Emla Information
Emla (Lidocaine)
Emla (Lidocaine) Description
Emla (Lidocaine) Cream (lidocaine 2.5% and prilocaine 2.5%) is an emulsion in which the oil phase is a eutectic mixture of lidocaine and prilocaine in a ratio of 1:1 by weight. This eutectic mixture has a melting point below room temperature and therefore both local anesthetics exist as a liquid oil rather than as crystals. It is packaged in 5 gram and 30 gram tubes. Lidocaine is chemically designated as acetamide, 2-(diethylamino)-N-(2,6-dimethylphenyl), has an octanol: water partition ratio of 43 at pH 7.4, and has the following structure:
Prilocaine is chemically designated as propanamide, N-(2-methylphenyl)-2-(propylamino), has an octanol: water partition ratio of 25 at pH 7.4, and has the following structure:
Each gram of Emla (Lidocaine) Cream contains lidocaine 25 mg, prilocaine 25 mg, polyoxyethylene fatty acid esters (as emulsifiers), carboxypolymethylene (as a thickening agent), sodium hydroxide to adjust to a pH approximating 9, and purified water to 1 gram. Emla (Lidocaine) Cream contains no preservative, however it passes the USP antimicrobial effectiveness test due to the pH. The specific gravity of Emla (Lidocaine) Cream is 1.00.
Emla (Lidocaine) Clinical Pharmacology
Emla (Lidocaine) Cream (lidocaine 2.5% and prilocaine 2.5%), applied to intact skin under occlusive dressing, provides dermal analgesia by the release of lidocaine and prilocaine from the cream into the epidermal and dermal layers of the skin and by the accumulation of lidocaine and prilocaine in the vicinity of dermal pain receptors and nerve endings. Lidocaine and prilocaine are amide-type local anesthetic agents. Both lidocaine and prilocaine stabilize neuronal membranes by inhibiting the ionic fluxes required for the initiation and conduction of impulses, thereby effecting local anesthetic action.
The onset, depth and duration of dermal analgesia on intact skin provided by Emla (Lidocaine) Cream depend primarily on the duration of application. To provide sufficient analgesia for clinical procedures such as intravenous catheter placement and venipuncture, Emla (Lidocaine) Cream should be applied under an occlusive dressing for at least 1 hour. To provide dermal analgesia for clinical procedures such as split skin graft harvesting, Emla (Lidocaine) Cream should be applied under occlusive dressing for at least 2 hours. Satisfactory dermal analgesia is achieved 1 hour after application, reaches maximum at 2 to 3 hours, and persists for 1 to 2 hours after removal. Absorption from the genital mucosa is more rapid and onset time is shorter (5 to 10 minutes) than after application to intact skin. After a 5 to 10 minute application of Emla (Lidocaine) Cream to female genital mucosa, the average duration of effective analgesia to an argon laser stimulus (which produced a sharp, pricking pain) was 15 to 20 minutes (individual variations in the range of 5 to 45 minutes).
Dermal application of Emla (Lidocaine) Cream may cause a transient, local blanching followed by a transient, local redness or erythema.
Emla (Lidocaine) Cream is a eutectic mixture of lidocaine 2.5% and prilocaine 2.5% formulated as an oil in water emulsion. In this eutectic mixture, both anesthetics are liquid at room temperature (see ) and the penetration and subsequent systemic absorption of both prilocaine and lidocaine are enhanced over that which would be seen if each component in crystalline form was applied separately as a 2.5% topical cream.
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When 60 g of Emla (Lidocaine) Cream was applied over 400 cm for 24 hours, peak blood levels of lidocaine are approximately 1/20 the systemic toxic level. Likewise, the maximum prilocaine level is about 1/36 the toxic level. In a pharmacokinetic study, Emla (Lidocaine) Cream was applied to penile skin in 20 adult male patients in doses ranging from 0.5 g to 3.3 g for 15 minutes. Plasma concentrations of lidocaine and prilocaine following Emla (Lidocaine) Cream application in this study were consistently low (2.5 to 16 ng/mL for lidocaine and 2.5 to 7 ng/mL for prilocaine). The application of Emla (Lidocaine) Cream to broken or inflamed skin, or to 2,000 cm or more of skin where more of both anesthetics are absorbed, could result in higher plasma levels that could, in susceptible individuals, produce a systemic pharmacologic response.
The absorption of Emla (Lidocaine) Cream applied to genital mucous membranes was studied in two open-label clinical trials. Twenty-nine patients received 10 g of Emla (Lidocaine) Cream applied for 10 to 60 minutes in the vaginal fornices. Plasma concentrations of lidocaine and prilocaine following Emla (Lidocaine) Cream application in these studies ranged from 148 to 641 ng/mL for lidocaine and 40 to 346 ng/mL for prilocaine and time to reach maximum concentration (t) ranged from 21 to 125 minutes for lidocaine and from 21 to 95 minutes for prilocaine. These levels are well below the concentrations anticipated to give rise to systemic toxicity (approximately 5000 ng/mL for lidocaine and prilocaine).
Emla (Lidocaine) Clinical Studies
Emla (Lidocaine) Cream application in adults prior to IV cannulation or venipuncture was studied in 200 patients in four clinical studies in Europe. Application for at least 1 hour provided significantly more dermal analgesia than placebo cream or ethyl chloride. Emla (Lidocaine) Cream was comparable to subcutaneous lidocaine, but was less efficacious than intradermal lidocaine. Most patients found Emla (Lidocaine) Cream treatment preferable to lidocaine infiltration or ethyl chloride spray.
Emla (Lidocaine) Cream was compared with 0.5% lidocaine infiltration prior to skin graft harvesting in one open label study in 80 adult patients in England. Application of Emla (Lidocaine) Cream for 2 to 5 hours provided dermal analgesia comparable to lidocaine infiltration.
Emla (Lidocaine) Cream application in children was studied in seven non-US studies (320 patients) and one US study (100 patients). In controlled studies, application of Emla (Lidocaine) Cream for at least 1 hour with or without presurgical medication prior to needle insertion provided significantly more pain reduction than placebo. In children under the age of seven years, Emla (Lidocaine) Cream was less effective than in older children or adults.
Emla (Lidocaine) Cream was compared with placebo in the laser treatment of facial port-wine stains in 72 pediatric patients (ages 5 to 16). Emla (Lidocaine) Cream was effective in providing pain relief during laser treatment.
Emla (Lidocaine) Cream alone was compared with Emla (Lidocaine) Cream followed by lidocaine infiltration and lidocaine infiltration alone prior to cryotherapy for the removal of male genital warts. The data from 121 patients demonstrated that Emla (Lidocaine) Cream was not effective as a sole anesthetic agent in managing the pain from the surgical procedure. The administration of Emla (Lidocaine) Cream prior to lidocaine infiltration provided significant relief of discomfort associated with local anesthetic infiltration and thus was effective in the overall reduction of pain from the procedure only when used in conjunction with local anesthetic infiltration of lidocaine.
Emla (Lidocaine) Cream was studied in 105 full term neonates (gestational age: 37 weeks) for blood drawing and circumcision procedures. When considering the use of Emla (Lidocaine) Cream in neonates, the primary concerns are the systemic absorption of the active ingredients and the subsequent formation of methemoglobin. In clinical studies performed in neonates, the plasma levels of lidocaine, prilocaine, and methemoglobin were not reported in a range expected to cause clinical symptoms.
Local dermal effects associated with Emla (Lidocaine) Cream application in these studies on intact skin included paleness, redness and edema and were transient in nature (see ).
The application of Emla (Lidocaine) Cream on genital mucous membranes for minor, superficial surgical procedures (eg, removal of condylomata acuminata) was studied in 80 patients in a placebo-controlled clinical trial (60 patients received Emla (Lidocaine) Cream and 20 patients received placebo). Emla (Lidocaine) Cream (5 to 10 g) applied between 1 and 75 minutes before surgery, with a median time of 15 minutes, provided effective local anesthesia for minor superficial surgical procedures. The greatest extent of analgesia, as measured by VAS scores, was attained after 5 to 15 minutes’ application. The application of Emla (Lidocaine) Cream to genital mucous membranes as pretreatment for local anesthetic infiltration was studied in a double-blind, placebo-controlled study in 44 female patients (21 patients received Emla (Lidocaine) Cream and 23 patients received placebo) scheduled for infiltration prior to a surgical procedure of the external vulva or genital mucosa. Emla (Lidocaine) Cream applied to the genital mucous membranes for 5 to 10 minutes resulted in adequate topical anesthesia for local anesthetic injection.
Emla (Lidocaine) Indications And Usage
Emla (Lidocaine) Cream (a eutectic mixture of lidocaine 2.5% and prilocaine 2.5%) is indicated as a topical anesthetic for use on:
– for local analgesia.
– for superficial minor surgery and as pretreatment for infiltration anesthesia.
Emla (Lidocaine) Cream is not recommended in any clinical situation when penetration or migration beyond the tympanic membrane into the middle ear is possible because of the ototoxic effects observed in animal studies (see ).
Emla (Lidocaine) Contraindications
Emla (Lidocaine) 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.
Emla (Lidocaine) Warnings
Application of Emla (Lidocaine) 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 ).
Patients treated with class III anti-arrhythmic drugs (et, 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 Emla (Lidocaine) Cream has an ototoxic effect when instilled into the middle ear. In these same studies, animals exposed to Emla (Lidocaine) Cream only in the external auditory canal, showed no abnormality. Emla (Lidocaine) Cream should not be used in any clinical situation when its penetration or migration beyond the tympanic membrane into the middle ear is possible.
Emla (Lidocaine) Precautions
Repeated doses of Emla (Lidocaine) Cream may increase blood levels of lidocaine and prilocaine. Emla (Lidocaine) 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.
Emla (Lidocaine) cream should not be applied to open wounds.
Care should be taken not to allow Emla (Lidocaine) 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 Emla (Lidocaine) 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, Emla (Lidocaine) 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 Emla (Lidocaine) Cream on injections of vaccines has not been determined.
When Emla (Lidocaine) Cream is used, the patient should be aware that the production of dermal analgesia may be accompanied by the block of all sensations in the treated skin. For this reason, the patient should avoid inadvertent trauma to the treated area by scratching, rubbing, or exposure to extreme hot or cold temperatures until complete sensation has returned.
Emla (Lidocaine) cream should not be applied near the eyes or on open wounds.
Emla (Lidocaine) Cream should be used with caution in patients receiving Class I antiarrhythmic drugs (such as tocainide and mexiletine) since the toxic effects are additive and potentially synergistic.
Specific interaction studies with lidocaine/prilocaine and class III anti-arrhythmic drugs (eg, amiodarone, bretylium, sotalol, doetilide) have not been performed, but caution is advised (see ).
Should Emla (Lidocaine) Cream be used concomitantly with other products containing lidocaine and/or prilocaine, cumulative doses from all formulations must be considered.
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 Emla (Lidocaine) Cream to 400 cm for 3 hours to a small person (50 kg). The typical application of Emla (Lidocaine) 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 toluidine, a metabolite of prilocaine, in mice (450 to 7200 mg/m; 60 to 960 times SDA) and rats (900 to 4,800 mg/m; 60 to 320 times SDA) have shown that 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/m in mice, 900 mg/m 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/m for the SDA calculations above.
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, Emla (Lidocaine) 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.
Controlled studies of Emla (Lidocaine) 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.
Emla (Lidocaine) Cream should be used with care in patients with conditions or therapy associated with methemoglobinemia (see subsection of ).
When using Emla (Lidocaine) 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 and ).
Studies have not demonstrated the efficacy of Emla (Lidocaine) Cream for heel lancing in neonates.
Of the total number of patients in clinical studies of Emla (Lidocaine) 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 Emla (Lidocaine) 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 Emla (Lidocaine) Cream.
Consideration should be given for those elderly patients who have enhanced sensitivity to systemic absorption (see ).
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 ).
Emla (Lidocaine) Adverse Reactions
During or immediately after treatment with Emla (Lidocaine) Cream on intact skin, the skin at the site of treatment may develop erythema or edema or may be the locus of abnormal sensation. Rare cases of discrete purpuric or petechial reactions at the application site have been reported. Rare cases of hyperpigmentation following the use of Emla (Lidocaine) Cream have been reported. The relationship to Emla (Lidocaine) Cream or the underlying procedure has not been established. In clinical studies on intact skin involving over 1,300 Emla (Lidocaine) Cream-treated subjects, one or more such local reactions were noted in 56% of patients, and were generally mild and transient, resolving spontaneously within 1 or 2 hours. There were no serious reactions that were ascribed to Emla (Lidocaine) Cream.
Two recent reports describe blistering on the foreskin in neonates about to undergo circumcision. Both neonates received 1.0 g of Emla (Lidocaine) Cream.
In patients treated with Emla (Lidocaine) Cream on intact skin, local effects observed in the trials included: paleness (pallor or blanching) 37%, redness (erythema) 30%, alterations in temperature sensations 7%, edema 6%, itching 2% and rash, less than 1%.
In clinical studies on genital mucous membranes involving 378 Emla (Lidocaine) Cream-treated patients, one or more application site reactions, usually mild and transient, were noted in 41% of patients. The most common application site reactions were redness (21%), burning sensation (17%) and edema (10%).
Emla (Lidocaine) Overdosage
Peak blood levels following a 60 g application to 400 cm of intact skin for 3 hours are 0.05 to 0.16 μg/mL for lidocaine and 0.02 to 0.10 μg/mL for prilocaine. Toxic levels of lidocaine (>5 μg/mL) and/or prilocaine (>6 μg/mL) cause decreases in cardiac output, total peripheral resistance and mean arterial pressure. These changes may be attributable to direct depressant effects of these local anesthetic agents on the cardiovascular system. In the absence of massive topical overdose or oral ingestion, evaluation should include evaluation of other etiologies for the clinical effects or overdosage from other sources of lidocaine, prilocaine or other local anesthetics. Consult the package inserts for parenteral Xylocaine (lidocaine HCl) or Citanest (prilocaine HCl) for further information for the management of overdose.
Emla (Lidocaine) Dosage And Administration
A thick layer of Emla (Lidocaine) Cream is applied to intact skin and covered with an occlusive dressing (see ).
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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 , in .
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 to 10 grams) of Emla (Lidocaine) Cream for 5 to 10 minutes.
Occlusion is not necessary for absorption, but may be helpful to keep the cream in place. Patients should be lying down during the Emla (Lidocaine) Cream application, especially if no occlusion is used. The procedure or the local anesthetic infiltration should be performed immediately after the removal of Emla (Lidocaine) Cream.
The following are the maximum recommended doses, application areas and application times for Emla (Lidocaine) 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 Emla (Lidocaine) Cream should be restricted to that which corresponds to the patient’s (see ).
Practitioners should carefully instruct caregivers to avoid application of excessive amounts of Emla (Lidocaine) Cream (see ).
When applying Emla (Lidocaine) Cream to the skin of young children, care must be taken to maintain careful observation of the child to prevent accidental ingestion of Emla (Lidocaine) Cream or the occlusive dressing. A secondary protective covering to prevent inadvertent disruption of the application site may be useful.
When Emla (Lidocaine) 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 ). The amount absorbed in the case of Emla (Lidocaine) Cream is determined by the area over which it is applied and the duration of application under occlusion (see in ).
Although the incidence of systemic adverse reactions with Emla (Lidocaine) 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 ).
Emla (Lidocaine) Instructions For Application:
To measure 1 gram of Emla (Lidocaine) , 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 Emla (Lidocaine) cream should be contained within the lines of the diagram shown below.
1.5 x 0.2 inches
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 Emla (Lidocaine) Cream, which can be harmful, if applied over too much skin at one time in young children.
When applying Emla (Lidocaine) 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 Emla (Lidocaine) Cream.
Emla (Lidocaine) 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 Emla (Lidocaine) Cream, and 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.
Emla (Lidocaine) How Supplied
Store at 20° to 25°C (68° to 77°F)[see USP Controlled Room Temperature].
Manufactured for:
451096A
Revised: November 2008
Emla (Lidocaine)
Emla (Lidocaine)
Emla (Lidocaine)
Emla (Lidocaine)
Emla (Lidocaine)
