MARCAINE HYDROCHLORIDE W/ EPINEPHRINE
Clinical safety rating: safe
Beta-blockers may antagonize cardiac effects and cause severe hypertension Can cause angina and arrhythmias in patients with heart disease.
Bupivacaine is an amide local anesthetic that blocks sodium channels on neuronal membranes, inhibiting the initiation and propagation of nerve impulses. Epinephrine is a vasoconstrictor that prolongs the duration of action and reduces systemic absorption.
| Metabolism | Bupivacaine is metabolized primarily in the liver via conjugation with glucuronic acid and via CYP3A4-mediated N-dealkylation to pipecolylxylidine. Epinephrine is metabolized by monoamine oxidase and catechol-O-methyltransferase. |
| Excretion | Bupivacaine is metabolized in the liver primarily via CYP3A4 and CYP1A2. Approximately 6% is excreted unchanged in urine. The major metabolite, pipecolylxylidine (PPX), is excreted renally (80–90% of dose) with 2–5% as desbutylbupivacaine. Fecal elimination accounts for <5%. Biliary excretion of metabolites occurs but is minimal. |
| Half-life | Terminal elimination half-life in adults is 2.7–3.4 hours (mean ~3.0 h). In neonates, it is prolonged (8–12 hours) due to immature hepatic function. Clinically, this supports continuous infusion intervals of 6–12 hours for epidural analgesia. |
| Protein binding | ~95% bound to alpha-1-acid glycoprotein (AAG) and, to a lesser extent, albumin. Binding is saturable; increased free fraction in acidosis or low AAG (e.g., neonates, pregnancy). |
| Volume of Distribution | Vd: 0.8–1.3 L/kg (mean ~0.9 L/kg). This indicates extensive tissue distribution, including highly perfused organs (brain, heart, liver). Higher Vd in neonates (~2.0 L/kg). |
| Bioavailability | Bioavailability via epidural administration: ~100% (systemic absorption from the epidural space). Intrathecal: ~100% (but small dose, usually 2–3 mg). Subcutaneous: ~100% (absorption delayed by vasoconstriction). Oral: not available; high first-pass metabolism. |
| Onset of Action | Epidural: 15–30 minutes (sensory block); 20–40 minutes (motor block). Caudal: 15–30 minutes. Peripheral nerve block: 10–20 minutes (e.g., brachial plexus). Subcutaneous infiltration: 2–10 minutes. Intrathecal: 2–5 minutes. |
| Duration of Action | Epidural: 2–4 hours (without epinephrine); extended to 4–6 hours with epinephrine. Peripheral nerve block: 6–12 hours (up to 24 hours with epinephrine). Subcutaneous infiltration: 2–4 hours (with epinephrine: 4–8 hours). Intrathecal: 1–2 hours. |
For local infiltration: 0.25-0.5% solution, up to 30 mL (75-175 mg bupivacaine) with epinephrine 1:200,000, not to exceed 3 mg/kg bupivacaine. For peripheral nerve block: 0.25-0.5% solution, up to 40 mL (100-200 mg). For epidural: 0.5% solution, 10-20 mL (50-100 mg). Maximum single dose: 225 mg with epinephrine.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (GFR >= 30 mL/min). For severe renal impairment (GFR < 30 mL/min): use with caution, reduce dose by 25-50% and monitor for systemic toxicity due to potential accumulation of metabolites. |
| Liver impairment | Child-Pugh Class A: no dose adjustment needed. Child-Pugh Class B: reduce dose by 25-50%. Child-Pugh Class C: avoid use or use with extreme caution, consider alternative local anesthetic. |
| Pediatric use | For infiltration: 0.25-0.5% solution, 0.5-2 mg/kg bupivacaine with epinephrine, maximum single dose 2 mg/kg. For caudal epidural: 0.25-0.5% solution, 1-2 mg/kg. For peripheral nerve block: 0.25-0.5% solution, up to 2 mg/kg. Maximum total dose: 2 mg/kg for children <12 years. |
| Geriatric use | Reduce dose by 20-30% due to decreased clearance and increased sensitivity. Use lower concentrations (0.25-0.375%) and titrate slowly. Maximum dose: 2 mg/kg bupivacaine with epinephrine, not to exceed 150 mg. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Beta-blockers may antagonize cardiac effects and cause severe hypertension Can cause angina and arrhythmias in patients with heart disease.
| FDA category | Animal |
| Breastfeeding | Bupivacaine is excreted into breast milk in small amounts (M/P ratio approximately 0.3). No adverse effects reported in nursing infants. Epinephrine is not orally bioavailable. Use with caution; infant exposure is minimal. |
| Teratogenic Risk | FDA Pregnancy Category C. First trimester: No adequate studies; animal studies show no teratogenicity at clinically relevant doses. Second trimester: No known teratogenic risk from bupivacaine; epinephrine may reduce uterine blood flow. Third trimester: Risk of fetal bradycardia, hypoxia, and acidosis with paracervical block; avoid in obstetric anesthesia due to potential for fetal acidosis and maternal seizures. |
■ FDA Black Box Warning
There have been reports of cardiac arrest and death during use of bupivacaine for epidural anesthesia in obstetrical patients. Resuscitation has been difficult or impossible despite adequate preparation and proper management. Bupivacaine with epinephrine is not recommended for obstetrical paracervical block anesthesia for the same reason.
| Common Effects | cardiac arrest |
| Serious Effects |
["Hypersensitivity to bupivacaine, epinephrine, or any component of the formulation","Severe hypertension or untreated thyrotoxicosis (due to epinephrine component)","Concurrent use with MAO inhibitors or tricyclic antidepressants (due to epinephrine component)","Use for paracervical block in obstetrics (black box warning)","Severe hypotension or cardiogenic shock","Complete heart block or severe conduction disturbances"]
| Precautions | ["Risk of cardiac toxicity, especially with inadvertent intravascular injection","Neurologic damage following spinal or epidural administration","Methemoglobinemia in susceptible patients","Avoid use in patients with severe hypotension or hypovolemia","Use caution in patients with hepatic impairment, as metabolism may be reduced","Increased risk of cardiotoxicity in elderly or debilitated patients","Avoid concurrent use with other local anesthetics or class I antiarrhythmics"] |
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| Fetal Monitoring | Monitor maternal heart rate, blood pressure, ECG, and oxygen saturation. Fetal heart rate monitoring is recommended during obstetric use. Observe for signs of local anesthetic toxicity (e.g., CNS depression, seizures, arrhythmias). |
| Fertility Effects | No evidence of impaired fertility in animal studies. Bupivacaine does not appear to affect spermatogenesis or oogenesis at therapeutic doses. Epinephrine may transiently reduce uterine blood flow but no long-term fertility effects. |