BUPIVACAINE HYDROCHLORIDE AND 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, inhibiting nerve impulse conduction. Epinephrine is a vasoconstrictor that prolongs bupivacaine's effect by reducing vascular absorption.
| Metabolism | Bupivacaine is metabolized primarily in the liver via CYP1A2 and CYP3A4 to pipecoloxylidine. Epinephrine is metabolized by catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO). |
| Excretion | Bupivacaine is primarily metabolized in the liver via CYP3A4 and is excreted renally as metabolites (approximately 95% in urine) and less than 5% unchanged. Epinephrine is rapidly metabolized by COMT and MAO and excreted renally as metabolites. |
| Half-life | Terminal elimination half-life of bupivacaine is approximately 2.7 hours (range 1.5–5.5 hours) in adults. In neonates, half-life is prolonged (8–12 hours) due to immature hepatic function. The half-life of epinephrine is very short (~1–2 minutes) due to rapid metabolism. |
| Protein binding | Bupivacaine is highly protein-bound (approximately 95%) primarily to alpha-1-acid glycoprotein (AAG) and albumin. Epinephrine is bound to AAG (30–40%) and albumin (10–20%). |
| Volume of Distribution | Bupivacaine Vd is 0.5–1.0 L/kg. Higher Vd in neonates (1.5–2.0 L/kg) due to increased body fat and decreased protein binding. Epinephrine Vd is 0.2–0.4 L/kg. |
| Bioavailability | Bupivacaine: Epidural: 100% (bypasses first-pass). Peripheral nerve block: 100%. Intrathecal: 100%. Oral: <10% due to extensive first-pass metabolism. Epinephrine: Bioavailability is 100% for parenteral routes; oral is negligible due to gastrointestinal and hepatic metabolism. |
| Onset of Action | Epidural: 5–15 minutes for surgical anesthesia. Peripheral nerve block: 10–20 minutes for motor block. Intrathecal: immediately to 5 minutes. Subcutaneous infiltration: 2–10 minutes. |
| Duration of Action | Epidural: 2–4 hours for sensory anesthesia, up to 6 hours with epinephrine. Peripheral nerve block: 4–8 hours (up to 12 hours with epinephrine). Intrathecal: 1.5–3 hours. Epinephrine prolongs duration by 30–50% via local vasoconstriction. |
Maximum dose of bupivacaine: 2 mg/kg (not to exceed 175 mg); with epinephrine: 3 mg/kg (not to exceed 225 mg). Administer via local infiltration, peripheral nerve block, epidural, or caudal block. Dose depends on the anesthetic procedure. Repeated doses may be given at intervals of 3-6 hours. Maximum single dose for epidural: 50 mg initially, then 10-25 mg per segment as needed.
| Dosage form | INJECTABLE |
| Renal impairment | No specific dose adjustment for bupivacaine is recommended for renal impairment. Use with caution in severe renal failure (GFR <15 mL/min) due to potential accumulation of metabolites. |
| Liver impairment | For Child-Pugh A: no adjustment. Child-Pugh B: reduce total dose by 25-50%. Child-Pugh C: contraindicated or use with extreme caution with significant dose reduction (e.g., 50-75% reduction) and close monitoring. |
| Pediatric use | For children >12 years, same as adult. For children ≤12 years, weight-based dosing: bupivacaine without epinephrine: 0.5-1 mg/kg; with epinephrine: 1-2 mg/kg. Maximum single dose: without epinephrine: 2 mg/kg; with epinephrine: 3 mg/kg. Administer by infiltration or regional block. Not recommended in infants <12 months. |
| Geriatric use | Reduce dose by 25-50% in elderly patients due to increased sensitivity and reduced clearance. Lower concentrations (e.g., 0.25%) may be used. Monitor for cardiotoxic effects. Use minimal effective dose. |
| 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. The milk-to-plasma (M/P) ratio is approximately 0.3-0.5. Epinephrine is poorly excreted and rapidly metabolized. The American Academy of Pediatrics considers bupivacaine compatible with breastfeeding. However, observe infant for signs of local anesthetic toxicity (e.g., irritability, apnea) if used repeatedly. |
| Teratogenic Risk |
■ FDA Black Box Warning
Risk of cardiac arrest and severe hypotension when used for epidural anesthesia in obstetrics; risk of severe neurologic injury (e.g., cauda equina syndrome) with continuous spinal anesthesia.
| Common Effects | cardiac arrest |
| Serious Effects |
Hypersensitivity to bupivacaine or epinephrine; severe hypotension; cardiogenic shock; use in intravenous regional anesthesia (Bier block) due to risk of toxicity; concomitant use with MAOIs or tricyclic antidepressants due to hypertensive crisis.
| Precautions | Risk of systemic toxicity (CNS and cardiovascular) with accidental intravascular injection; use with caution in patients with hepatic disease, severe hypertension, or cardiovascular disease; avoid in patients with arrhythmias or hypotension. |
| Food/Dietary |
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| Bupivacaine with epinephrine is classified as FDA Pregnancy Category C. Animal studies have shown adverse fetal effects at high doses, but no adequate human studies exist. First trimester: Risk cannot be ruled out; use only if clearly needed. Second/third trimester: May cause fetal bradycardia and acidosis if absorbed systemically, especially with paracervical block. Avoid use during delivery due to potential for neonatal depression and reduced uterine blood flow from epinephrine. |
| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and respiratory status continuously. For regional anesthesia, assess for signs of systemic toxicity (e.g., perioral numbness, tinnitus, seizures). Fetal heart rate monitoring is recommended, especially during paracervical block, due to risk of bradycardia. Observe neonate for respiratory depression and hypotonia if used near delivery. |
| Fertility Effects | In animal studies, bupivacaine did not impair fertility at clinically relevant doses. Epinephrine at high doses may cause uterine vasoconstriction and reduce implantation rates, but no human data indicate adverse effects on fertility with standard use. |
| No significant food interactions. Avoid alcohol consumption until effects of anesthesia have worn off to prevent dizziness or syncope. |
| Clinical Pearls | Bupivacaine-epinephrine combination provides prolonged local anesthesia with vasoconstriction. Maximum dose: bupivacaine 2 mg/kg (3 mg/kg with epinephrine). Avoid in paracervical block (0.25% bupivacaine with epinephrine) due to risk of fetal bradycardia. Contraindicated in severe hypotension, hypovolemia, or concurrent MAOI use. Do not use in patients with sulfite allergy (bisulfite preservative). Epinephrine concentration is 1:200,000 (5 mcg/mL). |
| Patient Advice | Report any signs of allergic reaction: hives, difficulty breathing, swelling of face/lips/tongue. · Numbness may last several hours; avoid chewing or testing the anesthetized area with hot objects. · If you experience chest pain, palpitations, severe headache, or shortness of breath after injection, seek immediate medical attention. · Do not drive or operate machinery until sensation fully returns. · Tell your doctor if you have high blood pressure, heart disease, thyroid problems, or are taking MAO inhibitors or tricyclic antidepressants. |