BUPIVACAINE HYDROCHLORIDE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for BUPIVACAINE HYDROCHLORIDE (BUPIVACAINE HYDROCHLORIDE).
Bupivacaine hydrochloride is an amide-type local anesthetic that blocks sodium ion channels in nerve cell membranes, thereby inhibiting the generation and propagation of action potentials and producing reversible local anesthesia.
| Metabolism | Primarily hepatic via conjugation with glucuronic acid; CYP3A4 and CYP1A2 involved in metabolism to pipecoloxylidine and desbutylbupivacaine. |
| Excretion | Primarily hepatic metabolism (CYP3A4, CYP1A2, and amidases) to pipecoloxylidine and desbutylbupivacaine; less than 5% excreted unchanged in urine; negligible biliary/fecal excretion. |
| Half-life | Terminal elimination half-life: 2.7 hours (adults); prolonged in neonates (8.1 hours) and patients with hepatic impairment; clinical context: half-life increases with repeated dosing due to accumulation. |
| Protein binding | Approximately 95% bound to alpha-1-acid glycoprotein (AAG) and albumin; binding is concentration-dependent and decreases in acidosis. |
| Volume of Distribution | Vd: 0.73 L/kg (range 0.5-1.0 L/kg) in adults; reflects extensive tissue binding; lower in neonates (0.3-0.6 L/kg) due to reduced adipose tissue. |
| Bioavailability | Not applicable for intravenous use; epidural: ~100% (systemic absorption from epidural space); peripheral nerve block: variable (systemic absorption depends on site and dose); oral: negligible (<5%) due to extensive first-pass metabolism. |
| Onset of Action | Epidural: 15-25 minutes; Peripheral nerve block: 15-30 minutes; Intrathecal: 5-10 minutes; Infiltration: 2-10 minutes. |
| Duration of Action | Epidural: 2-4 hours (with epinephrine up to 6 hours); Peripheral nerve block: 4-12 hours; Intrathecal: 2-3 hours; Infiltration: 2-4 hours; prolonged with epinephrine due to vasoconstriction. |
0.25% to 0.5% solution infiltrated locally, up to 175 mg (without epinephrine) or 225 mg (with epinephrine 1:200,000) per dose; maximum 400 mg per 24 hours. For epidural: 0.5% to 0.75% solution, 15-20 mL for surgical anesthesia.
| Dosage form | INJECTABLE |
| Renal impairment | No specific dose adjustment required for GFR >30 mL/min. For GFR 10-30 mL/min: use with caution, reduce dose by 25% and monitor for toxicity. For GFR <10 mL/min: avoid or reduce dose by 50% with close monitoring. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 25-50%. Child-Pugh C: contraindicated or use minimal effective dose with extreme caution. |
| Pediatric use | Infants and children: 0.25-0.5% solution, maximum 2 mg/kg (without epinephrine) or 3 mg/kg (with epinephrine), not to exceed 175 mg total. |
| Geriatric use | Elderly patients: reduce dose by 25-50% due to decreased clearance and increased sensitivity; consider lower concentrations and volumes; avoid rapid infusion. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for BUPIVACAINE HYDROCHLORIDE (BUPIVACAINE HYDROCHLORIDE).
| Breastfeeding | Bupivacaine is excreted into breast milk in small amounts. The milk-to-plasma (M/P) ratio is approximately 0.30. It is considered compatible with breastfeeding; however, monitor infant for signs of local anesthetic toxicity such as drowsiness or irritability. |
| Teratogenic Risk | Bupivacaine is classified as FDA Pregnancy Category C. In first trimester, no well-controlled studies; animal studies have shown potential for fetal toxicity at high doses. Second and third trimesters: risk of fetal bradycardia and acidosis due to placental transfer. Epidural use may cause maternal hypotension reducing uteroplacental perfusion. Avoid paracervical block in pregnancy due to risk of fetal bradycardia. |
■ FDA Black Box Warning
Risk of cardiac arrest and death following unintended intravenous injection or administration of high doses; resuscitation may be difficult and prolonged.
| Serious Effects |
["Hypersensitivity to bupivacaine or other amide anesthetics","Severe hypotension (e.g., hypovolemic shock)","Inflammation or sepsis at injection site","Paracervical block in obstetrics (associated with fetal bradycardia)","Use for intravenous regional anesthesia (Bier block)"]
| Precautions | ["Risk of systemic toxicity if injected intravascularly","Use with caution in patients with hepatic impairment","Avoid for spinal anesthesia when high doses are needed due to neurotoxicity risk","Monitor for signs of CNS and cardiovascular toxicity","Use in pregnant women only if clearly needed (Category C)"] |
| Food/Dietary | No known food interactions. Grapefruit juice may affect hepatic metabolism via CYP3A4 inhibition, but clinical significance is minimal. Maintain normal diet. |
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| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and oxygen saturation. Fetal heart rate monitoring during epidural or spinal anesthesia. Assess for signs of local anesthetic systemic toxicity (LAST): perioral numbness, tinnitus, metallic taste, seizures, cardiac arrhythmias. Watch for maternal hypotension and treat promptly to maintain uteroplacental perfusion. |
| Fertility Effects | No known direct adverse effects on fertility in humans. Animal studies have not shown impaired fertility at clinically relevant doses. However, any prolonged opioid or anesthetic exposure may affect reproductive hormones indirectly. |
| Clinical Pearls | Bupivacaine is a long-acting amide local anesthetic. Maximum single dose is 2.5 mg/kg (with epinephrine 3 mg/kg). Cardiotoxicity is greater than lidocaine; avoid intravascular injection. Use with caution in hepatic impairment. For labor analgesia, 0.0625-0.125% with fentanyl is common. Adding epinephrine prolongs duration and reduces peak plasma concentration. |
| Patient Advice | Report any numbness or tingling beyond expected area of anesthesia. · Seek immediate medical attention if you experience ringing in ears, metallic taste, dizziness, or seizures. · Inform your healthcare provider if you have liver disease or are taking antiarrhythmics. · Avoid driving or operating machinery until full sensation returns. · Do not apply heat or cold to the numb area to prevent burns or frostbite. |