SYNERA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SYNERA (SYNERA).
Lidocaine is an amide-type local anesthetic that stabilizes neuronal membranes by inhibiting sodium ion influx, thereby blocking nerve impulse initiation and conduction. Tetracaine is an ester-type local anesthetic that similarly inhibits sodium channels. The combination provides local dermal anesthesia.
| Metabolism | Lidocaine: Hepatic metabolism primarily via CYP3A4, also CYP1A2; major metabolite monoethylglycinexylidide (MEGX). Tetracaine: Hydrolysis by plasma pseudocholinesterase to para-aminobenzoic acid (PABA) and diethylaminoethanol. |
| Excretion | Renal excretion of lidocaine and prilocaine metabolites: lidocaine <10% unchanged, prilocaine negligible unchanged. Metabolites primarily renal. |
| Half-life | Lidocaine: 1.5–2 hours; prilocaine: 1–1.5 hours. Terminal half-life similar for both. Note: prolonged in hepatic impairment or neonates. |
| Protein binding | Lidocaine: ~70% bound to alpha-1-acid glycoprotein; prilocaine: ~55% bound to albumin. |
| Volume of Distribution | Lidocaine: 0.7–1.5 L/kg; prilocaine: 0.5–1.0 L/kg. Indicates distribution into peripheral tissues. |
| Bioavailability | Transdermal absorption: ~0.8–3.5% of applied dose systemically absorbed, resulting in low plasma concentrations. |
| Onset of Action | Onset of analgesia: approximately 1 hour after application to intact skin; maximal effect at 2–3 hours. |
| Duration of Action | Duration of analgesia: 1–2 hours after removal of patch; sufficiently long for minor procedures. |
| Molecular Weight | Lidocaine: 234.34 Da; Tetracaine: 264.36 Da (combined product: 234.34 + 264.36) |
Apply 1 patch (70 mg lidocaine and 70 mg tetracaine) to intact skin over the intended venipuncture site or superficial dermatologic procedure site 20-30 minutes prior to procedure; maximum 1 patch per procedure.
| Dosage form | PATCH |
| Renal impairment | No dose adjustment required for renal impairment. Use with caution in severe renal impairment due to potential accumulation of metabolites. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment. Use with caution in severe hepatic impairment (Child-Pugh class C) due to reduced metabolism of lidocaine and tetracaine. |
| Pediatric use | Children aged 3 years and older: Apply 1 patch to intact skin over the intended site 20-30 minutes prior to procedure. Safety and efficacy not established in children under 3 years. |
| Geriatric use | No specific dose adjustment recommended; use with caution due to potential increased sensitivity to adverse effects such as dizziness or hypotension. |
| 1st trimester | SYNERA (lidocaine 70 mg and tetracaine 70 mg topical patch) is classified as FDA Pregnancy Category B. There are no adequate and well-controlled studies in pregnant women. In animal studies, lidocaine and tetracaine did not show teratogenic effects at doses up to 5 times the human dose. However, because animal studies are not always predictive of human response, use during first trimester only if clearly needed. |
| 2nd trimester | Use during second trimester only if clearly needed. No known increased risk of fetal harm has been reported, but systemic absorption of local anesthetics may cause maternal and fetal bradycardia or hypotension if applied over large areas or compromised skin. |
| 3rd trimester | Use during third trimester with caution. Lidocaine and tetracaine may cross the placenta and can cause fetal bradycardia or CNS depression if maternal plasma levels become elevated. Avoid use near term or during labor if delivery is anticipated, as lidocaine can reduce uterine contractility and increase risk of instrumental delivery. |
Clinical note
Comprehensive clinical and safety monograph for SYNERA (SYNERA).
| Placental transfer | Lidocaine crosses the placenta by passive diffusion. The degree of transfer is concentration-dependent and influenced by protein binding (lidocaine ~70% bound). Tetracaine is expected to cross the placenta due to its low molecular weight, but specific data on placental transfer of tetracaine are limited. In clinical use, systemic absorption from topical patches is low (peak plasma concentrations of lidocaine ~0.1-0.2 μg/mL), which is well below the fetal toxic threshold. |
■ FDA Black Box Warning
None.
| Serious Effects |
Known hypersensitivity to lidocaine, tetracaine, amide-type local anesthetics, or any component of the formulationApplication to open wounds, broken or irritated skinApplication to mucosal membranes or eyesKnown history of porphyria (lidocaine may exacerbate)Severe hepatic impairment (risk of systemic toxicity due to decreased metabolism)
| Precautions | Methemoglobinemia risk, especially in patients with glucose-6-phosphate dehydrogenase deficiency, congenital or idiopathic methemoglobinemia, or concurrent oxidant exposure., Use with caution in patients with hepatic impairment, severe renal impairment, or those taking class III antiarrhythmics., Avoid application to broken skin or mucous membranes., May cause local skin reactions (erythema, edema, blanching)., Do not use on large body surface areas. |
| Food/Dietary | No clinically significant food interactions. Avoid excessive alcohol consumption as it may potentiate sedative effects if systemic absorption occurs (unlikely with proper use). |
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| Breastfeeding | Lidocaine is excreted into human breast milk in small amounts (milk:plasma ratio ~0.4). Tetracaine is not known to be excreted in breast milk, but due to its low systemic absorption from topical use, exposure to the infant is expected to be minimal. However, the safety of topical anesthetics in breastfeeding infants has not been established. Use with caution in nursing mothers, and consider applying the smallest effective area for the shortest duration. Monitor the infant for signs of local anesthetic toxicity (irritability, drowsiness, poor feeding). |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | SYNERA (lidocaine 70 mg and tetracaine 70 mg topical patch) is classified as FDA Pregnancy Category B. Animal reproduction studies have not demonstrated fetal risk, but no adequate and well-controlled studies in pregnant women. Lidocaine and tetracaine can cross the placenta. In the first trimester, theoretical risk of teratogenicity is considered low due to minimal systemic absorption from topical application. In the second and third trimesters, no specific fetal risks are documented, but caution remains due to potential systemic effects (e.g., maternal hypotension or arrhythmias) that could reduce placental perfusion. Use only if clearly needed. |
| Fetal Monitoring | Monitor maternal vital signs (heart rate, blood pressure) for signs of systemic toxicity (e.g., CNS excitement, arrhythmias). Assess for local skin reactions (erythema, edema). In pregnancy, monitor fetal heart rate and uterine activity if used during labor. No specific fetal monitoring is mandated for outpatient use, but vigilance for maternal adverse effects that could affect the fetus is recommended. |
| Fertility Effects | No evidence that SYNERA impairs fertility in humans. Animal studies have not shown effects on mating or fertility. Lidocaine and tetracaine are not known to affect reproductive organs or gamete function. |
| Clinical Pearls | SYNERA (lidocaine 70 mg / tetracaine 70 mg topical patch) is a local anesthetic system for intact skin prior to superficial dermatologic procedures. Apply to dry, intact skin 30 minutes before procedure. Avoid application to broken skin or mucous membranes. Maximum of 4 patches simultaneously in adults; reduce dose in pediatric patients. Monitor for signs of methemoglobinemia, especially in patients with G6PD deficiency or concurrent use of methemoglobin-inducing drugs. Remove patch immediately if burning or irritation occurs. |
| Patient Advice | Apply SYNERA patch to clean, dry skin only 30 minutes before your procedure. Do not apply to cuts, scrapes, or rashes. · Do not touch the sticky gel side of the patch or let it contact your eyes or mouth. · You may feel a warm or tingling sensation under the patch; this is normal. If you experience severe burning or redness, remove the patch and tell your healthcare provider. · Do not use more than 4 patches at a time. Keep patches out of reach of children and pets. · After removal, wash the application area with mild soap and water. Do not reuse a patch. · If you have a history of methemoglobinemia or are taking medications that affect hemoglobin, inform your doctor before using SYNERA. · Store patches at room temperature, away from heat and moisture. |