PROCAINE HYDROCHLORIDE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PROCAINE HYDROCHLORIDE (PROCAINE HYDROCHLORIDE).
Blocks voltage-gated sodium channels, inhibiting nerve impulse conduction by stabilizing the neuronal membrane and preventing depolarization.
| Metabolism | Hydrolyzed in plasma by pseudocholinesterase to para-aminobenzoic acid (PABA) and diethylaminoethanol. |
| Excretion | Primarily renal excretion of metabolites (para-aminobenzoic acid and diethylaminoethanol) and unchanged drug. Approximately 80% of a dose is excreted in urine as para-aminobenzoic acid and conjugates; <2% excreted unchanged. Biliary/fecal elimination is negligible. |
| Half-life | Terminal elimination half-life is approximately 7.7 minutes in adults with normal hepatic function. This short half-life reflects rapid hydrolysis by plasma pseudocholinesterases. In patients with pseudocholinesterase deficiency, half-life may be prolonged to 20-30 minutes. |
| Protein binding | Approximately 5-10% bound to plasma proteins (primarily albumin). Low binding limits drug accumulation and facilitates rapid redistribution. |
| Volume of Distribution | Volume of distribution is approximately 0.7-1.2 L/kg, indicating rapid distribution into total body water and extensive tissue uptake. Vd is larger than blood volume due to rapid uptake by highly perfused organs. |
| Bioavailability | Bioavailability is route-dependent: Intravenous: 100%; Intramuscular: approximately 90-95% (rapid absorption); Oral: negligible due to extensive first-pass hepatic metabolism; Topical: variable, approximately 20-50% on mucous membranes depending on vascularity. |
| Onset of Action | Intravenous: 30-60 seconds; Intrathecal: 2-5 minutes; Epidural: 5-10 minutes; Peripheral nerve block: 2-5 minutes; Topical (mucous membranes): 2-5 minutes; Intramuscular: 5-10 minutes. |
| Duration of Action | Duration of anesthesia depends on dose and route. Intravenous: 10-20 minutes; Intrathecal: 45-90 minutes; Epidural: 30-60 minutes; Peripheral nerve block: 30-60 minutes. Duration is shorter than other aminoester anesthetics due to rapid hydrolysis. |
Local infiltration: 0.5% solution, up to 200 mg (40 mL) per dose. Nerve block: 0.5% solution, 100-200 mg (20-40 mL) per dose. Intravenous regional anesthesia (Bier block): 0.5% solution, 50-100 mg (10-20 mL) per dose. Maximum total dose: 200 mg without epinephrine, 250 mg with epinephrine 1:200,000.
| Dosage form | INJECTABLE |
| Renal impairment | GFR > 60 mL/min: No adjustment. GFR 30-60 mL/min: Reduce dose by 25%. GFR 15-29 mL/min: Reduce dose by 50%. GFR < 15 mL/min: Avoid use or use with extreme caution; maximum single dose 100 mg. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Reduce dose by 50%. Child-Pugh C: Avoid use or use minimal effective dose (maximum 50 mg per dose) with close monitoring. |
| Pediatric use | Infiltrative anesthesia: 0.5% solution, maximum 4 mg/kg per dose. Nerve block: 0.5% solution, maximum 4-5 mg/kg per dose. Intravenous regional: 0.5% solution, 1.5-2 mg/kg per dose. Do not exceed 200 mg total per dose. |
| Geriatric use | Reduce initial dose by 20-30% due to increased sensitivity and decreased clearance. Use lowest effective concentration (0.25-0.5%). Monitor for cardiovascular and neurological toxicity. Maximum single dose: 150 mg. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PROCAINE HYDROCHLORIDE (PROCAINE HYDROCHLORIDE).
| Breastfeeding | It is unknown if procaine is excreted in human breast milk. The M/P ratio has not been determined. Due to the short half-life and rapid metabolism, exposure to the infant is likely minimal. Caution is advised; the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for procaine and any potential adverse effects on the breastfed infant. |
| Teratogenic Risk | Procaine hydrochloride is an ester-type local anesthetic. Animal reproduction studies have not been conducted with procaine. There are no adequate and well-controlled studies in pregnant women. Procaine crosses the placenta. Use during the first trimester should be avoided unless clearly necessary. During second and third trimesters, use with caution due to potential fetal bradycardia and acidosis. High doses or prolonged use may cause fetal CNS depression. |
■ FDA Black Box Warning
Not to be used for prolonged or repeated administration, as it may cause methemoglobinemia, particularly in patients with glucose-6-phosphate dehydrogenase deficiency.
| Serious Effects |
["Hypersensitivity to procaine or PABA","Severe hypotension","Complete heart block","Myasthenia gravis (relative)","Concurrent use with sulfonamides (due to PABA antagonism)"]
| Precautions | ["Risk of methemoglobinemia, especially with high doses or in susceptible patients","Hypotension and bradycardia with high doses","Systemic toxicity including convulsions and cardiorespiratory arrest","Avoid in patients with pseudocholinesterase deficiency"] |
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| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and oxygen saturation. Observe for signs of systemic toxicity (e.g., seizures, arrhythmias, hypotension). Fetal heart rate monitoring is recommended during continuous infusion or repeated dosing. Monitor uterine activity if used in obstetric procedures. Assess for fetal bradycardia or acidosis. |
| Fertility Effects | No specific human data on fertility effects. Animal studies have not been reported. Local anesthetics may affect sperm motility if used in reproductive procedures, but systemic effects are unlikely. No known impact on female fertility. |