ATC Class:N01BB54

VA Class:CN204

AHFS Class:

• Local Anesthetics 72:00

Generic Name(s):

• Prilocaine Hydrochloride

Prilocaine hydrochloride is an intermediate-acting local anesthetic of the amide type.

Prilocaine hydrochloride is used in dentistry for infiltration anesthesia and for nerve block anesthesia.

Prilocaine hydrochloride may be administered by infiltration or by peripheral nerve block. Partially used dental cartridges of the drug should be discarded. Dosage of prilocaine hydrochloride varies with the anesthetic procedure, the degree of anesthesia required, and individual patient response. The smallest dose required to produce the desired effect should be used. Resuscitative equipment and drugs which may be required for treatment of adverse reactions should be immediately available when prilocaine is administered. For specific procedures and techniques of administration, specialized references should be consulted.

For most routine dental procedures either by infiltration or major nerve block in adults, an initial dose of 1-2 mL (40-80 mg) of a 4% prilocaine hydrochloride solution is usually sufficient. A single dose in adults should not exceed 600 mg (8 mg/kg), and no more than 600 mg should be administered within a 2-hour period in healthy adults. Children younger than 10 years of age rarely require more than 1 mL of a 4% solution (40 mg). The maximum dose in children younger than 10 years of age who have normal lean body mass and body development may be determined using standard pediatric dose formulas (e.g., Clark's rule).

Prilocaine hydrochloride shares the toxic potentials of local anesthetics, and the usual precautions of local anesthetic therapy should be observed. (See Cautions in the Local Anesthetics, Parenteral, General Statement 72:00.)

A metabolite of prilocaine hydrochloride, probably an N -hydroxy metabolite of o -toluidine, may produce methemoglobin concentrations up to 15% and cyanosis, particularly when 600 mg or more of prilocaine hydrochloride is administered in adults. Other clinical symptoms of methemoglobinemia (namely, tachycardia, fatigue, headache, lightheadedness, and dizziness) may occur with higher doses. If the recommended dose of prilocaine hydrochloride has not been exceeded, symptoms of hypoxia are probably related to improper ventilation and should be treated with oxygen. If hypoxia persists following alveolar ventilation with oxygen, then methylene blue therapy should be instituted. IV infusion of methylene blue as a 1% solution in a dose of 1-2 mg/kg given over a 5-minute period will usually correct methemoglobinemia. In patients with anemia or cardiac failure in whom available oxygen is already at a minimum, the disadvantage of further hypoxia caused by the production of methemoglobinemia by prilocaine should be kept in mind.

Some commercially available formulations of prilocaine hydrochloride contain sodium metabisulfite, a sulfite that may cause allergic-type reactions, including anaphylaxis and life-threatening or less severe asthmatic episodes, in certain susceptible individuals. The overall prevalence of sulfite sensitivity in the general population is unknown but probably low; such sensitivity appears to occur more frequently in asthmatic than in nonasthmatic individuals.

Prilocaine is contraindicated in patients with known hypersensitivity to local anesthetics of the amide type and in those with congenital or idiopathic methemoglobinemia.

There is limited experience with the use of prilocaine hydrochloride in children younger than 10 years of age. Animal studies to determine the carcinogenic and mutagenic potential of prilocaine have not been performed to date; however, long-term studies in rats and mice receiving 150-800 and 150-4800 mg/kg, respectively, of o -toluidine, a metabolite of prilocaine (corresponding to about 50-267 and 50-1600 times the usual human dose of prilocaine respectively) have shown the metabolite to be carcinogenic. Studies have not been performed to date to determine whether prilocaine has an effect on fertility.

Serious adverse effects (e.g., seizures, coma, irregular heart beat, respiratory depression) have been reported following topical application of local anesthetics to the skin. These events have occurred following application of extemporaneously prepared topical preparations containing high concentrations of anesthetics for cosmetic procedures and following use for indications approved by the US Food and Drug Administration (FDA).

Life-threatening adverse effects (e.g., irregular heart beat, seizures, breathing difficulties, coma, death) may occur when topical anesthetics are applied to a large area of skin, when the area of application is covered with an occlusive dressing, if a large amount of topical anesthetic is applied, if the anesthetic is applied to irritated or broken skin, or if the skin temperature increases (from exercise or use of a heating pad).101,102 When applied in such a manner, the amount of anesthetic that is absorbed systemically is unpredictable and the plasma concentrations achieved may be high enough to cause life-threatening adverse effects.101,102 Use of lidocaine gel has been investigated to reduce discomfort during mammography.101,103 During the study, the topical anesthetic was spread over a wide area of the chest and covered with an occlusive dressing.101,103 Whether such use could result in serious reactions has not been determined.101,103 Patients should speak with their clinician if they are considering using a topical anesthetic before obtaining a mammogram.101

When a topical anesthetic is needed for a procedure, use of a preparation approved by the FDA has been recommended. A preparation containing the lowest concentration of anesthetic likely to be effective should be used; a small amount of topical anesthetic should be applied to the affected area for the shortest period necessary for the desired effect. The patient should apply the topical preparation as directed by a clinician, and should not apply the topical preparation to broken or irritated skin.101

Pharmacology

Prilocaine hydrochloride produces less vasodilation than does an equal dose of lidocaine hydrochloride.

Pharmacokinetics

Absorption

When used for block or infiltration anesthesia without epinephrine, the duration of anesthesia produced by prilocaine is longer than that of an equal dose of lidocaine. When epinephrine is added to both drugs, the duration of anesthesia of lidocaine is lengthened to a greater extent than that of prilocaine. Following infiltration of 0.75-1 mL of a 4% prilocaine hydrochloride solution for dental anesthesia, the onset of anesthesia averages less than 2 minutes and the drug provides pulp analgesia of 10-15 minutes duration; depending on the dose administered, the duration of soft tissue anesthesia averages about 1-2 hours. When a 4% solution is used for inferior alveolar nerve block, the onset of anesthesia averages less than 3 minutes and the duration of soft tissue anesthesia averages about 2.5 hours.

Distribution

At a concentration of 0.5-1 mcg/mL, approximately 55% of prilocaine is bound to plasma proteins. Prilocaine crosses the blood-brain barrier and the placenta. It is not known if the drug is distributed into milk.

Elimination

Prilocaine hydrochloride is metabolized principally in the liver to o -toluidine and l- N -n-propylamine which may undergo further degradation. Some metabolism of prilocaine may also occur in the kidneys. Prilocaine is excreted in urine as various metabolites and less than 1% as unchanged drug.

Chemistry and Stability

Chemistry

Prilocaine hydrochloride is a local anesthetic of the amide type with an intermediate duration of action. Prilocaine hydrochloride occurs as a white, crystalline powder with a bitter taste and is freely soluble in water and in alcohol. The pK_a of prilocaine hydrochloride is 7.89. The commercially available prilocaine hydrochloride 4% injection has a pH of 5-7; the epinephrine-containing injection has a pH of 3.3-5.5.

Stability

Prilocaine hydrochloride injections should be stored at 15-30°C. Prilocaine hydrochloride solutions are stable to autoclaving; dental cartridges, however, should not be autoclaved because the closures used in the cartridges will not withstand autoclaving. Prolonged contact of prilocaine hydrochloride solutions with metal should be avoided.

Additional Information

For further information on chemistry and stability, pharmacology, pharmacokinetics, uses, cautions, and dosage and administration of prilocaine hydrochloride, see the Local Anesthetics, Parenteral, General Statement 72:00.

Only references cited for selected revisions after 1984 are available electronically.

101. Food and Drug Administration. FDA Public Health Advisory: Potential hazards of skin products containing numbing ingredients for relieving pain from mammography and other medical tests and conditions. 2009 Jan 16. From FDA website ([Web]).

102. Food and Drug Administration. Topical Anesthetics. MedWatch alert. Rockville, MD; 2009 Jan 16. From FDA website ([Web]

103. Lambertz CK, Johnson CJ, Montgomery PG et al. Premedication to reduce discomfort during screening mammography. Radiology . 2008; 248:765-72. [PubMed 18647845]