MARCAINE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for MARCAINE (MARCAINE).

How it works

Bupivacaine blocks sodium ion channels in nerve cell membranes, inhibiting the generation and propagation of action potentials, resulting in local anesthesia.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for MARCAINE (MARCAINE).

Breastfeeding	Excreted in breast milk in very low amounts; M/P ratio approximately 0.2-0.4. Oral bioavailability poor in infants. Considered compatible with breastfeeding; monitor for infant drowsiness, irritability.
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.

Warnings & precautions

■ 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).

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to bupivacaine or other amide anesthetics","Intravenous regional anesthesia (Bier block)","Severe hypotension or shock","Local infection at injection site","Severe coagulation disorders"]

Clinical Precautions

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"]

Clinical Tips & Counseling

Drug interactions

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MARCAINE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for MARCAINE (MARCAINE).

How it works

Bupivacaine blocks sodium ion channels in nerve cell membranes, inhibiting the generation and propagation of action potentials, resulting in local anesthesia.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for MARCAINE (MARCAINE).

Breastfeeding	Excreted in breast milk in very low amounts; M/P ratio approximately 0.2-0.4. Oral bioavailability poor in infants. Considered compatible with breastfeeding; monitor for infant drowsiness, irritability.
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.

Warnings & precautions

■ 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).