Cleviprex 0,5 mg/ml, emulsie voor injectie

Cleviprex contains the active substance clevidipine.

Clevidipine is a calcium channel blocker. Calcium channel blockers are medicines which lower blood pressure.

The Medicines Company

25 June 2013

Clevidipine (EU Core for NL)	Module 1, 1.3.1.1 Product Information (English)
Confidential	Page 3

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

Do not use Cleviprex:

• if you are allergic (hypersensitive) to clevidipine, soybeans, soya-bean oil, soy products, peanut, eggs or egg products or to any of the other ingredients of Cleviprex
• if you have a condition where you have extremely high levels of fat in your blood including acute inflammation of the pancreas or kidney problems
• if you have a kidney disorder that causes loss of protein in urine

Check with your doctor if you are unsure.

Warnings and precautions

Talk to your doctor before using Cleviprex:

• if you have a heart condition where the aortic valve in your heart does not open completely
• if you have an abnormally large heart caused by narrow blood vessels (hypertrophic obstructive cardiomyopathy)
• if you have a heart condition where a valve is narrowed (stenosis of the mitral valve)
• if you have a tear in the main artery of the body (aortic dissection)
• if you have a tumour of the gland on top of the kidney (adrenal gland) that causes high blood pressure (pheochromocytoma)
• if you have had a heart attack
• if you have a condition where your heart cannot increase in rate in order to compensate for reduced blood pressure such as

o an electrical problem with your heart

o you are fitted with a pacemaker

The Medicines Company

25 June 2013

Clevidipine (EU Core for NL)	Module 1, 1.3.1.1 Product Information (English)
Confidential	Page 4

Other medicines and Cleviprex

Please tell your doctor if you are taking, have recently taken or might take any other medicines.

It is particularly important that you tell your doctor if you have been taking any medicines to lower your blood pressure.

Pregnancy and breast-feeding

You must tell the doctor if:

• you are pregnant or think you may be pregnant
• you are planning on becoming pregnant
• you are breast-feeding

There is no adequate information on the use of Cleviprex in pregnant women. Cleviprex should not be used during pregnancy unless clearly necessary. Your doctor will decide whether or not this treatment is appropriate for you.

It is not known whether Cleviprex is excreted in breast-milk. If you are breast-feeding, the doctor will decide whether Cleviprex should be used.

Driving and using machines

Cleviprex is used to lower your blood pressure, which may make you feel light-headed or dizzy and could affect your ability to drive or use machines.

You must not drive or operate machinery until the effects of Cleviprex have worn off. Check with your doctor before leaving hospital if you are unsure.

Cleviprex contains soya oil

If you are allergic to peanut or soya, do not use this medicinal product.

This medicinal product contains less than 1 mmol sodium (23 mg) per vial, i.e. essentially ‘sodium- free’.

The Medicines Company

25 June 2013

Clevidipine (EU Core for NL)	Module 1, 1.3.1.1 Product Information (English)
Confidential	Page 5

Cleviprex is for infusion (drip) into a vein. This is administered by a doctor.

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

• Throughout your treatment, the doctor will check your blood pressure
• Before the start of infusion the doctor will tell you about the signs of allergic reaction
• The dose and duration of infusion depends upon the kind of treatment you are undergoing

Dosage

An infusion of Cleviprex should be started at 4 ml/hour (2 mg/hour) and increased as tolerated in doubling amounts (i.e. 4 to 8, 8 to 16, 16 to 32, 32 to 64 ml/hour [2 to 4, 4 to 8, 8 to 16, 16 to

32 mg/hour]) every 90 seconds.

Cleviprex will reduce blood pressure for most patients 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 have more Cleviprex than you should

These doses are carefully checked by the doctor, so an overdose is very unlikely. In the event of taking too much Cleviprex, the infusion will be reduced or stopped.

If you are concerned that you may have been given too much Cleviprex, talk to your doctor or other medical staff immediately.

If you forget to have Cleviprex

Since treatment with Cleviprex is administered and supervised by a doctor, this is very unlikely. If you are concerned that you may have missed a dose, talk to your doctor immediately.

While you are receiving Cleviprex

If you develop severe allergic reactions, like swelling of your face and/or throat or fever tell your doctor immediately.

If you have further questions on the use of this product, ask your doctor.

The Medicines Company

25 June 2013

Clevidipine (EU Core for NL)	Module 1, 1.3.1.1 Product Information (English)
Confidential	Page 6

Like all medicines, this medicine can cause side effects, although not everybody gets them. The side effects are usually mild and do not last very long.

Very common: may affect more than 1 in 10 people

• headache
• atrial fibrillation (irregular heart beat)
• tachycardia (fast heart beat)
• hypotension (low blood pressure)

Common: may affect up to 1 in 10 people

• dizziness
• nausea
• polyuria (producing large volumes of urine)
• oedema (swelling) at the injection site
• flushing (reddening of the skin)
• feeling hot
• itching
• chest discomfort or pain
• allergic reaction
• vomiting

Uncommon: may affect up to 1 in 100 people

• atrial flutter (abnormal heart rhythm)
• hypoxia (lower blood oxygen levels)
• heart failure
• slow heart beat
• atrioventricular block (feeling your heart beat)
• constipation
• hyperlipidaemia (high fat levels in the blood)
• lung congestion

Rare: may affect up to 1 in 1000 people

- ileus (constipation; obstruction of the digestive system [bowel])

Reporting side effects

If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

The Medicines Company

25 June 2013

Clevidipine (EU Core for NL)	Module 1, 1.3.1.1 Product Information (English)
Confidential	Page 7

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 the carton after ‘EXP’. The expiry date refers to the last day of that month.

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

May be stored below 25 C for a period not to exceed 2 months. Do not return to refrigerated storage after beginning 25°C storage. Once the container is opened, any remaining product should be discarded after 12 hours.

Keep vial in the outer carton in order to protect from light

The emulsion should be milky white.

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

Do not throw away medicines via wastewater or household waste. The healthcare professional administering Cleviprex will be responsible for ensuring that any unused product or waste material is disposed of in accordance with local requirements. These measures will help protect the environment.

What Cleviprex contains

• The active substance is clevidipine 1 ml emulsion for injection contains 0.5 mg clevidipine. One vial of 50 ml of emulsion contains 25 mg of clevidipine One vial of 100 ml of emulsion contains 50 mg of clevidipine
• The other ingredients are soya-bean oil refined, glycerol, egg phospholipids, oleic acid, disodium edetate, water for injections and sodium hydroxide (for pH adjustment)

What Cleviprex looks like and contents of the pack

Cleviprex is a milky white emulsion in a glass vial

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

Not all vial sizes may be marketed.

The Medicines Company

25 June 2013

Clevidipine (EU Core for NL)	Module 1, 1.3.1.1 Product Information (English)
Confidential	Page 8

Marketing Authorisation Holder

The Medicines Company UK Ltd.

115L Milton Park

Abingdon

Oxfordshire

OX14 4SA

United Kingdon

Manufacturer

Hälsa Pharma GmbH

Nikolaus-Dürkopp-Str. 4A,

D-33602 Bielefeld,

Germany

This medicinal product is authorised in the Member States of the EEA under the following names:

Austria: Cleviprex 0,5 mg/ml emulsion zur injektion

Belgium: Cleviprex 0,5 mg/ml émulsion injectable; Cleviprex 0,5 mg/ml, emulsie voor injectie; Cleviprex 0,5 mg/ml emulsion zur injektion

France: Cleviprex 0,5 mg/ml émulsion injectable Germany: Cleviprex 0,5 mg/ml emulsion zur injektion Italy: Cleviprex 0,5 mg/ml emulsione iniettabile Luxembourg: Cleviprex 0,5 mg/ml émulsion injectable Netherlands: Cleviprex 0,5 mg/ml, emulsie voor injectie Spain: Cleviprex 0,5 mg/ml emulsión inyectable Sweden: Cleviprex 0,5 mg/ml injektionsvätska, emulsion UK: Cleviprex 0.5 mg/ml emulsion for injection

This leaflet was last revised in 06/2013.

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

--

The following information is intended for medical or healthcare professionals only:

The Medicines Company

25 June 2013

Clevidipine (EU Core for NL)	Module 1, 1.3.1.1 Product Information (English)
Confidential	Page 9

Cleviprex 0,5 mg/ml, emulsie voor injectie

Clevidipine

Healthcare professionals should refer to the Summary of Product Characteristics for full prescribing information.

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

Instructions for use

For single use only.

Use strict aseptic technique. Once stopper is punctured, use within 12 hours; discard unused portion in accordance with local requirements.

Cleviprex is a sterile, white opaque emulsion. Visually inspect prior to use. Solutions that are discoloured or contain particulate matter should not be used.

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

Cleviprex should be administered via a vented spike and infusion device. Do not dilute.

Lipid filters with a 1.2 micron pore size may be used when administering Cleviprex.

Cleviprex should not be administered in the same line as other medications; however, Cleviprex can be administered with the following:

• Water for injections
• Sodium Chloride (0.9%) Injection
• 5% glucose solution
• 5% glucose solution in Sodium Chloride (0.9%) Injection
• 5% glucose solution in Ringers Lactate Injection
• Lactated Ringers Injection
• 10% amino acid

Contraindications

Hypersensitivity to soybeans, soya-bean oil refined, soy products, peanut, eggs or egg products or to any of the other excipients. Clevidipine must not be used in patients with defective lipid metabolism (see section 4.3 of SmPC).

Special Warnings and Precautions

The Medicines Company

25 June 2013

Clevidipine (EU Core for NL)	Module 1, 1.3.1.1 Product Information (English)
Confidential	Page 10

Rapid pharmacologic reductions in blood pressure may produce systemic hypotension and reflex tachycardia. If either occurs, consider decreasing the dose by half or stopping the infusion. Full recovery of BP is achieved in 5-15 minutes (see section 5.1 of SmPC).

Clevidipine should be used with caution in patients who cannot compensate for reduced blood pressure such as those with left bundle-branch block or primary ventricular pacing or severe aortic stenosis (see section 4.4 of SmPC).

Drug-drug interaction: Clevipine is metabolized by esterases. At clinical doses, there is no potential for CYP interaction. Patients receiving oral or IV anti-hypertensive agents while on clevidipine should be observed closely for increased anti-hypertensive effects.

Hepatic or Renal Impairment: No dose adjustment required.

Administration

Clevidipine is for intravenous use. Titrate to achieve the desired blood pressure reduction

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

Maintenance dose: The desired therapeutic response for most patients 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). No more than 1000 ml of clevidipine infusion is recommended in the initial 24-hour period due to associated lipid load. There is limited experience with infusion durations beyond 72 hours at any dose.

Transition to an oral antihypertensive agent: Discontinue clevidipine or titrate downward while appropriate oral therapy is established.

Shelf life

2 years refrigerated (2-8ºC) of which 2 months may be below 25ºC

Do not return to refrigerated storage after beginning 25ºC storage

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

The Medicines Company

25 June 2013