BUPIVACAINE HYDROCHLORIDE KIT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for BUPIVACAINE HYDROCHLORIDE KIT (BUPIVACAINE HYDROCHLORIDE KIT).
Bupivacaine is an amide-type local anesthetic that blocks sodium channels in neuronal cell membranes, inhibiting the propagation of action potentials and thus producing local anesthesia and analgesia.
| Metabolism | Primarily hepatic metabolism via CYP3A4 and CYP1A2, forming pipecoloxylidine and desbutylbupivacaine. |
| Excretion | Primarily hepatic metabolism (approx. 95%) to metabolites (e.g., pipecoloxylidine, desbutylbupivacaine); less than 5% excreted unchanged in urine. Biliary/fecal elimination accounts for a minor fraction. Renal clearance of unchanged drug is about 2-6%. |
| Half-life | Terminal elimination half-life is 2.7 to 3.5 hours in adults, prolonged in neonates (8-14 hours) and patients with hepatic impairment. Clinically, this supports intermittent dosing or continuous infusion monitoring. |
| Protein binding | Approximately 95% bound primarily to alpha-1-acid glycoprotein (AAG) and, to a lesser extent, albumin. Binding is more extensive in adults (95%) than in neonates (80-85%). |
| Volume of Distribution | Volume of distribution at steady state (Vdss) is 0.8-1.1 L/kg, indicating moderate distribution into tissues. Higher Vd in neonates (2.0-2.5 L/kg). |
| Bioavailability | Not applicable for intravenous use (100% bioavailable). Epidural: nearly 100% due to absorption; Peripheral nerve block: highly variable but typically >90% systemic absorption. Oral bioavailability is low (~30-40%) due to extensive first-pass metabolism. |
| Onset of Action | Epidural: 5-10 minutes; Intrathecal: rapid (1-5 minutes); Peripheral nerve block: 10-20 minutes; Local infiltration: 2-5 minutes. |
| Duration of Action | Epidural: 2-4 hours (with epinephrine: 3-6 hours); Peripheral nerve block: 3-8 hours (varies by technique, dose, and use of epinephrine); Intrathecal: 1.5-2 hours. Duration is dose-dependent and prolonged by vasoconstrictors. |
| Molecular Weight | 342.9 |
0.25% to 0.5% solution administered via epidural, peripheral nerve block, or local infiltration; maximum single dose 175 mg (without epinephrine) or 225 mg (with epinephrine 1:200,000); may repeat every 3-6 hours as needed, not to exceed 400 mg in 24 hours.
| Dosage form | INJECTABLE |
| Renal impairment | No specific dose adjustment required for GFR >30 mL/min; use with caution in severe renal impairment (GFR <30 mL/min) due to potential accumulation of metabolites, consider reducing dose or increasing interval. |
| Liver impairment | Child-Pugh Class A: no adjustment; Class B: reduce dose by 50% and monitor for toxicity; Class C: contraindicated or use only if benefits outweigh risks with extreme caution and reduced dose (e.g., 25% of normal). |
| Pediatric use | Neonates and infants: 0.1-0.2 mL/kg of 0.25% solution for caudal block (max 2 mg/kg); children: 0.25-0.5% solution for local infiltration, max 2 mg/kg (with epinephrine 3 mg/kg); not recommended for intravenous regional anesthesia. |
| Geriatric use | Elderly patients (≥65 years) may require reduced doses due to decreased clearance and increased sensitivity; consider a 20-25% reduction in maximum dose and avoid repeated administration without careful monitoring of CNS and cardiovascular effects. |
| 1st trimester | Bupivacaine crosses the placenta. No well-controlled studies in first trimester; use only if clearly needed. Risk of fetal bradycardia and acidosis with high doses. |
| 2nd trimester | Use with caution. May cause fetal bradycardia; monitor fetal heart rate. Avoid paracervical block in second trimester due to risk of fetal bradycardia. |
| 3rd trimester | Use with caution near term. May cause neonatal respiratory depression, bradycardia, and neurobehavioral effects. Avoid high doses. |
Clinical note
Comprehensive clinical and safety monograph for BUPIVACAINE HYDROCHLORIDE KIT (BUPIVACAINE HYDROCHLORIDE KIT).
| Placental transfer | Rapidly crosses placenta; fetal/maternal ratio approximately 0.2-0.4. Protein binding (95%) limits transfer but fetal acidosis may increase trapping. |
| Breastfeeding | Excreted into breast milk in low amounts; unlikely to cause adverse effects in infants. Use with caution, especially with prolonged or high-dose maternal therapy. |
■ FDA Black Box Warning
Risk of cardiac arrest and death following inadvertent intravascular injection, particularly in elderly patients and those with preexisting cardiac disease. Use of bupivacaine in obstetric paracervical block is contraindicated due to fetal bradycardia and death.
| Serious Effects |
Known hypersensitivity to bupivacaine or other amide anestheticsSevere hypotension or shockInfectious or inflammatory conditions at injection siteSevere bleeding diathesis or coagulopathy (e.g., thromboplastin time >1.5 times normal)Severe hepatic impairment (e.g., decompensated cirrhosis)Intravenous regional anesthesia (Bier block) with bupivacaine 0.5%Paracervical block in obstetrics (risk of fetal bradycardia)
| Precautions | Avoid intravascular injection; aspirate before injection to prevent accidental intravascular administration., Monitor for signs of systemic toxicity (CNS excitation, respiratory depression, cardiac arrhythmias)., Use with caution in patients with hepatic impairment, as metabolism may be reduced., May cause cardiac conduction abnormalities with high doses., Epidural injection may result in inadvertent subarachnoid injection leading to high spinal anesthesia., Risk of methemoglobinemia, especially in patients with glucose-6-phosphate dehydrogenase deficiency. |
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| Lactation Rating | L2 - Safer |
| Teratogenic Risk | Bupivacaine is classified as FDA Pregnancy Category C. Animal studies have shown adverse effects on fetal development at doses 9-16 times the human dose, with increased rates of fetal mortality and skeletal anomalies. In humans, no well-controlled studies exist; however, local anesthetics of the amide type can cross the placenta. Use in the first trimester is generally avoided unless benefits outweigh risks. During the second and third trimesters, close monitoring for fetal bradycardia and acidosis is recommended due to potential for high maternal plasma levels. Paracervical block with bupivacaine has been associated with fetal bradycardia. |
| Fetal Monitoring | Continuous maternal monitoring for signs of systemic toxicity (e.g., hypotension, arrhythmias, seizures) is required. Fetal heart rate monitoring should be performed throughout administration, especially during epidural or paracervical block, to detect fetal bradycardia or distress. Assess maternal vital signs (blood pressure, heart rate, oxygen saturation) frequently. Monitor for signs of local anesthetic systemic toxicity (LAST). |
| Fertility Effects | No significant adverse effects on fertility have been reported in animal studies at clinically relevant doses. Bupivacaine is not known to impair fertility in humans. However, high doses of local anesthetics may transiently affect sperm motility or ovarian function, but data are limited and not dose-dependent. |
| Food/Dietary | No known food interactions. Grapefruit juice may theoretically increase bupivacaine levels due to CYP3A4 inhibition, but clinical significance is minimal. Avoid alcohol consumption as it may exacerbate CNS side effects. |
| Clinical Pearls | Bupivacaine hydrochloride is a long-acting amide local anesthetic. Maximum single dose should not exceed 2.5 mg/kg (175 mg for a 70 kg patient) to avoid CNS and cardiovascular toxicity. Epinephrine-containing solutions can prolong duration and reduce systemic absorption but are contraindicated in digital blocks. Use with caution in hepatic impairment and elderly patients. Resuscitation equipment and lipid emulsion (Intralipid 20%) must be immediately available for management of local anesthetic systemic toxicity (LAST). |
| Patient Advice | Avoid driving or operating machinery until numbness resolves. · Report any signs of allergic reaction such as rash, swelling, or difficulty breathing. · Do not apply heat or cold directly to the numbed area. · Seek immediate medical attention if you experience blurred vision, ringing in ears, metallic taste, or seizures. · Inform your doctor if you have liver disease, heart problems, or are pregnant/breastfeeding. |