Label: information for the user

Cleviprex 0.5mg/ml injectable emulsion

Clevidipine

Read this label carefully before starting to use this medication, as it contains important information for you.

• Keep this label, as you may need to read it again.
• If you have any questions, consult your doctor.
• If you experience any adverse effects, consult your doctor, even if they are not listed in this label.See section 4.

1.What Cleviprex is and for what it is used

2.What you need to know before starting to use Cleviprex

3.How to use Cleviprex

4.Possible adverse effects

1. Storage of Cleviprex

6.Contents of the package and additional information

Cleviprex contains the active ingredient clevidipine.

Clevidipine is a calcium channel blocker. Calcium channel blockers are medications that lower blood pressure.

Cleviprex is used to reduceblood pressure inadult patients beforesurgery, during surgery, or immediately after surgery.

Do not use Cleviprex:

• if you are allergic (hypersensitive) to clevidipine, soy, soybean oil, soy products, peanuts, eggs, or egg products, or any other component of this medication (listed in section 6).
• if you have lipid metabolism disorders (difficulty processing fats), such as extremely high levels of fat in the blood (pathological hyperlipidemia), a kidney disorder that causes protein loss in the urine (nephrotic syndrome), or acute pancreatitis if accompanied by high levels of fat in the blood (hyperlipidemia).
• if you have severe aortic stenosis (severe narrowing of one of the heart valves).

In case of doubt, ask your doctor.

Warnings and precautions

Consult your doctor before starting to use Cleviprex:

• if you have a heart disease in which the aortic valve of the heart does not open completely
• if your heart is abnormally large due to narrowing of the blood vessels (hypertrophic obstructive cardiomyopathy)
• if you have a heart disease in which there is narrowing of a valve (mitral valve stenosis)
• if you have a tear in the main artery of the body (aortic dissection)
• if you have a tumor of the gland above the kidney that produces high blood pressure (pheochromocytoma)
• if you have had a heart attack
• if you have a chronic disease in which the heart cannot increase speed to compensate for the reduction in blood pressure, such as:
• • an electrical problem with the heart
  • you wear a pacemaker

Cleviprex with other medications

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

It is especially important to inform your doctor if you have been taking any medication to reduce blood pressure.

Pregnancy and breastfeeding

You must inform your doctor if:

- you are pregnant or think you may be

• you intend to become pregnant
• you are breastfeeding

There is not enough information available about the use ofCleviprex in pregnant women. Cleviprex should not be used during pregnancy unless it is clearly necessary. Your doctor will decide if this treatment is suitable for you.

It is unknown if Cleviprex is excreted in breast milk. If you are breastfeeding, your doctor will decide if Cleviprex should be used.

Driving and operating machinery

Cleviprex is used to reduce blood pressure, which may make you feel dizzy or nauseous and may affect your ability to drive or operate machinery.

You should not drive or operate machinery until the effects of Cleviprex have disappeared. In case of doubt, consult your doctor before leaving the hospital.

Cleviprex contains soybean oil and sodium

This medication contains soybean oil. It should not be used in case of allergy to peanuts or soy.

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

Cleviprex is administered through infusion (drip) in a vein. A doctor will administer it.

The treatment with Cleviprex will be supervised by a doctor since Cleviprex is administered in the hospital. The doctor will decide how much Cleviprex you will receive and prepare the medication.

• During the entire treatment, the doctor will monitor your blood pressure.
• Before starting the infusion, the doctor will inform you about the signs of an allergic reaction.
• The dose and duration of the infusion depend on the type of treatment you are undergoing.

Dose

The infusion of Cleviprex should start at 4ml/hour (2mg/hour) and will be increased according to tolerance, doubling the amount (i.e., from4 to8, from8 to16, from16 to32 and from32 to64ml/hour [2 to 4,4 to 8,8 to 16 and16 to 32mg/hour]) every 90 seconds.

Cleviprex will reduce blood pressure in most patients with doses of up to 32ml/hour (16mg/hour).

Some patients may require a dose of up to 64ml/hour (32mg/hour).

If you use more Cleviprex than you should

The doctor will carefully check these doses, so it is very unlikely that an overdose will occur. If you take too much Cleviprex, the infusion will be reduced or stopped.

An overdose of Cleviprex may make you feel dizzy or lightheaded or may make your heart beat faster.

If you think you have been given too much Cleviprex, talk to the doctor or other medical staff immediately.

If you forget to use Cleviprex

Since the treatment with Cleviprex is administered and supervised by a doctor, it is very unlikely that this will happen. If you think you may have forgotten a dose, talk to the doctor immediately.

While receiving Cleviprex

If you develop severe allergic reactions, such as swelling of the face and/or throat or fever, inform your doctor immediately.

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

Like all medications, Cleviprex can produce adverse effects, although not everyone will experience them. Adverse effects are usually mild and do not last long.

Cleviprex can produce atrial fibrillation (irregular heart rhythm), chest discomfort or hypoxia (lower oxygen levels in the blood, which can cause dizziness or lightheadedness). If this occurs, consult your doctor or another healthcare professional immediately, who will decide whether to continue treatment with Cleviprex.

Frequent: may affect up to 1 in 10 people
- tachycardia (rapid heart rate)

- atrial fibrillation (irregular heartbeats)

- hypoxia (lower oxygen levels in the blood)

- chest discomfort

- hypotension (low blood pressure)
- polyuria (excessive urine production)
- edema (swelling) at the injection site
- hot flashes (redness of the skin)
- sensation of heat

- acute renal failure (kidney damage)

Less frequent: may affect up to 1 in 100 people
- atrial flutter (abnormal heart rhythm)
- heart failure
- bradycardia (slow heart rate)
- atrioventricular block (feeling of heartbeats)
- constipation
- pulmonary congestion
- headache
- dizziness
- nausea
- vomiting
- allergic reaction

• high levels of triglycerides in the blood

Rare: may affect up to 1 in 1,000 people
- ileus (constipation; obstruction of the digestive system [intestine])

If you experience adverse effects, consult your doctor, even if they are not listed in this prospectus.

Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor, even if it is a possible adverse effect not listed in this prospectus. You can also report them directly throughthe Spanish System for Pharmacovigilance of Medicines for Human Use https://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.

Do not use this medication after the expiration date that appears on the label and the box after CAD. The expiration date is the last day of the month indicated.

Store and transport refrigerated (2°C – 8°C). Do not freeze.

Once the vial is opened, discard any unused remainder after 12 hours.

Store the vial in the outer packaging to protect it from light.

The emulsion must be milky and white.

The doctor will check the emulsion and discard it if it contains particles or is discolored.

Medicines should not be disposed of through drains or in the trash. The healthcare professional administering Cleviprex will be responsible for ensuring that the disposal of unused medication and all materials that have come into contact with it is carried out in accordance with regulations. This will help protect the environment.

Composition ofCleviprex

• The active ingredient is clevidipine.

1ml of injectable emulsion contains 0.5mg of clevidipine.

One vial of 50ml of emulsion contains 25mg of clevidipine.

One vial of 100ml of emulsion contains 50mg of clevidipine.

• The other components are refined soybean oil, glycerol, egg phospholipids, oleic acid, disodium edetate, water for injection, and sodium hydroxide (for pH adjustment).

Appearance of the product and contents of the package

Cleviprex is a white, milky emulsion in a glass vial.

Cleviprex is presented in boxes containing 10 vials of 50ml and 10 vials of 100ml.

Only some package sizes may be commercially available.

Marketing Authorization Holder

Chiesi España, S.A.U.

Plaça d’Europa, 41-43, 10th floor

08908 L’Hospitalet de Llobregat

Barcelona

Spain

Responsible for manufacturing

Diapharm GmbH & CO. KG

Am Mittelhafen 56

48155 Münster

Germany

Amryt Pharmaceuticals Designated Activity Company

45 Mespil Road,

Dublin 4, D04 W2F1,

Ireland

Further information about this medicinal product can be obtained by contacting the local representative of the marketing authorization holder

Ferrer Farma, S.A.

Av. Diagonal, 549 5th floor

08029 Barcelona (Spain)

Last review date of this leaflet:October 2024

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

This information is intended solely for healthcare professionals:

Cleviprex 0.5mg/ml injectable emulsion

Clevidipine

Healthcare professionals should consult the product's technical file or summary of product characteristics for complete prescribing information.

Cleviprex is indicated for the rapid reduction of blood pressure in the perioperative setting. The safety and efficacy have not been established in children or pregnant women.

Instructions for use

For single use only.

Use aseptic technique. Once the stopper is pierced, use within 12 hours; discard any unused remainder according to local regulations.

Cleviprex is a sterile, white, and opaque emulsion. Visually inspect before use. Discolored or particulate-containing solutions should not be used.

Invert the vial gently before use to ensure uniformity of the emulsion.

Cleviprex should be administered using a needle with air intake and a perfusion device. Do not dilute.

Cleviprex may be administered through lipid filters with a pore size of 1.2microns.

Cleviprex should not be administered through the same route as other medications, although Cleviprex may be administered with the following:

• Water for injection
• Sodium chloride (0.9%) for injection
• 5% glucose solution
• 5% glucose solution in sodium chloride (0.9%) for injection
• 5% glucose solution in lactated Ringer's solution for injection
• Lactated Ringer's solution for injection
• 10% amino acid solution.

Contraindications

Hypersensitivity to soy, refined soybean oil, soy products, peanuts, egg products, or any of the excipients. Clevidipine should not be used in patients with defects in lipid metabolism or severe aortic stenosis (see section 4.3 of the product's technical file or summary of product characteristics).

Warnings and precautions

Rapid pharmacological reductions in blood pressure may cause systemic hypotension and reflex tachycardia. If either of these phenomena occurs with clevidipine, consider reducing the dose to half or suspending the infusion. Complete recovery of blood pressure is achieved within 5-15 minutes (see section 5.1 of the product's technical file or summary of product characteristics).

Clevidipine should be used with caution in patients who cannot compensate for the reduction in blood pressure, such as patients with left bundle branch block or primary ventricular pacemaker or severe aortic stenosis (see section 4.4 of the product's technical file or summary of product characteristics).

Drug interactions:Clevidipine is metabolized by esterases. At clinical doses, there is no potential for interaction with CYP. Patients receiving oral or intravenous antihypertensives while receiving clevidipine should be closely monitored for increased antihypertensive effects.

Renal or hepatic impairment:No dose adjustment is required.

Administration

Clevidipine is administered intravenously. Adjust the medication dose to achieve the desired reduction in blood pressure.

Initial dose: Start the infusion at 4ml/h (2mg/h); the dose may be doubled every 90 seconds as a minimum. Continue adjusting the dose until the desired interval is achieved.

Maintenance dose: In most patients, the desired therapeutic response is achieved at doses of 8-12ml/h (4-6mg/h).

Maximum dose: The maximum recommended dose is 64ml/h (32mg/h). It is recommended not to administer more than 1000ml of clevidipine for infusion within the initial 24 hours due to the associated lipid load. Clinical experience is limited with clevidipine infusions lasting more than 72 hours at any dose.

Transition to oral antihypertensive therapy: Discontinue clevidipine or gradually reduce the dose while establishing oral therapy.

Storage

Store and transport refrigerated (between2°Cand8°C).

Do not freeze. The freezing point of Cleviprex is between-1°Cand0°C.