FDA label 419579dc-b200-4c27-9b5e-527b2cef3074

WARNINGS Application of Synera (lidocaine 70 mg and tetracaine 70 mg) topical patch for longer duration than recommended, or the simultaneous or sequential application of multiple Synera patches, could result in sufficient absorption of lidocaine and tetracaine to result in serious adverse effects (see Overdosage). Even a used Synera patch contains a large amount of lidocaine and tetracaine (at least 90% of the initial amount). The potential exists for a child or pet to suffer serious adverse effects from chewing or ingesting a new or used Synera patch. It is important for patients to store and dispose of Synera out of the reach of children and pets.

ADVERSE REACTIONS Three different formulations were studied during clinical development of Synera: Developmental A (n=138), Developmental B (n=30), and the Synera final formulation (n=1281). The developmental patch formulations each contained the same amount of the active drug (70 mg each of lidocaine and tetracaine) as the final patch formulation, but varying amounts of excipients, principally polyvinyl alcohol and water. Data obtained from studies utilizing the developmental patches have been included in the overall evaluation of Synera safety (calculation of adverse event incidence). Localized Reactions: During or immediately after treatment with Synera, the skin at the site of treatment may develop erythema, blanching, edema, or abnormal sensation. In clinical studies involving 1449 Synera-treated subjects, the most common local reactions were erythema (71%), blanching (12%) and edema (12%). These reactions were generally mild, resolving spontaneously soon after treatment. There were no treatment-related serious adverse events. Combined, other application site reactions of various types (contact dermatitis, rash, skin discoloration) occurred in less than 4% of Synera-treated patients during clinical trials. Most were mild, resolving spontaneously soon after patch removal. Adverse events that each occurred in 1% or less of Synera-treated subjects included rash, application site reaction, pruritus, dizziness, headache, pain, nausea, contact dermatitis, infection, skin discoloration, somnolence, allergic reaction, blister, paresthesia, urticaria, vesiculobullous rash, and vomiting. Allergic Reactions: Allergic or anaphylactoid reactions can occur with the active or inactive components of Synera. They may be characterized by urticaria, angioedema, bronchospasm, and shock. If an allergic reaction occurs, medical management should be by conventional means. Systemic (Dose-Related) Reactions: Systemic adverse reactions following appropriate use of Synera are unlikely (see CLINICAL PHARMACOLOGY, Pharmacokinetics). 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, sensations 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.