Urasap

Patient Information Leaflet

URASAP 25 mg/5 ml injectable solution for intravenous use, 50 mg/10 ml injectable solution for intravenous use, 100 mg/20 ml injectable solution for intravenous use

Urapidil
Equivalent medicine
Please read all of this leaflet carefully before using this medicine as 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 pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Urasap is and what it is used for

Urasap contains the active substance urapidil
Urasap belongs to a group of medicines called alpha-blockers. The site of action of this
medicine is located in the blood vessels (e.g. arteries or veins). It reduces blood pressure
by relaxing the walls of the blood vessels.
Urasap is used for:

• hypertensive emergencies (e.g. a dangerous rise in blood pressure)
• severe to extremely severe forms of high blood pressure
• high blood pressure not otherwise treatable
• controlled reduction of blood pressure in patients with elevated blood pressure during or after surgical procedures.

2. What you need to know before using URASAP

Do not take URASAP

• if you are allergic to urapidil or to any of the other ingredients of this medicine (listed in section 6).
• in patients with narrowing of the main artery (aortic isthmus stenosis) and an abnormal connection between an artery and a vein (arteriovenous shunt – exception: hemodynamically ineffective dialysis shunt).

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Urasap.
Before using URASAP, your doctor must consider:

• If you have had diarrhea or vomiting (or any other condition causing reduced fluid levels in your body)
• If your blood sodium levels are decreased.

Be especially careful with URASAP, particularly if:

• you have mechanical heart failure, e.g. caused by narrowing of heart valves (aortic or mitral valve stenosis), if you have pulmonary embolism, or reduced heart function due to pericardial disease (affecting the sac surrounding the heart)
• in children (0–18 years), as there are insufficient studies available
• in patients with hepatic dysfunction
• in patients with moderate to severe renal impairment
• in elderly patients
• in patients receiving cimetidine (a medicine used to reduce stomach acidity) (see section “Other medicines and Urasap”). In each of these cases, contact your doctor.

If Urasap is administered as additional treatment for high blood pressure:
Sufficient time must be allowed for the previous antihypertensive medication to exert its effect.
Accordingly, your doctor will select a lower dose of Urasap. If blood pressure reduction occurs too rapidly, bradycardia (slow heart rate) or a heart attack may occur.
The antihypertensive effect of Urasap may be enhanced by the following factors:

• dehydration, which may be caused by diarrhea or vomiting
• alcohol consumption.

Other medicines and Urasap
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Inform your doctor if you are taking any of the following medicines, as they may interact with Urasap, potentially altering their effectiveness or increasing the risk of adverse effects:

• Alpha-blockers, used not only as antihypertensives but also for urinary problems due to prostate disorders. Any drug that lowers blood pressure
• Baclofen (used to treat muscle spasms)
• Cimetidine (used to inhibit gastric acid production)
• Imipramine and neuroleptics (used to treat depression)
• Corticosteroids (anti-inflammatory agents, also known as steroids).

Pregnancy and breastfeeding
Ask your doctor or pharmacist for advice before taking any medicine.
The use of Urasap during pregnancy is not recommended.
However, if blood pressure rises during pregnancy and Urasap must be used, blood pressure reduction should be gradual and always monitored by a doctor.
Urasap must not be administered during breastfeeding.
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor before taking this medicine.

Driving and using machines
Do not drive or operate tools or machinery, as your reaction ability may be impaired. This is particularly likely at the beginning of treatment, when the dose is increased, after switching from another medicine, or when alcohol is consumed.
If you feel unwell, do not drive or use machinery until symptoms have resolved.

URASAP contains propylene glycol
This medicine contains 100 mg of propylene glycol per ml of solution.
If you are pregnant or breastfeeding, do not take this medicine unless otherwise advised by your doctor.
If you have liver or kidney disease, do not take this medicine unless otherwise advised by your doctor.
Propylene glycol in this medicine may produce effects similar to those of alcohol and may increase the likelihood of side effects.
Do not use this medicine in children under 5 years of age. Use this medicine only if recommended by your doctor. Your doctor may perform additional monitoring during treatment.

URASAP contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per vial, i.e. it is essentially sodium-free.

3. How to use URASAP

Use this medicine exactly as instructed by your doctor. If you have any doubts, consult your
doctor or pharmacist.
URASAP is administered by your doctor, who will determine the most appropriate dose for you and the
necessary duration of treatment.
URASAP is administered intravenously as an injectable solution or infusion, with the patient lying down.
Both single or repeated injections and long-term intravenous infusions are possible. Injections may be
combined with a subsequent long-term infusion. During acute therapy, either overlapping with injections or
infusion, transition to oral antihypertensive therapy in the form of tablets, capsules or similar formulations
may be performed.
A treatment duration of 7 days is considered safe and should not be exceeded.
How often and how much URASAP should be used?
For marked and critical increases in blood pressure (hypertensive emergency), severe and extremely
severe forms of hypertension, and therapy-resistant hypertension:
1) Intravenous injection:
10–50 mg of urapidil should be administered by slow intravenous injection, with continuous monitoring of
blood pressure.
The blood pressure-lowering effect is expected within 5–10 minutes after injection.
Depending on the blood pressure response, the Urasap injection may be repeated.
2) Slow intravenous infusion (drip infusion) or continuous infusion via an infusion pump (dosage pump
used for continuous intravenous drug administration):
To maintain blood pressure levels achieved after the initial injection, infusion solutions should be
reconstituted as described in section 5.
Administration rate:
The infusion rate should be based on the individual blood pressure response.
Recommended initial rate: 2 mg/minute.
Maintenance dose: average 9 mg/hour: when 250 mg of urapidil are added to 500 ml of infusion
solution, 1 mg corresponds to 2.2 ml = 44 drops.
Controlled reduction of blood pressure in patients with elevated blood pressure during or after surgery
To maintain blood pressure levels achieved by injection, a slow infusion (drip infusion) or continuous
infusion via an infusion pump is initiated.
Dosing schedule:
Intravenous injection of if blood pressure
25 mg urapidil decreases after 2 min
(= 5 ml of injectable solution)
none Stabilization of blood
after 2 min pressure response by
infusion
Initially, up to
6 mg within 1–2
minutes,
followed by dose
reduction
Intravenous injection of if blood pressure
25 mg urapidil decreases after 2 min
(= 5 ml of injectable solution)
none
after 2 min pressure
response
Slow intravenous injection of if blood pressure
50 mg urapidil decreases after 2 min
(= 10 ml of injectable solution)

Special patient groups
Use in children and adolescents
Use in children and adolescents under 18 years of age is not recommended due to lack of safety and
efficacy data.
In elderly patients, a dose reduction may be necessary.
If you have renal or hepatic impairment, the dose must be reduced.
Special precautions must be taken if you have heart failure caused by functional damage of mechanical
origin.
If you are given more URASAP than you should
An overdose may lead to an increase in adverse effects, such as:

• circulatory-related: dizziness, tinnitus, black spots in front of the eyes (orthostatic syndrome), collapse
• central nervous system-related: fatigue and slowed reflexes (see also section 4. Possible adverse effects).

Treatment in case of overdose:
Excessive drop in blood pressure may be corrected by elevating the legs and administering infusion
solutions capable of stabilizing blood circulation (volume-replenishing agents). If these measures are
inadequate, vasoconstrictors may be administered by slow intravenous injection, with simultaneous
monitoring of blood pressure. Administration of catecholamines is required only in very rare cases (e.g.,
adrenaline 0.5–1 mg diluted to 10 ml with isotonic saline solution).
If you have further questions about the use of this product, please consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them. If any of the side effects listed below worsen, or if you notice any side effects not listed in this leaflet, inform your doctor or pharmacist.

Common (may affect up to 1 in 10 people): dizziness, headache, nausea;
Uncommon (may affect up to 1 in 100 people): palpitations, fast or slow heartbeat (tachycardia or bradycardia), sensation of pressure or pain in the chest (symptoms similar to angina pectoris), shortness of breath (dyspnea), drop in blood pressure when changing position, e.g. upon standing up from a lying position (orthostatic dysregulation), sudden sweating, fatigue, vomiting, irregular heartbeat.
Rare (may affect up to 1 in 1,000 people): nasal congestion, allergic symptoms (itching, skin redness, rash), prolonged erection (priapism);
Very rare (may affect up to 1 in 10,000 people): restlessness, sleep disturbances, involuntary loss of urine (urinary incontinence), involuntary loss of urine during the night (nocturnal enuresis), blood clotting problems (reduced platelet count);
Frequency not known (frequency cannot be estimated from the available data): swelling of the face, mouth, tongue, throat (angioedema), skin rash with itching (urticaria).

In most cases, the above-listed side effects are due to an excessive drop in blood pressure. However, experience has shown that they disappear within a few minutes, even during long-term infusion.

Depending on the severity of the side effects, a decision may need to be made as to whether treatment should be discontinued.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, 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 URASAP

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label and the carton after
Exp. The expiry date refers to the last day of that month.
Storage conditions
Do not store above 25°C.
Notes on shelf life after opening or reconstitution
The chemical and physical stability of the ready-to-use solution has been demonstrated for 24 hours at 25°C.
From a microbiological standpoint, the ready-to-use preparation should be used immediately.
If not used immediately, the times and conditions of storage after opening are the responsibility of the user.
For opened vials, a shelf life of 24 hours has been demonstrated when stored at 2-8°C.
For single use only.
Use immediately after first opening of the vials.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Urasap contains

• The active substance is urapidil. 1 ml of injectable solution contains 5 mg of urapidil.
• The other components are: propylene glycol, disodium hydrogen phosphate dihydrate, sodium dihydrogen phosphate, water for injections, and (for pH adjustment): hydrochloric acid 36%, sodium hydroxide.

Description of the appearance of Urasap and contents of the pack
Urasap injectable solution for intravenous use is a clear, colourless solution contained in
glass ampoules with break-point (clear glass of type I, compliant with the requirements of the European Pharmacopoeia).
Urasap is available in the following presentations:
“25 mg/5 ml injectable solution for intravenous use”, 1 vial of 5 ml (= 25 mg urapidil)
“50 mg/10 ml injectable solution for intravenous use”, 5 vials of 10 ml (= 50 mg urapidil)
“100 mg/20 ml injectable solution for intravenous use”, 5 vials of 20 ml (= 100 mg urapidil).
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
INCA-Pharm S.r.l.
Via Marittima, 38 – 03100 Frosinone, Italy
Responsible manufacturers for batch release:
Haupt Pharma Wülfing GmbH
Bethelner Landstrasse, 18 – 31028 Gronau/Leine, Germany
Haupt Pharma Livron S.A.S.
1 rue Comte de Sinard - 26250 Livron-sur-Drôme, France

The following information is intended for healthcare professionals only:

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

Special precautions for use:
The 100 mg vials may only be used to stabilize blood pressure during infusion.
For initiating treatment, vials containing 25 mg and 50 mg of urapidil are available.
Dilution must be performed under aseptic conditions.
Before administration, visually inspect the solution for the presence of particles and any changes in color. Use only clear and colorless solutions.

Preparation of diluted solution:

• Intravenous infusion: Dilute 200–250 mg of urapidil (4–5 vials of Urasap 50 mg/10 ml injectable solution or 2 vials of Urasap 100 mg/20 ml injectable solution + 1 vial of Urasap 50 mg/10 ml injectable solution) with 500 ml of a compatible infusion solution (see below).
• When using a syringe pump for continuous infusion, draw 20 ml of injectable solution (= 100 mg of urapidil, equivalent to 2 vials of Urasap 50 mg/10 ml injectable solution or 1 vial of Urasap 100 mg/20 ml injectable solution) into the syringe and dilute to a final volume of 50 ml with a compatible infusion solution (see below). The maximum compatible concentration of urapidil is 4 mg/ml.

Compatible diluents for dilution:
Sodium chloride 0.9% solution, 5% or 10% glucose solution.
For single use only.
Any unused medicine and waste material must be disposed of in accordance with local regulations.