PRILOCAINE HYDROCHLORIDE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PRILOCAINE HYDROCHLORIDE (PRILOCAINE HYDROCHLORIDE).
Prilocaine hydrochloride is an amino amide local anesthetic that reversibly blocks sodium channels in nerve cell membranes, inhibiting nerve impulse propagation.
| Metabolism | Metabolized primarily in the liver by amidases (includes CYP450 isoenzymes, notably CYP2E1, CYP1A2, and CYP3A4) to o-toluidine and other metabolites, which are further oxidized and conjugated. |
| Excretion | Renal: ~95% as metabolites (primarily o-toluidine and 4-hydroxy-2-methylaniline) and <5% unchanged. Biliary/fecal: minimal (<2%). |
| Half-life | Terminal half-life: 1.5-2 hours (adults, normal hepatic function). Prolonged in neonates (up to 8-12 hours) due to immature hepatic metabolism and reduced clearance; may cause methemoglobinemia. Hepatic impairment increases half-life. |
| Protein binding | ~55% bound, primarily to alpha-1-acid glycoprotein and albumin. |
| Volume of Distribution | Vd: 1.5-2.0 L/kg. Moderate distribution into tissues; higher Vd in neonates (up to 3-4 L/kg) due to increased total body water. |
| Bioavailability | Subcutaneous: near 100%. Epidural: near 100%. Oral: low (~10-20%) due to extensive first-pass metabolism. Topical: variable, 10-30% depending on application site and condition. |
| Onset of Action | Subcutaneous infiltration: 2-5 minutes. Epidural: 5-15 minutes. Peripheral nerve block: 10-20 minutes. Topical (cream): 30-60 minutes; dental topical: 2-5 minutes. |
| Duration of Action | Infiltration anesthesia: 1-2 hours (with epinephrine: 2-4 hours). Epidural: 1.5-3 hours. Nerve block: 2-4 hours. Topical: 1-2 hours. Duration may be prolonged in elderly or hepatic impairment. |
| Molecular Weight | 256.77 |
Adults: 4 mg/kg (max 200 mg) via infiltration or nerve block; may repeat after 2 hours with 50% of initial dose.
| Dosage form | INJECTABLE |
| Renal impairment | No specific adjustment; use caution in severe impairment (eGFR <30 mL/min) due to potential metabolite accumulation. |
| Liver impairment | Child-Pugh A: no reduction; Child-Pugh B: reduce dose by 50%; Child-Pugh C: contraindicated. |
| Pediatric use | Weight-based: 1-2 mg/kg (max 4 mg/kg) as local infiltration; dose per block adjusted for body weight. |
| Geriatric use | Reduce dose by 20-30% and titrate slowly due to decreased clearance and increased sensitivity. |
| 1st trimester | Limited human data; animal studies suggest risk. Use only if clearly needed. |
| 2nd trimester | Crosses placenta; use only if benefit outweighs risk. Monitor for fetal bradycardia. |
| 3rd trimester | Use near term may cause neonatal methemoglobinemia and CNS depression. Avoid for paracervical block. |
Clinical note
Comprehensive clinical and safety monograph for PRILOCAINE HYDROCHLORIDE (PRILOCAINE HYDROCHLORIDE).
| Placental transfer | Readily crosses placenta; cord blood levels approximate maternal levels. |
| Breastfeeding | Excreted into breast milk in small amounts; unlikely to harm infant if used locally. Avoid prolonged or high-dose systemic use. |
| Lactation Rating |
■ FDA Black Box Warning
Methemoglobinemia: Prilocaine can cause methemoglobinemia, especially in infants and patients with glucose-6-phosphate dehydrogenase deficiency. Avoid use in patients with congenital or idiopathic methemoglobinemia.
| Serious Effects |
Hypersensitivity to prilocaine or amide-type anestheticsSevere methemoglobinemia or history thereofInfants under 6 months of age (risk of methemoglobinemia)Severe hypotension or heart block
| Precautions | Methemoglobinemia risk in infants, elderly, and those with G6PD deficiency, CNS and cardiac toxicity from inadvertent intravascular injection, Use caution in patients with hepatic impairment, Avoid in pregnant women unless clearly needed (Category B), Risk of anaphylaxis in patients with amide local anesthetic allergy |
| Food/Dietary | No specific food interactions, but avoid excessive alcohol intake as it may enhance sedation or hypotension. |
Loading safety data…
| L2 |
| Teratogenic Risk | FDA Pregnancy Category B. Animal studies have not demonstrated fetal risk, but no adequate human studies in pregnant women. Prilocaine crosses the placenta. Methemoglobinemia risk to fetus if high doses used. First trimester: no known teratogenicity. Second/third trimesters: possible fetal bradycardia with paracervical block; avoid large doses near delivery due to neonatal methemoglobinemia. |
| Fetal Monitoring | Maternal: ECG, blood pressure, heart rate, oxygen saturation; monitor for CNS (seizures, drowsiness) and cardiovascular (hypotension, arrhythmias) toxicity. Fetal: heart rate monitoring during labor; assess for neonatal methemoglobinemia if large doses used. |
| Fertility Effects | No known adverse effects on human fertility. Animal studies have not shown impaired fertility. |
| Clinical Pearls | Do not exceed recommended doses to avoid methemoglobinemia, especially in infants, elderly, or patients with G6PD deficiency. Use with caution in patients with liver disease as prilocaine is metabolized hepatically. For epidural use, aspirate before injection to avoid intravascular administration. |
| Patient Advice | Inform your healthcare provider if you have any blood disorders, especially G6PD deficiency. · This medication may cause numbness for several hours; avoid injury to the numbed area. · Seek immediate medical attention if you experience bluish skin, chest discomfort, or shortness of breath. · Do not drive or operate machinery until numbness resolves. · Store at room temperature away from light and moisture. |