Pliaglis

Warnings
Precautions

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

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].
  • 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 child-proof 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 methemoglobininducing 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.

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 (35-fold higher than the level of lidocaine contained in the lowest approved dose of PLIAGLIS Cream based on a mg/m² body surface area comparison). Lidocaine treatment did not affect overall fertility in male rats when given as subcutaneous doses up to 60 mg/kg (8-fold higher than the level of lidocaine contained in the lowest approved dose of PLIAGLIS Cream based on a mg/m² basis), although the treatment caused an increased copulatory interval and led to a dose-related decrease in homogenization resistant sperm head count, daily sperm production, and spermatogenic efficiency. Tetracaine did not affect fertility in male or female rats when given as subcutaneous doses up to 7.5 mg/kg (equivalent to the level of tetracaine in the lowest approved dose of PLIAGLIS Cream on a mg/m²basis).

Use In Specific Populations

Pregnancy

Pregnancy Category B

No adequate and well-controlled studies have been conducted in pregnant women. PLIAGLIS Cream should be used during pregnancy only if the potential benefit justifies risk to the fetus. Lidocaine was not teratogenic in rats at doses up to 60 mg/kg (8-fold higher than the level of lidocaine contained in the lowest approved dose of PLIAGLIS Cream based on a mg/m² body surface area comparison). Lidocaine was not teratogenic in rabbits at doses up to 15 mg/kg (4-fold higher than the level of lidocaine in the lowest approved dose of PLIAGLIS Cream on a mg/m²basis). Tetracaine was not teratogenic in rats given subcutaneous doses up to 10 mg/kg or in rabbits up to 5 mg/kg (equivalent to the level of tetracaine in the lowest approved dose of PLIAGLIS Cream on a mg/m² basis). Lidocaine and tetracaine given as a 1:1 eutectic mixture of 10 mg/kg each was not teratogenic in rats (equivalent to the level of the active components in the lowest approved dose of PLIAGLIS Cream on a mg/m² basis. Lidocaine and tetracaine given as a 1:1 eutectic mixture of 5 mg/kg each was not teratogenic in rabbits (equivalent to the level of the active components in the lowest approved dose of PLIAGLIS Cream on a mg/m² basis).

Lidocaine containing 1:100,000 epinephrine at a dose of 6 mg/kg (approximately equivalent to the level of lidocaine in the lowest approved dose PLIAGLIS Cream on a mg/m² basis) injected into the masseter muscle of the jaw or into the gum of the lower jaw of pregnant Long-Evans hooded 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 post-natal 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 (equivalent to the level of tetracaine in the lowest approved dose of PLIAGLIS Cream on a mg/m² basis).

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 PLIAGLIS Cream 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 Cream 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 Cream 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

Safety and effectiveness of PLIAGLIS Cream in pediatric patients have not been established. Unintended exposure in pediatric patients could possibly lead to serious adverse effects [see WARNINGS AND PRECAUTIONS]. In a trial of PLIAGLIS Cream in pediatric patients aged 5-17 years undergoing venipuncture (blood draw or intravenous line placement), PLIAGLIS Cream applied for 30 minutes failed to show efficacy over placebo in reducing the pain associated with the procedure.

Geriatric Use

Of the total number of subjects treated with PLIAGLIS Cream 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 [see CLINICAL PHARMACOLOGY].

Last reviewed on RxList: 12/12/2013
This monograph has been modified to include the generic and brand name in many instances.

Warnings
Precautions
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