Application of Pliaglis (lidocaine and tetracaine) for longer times than those recommended or application of Pliaglis (lidocaine and tetracaine) 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 section).

Even used Pliaglis may contain a large amount of lidocaine and tetracaine. The potential exists for a small child or pet to suffer serious adverse effects from chewing or ingesting new or used Pliaglis (lidocaine and tetracaine) , although this risk with Pliaglis (lidocaine and tetracaine) has not been evaluated. After use, the child-proof cap should be put back securely on the tube. It is important to store and dispose of Pliaglis out of the reach of children and pets (see Handling and Disposal section).

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 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 (lidocaine and tetracaine) . However, providers are cautioned to carefully apply Pliaglis (lidocaine and tetracaine) to ensure that the doses, areas of application, and duration of application are consistent with those recommended for the intended population.

General

Pliaglis (lidocaine and tetracaine) should be used with caution in patients who may be more sensitive to the systemic effects of lidocaine and tetracaine, including the acutely ill or debilitated.

When Pliaglis (lidocaine and tetracaine) is used concomitantly with other products containing local anesthetic agents, the amount absorbed from all formulations should be considered since the systemic toxic effects are thought to be additive and potentially synergistic with lidocaine and tetracaine.

Allergic or anaphylactoid reactions associated with lidocaine, tetracaine, or other components of Pliaglis (lidocaine and tetracaine) can occur. They are characterized by urticaria, angioedema, bronchospasm, and shock. If an allergic reaction occurs, it should be managed by conventional means.

Contact of Pliaglis (lidocaine and tetracaine) 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.

Pliaglis (lidocaine and tetracaine) 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.

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.

Lidocaine has been shown to inhibit viral and bacterial growth. The effect of Pliaglis (lidocaine and tetracaine) on intradermal injections of live vaccines has not been determined.

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 2-fold higher than the single dermal administration [SDA]). Although lidocaine treatment of male rats increased the copulatory interval and led 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 < 1-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 1 g of Pliaglis (lidocaine and tetracaine) applied to 10 cm² for 60 minutes to a 60 kg person (645 mg/m²).

Use in Pregnancy

Teratogenic Effects: Pregnancy Category B. Lidocaine was not teratogenic in rats at doses up to 60 mg/kg (360 mg/m² or < 1-fold the SDA), nor in rabbits at doses up to 15 mg/kg (180 mg/m²or < 1-fold the SDA). Tetracaine was not teratogenic in rats given subcutaneous doses up to 10 mg/kg (60 mg/m²), nor in rabbits at doses up to 5 mg/kg (60 mg/m²or < 1-fold the SDA), or in rabbits up to 5 mg/kg (60 mg/m² or < 1-fold the SDA). Pliaglis active components (lidocaine and tetracaine given as a 1:1 eutectic mixture) was not teratogenic in rats (60 mg/m² or < 1-fold the SDA) or rabbits (120 mg/m² or < 1-fold the SDA).

Nonteratogenic Effects: Lidocaine containing 1:100,000 epinephrine at a dose of 6 mg/kg ( < 1-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, lead 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, Pliaglis (lidocaine and tetracaine) should be used during pregnancy only if the potential benefit justifies 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 conduction 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 conduction anesthetic for cesarean section without apparent adverse effects on offspring. Should Pliaglis (lidocaine and tetracaine) 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 Pliaglis (lidocaine and tetracaine) 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 mcg/kg. Based on these data and the low concentrations of lidocaine and tetracaine found in the plasma after topical administration of Pliaglis (lidocaine and tetracaine) 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, Pharmacokinetics).

Pediatric Use

Safety and effectiveness of Pliaglis (lidocaine and tetracaine) in pediatric patients have not been established.

Use in Geriatric Patients

Of the total number of subjects treated with Pliaglis (lidocaine and tetracaine) in controlled clinical studies, 161 subjects were 65 years and older, while 50 subjects were over 75 years of age. No overall differences in safety and effectiveness were observed between these subjects and younger subjects. However, increased sensitivity in individual patients aged 65 years and older cannot be ruled out.

Last reviewed on RxList: 1/16/2009
This monograph has been modified to include the generic and brand name in many instances.