MARCAINE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MARCAINE (MARCAINE).
Bupivacaine blocks sodium ion channels in nerve cell membranes, inhibiting the generation and propagation of action potentials, resulting in local anesthesia.
| Metabolism | Hepatic via conjugation with glucuronic acid; major metabolite is 2,6-pipecoloxylidide (PPX). Involves CYP3A4 and CYP1A2 enzymes. |
| Excretion | Renal excretion of metabolites (approximately 90-95% as para-aminobenzoic acid and other metabolites); less than 5% unchanged in urine. Biliary/fecal excretion is minimal. |
| Half-life | Terminal elimination half-life: 2.5-4 hours in adults (longer in neonates and hepatic impairment; up to 8-12 hours). Clinically, accumulation occurs with continuous infusion or repeated doses. |
| Protein binding | Approximately 95% bound to alpha-1-acid glycoprotein (AAG) and, to a lesser extent, albumin. Binding is concentration-dependent and saturable. |
| Volume of Distribution | Volume of distribution (Vd): 0.8-1.5 L/kg. This large Vd indicates extensive tissue distribution, particularly to highly perfused organs. Lower Vd in neonates (~0.6 L/kg) and elderly. |
| Bioavailability | Oral: negligible (<5%) due to extensive first-pass metabolism; Intravenous: 100%; Epidural: nearly 100% systemic absorption over time; Topical: minimal (not available as topical formulation). |
| Onset of Action | Infiltration: 2-10 minutes; Epidural: 15-25 minutes; Caudal: 5-15 minutes; Peripheral nerve block: 10-20 minutes; Intrathecal: immediate to 5 minutes. |
| Duration of Action | Infiltration: 2-4 hours (with epinephrine: 3-6 hours); Epidural: 1.5-2 hours (with epinephrine: 2-3 hours); Peripheral nerve block: 4-8 hours (with epinephrine: 6-10 hours); Intrathecal: 1-2 hours. Duration is dose-dependent and prolonged with epinephrine. |
| Molecular Weight | 288.43 |
Local infiltration: 0.25-0.5% solution, up to 30 mL; peripheral nerve block: 0.25-0.5% solution, 30-40 mL; epidural: 0.5-0.75% solution, 15-30 mL. Maximum dose: 2 mg/kg (with epinephrine), 1.5 mg/kg (without epinephrine).
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for mild-to-moderate renal impairment. Use with caution in severe renal impairment (eGFR <30 mL/min) due to potential for accumulation of metabolites. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 25-50%; Child-Pugh C: contraindicated or use only if benefit outweighs risk with extreme caution. |
| Pediatric use | Weight-based: 0.5-2 mg/kg for infiltration; maximum single dose 2.5 mg/kg with epinephrine, 2 mg/kg without epinephrine. Not recommended for children under 12 for epidural use. |
| Geriatric use | Elderly patients: reduce dose by 20-30% due to decreased clearance and increased sensitivity; monitor for CNS and cardiac toxicity. |
| 1st trimester | Bupivacaine is classified as FDA Pregnancy Category C. Animal studies have shown an increased risk of fetal harm, but there are no adequate and well-controlled studies in pregnant women. Use only if the potential benefit justifies the potential risk. |
| 2nd trimester | Similar to T1, Category C. May be used for obstetric anesthesia when indicated, but caution is advised due to potential fetal effects. |
| 3rd trimester | Category C. Use in obstetrics is common but monitor for maternal hypotension and fetal bradycardia. Avoid use if signs of uteroplacental insufficiency. |
Clinical note
Comprehensive clinical and safety monograph for MARCAINE (MARCAINE).
| Placental transfer | Bupivacaine readily crosses the placenta, with a maternal-to-fetal ratio of approximately 0.2-0.5. It is highly protein-bound, which may limit transfer, but accumulation in the fetus can occur with repeated doses. |
| Breastfeeding |
■ FDA Black Box Warning
Risk of cardiac arrest and death following unintentional intravascular injection or excessive dosing. Resuscitation may be difficult. Do not use for intravenous regional anesthesia (Bier block).
| Serious Effects |
Hypersensitivity to bupivacaine or any amide-type local anestheticsIntravenous regional anesthesia (Bier block)Severe hypotension or shockPatients with untreated hypotension or hypovolemiaUse in paracervical block in obstetrics (due to risk of fetal bradycardia)Patients with severe conduction abnormalities or advanced heart block
| Precautions | Avoid intravascular injection; use incremental dosing and aspiration, Risk of systemic toxicity (CNS and cardiovascular), Caution in patients with hepatic impairment, Caution in elderly or debilitated patients, May cause methemoglobinemia (especially with higher doses), Chondrolysis risk with intra-articular infusions |
| Food/Dietary | No specific food interactions. Avoid alcohol until effects of anesthesia subside (may increase dizziness). |
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| Bupivacaine is excreted into breast milk in low amounts. The relative infant dose is approximately 0.5-1.5% of the maternal weight-adjusted dose. It is generally considered compatible with breastfeeding, but monitor the infant for signs of local anesthetic toxicity such as irritability or drowsiness. |
| Lactation Rating | L2 (Safer) |
| Teratogenic Risk | FDA Pregnancy Category C. First trimester: No adequate human studies; animal studies show no teratogenicity at doses up to 13 mg/kg SC. Second/third trimesters: Local anesthetics may cause fetal bradycardia and acidosis if high concentrations reach fetus. Not associated with major malformations. Transient neonatal neurobehavioral effects possible after paracervical block. |
| Fetal Monitoring | Monitor maternal ECG, blood pressure, heart rate, respiratory rate, and level of consciousness. Continuous fetal heart rate monitoring during labor epidural or paracervical block. Assess for signs of systemic toxicity: perioral numbness, metallic taste, tinnitus, seizures, arrhythmias. |
| Fertility Effects | No known adverse effects on human fertility. Animal studies at high doses showed no impact on reproductive performance. |
| Clinical Pearls | Marcaing (bupivacaine) is a long-acting amide local anesthetic. Avoid intravascular injection; use incremental dosing and frequent aspiration. Maximum dose: 2 mg/kg (with epinephrine: 3 mg/kg). Risk of cardiotoxicity if inadvertently injected IV; use lipid emulsion 20% (Intralipid) in resuscitation. Duration: 2-4 hours for infiltration, up to 8 hours with epinephrine. Contraindicated in obstetrical paracervical block (fetal bradycardia). |
| Patient Advice | Report any numbness or weakness lasting beyond expected duration. · Seek medical attention for signs of allergic reaction (rash, difficulty breathing, swelling). · Avoid driving or operating machinery until sensation and motor function fully return. · Inform your doctor if you have liver disease, heart block, or are taking antiarrhythmics. · The injection site may be tender; avoid hot baths or strenuous activity until numbness resolves. |