FDA label dce78d8f-b1b2-4ed3-961c-10d13a3e851e

5 WARNINGS AND PRECAUTIONS Use with caution in patients who may be more sensitive to systemic effects of lidocaine and tetracaine, including acutely ill or debilitated. (5.1) When used concomitantly with other products containing local anesthetic agents, amount absorbed from all formulations should be considered since systemic toxic effects are thought to be additive and potentially synergistic with lidocaine and tetracaine. (5.1) Do not apply to mucous membranes or broken or inflamed skin. Use only on intact skin. (5.1) Do not apply for longer times than those recommended or over larger surface areas than those recommended, which could result in absorption of lidocaine and tetracaine at doses that could lead to serious adverse effects. (5.1) Keep PLIAGLIS Cream away from children and pets due to the risk of accidental exposure and resulting toxicity. (5.2) Tetracaine has been associated with methemoglobinemia. Risk of methemoglobinemia is greatest for patients with congenital or idiopathic methemoglobinemia, and infants under age of twelve months who are receiving treatment with methemoglobin-inducing agents. (5.3) Allergic reactions have been associated with lidocaine, tetracaine, and other components of PLIAGLIS Cream. (5.4) Avoid contact with eyes due to possibility of severe eye irritation. (5.5) 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. (5.7) 5.1 Overexposure Application of PLIAGLIS Cream for longer times than those recommended or application of PLIAGLIS Cream 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 Overdosage (10)]. When PLIAGLIS Cream is used concomitantly with other products containing local anesthetic agents, consider the amount absorbed from all formulations since the systemic toxic effects are thought to be additive and potentially synergistic with lidocaine and tetracaine. PLIAGLIS Cream 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. Use PLIAGLIS Cream with caution in patients who may be more sensitive to the systemic effects of lidocaine and tetracaine, including the acutely ill or debilitated. 5.2 Risks of Secondary Exposure to Children and Pets Used PLIAGLIS Cream contains a large amount of lidocaine and tetracaine. The potential exists for a small child or pet to suffer serious adverse effects from ingesting PLIAGLIS Cream, although this risk with PLIAGLIS Cream has not been evaluated. After use, replace the cap securely on the tube. It is important to store and dispose of PLIAGLIS Cream out of the reach of children and pets. 5.3 Methemoglobinemia Several local anesthetics, including tetracaine, have been associated with methemoglobinemia. The risk of methemoglobinemia is greatest for patients with congenital or idiopathic methemoglobinemia, and 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 concomitant drugs associated with drug-induced methemoglobinemia such as sulfonamides, acetaminophen, acetanilide, aniline dyes, benzocaine, chloroquine, dapsone, naphthalene, nitrates and nitrites, nitrofurantoin, nitroglycerin, nitroprusside, pamaquine, para-aminosalicylic acid, phenacetin, phenobarbital, phenytoin, primaquine, and quinine are also at greater risk for developing methemoglobinemia. There were no reports of methemoglobinemia in the trials of PLIAGLIS Cream; however, providers are cautioned to carefully apply PLIAGLIS Cream to ensure that the doses, areas of application, and duration of application are consistent with those recommended for the intended population. 5.4 Allergic Reactions Allergic or anaphylactoid reactions associated with lidocaine, tetracaine, or other components of PLIAGLIS Cream can occur. They are characterized by urticaria, angioedema, bronchospasm, and shock. If an allergic reaction occurs, it should be managed by conventional means. PLIAGLIS is contraindicated in patients with known hypersensitivity reactions to lidocaine, tetracaine, or local anesthetics of the amide or ester type. 5.5 Eye Irritation Avoid contact of PLIAGLIS Cream with the eyes 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. 5.6 Vaccination Lidocaine has been shown to inhibit viral and bacterial growth. The effect of PLIAGLIS Cream on intradermal injections of live vaccines has not been determined. 5.7 Special patient population Use PLIAGLIS Cream with caution in patients who may be more sensitive to the systemic effects of lidocaine and tetracaine particularly the acutely ill or debilitated. 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.

6 ADVERSE REACTIONS Most common local reactions were erythema (47%), skin discoloration (16%), and edema (14%). ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Galderma Laboratories, L.P. at 1-866-735-4137 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Studies Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates 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. PLIAGLIS Cream has been evaluated for safety in 2159 persons undergoing a superficial dermal procedure. PLIAGLIS Cream 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 Cream. Adverse reactions were assessed by collecting spontaneously reported adverse events, and observations made on formal evaluation of the skin for specific reactions. Most common adverse events in clinical trials Localized Reactions: During or immediately after treatment with PLIAGLIS Cream, the skin at the site of treatment may develop erythema, blanching or edema. In clinical studies, the most common local reactions were erythema (47%), skin discoloration (e.g., blanching, ecchymosis, and purpura) (16%), and edema (14%). There were no serious adverse events. However, one patient withdrew due to burning pain at the treatment site. Other Localized Reactions: The following dermal adverse events occurred in 1% or less of PLIAGLIS Cream -treated patients: ecchymosis, petechial rash, vesiculobullous rash, perifollicular erythema, perifollicular edema, pruritus, rash, maculopapular rash, dry skin, contact dermatitis, and acne. Systemic (Dose-Related) Reactions: Across all trials, 19 subjects experienced a systemic adverse event, 15 of who were treated with PLIAGLIS Cream and 4 with placebo. The frequency of systemic adverse events was greater for the PLIAGLIS Cream group (1%) than the placebo group (0.3%). The most common systemic adverse events were headache, vomiting, dizziness, and fever, all of which occurred with a frequency of <1%. Other systemic reactions were syncope, nausea, confusion, dehydration, hyperventilation, hypotension, nervousness, paresthesia, pharyngitis, stupor, pallor, and sweating. 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 at 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. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of PLIAGLIS Cream. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Eye disorders: Eyelid swelling Skin: Pruritus, Rash, Skin Burning Sensation, Erythema, Urticaria Other: Drug ineffective