Bupivacaine grindeks

Package leaflet: Information for the patient

Bupivacaine Grindeks, 5 mg/ml, solution for injection
Bupivacaini hydrochloridum
Please read the entire leaflet carefully before use, as it contains
important information for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, please consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. This medicine may harm others, even if their symptoms are identical.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Leaflet contents:

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

1. What Bupivacaine Grindeks is and what it is used for

Bupivacaine Grindeks contains the active substance bupivacaine hydrochloride. This medicine belongs to a group of medicines called local anaesthetics.
Bupivacaine Grindeks prevents the sensation of pain, heat, and cold in the area of injection.
However, sensation of pressure and touch may still be possible.
In this way, specific parts of the body innervated by the targeted nerves become anaesthetized.
In many cases, the motor nerves to the muscles in the affected area are also blocked,
leading to temporary muscle weakness or paralysis.
Bupivacaine Grindeks is used to anaesthetize specific parts of the body during surgical procedures, as well as for pain relief.
Bupivacaine Grindeks is administered by injection:

• into tissues where the surgical procedure will be performed;
• near a nerve or group of nerves supplying the area to be operated on, e.g. an injection under the arm before forearm or hand surgery;
• epidurally (into the so-called epidural space of the spine).

Bupivacaine Grindeks is particularly recommended for postoperative anaesthesia or anaesthesia during childbirth.

2. Important information before using Bupivacaine Grindeks

When not to use Bupivacaine Grindeks

• if the patient is allergic to bupivacaine hydrochloride or any of the other ingredients of this medicine (listed in section 6);
• if the patient has allergic reactions to amide-type local anaesthetics;
• in conditions contraindicating epidural anaesthesia, regardless of the type of anaesthetic used, including: meningitis, myelitis, intracranial haemorrhage, subacute combined degeneration of the spinal cord in pernicious anaemia, brain or spinal tumours, spinal tuberculosis, purulent skin infection at the intended injection site, coagulation disorders or current anticoagulant therapy;
• in the event of cardiogenic or hypovolemic shock – a syndrome of symptoms such as cold, sweaty pale skin, lowered body temperature, rapid shallow breathing, decreased arterial blood pressure, rapid and weak pulse, and disturbances of consciousness due to ischemia or hypoxia of organs and tissues caused by cardiac insufficiency or insufficient blood volume in the circulatory system;
• in intravenous regional anaesthesia (Bier's block).

Warnings and precautions
Before starting treatment with Bupivacaine Grindeks, discuss this with your doctor or nurse.
Before administering Bupivacaine Grindeks, the doctor should be informed about:

• all the patient's medical conditions;
• any heart, liver or kidney diseases, in order to appropriately adjust the dose;
• all medications currently taken by the patient.

Hypovolemia (reduced circulating blood volume) should be avoided before starting anaesthesia with Bupivacaine Grindeks.
Bupivacaine Grindeks with other medicines
Tell your doctor or nurse about all medicines the patient is currently taking or has recently taken, including those obtained without a prescription, as well as any medicines the patient plans to take.
In particular, inform the doctor if the patient is taking:

• other local anaesthetics;
• antiarrhythmic drugs (used for heart rhythm disorders, e.g. amiodarone).
  Bupivacaine Grindeks may affect the action of other medicines, and some medicines may affect the action of Bupivacaine Grindeks and the selection of an appropriate dose.

Bupivacaine Grindeks, food, drink and alcohol
Not applicable.
Pregnancy, breastfeeding and fertility
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor before using this medicine.
There is no evidence of harmful effects of Bupivacaine Grindeks on pregnancy.
Animal studies have shown adverse effects on embryonic development and offspring survival.
Therefore, bupivacaine should not be used during early pregnancy.
In patients with advanced pregnancy, the dose of anaesthetic should be reduced.
Inform the doctor about breastfeeding before administering Bupivacaine Grindeks.
There is no evidence of harmful effects of Bupivacaine Grindeks during breastfeeding.
Driving and operating machinery
After injection of Bupivacaine Grindeks, driving vehicles or operating machinery should be avoided, as the medicine may affect the ability to perform these activities.
Bupivacaine Grindeks contains sodium
The medicine contains 31.5 mg of sodium (the main component of table salt) in each ampoule (10 ml).
This corresponds to 1.57% of the maximum recommended daily dietary sodium intake for adults.

3. How to use Bupivacaine Grindeks

Bupivacaine Grindeks is administered to the patient by a doctor or by a nurse under the supervision of a doctor. Bupivacaine anesthesia is performed in appropriately equipped centers where the necessary equipment and medications for patient monitoring and resuscitation are available. The physician performing the anesthesia will take special precautions to avoid intravascular injection. The physician is adequately trained and familiar with methods for diagnosing and managing adverse reactions, general signs of drug intoxication, and other complications.

The physician determines the appropriate dose for the patient, taking into account the desired clinical objective and the patient's physical condition.

Bupivacaine Grindeks will be administered to the patient by injection (see section 1).

Use in children and adolescents
The dose of the drug depends on the patient's age and body weight and is determined by the anesthesiologist.

Bupivacaine Grindeks is intended:

• for children over 12 years of age for regional anesthesia of specific body parts during surgical procedures
• for children over 1 year of age for pain relief

Use of a higher than recommended dose of Bupivacaine Grindeks
Severe adverse reactions following overdose occur very rarely, but require specific treatment. The attending physician must be prepared for such a situation.

Early signs of overdose include:

• dizziness,
• numbness of the lips and perioral area,
• tongue numbness,
• visual and hearing disturbances.

To prevent severe adverse reactions, the physician will discontinue administration of Bupivacaine Grindeks immediately if any of the above overdose symptoms occur. The physician must be informed immediately if even one of the above symptoms appears.

Severe symptoms of overdose include difficulty speaking, muscle stiffness, tremor, seizures, or loss of consciousness.

If you have any further doubts regarding the use of this medicine, consult your doctor or nurse.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
Inform your doctor immediately if you feel unwell during administration of Bupivacaine Grindeks.

Severe allergic reactions (occur rarely, no more frequently than in 1 out of 1,000 patients):
If a patient experiences a severe allergic reaction, inform the doctor immediately.
Symptoms may include sudden onset of:

• rash or itching (especially of the skin all over the body), swelling of the face, lips, tongue and (or) throat, which may cause difficulty in breathing and speaking, shortness of breath;
• anaphylactic reaction (wheezing during breathing; difficulty swallowing, sensation of skin itching and flushing, dizziness);
• anaphylactic shock (life-threatening sudden drop in blood pressure, pallor, fainting or collapse).

Other possible adverse reactions:
Very common (occur in more than 1 out of 10 patients):

• significantly low blood pressure;
• nausea.

Common (occur in no more than 1 out of 10 patients):

• abnormal sensation (numbness and tingling);
• dizziness;
• slowed heart rate;
• high blood pressure;
• vomiting;
• urinary retention (difficulty passing urine).

Uncommon (occur in no more than 1 out of 100 patients):

• seizures;
• numbness around the mouth and tongue;
• tinnitus, sound sensitivity;
• blurred vision;
• loss of consciousness;
• muscle tremor;
• feeling of emptiness in the head;
• speech disturbances.

Rare (occur in up to 1 out of 1,000 patients):

• neuropathy (nerve damage), peripheral nerve injury (manifested by sensation of weakness, tingling or numbness in limbs);
• meningitis (inflammation of the membrane surrounding the spinal cord);
• double vision;
• heart rhythm disorders;
• respiratory depression or respiratory arrest, or cardiac arrest. These may be life-threatening.

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor or nurse. Adverse reactions can be reported directly to the Department of Monitoring of Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warszawa
Tel.: + 48 22 49 21 301
Fax: + 48 22 49 21 309
e-mail: [email protected]
Reporting adverse reactions helps to provide more information on the safety of the medicine.
Adverse reactions can also be reported to the responsible entity.

5. How to store Bupivacaine Grindeks

Do not store above 25°C.
Keep in the original outer packaging to protect from light.
Do not freeze.
Keep the medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging following EXP. The expiry date refers to the last day of the stated month.
Do not use this medicine if the packaging is damaged.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures will help protect the environment.

6. Contents of the packaging and other information

What Bupivacaine Grindeks contains

• The active substance is bupivacaine hydrochloride (Bupivacaini hydrochloridum). 1 ml of solution contains 5 mg of bupivacaine hydrochloride. One ampoule (10 ml) contains 50 mg of bupivacaine hydrochloride.
• Other ingredients: sodium chloride, sodium hydroxide (for pH 4.0–6.5), hydrochloric acid (for pH 4.0–6.5), water for injections.

What Bupivacaine Grindeks looks like and contents of the pack
A clear, colourless solution.
The medicine is packed in ampoules made of colourless glass (type I), each containing 10 ml of solution.
The pack contains 5 ampoules in a PVC blister, in a cardboard box.

Marketing Authorisation Holder
AS GRINDEKS
Krustpils iela 53, Riga, LV-1057, Latvia
Tel.: +371 67083205
Fax: +371 67083505
E-mail: [email protected]

Manufacturer
JSC GRINDEKS
Krustpils St 53, Riga, LV-1057, Latvia
Tel.: +371 67083205
Fax: +371 67083505

Date of the latest revision of the leaflet:

Information intended exclusively for medical professionals:

Dosage and administration
Dosage
Adults and children aged 12 years and older
The table below presents the recommended dosages for the more commonly used
anesthetic techniques.
To determine the appropriate dose, the physician should have adequate experience and precise
information regarding the patient's health status.
When prolonging anesthesia through continuous infusion or repeated administration of a high dose (bolus), consider the risk of toxic increase in plasma drug concentration or local nerve damage.
Table 1. Dosage recommendations for adults

Remarks:
The above amounts include the test dose.

1. In the case of plexus block, the dose should be adjusted according to the site of injection
   and the patient's health status. Brachial plexus block may be associated with a higher incidence
   of adverse effects related to unintentional intra-arterial administration of the local anaesthetic (see Special Warnings and Precautions for Use below).
2. Maximum dose ≤400 mg per day.
3. Bupivacaine solution is frequently used in epidural anaesthesia in combination
   with appropriate opioids administered for pain relief (including during labour). The total dose should not exceed ≤400 mg per day.
4. When the patient is simultaneously receiving additional doses of bupivacaine for another purpose, the limit of 150 mg per single dose should not be exceeded.
5. In the case of repeated doses, up to 50 mg of bupivacaine hydrochloride may be administered at 2-hour intervals.
   The doses presented in the Table above usually ensure the desired anaesthetic effect.
   Minor variations may occur in the onset and duration of anaesthesia. Excessively high doses should be avoided in local anaesthesia.
   Generally, to achieve complete anaesthesia of all nerve fibres in larger nerves, a higher concentration of anaesthetic agent is required. For smaller nerves or analgesia (e.g., labour pain), a lower concentration is sufficient. The volume of solution should be determined according to the area to be anaesthetized.
   To avoid accidental intravascular administration, careful aspiration is recommended before and during injection. The main dose should be administered slowly, at a rate of 25 to 50 mg/min. When increasing the dose, vital functions should be carefully monitored and verbal contact with the patient maintained. In epidural anaesthesia, it is recommended to administer a test dose of 3 to 5 ml of bupivacaine solution with adrenaline. Unintentional intravascular injection may cause transient tachycardia, whereas accidental intrathecal administration may lead to symptoms of spinal anaesthesia.
   If signs of toxicity occur, administration of the product should be stopped immediately.
   Available experience indicates that, with an average daily dose of 400 mg of bupivacaine in adults, no toxic effects have been observed.
   Children aged 1 to 12 years
   Table 2. Dosing recommendations for children aged 1 to 12 years

The dose for children is calculated as follows: 2 mg of the product per 1 kg of body weight.
If the volume of the product to be administered to a child (based on calculation) exceeds 20 ml, a 0.20% solution should be used instead of the 0.25% solution, in the calculated volume.
The above table provides basic dosing recommendations for use in pediatric practice.
Dosage adjustments may be acceptable in individual cases.

Route of administration
Epidural and peripheral nerve block administration.

Pharmaceutical incompatibility
The solubility of bupivacaine hydrochloride decreases at pH > 6.5. Caution should be exercised when adding alkaline solutions, e.g. carbonates, as this may cause precipitation.
Bupivacaine is compatible when mixed with buprenorphine, diamorphine, epinephrine, fentanyl, hydromorphone, morphine, and sufentanil, but incompatible with other drugs.

Special precautions for disposal and preparation of the medicinal product for use
The Bupivacaine Grindeks product does not contain preservatives. Each ampoule is intended for single use only. Re-sterilization is not permitted.
Any unused medicinal product or waste material should be disposed of in accordance with local regulations.

Special warnings and precautions for use
Cases of cardiac arrest and death have been reported during administration of bupivacaine for spinal or peripheral nerve block anesthesia. In some cases, resuscitation was unsuccessful despite correct procedures being followed.
Bupivacaine, like all other local anesthetics, may cause central nervous system (CNS) and cardiovascular system toxicity when administration for local anesthesia results in high plasma concentrations of the drug. This is particularly relevant in cases of accidental intravascular injection.
At high plasma concentrations of bupivacaine, ventricular arrhythmias, ventricular fibrillation, cardiovascular collapse, and death have been reported.
Anesthesia with bupivacaine should be performed in appropriately equipped facilities where appropriate monitoring and resuscitation equipment and medications are available. Prior to performing anesthesia, venous access should be secured.
The physician administering the anesthetic should take special precautions to avoid intravascular injection (see Dosage and administration), and must be adequately trained and familiar with methods for diagnosing and managing adverse reactions, general toxic effects, and other complications (see Overdose).

Large nerve blocks require large volumes of local anesthetic. These areas are often highly vascularized or performed near large blood vessels, increasing the risk of intravascular injection and/or systemic absorption. This may lead to high plasma concentrations of the drug.

Special precautions should be taken when administering local anesthesia to patients in poor general health due to age or hepatic or renal impairment, even though regional anesthesia may be the optimal choice for this patient group.

Patients with partial or complete atrioventricular block require special attention during local anesthesia, as local anesthetics may further impair atrioventricular conduction. Patients receiving Class III antiarrhythmics (e.g. amiodarone) should be under close observation and ECG monitoring, as effects on cardiac function may be additive.

Local anesthesia with Bupivacaine Grindeks should not be initiated in hypovolemic patients until fluid deficits have been corrected.

Epidural anesthesia may cause hypotension and bradycardia. The risk of these effects can be reduced by administration of vasopressors. In the event of hypotension, intravenous ephedrine should be administered immediately at a dose of 5–10 mg, and repeated if necessary. In children, ephedrine should be administered in doses adjusted according to age and body weight.

Central block (spinal and epidural) may lead to circulatory failure, especially under conditions of hypovolemia. Epidural anesthesia should be performed cautiously in patients with cardiac insufficiency.

Local anesthesia in the head and neck area may be associated with an increased frequency of adverse reactions, regardless of the anesthetic agent used. Accidental intra-arterial injection, even of small doses, may cause severe brain damage.

Peribulbar injections may rarely reach the subarachnoid space, causing transient blindness, cardiovascular collapse, apnea, seizures, and other effects. These symptoms should be rapidly diagnosed and immediately treated.

Cases of respiratory arrest following peribulbar anesthesia have been reported. Therefore, as with other regional anesthetics, trained personnel, essential equipment, and medications should be available during the procedure.

Peri- and retrobulbar anesthesia may carry a small risk of permanent dysfunction of the eye muscles. The main causes are trauma and/or local toxic effects on muscles and/or nerves. The severity of tissue reaction is related to the degree of trauma, drug concentration, and duration of tissue exposure to the local anesthetic. Therefore, as with other local anesthetics, the lowest effective concentration and dose should be used. Vasoconstrictors and other additives may increase tissue reactivity and should only be used when necessary.

Cervical plexus block may in some cases cause bradycardia or tachycardia; therefore, fetal heart rate should be monitored.

Intra-articular injection of bupivacaine after surgical procedures involving significant intra-articular trauma or large exposed joint surfaces requires special caution, as increased absorption and high plasma concentrations of the active substance may occur.

Allergic reactions have been reported following administration of amide-type local anesthetics (anaphylactic shock observed in the most severe cases).

No allergic reactions have been observed following administration of amide-structure drugs (e.g. bupivacaine) in patients who previously experienced allergic reactions to ester-type local anesthetics (procaine, tetracaine, benzocaine).

Bupivacaine is metabolized in the liver. Therefore, bupivacaine should be used with caution in patients with hepatic disease or reduced hepatic blood flow.

Special precautions should be taken when Bupivacaine Grindeks is administered to patients concurrently receiving other local anesthetics or drugs with similar amide structure, such as certain antiarrhythmics (e.g. lidocaine, mexiletine), as systemic toxic effects of these drugs may be additive.

Overdose
Acute systemic toxic reactions
Systemic toxic reactions most commonly involve the central nervous system (CNS) and cardiovascular system. These reactions are caused by high plasma concentrations of the local anesthetic, which may result from accidental intravascular injection, overdose, or rapid absorption from highly vascularized areas (see "Special warnings and precautions for use").
CNS reactions are similar for all amide-type local anesthetics, whereas cardiovascular reactions vary both qualitatively and quantitatively depending on the specific drug. Accidental intravascular injection may cause immediate (within seconds or minutes) systemic toxic reactions. In cases of overdose, systemic toxicity appears later (15–60 minutes after injection) due to slower rise in blood concentration of the anesthetic.

Central nervous system
CNS toxicity is a progressive process, with symptoms intensifying over time. Initial signs of toxicity usually include circumoral paresthesia, tongue numbness, dizziness, auditory hypersensitivity, tinnitus, and visual disturbances.
Dysarthria, muscle twitching, or tremors are more severe symptoms preceding seizures. These symptoms must be correctly diagnosed to avoid confusion with neurotic behavior. Loss of consciousness and generalized tonic-clonic seizures lasting from several seconds to several minutes may occur. Following seizures, increased muscular activity rapidly leads to hypoxia and hypercapnia, accompanied by respiratory disturbances. In severe cases, apnea may occur. Acidosis, hyperkalemia, and hypoxia increase and prolong the toxic effects of local anesthetics.
Recovery occurs through redistribution of the local anesthetic from the CNS, followed by metabolism and elimination. Recovery may be rapid, provided large amounts of the anesthetic have not been administered.

Cardiovascular system
Cardiovascular toxicity may occur in severe cases and is usually preceded by CNS toxicity symptoms. In patients under the influence of strong sedatives or general anesthesia, early CNS warning signs may be absent. High plasma concentrations of local anesthetic may lead to hypotension, bradycardia, arrhythmias, or even cardiac arrest, even in the absence of CNS warning signs. In the event of cardiac arrest following bupivacaine administration, resuscitation procedures should be initiated, including electrical defibrillation. Restoration of hemodynamically effective cardiac function may require prolonged resuscitation efforts. In children undergoing nerve blocks under general anesthesia, early signs of local anesthetic toxicity may be difficult to detect.

Treatment of acute toxicity
If signs of acute systemic toxicity appear, administration of the local anesthetic should be immediately discontinued.
If seizures occur, treatment is essential. All necessary medications and resuscitation equipment must be readily available. The goals of treatment are adequate oxygenation, termination of seizures, and maintenance of circulation. If necessary, assisted or controlled ventilation should be initiated. If seizures do not cease spontaneously within 15–20 seconds, an intravenous anticonvulsant should be administered. Seizures should be treated with thiopental at a dose of 100–150 mg or diazepam at a dose of 5–10 mg (the latter has a slower onset). In cases of persistent seizures, a muscle relaxant (e.g. suxamethonium) may be used to ensure oxygen delivery and ventilation. In such cases, endotracheal intubation and controlled ventilation are required.

If signs of dangerous circulatory depression (hypotension, bradycardia) occur, intravenous ephedrine should be administered at a dose of 5–10 mg, repeated every 2–3 minutes if necessary. Atropine may be given for bradycardia. In case of circulatory arrest, immediate resuscitation should be initiated. The key factors in treating acute toxicity are optimal oxygen delivery, ensuring adequate ventilation and circulation, and correction of acidosis.