Dexdor - patient leaflet, side effects, dosage

1. What Dexdor is and what it is used for

Dexdor contains an active substance called dexmedetomidine which belongs to a medicine group called sedatives. It is used to provide sedation (a state of calm, drowsiness or sleep) for adult patients in hospital intensive care settings or awake sedation during different diagnostic or surgical procedures.

2. What you need to know before you are given Dexdor

You must not be given Dexdor

• – if you are allergic to dexmedetomidine or any of the other ingredients of this medicine (listed in

section 6)

• – if you have some disorders of heart rhythm (heart block grade 2 or 3)

• – if you have very low blood pressure which does not respond to treatment

• – if you have recently had a stroke or other serious condition affecting blood supply to the brain.

Warnings and precautions

Before you have this medicine, tell your doctor or nurse if any of the following apply as Dexdor should be used cautiously:

• – if you have an abnormally slow heart rate (either due to illness or high levels of physical fitness)

as it may increase the risk for cardiac arrest

• – if you have low blood pressure

• – if you have low blood volume, for example after bleeding

• – if you have certain heart disorders

• – if you are elderly

• – if you have a neurological disorder (for instance head or spinal cord injury or stroke)

• – if you have severe liver problems

• – if you have ever developed a serious fever after some medicines, especially anaesthetics.

This medicine may cause large amount of urine and excessive thirst, contact a doctor if these side effects occur. See section 4 for more information.

Other medicines and Dexdor

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

The following medicines may enhance the effect of Dexdor:

• – medicines that help you sleep or cause sedation (e.g. midazolam, propofol)

• – strong pain medicines (e.g. opioids such as morphine, codeine)

• – anaesthetic medicines (e.g. sevoflurane, isoflurane).

If you are using medicines which lower your blood pressure and heart rate, co-administration with Dexdor may enhance this effect. Dexdor should not be used with medicines that cause temporary paralysis.

Pregnancy and breast-feeding

Dexdor should not be used during pregnancy or breast-feeding unless clearly necessary.

Ask your doctor for advice before having this medicine

Driving and using machines

Dexdor has major impact on the ability to drive and use machines. After you have been given Dexdor you must not drive, operate machinery, or work in dangerous situations until the effects are completely gone. Ask your doctor when you can start doing these activities again and when you can go back to this kind of work.

Excipients

Dexdor contains less than 1 mmol sodium (23 mg) per ml, that is to say essentially ‘sodium-free’.

3. How to use Dexdor

Hospital intensive care

Dexdor is administered to you by a doctor or nurse in hospital intensive care.

Procedural sedation/awake sedation

Dexdor is administered to you by a doctor or a nurse prior to and/or during diagnostic or surgical procedures requiring sedation, i.e. procedural/awake sedation.

Your doctor will decide on a suitable dose for you. The amount of Dexdor depends on your age, size, general condition of health, the level of sedation needed and how you respond to the medicine. Your doctor may change your dose if needed and will monitor your heart and blood pressure during the treatment.

Dexdor is diluted and it is given to you as an infusion (drip) into your veins.

After sedation/wake-up

• – The doctor will keep you under medical supervision for some hours after the sedation to make

sure that you feel well.

• – You should not go home unaccompanied.

• – Medicines to help you sleep, cause sedation or strong painkillers may not be appropriate for

some time after you have been given Dexdor. Talk to your doctor about the use of these medicines and about the use of alcohol.

If you have been given more Dexdor than you should

If you are given too much Dexdor, your blood pressure may go up or down, your heartbeat may slow down, you may breathe more slowly and you may feel more drowsy. Your doctor will know how to treat you based on your condition.

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

4. POSSIBLE SIDE EFFECTS

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Very common (may affect more than 1 in 10people

• – slow heart rate

• – low or high blood pressure

• – change in breathing pattern or stopping breathing.

Common (may affect up to 1 in 10peoplef.

• – chest pain or heart attack

• – fast heart rate

• – low or high blood sugar

• – nausea, vomiting or dry mouth

• – restlessness

• – high temperature

• – symptoms after stopping the medicine.

Uncommon (may affect up to 1 in 100people

• – reduced heart function, cardiac arrest

• – swelling of the stomach

• – thirst

• – a condition where there is too much acid in the body

• – low albumin level in blood

• – shortness of breath

• – hallucinations

• – the medicine is not effective enough.

Not known (frequency cannot be estimated from the available data

• – large amount of urine and excessive thirst – may be symptoms of a hormonal disorder called

diabetes insipidus. Contact a doctor if these occur.

Reporting of side effects

If you get any side effects, talk to your doctor or nurse. 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 By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Dexdor

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 carton after EXP.

This medicine does not require any special temperature storage conditions. Keep the ampoules or vials in the outer carton in order to protect from light.

6. Contents of the pack and other information

What Dexdor contains

• – The active substance is dexmedetomidine. Each ml of concentrate contains dexmedetomidine

hydrochloride equivalent to 100 micrograms dexmedetomidine.

• – The other ingredients are sodium chloride and water for injections.

What Dexdor looks like and contents of the pack

Concentrate for solution for infusion (sterile concentrate).

The concentrate is a clear, colourless solution.

Containers

2 ml glass ampoules

2, 5 or 10 ml glass vials

Pack sizes

5 × 2 ml ampoules

25 × 2 ml ampoules

5 × 2 ml vials

4 × 4 ml vials

4 × 10 ml vials

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Orion Corporation

Orionintie 1

FI-02200 Espoo

Finland

Manufacturer

Orion Corporation Orion Pharma

Orionintie 1

FI-02200 Espoo

Finland

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

Belgie/Belgiqu­e/Belgien

Luxembourg/Lu­xemburg

Orion Pharma BVBA/SPRL

Tél/Tel: +32 (0)15 64 10 20

Nederland Orion Pharma BVBA/SPRL Tel: +32 (0)15 64 10 20	Danmark Orion Pharma A/S Tlf: +45 8614 00 00
Česká republika Orion Pharma s.r.o. Tel: +420 234 703 305	Eesti Orion Pharma Eesti Oü Tel: +372 6 644 550
Deutschland Österreich Orion Pharma GmbH	España Orion Pharma S.L. Tel: + 34 91 599 86 01

Tel: + 49 40 899 6890

EZZáSa Orion Pharma Hellas M.E.n.E Tql: + 30 210 980 3355	Ireland Orion Pharma (Ireland) Ltd. Tel: + 353 1 428 7777
France Orion Pharma Tél: +33 (0) 1 85 18 00 00	Italia Orion Pharma S.r.l. Tel: + 39 02 67876111
Ísland Vistor hf. Simi: +354 535 7000	Latvija Orion Corporation Orion Pharma pärstävnieciba Tel: +371 20028332
Kúnpog Lifepharma (ZAM) Ltd Tql.: +357 22347440	Magyarorszag Orion Pharma Kft. Tel.: +36 1 239 9095
Lietuva UAB Orion Pharma Tel: +370 5 276 9499	Polska Orion Pharma Poland Sp. z.o.o. Tel.: + 48 22 8 333 177
Norge Orion Pharma AS Tlf: + 47 4000 4210	Slovenija Orion Pharma d.o.o. Tel: +386 (0) 1 600 8015
Portugal Orionfin Unipessoal Lda Tel: + 351 21 154 68 20	Suomi/Finland Orion Corporation Puh/Tel: + 358 10 4261
Efcnrapua Orion Pharma Poland Sp. z.o.o. Ten.: + 48 22 8 333 177	Hrvatska PHOENIX Farmacija d.o.o. Tel: +385 1 6370450
Malta Orion Corporation Tel: +358 10 4261	Romania Orion Corporation Tel: +358 10 4261
Slovenská republika Orion Pharma s.r.o.	United Kingdom (Northern Ireland): Orion Pharma (Ireland) Ltd.

Sverige

Orion Pharma AB

Tel: + 46 8 623 6440

This leaflet was last revised in

Detailed information on this medicine is available on the European Medicines Agency web site:

The following information is intended for healthcare professionals only:

Dexdor 100 micrograms/ml concentrate for solution for infusion

Method of administration

Dexdor should be administered by healthcare professionals skilled in the management of patients requiring intensive care or in the anaesthetic management of patients in the operating room. It must be administered only as a diluted intravenous infusion using a controlled infusion device

Preparation of solution

Dexdor can be diluted in glucose 50 mg/ml (5%), Ringers, mannitol or sodium chloride 9 mg/ml (0.9%) solution for injection to achieve the required concentration of either 4 micrograms/ml or 8 micrograms/ml prior to administration. Please see below in tabulated form the volumes needed to prepare the infusion.

In the case the required concentration is 4 micrograms/ml:

Volume of Dexdor 100 micrograms/ml concentrate for solution for infusion	Volume of diluent	Total volume of infusion
2 ml	48 ml	50 ml
4 ml	96 ml	100 ml
10 ml	240 ml	250 ml
20 ml	480 ml	500 ml

In the case the required concentration is 8 micrograms/ml:

Volume of Dexdor 100 micrograms/ml concentrate for solution for infusion	Volume of diluent	Total volume of infusion
4 ml	46 ml	50 ml
8 ml	92 ml	100 ml
20 ml	230 ml	250 ml
40 ml	460 ml	500 ml

The solution should be shaken gently to mix well.

Dexdor should be inspected visually for particulate matter and discoloration prior to administration.

Dexdor has been shown to be compatible when administered with the following intravenous fluids and medicinal products:

Lactated Ringers, 5% glucose solution, sodium chloride 9 mg/ml (0.9%) solution for injection, mannitol 200 mg/ml (20%), thiopental sodium, etomidate, vecuronium bromide, pancuronium bromide, succinylcholine, atracurium besylate, mivacurium chloride, rocuronium bromide, glycopyrrolate bromide, phenylephrine HCl, atropine sulfate, dopamine, noradrenaline, dobutamine, midazolam, morphine sulfate, fentanyl citrate, and a plasma-substitute.

Compatibility studies have shown potential for adsorption of dexmedetomidine to some types of natural rubber. Although dexmedetomidine is dosed to effect, it is advisable to use components with synthetic or coated natural rubber gaskets.

Shelf life

Chemical and physical in-use stability has been demonstrated for 24 hours at 25°C.

From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to the use are the responsibility of the user and would not normally be longer than 24 hours at 2° to 8°C, unless dilution has taken place in controlled and validated aseptic conditions.

ANNEX IV

SCIENTIFIC CONCLUSIONS AND GROUNDS FOR THE VARIATION TO THE TERMS OF THE MARKETING AUTHORISATION(S)

Scientific conclusions

Taking into account the PRAC Assessment Report on the PSUR(s) for dexmedetomidine, the scientific conclusions of the CHMP are as follows:

In view of available data on diabetes insipidus from the literature, spontaneous reports including in several cases a close temporal relationship, a positive de-challenge and in view of a plausible mechanism of action, the PRAC considers a causal relationship between dexmedetomidine and diabetes insipidus is established. The PRAC concluded that the product information of products containing dexmedetomidine should be amended.

The CHMP agrees with the scientific conclusions made by the PRAC.

Grounds for the variation to the terms of the Marketing Authorisation(s)

On the basis of the scientific conclusions for dexmedetomidine the CHMP is of the opinion that the benefit-risk balance of the medicinal product(s) containing dexmedetomidine is unchanged subject to the proposed changes to the product information.

The CHMP recommends that the terms of the Marketing Authorisation(s) should be varied.

33