ROPSINE 2 mg/ml INJECTABLE SOLUTION

2. What you need to know before you use Ropsine

Do not useRopsine

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

Warnings and precautions

Talk to your doctor or pharmacist before you start using Ropsine

• In newborn babies, as they are more susceptible to Ropsine.
• In children under 12 years of age, as the use of Ropsine injections to numb a part of the body has not been established.

Special care should be taken to avoid any injectionof Ropsine directly into a blood vesselto prevent any immediate toxic effect. The injection should not be performed in an inflamed area.

Tell your doctor:

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

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

Tell your doctor:

• if you have acute porphyria(problems with the production of red blood cell 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 anesthetic.

Using Ropsine with other medicines

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines.

Caution should be exercised if you are receiving:

• Other local anesthetics(e.g., lidocaine) or structurally related agents to amide-type local anesthetics, e.g., certain medicines used to treat irregular heartbeats (arrhythmias), such as mexiletine or amiodarone,
• General anestheticsor 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 are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine. It is not known whether ropivacaine hydrochloride affects pregnancy or passes into breast milk.

Driving and using machines

Ropsine may cause drowsiness and affect your reaction speed. Do not drive or use tools or machines after taking Ropsine, until the next day.

Ask 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 major component of cooking/table salt) per ml. This is equivalent to 0.2% of the maximum recommended daily intake of sodium for an adult.

3. How to use Ropsine

Method of administration

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

Dose

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

The smallest dose that can produce a numbing effect (anesthesia) of the required area should be used.

The usual dose

• for adultsand adolescents over 12 years of ageis between 2 mg and 300 mgof ropivacaine hydrochloride.
• in infants and children(from 0 to 12 years of age, inclusive) is between 1-3 mg per kilogramof body weight.

Duration of treatment

The administration of ropivacaine hydrochloride usually lasts between 2 and 10 hoursin the case of anesthesiabefore certain surgeries and may last up to 72 hoursin the case of pain reliefduring or after surgery.

If you are given too much Ropsine

The first symptoms of being given too much ropivacaine hydrochloride are usually problems related to:

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

These symptoms can precede a heart attack, respiratory arrest, or severe seizures.

If you experience any of these symptoms or think you may have been given too much Ropsine, tell your doctor or healthcare personnel immediately.

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

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

4. Possible side effects

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

Important side effects to look out for:

Sudden, potentially life-threatening allergic reactions (e.g., anaphylaxis, including anaphylactic shock) are rare and affect 1 to 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 loss of consciousness.

If you think you are having an allergic reaction to Ropsine, tell your doctor or healthcare personnel immediately.

Other possible side effects:

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

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

Common(may affect up to 1 in 10 people)

• Headache, tingling (paresthesia), feeling dizzy.
• Slow or fast heartbeat (bradycardia, tachycardia).
• High blood pressure (hypertension).
• Feeling sick (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 was accidentally given into a blood vessel or if you were given too much Ropsine (see also section 3 "If you are given too much Ropsine" above). These include seizures (convulsions), feeling dizzy or faint, numbness of the lips and around the mouth, numbness of the tongue, hearing problems, vision problems (vision), speech problems (dysarthria), muscle stiffness, and tremor, decreased 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).

Other possible side effects that may be caused by Ropsine, which have been reported with other local anesthetics, include:

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

• Nerve damage. Rarely, it can cause permanent problems.
• If too much Ropsine is administered into the spinal fluid, it can numb the entire body (anesthetized).

Additional side effects in children

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

If you think any of the side effects you are experiencing are serious, or if you notice any side effects not listed in this leaflet, tell your doctor or pharmacist.

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly to the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storing Ropsine

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

Do not use Ropsine after the expiry date which is stated on the ampoule or carton. The expiry date is the last day of the month stated.

Do not freeze.

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

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

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Container Content and Additional Information

Composition ofRopsine

• The active ingredient 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 injectable preparations.

Appearance of the Product and Container Content

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

Ropsine 2 mg/ml injectable solution EFG is available in 10 ml and 20 ml transparent polypropylene ampoules.

Package size:

10 sterile ampoules in a plastic blister pack.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder:

Sintetica GmbH

Albersloher Weg 11

48155 Münster

Germany

Manufacturer:

Sintetica GmbH

Albersloher Weg 11

48155 Münster

Germany

Date of Last Revision of this Leaflet: September 2018

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

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This information is intended exclusively for doctors or healthcare professionals:

Handling

Ropsine should be used by, or under the supervision of, experienced physicians in regional anesthesia (see section 3)

1. Keep the ampoule in a vertical position and twist the neck to eliminate any remaining solution.

Open by sharply twisting the top part of the ampoule.

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

The ampoules are suitable for both Luerfit and LuerLock syringes.

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

Shelf life before opening

3 years

Shelf life after opening

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

Ropsine medications are preservative-free products intended for single use. Discard any unused solution.

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

The intact container should not be re-introduced into the autoclave.

Posology

Adults and adolescents over 12 years of age

The table below is a guide to the most commonly used doses in different types of blocks. The smallest dose required to produce an effective block should be used. Clinical experience and knowledge of the patient's clinical condition are important factors in deciding the dose.

Generally, anesthesia in surgery (e.g., epidural administration) requires the use of higher concentrations and doses. For surgical procedures that require deep motor block, it is recommended to use epidural anesthesia with Ropsine 10 mg/ml formulation. For analgesia (e.g., epidural administration for acute pain treatment), lower concentrations and doses are recommended.

Method of administration

Perineural and epidural administration by injection.

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

Aspiration will be performed before and during the administration of the main dose, which will be injected slowly or in increasing doses, at a rate of 25-50 mg/minute, while constantly monitoring the patient's vital functions and maintaining verbal contact with them. If toxic symptoms appear, the administration of the medication should be interrupted immediately.

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

In block of the brachial plexus in a limited number of patients, a single dose of 300 mg has been used, which has been well tolerated.

When prolonged peripheral nerve blocks are required, either through continuous infusion or repeated injections, the risks of reaching a toxic plasma concentration or inducing local neural injury should be considered. Accumulated doses of up to 675 mg of ropivacaine hydrochloride for surgery and post-operative analgesia administered over 24 hours were well tolerated in adults, as well as continuous post-operative 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 post-operative pain treatment, the following technique is recommended: Unless treatment with Ropivacaine is started before the intervention, an epidural block is induced with it at a concentration of 7.5 mg/ml using an epidural catheter. Analgesia is maintained with a perfusion of Ropsine 2 mg/ml. Perfusion rates of 6-14 ml (12-28 mg) per hour provide adequate analgesia with only a slight and non-progressive motor block in most cases with moderate to severe post-operative 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 the pain allows it. With this technique, a significant reduction in the need to use opioids has been observed.

In clinical studies, an epidural infusion of 2 mg/ml of ropivacaine hydrochloride alone or mixed with 1-4 μg/ml of fentanyl for post-operative pain treatment has been administered for up to 72 hours. This combination of ropivacaine hydrochloride and fentanyl provided better pain relief but caused opioid-related side effects; this combination has only been investigated for ropivacaine hydrochloride 2 mg/ml.

When prolonged peripheral nerve blocks are applied, either through continuous infusion or repeated injections, the risks of reaching a toxic plasma concentration or inducing local neural injury should 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, before surgery; then maintaining analgesia with ropivacaine hydrochloride 2 mg/ml. Perfusion rates or intermittent injections of 10-20 mg per hour for 48 hours provided adequate analgesia and were well tolerated.

Pediatric Patients from0 to 12 years of age inclusive

1. It is recommended to use doses at the lower end of the dose range for thoracic epidural blocks, while for lumbar or caudal epidural blocks, doses at the upper end of the range are recommended.
2. Recommended for lumbar epidural block. It is appropriate to reduce the bolus dose for thoracic epidural analgesia.

Infants from 1 year and children up to 12 years:

The proposed doses of ropivacaine hydrochloride for peripheral block in infants and children provide guidelines for use in children without severe illness. For children with severe illnesses, 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 should be interrupted immediately.

A single epidural caudal injection of 2 mg/ml of ropivacaine hydrochloride produces adequate 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 epidural caudal injection can be adjusted to obtain a different distribution of the sensory block, as recommended in the literature. Doses of up to 3 mg/kg of a ropivacaine hydrochloride concentration of 3 mg/ml have been studied in children over 4 years; however, this concentration is associated with a higher incidence of motor block.

It is recommended to fractionate the calculated dose of local anesthetic, regardless of the route of administration.

If infusion of ropivacaine hydrochloride is recommended, Ropsine injectable solution can be used.

Incompatibilities

Compatibilities with other solutions have not been investigated, so this medication should not be mixed with other medications.

Precipitation can occur in alkaline solutions since ropivacaine hydrochloride shows poor solubility at pH > 6.0.

Elimination

The elimination of unused medication and all materials that have come into contact with it will be carried out in accordance with local regulations.