PRILOCAINE HYDROCHLORIDE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for PRILOCAINE HYDROCHLORIDE (PRILOCAINE HYDROCHLORIDE).

How it works

Prilocaine hydrochloride is an amino amide local anesthetic that reversibly blocks sodium channels in nerve cell membranes, inhibiting nerve impulse propagation.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for PRILOCAINE HYDROCHLORIDE (PRILOCAINE HYDROCHLORIDE).

Breastfeeding	Excreted in breast milk in small amounts. M/P ratio not established. Considered compatible with breastfeeding at typical doses. Monitor infant for signs of methemoglobinemia (cyanosis, lethargy) with prolonged or high maternal doses.
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.

Warnings & precautions

■ 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.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to prilocaine or other amide anesthetics","Congenital or idiopathic methemoglobinemia","Severe anemia","Significant hepatic impairment","Use in infants less than 6 months of age (due to methemoglobinemia risk)"]

Clinical Precautions

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"]

Clinical Tips & Counseling

Drug interactions

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PRILOCAINE HYDROCHLORIDE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for PRILOCAINE HYDROCHLORIDE (PRILOCAINE HYDROCHLORIDE).

How it works

Prilocaine hydrochloride is an amino amide local anesthetic that reversibly blocks sodium channels in nerve cell membranes, inhibiting nerve impulse propagation.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for PRILOCAINE HYDROCHLORIDE (PRILOCAINE HYDROCHLORIDE).

Breastfeeding	Excreted in breast milk in small amounts. M/P ratio not established. Considered compatible with breastfeeding at typical doses. Monitor infant for signs of methemoglobinemia (cyanosis, lethargy) with prolonged or high maternal doses.
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.