STORAGE AND HANDLING SECTION.

KEEP THIS AND ALL MEDICATIONS OUT OF REACH OF CHILDREN.. All prescriptions using this product shall be pursuant to state statutes asapplicable.This is not an Orange Book product. This product may beadministered only under physicians supervision. There are no impliedor explicit claims on the therapeutic equivalence.Manufactured for: Seton Pharmaceuticals Manasquan, NJ 08736 1-800-510-3401Iss. 5/11 Rx Only Seton Pharmaceuticals.

CLINICAL PHARMACOLOGY SECTION.

CLINICAL PHARMACOLOGY:. MECHANISM OF ACTION:. Product releases lidocaine to stabilize the neuronal membrane by inhibiting the ionic fluxes required for initiation and conduction of impulses, thereby effecting local anesthetic action. Hydrocortisone acetate provides relief of inflammatory and pruritic manifestations of corticosteroid responsive dermatoses. Lidocaine is chemically designated as acetamide, 2-(diethylamino)-N-(2,6-dimethylphenyl), and has the following structure:Hydrocortisone acetate has chemical name pregn-4-ene-3, 20-dione, 21-(acetyloxy)- 11,17- dihydroxy-(11ss)-. It has the following structural formula:. PHARMACOKINETICS:. Lidocaine may be absorbed following topicaladministration to mucous membranes, its rate and extent of absorptiondepending upon the specific site of application, duration of exposure,concentration, and total dosage. In general, the rate of absorption of localanesthetic agents following topical application occurs most rapidly afterintratracheal administration. Lidocaine is also well-absorbed from thegastrointestinal tract, but little intact drug appears in the circulation becauseof biotransformation in the liver.Lidocaine is metabolized rapidly by the liver, and metabolites and unchangeddrug are excreted by the kidneys. Biotransformation includes oxidativeN-dealkylation, ring hydroxylation, cleavage of the amide linkage, andconjugation. N-dealkylation, major pathway of biotransformation, yields themetabolites monoethylglycinexylidide and glycinexylidide. Thepharmacological/toxicological actions of these metabolites are, similar to butless potent than, those of lidocaine. Approximately 90% of lidocaineadministered is excreted in the form of various metabolites, and less than10% is excreted unchanged. The primary metabolite in urine is conjugateof 4-hydroxy-2, 6-dimethylaniline. The plasma binding of lidocaine isdependent on drug concentration, and the fraction bound decreases withincreasing concentration. At concentrations of to g of free base per mL,60 to 80 percent of lidocaine is protein bound. Binding is also dependent onthe plasma concentration of the alpha-1-acid glycoprotein. Lidocaine crossesthe blood-brain and placental barriers, presumably by passive diffusion.Studies of lidocaine metabolism following intravenous bolus injections haveshown that the elimination half-life of this agent is typically 1.5 to hours.Because of the rapid rate at which lidocaine is metabolized, any conditionthat affects liver function may alter lidocaine kinetics. The half-life may beprolonged two-fold or more in patients with liver dysfunction. Renaldysfunction does not affect lidocaine kinetics but may increase theaccumulation of metabolites. Factors such as acidosis and the use of CNSstimulants and depressants affect the CNS levels of lidocaine required toproduce overt systemic effects. Objective adverse manifestations becomeincreasingly apparent with increasing venous plasma levels above g freebase per mL. In the rhesus monkey arterial blood levels of 18-21 g/mL havebeen shown to be threshold for convulsive activity.The extent of percutaneous absorption of topical corticosteroids isdetermined by many factors including the vehicle, the integrity ofthe epidermal barrier, and the use of occlusive dressings.Topical corticosteroids can be absorbed from normal intact skin.Inflammation and/or other disease processes in the skin increasepercutaneous absorption. Occlusive dressings substantiallyincrease the percutaneous absorption of topical corticosteroids.Thus, occlusive dressings may be valuable therapeutic adjunctfor treatment of resistant dermatoses.Once absorbed through the skin, topical corticosteroids are handledthrough pharmacokinetic pathways similar to systemicallyadministered corticosteroids. Corticosteroids are bound to plasmaprotein in varying degrees. Corticosteroids are metabolizedprimarily in the liver and are then excreted by the kidneys. Some ofthe topical corticosteroids and their metabolites are also excretedinto the bile.

ADVERSE REACTIONS SECTION.

ADVERSE REACTIONS:. During, immediately, or following application ofproduct, there may be transient stinging or burning from open areas ofskin, or transient blanching (lightening), or erythema (redness) of the skin.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

CARCINOGENESIS, MUTAGENESIS, AND IMPAIRMENT OF FERTILITY:. Long-term animal studies have not been performed to evaluate thecarcinogenic potential or the effect on fertility of topical corticosteroids.Studies to determine mutagenicity with prednisolone and hydrocortisonehave revealed negative results. Studies of lidocaine in animals to evaluatethe carcinogenic and mutagenic potential of the effect on fertility have notbeen conducted.

CONTRAINDICATIONS SECTION.

CONTRAINDICATIONS:. Product should not be used in patients witha history of sensitivity to any of its ingredients or adverse reactionsto lidocaine or amide anesthetics, which usually do not cross-reactwith caine ester type anesthetics. If excessive irritation andsignificant worsening occur, discontinue use and seek the advice ofyour physician. Product and topical lidocaine should be usedcautiously in those with impaired liver function, as well as the veryill or very elderly and those with significant liver disease. Productshould be used with caution on patients receiving antiarrhythmicdrugs of Class since the adverse effects are additive and generallysynergistic. This product is contraindicated for tuberculous orfungal lesions or skin vaccinia, varicella and acute herpes simplex.Topical corticosteroids are contraindicated in those patients with ahistory of hypersensitivity to any of the components of thepreparation.. structure. structure2.

DESCRIPTION SECTION.

DESCRIPTION:. Lidocaine 3% Hydrocortisone 0.5% Cream is indicated for the anti-inflammatory and anesthetic relief of itching, pain, soreness, and discomfort due to hemorrhoids, anal fissures, pruritus ani and similar conditions of the anal area.

DOSAGE & ADMINISTRATION SECTION.

DOSAGE AND ADMINISTRATION:. Apply product to the affected area(s) twice daily or as directed by aphysician. If the condition does not respond to repeated courses ofproduct or should worsen, discontinue use and seek the advice of thephysician.

HOW SUPPLIED SECTION.

HOW SUPPLIED:. Lidocaine 3% Hydrocortisone 0.5% Cream is supplied as white cream in: oz (28.35 g) tubes NDC 13925-160-01 oz (85 g) tubes NDC 13925-160-03 Store at 25C (77F); excursions permitted to 15-30C (59-77F). See USP Controlled Room Temperature. Protect from freezing.

INACTIVE INGREDIENT SECTION.

ACTIVE INGREDIENTS: Each gram of Lidocaine 3% Hydrocortisone 0.5% Cream contains lidocaine hydrochloride 3% (30mg) and hydrocortisone acetate 0.5% (5 mg).INACTIVE INGREDIENTS: aluminum sulfate, calcium acetate, cetyl alcohol, hydrochloric acid, methylparaben, mineral oil, polysorbate 60, propylene glycol, propylparaben, purified water, sodium hydroxide, sorbitan stearate, stearic acid, stearyl alcohol, and white petrolatum.

INDICATIONS & USAGE SECTION.

INDICATIONS:. Product is used for the anti-inflammatory and anesthetic relief of pruritus, pruritic eczemas, abrasions, minor burns, insect bites, pain, soreness and discomfort due to pruritus ani, pruritus vulvae, hemorrhoids, anal fissures and similar conditions of the skin and mucous membranes.

MECHANISM OF ACTION SECTION.

MECHANISM OF ACTION:. Product releases lidocaine to stabilize the neuronal membrane by inhibiting the ionic fluxes required for initiation and conduction of impulses, thereby effecting local anesthetic action. Hydrocortisone acetate provides relief of inflammatory and pruritic manifestations of corticosteroid responsive dermatoses. Lidocaine is chemically designated as acetamide, 2-(diethylamino)-N-(2,6-dimethylphenyl), and has the following structure:Hydrocortisone acetate has chemical name pregn-4-ene-3, 20-dione, 21-(acetyloxy)- 11,17- dihydroxy-(11ss)-. It has the following structural formula:.

NURSING MOTHERS SECTION.

NURSING MOTHERS:. Lidocaine is excreted in human milk. The clinicalsignificance of this observation is unknown. Caution should be exercisedwhen lidocaine is administered to nursing woman.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL. Rx Only NDC-13925-160-03 Net Wt. oz. (85 g) Lidocaine 3% Hydrocortisone 0.5% Cream Anti-Inflammatory Anesthetic FOR EXTERNAL USE ONLY. NOT FOR OPHTHALMIC USE. SETON PHARMACEUTICALS. Lidocaine 3% Hydrocortisone 0.5% Cream.

PHARMACOKINETICS SECTION.

PHARMACOKINETICS:. Lidocaine may be absorbed following topicaladministration to mucous membranes, its rate and extent of absorptiondepending upon the specific site of application, duration of exposure,concentration, and total dosage. In general, the rate of absorption of localanesthetic agents following topical application occurs most rapidly afterintratracheal administration. Lidocaine is also well-absorbed from thegastrointestinal tract, but little intact drug appears in the circulation becauseof biotransformation in the liver.Lidocaine is metabolized rapidly by the liver, and metabolites and unchangeddrug are excreted by the kidneys. Biotransformation includes oxidativeN-dealkylation, ring hydroxylation, cleavage of the amide linkage, andconjugation. N-dealkylation, major pathway of biotransformation, yields themetabolites monoethylglycinexylidide and glycinexylidide. Thepharmacological/toxicological actions of these metabolites are, similar to butless potent than, those of lidocaine. Approximately 90% of lidocaineadministered is excreted in the form of various metabolites, and less than10% is excreted unchanged. The primary metabolite in urine is conjugateof 4-hydroxy-2, 6-dimethylaniline. The plasma binding of lidocaine isdependent on drug concentration, and the fraction bound decreases withincreasing concentration. At concentrations of to g of free base per mL,60 to 80 percent of lidocaine is protein bound. Binding is also dependent onthe plasma concentration of the alpha-1-acid glycoprotein. Lidocaine crossesthe blood-brain and placental barriers, presumably by passive diffusion.Studies of lidocaine metabolism following intravenous bolus injections haveshown that the elimination half-life of this agent is typically 1.5 to hours.Because of the rapid rate at which lidocaine is metabolized, any conditionthat affects liver function may alter lidocaine kinetics. The half-life may beprolonged two-fold or more in patients with liver dysfunction. Renaldysfunction does not affect lidocaine kinetics but may increase theaccumulation of metabolites. Factors such as acidosis and the use of CNSstimulants and depressants affect the CNS levels of lidocaine required toproduce overt systemic effects. Objective adverse manifestations becomeincreasingly apparent with increasing venous plasma levels above g freebase per mL. In the rhesus monkey arterial blood levels of 18-21 g/mL havebeen shown to be threshold for convulsive activity.The extent of percutaneous absorption of topical corticosteroids isdetermined by many factors including the vehicle, the integrity ofthe epidermal barrier, and the use of occlusive dressings.Topical corticosteroids can be absorbed from normal intact skin.Inflammation and/or other disease processes in the skin increasepercutaneous absorption. Occlusive dressings substantiallyincrease the percutaneous absorption of topical corticosteroids.Thus, occlusive dressings may be valuable therapeutic adjunctfor treatment of resistant dermatoses.Once absorbed through the skin, topical corticosteroids are handledthrough pharmacokinetic pathways similar to systemicallyadministered corticosteroids. Corticosteroids are bound to plasmaprotein in varying degrees. Corticosteroids are metabolizedprimarily in the liver and are then excreted by the kidneys. Some ofthe topical corticosteroids and their metabolites are also excretedinto the bile.

PRECAUTIONS SECTION.

PRECAUTIONS:. If irritation or sensitivity occurs or infectionappears, discontinue use and institute appropriate therapy. Ifextensive areas are treated, the possibility of systemic absorptionexists. Systemic absorption of topical steroids has producedreversible hypothalamic pituitary-adrenal (HPA) axis suppression,manifestations of Cushings syndrome, hyperglycemia, andglycosuria in some patients. Conditions which augment systemicabsorption include the application of the more potent steroids, useover large surface areas, prolonged use, and the addition ofocclusive dressings. Therefore, patients receiving large dose ofpotent topical steroids applied to large surface area, or under anocclusive dressing, should be evaluated periodically for evidence ofHPA axis suppression. If noted, an attempt should be made towithdraw the drug to reduce the frequency of application, or tosubstitute less potent steroid.Recovery of the HPA axis function is generally prompt and complete upondiscontinuation of the drug. Infrequently, signs and symptoms of steroidwithdrawal may occur, requiring supplemental systemic corticosteroids.Children may absorb proportionately larger amounts of topicalcortico-steroids and thus be more susceptible to systemic toxicity. Ifirritation develops, topical steroids should be discontinued andappropriate therapy instituted. In the presence of dermatologicalinfections, the use of an appropriate antifungal or antibacterial agentshould be instituted. If favorable response does not occur promptly, thecorticosteroid should be discontinued until the infection has beenadequately controlled.

PREGNANCY SECTION.

USE IN PREGNANCY:. Teratogenic Effects:. Pregnancy Category C.Reproduction studies have been performed for lidocaine in rats at dosesup to 6.6 times the human dose and have revealed no evidence of harmto the fetus caused by lidocaine. There are, however, no adequate andwell-controlled studies in pregnant women. Animal reproduction studiesare not always predictive of human response. General considerationshould be given to this fact before administering lidocaine to women ofchildbearing potential, especially during early pregnancy when maximumorganogenesis takes place. Corticosteroids are generally teratogenic inlaboratory animals when administered systemically at relatively lowdosage levels. The more potent corticosteroids have been shown to beteratogenic after dermal application in laboratory animals. There are noadequate and well controlled studies in pregnant women on teratogeniceffects from topically applied corticosteroids. Therefore, topicalcorticosteroids should be used during pregnancy only if the potentialbenefit justifies the potential risk to the fetus. Drugs of this class shouldnot be used extensively on pregnant patients, in large amounts, or forprolonged periods of time.

SPL UNCLASSIFIED SECTION.

Rx OnlyAnti-Inflammatory Anesthetic for Relief of Hemorrhoid Pain Swelling and Inflammation.

TERATOGENIC EFFECTS SECTION.

Teratogenic Effects:. Pregnancy Category C.Reproduction studies have been performed for lidocaine in rats at dosesup to 6.6 times the human dose and have revealed no evidence of harmto the fetus caused by lidocaine. There are, however, no adequate andwell-controlled studies in pregnant women. Animal reproduction studiesare not always predictive of human response. General considerationshould be given to this fact before administering lidocaine to women ofchildbearing potential, especially during early pregnancy when maximumorganogenesis takes place. Corticosteroids are generally teratogenic inlaboratory animals when administered systemically at relatively lowdosage levels. The more potent corticosteroids have been shown to beteratogenic after dermal application in laboratory animals. There are noadequate and well controlled studies in pregnant women on teratogeniceffects from topically applied corticosteroids. Therefore, topicalcorticosteroids should be used during pregnancy only if the potentialbenefit justifies the potential risk to the fetus. Drugs of this class shouldnot be used extensively on pregnant patients, in large amounts, or forprolonged periods of time.

WARNINGS SECTION.

WARNINGS:. For external use only. Not for ophthalmic use. Topical formulations of lidocaine may be absorbed to greaterextent through mucous membranes and abraded, fissured orirritated skin than through intact skin. Product should not beingested or applied into the mouth, inside of the nose or in theeyes. Product should not be used in the ears. Any situation wherelidocaine penetrates beyond the tympanic membrane into themiddle ear is contraindicated because of ototoxicity associated withlidocaine observed in animals when instilled in the middle ear.Product should not come into contact with the eye or be appliedinto the eye because of the risk of severe eye irritation and the lossof eye surface sensation which reduces protective reflexes and canlead to corneal irritation and possibly abrasion. If eye contactoccurs, rinse out the eye immediately with saline or water andprotect the eye surface until sensation is restored.