Valecaine (Solution) Instructions for Use

Marketing Authorization Holder

Kraspharma, PJSC (Russia)

ATC Code

N01BB01 (Bupivacaine)

Active Substance

Bupivacaine (Rec.INN registered by WHO)

Dosage Form

Valecaine

Solution for injection 5 mg/1 ml: fl. 4 ml 1 or 5 pcs., 10 ml 5, 10 or 20 pcs.

Dosage Form, Packaging, and Composition

Solution for injection transparent, colorless.

Excipients : sodium chloride – 8 mg, sodium hydroxide solution 1M or hydrochloric acid solution 1M – to pH 4.0-6.5.

4 ml – bottles (1) – cardboard packs.
4 ml – bottles (5) – contour cell packs (1) – cardboard packs.
10 ml – bottles (5) – contour cell packs (1) – cardboard packs.
10 ml – bottles (5) – contour cell packs (2) – cardboard packs.
10 ml – bottles (5) – contour cell packs (4) – cardboard packs.

Clinical-Pharmacological Group

Local anesthetic

Pharmacotherapeutic Group

Local anesthetic agent

Pharmacological Action

Long-acting amide-type local anesthetic, four times more potent than lidocaine. It reversibly blocks impulse conduction along the nerve fiber by affecting sodium channels. It can exert a similar effect in the brain and myocardium.

It has a hypotensive effect and slows the heart rate. Postoperative analgesia is maintained for 7-14 hours with intercostal block. After a single epidural injection, the duration of effect when using a concentration of 5 mg/ml ranges from 2 to 5 hours, and up to 12 hours with peripheral nerve block.

The use of solutions at a concentration of 2.5 mg/ml has a lesser effect on motor nerves.

Pharmacokinetics

The systemic absorption of bupivacaine depends on the dose, the method of its administration, and the vascularity of the injection site.

The anesthetic effect occurs quickly; compared to other local anesthetics, the anesthetic effect of bupivacaine is significantly longer. It has been noted that after the return of sensation, an analgesic effect persists for some time, which makes it possible to reduce the doses of analgesics. Bupivacaine is completely absorbed from the epidural space; absorption is biphasic. T_Cmax in blood plasma during caudal epidural and conduction anesthesia is 30-45 minutes, followed by a decrease to a negligible level within 3-6 hours. The total plasma clearance of bupivacaine is 580 ml/min, V_d – 73 L. Terminal T_1/2 – 2.7 hours.

Bupivacaine is metabolized in the liver, mainly by conjugation with glucuronic acid.

Bupivacaine is excreted mainly by the kidneys, with only 6% excreted unchanged in the urine.

Bupivacaine crosses the placenta by passive diffusion. Protein binding in the fetal body is lower than in the maternal body, the concentration of the unbound fraction in the fetal and maternal body is the same. It is secreted into breast milk.

Pharmacokinetic parameters can be significantly altered by factors affecting urine pH and renal blood flow, depending on the route of administration of bupivacaine and the patient’s age, as well as in patients with liver and kidney diseases.

Indications

Surgical anesthesia in adults and children over 12 years of age; infiltration anesthesia when a long-lasting anesthetic effect is required, for example, for postoperative pain; conduction anesthesia with prolonged effect or epidural anesthesia in cases where the addition of epinephrine is contraindicated and significant muscle relaxation is not required; anesthesia in obstetrics.

ICD codes

Dosage Regimen

Determine the dosage individually based on the type of nerve block, surgical procedure, and patient’s physical status and age.

Administer the lowest effective dose and lowest effective concentration to achieve the desired anesthetic effect.

For epidural anesthesia in lumbar region for non-obstetrical surgery, use an initial dose of 15-30 ml of a 5 mg/ml solution. For caudal epidural block, use 15-30 ml of a 5 mg/ml solution. For epidural anesthesia in obstetrics, use a test dose of 3 ml of a 5 mg/ml solution. The total initial dose for lumbar epidural administration should not exceed 20 ml of a 5 mg/ml solution. Repeat doses may be given at intervals of at least 2 hours.

For peripheral nerve blocks, use 5 to 70 ml of a 5 mg/ml solution. The specific volume and total dose depend on the anatomical site of injection. For retrobulbar block, use 2-4 ml of a 5 mg/ml solution. For sympathetic block, use 20-50 ml of a 5 mg/ml solution.

For infiltration anesthesia, the maximum single dose is 150 mg (30 ml of a 5 mg/ml solution).

Reduce the total dose for elderly or debilitated patients and for patients with severe hepatic impairment.

Aspirate frequently and inject slowly to avoid inadvertent intravascular injection. Continuously monitor cardiovascular and respiratory vital signs and the patient’s state of consciousness during and after injection.

Adverse Reactions

From the CNS and peripheral nervous system numbness of the tongue, dizziness, blurred vision, muscle tremor, drowsiness, convulsions, loss of consciousness, neuropathy, peripheral nerve damage, arachnoiditis, paresis, paraplegia. In the area of anesthesia, paresthesia, weakening of sphincter tone are possible.

From the cardiovascular system decreased cardiac output, heart block, arterial hypotension, bradycardia, ventricular arrhythmias, cardiac arrest, arrhythmia.

From the digestive system nausea, vomiting.

From the urinary system: urinary retention.

From the respiratory system apnea.

From the organ of vision: diplopia.

Allergic reactions skin manifestations, in severe cases – anaphylactic shock.

Contraindications

Hypersensitivity to bupivacaine or to other amide-type local anesthetics; conditions in which epidural anesthesia is contraindicated: current diseases of the CNS, such as meningitis, poliomyelitis, intracranial hemorrhage, as well as CNS neoplasms; spinal tuberculosis; pernicious anemia with subacute combined degeneration of the spinal cord; pustular skin lesion at the intended puncture site or adjacent to the puncture site; cardiogenic or hypovolemic shock; blood clotting disorders or concomitant anticoagulant therapy; children under 12 years of age.

Bupivacaine is not used for intravenous regional anesthesia (Bier’s block).

With caution elderly age; debilitated patients; AV block II and III degree; severe impairment of liver and kidney function; pregnancy; concomitant use with class III antiarrhythmic drugs (e.g., amiodarone); concomitant use with other local anesthetics or drugs structurally similar to amide-type local anesthetics, such as class lB antiarrhythmic drugs (e.g., lidocaine, mexiletine); paracervical block.

Use in Pregnancy and Lactation

Use during pregnancy is possible only in cases where the expected benefit to the mother outweighs the potential risk to the fetus. Performing a paracervical block is contraindicated.

If it is necessary to use bupivacaine during lactation, breastfeeding should be discontinued.

Use in Hepatic Impairment

Should be used with caution in patients with severe hepatic impairment.

Use in Renal Impairment

Should be used with caution in patients with severe renal impairment.

Pediatric Use

Contraindicated for use in children under 12 years of age.

Geriatric Use

Should be used with caution in elderly patients.

Special Precautions

Certain types of blocks may be associated with serious adverse reactions.

Epidural anesthesia may be accompanied by depression of the cardiovascular system, especially against the background of hypovolemia. Therefore, caution should be exercised in patients with impaired cardiovascular function.

In rare cases, with retrobulbar administration, bupivacaine may penetrate into the cranial subarachnoid space, resulting in temporary blindness, cardiovascular collapse, apnea, and convulsions. These symptoms require immediate treatment.

With retrobulbar and peribulbar administration of local anesthetics, there is a small risk of persistent impairment of ocular muscle function. The main causes are trauma and/or local toxic effect of the administered bupivacaine on the muscles and/or nerves.

Accidental intravascular injection of local anesthetics in the head and neck area, even in low doses, can cause symptoms of CNS toxicity.

Paracervical block sometimes leads to bradycardia/tachycardia in the fetus, so the fetal heart rate should be carefully monitored.

Caution should be exercised in patients with atrioventricular block of stage II or III, since local anesthetics may reduce myocardial conductivity. Caution should be exercised in patients with severe impairment of liver or kidney function, elderly or debilitated patients.

Patients receiving class III antiarrhythmic drugs (e.g., amiodarone) should be under close supervision with ECG monitoring due to the risk of cardiovascular complications due to a possible additive effect.

Drug Interactions

With simultaneous use with antiarrhythmic drugs that have local anesthetic activity, the risk of additive toxic effects increases.

With simultaneous use with barbiturates, a decrease in the concentration of bupivacaine in the blood is possible.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.