FDA Label for Dermacinrx Prikaan

Description

Lidocaine 2.5% and Prilocaine 2.5% Cream, USP is an emulsion in which the oil phase is a eutectic mixture of lidocaine and prilocaine cream 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:

image description - lidocaine and prilocaine cream usp 1

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 lidocaine and prilocaine 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. Lidocaine and prilocaine cream contains no preservative, however it passes the USP antimicrobial effectiveness test due to the pH. The specific gravity of lidocaine and prilocaine cream is 1.00.

Clinical Studies

Lidocaine and prilocaine 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. Lidocaine and prilocaine cream was comparable to subcutaneous lidocaine, but was less efficacious than intradermal lidocaine. Most patients found lidocaine and prilocaine cream treatment preferable to lidocaine infiltration or ethyl chloride spray.

Lidocaine and prilocaine 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 lidocaine and prilocaine cream for 2 to 5 hours provided dermal analgesia comparable to lidocaine infiltration.

Lidocaine and prilocaine cream application in children was studied in seven non-US studies (320 patients) and one US study (100 patients). In controlled studies, application of lidocaine and prilocaine 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, lidocaine and prilocaine cream was less effective than in older children or adults.

Lidocaine and prilocaine cream was compared with placebo in the laser treatment of facial port-wine stains in 72 pediatric patients (ages 5 to 16). Lidocaine and prilocaine cream was effective in providing pain relief during laser treatment.

Lidocaine and prilocaine cream alone was compared with lidocaine and prilocaine 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 lidocaine and prilocaine cream was not effective as a sole anesthetic agent in managing the pain from the surgical procedure. The administration of lidocaine and prilocaine 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.

Lidocaine and prilocaine cream was studied in 105 full term neonates (gestational age: 37 weeks) for blood drawing and circumcision procedures. When considering the use of lidocaine and prilocaine 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 lidocaine and prilocaine cream application in these studies on intact skin included paleness, redness and edema and were transient in nature (see ADVERSE REACTIONS).

The application of lidocaine and prilocaine 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 lidocaine and prilocaine cream and 20 patients received placebo). Lidocaine and prilocaine 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 lidocaine and prilocaine 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 lidocaine and prilocaine cream and 23 patients received placebo) scheduled for infiltration prior to a surgical procedure of the external vulva or genital mucosa. Lidocaine and prilocaine cream applied to the genital mucous membranes for 5 to 10 minutes resulted in adequate topical anesthesia for local anesthetic injection.

Indications And Usage

Lidocaine and prilocaine cream (a eutectic mixture of lidocaine 2.5% and prilocaine 2.5%) is indicated as a topical anesthetic for use on:

    - normal intact skin for local analgesia.

    - genital mucous membranes for superficial minor surgery and as pretreatment for infiltration anesthesia.

Lidocaine and prilocaine 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 WARNINGS).

Contraindications

Lidocaine and prilocaine 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 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 (e.g., 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 lidocaine and prilocaine cream has an ototoxic effect when instilled into the middle ear. In these same studies, animals exposed to lidocaine and prilocaine cream only in the external auditory canal, showed no abnormality. 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.

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, 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.

Overdosage

Peak blood levels following a 60 g application to 400 cm ² 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.

Adult Patients-Intact Skin

A thick layer of lidocaine and prilocaine cream is applied to intact skin and covered with an occlusive dressing (see INSTRUCTIONS FOR APPLICATION).

Minor Dermal Procedures: For minor procedures such as intravenous cannulation and venipuncture, apply 2.5 grams of lidocaine and prilocaine cream (1/2 the 5 g tube) over 20 to 25 cm ² of skin surface for at least 1 hour. In controlled clinical trials using 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 lidocaine and prilocaine cream per 10 cm ² 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 lidocaine and prilocaine cream (1 g/10 cm ² ) to the skin surface for 15 minutes. Local anesthetic infiltration should be performed immediately after removal of lidocaine and prilocaine cream.

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 to 10 grams) of lidocaine and prilocaine 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 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 lidocaine and prilocaine cream.

Pediatric Patients-Intact Skin

The following are the maximum recommended doses, application areas and application times for 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 lidocaine and prilocaine cream should be restricted to that which corresponds to the patient's weight (see INSTRUCTIONS FOR APPLICATION).

Practitioners should carefully instruct caregivers to avoid application of excessive amounts of lidocaine and prilocaine cream (see PRECAUTIONS).

When applying 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 lidocaine and prilocaine cream or the occlusive dressing. A secondary protective covering to prevent inadvertent disruption of the application site may be useful.

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 lidocaine and prilocaine 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 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 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).

Instructions For Application:

To measure 1 gram of lidocaine and prilocaine cream, 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 lidocaine and prilocaine cream should be contained within the lines of the diagram shown below.

image description - lidocaine and prilocaine cream usp 3

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 lidocaine and prilocaine cream, which can be harmful, if applied over too much skin at one time in young children.

When applying lidocaine and prilocaine cream 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 lidocaine and prilocaine cream.

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 lidocaine and prilocaine 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.

Precautions

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

How Supplied

Lidocaine 2.5% and Prilocaine 2.5% Cream, USP is available as the following:

NDC 0591-2070-30 30 gram/tube packed individually, in a child-resistant tube.

KEEP CONTAINER TIGHTLY CLOSED AT ALL TIMES WHEN NOT IN USE.NOT FOR OPHTHALMIC USE.

Storage: Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].

Rx only

Keep out of the reach of children.

For all medical inquiries contact:
ACTAVIS
Medical Communications
Parsippany, NJ 07054
1-800-272-5525

Manufactured By:
IGI Laboratories Inc.
Buena, NJ 08310 USA

Dermacinrx ® Prikaan™ (Lidocaine 2.5% And Prilocaine 2.5% Cream, Usp And Frame Style Transparent Dressing)

Packaged in the USA by:

PureTek Corporation

San Fernando, CA 91340

For questions or information

call toll-free: 877-921-7873

visit: dermacinrx.com

Rev. 36744

image description - Prikaan v4 jn OK clean