Pliaglis Information
Pliaglis (Lidocaine)
Pliaglis (Lidocaine) Description
Pliaglis (Lidocaine) ™ (lidocaine and tetracaine) Cream 7% / 7% is a topical local anesthetic cream that forms a pliable peel on the skin when exposed to air. The drug formulation is an emulsion in which the oil phase is a 1:1 eutectic mixture of lidocaine 7% and tetracaine 7%. The eutectic mixture has a melting point below room temperature and therefore both local anesthetics exist as a liquid oil rather than as crystals. The net weight of lidocaine is 2.1 g and of tetracaine is 2.1 g per tube.
Lidocaine is chemically designated as acetamide, 2-(diethylamino)-N-(2,6-dimethylphenyl) and has an octanol:water partition ratio of 182 at pH 7.3. The molecular weight of lidocaine is 234.3, and the molecular formula is CHNO. The structural formula is:
Tetracaine is chemically designated as 2-dimethylaminoethyl 4-n-butylaminobenzoate and has an octanol:water partition ratio of 5370 at pH 7.3. The molecular weight of tetracaine is 264.4, and the molecular formula is CHNO. The structural formula is:
Each gram of Pliaglis (Lidocaine) ™ contains lidocaine 70 mg and tetracaine 70 mg in a 1:1 eutectic mixture and it also contains the following inactive ingredients: dibasic calcium phosphate, methylparaben, petrolatum, polyvinyl alcohol, propylparaben, sorbitan monopalmitate and water.
Pliaglis (Lidocaine) Clinical Pharmacology
Mechanism of Action:
Absorption
Table 1
Application of 59 g of Pliaglis (Lidocaine) ™ over 400 cm for up to 120 minutes to adults produces peak plasma concentrations of lidocaine of 220 ng/mL. Tetracaine plasma levels were not measurable (
Distribution
Volume of distribution and protein binding have not been determined for tetracaine due to rapid hydrolysis in plasma.
Metabolism
Tetracaine undergoes rapid hydrolysis by plasma esterases. Primary metabolites of tetracaine include para-aminobenzoic acid and diethylaminoethanol, both of which have an unspecified activity.
Elimination
The half-life and clearance for tetracaine has not been established for humans, but hydrolysis in the plasma is rapid.
Special Populations
Elderly
Cardiac, Renal and Hepatic Impairment
Pliaglis (Lidocaine) Clinical Studies
In four clinical trials, adult patients were treated with Pliaglis (Lidocaine) and/or placebo prior to undergoing a superficial dermatologic procedure. Drug was applied for 20 or 30 minutes for dermatologic procedures such as dermal filler injection, pulsed dye laser therapy, and facial laser resurfacing. Drug was applied for 60 minutes for laser-assisted tattoo removal. Treatment with Pliaglis (Lidocaine) resulted in statistically significantly less pain compared to placebo treatment, as measured by a 100 mm visual analog scale (VAS). Patient efficacy ratings are shown in Table 2.
In a trial of Pliaglis (Lidocaine) in pediatric patients aged 5-17 years undergoing venipuncture (blood draw or intravenous line placement), Pliaglis (Lidocaine) applied for 30 minutes failed to show efficacy over placebo in reducing the pain associated with the procedure.
Pliaglis (Lidocaine) Indication And Usage
Pliaglis (Lidocaine) is indicated for use on intact skin in adults to provide topical local analgesia for superficial dermatological procedures such as dermal filler injection, pulsed dye laser therapy, facial laser resurfacing, and laser-assisted tattoo removal.
Pliaglis (Lidocaine) Contraindications
Pliaglis (Lidocaine) is contraindicated in patients with a known history of sensitivity to lidocaine or tetracaine, or local anesthetics of the amide or ester type. Pliaglis (Lidocaine) is also contraindicated in patients with para-aminobenzoic acid (PABA) hypersensitivity and in patients with a known history of sensitivity to any other component of the product.
Pliaglis (Lidocaine) Warnings
Application of Pliaglis (Lidocaine) for longer times than those recommended or application of Pliaglis (Lidocaine) over larger surface areas than those recommended could result in absorption of lidocaine and tetracaine at doses that could lead to serious adverse effects (see section).
Even Pliaglis (Lidocaine) may contain a large amount of lidocaine and tetracaine. The potential exists for a small child or pet to suffer serious adverse effects from chewing or ingesting new or used Pliaglis (Lidocaine) , although this risk with Pliaglis (Lidocaine) has not been evaluated. After use, the child-proof cap should be put back securely on the tube. It is important to store and dispose of Pliaglis (Lidocaine) out of the reach of children and pets (see section).
Pliaglis (Lidocaine) Precautions
Pliaglis (Lidocaine) should be used with caution in patients who may be more sensitive to the systemic effects of lidocaine and tetracaine, including the acutely ill or debilitated.
When Pliaglis (Lidocaine) is used concomitantly with other products containing local anesthetic agents, the amount absorbed from all formulations should be considered since the systemic toxic effects are thought to be additive and potentially synergistic with lidocaine and tetracaine.
Allergic or anaphylactoid reactions associated with lidocaine, tetracaine, or other components of Pliaglis (Lidocaine) can occur. They are characterized by urticaria, angioedema, bronchospasm, and shock. If an allergic reaction occurs, it should be managed by conventional means.
Contact of Pliaglis (Lidocaine) with the eyes should be avoided based on the findings of severe eye irritation with the use of similar products in animals. Also, the loss of protective reflexes may predispose to corneal irritation and potential abrasion. If eye contact occurs, immediately wash out the eye with water or saline and protect the eye until sensation returns.
Pliaglis (Lidocaine) is not recommended for use on mucous membranes or on areas with a compromised skin barrier because these uses have not been adequately studied. Application to broken or inflamed skin may result in toxic blood concentrations of lidocaine and tetracaine from increased absorption.
Patients with severe hepatic disease or pseudocholinesterase deficiency, because of their inability to metabolize local anesthetics normally, are at a greater risk of developing toxic plasma concentrations of lidocaine and tetracaine.
Lidocaine has been shown to inhibit viral and bacterial growth. The effect of Pliaglis (Lidocaine) on intradermal injections of live vaccines has not been determined.
Antiarrhythmic Drugs:
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Local Anesthetics:
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Carcinogenesis:
Impairment of Fertility:
Labor and Delivery:
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Nursing Mothers:
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CLINICAL PHARMACOLOGY, Pharmacokinetics
Pediatric Use:
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Use in Geriatric Patients:
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Pliaglis (Lidocaine) Adverse Reactions
Pliaglis (Lidocaine) has been evaluated for safety in 2159 persons undergoing a superficial dermal procedure. Pliaglis (Lidocaine) was studied in 11 placebo-controlled and 1 active-controlled trials, and in open-label safety trials. All 2159 persons were exposed to only a single application of Pliaglis (Lidocaine) .
Adverse reactions were assessed by collecting spontaneously reported adverse events, and observations made on formal evaluation of the skin for specific reactions.
Because clinical trials are conducted under widely varying conditions, the frequencies of adverse reactions observed in the clinical trials of a drug may not reflect the frequencies observed in practice. However, the adverse reaction information from clinical trials does provide a basis for identifying the adverse events that appear to be related to drug use and for approximating their incidence in clinical practice.
Overall, systemic adverse reactions following appropriate use of Pliaglis (Lidocaine) are unlikely, due to the small dose absorbed (see ). Systemic adverse effects of lidocaine and tetracaine are similar in nature to those observed with other amide and ester local anesthetic agents, including CNS excitation and/or depression (light-headedness, nervousness, apprehension, euphoria, confusion, dizziness, drowsiness, tinnitus, blurred or double vision, vomiting, sensation of heat, cold or numbness, twitching, tremors, convulsions, unconsciousness, respiratory depression and arrest). Excitatory CNS reactions may be brief or not occur at all, in which case the first manifestation may be drowsiness merging into unconsciousness. Signs of CNS toxicity may start at plasma concentrations of lidocaine as low as 1000 ng/mL. The plasma concentrations at which tetracaine toxicity may occur are less well characterized; however, systemic toxicity with tetracaine is thought to occur with much lower plasma concentrations compared with lidocaine. The toxicity of co-administered local anesthetics is thought to be at least additive. Cardiovascular manifestations may include bradycardia, hypotension and cardiovascular collapse leading to arrest.
Pliaglis (Lidocaine) Overdosage
Application of 59 g of Pliaglis (Lidocaine) over 400 cm for up to 120 minutes to adults produces peak plasma concentrations of lidocaine of 220 ng/mL. Toxic levels of lidocaine (>5000 ng/mL) cause CNS toxicity, including the risk of seizure. Signs of CNS toxicity may start at plasma concentrations of lidocaine as low as 1000 ng/mL, and the risk of seizures generally increases with increasing plasma levels. Very high levels of lidocaine can cause respiratory arrest, coma, decreases in cardiac output, total peripheral resistance and mean arterial pressure, ventricular arrhythmias and cardiac arrest. Tetracaine is associated with a profile of systemic CNS and cardiovascular adverse events similar to lidocaine, although toxicity associated with tetracaine is thought to occur at lower doses compared to lidocaine. The toxicity of co-administered local anesthetics is thought to be at least additive. In the absence of massive topical overdose or oral ingestion, other etiologies for the clinical effects or overdosage from other sources of lidocaine, tetracaine or other local anesthetics should be considered. The management of overdosage includes close monitoring, supportive care and symptomatic treatment. Dialysis is of negligible value in the treatment of acute overdosage of lidocaine or tetracaine.
Pliaglis (Lidocaine) Dosage And Administration
Pliaglis (Lidocaine) should only be applied to intact skin.
In order to minimize the risk of systemic toxicity, do not exceed the recommended amount of drug to apply or the duration of the application (see section).
The dose of Pliaglis (Lidocaine) that provides effective local dermal analgesia depends on the duration of the application. Although not specifically studied, a shorter duration of application may result in a less complete dermal analgesia or a shorter duration of adequate dermal analgesia.
The amount (length) of Pliaglis (Lidocaine) that should be dispensed is determined by the size of the area to be treated (see ). Using the ruler supplied on the carton and in the section, squeeze out and measure the amount of Pliaglis (Lidocaine) that approximates the amount required to achieve proper coverage. Then spread Pliaglis (Lidocaine) evenly and thinly (approximately 1 mm or the thickness of a dime) across the treatment area using a flat-surfaced tool such as a metal spatula or tongue depressor. After waiting the required application time, remove the Pliaglis (Lidocaine) by grasping a free-edge with your fingers and pulling it away from the skin.
If skin irritation or a burning sensation occurs during application, remove Pliaglis (Lidocaine) .
Pliaglis (Lidocaine) Handling And Disposal
Upon removal from the treatment site, discard the used Pliaglis (Lidocaine) in a location that is out of the reach of children and pets.
Hands should be washed after handling Pliaglis (Lidocaine) , and eye contact with Pliaglis (Lidocaine) should be avoided. Access to Pliaglis (Lidocaine) by children or pets should be prevented during usage and storage of the product.
Used Pliaglis (Lidocaine) tubes should be disposed of immediately.
Pliaglis (Lidocaine) How Supplied
Pliaglis (Lidocaine) (lidocaine and tetracaine) Cream 7% / 7% is available as the following: 0299-6100-30 30 gram tubeStore in a refrigerator, temperature 2 - 8°C (36 - 46°F). Do not freeze.
Manufactured for:GALDERMA LABORATORIES, L.P.Fort Worth, Texas 76177 USAManufactured by:Galderma Production Canada Inc.Baie d’Urfe’, QC H9X 3S4 CanadaMade in CanadaPliaglis (Lidocaine) is a trademark of Galderma.© Copyright 2007 GaldermaRevised April 200710156700-0407
Pliaglis (Lidocaine) Package Label
(lidocaine & tetracine) Cream 7%/7%
Marketed by:GALDERMA LABORATORIES, L.P.Fort Worth, Texas 76177 USAManufactured by:Galderma Production Canada Inc.Baie d’Urfé, QC, H9X 3S4 CanadaMade in Canada.Galderma is a registered trademark
See end flap for lot no. and expiration date.
