URAPIDIL KALCEKS 5 mg/ml INJECTABLE SOLUTION AND PERFUSION SOLUTION

Introduction

Package Leaflet: Information for the User

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

urapidil

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

Contents of the pack

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

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

Urapidil Kalceks contains the active substance urapidil. Urapidil is a medicine that lowers blood pressure (antihypertensive) and belongs to a group of medicines called alpha-adrenergic blockers. This medicine works on the blood vessels (i.e., arteries and veins). It lowers blood pressure by relaxing the walls of the blood vessels.

This medicine is used in adults:

• in case of emergency due to high 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 lower high blood pressure during and/or after surgery.

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

Do not useUrapidil Kalceks

• if you are allergic to urapidil or any of the other ingredients of this medicine (listed in section 6);
• if you have a narrowing of the main artery (aortic stenosis) or a blood vessel anomaly called shunt(bypass) arteriovenous (except for arteriovenous shunt for hemodialysis that is hemodynamically inactive);
• breast-feeding

Warnings and precautions

If your blood pressure drops too quickly, it can cause a decrease in heart rate or cardiac arrest.

Talk to your doctor or nurse before you start using this medicine if any of the following situations apply to you, as special precautions may be necessary:

• you have had diarrhea or vomiting (or any other cause of fluid loss in your body);
• in patients with heart failure caused by a mechanical obstruction, such as a narrowing of the heart valve (aortic or mitral stenosis);
• in patients with a blockage of an artery in the lungs (pulmonary embolism);
• in patients with heart failure caused by inflammation of the tissue surrounding the heart (pericardial disease);

• in patients with liver problems;
• in patients with moderate or severe kidney problems;
• in elderly patients;
• in patients who are taking cimetidine at the same time (a medicine to reduce stomach acidity).

If you are not sure if any of the above situations apply to you, talk to your doctor or nurse.

If you are undergoing eye surgery due to cataracts, inform your ophthalmologist before the operation that you are using or have previously used urapidil. This is because urapidil can cause complications during surgery that can be managed if your specialist is prepared in advance.

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

Children

This medicine must not be used in children or adolescents.

Other medicines and Urapidil Kalceks

Tell your doctor or nurse if you are taking, have recently taken, or might take any other medicines.

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

• alpha-adrenergic blockers (medicines used to treat disorders of the urinary tract associated with prostate disease);
• any medicine to lower blood pressure;
• cimetidine (used to inhibit stomach acid production);
• barbiturates (medicines used to treat epilepsy).

Using Urapidil Kalceks with alcohol

Alcohol may increase the effect of this medicine.

Pregnancy, breast-feeding, and fertility

If you are pregnant or breast-feeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before you are given this medicine.

There is not enough data on the safety of urapidil in pregnant women. This medicine should not be used during pregnancy unless the clinical condition of the woman requires treatment. If there is an increase in blood pressure during pregnancy and you need to be treated with this medicine, the reduction in blood pressure should be gradual and always monitored by a doctor.

It is not known whether this medicine is excreted in breast milk, so, for safety reasons, this medicine should not be used during breast-feeding.

This medicine is not recommended in women who may become pregnant and are not using a contraceptive method.

Studies in animals have shown that urapidil affects fertility. However, it is not known whether this influence occurs in humans.

Driving and using machines

This medicine may affect your ability to drive or use machines, especially at the start of treatment, when increasing the dose, or when changing medication, and in combination with alcohol.

Urapidil Kalceks contains propylene glycol (E1520) and sodium

Propylene glycol:

• This medicine contains 1,000 mg of propylene glycol per 10 ml of solution, which is equivalent to 100 mg/ml.
• If you are pregnant or breast-feeding, you should not be given this medicine unless your doctor has recommended it. Your doctor may perform additional checks while you are being given this medicine.
• If you have liver or kidney disease, you should not be given this medicine unless your doctor has recommended it. Your doctor may perform additional checks while you are being given this medicine.
• The propylene glycol in this medicine may have the same effects as alcohol and increase the likelihood of side effects.

Sodium:

This medicine contains less than 1 mmol of sodium (23 mg) per ml of solution; this is essentially "sodium-free".

3. How to use Urapidil Kalceks

How to use this medicine

• This medicine will be administered by a healthcare professional.

• This medicine will be administered as an injection or infusion into a vein. It can be administered as a single injection or as repeated injections, or as prolonged infusions. Injections can be combined with (subsequent) prolonged infusions.
• You should be in a supine position while you are being given this medicine.
• During treatment, your blood pressure will be constantly monitored.

Dose

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

Hypertensive crises and severe or extremely severe high blood pressure or high blood pressure that does not respond to treatment

By injection into a vein

As an injection, 10-50 mg of urapidil is administered intravenously, slowly, with continuous monitoring of blood pressure. A decrease in blood pressure is expected within 5 minutes after the injection. The injection of urapidil can be repeated depending on how the blood pressure responds.

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

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

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

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

Lowering high blood pressure during and/or after surgery

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

By injection into a vein

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

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

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

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

Special patient groups

The dose may need to be reduced in patients with liver and/or kidney disorders.

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

Duration of treatment

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

If you are given more Urapidil Kalceks than you should

If you are given too much of this medicine, you may experience dizziness, slight drowsiness, or fainting when standing up, fatigue, and a slower reaction time. In this case, lie down with your legs raised. If the symptoms persist, inform your doctor or nurse immediately.

If you have any further questions about the use of this medicine, ask your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

The side effects described below are generally the result of a sudden drop in blood pressure.

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

Common(may affect up to 1 in 10 people)

Dizziness, headache, nausea.

Uncommon(may affect up to 1 in 100 people)

Sleep disorders, palpitations, increased or decreased heart rate, feeling of pressure or pain in the chest (such as angina pectoris), breathing difficulties, decrease in blood pressure when standing up from a sitting or lying position (orthostatic dysregulation), vomiting, diarrhea, dry mouth, sweating, fatigue, irregular heartbeat.

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

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

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

Restlessness, increased urge to urinate, increased urinary incontinence, decrease in the number of platelets (blood cells that help the body form clots to stop bleeding).

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

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

Reporting side effects

If you experience any side effects, talk to your doctor or nurse, even if they are 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. Storing Urapidil Kalceks

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

This medicine does not require any special storage conditions.

After dilution

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

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

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

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Container Contents and Additional Information

Urapidil Kalceks Composition

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

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

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

Product Appearance and Container Contents

Transparent and colorless solution, free from visible particles.

Transparent glass ampoules of 10 ml with a break point.

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

Marketing Authorization Holder and Manufacturer

AS KALCEKS

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

Tel.: +371 67083320

E-mail: kalceks@kalceks.lv

For further information on this medicinal product, please contact the local representative of the marketing authorization holder

EVER Pharma Therapeutics Spain SL

c/ Toledo 170

28005 Madrid

Spain

This medicinal product is authorized in the Member States of the European Economic Area under the following names:

Estonia, Czech Republic, Italy, Portugal: Urapidil Kalceks

Austria Urapidil Kalceks 25 mg, 50 mg Injektions-/Infusionslösung

France URAPIDIL KALCEKS 25 mg/5 ml, solution injectable/pour perfusion

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

Germany Urapidil Ethypharm 25 mg, 50 mg Injektions-/Infusionslösung

Hungary Urapidil Kalceks 25 mg, 50 mg oldatos injekció vagy infúzió

Latvia Urapidil Kalceks 25 mg, 50 mg šķidums injekcijām/infūzijām

Poland Urapidil KALCEKS

Romania Urapidil Kalceks 25 mg, 50 mg soluție injectabilă/perfuzabilă

Slovakia Urapidil Kalceks 25 mg, 50 mg injekčný/infúzny roztok

Spain Urapidil Kalceks 5 mg/ml solución inyectable y para perfusión

The Netherlands Urapidil Kalceks 25 mg, 50 mg oplossing voor injectie/infusie

Date of the last revision of this prospect:February 2021

Detailed information on this medicinal product 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 for healthcare professionals only:

Dosage

Hypertensive emergencies, severe or extremely severe forms of hypertensive disease, resistant hypertension

• Intravenous injection

As an injection, 10-50 mg of urapidil is administered by slow intravenous injection, with continuous monitoring of blood pressure.

A hypotensive effect is expected within 5 minutes after injection. The injection of urapidil may be repeated according to the response of blood pressure.

• Infusion by intravenous drip or syringe pump

To maintain the blood pressure values achieved with the injection, continuous infusion is used by syringe pump or intravenous drip. 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 4 mg of urapidil per ml of infusion solution.

Administration rate

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

Initial reference rate: 2 mg/min.

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

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

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

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

Administration schedule

Special patient groups

The dose of urapidil may need to be reduced in patients with hepatic and/or renal dysfunction.

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

Pediatric population

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

Method of administration

Intravenous route.

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

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

In case of overlap with brief or urgent parenteral treatment, it can be switched to maintenance treatment with oral antihypertensives.

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

Incompatibilities

This medicinal product must not be mixed with alkaline solutions for injection or infusion, as it may cause clouding or flocculation due to the acidic properties of the solution.

This medicinal product must not be mixed with other medicinal products, except for those mentioned below.

Instructions for use and disposal

For single use.

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

The medicinal product must be visually inspected before use. It should only be used if the solution is transparent and particle-free.

Preparation of the diluted solution

• Intravenous drip infusion: add 250 mg of urapidil to 500 ml of a compatible infusion solution (see below).
• Syringe pump: extract 20 ml of injectable and infusion solution (= 100 mg of urapidil) into a syringe pump and dilute to a volume of 50 ml with a compatible infusion solution (see below).

It can be diluted with:

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

Instructions for opening the ampoule:

1. Hold the ampoule with the colored point facing upwards. If some solution remains in the upper part of the ampoule, gently tap with your finger to make the solution flow down to the lower part of the ampoule.
2. Use both hands to open it, and 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 direction opposite to the colored point (see the images below).

Disposal of unused medicinal products and all materials that have come into contact with them will be carried out in accordance with local regulations.