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. |
| Molecular Weight | Lidocaine: 234.34 Da; Prilocaine: 220.31 Da |
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 | Lidocaine and prilocaine cross the placenta. Use only if clearly needed and potential benefit outweighs risk. Limited human data; animal studies have shown no teratogenicity at clinically relevant doses. |
| 2nd trimester | Use with caution. Both drugs are pregnancy category B (lidocaine) and may be used if indicated. Avoid high doses or repeated applications due to risk of fetal methemoglobinemia with prilocaine. |
| 3rd trimester | Use cautiously near term. Prilocaine may cause methemoglobinemia in the neonate if used in high doses or close to delivery. Lidocaine is generally safe but monitor for maternal toxicity. |
Clinical note
Beta-blockers may increase the risk of lidocaine toxicity Can cause CNS toxicity (seizures) and cardiovascular collapse.
| FDA category | Animal |
| Placental transfer | Both lidocaine and prilocaine cross the placenta. Lidocaine achieves fetal/maternal ratios of 0.5-0.7; prilocaine has similar transfer. The degree of transfer is significant and can cause fetal methemoglobinemia with prilocaine. |
■ 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 any amide-type local anestheticsHistory of methemoglobinemiaSevere hepatic impairment (for prilocaine due to methemoglobin risk)Infants less than 12 months of age receiving concomitant methemoglobin-inducing agents
| 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). |
| Food/Dietary |
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| Breastfeeding | Lidocaine and prilocaine are excreted into breast milk in small amounts. The American Academy of Pediatrics considers lidocaine compatible with breastfeeding. Use caution with prilocaine due to potential for methemoglobinemia in infants, especially those with G6PD deficiency. Avoid application to the breast area to prevent infant ingestion. |
| Lactation Rating | L2 (Lidocaine), L3 (Prilocaine) |
| Teratogenic Risk | 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. |
| None known. Lidocaine and prilocaine do not interact with food. However, avoid excessive alcohol consumption as it may increase the risk of systemic side effects. |
| Clinical Pearls | Apply thick layer under occlusion for at least 60 minutes for maximal dermal analgesia; avoid use on broken skin or mucous membranes; monitor for methemoglobinemia in infants, especially those <3 months or on sulfonamides; do not exceed recommended application area and time to prevent systemic toxicity. |
| Patient Advice | Apply a thick layer of cream to the skin and cover with an occlusive dressing as directed. · Leave the cream on for at least 60 minutes before the procedure; do not exceed 5 hours total. · Do not use on open wounds, eyes, or inside the mouth unless specifically instructed. · Seek immediate medical attention if you experience dizziness, shortness of breath, or bluish skin (signs of methemoglobinemia). · Keep out of reach of children; accidental ingestion can be fatal. |