Ropsine 2 mg/ml solution for injection EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Ropsine 2 mg/ml injection solution EFG

Ropivacaine hydrochloride

Read the entire leaflet carefully before you start using this medicine.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only; do not give it to others, even if they have the same symptoms as you, because it could harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are effects not listed in this leaflet. See section 4.

Leaflet contents:

1. What Ropsine is and what it is used for
2. What you need to know before using Ropsine
3. How to use Ropsine
4. Possible side effects
5. How to store Ropsine
6. Contents of the pack and other information

1. What Ropsine is and what it is used for

Ropsine contains the active substance ropivacaine hydrochloride, which belongs to a class of medicines called local anaesthetics.

Ropsine 2 mg/ml solution for injection is used in adults and children of all ages for the treatment of acute pain. It numbs (anaesthetizes) a part of the body, for example, after surgery.

2. What you need to know before using Ropsine

Do not use Ropsine

• if you are allergic (hypersensitive) to ropivacaine hydrochloride, to any other amide-type local anaesthetic, or to any of the other ingredients of Ropsine (listed in section 6),
• if you have reduced blood volume (hypovolemia). This will be assessed by healthcare personnel,
• to inject it into a blood vessel to numb a specific area of your body,
• to inject it into the cervix to relieve pain during childbirth.

Warnings and precautions

Talk to your doctor or pharmacist before using Ropsine

• In newborn infants, as they are more susceptible to the effects of Ropsine.
• In children under 12 years of age, as the use of Ropsine injections for regional anaesthesia has not been established.

Special care must be taken to avoid any injection of Ropsine directly into a blood vessel to prevent any immediate toxic effects. The injection should not be administered into an inflamed area.

Inform your doctor:

• if you have poor general health due to age or other factors,
• if you have heart problems (partial or complete cardiac conduction block),
• if you have severe liver disease,
• if you have severe kidney problems.

Tell your doctor if you have any of these conditions, as your doctor may need to adjust your dose of Ropsine.

Inform your doctor:

• if you suffer from acute porphyria (problems with the production of red blood pigments, sometimes resulting in neurological symptoms).

Tell your doctor if you or a family member has porphyria, as your doctor may need to use a different anaesthetic.

Using Ropsine with other medicines

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

Caution is required if you are receiving:

• Other local anaesthetics (e.g., lidocaine) or structurally related agents such as certain medicines used to treat irregular heartbeats (arrhythmias), for example, 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 breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine. It is unknown whether ropivacaine hydrochloride affects pregnancy or passes into breast milk.

Driving and using machines

Ropsine may cause drowsiness and affect your reaction time. Do not drive or operate tools or machinery after taking Ropsine until the following day.

Consult your doctor or pharmacist if you have any doubts.

Important information about some of the ingredients of Ropsine

This medicine contains 3.39 mg of sodium (a main component of table/cooking salt) per ml. This corresponds to 0.2% of the maximum daily recommended sodium intake for an adult.

3. How to use Ropsine

Method of administration

Ropsine will be administered to you by your doctor. It will be given by injection.

Dosage

The recommended dose will depend on what it is being used for, as well as your health, age, and weight.

The smallest dose that produces adequate regional anesthesia (numbing) should be used.

The usual dose

• for adults and adolescents over 12 years of age is between 2 mg and 300 mg of ropivacaine hydrochloride.
• for infants and children (from 0 up to 12 years of age, inclusive) is between 1–3 mg per kilogram of body weight.

Duration of treatment

Administration of ropivacaine hydrochloride usually lasts between 2 and 10 hours in the case of anesthesia prior to certain surgeries, and may last up to 72 hours in the case of pain relief during or after surgery.

If you are given more Ropsine than you should

The first symptoms of having received too much ropivacaine hydrochloride are usually related to:

• ears and vision,
• numbness around the mouth,
• dizziness or fainting,
• tingling,
• speech disturbances characterized by poor articulation (dysarthria),
• muscle stiffness, muscle spasms, seizures (convulsions),
• low blood pressure,
• slow or irregular heartbeat.

These symptoms may precede cardiac arrest, respiratory arrest, or severe convulsions.

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

In case of acute toxicity, appropriate corrective measures will be taken immediately by healthcare personnel.

If you have any further questions about the use of this product, ask your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, Ropsine may cause adverse effects, although not everyone experiences them.

Important adverse effects to be aware of:

Sudden and potentially life-threatening allergic reactions (e.g., anaphylaxis, including anaphylactic shock) are rare and affect between 1 and 10 people in 10,000. Possible symptoms include:

• sudden onset of rash, itching, or hives (urticaria);
• itching or rash with swelling (urticaria);
• swelling of the face, lips, tongue, or other parts of the body;
• shortness of breath, wheezing, or difficulty breathing;
• and a feeling of losing consciousness.

If you think Ropsine is causing you an allergic reaction, inform your doctor or healthcare professional immediately.

Other possible adverse effects:

Very common (may affect more than 1 in 10 people)

• Low blood pressure (hypotension). This may make you feel dizzy or lightheaded.
• Feeling unwell (nausea).

Common (may affect up to 1 in 10 people)

• Headache, tingling (paresthesia), dizziness.
• Slow or fast heartbeat (bradycardia, tachycardia).
• High blood pressure (hypertension).
• Feeling unwell (vomiting).
• Difficulty urinating (urinary retention).
• Back pain, high temperature, muscle stiffness.

Uncommon (may affect up to 1 in 100 people)

• Anxiety.
• Some symptoms may occur if the injection is accidentally administered into a blood vessel, or if you have been given more Ropsine than you should (see also section 3 “If you are given more Ropsine than you should” above). These include seizures (convulsions, fits), dizziness or lightheadedness, numbness of the lips and around the mouth, numbness of the tongue, hearing problems, vision problems (vision), speech problems (dysarthria), muscle stiffness and tremor, reduced sense of touch (hypoesthesia).
• Fainting (syncope).
• Difficulty breathing (dyspnea).
• Low body temperature.

Rare (may affect up to 1 in 1,000 people)

• Heart attack, irregular heartbeat (arrhythmias).

Possible adverse effects observed with other local anesthetics that could also be caused by Ropsine include:

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

• Nerve damage. Rarely, this may cause permanent problems.

• If too much Ropsine is administered into the spinal fluid, it may numb the entire body (anesthetized).

Additional adverse effects in children

In children, the adverse effects are the same as in adults, except for low blood pressure, which is less common in children (affects fewer than 1 in 10 children), and feeling unwell, which is more common in children (affects more than 1 in 10 children).

If you consider any of the adverse effects you experience to be severe, or if you notice any adverse effects not mentioned in this leaflet, inform your doctor or pharmacist.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Ropsine

Keep this medicine out of the sight and reach of children.

Do not use Ropsine after the expiry date stated on the ampoule or packaging. The expiry date refers to the last day of the month indicated.

Do not freeze.

Do not use Ropsine if you notice any precipitation in the injectable solution.

Normally, your doctor or hospital will store Ropsine and are responsible for maintaining the product's quality if it is not used immediately after opening. They are also responsible for the proper disposal of any unused Ropsine.

Medicines must not be disposed of via wastewater drains or household waste. Ask your pharmacist how to properly dispose of unused medicines and their packaging. This will help protect the environment.

6. Contents of the pack and other information

Composition of Ropsine

• The active substance is ropivacaine hydrochloride 2 mg/ml. Each 10 ml polypropylene ampoule contains 20 mg of ropivacaine (as hydrochloride).

Each 20 ml polypropylene ampoule contains 40 mg of ropivacaine (as hydrochloride).

• The other components are sodium chloride, sodium hydroxide (for pH adjustment), and water for injections.

Appearance of the product and contents of the pack

Ropsine injectable solution is a sterile, isotonic, isobaric, clear, colourless aqueous solution.

Ropsine 2 mg/ml solution for injection EFG is available in clear polypropylene ampoules of 10 ml and 20 ml.

Pack size:

10 sterile ampoules in a plastic blister.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder:

Sintetica GmbH

Albersloher Weg 11

48155 Münster

Germany

Manufacturer:

Sintetica GmbH

Albersloher Weg 11

48155 Münster

Germany

Date of the most recent revision of this leaflet: September 2018

Detailed and up-to-date information on this medicinal product is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS) http://www.aemps.gob.es/.

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This information is intended for healthcare professionals only:

Handling

Ropsine must be used by, or under the supervision of, physicians experienced in regional anaesthesia (see section 3).

1. Hold the ampoule in an upright position and twist the neck to remove any residual solution.

Open by sharply twisting off the top portion of the ampoule.

2. The ampoule can be directly connected to the syringe as shown in Fig. 2.

The ampoules are compatible with both Luer-slip and Luer-lock syringes.

3. Hold the syringe with the ampoule pointing upwards. Without squeezing the ampoule, withdraw the solution. Maintain downward pressure on the syringe plunger after the solution has been withdrawn and until the empty ampoule is discarded.

Shelf life prior to opening

3 years

Shelf life after opening

From a microbiological point of view, the product should be used immediately. If not used immediately, storage during use and the conditions prior to use are the responsibility of the user and should generally not exceed 24 hours at 2–8°C.

Ropsine medicinal products are preservative-free and are intended for single use only. Any unused solution should be discarded.

The medicine should be inspected visually before use. The solution should only be used if it is clear, practically free of particles, and if the container is intact.

The intact container must not be re-sterilised in an autoclave.

Dosage

Adults and adolescents over 12 years of age

The table below provides guidance on the most commonly used doses for different types of block. The smallest dose required to achieve effective block should be used. Clinical experience and knowledge of the patient's clinical condition are important factors in determining the dose.

Indication	Concentration mg/ml	Volume ml	Dose mg	Onset of action minutes	Duration hours
Lumbar epidural administration
Bolus	2.0	10–20	20–40	10–15	0.5–1.5
Intermittent injections (top-up) (e.g. labor pain management)	2.0	10–15 (minimum interval 30 minutes)	20–30	--	--
Continuous infusion (e.g. labor pain)	2.0	6–10 ml/h	12–20 mg/h	--	--
Postoperative pain management	2.0	6–14 ml/h	12–28 mg/h	--	--
Thoracic epidural administration
Continuous infusion (postoperative pain management)	2.0	6–14 ml/h	12–28 mg/h	--	--
Peripheral block
(e.g. minor nerve blocks and infiltration)	2.0	1–100	2.0–200	1–5	2–6
Peripheral nerve block (e.g. femoral or intercostal block)
Continuous infusion or intermittent injections (e.g. postoperative pain management)	2.0	5–10 ml/h	10–20 mg/h	--	--
The doses listed in the table are those considered necessary to achieve an adequate block and should be regarded as usage recommendations for adults. Individual variations in onset and duration of action may occur. Figures in the “Dose” column reflect the expected average dose range. Appropriate literature should be consulted regarding factors affecting specific block techniques and individual patient requirements.

In general, anesthesia for surgery (e.g., epidural administration) requires the use of higher concentrations and doses. For surgical procedures requiring profound motor block, epidural anesthesia using the Ropsine 10 mg/mL formulation is recommended. For analgesia (e.g., epidural administration for treatment of acute pain), lower concentrations and doses are advised.

Route of administration

Perineural and epidural injection.

Before and during injection, careful aspiration is recommended to prevent intravascular injection. When a higher dose is to be administered, a test dose of 3–5 mL of 2% lidocaine (lignocaine) with adrenaline (epinephrine) 1:200,000 is advised. Accidental intravascular injection may be recognized by a transient increase in heart rate, and accidental intrathecal injection by signs of spinal block.

Aspiration should be performed before and during administration of the main dose, which should be injected slowly or in incremental doses at a rate of 25–50 mg/minute, while continuously monitoring the patient's vital functions and maintaining verbal contact. If toxic symptoms occur, drug administration must be stopped immediately.

In epidural block for surgery, single doses of up to 250 mg of ropivacaine hydrochloride have been used and were well tolerated.

In a limited number of patients, a single dose of 300 mg has been used for brachial plexus block and was well tolerated.

When prolonged blocks are required via continuous infusion or repeated bolus administration, the risks of achieving toxic plasma concentrations or inducing local neural injury must be considered. Cumulative doses of up to 675 mg of ropivacaine hydrochloride for surgery and postoperative analgesia administered over 24 hours were well tolerated in adults, as were continuous postoperative epidural infusions at rates of 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 postoperative pain treatment, the following technique is recommended: Unless treatment with ropivacaine is initiated prior to surgery, an epidural block is induced with ropivacaine at a concentration of 7.5 mg/mL using an epidural catheter. Analgesia is maintained with an infusion of Ropsine 2 mg/mL. Infusion rates of 6–14 mL (12–28 mg) per hour provide adequate analgesia with only mild 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 the analgesic effect should be performed in order to remove the catheter as soon as pain allows. With this technique, a significant reduction in opioid requirements has been observed.

In clinical studies, an epidural infusion of 2 mg/mL ropivacaine hydrochloride alone or mixed with 1–4 μg/mL fentanyl has been administered for postoperative pain management for up to 72 hours. This combination of ropivacaine hydrochloride and fentanyl provided better pain relief but caused opioid-type side effects; this combination has been studied only with ropivacaine hydrochloride 2 mg/mL.

When prolonged peripheral nerve blocks are performed, either via continuous infusion or repeated injections, the risks of achieving toxic plasma concentrations or inducing local neural injury must be considered. In clinical studies, a femoral nerve block was established with 300 mg of ropivacaine hydrochloride 7.5 mg/mL and an interscalene block with 225 mg of ropivacaine hydrochloride 7.5 mg/mL, respectively, prior to surgery; analgesia was then maintained with ropivacaine hydrochloride 2 mg/mL. Infusion rates or intermittent injections of 10–20 mg per hour over 48 hours provided adequate analgesia and were well tolerated.

Pediatric patients from 0 to 12 years of age inclusive

Indication	Concentration mg/ml	Volume ml/kg	Dose mg/kg
Single caudal epidural block	2.0	1	2
Inferior blocks to T12, in children with a body weight of up to 25 kg
Continuous epidural infusion In children with a body weight of up to 25 kg
0 to 6 months
Bolus dosea	2.0	0.5–1	1–2
Infusion up to 72 hours	2.0	0.1 ml/kg/h	0.2 mg/kg/h
6 to 12 months
Bolus dosea	2.0	0.5–1	1–2
Infusion up to 72 hours	2.0	0.2 ml/kg/h	0.4 mg/kg/h
1 to 12 years
Bolus doseb	2.0	1	2
Infusion up to 72 hours	2.0	0.2 ml/kg/h	0.4 mg/kg/h
The doses listed in the table should be considered as guidelines for use in paediatrics. Individual variations exist. In children with high body weight, a gradual dose reduction is often required, based on ideal body weight. The volume for single caudal epidural block and for bolus epidural doses should not exceed 25 ml in any patient. Appropriate literature should be consulted regarding factors affecting specific block techniques and individual patient requirements.

1. It is recommended to use doses at the lower end of the dose range for thoracic epidural blocks, whereas for lumbar or caudal epidural blocks, doses at the upper end of the range are recommended.

2. Recommended for lumbar epidural block. A reduced bolus dose is appropriate for thoracic epidural analgesia.

Infants from 1 year and children up to 12 years of age:

The proposed doses of ropivacaine hydrochloride for peripheral nerve block in infants and children provide guidance for use in children without serious disease. For children with serious illness, a more conservative dose and close monitoring are recommended.

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 is recommended at 0.2–0.6 mg/kg/h (0.1–0.3 ml/kg/h) for up to 72 hours.

The use of ropivacaine hydrochloride in premature infants has not been documented.

Method of administration

Epidural administration by injection.

Careful aspiration is recommended before and during injection to prevent intravascular injection. The patient's vital functions should be closely monitored during injection. If toxic symptoms occur, the injection must be stopped immediately.

A single caudal epidural injection of 2 mg/ml ropivacaine hydrochloride produces optimal post-surgical analgesia below T12 in most patients when a dose of 2 mg/kg in a volume of 1 ml/kg is used. The volume of the caudal epidural injection may be adjusted to achieve a different extent of sensory block, as recommended in the literature. Doses up to 3 mg/kg of a 3 mg/ml ropivacaine hydrochloride concentration have been studied in children over 4 years of age; however, this concentration is associated with a higher incidence of motor block.

It is recommended to divide the calculated local anesthetic dose into fractions, regardless of the route of administration.

If ropivacaine hydrochloride infusion is indicated, Ropsine injectable solution may be used.

Incompatibilities

Compatibility with other solutions has not been investigated; therefore, this medicinal product must not be mixed with other medicinal products.

Precipitation may occur in alkaline solutions, since ropivacaine hydrochloride has low solubility at pH > 6.0.

Disposal

The disposal of unused medicine and all materials that have come into contact with it must be carried out in accordance with local regulations.