Bupivacaine Grindeks

Leaflet attached to the packaging: patient information

Bupivacaine Grindeks, 5 mg/ml, solution for injection

Bupivacaine hydrochloride

You should carefully read the contents of the leaflet before using the medicine, as it contains important information for the patient.

• You should keep this leaflet, so that you can read it again if you need to.
• If you have any doubts, you should consult a doctor, pharmacist, or nurse.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, you should tell your doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet:

• 1. What is Bupivacaine Grindeks and what is it 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 packaging and other information

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

Bupivacaine Grindeks contains the active substance bupivacaine hydrochloride. This medicine belongs to a group of medicines called local anesthetics.
Bupivacaine Grindeks prevents the feeling of pain, heat, and cold in the area of injection.
However, there is a possibility of feeling pressure and touch.
In this way, certain parts of the body in the area of the relevant nerves become numb.
In many cases, the nerve muscles in the affected area are also blocked, which causes temporary weakness or paralysis.
Bupivacaine Grindeks is used for anesthesia of certain parts of the body during surgical procedures, as well as for pain relief.
Bupivacaine Grindeks is administered by injection:

• into tissues where a surgical procedure will be performed;
• in the area of a nerve or group of nerves that innervate the operated part of the body, e.g., injection under the armpit before forearm or hand surgery;
• epidurally (administration into the so-called epidural space of the spine).

Bupivacaine Grindeks is particularly recommended for postoperative anesthesia or anesthesia 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 anesthetic agents of the amide type;
• in cases of diseases that are contraindications to the use of epidural anesthesia, regardless of the type of anesthetic used, including: meningitis, encephalitis, intracranial hemorrhage, subacute degeneration of the spinal cord in the course of malignant anemia, brain and spinal cord tumors, spinal tuberculosis, infectious skin infection at the planned injection site, coagulation disorders or current anticoagulant treatment;
• in case of cardiogenic or hypovolemic shock - a set of symptoms such as: cold, sweaty pale skin, decreased body temperature, rapid, shallow breathing, decreased blood pressure, rapid and weak pulse, and impaired consciousness related to inadequate perfusion or oxygenation of organs and tissues caused by heart failure or insufficient blood volume in the circulatory system;
• in regional intravenous anesthesia (Bier's block).

Warnings and precautions

Before starting treatment with Bupivacaine Grindeks, you should discuss it with your doctor or nurse.
Before using Bupivacaine Grindeks, the doctor should be informed about:

• all the patient's diseases;
• all heart, liver, or kidney diseases, in order to adjust the dose accordingly;
• all medicines regularly taken by the patient.

It is necessary to prevent hypovolemia (decrease in circulating blood volume) before starting anesthesia with Bupivacaine Grindeks.

Bupivacaine Grindeks and other medicines

You should tell your doctor or nurse about all medicines you are currently taking or have recently taken, including those that are available without a prescription, as well as medicines you plan to take.
In particular, you should inform your doctor if you are taking:

• other local anesthetics;
• anti-arrhythmic drugs (used in 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 its appropriate dose.

Bupivacaine Grindeks with food, drink, and alcohol

This does not apply.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, you should consult your doctor before using this medicine.
There is no evidence of harmful effects of Bupivacaine Grindeks on the course of pregnancy.
Studies conducted on animals have shown an adverse effect on the development of embryos and the survival of offspring.
Therefore, bupivacaine should not be used in early pregnancy.
In the case of advanced pregnancy, the dose of the anesthetic should be reduced.
You should inform your doctor about breastfeeding before administering Bupivacaine Grindeks.
There is no evidence of harmful effects of Bupivacaine Grindeks during breastfeeding.

Driving and using machines

After injection of Bupivacaine Grindeks, you should not drive vehicles or operate machines, as the medicine may affect your 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 dose of sodium in the diet 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 there is access to the necessary equipment and medicines for monitoring and resuscitation of the patient. The doctor performing the anesthesia will take special precautions to avoid intravascular administration. He is properly trained and knows the methods of diagnosing and treating adverse reactions, general symptoms of poisoning, and other complications.
The doctor decides what dose is suitable for the patient, taking into account the desired clinical effect 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 medicine depends on the patient's age and weight and is determined by the anesthesiologist.
Bupivacaine Grindeks is intended

• for children over 12 years old for anesthesia of individual parts of the body during surgical procedures
• for children over 1 year old for pain relief

Using a higher dose of Bupivacaine Grindeks than recommended

Severe adverse reactions due to overdose are very rare, but they require special treatment. The doctor performing the anesthesia must be prepared for such a situation.
The first symptoms of overdose are:

• dizziness;
• numbness of the mouth and surrounding area;
• numbness of the tongue;
• visual and hearing disturbances. To prevent the occurrence of severe adverse reactions, the doctor will stop administering Bupivacaine Grindeks as soon as any of the overdose symptoms appear. You should immediately inform your doctor if you experience any of the above symptoms.

Severe symptoms of overdose are difficulty speaking, muscle stiffness, tremors, seizures, or loss of consciousness.
If you have any further doubts about the use of this medicine, you should consult your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
You should immediately inform your doctor if you feel unwell during the injection of Bupivacaine Grindeks.
Severe allergic reactions(occurring rarely, no more often than 1 in 1000 patients):
If you experience a severe allergic reaction, you should immediately tell your doctor.
Symptoms may include sudden onset of:

• rash or itching (especially of the whole body), swelling of the face, lips, tongue, and/or throat, which can cause difficulty breathing and speaking, shortness of breath;
• anaphylactic reaction (wheezing during breathing; difficulty swallowing, feeling of itching and flushing of the skin, dizziness);
• anaphylactic shock (life-threatening sudden decrease in blood pressure, paleness, fainting, or collapse).

Other possible side effects:

Very common(occurring more often than 1 in 10 patients):

• significantly low blood pressure;
• nausea.

Common(occurring no more often than 1 in 10 patients):

• abnormal sensation (numbness and tingling);
• dizziness;
• slow heart rate;
• high blood pressure;
• vomiting;
• urinary retention (problems with urination).

Uncommon(occurring no more often than 1 in 100 patients):

• seizures;
• numbness of the mouth and tongue;
• tinnitus, sensitivity to sounds;
• blurred vision;
• loss of consciousness;
• muscle tremors
• feeling of emptiness in the head;
• speech disorders.

Rare(occurring in no more than 1 in 1000 patients):

• neuropathy (nerve damage), peripheral nerve damage (manifested by a feeling of weakness, tingling, or numbness of the limbs);
• arachnoiditis (inflammation of the membrane surrounding the spinal cord);
• double vision;
• heart rhythm disturbances;
• inhibition or cessation of respiratory or cardiac function. This can be life-threatening.

Reporting side effects

If you experience any side effects, including any not listed in the leaflet, you should tell your doctor or nurse. Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocides
Al. Jerozolimskie 181C
02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
e-mail: ndl@urpl.gov.pl
By reporting side effects, you can help gather more information on the safety of the medicine.
Side effects can also be reported to the marketing authorization holder.

5. How to store Bupivacaine Grindeks

Do not store above 25°C.
Store in the original outer packaging to protect from light.
Do not freeze.
The medicine should be stored out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after the EXP expiry date. The expiry date refers to the last day of the specified month.
Do not use this medicine if you notice damage to the packaging.
Medicines should not be disposed of via wastewater or household waste. You should ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the packaging and other information

What Bupivacaine Grindeks contains

• The active substance of the medicine is bupivacaine hydrochloride (Bupivacaine hydrochloride). 1 ml of the solution contains 5 mg of bupivacaine hydrochloride. One ampoule (10 ml) contains 50 mg of bupivacaine hydrochloride.
• The other ingredients are: 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 what the packaging contains

Clear, colorless solution.
The medicine is packaged in ampoules made of colorless glass (type I) containing 10 ml of solution.
The packaging contains 5 ampoules in a PVC blister pack, in a cardboard box.

Marketing authorization holder

AS GRINDEKS
Krustpils iela 53, Riga, LV-1057, Latvia
phone: +371 67083205
fax: +371 67083505
e-mail: grindeks@grindeks.lv

Manufacturer

JSC GRINDEKS
Krustpils ST 53, Riga, LV-1057, Latvia
phone: +371 67083205
fax: +371 67083505

Date of last update of the leaflet:

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Information intended only for healthcare professionals:

Dosage and administration

Dosage
Adults and children from 12 years of age
The table below shows the recommended dosages for more commonly used anesthesia methods.
In order to determine the dose, the doctor should have the necessary experience and detailed information about the patient's health.
In the case of prolonging anesthesia through continuous infusion or by administering a large dose of the medicine (bolus), it is necessary to consider the risk of toxic increase in the concentration of the medicine in the blood and local nerve damage.

Table 1. Dosage recommendations for adults

Notes:
The above amounts are given in total with the test dose.

• 1) In the case of nerve plexus block, the dose should be used in accordance with the injection site and the patient's health condition. Brachial plexus anesthesia may be associated with a higher frequency of adverse reactions related to unintentional intravascular administration of the anesthetic (see Special warnings and precautions for use below).
• 2) The maximum dose is ≤400 mg per day.
• 3) The bupivacaine solution is often used in epidural anesthesia in combination with appropriate opioids administered for pain relief (including during childbirth). The total dose is ≤400 mg per day.
• 4) In the case where the patient is taking additional doses of bupivacaine for another purpose, the limit of 150 mg of a single dose should not be exceeded.
• 5) In the case of repeated doses, up to 50 mg of bupivacaine hydrochloride can be administered at 2-hour intervals.

The doses presented in the Table above usually provide the intended anesthetic effect.
Small differences may appear in the initial period of anesthesia and its duration. It is necessary to avoid using too large doses in local anesthesia.
Usually, in order to achieve more complete anesthesia of all nerve fibers in larger nerves, a higher concentration of the anesthetic is necessary. For anesthesia of smaller nerves or pain relief (e.g., during childbirth), a lower concentration will be sufficient. The volume of the solution is determined based on the area of anesthesia.
In order to avoid accidental intravascular administration of the product, aspiration is recommended before and during injection. The main dose should be administered slowly, at a rate of 25 to 50 mg/min, and the patient's vital functions should be carefully monitored and verbal contact with the patient should be maintained. During epidural anesthesia, it is recommended to administer a test dose of 3 to 5 ml of bupivacaine solution with adrenaline. Unintentional intravascular administration may cause a short-term increase in heart rate, while unintentional subarachnoid administration may cause symptoms of spinal anesthesia.
In the event of toxic symptoms, administration of the product should be stopped immediately. Previous experience indicates that with an average dose for an adult of 400 mg of bupivacaine per day, no toxic symptoms were observed.
Children from 1 to 12 years of age

Table 2. Dosage recommendations for children from 1 to 12 years of age

The dose for children is calculated based on 2 mg of the product per 1 kg of body weight.
If the volume of the product to be administered to the child (calculated) is greater than 20 ml, a solution with a concentration of 0.20% should be administered instead of 0.25% in the calculated volume.
The above table shows the basic doses for use in pediatric practice.
In individual cases, changes in dosing are permissible.
Administration method
Administration is epidural or perineural.

Incompatibility

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

Special precautions for disposal and preparation of the medicine for administration

Bupivacaine Grindeks does not contain preservatives. Each ampoule is intended for single use. Do not re-sterilize.
Any unused 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 the use of bupivacaine for epidural or peripheral nerve anesthesia. In some cases, resuscitation was unsuccessful, despite being performed correctly. Bupivacaine, like all other local anesthetics, can cause systemic toxicity in the central nervous system (CNS) and cardiovascular system, in the event of local anesthesia resulting in high concentrations of the medicine in the blood. This applies in particular to cases of unintentional intravascular administration. Bupivacaine anesthesia should be performed in appropriately equipped centers, where there is access to the necessary equipment and medicines for monitoring and resuscitation of the patient. The doctor performing the anesthesia should take special precautions to avoid intravascular administration (see Dosage and administration), and be properly trained and know the methods of diagnosing and treating adverse reactions, general symptoms of poisoning, and other complications (see Overdose).
Blockade of large nerve trunks requires the use of large volumes of local anesthetic. These areas are often well-vascularized or anesthesia is performed in the vicinity of large vessels, which increases the risk of intravascular injection of the medicine and/or its absorption into the systemic circulation. This can lead to high concentrations of the medicine in the blood.
Special precautions should be taken when using local anesthesia in patients with poor overall health due to age or liver or kidney dysfunction, even though regional anesthesia during surgery is the optimal solution for this group of patients.
Patients with partial or complete atrioventricular block require special attention when performing local anesthesia, as local anesthetics can reduce atrioventricular conduction. Patients taking anti-arrhythmic drugs of class III (e.g., amiodarone) should be under close surveillance and monitored by ECG, as the effect on the heart may be additive.
In patients with hypovolemia, anesthesia with Bupivacaine Grindeks should not be started until fluid deficiency is corrected.
Epidural anesthesia may cause a decrease in blood pressure and bradycardia. The risk of these symptoms can be reduced by administering vasoconstrictor drugs. In the event of hypotension, ephedrine should be administered intravenously in a dose of 5-10 mg, and if necessary, the administration should be repeated. In children, ephedrine should be administered in doses appropriate for the age and weight of the child.
Central blockade (spinal and epidural) may cause circulatory failure, especially in hypovolemic conditions. Epidural anesthesia should be performed with caution in patients with heart failure.
Local anesthetics performed in the head and neck area may be associated with an increased frequency of adverse reactions, regardless of the anesthetic used. Unintentional intravascular administration of even small doses of the medicine can cause serious brain damage.
Peribulbar injections can rarely reach the subarachnoid space, causing temporary blindness, cardiovascular collapse, apnea, seizures, and other symptoms. These symptoms should be quickly diagnosed and treated immediately.
In patients who have undergone peribulbar anesthesia, cases of respiratory arrest have been reported after anesthesia. Therefore, during peribulbar anesthesia, as with other regional anesthetics, trained personnel, necessary equipment, and medicines should be present.
Peri- and retrobulbar anesthesia may cause a small risk of permanent eye muscle function disorders. The main causes are injuries and/or local toxic symptoms in the muscles and/or nerves. The severity of the tissue reaction to anesthesia is related to the degree of injury, the concentration of the medicine, and the duration of tissue exposure to the local anesthetic. For this reason, as with other local anesthetics, the smallest effective concentration and dose of the medicine should be used during local anesthesia. Vasoconstrictor drugs and other substances may increase the tissue reaction, so they should only be used when necessary.
Cervical anesthesia may occasionally cause bradycardia or tachycardia, so fetal heart rate should be monitored.
In the case of significant intra-articular trauma or extensive exposed surface of the joint after surgical procedures, intra-articular injection of bupivacaine requires special caution, as it may lead to increased absorption and high concentrations of the active substance in the blood.
In individual cases, allergic reactions have been reported after the use of local anesthetics of the amide type (in the most severe cases, anaphylactic shock was observed).
No allergic reactions have been observed after the administration of amide-type anesthetics (e.g., bupivacaine) in patients who have 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 liver disease or reduced liver blood flow.
Special precautions should be taken if Bupivacaine Grindeks is administered to patients who are also taking other local anesthetics or medicines with a similar amide structure, such as certain anti-arrhythmic drugs, e.g., lidocaine, mexiletine, as the systemic toxic effects of these medicines may be additive.

Overdose

Acute systemic toxic reactions

Systemic toxic reactions most often affect the central nervous system and cardiovascular system. These reactions are caused by high concentrations of the local anesthetic in the blood, which may be the result of unintentional intravascular administration of the medicine, overdose, or rapid absorption from a surface with high vascularization (see Special warnings and precautions for use).
Reactions of the central nervous system are similar in the case of all amide-type local anesthetics, while reactions of the cardiovascular system depend both qualitatively and quantitatively on the specific medicine. Accidental intravascular administration of the anesthetic can cause immediate (within a few seconds or minutes) systemic toxic reactions. In the case of overdose, systemic toxicity manifests later (15-60 minutes after injection) due to the slower increase in the concentration of the anesthetic in the blood.
Central nervous system
Systemic toxicity of the central nervous system is a gradual process, in which symptoms worsen over time. The first signs of toxicity are usually perioral paresthesia, numbness of the tongue, dizziness, hyperacusis, tinnitus, and visual disturbances.
Dysarthria, muscle twitching, or tremors are more severe symptoms preceding seizures.
Loss of consciousness and seizures may occur, lasting from a few seconds to several minutes. Following seizures, due to increased muscle activity, hypoxia and hypercapnia develop rapidly, along with 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 central nervous system, and then its metabolism and excretion. Recovery may be rapid, provided that large amounts of the anesthetic have not been administered.
Cardiovascular system
Cardiovascular toxicity may occur in severe cases and is usually preceded by symptoms of central nervous system toxicity. In patients under the influence of strong sedatives or general anesthesia, the preceding symptoms of the central nervous system may not occur. High concentrations of the local anesthetic in the blood can lead to hypotension, bradycardia, arrhythmia, and even cardiac arrest, without preceding symptoms of the central nervous system. In the case of cardiac arrest after the use of bupivacaine, resuscitation measures should be taken, including electrical defibrillation. The return of hemodynamically efficient cardiac function may require prolonged resuscitation. In children during general anesthesia, early symptoms of local anesthetic toxicity may be difficult to detect.

Treatment of acute toxicity

In the event of signs of acute systemic toxicity, administration of the local anesthetic should be stopped immediately.
In the event of seizures, treatment is necessary. All necessary medicines and equipment for resuscitation should be readily available. The goal of treatment is to ensure adequate oxygenation, stop the seizure, and maintain blood circulation. If necessary, assisted or controlled ventilation should be used. If seizures do not stop spontaneously within 15-20 seconds, an anticonvulsant drug should be administered intravenously. Seizures can be treated with thiopental in a dose of 100-150 mg or diazepam in a dose of 5-10 mg (the effect is slower). In the case of prolonged seizures, a muscle relaxant (e.g., suxamethonium) may be used to ensure oxygen supply and breathing in the patient. However, in this case, the patient should be intubated and ventilation should be controlled.
In the event of signs of severe cardiovascular depression (hypotension, bradycardia), ephedrine should be administered intravenously in a dose of 5-10 mg, and if necessary, the administration should be repeated after 2-3 minutes. In the case of bradycardia, atropine can be administered. In the event of cardiac arrest, resuscitation measures should be taken immediately. The decisive factors in the treatment of acute toxicity are optimal oxygen supply, ensuring breathing and proper blood circulation, and treatment of acidosis.