Prilocaine: Amide Type Local Anesthetic in EMLA Cream, Dentistry and Spinal Anesthesia

Prilocaine is an intermediate acting amide type local anesthetic. Known brand names are Xylonest (in Germany), Citanest (internationally), and as a component of EMLA cream together with Lidocaine. In dentistry, prilocaine is usually combined with the vasoconstrictor Felypressin, in anesthesiology as a hyperbaric 2 percent solution for spinal anesthesia and as a 1 or 2 percent solution for peripheral nerve blocks.

Prilocaine has found a special clinical niche in ambulatory spinal anesthesia for short surgical procedures (approximately 30 to 60 minutes), because its duration of action is shorter than that of Bupivacaine and patients can be mobilized more quickly. This makes it the first choice in modern day surgery concepts. Compared to other local anesthetics, prilocaine has the lowest systemic toxicity potential, however methemoglobinemia is a specific adverse effect that must be considered in selection and dosage.

Mechanism of Action

Prilocaine blocks voltage dependent sodium channels in nerve fibers. The active substance diffuses into the nerve cell, binds intracellularly to open or inactivated sodium channels and thus prevents sodium influx during depolarization. Without sodium influx, no action potential can be conducted, nerve conduction is interrupted.

Clinically, pain fibers (C and A delta) are blocked first, followed by pressure and temperature sensation, later motor A alpha fibers follow. This differentiated blockade allows purely sensory anesthesia without motor blockade at low concentrations, especially in obstetrics.

Metabolism occurs rapidly in the liver to o-toluidine, a metabolite responsible for methemoglobinemia. The half-life of prilocaine itself is approximately 90 minutes. In infants, methemoglobin reductase activity is still immature, the risk for methemoglobinemia is correspondingly increased.

Indications

• Dentistry: Local anesthesia for dental procedures, often with Felypressin as vasoconstrictor (Xylonest with Octapressin)
• EMLA Cream: Lidocaine Prilocaine mixture (2.5 percent each) for skin anesthesia before punctures, biopsies or minor dermatological procedures
• Spinal anesthesia: hyperbaric 2 percent solution for ambulatory operations with short duration of action (30 to 60 minutes), e.g. anorectal procedures, knee arthroscopy
• Peripheral nerve blocks: brachial plexus, femoral block, ankle block
• Intravenous regional anesthesia (Bier block): for the upper extremity
• Local infiltration anesthesia: minor surgical procedures

Dosage and Administration

Maximum single dose adults: 6 mg/kg without vasoconstrictor, 8 mg/kg with vasoconstrictor, absolute maximum dose 600 mg per session. Spinal anesthesia: 50 to 80 mg hyperbaric 2 percent solution intrathecal.

EMLA Cream: apply thickly to intact skin, cover occlusively with film; onset of action after 60 minutes, duration of action 1 to 2 hours after removal. In infants under three months and patients with methemoglobinemia risk do not use or use with caution.

In children: maximum dose 5 mg/kg; in infants under six months particular restraint due to methemoglobinemia risk.

Adverse Effects

Common: local burning or stinging at injection site, transient hypotension and bradycardia during spinal anesthesia, transient motor blockade.

Occasional to rare: methemoglobinemia (especially at doses over 600 mg, in infants, with glucose-6-phosphate dehydrogenase deficiency or congenital hemoglobinopathies), allergic reactions, nausea, tinnitus, perioral paresthesias, visual disturbances.

Serious: systemic toxicity following accidental intravascular injection or overdose with CNS symptoms (convulsion, unconsciousness) and cardiovascular effects (arrhythmia, cardiac arrest). In case of systemic toxicity, lipid emulsion (Intralipid) is the first choice as antidote.

Important, methemoglobinemia: when skin pallor, cyanosis despite normal oxygen saturation on pulse oximetry and chocolate colored blood are present, methemoglobinemia should be considered. Treatment with methylene blue 1 to 2 mg/kg intravenously.

Drug Interactions

• Other methemoglobinemia inducing agents (Sulfonamides, Dapsone, Chloroquine, Phenazopyridine): additive methemoglobinemia risk
• Other local anesthetics: additive systemic toxicity, maximum doses add up
• Antiarrhythmic agents class Ia and III (Procainamide, Amiodarone): additive cardiac toxicity
• Vasoconstrictors (Epinephrine, Felypressin): prolong local effect and reduce systemic absorption
• Cimetidine and Beta blockers: reduce hepatic metabolism, enhance systemic toxicity

Special Precautions

Pregnancy: Prilocaine is rather avoided in pregnancy because of the risk of fetal methemoglobinemia and Lidocaine as an alternative has a broader data base. Breast-feeding: short-term use is considered safe.

Contraindications: known methemoglobinemia, congenital or idiopathic methemoglobinemia, glucose-6-phosphate dehydrogenase deficiency, severe anemia, severe renal insufficiency.

Infants under six months: caution with any prilocaine use due to immature methemoglobin reductase. EMLA cream is contraindicated in infants under three months.

Spinal anesthesia: according to EMA requirement, spinal anesthesia is only permitted in facilities with the capability of continuous monitoring of breathing, cardiac function and circulation.

You might also be interested in

• Lidocaine, classical amide local anesthetic
• Bupivacaine, long acting local anesthetic
• Ropivacaine, modern local anesthetic with better profile
• Mepivacaine, intermediate acting local anesthetic
• Articaine, standard in dentistry

Frequently Asked Questions

Sources

• Gelbe Liste, Prilocaine Active Ingredient Profile
• AWMF S1 Guideline Local Anesthetics in Dentistry and DGAI Recommendations
• BfArM, Federal Institute for Drugs and Medical Devices
• EMA Product Information Prilocaine Preparations