Cleviprex 0.5 mg/ml emulsion for injection

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Cleviprex 0.5 mg/ml injectable emulsion

Clevidipine

Read the entire 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, ask your doctor.
• If you experience any adverse reactions, consult your doctor, even if they are adverse reactions not listed in this leaflet. See section 4.

Leaflet contents

1. What Cleviprex is and what it is used for

2. What you need to know before using Cleviprex

3. How to use Cleviprex

4. Possible side effects

5. How to store Cleviprex

6. Contents of the pack and other information

1. What Cleviprex is and what it is used for

Cleviprex contains the active substance clevidipine.

Clevidipine is a calcium channel blocker. Calcium channel blockers are medicines that reduce blood pressure.

Cleviprex is used to lower blood pressure in adult patients in preparation for surgery, during surgery, or immediately after surgery.

2. What you need to know before using Cleviprex

Do not use Cleviprex:

• if you are allergic (hypersensitive) to clevidipine, soy, soy oil, soy products, peanut, egg or egg-derived products, or to any of the other components of this medicine (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), kidney disease causing loss of protein in the urine (lipoid nephrosis), or inflammation of the pancreas (acute pancreatitis) when accompanied by high levels of fat in the blood (hyperlipidemia).
• if you have severe aortic stenosis (severe narrowing of one of the heart valves).

If in doubt, ask your doctor.

Warnings and precautions

Talk to your doctor before starting Cleviprex:

• if you have a heart condition in which the aortic valve of the heart does not open fully
• if your heart is abnormally enlarged due to narrowing of blood vessels (obstructive hypertrophic cardiomyopathy)
• if you have a heart condition involving 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 located above the kidney (adrenal gland) that causes high blood pressure (pheochromocytoma)
• if you have had a heart attack
• if you have a chronic condition in which the heart cannot increase its rate to compensate for the drop in blood pressure, such as:
  • an electrical problem of the heart
  • you have a pacemaker

Cleviprex with other medicines

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

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

Pregnancy and breastfeeding

You should inform your doctor if:

• you are pregnant or think you might be
  • you intend to become pregnant
  • you are breastfeeding

There is insufficient information on the use of Cleviprex in pregnant women. Cleviprex must not be used during pregnancy unless clearly necessary. Your doctor will decide whether this treatment is appropriate for you.

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

Driving and using machines

Cleviprex is used to reduce blood pressure, which may cause dizziness or lightheadedness and could affect your ability to drive or operate machinery.

You should not drive or operate machinery until the effects of Cleviprex have worn off. If in doubt, consult your doctor before leaving the hospital.

Cleviprex contains soybean oil and sodium

This medicine contains soybean oil. It must not be used if you are allergic to peanut or soy.

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

3. How to use Cleviprex

Cleviprex is administered by intravenous infusion (drip). It will be given by a doctor.

Treatment with Cleviprex will be supervised by a doctor, as Cleviprex is used in a hospital setting. The doctor will decide how much Cleviprex you will receive and will prepare the medicine.

• Throughout the treatment, your doctor will monitor your blood pressure.
• Before starting the infusion, your 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 receiving.

Dosage

The Cleviprex infusion should start at 4 ml/hour (2 mg/hour) and will be increased according to tolerance, doubling the rate (i.e., from 4 to 8, from 8 to 16, from 16 to 32, and from 32 to 64 ml/hour [2 to 4, 4 to 8, 8 to 16, and 16 to 32 mg/hour]) every 90 seconds.

Cleviprex will lower blood pressure in most patients at doses up to 32 ml/hour (16 mg/hour).

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

If you receive more Cleviprex than you should

Your doctor carefully monitors these doses, so an overdose is very unlikely. In the event of an overdose, the infusion will be reduced or stopped.

An overdose of Cleviprex may cause dizziness, lightheadedness, or a rapid heartbeat.

If you think you have been given too much Cleviprex, speak to your doctor or other healthcare professional immediately.

If you miss a dose of Cleviprex

Since Cleviprex treatment is administered and supervised by a doctor, it is highly unlikely that this will occur. If you think a dose may have been missed, speak to your 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 further questions about the use of this medicine, ask your doctor.

4. Possible adverse effects

Like all medicines, Cleviprex may cause adverse effects, although not everyone experiences them. Adverse effects are usually mild and do not last long.

Cleviprex may cause atrial fibrillation (irregular heartbeat), chest discomfort, or hypoxia (lower levels of oxygen in the blood, which may make you feel confused or dizzy). If this happens, consult your doctor or another healthcare professional immediately. They will decide whether treatment with Cleviprex should be continued.

Frequent: may affect up to 1 in 10 people

• Tachycardia (fast heartbeat)
• Atrial fibrillation (irregular heartbeats)
• Hypoxia (low oxygen levels in the blood)
• Chest discomfort
• Hypotension (low blood pressure)
• Polyuria (production of a large volume of urine)
• Edema (swelling) at the injection site
• Flushing (redness of the skin)
• Feeling of warmth
• Acute renal failure (kidney damage)

Uncommon: may affect up to 1 in 100 people

• Atrial flutter (abnormal heart rhythm)
• Heart failure
• Slow heartbeat
• Atrioventricular block (irregular heartbeat sensation)
• Constipation
• Pulmonary congestion
• Headache
• Dizziness
• Nausea
• Vomiting
• Allergic reaction
  • Elevated blood triglycerides

Rare: may affect up to 1 in 1,000 people

• Ileus (bowel obstruction; gastrointestinal [intestinal] obstruction)

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

Reporting of adverse effects

If you experience any type of adverse effect, talk to your doctor, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Cleviprex

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 the month indicated.

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

After opening the vial, discard any unused portion after 12 hours.

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

The emulsion should be milky and white.

The physician will inspect the emulsion and discard it if it contains particles or is discolored.

Medicines should not be disposed of via wastewater or household waste. The healthcare professional administering Cleviprex is responsible for ensuring that unused medicine and all materials that have come into contact with it are disposed of in accordance with applicable regulations. This helps protect the environment.

6. Package contents and other information

Composition of Cleviprex

• The active substance is clevidipine.

1 ml of injectable emulsion contains 0.5 mg of clevidipine.

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

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

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

Appearance of the product and contents of the container

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

Cleviprex is supplied in cartons containing 10 vials of 50 ml and 10 vials of 100 ml.

Only certain pack sizes may be marketed.

Marketing Authorization Holder

Chiesi España, S.A.U.

Plaça d’Europa, 41-43, planta 10
08908 L’Hospitalet de Llobregat
Barcelona
Spain

Manufacturer

Diapharm GmbH & Co. KG
Am Mittelhafen 56
48155 Münster
Germany

Amryt Pharmaceuticals Designated Activity Company
45 Mespil Road,
Dublin 4, D04 W2F1,
Ireland

Date of latest review of this leaflet: October 2022

This information is intended for healthcare professionals only:

Cleviprex 0.5 mg/ml injectable emulsion

Clevidipine

Healthcare professionals should consult the Summary of Product Characteristics for complete prescribing information.

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

Instructions for use

For single use only.

Use strict aseptic technique. After puncturing the stopper, use within the next 12 hours; discard any unused residue according to local regulations.

Cleviprex is a sterile, white, opaque emulsion. Visually inspect before use. Do not use discolored solutions or those containing particles.

Gently invert the vial before use to ensure uniformity of the emulsion.

Cleviprex must be administered using a vented spike and an infusion device. Do not dilute.

When administering Cleviprex, lipid filters with a pore size of 1.2 microns may be used.

Cleviprex must not be administered through the same line as other medications, although Cleviprex may be administered concomitantly with the following:

• Water for injections
• Sodium chloride (0.9%) for injections
• 5% glucose solution
• 5% glucose in sodium chloride (0.9%) for injections
• 5% glucose in Ringer's lactate for injections
• Ringer's lactate for injections
• 10% amino acid solution

Contraindications

Hypersensitivity to soy, refined soybean oil, soy products, peanuts, eggs or egg-derived products, or to any of the excipients. Clevidipine must not be used in patients with lipid metabolism disorders or severe aortic stenosis (see section 4.3 of the Summary of Product Characteristics).

Warnings and special precautions

Rapid pharmacological reductions in blood pressure may result in systemic hypotension and reflex tachycardia. If either of these occurs with clevidipine, consider reducing the dose by half or stopping the infusion. Full recovery of blood pressure occurs within 5–15 minutes (see section 5.1 of the Summary of Product Characteristics).

Clevidipine should be used with caution in patients who cannot compensate for blood pressure reduction, such as patients with left bundle branch block, primary ventricular pacemaker, or severe aortic stenosis (see section 4.4 of the Summary of Product Characteristics).

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

Hepatic or renal impairment: No dose adjustment is required.

Administration

Clevidipine is administered by intravenous infusion. Adjust the dose to achieve the desired reduction in blood pressure.

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

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

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

Transition to oral antihypertensive therapy: Discontinue or gradually taper clevidipine while initiating appropriate oral antihypertensive therapy.

Storage

Store and transport refrigerated (between 2°C and 8°C).

Do not freeze. The freezing point of Cleviprex is between -1°C and 0°C.