporting Adverse Effects

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

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

This medication does not require special conditions of conservation.

After dilution

The chemical and physical stability of the prepared formulation has been demonstrated for use within 50 hours at 25 °C and 2-8 °C when diluted in a perfusion solution of 9 mg/ml (0.9%) sodium chloride or in 50 mg/ml (5%) glucose or in 100 mg/ml (10%) glucose.

From a microbiological point of view, the diluted solution should be used immediately. If not used immediately, storage times in use and pre-use conditions are the responsibility of the user and should normally not exceed 24 hours at a temperature of 2 to 8 °C, unless the dilution was performed in controlled and validated aseptic conditions.

Do not use this medication after the expiration date appearing on the carton box and on the ampoule after CAD. The expiration date is the last day of the month indicated.

Medications should not be disposed of through the drains or in the trash. Dispose of the containers and medications you no longer need at the SIGRE point of the pharmacy. If in doubt, ask your pharmacist how to dispose of the containers and medications you no longer need. In this way, you will help protect the environment.

Composition Urapidil Kalceks

?The active ingredient is urapidil. 1ml of solution contains 5mg of urapidil.

Each ampoule of 10ml of solution contains 50mg of urapidil.

?The other ingredients are concentrated hydrochloric acid, dihydrogen phosphate of sodium dihydrate, dihydrated sodium phosphate, propylene glycol (E1520), sodium hydroxide (for pH adjustment), and water forinjectable preparations.

Aspect of the product and content of the packaging

Clear and colorless solution, free of visible particles.

10ml transparent glass ampoules with a cutting point.

The ampoules are packaged in a tray of 5 ampoules. The tray is packaged in a cardboard box.

Holder of the marketing authorization and responsible for manufacturing

AS KALCEKS

Krustpils iela 71E, Riga, LV‑1057, Latvia

Phone: +37167083320

E‑mail:[email protected]

You can request more information about this medication by contacting the local representative of the marketing authorization holder

EVER Pharma Therapeutics Spain SL

c/ Toledo 170

28005 Madrid

Spain

This medication is authorized in the member states of the European Economic Area with the following names:

Estonia,Republic of Czech, Italy, Portugal:Urapidil Kalceks

AustriaUrapidil Kalceks 25 mg, 50 mg Injektions-/Infusionslösung

FranceURAPIDIL KALCEKS 25 mg/5 ml, solution injectable/pour perfusion

URAPIDIL KALCEKS 50 mg/10 ml, solution injectable/pour perfusion

GermanyUrapidil Ethypharm 25 mg, 50 mg Injektions-/Infusionslösung

HungaryUrapidil Kalceks 25 mg, 50 mg oldatos injekció vagy infúzió

LatviaUrapidil Kalceks 25 mg, 50 mg škidums injekcijam/infuzijam

PolandUrapidil KALCEKS

RomaniaUrapidil Kalceks 25 mg, 50 mg solu?ie injectabila/perfuzabila

SlovakiaUrapidil Kalceks 25 mg, 50 mg injekcný/infúzny roztok

SpainUrapidil Kalceks 5 mg/ml solución inyectable y para perfusion

NetherlandsUrapidil Kalceks 25 mg, 50 mg oplossing voor injectie/infusie

Last review date of this prospectus:February 2021

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

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This information is intended solely for healthcare professionals:

Dosage

Urgent hypertension, severe or extremely severe forms of hypertension, resistant hypertension

• Intravenous injection

As an injection, 10‑50mg of urapidil are administered intravenously slowly, with continuous monitoring of blood pressure.

It is expected that a hypotensive effect will occur within 5minutes after injection. Urapidil injection can be repeated based on the response of blood pressure.

• Perfusion via intravenous drip or syringe pump

To maintain the blood pressure values achieved with the injection, continuous perfusion via syringe pump or intravenous drip is used. For instructions on how to prepare the diluted solution, see ”Instructions for use and disposal” and ”Preparation of the diluted solution” below.

The maximum compatible amount is 4mg of urapidil per ml of perfusion solution.

Administration rate

The administration rate should be adjusted to the response of each patient to blood pressure.

Initial reference administration rate: 2mg/min.

The degree of blood pressure reduction is determined by the perfused dose in the first 15minutes. Subsequently, the established blood pressure can be maintained with significantly lower doses.

Maintenance dose: 9mg/h as an average, based on 250mg of urapidil in 500ml of perfusion solution, equivalent to 1mg = 44drops = 2.2ml.

Controlled reduction of blood pressure in hypertension peri and/or postoperative

To maintain the blood pressure values achieved with the injection, continuous perfusion via syringe pump or intravenous drip is used.

Dosage regimen

Special patient groups

It may be necessary to reduce the dose of urapidil in patients with liver and/or kidney dysfunction.

In elderly patients, antihypertensive drugs should be administered with caution and in smaller doses at the beginning of treatment, as sensitivity to these drugs is often altered in these patients.

Pediatric population

The safety and efficacy of urapidil have not been established in children and adolescents. There are no data.

Administration form

Routeintravenous.

Urapidil Kalceks is administered intravenously as an injection or intravenous perfusion in patients in a supine position.

It can be administered as a single injection or multiple injections, as well as prolonged perfusions. Injections can be combined with subsequent prolonged perfusions.

In case of overlapping with brief or urgent parenteral treatment, it can be changed to a maintenance treatment with oral antihypertensive drugs.

As a preventive measure against toxic effects, the treatment should not exceed a period of 7days, which is also the case with parenteral antihypertensive treatments. Parenteral treatment can be repeated if hypertension reappears.

Incompatibilities

This medication should not be mixed with alkaline injection or perfusion solutions, as it may cause turbidity or flocculation due to the acidic properties of the solution.

This medication should not be mixed with other medications, except for those mentioned below.

Instructions for use and disposal

For single use.

Use immediately after opening the ampoule. Discard any unused portion.

The medication should be visually inspected before use. It should only be used if the solution is transparent and free of particles.

Preparation of the diluted solution

• Perfusion via intravenous drip: add 250mg of urapidil to 500ml of a compatible perfusion solution (see below).
• Syringe pump:20ml of injectable and perfusion solution (=100mg of urapidil) are extracted in a syringe pump and diluted to a volume of 50ml with a compatible perfusion solution (see below).

It can be diluted with:

• 9mg/ml (0.9%) of sodium chloride solution for perfusion;
• 50mg/ml (5%) of glucose solution for perfusion;
• 100mg/ml (10%) of glucose solution for perfusion.

Instructions for opening the ampoule:

1. Hold the ampoule with the colored point upwards. If there is any solution left in the upper part of the ampoule, gently tap it with your finger to let all the solution flow to the lower part of the ampoule.
2. Use both hands to open it, while holding the lower part of the ampoule with one hand, use the other hand to break the upper part of the ampoule in the opposite direction to the colored point (see the images below).

The disposal of unused medication and all materials that have come into contact with it will be carried out in accordance with local regulations.