BUPIVACAINE/ADRENALINE PHYSAN 2.5 mg/mL + 0.005 mg/mL INJECTABLE SOLUTION

2. What you need to know before you use Bupivacaine/Adrenaline Physan 2.5 mg/ml + 0.005 mg/ml

Do not use Bupivacaine/Adrenaline Physan 2.5 mg/ml + 0.005 mg/ml:

• If you are allergic to bupivacaine hydrochloride, adrenaline, or any of the other ingredients of Bupivacaine/Adrenaline Physan 2.5 mg/ml + 0.005 mg/ml (listed in section 6).
• If you are allergic to any other local anesthetic of the same group (e.g., articaine, mepivacaine, lidocaine, or prilocaine).
• If it is used as intravenous regional anesthesia (Bier block), as the unintended passage of bupivacaine into the bloodstream can lead to acute systemic toxicity reactions.
• If you have any of the following conditions, epidural anesthesia should not be performed:

• Pre-existing central nervous system disease due to infection, tumors, or other causes.
• Spinal deformity and active disease (e.g., spondylitis, tumor, tuberculosis) or recent injury (e.g., fracture) of the spine.
• Skin infection at the injection site or in close proximity.
• Cardiovascular disease, especially heart block or hypovolemic shock.
• Coagulation disorders or ongoing anticoagulant treatment.

Warnings and precautions

Consult your doctor before starting to use Bupivacaine/Adrenaline Physan 2.5 mg/ml + 0.005 mg/ml:

• If you have any type of heart block
• If you have heart rhythm disorders
• If you have low blood pressure
• If you have bleeding
• If you have any type of infection
• If you have liver or kidney disorders
• If you have severe or untreated hypertension (high blood pressure)
• If you have uncontrolled thyroid gland disease
• If you have circulatory disorders in the brain
• If you have advanced diabetes

Children

Bupivacaine should be used with caution in children from 1 to 12 years old, as they have a higher probability of systemic toxicity.

Other medicines and Bupivacaine/Adrenaline Physan 2.5 mg/ml + 0.005 mg/ml

Tell your doctor or pharmacist if you are using or have recently used or may need to use any other medicine, including those obtained without a prescription.

Bupivacaine should be used with caution in patients receiving treatment with structurally similar agents to amide-type local anesthetics, as it may increase systemic toxic effects.

Tell your doctor if you are taking any of the following medicines, as they may alter the effects of Bupivacaine/Adrenaline Physan 2.5 mg/ml + 0.005 mg/ml:

• Anticoagulants, such as heparin,
• Non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, to combat inflammation, pain, or fever.
• Plasma substitutes (dextran).
• Tricyclic antidepressants.
• Ergotamine-type oxytocics (medicines used to induce labor).
• Phenothiazines and butyrophenones for the treatment of psychotic disorders.
• Non-selective beta-blockers such as propranolol for the treatment of high blood pressure.
• Inhaled general anesthetics, such as halothane.

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.

Pregnancy

In case you are pregnant, your doctor will prescribe Bupivacaine/Adrenaline Physan 2.5 mg/ml + 0.005 mg/ml, taking into account the benefit to you and the risk to your baby.

Breastfeeding

Bupivacaine is excreted in breast milk, but at therapeutic doses of this medicine, no effects are expected in breastfed children. There is not enough information available on the excretion of adrenaline in breast milk, but it is unlikely to affect the breastfed child.

Driving and using machines

Bupivacaine/Adrenaline Physan 2.5 mg/ml + 0.005 mg/ml may temporarily alter your ability to move, attention, and coordination. Your doctor will indicate if you can drive or use machines.

Bupivacaine/Adrenaline Physan 2.5 mg/ml + 0.005 mg/ml contains sodium metabisulfite and sodium

This medicine may cause severe allergic reactions and bronchospasm (sudden feeling of suffocation) because it contains sodium metabisulfite.

This medicine contains 32.8 mg of sodium (main component of table salt/cooking salt) per 10 ml ampoule. This is equivalent to 1.64% of the maximum recommended daily sodium intake for an adult.

3. How to use Bupivacaine/Adrenaline Physan 2.5 mg/ml + 0.005 mg/ml

This medicine should only be administered under the supervision of a doctor with experience in the use of this type of medicine.

Bupivacaine/Adrenaline Physan 2.5 mg/ml + 0.005 mg/ml is administered by injection through infiltration, subcutaneously, intramuscularly, epidurally, intra-articularly, perineurally, and periosteally.

The dose, rate of administration, and duration of treatment will vary depending on the anesthetic procedure, the area to be anesthetized, and the patient's weight, clinical situation, and response.

If you use more Bupivacaine/Adrenaline Physan 2.5 mg/ml + 0.005 mg/ml than you should

As with other local anesthetics, due to excessive dosing, rapid absorption, or accidental injection into blood vessels, symptoms of intoxication may occur, which can manifest:

• On the central nervous system:

Characterized by tingling, numbness of the tongue, slight fainting, ringing in the ears, blurred vision, and muscle tremors. Then, convulsions and loss of consciousness may appear, followed by breathing problems.

• On the cardiovascular system:

Low blood pressure (hypotension),

decreased heart rate, arrhythmia, and cardiac arrest.

If toxic effects occur, the first measure is to stop the administration of the local anesthetic. The subsequent treatment consists of stopping the convulsions and ensuring adequate breathing with oxygen, if necessary by assisted breathing. If convulsions occur, they can be treated with 100-150 mg of thiopental i.v. or 5-10 mg of diazepam i.v. If there is hypotension, a vasopressor should be administered intravenously, for example, 5-10 mg of ephedrine. If cardiac arrest occurs, cardiopulmonary resuscitation should be applied immediately, and 0.1-0.2 mg of adrenaline should be administered intravenously or intracardially as soon as possible. If cardiac arrest occurs, prolonged resuscitation efforts should be applied.

In case of overdose or accidental administration, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone 91 562 04 20, indicating the medicine and the amount administered.

4. Possible side effects

Like all medicines, Bupivacaine/Adrenaline Physan 2.5 mg/ml + 0.005 mg/ml can cause side effects, although not everybody gets them.

The side effects you may experience can be classified by frequency as:

• Very common (may affect more than 1 in 10 people): decrease in blood pressure and nausea.
• Common (may affect up to 1 in 10 people): tingling, dizziness, decreased heart rate, increased blood pressure, vomiting, urinary retention.
• Uncommon (may affect up to 1 in 100 people): convulsions, tingling around the mouth, numbness of the tongue, increased hearing sensitivity, visual disturbances, loss of consciousness, tremors, mild headache, ringing in the ears, difficulty speaking correctly.
• Rare (may affect up to 1 in 1,000 people): allergic reactions, anaphylactic shock, nervous disorders, double vision, cardiac arrest, arrhythmias, breathing difficulties.

Reporting of side effects

If you experience any side effects, talk to your doctor, even if it is possible side effects not listed in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Bupivacaine/Adrenaline Physan 2.5 mg/ml + 0.005 mg/ml

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

Do not store above 25°C. Do not freeze. Protect from light.

Do not use this medicine after the expiry date stated on the ampoule and carton. The expiry date is the last day of the month indicated.

The solutions do not contain preservatives and should be used immediately after opening. Any remaining solution should be discarded.

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. Contents of the pack and other information

Composition of Bupivacaine/Adrenaline Physan 2.5 mg/ml + 0.005 mg/ml

• The active ingredients are bupivacaine hydrochloride and epinephrine (adrenaline). One ml contains 5 mg of bupivacaine hydrochloride and 0.005 mg of epinephrine (adrenaline) (as bitartrate). Each 10 ml ampoule contains 25 mg of bupivacaine hydrochloride and 0.05 mg of epinephrine (adrenaline) (as bitartrate).
• The other ingredients are: sodium chloride, sodium metabisulfite (E-223), sodium hydroxide (E-524), and/or hydrochloric acid (for pH adjustment) and water for injections.

Appearance and packaging of the product

Bupivacaine/Adrenaline Physan 2.5 mg/ml + 0.005 mg/ml is packaged in glass ampoules.

This medicine is presented in clinical packs containing 50 or 100 glass ampoules of 10 ml.

Not all pack sizes may be marketed.

Marketing authorization holder

LAPHYSAN S.A.U.

Anabel Segura, 11 Edificio A, Planta 4, Puerta D,

28108 Alcobendas

MADRID. SPAIN

Manufacturer

Laboratórios Basi - Indústria Farmacéutica S.A.

Parque Industrial Lourenço Ferreira, Nº8, Nº15 y Nº16.

3450-232 Mortágua, Portugal

This information is intended only for healthcare professionals

The solutions should be used immediately after opening. Any remaining solution should be discarded.

Due to the instability of adrenaline, products containing it should not be sterilized.

Appropriate precautions should be taken to avoid prolonged contact between anesthetic solutions containing adrenaline (low pH) and metal surfaces (e.g., needles and metal parts of syringes), as metal ions, mainly copper ions, can dissolve, causing local irritation (swelling, edema) at the injection site and accelerated degradation of adrenaline.

Precautions should be taken to prevent acute toxicity reactions, avoiding intravascular injection. Aspiration is recommended before and during administration. When high doses are administered, for example, in the case of epidural block, a test dose with 3-5 ml of bupivacaine with epinephrine is recommended. Accidental intravascular injection can be detected by a temporary increase in heart rate. The maximum dose should be administered very slowly, at a rate of 25-50 mg/min, or in dose increments, maintaining constant verbal contact with the patient. If symptoms of toxicity appear, administration should be stopped immediately.

Regional or local anesthesia procedures, except for those of a trivial nature, should always be performed by properly trained professionals and in areas with immediate access to resuscitation equipment and medicines. When performing major blocks, an intravascular catheter should be inserted beforehand at the injection site of the local anesthetic. Doctors should receive adequate training according to the procedure they will perform and be familiar with the diagnosis and treatment of side effects, systemic toxicity, and other complications.

In any case, and considering that the dosage should be calculated based on several factors, we recommend consulting the information provided in the Technical Sheet before using this medicine.

Incompatibilities

Bupivacaine has limited solubility at pH above 6.5. This should be taken into account in case alkaline solutions need to be added, e.g., carbonates, as precipitation may occur. As it contains adrenaline, mixing with alkaline solutions leads to rapid degradation of adrenaline.

Last revision of the leaflet: October 2020

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