Pliaglis

• Galderma Laboratories, L.P.

Pliaglis is part of the drug classes:

• Anesthetics for topical use

• Esters of aminobenzoic acid

• Amides

• Analgesics and anesthetics

• Anesthetics, local

• Antiarrhythmics, class Ib

Follow all directions on your prescription label. Never use this medicine in larger amounts, or for longer than prescribed.

Lidocaine and tetracaine topical is usually applied 20 to 30 minutes before your procedure (or 60 minutes before tattoo removal).

If you use this medicine at home, read all patient information, medication guides, and instruction sheets provided to you. Ask your doctor or pharmacist if you have any questions.

Lidocaine and tetracaine topical comes in a cream or a skin patch.

Do not take by mouth. Topical medicine is for use only on the skin. If this medicine gets in your mouth, nose, rectum, or vagina, rinse with water.

The lidocaine and tetracaine topical cream should not be used on a child younger than 3 years old. The skin patch is not approved for use by anyone younger than 18 years old.

For a cosmetic procedure, a healthcare professional or other care provider will apply lidocaine and tetracaine topical cream to your skin.

As it dries, the cream turns into a film that can be peeled off after the prescribed amount of numbing time. Your care provider will remove the cream and clean your skin before your procedure.

If you use a lidocaine and tetracaine topical skin patch, apply it only to clean, dry, healthy skin on the area to be numbed. Press firmly into place. You may begin to feel a warming sensation. Mild warmth from the skin patch is normal, but it should not feel unpleasantly hot.

Wash your hands after applying a skin patch.

After your prescribed amount of numbing time, remove the skin patch, then clean and disinfect the skin as recommended by your doctor.

After removing a skin patch: fold it in half with the sticky side in, and throw it away in a place out of the reach of children or pets.

Store unused skin patches at room temperature away from moisture and heat.

Both used and unused skin patches should be kept out of the reach of children or pets. The amount of medicine in the skin patches could be harmful to a child or pet who accidentally sucks on or swallows a patch. Seek emergency medical attention if this happens.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose of numbing medicine can cause fatal side effects if too much of the medicine is absorbed through your skin and into your blood.

Your body may absorb too much of this medicine if:

• you apply more than the recommended dose;
• you apply the medicine to skin that is cut or irritated; or
• you leave a skin patch on your skin for too long.

Overdose symptoms may include numbness or tingling in your face, ringing in your ears, drowsiness, nausea, and slurred speech. Serious complications of lidocaine or tetracaine overdose may include seizure (convulsions), slowed breathing, coma, heart failure, or respiratory failure (breathing stops).

Since lidocaine and tetracaine topical is used as a single dose, it does not have a daily dosing schedule.

Lidocaine and tetracaine are local anesthetics (numbing medicines). They work by blocking nerve signals in your body.

Lidocaine and tetracaine topical (for use on the skin) is a combination medicine used to numb a small area of your skin. This can help prevent pain during certain medical procedures such as a skin biopsy, minor skin surgery, insertion of an intravenous (IV) needle, or other needle-stick procedures.

Lidocaine and tetracaine topical is also used to numb a skin area during minor cosmetic procedures such as a Botox injection, laser treatment, or tattoo removal.

Lidocaine and tetracaine topical may also be used for purposes not listed in this medication guide.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of methemoglobinemia like a blue or gray color of the lips, nails, or skin; a heartbeat that does not feel normal; seizures; very bad dizziness or passing out; very bad headache; feeling very sleepy; feeling tired or weak; or shortness of breath.
• Very bad skin irritation.
• Burning.
• Feeling of warmth.
• Feeling cold.
• Trouble breathing, slow breathing, or shallow breathing.
• Feeling confused.
• Mood changes.
• Very nervous and excitable.
• Twitching.
• Shakiness.
• Upset stomach or throwing up.
• Ringing in ears.
• Change in eyesight.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Skin irritation.
• Pale skin, redness, or swelling where the patch is put on.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

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.

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.

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.

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.

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.

Vaccinations

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.

Special patient populations

• 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.

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.

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

Pliaglis (lidocaine and tetracaine) Cream (70 mg of lidocaine and 70 mg of tetracaine in 1 gram), 7% / 7%, appears smooth and white to off-white and is available as the following:

NDC 0299-6100-30 30 gram tube (with Child Resistant Cap)

NDC 0299-6100-35 30 gram tube

NDC 0299-6100-60 60 gram tube

NDC 0299-6100-10 100 gram tube

Refrigerate at 2 - 8°C (36 - 46°F). Do not freeze.

Pliaglis can be stored at room temperature for up to 3 months.

Discard Pliaglis after storing at room temperature for 3 months.

Common side effects of Pliaglis include: edema, erythema, and localized blanching. See below for a comprehensive list of adverse effects.