Zalviso

Основна информация

  • Търговско наименование:
  • Zalviso
  • Използвай за:
  • Хората
  • Вид на лекарството:
  • алопатични наркотици

Документи

Локализация

  • Предлага се в:
  • Zalviso
    Европейски съюз
  • Език:
  • английски

Терапевтична информация

  • Терапевтична група:
  • ANESTHETICS
  • Терапевтична област:
  • Pain, Postoperative
  • Терапевтични показания:
  • Zalviso is indicated for the management of acute moderate to severe post-operative pain in adult patients.
  • Каталог на резюме:
  • Revision: 4

Състояние

  • Източник:
  • EMA - European Medicines Agency
  • Статус Оторизация:
  • Authorised
  • Номер на разрешението:
  • EMEA/H/C/002784
  • Дата Оторизация:
  • 17-09-2015
  • EMEA код:
  • EMEA/H/C/002784
  • Последна актуализация:
  • 27-12-2019

Доклад обществена оценка

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© European Medicines Agency, 2015. Reproduction is authorised provided the source is acknowledged.

EMA/505468/2015

EMEA/H/C/002784

EPAR summary for the public

Zalviso

sufentanil

This is a summary of the European public assessment report (EPAR) for Zalviso. It explains how the

Agency assessed the medicine to recommend its authorisation in the EU and its conditions of use. It is

not intended to provide practical advice on how to use Zalviso.

For practical information about using Zalviso, patients should read the package leaflet or contact their

doctor or pharmacist.

What is Zalviso and what is it used for?

Zalviso is an opioid (a strong painkiller) that is used to treat pain occurring in adults after an operation.

It contains the active substance sufentanil.

Zalviso is a ‘hybrid medicine’. This means that it is similar to a ‘reference medicine’ containing the

same active substance, but Zalviso is available in a different form. The reference medicine for Zalviso

is called Sufenta Forte, and is available as a solution for injection, whereas Zalviso is available as

sublingual tablets (tablets to be dissolved under the tongue).

How is Zalviso used?

Zalviso is available as sublingual tablets containing 15 micrograms of sufentanil. The tablets are only

for use in hospital and can only be obtained with a prescription from a doctor experienced in treating

patients with opioids.

The patient places the Zalviso tablets under their tongue when needed using a special device. The

device locks for 20 minutes after the patient has taken a tablet and does not allow the patient to take

more than 3 doses in one hour. The device also uses an identifier so that only the patient who has

been given a special thumb tag can release tablets. The tablets must be allowed to dissolve under the

tongue and must not be chewed or swallowed. Treatment is continued over a period of up to 72 hours.

Zalviso

EMA/505468/2015

Page 2/3

For further information, see the package leaflet.

How does Zalviso work?

The active substance in Zalviso, sufentanil, is an opioid. It is a well-known substance, which has been

used to control pain for many years. When the patient places a Zalviso tablet under the tongue, a dose

of sufentanil is rapidly absorbed into the blood stream through the blood vessels in the lining of the

mouth. This allows the medicine to be transported to receptors in the brain and spinal cord where

sufentanil acts to relieve pain.

What benefits of Zalviso have been shown in studies?

Because Zalviso is a hybrid generic, the applicant presented data on the reference medicine in addition

to results from its own studies.

One main study involved 178 patients who had abdominal surgery (surgery on the belly) and another

involved 426 patients who had surgery on the knee or hip. In both cases Zalviso was compared with

placebo (a dummy treatment). The main measure of effectiveness was based on a patient score that

measured the decrease in intensity of pain over 48 hours of treatment. For abdominal surgery, the

average decrease in pain intensity was 50 points greater with Zalviso than with placebo (106 versus

56). For knee and hip surgery the decrease in pain intensity was around 88 points greater with Zalviso

(76 versus -11) than with placebo.

A third main study compared Zalviso with a patient-controlled pain relief system using morphine,

another opioid, and involved 359 patients who had undergone major abdominal, knee or hip surgery.

Of 177 patients using Zalviso, 139 rated their pain control as excellent or good (79%), compared with

118 of 180 (66%) using morphine.

What are the risks associated with Zalviso?

The most common side effects with Zalviso (which may affect more than 1 in 10 people) are nausea

(feeling sick) and vomiting. The most serious side effect is respiratory depression (impaired breathing)

which could potentially lead to the patient stopping breathing altogether. Zalviso must not be used in

patients who already have significant impaired breathing.

For the full list of side effects and restrictions with Zalviso, see the package leaflet.

Why is Zalviso approved?

The Agency’s Committee for Medicinal Products for Human Use (CHMP) decided that Zalviso’s benefits

are greater than its risks and recommended that it be approved for use in the EU. The Committee

considered that an additional option for patient-controlled pain relief immediately after surgery, when

the pain is worst, was beneficial, especially since it did not need to be given into a vein. Regarding

safety, the side effects were those expected of opioids, and were considered manageable. However,

considering the fact that post-operative pain improves by itself over time as well as the potential for

addiction or the body becoming used to the opioid and requiring larger doses, the medicine and its

administration device should only be used in a hospital setting, and restricted to use for a maximum

duration of 72 hours.

Zalviso

EMA/505468/2015

Page 3/3

What measures are being taken to ensure the safe and effective use of

Zalviso?

A risk management plan has been developed to ensure that Zalviso is used as safely as possible.

Based on this plan, safety information has been included in the summary of product characteristics and

the package leaflet for Zalviso, including the appropriate precautions to be followed by healthcare

professionals and patients.

Further information can be found in the summary of the risk management plan

Other information about Zalviso

The European Commission granted a marketing authorisation valid throughout the European Union for

Zalviso on 18 September 2015.

The full EPAR and risk management plan summary for Zalviso can be found on the Agency’s website:

ema.europa.eu/Find medicine/Human medicines/European public assessment reports. For more

information about treatment with Zalviso, read the package leaflet (also part of the EPAR) or contact

your doctor or pharmacist.

This summary was last updated in 08-2015.

Листовка за пациента: състав, показания, Нежелани лекарствени реакции, дозиране, взаимодействия, бременност, кърмене

B. PACKAGE LEAFLET

Package leaflet: Information for the patient

Zalviso 15 micrograms sublingual tablets

Sufentanil

Read all of this leaflet carefully before you start taking this medicine because it contains

important information for you.

Keep this leaflet. You may need to read it again.

If you have any further questions, ask your doctor or nurse.

If you get any side effects, talk to your doctor or nurse. This includes any possible side effects

not listed in this leaflet. See section 4.

What is in this leaflet

What Zalviso is and what it is used for

What you need to know before you take Zalviso

How to take Zalviso

Possible side effects

How to store Zalviso

Contents of the pack and other information

1.

What Zalviso is and what it is used for

The active substance of Zalviso is sufentanil, which belongs to a group of strong pain-relieving

medicines called opioids.

Zalviso is used to treat acute moderate to severe pain after an operation in adults.

2.

What you need to know before you take Zalviso

Do not take Zalviso:

if you are allergic to sufentanil or any of the other ingredients of this medicine (listed in section

if you have severe breathing problems.

Warnings and precautions

Talk to your doctor or nurse before taking Zalviso.

Tell your doctor or nurse before treatment if you:

are suffering from any condition that affects your breathing (such as asthma, wheezing, or

shortness of breath). As Zalviso may affect your breathing, your doctor or nurse will check your

breathing during treatment;

have a head injury or brain tumour;

have problems with your heart and circulation, especially slow heart rate, irregular heart beats, low

blood volume or low blood pressure;

have moderate to severe liver or severe kidney problems, as these organs have an effect on the

way in which your body breaks down and eliminates the medicine;

have a history of medicine or alcoholabuse;

are regularly using a prescribed opioid medicine (e.g. codeine, fentanyl, hydromorphone,

oxycodone);

have abnormally slow bowel movements;

have a disease of the gall bladder or pancreas.

Taking the sublingual tablets with the device

Before you start using Zalviso, your doctor or nurse will show you how to use the Zalviso

administration device. You will then be able to take a tablet as needed to relieve your pain. Follow the

instructions carefully. Talk to your doctor or nurse if you did not fully understand the instructions or

are unsure about the correct handling of the administration device.

Children and adolescents

Zalviso should not be used in children and adolescents below 18 years.

Other medicines and Zalviso

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

tell your doctor if you are taking any of the following:

Any medicines that might have an effect on the way in which your body breaks down Zalviso e.g.

ketoconazole, which is used for the treatment of fungal infections.

Any medicines to treat anxiety, tranquillisers or other opioid medicines, as they can increase the

risk of severe breathing problems.

Medicines for the treatment of depression known as Monoamine Oxidase Inhibitors (MAOIs).

These medicines must not be taken in the 2 weeks before or at the same time as Zalviso is given.

Medicines for the treatment of depression known as Selective Serotonin Reuptake Inhibitors

(SSRIs) and Serotonin Norepinephrine Reuptake Inhibitors (SNRIs). It is not recommended to use

these medicines at the same time as Zalviso.

Other medicines which are also taken sublingually (medicines that are placed under the tongue

where they dissolve) or medicines which dilute or take effect in your mouth (e.g. nystatin, a liquid

or pastilles you hold in your mouth to treat fungus infections), as the effect on Zalviso has not

been studied.

Concomitant

Zalviso

sedating

medicines

such

benzodiazepines

related

drugs

increases the risk of drowsiness, difficulties in breathing (respiratory depression), coma and may be

life-threatening. Because of this, concomitant use should only be considered when other treatment

options are not possible.

However

your

doctor

prescribes

Zalviso

together

with

sedating

medicines

duration

concomitant treatment should be limited by your doctor.

Please tell your doctor about all sedating medicines you are taking, and follow your doctor’s dose

recommendation closely. It could be helpful to inform friends or relatives to be aware of the signs and

symptoms stated above. Contact your doctor when experiencing such symptoms.

Zalviso with alcohol

Do not drink alcohol while using Zalviso. It can increase the risk of experiencing severe breathing

problems.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask

your doctor for advice before taking this medicine.

Zalviso should not be used during pregnancy or if you are a woman of childbearing potential not using

contraception.

Sufentanil passes into breast milk and can cause side effects in the breast-fed child. Breastfeeding is

not recommended when you take Zalviso.

Driving and using machines

Zalviso affects your ability to drive or use machines as it may cause sleepiness, dizziness or visual

disturbances. You should not drive or operate machinery if you experience any of these symptoms

whilst or after being treated with Zalviso. You should only drive and use machines if sufficient time as

elapsed after your last dose of Zalviso.

Zalviso contains sunset yellow FCF Aluminium Lake (E110)

Zalviso contains the colouring agent sunset yellow FCF Aluminium Lake (E110), which may cause

allergic reactions.

Zalviso contains sodium

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

3.

How to take Zalviso

Always take this medicine exactly as your doctor has told you. Check with your doctor if you are not

sure.

The sublingual tablets are taken using the Zalviso administration device, which is a system that

delivers a single dose upon activation. After receiving a dose you will not be able to release another

dose for 20 minutes and you will not be able to take more than 3 doses in one hour.

The device will work for 3 days (72 hours), which is also the maximum recommended duration of

your treatment.

Zalviso is placed under the tongue using the Zalviso administration device. You can control your

treatment and should only activate the device when in need of pain relief.

The tablets dissolve under your tongue and should not be crushed, chewed, or swallowed. You should

not eat or drink and should talk as little as possible for 10 minutes after each dose.

Zalviso is only to be taken in a hospital setting. It is only prescribed by physicians who are

experienced in the use of strong pain killers like Zalviso and know the effects it may have on you, in

particular on your breathing (see “Warnings and precautions” above).

Do not use the device if any component is visibly damaged.

After your treatment the medical staff will take the Zalviso administration device and dispose of any

unused tablets accordingly. The device is constructed so that you will not be able to open it.

If you take more Zalviso than you should

The administration device will make you wait 20 minutes between doses to prevent you from taking

more Zalviso than you should. However, symptoms of overdose include severe breathing problems

like slow and shallow breathing, loss of conciousness, extreme low blood pressure, collapse and

muscle rigidity. If these start to develop, tell a doctor or nurse immediately.

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

4.

Possible side effects

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

The most serious side effects are severe breathing problems like slow and shallow breathing, which

may even lead to stopping breathing or inability to breathe.

In case you experience any of the above mentioned side effects, stop taking Zalviso and tell your

doctor or nurse immediately.

Very common side effects (may affect more than 1 in 10 people): nausea, vomiting, fever.

Common side effects (may affect up to 1 in 10 people):

confusion, dizziness, headache, drowsiness, increased heart rate, high blood pressure, low blood

pressure, constipation, indigestion, itching of the skin, involuntary muscle cramps, muscle twitching,

difficulty passing urine.

Uncommon side effects (may affect up to 1 in 100 people): allergic reactions, lack of interest or

emotion, nervousness, sleepiness, abnormal sensation of the skin, problems coordinating muscle

movements, muscle contractions, exaggeration of reflexes, vision disturbances, decreased heart rate,

dry mouth, excessive sweating, rash, dry skin, chills, weakness.

Frequency not known (frequency cannot be estimated from the available data): severe allergic

reactions (anaphylactic shock), convulsion (fits), coma, small pupil size, redness of the skin,

withdrawal syndrome.

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

Appendix V.

By reporting side effects, you can help provide more information on the safety of this medicine.

5.

How to store Zalviso

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 carton and sachet after EXP.

Store in the original package in order to protect from light.

Do not throw away any medicines via wastewater or household waste. Ask the medical staff how to

throw away medicines you no longer use. These measures will help protect the environment.

6.

Contents of the pack and other information

What Zalviso contains

The active substance is sufentanil. Each sublingual tablet contains 15 micrograms sufentanil (as

citrate).

The other ingredients are mannitol (E421), calcium hydrogen phosphate (anhydrous),

hypromellose, croscarmellose sodium, stearic acid, magnesium stearate, sunset yellow FCF

Aluminium Lake (E110) (see section 2 “What you need to know before you take Zalviso”)

What Zalviso looks like and contents of the pack

Zalviso sublingual tablets are orange-coloured flat-faced tablets with rounded edges. The sublingual

tablets measure 3 mm in diameter.

The sublingual tablets are supplied in cartridges; each cartridge contains 40 sublingual tablets. One

cartridge is packed in a sachet including an oxygen absorber.

Zalviso sublingual tablets are available in pack sizes of 1, 10 and 20 cartridges and in multipacks

containing 40 (2 packs of 20), 60 (3 packs of 20) and 100 (5 packs of 20) cartridges, equivalent to 40,

400, 800, 1,600, 2,400 and 4,000 sublingual tablets, respectively.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Grünenthal GmbH

Zieglerstraße 6

52078 Aachen

Germany

Tel.: +49-241-569-0

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

Authorisation Holder:

België/Belgique/Belgien

Luxemburg/Luxembourg

S.A. Grünenthal N.V.

Lenneke Marelaan 8

1932 Sint-Stevens-Woluwe

België/Belgique/Belgien

Tél/Tel: + 32 (0)2 290 52 00

beinfo@grunenthal.com

Lietuva

Grünenthal GmbH

Tel: + 49 241 569-0

България

Grünenthal GmbH

Teл.: + 49 241 569-0

Magyarország

Grünenthal GmbH

Tel.: + 49 241 569-0

Česká republika

Grünenthal GmbH

Tel: + 49 241 569-0

Malta

Grünenthal GmbH

Tel.: + 49 241 569-0

Danmark

Grünenthal Denmark ApS

Arne Jacobsens Allé 7

2300 København S

Tlf: +45 88883200

Nederland

Grünenthal B.V.

De Corridor 21K

NL-3621 ZA Breukelen

Tel:+31 (0)30 6046370

info.nl@grunenthal.com

Deutschland

Grünenthal GmbH

Zieglerstr. 6

DE-52078 Aachen

Tel: + 49 241 569-1111

service@grunenthal.com

Norge

Grünenthal Norway AS

C.J. Hambros Plass 2C

0164 Oslo

Tlf: +47 22996054

Eesti

Grünenthal GmbH

Tel: + 49 241 569-0

Österreich

Grünenthal GmbH

Campus 21, Liebermannstraße A01/501

2345 Brunn am Gebirge

Tel: +43(0)2236 379 550-0

Ελλάδα

Grünenthal GmbH

Τηλ: + 49 241 569-0

Polska

Grünenthal GmbH

Tel.: + 49 241 569-0

España

Grünenthal Pharma, S.A.

C/Dr. Zamenhof, 36

E-28027 Madrid

Tel: +34 (91) 301 93 00

Portugal

Grünenthal, S.A.

Alameda Fernão Lopes, 12-8.º A

P-1495 - 190 Algés

Tel: +351 / 214 72 63 00

France

Laboratoires Grünenthal SAS

România

Grünenthal GmbH

Immeuble Eurêka

19 rue Ernest Renan

CS 90001

F- 92024 Nanterre Cedex

Tél: + 33 (0)1 41 49 45 80

Tel: + 49 241 569-0

Hrvatska

Grünenthal GmbH

Tel: + 49 241 569-0

Slovenija

Grünenthal GmbH

Tel: + 49 241 569-0

Ireland

Grünenthal Pharma Ltd

4045 Kingswood Road,

Citywest Business Park

IRL – Citywest Co., Dublin

Tel: +44 (0)870 351 8960

medicalinformationie@grunenthal.com

Slovenská republika

Grünenthal GmbH

Tel: + 49 241 569-0

Ísland

Grünenthal GmbH

Sími: + 49 241 569-0

Suomi/Finland

Grünenthal GmbH

Puh/Tel: + 49 241 569-0

Italia

Grünenthal Italia S.r.l.I

Tel: +39 02 4305 1

Sverige

Grunenthal Sweden AB

Tel: +46 (0)86434060

Κύπρος

Grünenthal GmbH

Τηλ: + 49 241 569-0

United Kingdom

Grünenthal Ltd

1 Stokenchurch Business Park

Ibstone Road, HP14 3FE – UK

Tel: +44 (0)870 351 8960

medicalinformationuk@grunenthal.com

Latvija

Grünenthal GmbH

Tel: + 49 241 569-0

This leaflet was last revised in

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

http://www.ema.europa.eu.

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 sufentanil, the scientific

conclusions of CHMP are as follows:

Sufentanil may increase plasma serotonin level and its concomitant use with other serotoninergic

agents may increase the risk of serotonin syndrome.

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 sufentanil the CHMP is of the opinion that the benefit-

risk balance of the medicinal product(s) containing sufentanil 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.