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. |
| Molecular Weight | 236.31 |
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 | Avoid; crosses placenta; potential fetal bradycardia and methemoglobinemia. |
| 2nd trimester | Avoid; use only if clearly needed with caution. |
| 3rd trimester | Avoid; may cause neonatal methemoglobinemia and bradycardia. |
Clinical note
Comprehensive clinical and safety monograph for PROCAINE HYDROCHLORIDE (PROCAINE HYDROCHLORIDE).
| Placental transfer | Crosses placenta by passive diffusion; fetal concentrations reach 50-100% of maternal levels. |
| Breastfeeding | Excreted into breast milk in low concentrations; however, due to risk of methemoglobinemia in infants, especially those with G6PD deficiency, avoid or use with caution. Monitor infant for signs of methemoglobinemia (cyanosis, lethargy). |
| Lactation Rating |
■ 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 derivativesMyasthenia gravisSevere bradycardiaHypotensionInfection at injection siteSevere anemiaMethemoglobinemia
| 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 |
| Food/Dietary | No clinically significant food interactions. However, patients with pseudocholinesterase deficiency should avoid foods that may inhibit the enzyme (e.g., organophosphates in some pesticides, but not common dietary items). Consuming alcohol is not recommended due to potential increased side effects like dizziness. |
Loading safety data…
| L3 (Moderately Safe) |
| 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. |
| 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. |
| Clinical Pearls | Procaine hydrochloride is an ester-type local anesthetic with slower onset and shorter duration than lidocaine. It is metabolized by plasma pseudocholinesterase to para-aminobenzoic acid (PABA); patients with pseudocholinesterase deficiency are at risk for prolonged effects. Allergy risk is higher than amides due to PABA metabolite. For local infiltration, use 0.5% solution; for nerve block, 1-2% up to 20 mL. Always aspirate to avoid intravascular injection. Do not use in patients with myasthenia gravis or on cholinesterase inhibitors. Monitor for CNS toxicity (perioral numbness, metallic taste) and cardiovascular collapse. |
| Patient Advice | This medication will numb the area where it is injected. Effects start within 2-5 minutes and last for about 30-60 minutes. · Avoid rubbing or touching the numb area to prevent accidental injury. Do not apply heat or ice to the site. · Seek immediate medical attention if you experience difficulty breathing, swelling of the face or throat, severe dizziness, or a rapid heartbeat. · Inform your dentist or doctor if you have a history of allergic reactions to anesthetics, especially procaine or other ester-type anesthetics. · Report any numbness, tingling, or weakness in areas beyond the injection site, as this may indicate systemic absorption. |