Liprikaine

La crema de liprikaína (una mezcla eutéctica de lidocaína al 2.5% y prilocaína al 2.5%) está indicada como un anestésico tópico para usar en:

- piel intacta normal para analgesia local.

- membranas mucosas genitales para cirugía menor superficial y como pretratamiento para anestesia de infiltración.

Liprikaine (lidocaína y prilocaína) La crema no se recomienda en ninguna situación clínica cuando es posible la penetración o migración más allá de la membrana timpánica en el oído medio debido a los efectos ototóxicos observados en los estudios en animales (ver ADVERTENCIAS).

Adult Patients - Intact Skin

A thick layer of Liprikaine (lidocaine and prilocaine) Cream is applied to intact skin and covered with an occlusive dressing (see Instruction For Application).

Minor Dermal Procedures: For minor procedures such as intravenous cannulation and venipuncture, apply 2.5 grams of Liprikaine (lidocaine and prilocaine) Cream (1/2 the 5 g tube) over 20 to 25 cm² of skin surface for at least 1 hour. In controlled clinical trials using Liprikaine (lidocaine and prilocaine) Cream, two sites were usually prepared in case there was a technical problem with cannulation or venipuncture at the first site.

Major Dermal Procedures: For more painful dermatological procedures involving a larger skin area such as split thickness skin graft harvesting, apply 2 grams of Liprikaine (lidocaine and prilocaine) Cream per 10 cm² of skin and allow to remain in contact with the skin for at least 2 hours.

Adult Male Genital Skin: As an adjunct prior to local anesthetic infiltration, apply a thick layer of Liprikaine (lidocaine and prilocaine) Cream (1 g/10 cm²) to the skin surface for 15 minutes. Local anesthetic infiltration should be performed immediately after removal of Liprikaine (lidocaine and prilocaine) Cream.

Dermal analgesia can be expected to increase for up to 3 hours under occlusive dressing and persist for 1 to 2 hours after removal of the cream. The amount of lidocaine and prilocaine absorbed during the period of application can be estimated from the information in Table 2, ** footnote, in Individualization of Dose.

Adult Female Patients - Genital Mucous Membranes

For minor procedures on the female external genitalia, such as removal of condylomata acuminata, as well as for use as pretreatment for anesthetic infiltration, apply a thick layer (5-10 grams) of Liprikaine (lidocaine and prilocaine) Cream for 5 to 10 minutes.

a href="/script/main/art.asp?articlekey=24885">Occlusion is not necessary for absorption, but may be helpful to keep the cream in place. Patients should be lying down during the Liprikaine (lidocaine and prilocaine) Cream application, especially if no occlusion is used. The procedure or the local anesthetic infiltration should be performed immediately after the removal of Liprikaine (lidocaine and prilocaine) Cream.

Pediatric Patients - Intact Skin

The following are the maximum recommended doses, application areas and application times for Liprikaine (lidocaine and prilocaine) Cream based on a child's age and weight:

Please note: If a patient greater than 3 months old does not meet the minimum weight requirement, the maximum total dose of Liprikaine (lidocaine and prilocaine) Cream should be restricted to that which corresponds to the patient's weight. (see Instruction For Application).

Practitioners should carefully instruct caregivers to avoid application of excessive amounts of Liprikaine Cream (see PRECAUTIONS).

When applying Liprikaine (lidocaine and prilocaine) Cream to the skin of young children, care must be taken to maintain careful observation of the child to prevent accidental ingestion of Liprikaine (lidocaine and prilocaine) Cream or the occlusive dressing. A secondary protective covering to prevent inadvertent disruption of the application site may be useful.

Liprikaine (lidocaine and prilocaine) Cream should not be used in neonates with a gestational age less than 37 weeks nor in infants under the age of 12 months who are receiving treatment with methemoglobin-inducing agents (see Methemoglobinemia subsection of WARNINGS).

When Liprikaine Cream (lidocaine 2.5% and prilocaine 2.5%) is used concomitantly with other products containing local anesthetic agents, the amount absorbed from all formulations must be considered (see Individualization of Dose). The amount absorbed in the case of Liprikaine (lidocaine and prilocaine) Cream is determined by the area over which it is applied and the duration of application under occlusion (see Table 2, ** footnote, in Individualization of Dose).

Although the incidence of systemic adverse reactions with Liprikaine (lidocaine and prilocaine) Cream is very low, caution should be exercised, particularly when applying it over large areas and leaving it on for longer than 2 hours. The incidence of systemic adverse reactions can be expected to be directly proportional to the area and time of exposure (see Individualization of Dose).

Instruction For Application

To measure 1 gram of Liprikaine (lidocaine and prilocaine) , the Cream should be gently squeezed out of the tube as a narrow strip that is 1.5 inches (3.8 cm) long and 0.2 inches (5 mm) wide. The strip of Liprikaine (lidocaine and prilocaine) cream should be contained within the lines of the diagram shown below.

≈1 g strip
1.5 X 0.2 inches

Use the number of strips that equals your dose, like the examples in the table below.

Dosing Information

1 gram = 1 strip
2 grams = 2 strips
2.5 grams = 2.5 strips

For adult and pediatric patients, apply ONLY as prescribed by your physician.

If your child is below the age of 3 months or small for their age, please inform your doctor before applying Liprikaine (lidocaine and prilocaine) Cream, which can be harmful, if applied over too much skin at one time in young children.

When applying Liprikaine (lidocaine and prilocaine) to the intact skin of young children, it is important that they be carefully observed by an adult in order to prevent the accidental ingestion of or eye contact with Liprikaine Cream.

Liprikaine® (lidocaine and prilocaine) Cream must be applied to intact skin at least 1 hour before the start of a routine procedure and for 2 hours before the start of a painful procedure. A protective covering of the Cream is not necessary for absorption but may be helpful to keep the cream in place.

If using a protective covering, your doctor will remove it, wipe off the Liprikaine® (lidocaine and prilocaine) Cream, clean the entire area with an antiseptic solution before the procedure. The duration of effective skin anesthesia will be at least 1 hour after removal of the protective covering.

PRECAUTIONS

1. Do not apply near eyes or on open wounds.
2. Keep out of reach of children.
3. If your child becomes very dizzy, excessively sleepy, or develops duskiness of the face or lips after applying Liprikaine (lidocaine and prilocaine) Cream, remove the cream and contact the child's physician at once.

Liprikaine Cream (lidocaine 2.5% and prilocaine 2.5%) is contraindicated in patients with a known history of sensitivity to local anesthetics of the amide type or to any other component of the product.

WARNINGS

Application of Liprikaine (lidocaine and prilocaine) Cream to larger areas or for longer times than those recommended could result in sufficient absorption of lidocaine and prilocaine resulting in serious adverse effects (see Individualization of Dose).

Patients treated with class III anti-arrhythmic drugs (eg, amiodarone, bretylium, sotalol, dofetilide) should be under close surveillance and ECG monitoring considered, because cardiac effects may be additive.

Studies in laboratory animals (guinea pigs) have shown that Liprikaine (lidocaine and prilocaine) Cream has an ototoxic effect when instilled into the middle ear. In these same studies, animals exposed to Liprikaine (lidocaine and prilocaine) Cream only in the external auditory canal, showed no abnormality. Liprikaine (lidocaine and prilocaine) Cream should not be used in any clinical situation when its penetration or migration beyond the tympanic membrane into the middle ear is possible.

Methemoglobinemia: Liprikaine (lidocaine and prilocaine) Cream should not be used in those rare patients with congenital or idiopathic methemoglobinemia and in infants under the age of twelve months who are receiving treatment with methemoglobin-inducing agents.

Very young patients or patients with glucose-6-phosphate dehydrogenase deficiencies are more susceptible to methemoglobinemia.

Patients taking drugs associated with drug-induced methemoglobinemia such as sulfonamides, acetaminophen, acetanilid, aniline dyes, benzocaine, chloroquine, dapsone, naphthalene, nitrates and nitrites, nitrofurantoin, nitroglycerin, nitroprusside, pamaquine, para-aminosalicylic acid, phenacetin, phenobarbital, phenytoin, primaquine, quinine, are also at greater risk for developing methemoglobinemia.

There have been reports of significant methemoglobinemia (20-30%) in infants and children following excessive applications of Liprikaine (lidocaine and prilocaine) Cream. These cases involved the use of large doses, larger than recommended areas of application, or infants under the age of 3 months who did not have fully mature enzyme systems. In addition, a few of these cases involved the concomitant administration of methemoglobin-inducing agents. Most patients recovered spontaneously after removal of the cream. Treatment with IV methylene blue may be effective if required.

Physicians are cautioned to make sure that parents or other caregivers understand the need for careful application of Liprikaine (lidocaine and prilocaine) Cream, to ensure that the doses and areas of application recommended in Table 2 are not exceeded (especially in children under the age of 3 months) and to limit the period of application to the minimum required to achieve the desired anesthesia.

Neonates and infants up to 3 months of age should be monitored for Met-Hb levels before, during, and after the application of Liprikaine (lidocaine and prilocaine) Cream, provided the test results can be obtained quickly.

PRECAUTIONS

General

Repeated doses of Liprikaine Cream may increase blood levels of lidocaine and prilocaine. Liprikaine (lidocaine and prilocaine) Cream should be used with caution in patients who may be more sensitive to the systemic effects of lidocaine and prilocaine including acutely ill, debilitated, or elderly patients.

Liprikaine (lidocaine and prilocaine) Cream should not be applied to open wounds.

Care should be taken not to allow Liprikaine (lidocaine and prilocaine) Cream to come in contact with the eye because animal studies have demonstrated severe eye irritation. Also the loss of protective reflexes can permit corneal irritation and potential abrasion. Absorption of Liprikaine (lidocaine and prilocaine) Cream in conjunctival tissues has not been determined. If eye contact occurs, immediately wash out the eye with water or saline and protect the eye until sensation returns.

Patients allergic to paraaminobenzoic acid derivatives (procaine, tetracaine, benzocaine, etc.) have not shown cross sensitivity to lidocaine and/or prilocaine; however, Liprikaine (lidocaine and prilocaine) Cream should be used with caution in patients with a history of drug sensitivities, especially if the etiologic agent is uncertain.

Patients with severe hepatic disease, because of their inability to metabolize local anesthetics normally, are at greater risk of developing toxic plasma concentrations of lidocaine and prilocaine.

Lidocaine and prilocaine have been shown to inhibit viral and bacterial growth. The effect of Liprikaine (lidocaine and prilocaine) Cream on intradermal injections of livevaccines has not been determined.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis: Long-term studies in animals designed to evaluate the carcinogenic potential of lidocaine and prilocaine have not been conducted.

Metabolites of prilocaine have been shown to be carcinogenic in laboratory animals. In the animal studies reported below, doses or blood levels are compared with the Single Dermal Administration (SDA) of 60 g of Liprikaine (lidocaine and prilocaine) Cream to 400 cm² for 3 hours to a small person (50 kg). The typical application of Liprikaine (lidocaine and prilocaine) Cream for one or two treatments for venipuncture sites (2.5 or 5 g) would be 1/24 or 1/12 of that dose in an adult or about the same mg/kg dose in an infant.

Chronic oral toxicity studies of ortho-toluidine, a metabolite of prilocaine, in mice (450 to 7200 mg/m²; 60 to 960 times SDA) and rats (900 to 4,800 mg/m²; 60 to 320 times SDA) have shown that ortho-toluidine is a carcinogen in both species. The tumors included hepatocarcinomas/adenomas in female mice, multiple occurrences of hemangiosarcomas/hemangiomas in both sexes of mice, sarcomas of multiple organs, transitional-cell carcinomas/papillomas of urinary bladder in both sexes of rats, subcutaneous fibromas/fibrosarcomas and mesotheliomas in male rats, and mammary gland fibroadenomas/adenomas in female rats. The lowest dose tested (450 mg/m² in mice, 900 mg/m² in rats, 60 times SDA) was carcinogenic in both species. Thus the no-effect dose must be less than 60 times SDA. The animal studies were conducted at 150 to 2,400 mg/kg in mice and at 150 to 800 mg/kg in rats. The dosages have been converted to mg/m² for the SDA calculations above.

Mutagenesis: The mutagenic potential of lidocaine HCl has been tested in a bacterial reverse (Ames) assay in Salmonella, an in vitro chromosomal aberration assay using human lymphocytes and in an in vivo micronucleus test in mice. There was no indication of mutagenicity or structural damage to chromosomes in these tests.

Ortho-toluidine, a metabolite of prilocaine, at a concentration of 0.5 µg/mL was genotoxic in Escherichia coliDNA repair and phage-induction assays. Urine concentrates from rats treated with ortho-toluidine (300 mg/kg orally; 300 times SDA) were mutagenic when examined in Salmonella typhimurium in the presence of metabolic activation. Several other tests on ortho-toluidine, including reverse mutations in five different Salmonella typhimurium strains in the presence or absence of metabolic activation and a study to detect single strand breaks in DNA of V79 Chinese hamster cells, were negative.

Impairment of Fertility: See Use in Pregnancy.

Use in Pregnancy: Teratogenic Effects: Pregnancy Category B.

Reproduction studies with lidocaine have been performed in rats and have revealed no evidence of harm to the fetus (30 mg/kg subcutaneously; 22 times SDA). Reproduction studies with prilocaine have been performed in rats and have revealed no evidence of impaired fertility or harm to the fetus (300 mg/kg intramuscularly; 188 times SDA). There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, Liprikaine (lidocaine and prilocaine) Cream should be used during pregnancy only if clearly needed.

Reproduction studies have been performed in rats receiving subcutaneous administration of an aqueous mixture containing lidocaine HCl and prilocaine HCl at 1:1 (w/w). At 40 mg/kg each, a dose equivalent to 29 times SDA lidocaine and 25 times SDA prilocaine, no teratogenic, embryotoxic or fetotoxic effects were observed.

Labor and Delivery: Neither lidocaine nor prilocaine are contraindicated in labor and delivery. Should Liprikaine (lidocaine and prilocaine) Cream be used concomitantly with other products containing lidocaine and/or prilocaine, cumulative doses from all formulations must be considered.

Nursing Mothers: Lidocaine, and probably prilocaine, are excreted in human milk. Therefore, caution should be exercised when Liprikaine (lidocaine and prilocaine) Cream is administered to a nursing mother since the milk: plasma ratio of lidocaine is 0.4 and is not determined for prilocaine.

Pediatric Use: Controlled studies of Liprikaine (lidocaine and prilocaine) Cream in children under the age of seven years have shown less overall benefit than in older children or adults. These results illustrate the importance of emotional and psychological support of younger children undergoing medical or surgical procedures.

Liprikaine (lidocaine and prilocaine) Cream should be used with care in patients with conditions or therapy associated with methemoglobinemia (see Methemoglobinemia subsection of WARNINGS).

When using Liprikaine (lidocaine and prilocaine) Cream in young children, especially infants under the age of 3 months, care must be taken to insure that the caregiver understands the need to limit the dose and area of application, and to prevent accidental ingestion (see DOSAGE AND ADMINISTRATION and Methemoglobinemia).

In neonates (minimum gestation age: 37 weeks) and children weighing less than 20 kg, the area and duration of application should be limited (see TABLE 2 in Individualization of Dose).

Studies have not demonstrated the efficacy of Liprikaine (lidocaine and prilocaine) Cream for heel lancing in neonates.

Geriatric Use: Of the total number of patients in clinical studies of Liprikaine (lidocaine and prilocaine) Cream, 180 were age 65 to 74 and 138 were 75 and over. No overall differences in safety or efficacy were observed between these patients and younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Plasma levels of lidocaine and prilocaine in geriatric and non-geriatric patients following application of a thick layer of Liprikaine (lidocaine and prilocaine) Cream are very low and well below potentially toxic levels. However, there are no sufficient data to evaluate quantitative differences in systemic plasma levels of lidocaine and prilocaine between geriatric and non-geriatric patients following application of Liprikaine (lidocaine and prilocaine) Cream.

Consideration should be given for those elderly patients who have enhanced sensitivity to systemic absorption. (See PRECAUTIONS.)

After intravenous dosing, the elimination half-life of lidocaine is significantly longer in elderly patients (2.5 hours) than in younger patients (1.5 hours). (See CLINICAL PHARMACOLOGY.)

Reacciones localizadas : Durante o inmediatamente después del tratamiento con Liprikaine (lidocaína y prilocaína) Crema en la piel intacta, la piel en el sitio del tratamiento puede desarrollar eritema o edema o puede ser el lugar de la sensación anormal. Se han informado casos raros de reacciones púrpuras o petequiales discretas en el sitio de aplicación. Se han informado casos raros de hiperpigmentación después del uso de Liprikaine (lidocaína y prilocaína) Crema. No se ha establecido la relación con Liprikaine (lidocaína y prilocaína) Cream o el procedimiento subyacente. En estudios clínicos sobre la piel intacta que involucran más de 1,300 Liprikaine (lidocaína y prilocaína), se observaron sujetos tratados con crema, una o más de esas reacciones locales en el 56% de los pacientes, y generalmente fueron leves y transitorios, resolviendo espontáneamente en 1 o 2 horas. No hubo reacciones graves que se atribuyeron a la crema de liprikaine (lidocaína y prilocaína).

Dos informes recientes describen ampollas en el prepucio en neonatos a punto de sufrir circuncisión. Ambos recién nacidos recibieron 1.0 g de crema de liprikaine (lidocaína y prilocaína).

En pacientes tratados con Liprikaine (lidocaína y prilocaína) Crema sobre piel intacta, los efectos locales observados en los ensayos incluyeron: palidez (palidez o blanqueamiento) 37%, enrojecimiento (eritema) 30%, alteraciones en las sensaciones de temperatura 7%, edema 6%, picazón 2% y erupción cutánea, menos del 1%.

En estudios clínicos sobre membranas mucosas genitales que involucran 378 Liprikaine (lidocaína y prilocaína), se observaron pacientes tratados con crema, una o más reacciones en el lugar de aplicación, generalmente leves y transitorias, en el 41% de los pacientes. Las reacciones más comunes en el sitio de aplicación fueron enrojecimiento (21%), sensación de ardor (17%) y edema (10%).

Reacciones alérgicas: Pueden ocurrir reacciones alérgicas y anafilactoides asociadas con lidocaína o prilocaína. Se caracterizan por urticaria, angioedema, broncoespasmo y shock. Si ocurren, deben ser manejados por medios convencionales. La detección de sensibilidad mediante pruebas cutáneas tiene un valor dudoso.

Reacciones sistémicas (relacionadas con la dosis): Reacciones adversas sistémicas después del uso apropiado de Liprikaine (lidocaína y prilocaína) La crema es poco probable debido a la pequeña dosis absorbida (ver Subsección de farmacocinética de la FARMACOLOGÍA CLÍNICA). Los efectos adversos sistémicos de lidocaína y / o prilocaína son similares en naturaleza a los observados con otros agentes anestésicos locales de amida, incluida la excitación y / o depresión del SNC (aturdimiento, nerviosismo, aprehensión, euforia, confusión, mareo, somnolencia, tinnitus, visión borrosa o doble, vómitos, sensaciones de calor, frío o entumecimiento, temblor, temblores, convulsiones, inconsciencia, depresión respiratoria y arresto). Las reacciones excitantes del SNC pueden ser breves o no ocurrir en absoluto, en cuyo caso la primera manifestación puede ser la somnolencia que se funde en la inconsciencia. Las manifestaciones cardiovasculares pueden incluir bradicardia, hipotensión y colapso cardiovascular que conducen a la detención.

Niveles sanguíneos máximos después de una aplicación de 60 g a 400 cm² de piel intacta durante 3 horas son de 0.05 a 0.16 µg / ml para lidocaína y de 0.02 a 0.10 µg / ml para prilocaína. Los niveles tóxicos de lidocaína (> 5 µg / ml) y / o prilocaína (> 6 µg / ml) causan disminuciones en el gasto cardíaco, resistencia periférica total y presión arterial media. Estos cambios pueden atribuirse a los efectos depresores directos de estos agentes anestésicos locales en el sistema cardiovascular. En ausencia de sobredosis tópica masiva o ingestión oral, la evaluación debe incluir la evaluación de otras etiologías para los efectos clínicos o la sobredosis de otras fuentes de lidocaína, prilocaína u otros anestésicos locales. Consulte los insertos del paquete para Xilocaína parenteral (lidocaína HCl) o Citanest (prilocaína HCl) para obtener más información sobre el tratamiento de la sobredosis.

Liprikaine Cream es una mezcla eutéctica de lidocaína al 2.5% y prilocaína al 2.5% formulada como una emulsión de aceite en agua. En esta mezcla eutéctica, ambos anestésicos son líquidos a temperatura ambiente (ver DESCRIPCIÓN) y la penetración y posterior absorción sistémica de prilocaína y lidocaína se mejoran sobre lo que se vería si cada componente en forma cristalina se aplicara por separado como una crema tópica al 2.5%.

Absorción: La cantidad de lidocaína y prilocaína absorbida sistémicamente de Liprikaine (lidocaína y prilocaína) Cream está directamente relacionada tanto con la duración de la aplicación como con el área sobre la cual se aplica. En dos estudios farmacocinéticos, se aplicaron 60 g de crema de liprikaína (lidocaína y prilocaína) (1,5 g de lidocaína y 1,5 g de prilocaína) a 400 cm² de piel intacta en el muslo lateral y luego cubierta por un apósito oclusivo. Luego, los sujetos fueron aleatorizados de tal manera que a la mitad de los sujetos se les quitó el aderezo oclusivo y la crema residual después de 3 horas, mientras que el resto dejó el aderezo en su lugar durante 24 horas. Los resultados de estos estudios se resumen a continuación.

TABLA 1: Absorción de lidocaína y prilocaína de Liprikaine (lidocaína y prilocaína) Crema: Voluntarios normales (N = 16)

Cuando se aplicaron 60 g de crema de liprikaine (lidocaína y prilocaína) sobre 400 cm² durante 24 horas, los niveles sanguíneos máximos de lidocaína son aproximadamente 1/20 del nivel tóxico sistémico. Del mismo modo, el nivel máximo de prilocaína es aproximadamente 1/36 del nivel tóxico. En un estudio farmacocinético, se aplicó crema de liprikaína (lidocaína y prilocaína) a la piel del pene en 20 pacientes varones adultos en dosis que oscilaron entre 0,5 ga 3,3 g durante 15 minutos. Concentraciones plasmáticas de lidocaína y prilocaína después de Liprikaine (lidocaína y prilocaína) La aplicación de crema en este estudio fue consistentemente baja (2.5-16 ng / ml para lidocaína y 2.5-7 ng / ml para prilocaína). La aplicación de Liprikaine (lidocaína y prilocaína) Crema sobre piel rota o inflamada, o hasta 2,000 cm² o más de piel donde se absorben más anestésicos, podría dar lugar a niveles plasmáticos más altos que podrían, en individuos susceptibles, producir una respuesta farmacológica sistémica.

La absorción de Liprikaine (lidocaína y prilocaína) Crema aplicada a las membranas mucosas genitales se estudió en dos ensayos clínicos abiertos. Veintinueve pacientes recibieron 10 g de Liprikaine (lidocaína y prilocaína) Cream solicitó de 10 a 60 minutos en los bifurcaciones vaginales. Concentraciones plasmáticas de lidocaína y prilocaína después de Liprikaine (lidocaína y prilocaína) La aplicación de crema en estos estudios varió de 148 a 641 ng / ml para lidocaína y de 40 a 346 ng / ml para prilocaína y tiempo para alcanzar la concentración máxima (tmax) varió de 21 a 125 minutos para lidocaína y de 21 a 95 minutos para prilocaína. Estos niveles están muy por debajo de las concentraciones previstas para dar lugar a toxicidad sistémica (aproximadamente 5000 ng / ml para lidocaína y prilocaína).

Distribución: Cuando cada medicamento se administra por vía intravenosa, el volumen de distribución en estado estacionario es de 1.1 a 2.1 L / kg (media 1.5, ± 0.3 SD, n = 13) para lidocaína y es de 0.7 a 4.4 L / kg (media 2.6, ± 1.3 SD, n = 13) para prilocaína. El mayor volumen de distribución de prilocaína produce las concentraciones plasmáticas más bajas de prilocaína observadas cuando se administran cantidades iguales de prilocaína y lidocaína. A concentraciones producidas por la aplicación de Liprikaine (lidocaína y prilocaína) Crema, la lidocaína se une aproximadamente en un 70% a las proteínas plasmáticas, principalmente a la glucoproteína ácida alfa-1. A concentraciones plasmáticas mucho más altas (1 a 4 µg / ml de base libre), la unión a proteínas plasmáticas de lidocaína depende de la concentración. La prilocaína se une en un 55% a las proteínas plasmáticas. Tanto la lidocaína como la prilocaína cruzan la barrera placentaria y cerebral sanguínea, presumiblemente por difusión pasiva.

Metabolismo: No se sabe si la lidocaína o la prilocaína se metabolizan en la piel. La lidocaína se metaboliza rápidamente por el hígado a varios metabolitos, incluidos monoetilglicinaxilidida (MEGX) y glicinexilidida (GX), los cuales tienen una actividad farmacológica similar pero menos potente que la de la lidocaína. El metabolito, 2,6-xilidina, tiene una actividad farmacológica desconocida. Después de la administración intravenosa, las concentraciones de MEGX y GX en suero varían del 11 al 36% y del 5 al 11% de las concentraciones de lidocaína, respectivamente. La prilocaína se metaboliza tanto en el hígado como en los riñones en medio de diversos metabolitos, incluidos orto-toluidina y N-n-propilalanina. No es metabolizado por las esterasas plasmáticas. Se ha demostrado que el metabolito orto-toluidina es cancerígeno en varios modelos animales (ver Subsección de carcinogénesis de PRECAUCIONES). Además, orto-toluidina puede producir metahemoglobinemia después de dosis sistémicas de prilocaína que se aproximan a 8 mg / kg (ver REACCIONES ADVERSAS). Los pacientes muy jóvenes, los pacientes con deficiencias de glucosa-6-fosfato deshidrogenasa y los pacientes que toman medicamentos oxidantes como los antipalúdicos y las sulfonamidas son más susceptibles a la metahemoglobinemia (ver Methemoglobinemia subsección de PRECAUCIONES).

Eliminación: La vida media de eliminación terminal de lidocaína del plasma después de la administración IV es de aproximadamente 65 a 150 minutos (media 110, ± 24 SD, n = 13). Más del 98% de una dosis absorbida de lidocaína se puede recuperar en la orina como metabolitos o fármaco original. El aclaramiento sistémico es de 10 a 20 ml / min / kg (media 13, ± 3 SD, n = 13). La vida media de eliminación de la prilocaína es de aproximadamente 10 a 150 minutos (media 70, ± 48 SD, n = 13). El aclaramiento sistémico es de 18 a 64 ml / min / kg (media 38, ± 15 SD, n = 13). Durante los estudios intravenosos, la vida media de eliminación de lidocaína fue estadísticamente significativamente más larga en pacientes de edad avanzada (2.5 horas) que en pacientes más jóvenes (1.5 horas). No hay estudios disponibles sobre la farmacocinética intravenosa de la prilocaína en pacientes de edad avanzada.

Pediatría: Algunos datos farmacocinéticos (PK) están disponibles en lactantes (de 1 mes a <2 años) y niños (de 2 a <12 años). Se realizó un estudio de PK en 9 neonatos a término (edad media: 7 días y edad gestacional media: 38,8 semanas). Los resultados del estudio muestran que los neonatos tenían concentraciones plasmáticas comparables de lidocaína y prilocaína y concentraciones de metahemoglobina en sangre como las encontradas en estudios pediátricos previos de PK y ensayos clínicos. Hubo una tendencia hacia un aumento en la formación de metahemoglobina. Sin embargo, debido a las limitaciones del ensayo y a la muy poca cantidad de sangre que se pudo recolectar de los recién nacidos, se encontraron grandes variaciones en las concentraciones reportadas anteriormente.

Poblaciones especiales : No se realizaron estudios específicos de PK. La vida media puede aumentar en la disfunción cardíaca o hepática. La vida media de la prilocaína también puede aumentar en la disfunción hepática o renal, ya que ambos órganos están involucrados en el metabolismo de la prilocaína.