Bupi0.5%

Bupi is a long-acting amide-type local anesthetic indicated for the production of local or regional anesthesia and analgesia in adults and, in specific clinical circumstances, older pediatric patients. Established, FDA-approved uses include:

• Local infiltration anesthesia for minor surgical procedures.
• Peripheral nerve blocks (e.g., brachial plexus, intercostal, pudendal) for surgical and postoperative analgesia.
• Sympathetic nerve blocks for pain management.
• Epidural anesthesia (lumbar and caudal), including for surgical procedures and obstetric labor analgesia, at appropriate concentrations.
• Retrobulbar block for ophthalmic surgery.
• Dental anesthesia (typically as a formulation combined with epinephrine).

Bupi is not recommended for intravenous regional anesthesia (Bier block) or obstetric paracervical block, and the 0.75% concentration must never be used for obstetric epidural anesthesia (see Contraindications). It is also used off-label, based on clinical experience, for continuous wound infiltration and intra-articular administration for postoperative pain, although intra-articular infusion is not an approved use and carries a specific risk (see Precautions and Warnings).

Each mL of injectable solution contains Bupivacaine Hydrochloride as the active ingredient, available in various concentrations (commonly 0.25%, 0.5%, and 0.75%), with or without added epinephrine (adrenaline) as a vasoconstrictor. Formulations may be preserved (multiple-dose vials) or preservative-free (single-dose ampoules/vials), and some preparations are combined with dextrose for hyperbaric spinal use.

Bupi is a long-acting local anesthetic of the amide class, chemically related to lidocaine and mepivacaine but with a longer duration of action. It is supplied as a sterile injectable solution for infiltration, peripheral nerve block, and neuraxial (epidural/spinal) administration. Bupi is widely used in surgical anesthesia, obstetric analgesia, and postoperative and chronic pain management because of its relatively prolonged duration of sensory blockade compared with shorter-acting local anesthetics.

Bupivacaine Hydrochloride blocks the generation and conduction of nerve impulses by reversibly binding to and inhibiting voltage-gated sodium channels in nerve cell membranes, thereby increasing the threshold for electrical excitation and slowing propagation of the nerve impulse. This produces a progressive blockade of sensory, motor, and autonomic nerve fibers, with sensory (pain) fibers typically blocked before motor fibers.

Onset of action is relatively slower than shorter-acting local anesthetics, but the duration of anesthesia is considerably longer (often several hours), which is the principal clinical advantage of Bupivacaine Hydrochloride. It is approximately 95% bound to plasma proteins and is metabolized primarily in the liver via amide hydrolysis, with metabolites excreted renally. The elimination half-life in adults is approximately 2.7 hours (systemic absorption) but can be considerably longer depending on the site and technique of administration.

Bupi has the following clinically significant drug interactions:

• Other local anesthetics or structurally related agents (e.g., class I antiarrhythmics such as lidocaine, mexiletine): Concurrent use may produce additive systemic toxic effects on the central nervous system and cardiovascular system; avoid concurrent use where possible and use with caution.
• MAO inhibitors and tricyclic antidepressants (with epinephrine-containing formulations): May cause severe, prolonged hypertension.
• Ergot-type oxytocic drugs (with epinephrine-containing formulations): May cause severe, persistent hypertension or cerebrovascular accidents.
• Nonselective beta-blockers (with epinephrine-containing formulations): May result in severe hypertension and reflex bradycardia.
• Potent general (inhalation) anesthetics: May increase the risk of serious cardiac arrhythmias when epinephrine-containing formulations of Bupi are used.
• Other drugs associated with methemoglobinemia (e.g., nitrates, sulfonamides, certain antimalarials): Concomitant use increases the risk of clinically significant methemoglobinemia.

Most adverse effects of Bupi are dose-related and result from high plasma concentrations due to rapid absorption, inadvertent intravascular injection, or metabolic slowing.

• Common/expected effects of the anesthetic block itself: hypotension, bradycardia, transient numbness, and, with neuraxial blocks, urinary retention.
• Central nervous system: lightheadedness, restlessness, anxiety, tinnitus, blurred vision, tremor, and, at higher levels, seizures, drowsiness, or unconsciousness.
• Cardiovascular: hypotension, bradycardia, arrhythmias, myocardial depression, and, rarely, cardiac arrest (which can be particularly resistant to resuscitation with Bupi).
• Hypersensitivity reactions: urticaria, pruritus, angioedema, and rarely anaphylaxis.
• Other: nausea and vomiting, backache (with neuraxial techniques), and methemoglobinemia (uncommon, but a recognized risk).

Bupi should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus, and only under the supervision of an experienced clinician. It is specifically contraindicated for obstetric paracervical block, and the 0.75% concentration must never be used for obstetric epidural anesthesia. Bupi readily crosses the placenta; fetal heart rate should be monitored continuously during epidural administration in labor, and the mother should be positioned to avoid aortocaval compression. There are no adequate and well-controlled human studies; animal studies have shown adverse fetal effects at doses associated with maternal toxicity.

Small amounts of Bupi are excreted in breast milk. It should be used with caution in breastfeeding women, and a physician should be consulted regarding the timing of breastfeeding relative to administration.

BOXED WARNING: Cardiac arrest with difficult resuscitation, or death, has occurred during use of Bupi for epidural anesthesia in obstetric patients, most often reported with the 0.75% concentration following inadvertent intravascular injection. The 0.75% concentration is contraindicated for obstetric epidural anesthesia. Resuscitative equipment, oxygen, and other resuscitation drugs must be immediately available whenever Bupi is administered for major nerve blocks.

• Systemic toxicity: Accidental intravascular injection of Bupi can cause severe central nervous system toxicity (seizures) and cardiovascular toxicity (arrhythmias, myocardial depression, cardiac arrest) that may be resistant to standard resuscitation; lipid emulsion therapy should be immediately available and administered per local anesthetic systemic toxicity (LAST) protocols if this occurs. Careful aspiration and incremental dosing are essential.
• Trained personnel required: Bupi should be administered only by, or under the supervision of, personnel trained in the diagnosis and management of dose-related and local anesthetic systemic toxicity, with continuous monitoring of cardiovascular and respiratory status and level of consciousness after each injection.
• Methemoglobinemia: Cases have been reported with local anesthetic use; patients with glucose-6-phosphate dehydrogenase deficiency, congenital or acquired methemoglobinemia, cardiac or pulmonary compromise, and infants under 6 months are at increased risk.
• Chondrolysis: Intra-articular continuous infusion of local anesthetics, including Bupi, is not an approved use and has been associated with chondrolysis, predominantly in the shoulder joint.
• Hepatic impairment: Patients with severe liver disease may be at greater risk of developing toxic plasma concentrations because of reduced metabolism of Bupi.
• Cardiac conduction disturbances/hypovolemia: Use with caution in patients with heart block, severe cardiac disease, or hypovolemia, as these patients may be less able to compensate for the physiologic effects of the block.
• Maximum recommended doses must be strictly observed and adjusted for patient age, weight, physical condition, and site of injection.

Overdosage or inadvertent intravascular injection of Bupi can rapidly produce signs of systemic toxicity, including circumoral numbness, tinnitus, dizziness, restlessness, tremors progressing to seizures, followed by drowsiness, unconsciousness, respiratory depression or arrest, and cardiovascular collapse (hypotension, bradycardia, arrhythmias, or cardiac arrest). This is a medical emergency requiring immediate medical attention. Management includes securing the airway, administering 100% oxygen, controlling seizures, and providing advanced cardiac life support, including lipid emulsion therapy for severe local anesthetic systemic toxicity; resuscitation may need to be prolonged. Anyone who suspects an overdose or toxic reaction to Bupi should seek emergency medical care or contact a poison control center immediately; do not attempt to manage a suspected overdose at home.

Store at room temperature (below 30°C), protected from light and freezing, and away from moisture. Do not use if the solution is discolored or contains particulate matter. Keep out of reach of children.

Pediatric use: The safety and efficacy of Bupi in children younger than 12 years have not been established for most indications, and its use in this age group is generally not recommended pending further clinical experience; when used off-label in younger children (e.g., caudal blocks in specialized settings), doses must be carefully calculated on a weight basis by clinicians experienced in pediatric regional anesthesia.

Elderly and debilitated patients: Use with caution; reduced doses may be required due to altered pharmacokinetics and increased sensitivity to systemic toxicity.

Hepatic impairment: Use with caution and consider dose reduction, as impaired metabolism may increase the risk of toxic plasma levels of Bupi.

Renal impairment: No specific dose adjustment is established, but caution is warranted since metabolites are renally excreted.

Cardiac disease: Use with caution in patients with heart block or severe cardiovascular disease.

Amide-type local anesthetic.

Category C (per legacy FDA pregnancy categories); contraindicated for obstetric paracervical block, and the 0.75% concentration is contraindicated for obstetric epidural anesthesia.

The safety and efficacy of Bupi in pediatric patients younger than 12 years have not been formally established for most indications, and its routine use in this age group is generally not recommended. In specialized pediatric anesthesia practice, Bupi is sometimes used off-label (e.g., caudal epidural block) with careful, weight-based dosing under the supervision of clinicians experienced in pediatric regional anesthesia, given the increased risk of systemic toxicity in this population.