LIDOCAINE AND PRILOCAINE
Clinical safety rating: safe
Beta-blockers may increase the risk of lidocaine toxicity Can cause CNS toxicity (seizures) and cardiovascular collapse.
Lidocaine and prilocaine are amide-type local anesthetics that stabilize neuronal membranes by inhibiting sodium ion channels, thereby blocking the initiation and conduction of nerve impulses.
| Metabolism | Lidocaine is primarily metabolized by CYP1A2 and CYP3A4 to monoethylglycinexylidide and glycinexylidide. Prilocaine is metabolized by amidases to o-toluidine, which can cause methemoglobinemia. |
| Excretion | Renal excretion of metabolites (lidocaine: 70-80% as 4-hydroxy-2,6-xylidine and conjugates; prilocaine: 85-95% as o-toluidine metabolites and conjugates). Less than 10% of parent drugs excreted unchanged. |
| Half-life | Lidocaine: 1.5-2 hours; prilocaine: 1.5-2 hours. In hepatic impairment, half-life may be prolonged up to 2-3 times. |
| Protein binding | Lidocaine: 65-75% bound to alpha-1-acid glycoprotein (AAG). Prilocaine: 55-70% bound to AAG and albumin. |
| Volume of Distribution | Lidocaine: 1.1-1.6 L/kg; prilocaine: 2.8-4.2 L/kg. Reflects extensive tissue distribution. |
| Bioavailability | Topical (cream): approximately 0-10% systemic absorption, dependent on application area and skin integrity. No oral bioavailability due to extensive first-pass metabolism. |
| Onset of Action | Topical application (cream/ointment): 30-60 minutes for dermal analgesia. Maximal effect at 2-3 hours. |
| Duration of Action | Dermal analgesia persists for 1-2 hours after removal of occlusive dressing; local anesthetic effect may last up to 4-5 hours after application. |
Apply 2.5 g cream (lidocaine 25 mg/prilocaine 25 mg) to intact skin under occlusive dressing; maximum single application area 400 cm², maximum application time 4 hours. For genital mucous membranes: apply 5-10 g for 5-10 minutes without occlusion. Not recommended for dental use.
| Dosage form | CREAM |
| Renal impairment | No dose adjustment required for GFR ≥30 mL/min. For GFR <30 mL/min: consider reduced dose or increased interval due to risk of metabolite accumulation; monitor for methemoglobinemia. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50% or increase dosing interval; monitor for toxicity. Child-Pugh C: avoid use or use with extreme caution; limited data. |
| Pediatric use | Children <3 months: maximum 1 g over 10 cm² for 1 hour. 3-12 months: maximum 2 g over 20 cm² for 4 hours. 1-6 years: maximum 10 g over 100 cm² for 4 hours. 7-12 years: maximum 20 g over 200 cm² for 4 hours. Adjust for body weight; do not exceed 1.5 g/kg. |
| Geriatric use | No specific dose adjustment recommended, but elderly may have increased risk of systemic absorption due to thinner skin; use smallest effective area and shortest application time. Monitor for methemoglobinemia and adverse effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Beta-blockers may increase the risk of lidocaine toxicity Can cause CNS toxicity (seizures) and cardiovascular collapse.
| FDA category | Animal |
| Breastfeeding | Both lidocaine and prilocaine are excreted into breast milk in small amounts. Lidocaine M/P ratio is approximately 0.9; prilocaine M/P ratio is about 0.4. Topical application results in negligible systemic absorption; thus, risk to nursing infant is low. However, caution is advised with large areas or prolonged use due to potential for infant methemoglobinemia from prilocaine. Use only if benefit outweighs risk. |
| Teratogenic Risk |
■ FDA Black Box Warning
Methemoglobinemia: Cases of methemoglobinemia have been reported, especially in infants, children, and patients with glucose-6-phosphate dehydrogenase deficiency. Avoid in patients with congenital or idiopathic methemoglobinemia.
| Common Effects | ventricular arrhythmias |
| Serious Effects |
Hypersensitivity to lidocaine, prilocaine, or amide-type anesthetics; congenital or idiopathic methemoglobinemia; infants <37 weeks gestational age (for prilocaine); application to large areas of broken skin or mucous membranes.
| Precautions | Risk of methemoglobinemia, especially in infants <12 months and those on methemoglobin-inducing agents. Avoid application to broken skin or mucous membranes. Use with caution in patients with hepatic impairment, severe renal disease, or G6PD deficiency. Monitor for systemic toxicity (CNS depression, seizures, arrhythmias). |
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| Lidocaine and prilocaine are pregnancy category B. Animal studies have not demonstrated fetal risk, but no adequate human studies exist. In first trimester, risk is considered low; however, use only if clearly needed. Second and third trimesters: No evidence of teratogenicity; lidocaine crosses placenta but is rapidly metabolized. Prilocaine may cause methemoglobinemia in fetus; avoid prolonged use near term. Overall, risk is minimal with short-term, topical use. |
| Fetal Monitoring | Monitor maternal and fetal heart rate and uterine activity during prolonged or high-dose use. Assess for signs of local anesthetic systemic toxicity (LAST): perioral numbness, tinnitus, seizures. For prilocaine, monitor for methemoglobinemia (cyanosis, hypoxia) in mother and neonate if used near delivery or in high doses. No specific fetal monitoring is routinely required for topical application. |
| Fertility Effects | No evidence of adverse effects on fertility in animal studies. Human data are lacking. Lidocaine and prilocaine are not known to impair reproductive function. Topical use is unlikely to affect fertility due to minimal systemic absorption. |