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Synera

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Synera

Warnings
Precautions

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Overexposure

Application of a SYNERA 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].

Storage And Disposal

Used SYNERA patches contain 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.

Avoidance Of Exposure To Eyes And Mucous Membranes

  • Contact of SYNERA 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.
  • SYNERA is not recommended for use on mucous membranes or on areas with a compromised skin barrier because these uses have not been studied. Application to broken or inflamed skin may result in toxic blood concentrations of lidocaine and tetracaine from increased absorption.

Magnetic Resonance Imaging

The integrated heating component contains iron powder; therefore, the SYNERA patch must be removed before a patient undergoes magnetic resonance imaging.

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 have an increased risk of 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 have been no reports of methemoglobinemia with SYNERA. However, providers are cautioned to carefully apply SYNERA to ensure that the 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 SYNERA can occur. They are characterized by urticaria, angioedema, bronchospasm, and shock. If an allergic reaction occurs, it should be managed by conventional means.

Special Patient Populations

  • SYNERA should be used 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.

Vaccinations

Lidocaine has been shown to inhibit viral and bacterial growth. The effect of SYNERA on intradermal injections of live vaccines has not been determined.

Patient Counseling Information

  • Advise patients to read the FDA-approved patient labeling (Instructions for Use).
  • Advise patients that SYNERA is a patch containing two medicines (lidocaine and tetracaine) that are known as local anesthetics, and a heating component. These medicines are used to lessen the pain associated with superficial venous access and superficial dermatological procedures such as excision, electrodessication and shave biopsy of skin lesions.
  • Advise patients that SYNERA should be applied immediately after opening the pouch. Instruct patients to not cut or remove the top cover of the patch as this could result in thermal injury.
  • Advise patients that keeping a patch on longer than recommended or applying multiple patches simultaneously or sequentially could result in systemic absorption sufficient to result in serious adverse effects that are typical of drugs in this class.
  • Advise patients that the patch must be removed before magnetic resonance imaging.
  • Advise patients that SYNERA is contraindicated in patients with a known history of sensitivity to lidocaine, tetracaine, local anesthetics of the amide or ester type, or any other component of the product and in patients with para-aminobenzoic acid (PABA) hypersensitivity.
  • Advise patients that SYNERA should be used with caution in patients who may be more sensitive to the systemic effects of lidocaine and tetracaine, including the acutely ill, the debilitated, and those with compromised hepatic function. Patients with severe hepatic disease or pseudocholinesterase deficiency are at greater risk of developing toxic plasma concentrations.
  • Advise patients that SYNERA should be used with caution in patients receiving class I antiarrhythmics and/or other local anesthetics, because the systemic toxic effects may be additive and potentially synergistic with lidocaine and tetracaine.
  • Advise patients not to use SYNERA if they have a history of methemoglobinemia.
  • Advise patients to avoid contact of SYNERA with the eyes due to potential irritation or abrasion. If contact occurs, immediately wash the eye with water or saline, and protect it until sensation returns.
  • Advise patients that SYNERA should only be applied to intact skin. Inform patients that exposure of the skin to SYNERA may result in erythema, blanching and edema; these reactions are generally mild, resolving spontaneously soon after the patch is removed.
  • Advise patients that SYNERA is not for use on mucous membranes or on areas with broken skin.
  • Advise patients that if skin irritation or a burning sensation occurs during application, the product should be removed.
  • Inform patients of the signs of an allergic or anaphylactoid reaction (urticaria, angioedema, bronchospasm, and shock). Instruct patients to seek immediate emergency help if these occur.
  • Advise patients that SYNERA may lead to diminished or blocked sensation in the treated skin; therefore, patients should avoid inadvertent trauma (rubbing, scratching, or exposure to heat or cold) before complete sensation returns.
  • Advise patients to contact their healthcare professional if they don't recall where to apply the patch.
  • Instruct patients to store SYNERA and to discard used patches out of the reach of children and pets.
  • The effect of SYNERA on intradermal injections of live vaccines has not been determined.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Carcinogenesis

Long-term studies in animals have not been performed to evaluate the carcinogenic potential of either lidocaine or tetracaine.

Mutagenesis

The mutagenic potential of lidocaine base and tetracaine base has been determined in the in vitro Ames Bacterial Reverse Mutation Assay, the in vitro chromosome aberration assay using Chinese hamster ovary cells, and the in vivo mouse micronucleus assay. Lidocaine was negative in all three assays. Tetracaine was negative in the in vitro Ames assay and the in vivo mouse micronucleus assay. In the in vitro chromosome aberration assay, tetracaine was negative in the absence of metabolic activation, and equivocal in the presence of metabolic activation.

Impairment of Fertility

Lidocaine did not affect fertility in female rats when given via continuous subcutaneous infusion via osmotic minipumps up to doses of 250 mg/kg/day (1500 mg/m² or 43-fold higher than the SDA). Although lidocaine treatment of male rats increased the copulatory interval and lead to a dose-related decreased homogenization resistant sperm head count, daily sperm production, and spermatogenic efficiency, the treatment did not affect overall fertility in male rats when given subcutaneous doses up to 60 mg/kg (360 mg/m² or 8-fold the SDA). Tetracaine did not affect fertility in male or female rats when given subcutaneous doses up to 7.5 mg/kg (45 mg/m² or 1-fold the SDA). Multiples of exposure are based on an SDA of 70 mg each of lidocaine and tetracaine in SYNERA patch for 30 minutes to a 60 kg person (43 mg/m²).

Use In Specific Populations

Pregnancy

Pregnancy Category B

Lidocaine was not teratogenic in rats given subcutaneous doses up to 60 mg/kg (360 mg/m² or 8-fold the Single Dermal Administration (SDA)) or in rabbits up to 15 mg/kg (180 mg/m² or 4-fold the SDA). Tetracaine was not teratogenic in rats given subcutaneous doses up to 10 mg/kg (60 mg/m² or 1-fold the SDA) or in rabbits up to 5 mg/kg (60 mg/m² or 1-fold the SDA). SYNERA components (lidocaine and tetracaine) given as a 1:1 eutectic mixture were not teratogenic in rats (60 mg/m² or 1-fold the SDA) or rabbits (120 mg/m² or 3-fold the SDA).

Lidocaine, contained 1:100,000 epinephrine, at a dose of 6 mg/kg (2-fold the SDA) injected into the masseter muscle of the jaw or into the gum of the lower jaw of Long-Evans hooded pregnant rats on Gestation Day 11 led to developmental delays in neonatal behavior among offspring. Developmental delays were observed for negative geotaxis, static righting reflex, visual discrimination response, sensitivity and response to thermal and electrical shock stimuli, and water maze acquisition. The developmental delays of the neonatal animals were transient with responses becoming comparable to untreated animals later in life. The clinical relevance of the animal data is uncertain.

Pre-and postnatal maturational, behavioral, or reproductive development was not affected by maternal subcutaneous administration of tetracaine during gestation and lactation up to doses of 7.5 mg/kg (45 mg/m² or 1-fold the SDA).

No adequate and well-controlled studies have been conducted in pregnant women. Because animal studies are not always predictive of human response, SYNERA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Labor And Delivery

Neither lidocaine nor tetracaine is contraindicated in labor and delivery. In humans, the use of lidocaine for labor neuraxial analgesia has not been associated with an increased incidence of adverse fetal effects either during delivery or during the neonatal period. Tetracaine has also been used as a neuraxial anesthetic for cesarean section without apparent adverse effects on offspring. Should SYNERA be used concomitantly with other products containing lidocaine and/or tetracaine, total doses contributed by all formulations must be considered.

Nursing Mothers

Lidocaine is excreted into human milk and it is not known if tetracaine is excreted into human milk. Therefore, caution should be exercised when SYNERA is administered to a nursing mother since the milk:plasma ratio of lidocaine is 0.4 and is not determined for tetracaine. In a prior report, when lidocaine was used as an epidural anesthetic for cesarean section in 27 women, a milk:plasma ratio of 1.07 ±0.82 was found by using AUC values. Following single dose administration of 20 mg of lidocaine for a dental procedure, the point value milk: plasma ratio was similarly reported as 1.1 at five to six hours after injection. Thus, the estimated maximum total daily dose of lidocaine delivered to the infant via breast milk would be approximately 36 μg/kg. Based on these data and the low concentrations of lidocaine and tetracaine found in the plasma after topical administration of SYNERA in recommended doses, the small amount of these primary compounds and their metabolites that would be ingested orally by a suckling infant is unlikely to cause adverse effects [see CLINICAL PHARMACOLOGY].

Pediatric Use

The safety and effectiveness of SYNERA have been established in pediatric patients 3 years and older based on adequate and well-controlled studies [see Clinical Studies]. While efficacy has not been established for children less than 3 years of age, the safety of SYNERA in infants has been evaluated in one study in which 34 infants 4 to 6 months of age received SYNERA. The recommended application time for the patch for pediatric patients is the same as for adults. Simultaneous or sequential application of more than two SYNERA patches to children is not recommended as it has not been adequately studied.

Use In Geriatric Patients

In the controlled clinical studies, 139 patients over 65 years of age, including 41 patients over 75 years of age, received SYNERA. Visual Analog Scale (VAS) pain score differences between SYNERA and placebo were considerably lower in the geriatric subjects than in the rest of the adult population. No overall differences in safety were observed between geriatric subjects and younger subjects. However, increased sensitivity in individual patients greater than 65 years of age cannot be ruled out. After intravenous dosing, the elimination half-life of lidocaine is significantly longer in elderly patients (2.5 hours) than in younger patients (1.5 hours).

Last reviewed on RxList: 3/28/2014
This monograph has been modified to include the generic and brand name in many instances.

Warnings
Precautions
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