PRILOCAINE HYDROCHLORIDE AND EPINEPHRINE BITARTRATE
Clinical safety rating: safe
Beta-blockers may antagonize cardiac effects and cause severe hypertension Can cause angina and arrhythmias in patients with heart disease.
Prilocaine is an amide local anesthetic that blocks sodium channels in neuronal cell membranes, inhibiting nerve impulse propagation. Epinephrine is a vasoconstrictor that prolongs local anesthetic action by reducing systemic absorption.
| Metabolism | Prilocaine is metabolized primarily in the liver by amidases; its major metabolite, o-toluidine, can cause methemoglobinemia. Epinephrine is metabolized by catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO). |
| Excretion | Renal excretion of metabolites (prilocaine metabolites: o-toluidine and 4-hydroxy-2-methylaniline, ~85%); epinephrine metabolites (metanephrine, vanillylmandelic acid) excreted renally; <5% excreted unchanged in urine; minimal biliary/fecal elimination (<2%). |
| Half-life | Prilocaine: terminal elimination half-life ~10–15 minutes (alpha phase) and 1.5–2 hours (beta phase); in hepatic impairment or methemoglobinemia, half-life prolonged (up to 3–4 hours). Epinephrine: short half-life ~2–3 minutes due to rapid uptake and metabolism. |
| Protein binding | Prilocaine: ~55% bound to plasma proteins (primarily alpha-1-acid glycoprotein and albumin). Epinephrine: ~50–60% bound to albumin and low-affinity binding to alpha-2-macroglobulin. |
| Volume of Distribution | Prilocaine: Vd ~0.9–1.7 L/kg (indicates extensive tissue distribution; larger in children). Epinephrine: Vd ~0.5–0.9 L/kg (limited to extracellular fluid). |
| Bioavailability | Prilocaine: 100% bioavailability by infiltration or topical application (topical absorption ~25–45% via intact skin; higher in mucous membranes). Epinephrine: bioavailability variable by route; negligible oral (extensive first-pass); 100% with injection; topical absorption <10%. |
| Onset of Action | Infiltration/nerve block: 2–5 minutes for prilocaine; epinephrine onset within 1 minute. |
| Duration of Action | Infiltration anesthesia: 30–90 minutes (prilocaine alone); with epinephrine 1:200,000: 120–360 minutes (dose-dependent, prolonged due to vasoconstriction). |
Local infiltration: 0.5% to 2% solution with epinephrine 1:200,000; maximum dose 7 mg/kg prilocaine, not to exceed 600 mg. Nerve block: 1% to 2% solution; maximum dose 7 mg/kg. Repeat administration at intervals of at least 2 hours.
| Dosage form | INJECTABLE |
| Renal impairment | No specific dose adjustment recommended; use with caution in severe renal impairment (GFR <30 mL/min) due to potential accumulation of metabolites. |
| Liver impairment | Child-Pugh Class A: No adjustment. Child-Pugh Class B: Reduce dose by 50%. Child-Pugh Class C: Avoid use or use lowest effective dose with monitoring. |
| Pediatric use | Local infiltration: Maximum 4-5 mg/kg of prilocaine with epinephrine 1:200,000; do not exceed 200 mg in children weighing <20 kg. Nerve block: 2-3 mg/kg; maximum 5 mg/kg. Use lowest effective dose. |
| Geriatric use | Start at the lower end of dosing range due to age-related decreased clearance and increased sensitivity; maximum single dose 400 mg prilocaine. Monitor for cardiovascular and CNS toxicity. |
| 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 | Prilocaine is excreted into breast milk; M/P ratio unknown. Potential for infant methemoglobinemia (especially neonates with G6PD deficiency). Epinephrine is poorly excreted into milk. Caution is advised; discontinue nursing or drug based on importance to mother. |
| Teratogenic Risk |
■ FDA Black Box Warning
Methemoglobinemia: Prilocaine can cause methemoglobinemia, especially in patients with glucose-6-phosphate dehydrogenase deficiency, hemoglobin M disease, or exposure to oxidizing agents. Do not use in patients with congenital or idiopathic methemoglobinemia.
| Common Effects | cardiac arrest |
| Serious Effects |
["Congenital or idiopathic methemoglobinemia","Hypersensitivity to amide anesthetics or epinephrine","Use in areas with poor blood supply (e.g., digits, nose, ears) due to vasoconstriction risk","Severe hypertension or uncontrolled hyperthyroidism (relative)"]
| Precautions | ["Methemoglobinemia risk; monitor for cyanosis, headache, and dyspnea","Do not exceed recommended doses to avoid systemic toxicity","Use with caution in patients with cardiovascular disease, diabetes, or hyperthyroidism due to epinephrine","Avoid accidental intravascular injection","May cause allergic reactions in patients with amide anesthetic hypersensitivity"] |
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| Prilocaine hydrochloride and epinephrine bitartrate: Prilocaine crosses the placenta. In early pregnancy, no well-controlled studies; risk cannot be excluded. Use only if clearly needed. In late pregnancy, prilocaine may cause methemoglobinemia in the fetus (especially with high doses or prolonged use). Epinephrine may reduce uterine blood flow and cause fetal hypoxia; particularly avoid in second stage of labor. Overall, avoid use during pregnancy unless benefit outweighs risks. |
| Fetal Monitoring | Monitor for maternal and fetal bradycardia, hypotension, and signs of methemoglobinemia (e.g., cyanosis, pulse oximetry). Fetal heart rate monitoring recommended during labor. Assess for maternal CNS toxicity and cardiac arrhythmias. |
| Fertility Effects | No human data on fertility impairment. Animal studies with prilocaine or epinephrine have not been reported. Theoretical risk from epinephrine on uterine contractility or implantation. Consider potential for transient contraceptive effect. |