Urapidil Kalceks

Package leaflet: Information for the user

Urapidil Kalceks 25 mg injectable/infusion solution, 50 mg injectable/infusion solution

Urapidil
Equivalent medicine
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 Urapidil Kalceks is and what it is used for
2. What you need to know before being given Urapidil Kalceks
3. How Urapidil Kalceks is administered
4. Possible side effects
5. How to store 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, a medicine that lowers blood pressure (antihypertensive agent) belonging to a group of medicines called “alpha-blockers”.
This medicine acts on the blood vessels (i.e. arteries and veins). It reduces blood pressure by relaxing the walls of the blood vessels.
This medicine is used in adults:

• in emergencies related to high blood pressure (e.g. sudden, severe increase in blood pressure, known as “hypertensive crisis”);
• for the treatment of severe to extremely severe forms of high blood pressure or high blood pressure resistant to therapy;
• to reduce high blood pressure during and/or after surgery.

2. What you need to know before receiving Urapidil Kalceks

Do not receive Urapidil Kalceks

• if you are allergic to urapidil or to any of the other ingredients of this medicine (listed in section 6);
• if you have narrowing of the main artery (aortic stenosis) or a blood vessel disorder called "cardiac shunt" (except for cardiac shunt in patients undergoing dialysis);
• if you are breastfeeding.

Warnings and precautions
If your blood pressure drops too quickly, this may lead to a reduced heart rate or cardiac arrest.
Contact your doctor or nurse before receiving this medicine if any of the following apply to you, as special caution is required:

• if you have had diarrhoea or vomiting (or any other condition causing reduced body fluids);
• patients with heart failure caused by mechanical obstruction, e.g. narrowing of a heart valve (aortic or mitral stenosis);
• patients with blockage of an artery in the lungs (pulmonary embolism);
• patients with impaired heart function due to inflammation of the sac of tissue surrounding the heart (pericardial disease);
• patients with liver disorders;
• patients with moderate to severe kidney disorders;
• elderly patients;
• patients who are taking cimetidine (a medicine used to reduce gastric acid) concomitantly.
  If you are unsure whether any of the above apply to you, consult your doctor or nurse.

If you are scheduled for cataract surgery (clouding of the lens), inform your ophthalmologist before the operation that you are currently using or have previously used urapidil. This is because urapidil may cause complications during surgery, which can be managed if the specialist is prepared in advance.
If another antihypertensive medicine was administered before urapidil, your doctor will wait a sufficient amount of time for the previous medicine to take effect. Your doctor will reduce the dose of urapidil. A too rapid decrease in blood pressure may cause a reduced heart rate or cardiac arrest.

Children and adolescents
This medicine must not be used in children and adolescents.

Other medicines and Urapidil Kalceks
Inform your doctor or nurse if you are taking, have recently taken, or might take any other medicines.
Inform your doctor or nurse before receiving 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 adverse effects:

• alpha-blockers (medicines used to treat urinary tract disorders associated with prostate diseases);
• any medicine for lowering blood pressure;
• cimetidine (used to inhibit acid production in the stomach);
• barbiturates (medicines used to treat epilepsy).

Urapidil Kalceks and alcohol
Alcohol may increase the effect of this medicine.

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor before receiving this medicine.
There are insufficient data to assess the safety of urapidil in pregnant women. This medicine should not be used during pregnancy unless clearly needed due to the woman's clinical condition. If high blood pressure requiring treatment with this medicine occurs during pregnancy, blood pressure reduction must be gradual and always under medical supervision.
It is unknown whether this medicine is excreted in human breast milk. For safety reasons, this medicine should not be used during breastfeeding.
This medicine is not recommended for women of childbearing potential who are not using contraceptive measures.
Animal studies have shown that urapidil affects fertility. However, the relevance of this effect in humans is unknown.

Driving and using machines
This medicine may affect your ability to drive or operate machinery, especially at the beginning of treatment, when the dose is increased or treatment is changed, or when taken together with alcohol.

Urapidil Kalceks contains propylene glycol (E1520) and sodium
Propylene glycol:

• This medicine contains 500 mg of propylene glycol per 5 ml of solution and 1,000 mg of propylene glycol per 10 ml of solution, equivalent to 100 mg/ml.
• If you are pregnant or breastfeeding, you should not receive this medicine unless recommended by your doctor. Your doctor may perform additional monitoring during treatment with this medicine.
• If you have liver or kidney disease, you should not receive this medicine unless recommended by your doctor. Your doctor may perform additional monitoring during treatment with this medicine.
• Propylene glycol in this medicine may produce effects similar to those of alcohol consumption and may increase the likelihood of side effects.

Sodium:

• This medicine contains less than 1 mmol (23 mg) of sodium per ml, i.e. essentially 'sodium-free'.

3. How Urapidil Kalceks is administered

How this medicine is administered

• This medicine will be administered by a healthcare professional.
• This medicine will be given as an injection or infusion into a vein. It may be administered as a single injection, repeated injections, or continuous infusions. Injections may be followed (continued) by continuous infusions.
• During administration of this medicine, you must lie in a supine position.
• During treatment, your blood pressure will be continuously monitored.

Dosage
The doctor will determine the appropriate dose based on your condition.

Hypertensive crisis and severe to extremely severe forms of high blood pressure or therapy-resistant high blood pressure
By intravenous injection
As an injection, 10–50 mg of urapidil are administered slowly, with continuous monitoring of blood pressure. A blood pressure-lowering effect can be expected within 5 minutes after injection. The urapidil injection may be repeated according to the blood pressure response.

By intravenous infusion (using an infusion set or syringe pump)
For continuous slow infusion, 250 mg of urapidil are added to 500 ml of a compatible infusion solution (0.9% sodium chloride or 5% or 10% glucose solution).
If a syringe pump is used, 100 mg of urapidil are 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 infusion rate is 2 mg/min. The maintenance dose averages 9 mg/hour. The extent of blood pressure reduction will be determined by the dose infused during the first 15 minutes.
Subsequently, the established blood pressure level may be maintained with significantly lower doses.

Reduction of high blood pressure during and/or after surgery
To maintain the blood pressure level achieved with injection, continuous infusion via a syringe pump or continuous slow infusion is used.

By intravenous injection
Initially, 25 mg of urapidil are administered. This dose will be repeated if sufficient blood pressure reduction is not achieved after 2 minutes. If blood pressure reduction remains insufficient within 2 minutes after the second dose, 50 mg of urapidil will be administered.

If sufficient blood pressure reduction is achieved within 2 minutes after the administered dose, maintenance dosing will be initiated.

By intravenous infusion (using an infusion set or syringe pump)
Initially, up to 6 mg will be administered over 1–2 minutes. The dose will then be reduced.

Special patient groups
In patients with liver and/or kidney disorders, dose reduction may be necessary.
In elderly patients, this medicine should be administered with caution. Lower initial doses will be used, as sensitivity to such medicines is often altered in these patients.

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

If you receive more Urapidil Kalceks than you should
If you receive an excessive amount of this medicine, symptoms such as dizziness, mental confusion, or fainting upon standing, fatigue, and reduced reaction speed may occur. In this case, lie down with your legs elevated. If symptoms persist, inform your doctor or nurse immediately.

If you have any doubts about the use of this medicine, consult 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 too rapid a reduction in blood pressure.
However, experience has shown that they resolve within a few minutes, even during long-term infusions.
The doctor will decide whether to stop 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 disturbances, palpitations, increased or decreased heart rate, sensation of tightness or pain in the chest (like angina pectoris), difficulty breathing, drop in blood pressure when standing up from a sitting or lying position (orthostatic dysregulation), vomiting, diarrhoea, 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 need to urinate, increased urinary incontinence, reduction in the number of platelets (blood cells that help form clots to stop bleeding).
Not known (frequency cannot be estimated from the available data)
Urticaria, severe allergic reaction with swelling of the face, lips, tongue and throat.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or nurse. You can also report side effects directly via the national reporting system at:
https://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 Urapidil Kalceks

Keep this medicine out of the sight and reach of children.
This medicine does not require any special storage conditions.

After dilution
Chemical and physical in-use stability has been demonstrated for 50 hours at a temperature of 25 °C and
2 °C – 8 °C, when diluted in infusion solutions of sodium chloride 9 mg/ml (0.9%), glucose
50 mg/ml (5%) or glucose 100 mg/ml (10%).

From a microbiological standpoint, the diluted solution should be used immediately. If not used immediately, the storage duration and conditions prior to use are the responsibility of the user and should normally not exceed 24 hours at 2 °C – 8 °C, unless the dilution has been carried out under controlled and validated aseptic conditions.

Do not use this medicine after the expiry date stated on the carton and vial after Exp./EXP. The expiry date refers to the last day of that month.

Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Urapidil Kalceks contains

• The active substance is urapidil. 1 ml of solution contains 5 mg of urapidil. Each 5 ml vial of solution contains 25 mg of urapidil. Each 10 ml vial of solution contains 50 mg of urapidil.
• The other components are concentrated hydrochloric acid, sodium dihydrogen phosphate dihydrate, disodium phosphate dihydrate, propylene glycol (E1520), sodium hydroxide (for pH adjustment), water for injections.

Description of the appearance of Urapidil Kalceks and contents of the pack
Clear, colourless solution, free from visible particles.
Clear glass vials of 5 ml or 10 ml with OPC snap-off system.
5 vials are packed in a pouch. The pouch is packaged in a cardboard box.
It is possible that not all pack sizes are marketed.

Marketing Authorisation Holder and Manufacturer
AS KALCEKS
Krustpils iela 71E, Rīga, LV-1057, Latvia
Tel.: +371 67083320
E-mail: [email protected]

This medicinal product is authorised in the European Economic Area Member States 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 Kalceks 25 mg, 50 mg Injektions-/Infusionslösung
Hungary: Urapidil Kalceks 25 mg, 50 mg oldatos injekció vagy infúzió
Latvia: Urapidil Kalceks 25 mg, 50 mg šķīdums 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 perfusion
Netherlands: Urapidil Kalceks 25 mg, 50 mg oplossing voor injectie/infusie

The following information is intended for healthcare professionals only:

Dosage
Hypertensive emergency, severe and extremely severe forms of hypertension, and treatment-resistant hypertension

• Intravenous injection: As an injection, 10–50 mg of urapidil are administered slowly intravenously with continuous monitoring of arterial pressure. The hypotensive effect manifests within 5 minutes after injection. Urapidil injection may be repeated according to the blood pressure response.
• Continuous slow intravenous infusion or continuous infusion via syringe pump: Continuous slow infusion or syringe pump infusion is used to maintain the arterial pressure level achieved with the initial injection. 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 concentration is 4 mg of urapidil per ml of infusion solution.

Rate of administration
The infusion rate should be based on the individual blood pressure response.
Recommended initial rate: 2 mg/min.
The extent of arterial pressure reduction is determined by the dose infused over the first 15 minutes.
Subsequently, the achieved arterial pressure can be maintained with significantly lower doses.
Maintenance dose: on average 9 mg/hour, based on 250 mg of urapidil added to 500 ml of infusion solution, equivalent to 1 mg = 44 drops = 2.2 ml.

Controlled reduction of arterial pressure in hypertension during and/or after surgery
To maintain the arterial pressure level achieved with the initial injection, continuous infusion via syringe pump or slow continuous infusion is used.

Dosage regimen
If a
Intravenous injection
reduction in arterial pressure
of 25 mg of urapidil
occurs
(= 5 ml of injectable/perfusion solution)
after 2 min
Arterial pressure
no response
after 2 min stabilized
by infusion
If a
Intravenous injection
reduction in arterial pressure
of 25 mg of urapidil
occurs
(= 5 ml of injectable/perfusion solution)
after 2 min Initially, up to 6 mg
within
no response
after 2 min 1–2 min,
then reduce
If a
Slow intravenous injection
reduction in arterial pressure
of 50 mg of urapidil
occurs
(= 10 ml of injectable/perfusion solution)
after 2 min

Special patient groups
In patients with hepatic and/or renal dysfunction, a reduction in the dose of urapidil may be necessary.
Antihypertensive agents should be administered with due caution and at lower initial doses in elderly patients, as sensitivity to these medicinal products is often altered in this population.

Paediatric population
The safety and efficacy of urapidil in children and adolescents have not been established. No data are available.

Method of administration
For intravenous use.
Urapidil Kalceks is administered intravenously as an injection or infusion to supine patients.
Single or repeated injections, as well as continuous infusions, may be given. Injections may be followed by continuous infusions.
During acute parenteral therapy, transition to oral antihypertensive maintenance therapy may be initiated.
To avoid toxicological effects, treatment duration should not exceed 7 days, which also represents the generally accepted limit for parenteral antihypertensive therapy. Parenteral treatment may be repeated if hypertension recurs.

Incompatibilities
This medicinal product must not be mixed with alkaline injectable or infusion solutions, as turbidity or flocculation may occur due to the acidic properties of the solution.
This medicinal product must not be mixed with other medicinal products except those listed below.

Instructions for use and disposal

For single use only.
Use immediately after opening the vial. Any unused portion must be discarded.
The medicine should be inspected visually before use. Only clear solutions free from particles should be used.
Preparation of the diluted solution

• Slow intravenous infusion: add 250 mg of urapidil to 500 ml of one of the compatible infusion solutions (see below).
• Syringe pump: 20 ml of injectable/infusion solution (= 100 mg of urapidil) are drawn into a syringe pump and diluted to a final volume of 50 ml with one of the compatible infusion solutions (see below).

Dilution may be performed with:

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

Instructions for opening the vial

1. Turn the vial with the coloured tip upwards. If any solution is present in the upper part of the vial, gently tap with the finger to bring all the solution to the lower part of the vial.
2. Use both hands to open; holding the lower part of the vial in one hand, break the upper part of the vial in the direction opposite to the coloured mark (see figures below).

Any unused medicine and waste material derived from this medicine must be disposed of in accordance with local regulations.