LIDOCAINE HYDROCHLORIDE AND EPINEPHRINE
Clinical safety rating: safe
Beta-blockers may increase the risk of lidocaine toxicity Can cause CNS toxicity (seizures) and cardiovascular collapse.
Lidocaine is a sodium channel blocker that stabilizes neuronal membranes and inhibits action potentials, providing local anesthesia. Epinephrine is an alpha- and beta-adrenergic agonist that causes vasoconstriction, prolonging lidocaine's effect and reducing systemic absorption.
| Metabolism | Lidocaine is primarily metabolized by CYP1A2 and, to a lesser extent, CYP3A4, forming active metabolites monoethylglycinexylidide (MEGX) and glycinexylidide (GX). Epinephrine is metabolized by catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO). |
| Excretion | Lidocaine is primarily metabolized in the liver; approximately 90% of a dose is excreted in the urine as metabolites (including monoethylglycinexylidide and glycinexylidide), with less than 10% excreted unchanged. Epinephrine is metabolized by catechol-O-methyltransferase and monoamine oxidase, with metabolites excreted in urine. |
| Half-life | Lidocaine: terminal elimination half-life is approximately 1.5–2.0 hours. With continuous infusion or hepatic impairment, half-life may be prolonged (up to 4–6 hours). Epinephrine: plasma half-life is about 2–3 minutes due to rapid uptake and metabolism. |
| Protein binding | Lidocaine: approximately 60–80% bound to plasma proteins, primarily alpha-1-acid glycoprotein. Epinephrine: negligible protein binding (<5%). |
| Volume of Distribution | Lidocaine: Vd is approximately 1.0–1.5 L/kg, indicating extensive distribution into tissues. Epinephrine: Vd is about 0.2–0.4 L/kg, reflecting limited extravascular distribution. |
| Bioavailability | Lidocaine: oral bioavailability is low (approximately 30–35%) due to extensive first-pass hepatic metabolism. For local infiltration or nerve block, bioavailability is virtually 100% at the site. Intramuscular: 70–80%. Epinephrine: not administered orally; bioavailability after subcutaneous or intramuscular injection is nearly 100%. |
| Onset of Action | Lidocaine (local anesthesia): infiltration – 2–5 minutes; peripheral nerve block – 5–15 minutes; epidural – 5–15 minutes; intravenous (for arrhythmia) – 45–90 seconds. Epinephrine: vasoconstriction occurs within 1–2 minutes after local injection. |
| Duration of Action | Lidocaine: infiltration – 0.5–2 hours; peripheral nerve block – 1–3 hours; epidural – 1–2 hours. With epinephrine, duration is prolonged by approximately 50–100% due to vasoconstriction. Epinephrine: vasoconstriction lasts 1–3 hours after local injection. |
| Molecular Weight | Lidocaine HCl: 270.80 Da; Epinephrine: 183.20 Da |
Local anesthesia: 1% or 2% solution with epinephrine 1:100,000 or 1:200,000; maximum dose 7 mg/kg lidocaine (500 mg) in adults; administer by infiltration or nerve block, not to exceed 1 hour between doses.
| Dosage form | INJECTABLE |
| Renal impairment | No specific dose adjustment required for lidocaine; epinephrine is not renally cleared. However, monitor for accumulation in severe renal impairment (GFR <30 mL/min) as metabolites may accumulate. |
| Liver impairment | Lidocaine undergoes extensive hepatic metabolism. In Child-Pugh Class B or C, reduce dose by 50% and monitor for toxicity. Maximum dose should not exceed 3 mg/kg (200 mg) in severe hepatic impairment. |
| Pediatric use | Infiltration anesthesia: maximum dose 4.5 mg/kg of lidocaine with epinephrine, not to exceed 7 mg/kg. Use lower concentrations (0.5-1%) to minimize toxicity. Administer as a single dose. |
| Geriatric use | Elderly patients may have reduced hepatic function and increased sensitivity. Use lower doses (e.g., 50-70% of adult dose) and titrate carefully. Maximum dose 4.5 mg/kg (300 mg) with epinephrine. |
| 1st trimester | Lidocaine with epinephrine: Use only if clearly needed. Lidocaine crosses placenta; epinephrine may reduce uteroplacental blood flow. No known teratogenicity in animal studies, but human data limited. |
| 2nd trimester | Similarly, use if benefits outweigh risks. Higher doses may cause fetal bradycardia or acidosis due to epinephrine. |
| 3rd trimester | Avoid near term or during labor: epinephrine can delay labor or cause uterine vasoconstriction. Lidocaine can accumulate in fetus. |
Clinical note
Beta-blockers may increase the risk of lidocaine toxicity Can cause CNS toxicity (seizures) and cardiovascular collapse.
| FDA category | Animal |
| Placental transfer | Lidocaine: extensive placental transfer, with fetal/maternal ratio ~0.5-0.7. Epinephrine: limited placental transfer due to metabolism, but may affect uterine blood flow. |
■ FDA Black Box Warning
Not for use in obstetrical paracervical block with certain preparations due to fetal bradycardia; not for intravenous regional anesthesia (Bier block) with lidocaine with epinephrine due to risk of cuff failure and systemic toxicity.
| Common Effects | ventricular arrhythmias |
| Serious Effects |
Hypersensitivity to lidocaine, epinephrine, or amide-type local anestheticsSevere hypertension or preeclampsia (epinephrine may worsen)Cerebrovascular insufficiencyConcurrent use of MAOIs or tricyclic antidepressants (within 14 days) due to hypertensive crisesSevere hypotensionCardiac conduction disturbances (e.g., Stokes-Adams syndrome, Wolff-Parkinson-White syndrome) if risk of arrhythmiaShockSevere bradycardiaPeripheral vascular disease or compromised blood flow (risk of ischemia)
| Precautions | Risk of local anesthetic systemic toxicity (LAST), including CNS and cardiac effects, Avoid inadvertent intravascular injection; use aspiration and slow incremental dosing, Use with caution in patients with hepatic impairment, severe hypertension, cardiac disease, or hyperthyroidism, May cause methemoglobinemia in rare cases |
Loading safety data…
| Breastfeeding | Lidocaine is excreted into breast milk in small amounts (milk:plasma ratio ~0.4-0.6). Oral bioavailability in infants is low. Epinephrine is rapidly metabolized and not expected to reach significant levels. However, use caution with repeated high doses or if infant has hepatic impairment. |
| Lactation Rating | L2 (Limited data - probably compatible) |
| Teratogenic Risk | Lidocaine: Pregnancy Category B. Epidural or local use not associated with major congenital malformations. Epinephrine: High doses may reduce uteroplacental blood flow; avoid paracervical block in first and second trimesters. Risk of uterine hypertonus and fetal hypoxia with inadvertent intravascular administration. |
| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and signs of systemic toxicity (e.g., CNS depression, arrhythmias). Fetal heart rate monitoring during labor. Observe for neonatal bradycardia or CNS effects post-delivery. |
| Fertility Effects | No evidence of adverse effects on fertility in humans. Animal studies with lidocaine and epinephrine at clinical doses show no impairment. |
| Food/Dietary | No specific food interactions. Maintain normal hydration to facilitate excretion. |
| Clinical Pearls | Lidocaine with epinephrine prolongs local anesthesia and reduces systemic absorption. Max dose: lidocaine 7 mg/kg with epinephrine, 4.5 mg/kg without. Avoid in areas with end arterioles (digits, penis, nose, ears) due to vasoconstriction risk. Use cautiously in patients with cardiovascular disease, hypertension, or thyrotoxicosis. Epinephrine can cause tachycardia and hypertension. Do not use in patients taking MAOIs or tricyclic antidepressants due to enhanced vasopressor effects. Check for allergies to amide anesthetics. Aspiration before injection prevents intravascular administration. |
| Patient Advice | Notify your doctor if you have heart disease, high blood pressure, thyroid problems, or are taking MAO inhibitors or antidepressants. · Avoid driving or operating machinery until numbness resolves. · Do not apply heat to the injection site as it may increase absorption and systemic effects. · Report any signs of allergic reaction such as rash, itching, swelling, or difficulty breathing. · Inform your dentist or doctor of all medications you are taking, including over-the-counter drugs and herbal supplements. |