Document: leaflet MAH GENERIC_PL 08828-0215 change

• leaflet MAH GENERIC_PL 08828-0215
• leaflet MAH GENERIC_PL 12762-0466

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01-59-18-008

Package leaflet: Information for the user

Ropivacaine 2 mg/ml solution for infusion

Ropivacaine hydrochloride

Read all of this leaflet carefully before you start using this medicine.

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

-    If you have any further questions, ask your doctor , pharmacist, nurse or any other healthcare professional.

-    If you get any side effects, talk to your doctor, pharmacist, nurse or any other healthcare professional. This includes any possible side effects not listed in this leaflet.

What is in this leaflet:

1.    What Ropivacaine is and what it is used for

2.    What you need to know before you use Ropivacaine

3.    How to use Ropivacaine

4.    Possible side effects

5.    How to store Ropivacaine

6.    Contents of the pack and other information

1. What Ropivacaine is and what it is used for

Ropivacaine 2 mg/ml solution for infusion contains the active substance ropivacaine hydrochloride which is a type of medicine called local anaesthetic. These are chemical substances that are used to numb an area of the body.

Ropivacaine 2 mg/ml solution for infusion is used in adults and children of all ages for acute pain management. It numbs (anaesthetises) parts of the body e.g. after surgery.

2. What you need to know before you use Ropivacaine

You must not be given Ropivacaine

-    if you are allergic to ropivacaine hydrochloride, other so called local anaesthetics of the amide type or any of the other ingredients of this medicines (listed in section 6),

-    if you have a decrease in blood volume (hypovolaemia). This is measured by healthcare personnel.

-    for infusion into a blood vessel to numb a specific area of your body,

-    for infusion into the neck of the womb to relieve pain during childbirth.

Talk to your doctor, pharmacist, nurse or any other healthcare professional before Ropivacaine is given to you

-    if you are in a poor general conditon due to your age or other factors.

-    if you have heart problems (partial or complete heart conduction block)

-    if you have advanced liver problems

-    if you have severe kidney problems.

Tell your doctor if you have any of these problems because your doctor may need to adjust the dose of Ropivacaine.

Talk to your doctor, pharmacist, nurse or any other healthcare professional before Ropivacaine is given to you

-    if you suffer from acute porphyria (problems with building up red blood pigment, sometimes resulting in neurological symptoms).

Tell your doctor if you or somebody in your family have porphyria because your doctor may need to use another anaesthetic.

Other medicines and Ropivacaine

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

Caution should be exercised if you are receiving:

-    Other local anaesthetics (e.g. lidocaine) or agents structurally related to amide-type local anaesthetics, e.g. certain medicines used to treat an irregular heart beat (arrhythmia), such as mexiletine or amiodarone

-    General anaesthetics or opioids, such as morphine or codeine

-    Medicines used to treat depression (e.g. fluvoxamine)

-    Certain antibiotics (e.g. enoxacin)

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 or pharmacist for advice before taking this medicine.

It is not known if ropivacaine hydrochloride affects pregnancy or passes into breast milk.

Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines

Ropivacaine may make you feel sleepy and affect the speed of your reactions. After you have been given Ropivacaine, you should not drive or use any tools or machines until the next day.

Discuss with your doctor or pharmacist if you are unsure about anything.

Ropivacaine contains sodium chloride.

This medicinal product contains a maximum of 0.148 mmol (or 3.4 mg) sodium per ml.

To be taken into consideration by patients on a controlled sodium diet.

3. How to use Ropivacaine Method of administration

Your doctor will administer Ropivacaine to you. It is administered by infusion.

Dosage

The dose used will depend on what it is being used for and also on your health, age and weight. The smallest dose that can produce effective numbing (anaesthesia) of the required area should be used.

The usual dose

-    for adults and adolescents older than 12 years of age is between 2 mg and 200 mg

of ropivacaine hydrochloride.

-    in infants and children (0 up to and including 12 years of age) is 1-2 mg for each kilogram of body weight.

Duration of treatment

Administration of ropivacaine hydrochloride usually takes between 0.5 to 6 hours but can take up to 72 hours in case of pain relief during or after surgery.

If you are given more Ropivacaine than you should be

The first symptoms of being given too much ropivacaine hydrochloride are usually problems with

-    hearing and sight,

-    numbness around the mouth,

-    dizziness or light-headedness,

-    tingling,

-    speech disorder characterised by poor articulation (dysarthria),

-    muscular stiffness, muscular twitching, fits (convulsions),

-    low blood pressure,

-    slow or irregular heart beat.

These symptoms may precede to cardiac arrest, breathing arrest or severe fits.

If you experience any of these symptoms or think you may have received too much Ropivacaine, tell your doctor or healthcare professional immediately.

In case of acute toxicity, appropriate corrective actions will be taken immediately by the healthcare professional.

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

Warning and precautions Children

-    In newborn children as they are more susceptible to Ropivacaine 2 mg/ml solution for infusion.

-    In children < 12 years as some injections of Ropivacaine 2 mg/ml solution for infusion in order to numb parts of the body are not established in younger children.

Special care should be taken to avoid any administration of Ropivacaine directly into a blood vessel to prevent any immediate toxic effects. Administration should not be performed in inflamed areas.

The following information is intended for healthcare professionals only:

Handling

Ropivacaine should only be used by, or under the supervision of, clinicians experienced in regional anaesthesia (see section 3).

Shelf life 2 years

Ropivacaine products are preservative free and are intended for single use only. Discard any unused solution.

The medicinal product should be visually inspected prior to use. The solution should only be used if it is clear, practically free from particles and if the container is undamaged.

The intact container must not be re-autoclaved. A bag wrapped in a foil overpouch should be chosen when a sterile outside is required.

Posology

Adults and children above 12 years of age

The following table is a guide to dosage for the more commonly used blocks in adults. The smallest dose required to produce an effective block should be used. The clinician's experience and knowledge of the patient's physical status are of importance when deciding the dose.

Method of administration

Perineural and epidural administration by infusion.

Careful aspiration before and during administration is recommended to prevent intravascular administration. When a large dose is to be injected, a test dose of 3-5 ml lidocaine (lignocaine) with adrenaline (epinephrine) 1:200.000 is recommended. An inadvertent intravascular infusion may be recognised by a temporary increase in heart rate and an accidental intrathecal injection by signs of a spinal block.

Aspiration should be performed prior to and during administration of the main dose, which should be injected slowly or in incremental doses, at a rate of 25-50 mg/min, while closely observing the patient's vital functions and maintaining verbal contact. If toxic symptoms occur, the infusion should be stopped immediately.

When prolonged blocks are used, either through continuous infusion or through repeated bolus administration, the risks of reaching a toxic plasma concentration or inducing local neural injury must be considered. Cumulative doses up to 675 mg ropivacaine hydrochloride for surgery and postoperative analgesia administered over 24 hours were well tolerated in adults, as were postoperative continuous epidural infusions at rates up to 28 mg/hour for 72 hours. In a limited number of patients higher doses of up to 800 mg/ day have been administered with relatively few adverse reactions.

For treatment of postoperative pain, the following technique can be recommended: Unless preoperatively instituted, an epidural block with Ropivacaine 7.5 mg/ml is induced via an epidural catheter. Analgesia is maintained with Ropivacaine 2 mg/ml infusion. Infusion rates of 6-14 ml (12-28 mg), per hour provide adequate analgesia with only slight and non-progressive motor block in most cases of moderate to severe postoperative pain.

The maximum duration of epidural block is 3 days. However, close monitoring of analgesic effect should be performed in order to remove the catheter as soon as the pain condition allows it. With this technique a significant reduction in the need for opioids has been observed.

In clinical studies an epidural infusion of ropivacaine hydrochloride 2 mg/ml alone or mixed with fentanyl 1-4 pg/ml has been given for postoperative pain management for up to 72 hours. The combination of ropivacaine hydrochloride and fentanyl provided improved pain relief but caused opioid side effects. The combination of ropivacaine hydrochloride and fentanyl has been investigated only for ropivacaine hydorchloride 2 mg/ml.

When prolonged peripheral nerve blocks are applied, either through continuous infusion or through repeated injections, the risks of reaching a toxic plasma concentration or inducing local neural injury must be considered. In clinical studies, femoral nerve block was established with 300 mg ropivacaine hydrochloride 7.5 mg/ml and interscalene block with 225 mg ropivacaine hydrochloride 7.5 mg/ml, respectively, before surgery. Analgesia was then maintained with ropivacaine hydrochloride 2 mg/ml. Infusion rates or intermittent injections of 10-20 mg per hour for 48 hours provided adequate analgesia and were well tolerated.

Infants and children aged 1-12 years:

The proposed ropivacaine doses for peripheral block in infants and children provide guidelines for use in children without severe disease. More conservative doses and close monitoring are recommended for children with severe disease.

Single injections for peripheral nerve block (e.g. ilioinguinal nerve block, brachial plexus block) should not exceed 2.5-3.0 mg/kg.

Continuous infusion for peripheral nerve block are recommended at 0.2-0.6 mg/kg/h (0.1-0.3 ml/kg/h) up to 72 h.

The use of ropivacaine in premature children has not been documented.

4. Possible side effects

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

Important side effects to look out for:

Sudden life-threatening allergic reactions (such as anaphylaxis, angioneurotic oedema and urticaria) are rare. Possible symptoms include

-    sudden onset of rash,

-    itching or lumpy rash (hives),

-    swelling of the face, lips, tongue or other parts of the body,

-    and shortness of breath, wheezing or difficulty breathing.

If you think that Ropivacaine is causing an allergic reaction, tell your doctor or healthcare personnel immediately.

Other possible side effects:

Very common

•    Low blood pressure (hypotension). This might make you feel dizzy or light-headed.

•    Feeling sick (nausea)

Common

•    Headache, pins and needles (paraesthesia), feeling dizzy

•    Slow or fast heart beat (bradycardia, tachycardia)

•    High blood pressure (hypertension)

•    Being sick (vomiting)

•    Difficulty in passing urine (urinary retention)

•    Back pain, increased temperature, muscular stiffness (rigor)

Uncommon

•    Anxiety

•    Some symptoms can happen if the infusion was given into a blood vessel by mistake, or if you have been given too much Ropivacaine (see also section 3 "If you are given more Ropivacaine than you should be" above). These include fits (convulsions, seizures), feeling dizzy or light-headed, numbness of the lips and around the mouth, numbness of the tongue, hearing problems, problems with your sight (vision), problems with your speech (dysarthria), muscular twitching and trembling, reduced sense of touch (hypoaesthesia)

•    Fainting (syncope)

•    Difficulty breathing (dyspnoea)

•    Low body temperature

Rare

•    Cardiac arrest, irregular heart beat (cardiac arrhythmias)

Possible side effects seen with other local anaesthetics which might also be caused by Ropivacaine include:

•    Numbness, due to nerve irritation caused by the needle or the injection. This does not usually last for long.

•    Damaged nerves. Rarely, this may cause permanent problems.

•    If too much Ropivacaine is given into the spinal fluid, the whole body may become numbed (anaesthetised).

Children

In children, the side effects are the same as in adults except for low blood pressure which happens less often in children (affecting less than 1 in 10 children) and being sick which happens more often in children (affecting more than 1 in 10 children).

If you get any side effects, talk to your doctor, pharmacist, nurse or any other healthcare professional. This includes any possible side effects not listed in this leaflet.

5. How to store Ropivacaine

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 bag. The expiry date refers to the last day of that month.

Store below 30°C.

Do not refrigerate or freeze.

Do not use Ropivacaine if you notice any precipitation in the solution for infusion.

Your doctor or the hospital will normally store Ropivacaine and they are responsible for the quality of the product when it has been opened if it is not used immediately. They are also responsible for disposing of any unused Ropivacaine correctly.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist 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 Ropivacaine contains

-    The active substance is ropivacaine hydrochloride.

-    Each 100 ml plastic bag contains 200 mg ropivacaine hydrochloride.

-    Each 200 ml plastic bag contains 400 mg ropivacaine hydrochloride.

-    The other excipients are sodium chloride, hydrochloric acid (for pH adjustment), sodium hydroxide (for pH adjustment), and water for injections.

What Ropivacaine looks like and contents of the pack

Ropivacaine solution for infusion is a clear, colourless solution.

Ropivacaine 2 mg/ml solution for infusion is available in 100 ml and 200 ml transparent plastic bags.

Pack sizes:

1 bag in foil overpouch 5 bags in foil overpouches 10 bags in foil overpouches

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Fresenius Kabi Limited

Cestrian Court, Eastgate Way, Manor Park,

Runcorn, Cheshire WA7 1NT United Kingdom

Manufacturer

Fresenius Kabi Norge AS NO-1753 Halden,

Norway

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

Ropivacaine Fresenius Kabi 2 mg/ml oplossing voor infusie Ropivacaine Fresenius Kabi 2 mg/ml oplossing voor infusie / solution pour perfusion / Infusionslosung Ropivacaine Kabi 2 mg/ml, SiaAupa Yia cyXuoti Ropivacain Fresenius Kabi

Ropivacain Fresenius Kabi 2 mg/ml infuusioneste, liuos Ropivacaine Kabi 2 mg/ml, solution pour perfusion Ropivacainhydrochlorid Kabi 2 mg/ml Infusionslosung Ropivacaine Kabi 2 mg/ml, SiaAupa Yia CYXuen Ropivacaina Kabi 2mg/ml soluzione per infusione Ropivacainhydrochlorid Kabi 2 mg/ml Infusionslosung Ropivacain Fresenius Kabi 2 mg/ml infusjonsv^ske, opplosning Ropivacafna Kabi 2 mg/mL solugao para perfusao Ropivacaina Kabi 2 mg/ml solucion para perfusion Ropivacain Fresenius Kabi

Ropivakainijev klorid Kabi 2 mg/ml raztopina za infundiranje Ropivacaine 2 mg/ml solution for infusion

This leaflet was last revised in July 2012.

Method of administration Epidural administration by infusion.

Careful aspiration before and during application is recommended to prevent intravascular application. The patient’s vital functions should be observed closely during the infusion. If toxic symptoms occur, the infusion should be stopped immediately.

A single caudal epidural injection of ropivacaine hydrochloride 2 mg/ml produces adequate postoperative analgesia below T12 in the majority of patients when a dose of 2 mg/kg is used in a volume of 1 ml/kg. The volume of the caudal epidural injection may be adjusted to achieve a different distribution of sensory block, as recommended in standard textbooks. In children above 4 years of age, doses up to 3 mg/kg of a concentration of ropivacaine hydrochloride 3 mg/ml have been studied. However, this concentration is associated with a higher incidence of motor block.

Fractionation of the calculated local anaesthetic dose is recommended, whatever route of administration.

In case injection of ropivacaine hydrochloride is recommended, Ropivacaine solution for injection can be used.

Incompatibilities

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

In alkaline solutions precipitation may occur as ropivacaine hydrochloride shows poor solubility at pH > 6.0.

Ropivacaine solution for infusion in plastic infusion bags is chemically and physically compatible with the following drugs:

Concentration of Ropivacaine 1-2 mg/ml
Additive	Concentration*
Fentanyl citrate	1.0 - 10.0 pg/ml
Sufentanil citrate	0.4 - 4.0 pg/ml
Morphine sulphate	20.0 - 100.0 pg/ml
Clonidine hydrochloride	5.0 - 50 pg/ml

* The concentration ranges stated in the table are wider than those used in clinical practice.

Epidural infusions of Ropivacaine/sufentanil citrate, Ropivacaine/morphine sulphate and Ropivacaine/clonidine hydrochloride have not been evaluated in clinical studies.

The mixtures are chemically and physically stable for 30 days at 20 to 30°C. From a microbiological point of view, the mixtures should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2-8°C.

Disposal

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

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