Cleviprex

PACKAGE LEAFLET: INFORMATION FOR THE USER

Cleviprex 0.5 mg/ml injectable emulsion

Clevidipine
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 pharmacist.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor. See section 4.

Contents of this leaflet:

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

2. What you need to know before using Cleviprex

Do not use Cleviprex:

• if you are allergic (hypersensitive) to clevidipine, soybeans, soybean oil, soy products, peanuts, eggs or egg products, or to any of the other ingredients of this medicine (listed in section 6)
• if you have lipid metabolism disorders (impaired fat processing), such as extremely high levels of fat in the blood (pathological hyperlipidemia), if you have a kidney disease causing loss of protein in the urine (lipoic nephrosis), or acute pancreatitis 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 you have any doubts, consult your doctor.
Warnings and precautions
Talk to your doctor before using Cleviprex:

• if you have a heart condition causing incomplete opening of the aortic valve in the heart
• if you have abnormal enlargement of the heart due to narrowing of blood vessels (obstructive hypertrophic cardiomyopathy)
• if you have a heart condition causing 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 (adrenal gland) causing high blood pressure (pheochromocytoma)
• if you have recently had a heart attack
• if you have a heart condition preventing an increase in heart rate sufficient to compensate for reduced blood pressure, such as electrical conduction disorders of the heart or if you have a pacemaker

Other medicines and Cleviprex
Inform your doctor if you are taking, have recently taken, or might take any other medicines.
It is particularly important that you inform your doctor if you have taken medicines to lower blood pressure.

Pregnancy and breastfeeding
You must inform your doctor if:

• you are pregnant or suspect you might be pregnant
• you are planning a pregnancy
• you are breastfeeding

There are inadequate data on the use of clevidipine in pregnant women. Clevidipine should not be used during pregnancy unless clearly needed. Your doctor will decide whether this treatment is appropriate for you.
It is not known whether Cleviprex is excreted in human milk. If you are breastfeeding, your doctor will decide whether Cleviprex should be used.

Driving and use of machines
Cleviprex is used to lower blood pressure and may cause dizziness or lightheadedness; this could impair your ability to drive or operate machinery.
You should not drive or operate machinery until the effects of Cleviprex have worn off. If you have any doubts, consult your doctor before being discharged from hospital.

Cleviprex contains soybean oil and sodium
Do not use this medicine if you are allergic to peanuts or soy.
This medicine contains less than 1 mmol of sodium (23 mg) per vial, i.e. it is essentially "sodium-free".

3. How to use Cleviprex

Cleviprex is administered by a doctor through an intravenous infusion (drip).
Since Cleviprex will be administered in a hospital setting, treatment with this medicine will be
carried out under medical supervision. The doctor will decide the amount of Cleviprex to administer
and will prepare the medicine.

• The doctor will monitor your blood pressure throughout the entire treatment.
• Before starting the infusion, the doctor will discuss with you the signs of an allergic reaction.
• The dose and duration of the infusion depend on the type of treatment you are receiving.

Dosage
An infusion of Cleviprex should be started at a dose of 4 ml/hour (2 mg/hour) and, if tolerated,
increased by doubling the amount (i.e. from 4 to 8, from 8 to 16, from 16 to 32, from 32 to 64 ml/hour [from 2 to
4, from 4 to 8, from 8 to 16, from 16 to 32 mg/hour]) every 90 seconds.
In most patients, Cleviprex reduces blood pressure at doses up to 32 ml/hour (16 mg/hour).
Some patients may require a dose up to 64 ml/hour (32 mg/hour).
If you receive more Cleviprex than you should
The doctor carefully monitors these doses, so cases of overdose are unlikely. If you receive more
Cleviprex than you should, the infusion will be reduced or stopped.
An overdose of Cleviprex may cause dizziness or lightheadedness, or a rapid heartbeat.
If you are concerned that you have received more Cleviprex than you should, contact your doctor or
medical staff immediately.
If you miss a dose of Cleviprex
Since the treatment is administered and monitored by a doctor, this situation is unlikely to occur. If you
are concerned that you have missed a dose, contact your doctor immediately.
During administration of Cleviprex
If you notice signs of severe allergic reactions, such as swelling of the face and/or throat or fever, inform
your doctor immediately.
If you have any questions about the use of this medicine, consult your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. Side effects are generally mild and do not last long. Cleviprex may cause atrial fibrillation (irregular heartbeat), chest discomfort or hypoxia (low levels of oxygen in the blood, which may cause a feeling of dizziness or lightheadedness). If this occurs, contact your doctor or other medical personnel immediately; they will decide whether treatment with Cleviprex should continue.

Common: may affect up to 1 in 10 people

• tachycardia (fast heartbeat)
• atrial fibrillation (irregular heartbeat)
• hypoxia (low blood oxygen levels)
• chest discomfort
• hypotension (low blood pressure)
• polyuria (passing large volumes of urine)
• oedema (swelling) at the injection site
• flushing (skin redness)
• sensation of warmth
• acute kidney injury (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
• increased blood triglycerides

Rare: may affect up to 1 in 1000 people

• ileus (intestinal obstruction; digestive system blockage)

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

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the label and on the carton after
"Exp." The expiry date refers to the last day of that month.
Store and transport in a refrigerator (2 °C – 8 °C). Do not freeze.
After opening the container, discard any remaining product after 12 hours.
Keep the vial in the outer packaging to protect the medicine from light.
The emulsion should be milky white in appearance.
The healthcare professional will inspect the emulsion and discard it if it contains particles or if the colour has changed.
Do not dispose of any medicine via wastewater or household waste. The healthcare professional administering Cleviprex is responsible for ensuring that unused medicine and waste materials derived from this medicine are disposed of in accordance with local regulations. This will help protect the environment.

6. Package contents and other information

What Cleviprex contains

• 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).

Description of the appearance of Cleviprex and contents of the pack
Cleviprex is a milky white emulsion in a glass vial.
Cleviprex is available in boxes containing 10 vials of 50 ml and 10 vials of 100 ml.
Not all pack sizes may be marketed.

Marketing Authorization Holder (MAH):
Chiesi Farmaceutici S.p.A
Via Palermo n. 26/A
43122 - Parma
Italy

Manufacturer:
Diapharm GmbH & Co. KG
Am Mittelhafen 56
48155 Münster
Germany
Amryt Pharmaceuticals Designated Activity Company
45 Mespil Road,
Dublin 4, D04 W2F1,
Ireland

The following information is intended exclusively for physicians or healthcare professionals:
Cleviprex 0.5 mg/ml injectable emulsion
Clevidipine
For complete prescribing information, healthcare professionals should consult the Summary of Product Characteristics (SmPC).
Cleviprex is indicated for the rapid reduction of arterial blood pressure during the perioperative period. The safety and efficacy of Cleviprex in children and pregnant women have not been established.

Instructions for use
For single use only.
Use strict aseptic technique. After piercing the stopper, use within 12 hours; dispose of any unused medicinal product in accordance with local regulations.
Cleviprex is a sterile, opaque white emulsion. Visually inspect before use. Do not use solutions that have changed color or contain particulate matter.
Gently invert the vial before use to ensure emulsion homogeneity.
Cleviprex must be administered using a vented spike and an infusion device. Do not dilute.
For administration of Cleviprex, lipid filters with 1.2 micron pore size may be used.
Cleviprex must not be administered through the same catheter used for other medicinal products; however, Cleviprex may be administered with:

• Water for injections
• Sodium chloride injection (0.9%)
• Sodium chloride injection (0.45%)
• 5% glucose solution
• 5% glucose in sodium chloride injection (0.9%)
• 5% glucose in Ringer's lactate solution
• Ringer's lactate injection
• Potassium chloride 40 mEq in 0.9% sodium chloride
• 10% amino acids

Contraindications
Hypersensitivity to the active substance, soybeans, refined soybean oil, soy products, peanuts, eggs or egg products, or to any of the other excipients. Clevidipine must not be used in patients with impaired lipid metabolism or severe aortic stenosis (see section 4.3 of the SmPC).

Warnings and precautions
Pharmacological rapid reduction of arterial blood pressure may cause systemic hypotension and reflex tachycardia. If either of these events occurs, consider halving the dose or stopping the infusion. Blood pressure is restored within 5–15 minutes (see section 5.1 of the SmPC).
Caution is required when administering clevidipine to patients unable to compensate for reduced blood pressure, such as those with left bundle branch block, primary ventricular pacing, or severe aortic stenosis (see section 4.4 of the SmPC).

Interactions with other medicines: Clevidipine is metabolized by esterases. At clinical doses, there is no potential for interaction with CYP enzymes. During treatment with clevidipine, patients receiving oral or intravenous antihypertensive agents should be closely monitored for enhanced antihypertensive effects.

Hepatic or renal impairment: No dose adjustment is required.

Instructions for use
Clevidipine is intended for intravenous use. Titrate the drug to achieve the desired reduction in arterial blood pressure.

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

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

Maximum dose: The maximum recommended dose is 64 ml/h (32 mg/h). Administration of more than 1000 ml of clevidipine within a 24-hour period is not recommended due to the associated lipid load. Experience with clevidipine infusions lasting longer than 72 hours at any dose is limited.

Transition to oral antihypertensive therapy: Discontinue or reduce the clevidipine infusion as appropriate oral therapy is initiated.

Storage
Store and transport refrigerated (2°C–8°C).
Do not freeze. The freezing temperature of Cleviprex ranges between -1°C and 0°C.