epinephrine bitartrate - Medications

ARTICADENT (articaine hydrochloride and epinephrine injection), for intraoral submucosal infiltration use, is a sterile, aqueous solution that contains articaine HCl 4% (40 mg/mL) and epinephrine bitartrate in an epinephrine 1:200,000 or epinephrine 1:100,000 strength. Articaine HCl is an amino amide local anesthetic, chemically designated as 4-methyl-3-[2-(propylamino)-propionamido]-2-thiophene-carboxylic acid, methyl ester hydrochloride and is a racemic mixture. Articaine HCl has a molecular weight of 320.84 and the following structural formula: Articaine HCl has a partition coefficient in n-octanol/Soerensen buffer (pH 7.35) of 17 and a pKa of 7.8. Epinephrine bitartrate, (-)-1-(3,4-Dihydroxyphenyl)-2-methylamino-ethanol (+) tartrate (1:1) salt, is a vasoconstrictor with a concentration of 1:200,000 or 1:100,000 (expressed as free base). It has a molecular weight of 333.3 and the following structural formula: ARTICADENT contains the following inactive ingredients: sodium chloride (1.6 mg/mL), and sodium metabisulfite (0.5 mg/mL). The product is formulated with a 15% overage of epinephrine. The pH is adjusted with sodium hydroxide. Chemical Structure Chemical Structure

Articaine HCl and Epinephrine, for intraoral submucosal infiltration use, is a sterile, aqueous solution that contains articaine HCl 4% (40 mg/mL) and epinephrine bitartrate in an epinephrine 1:200,000 or epinephrine 1:100,000 strength. Articaine HCl is an amino amide local anesthetic, chemically designated as 4-methyl-3-[2-(propylamino)-propionamido]-2-thiophene-carboxylic acid, methyl ester hydrochloride and is a racemic mixture. Articaine HCl has a molecular weight of 320.84 and the following structural formula: Articaine HCl has a partition coefficient in n-octanol/Soerensen buffer (pH 7.35) of 17 and a pKa of 7.8. Epinephrine bitartrate, (-)-1-(3,4-Dihydroxyphenyl)-2-methylamino-ethanol (+) tartrate (1:1) salt, is a vasoconstrictor with a concentration of 1:200,000 or 1:100,000 (expressed as free base). It has a molecular weight of 333.3 and the following structural formula: Articaine HCl and Epinephrine contains the following inactive ingredients: sodium chloride (1.6 mg/mL) and sodium metabisulfite (0.5 mg/mL). The product is formulated with a 15% overage of epinephrine. The pH is adjusted with sodium hydroxide. structural formula structural formula

Articaine HCl and Epinephrine, for intraoral submucosal infiltration use, is a sterile, aqueous solution that contains articaine HCl 4% (40 mg/mL) and epinephrine bitartrate in an epinephrine 1:200,000 or epinephrine 1:100,000 strength. Articaine HCl is an amino amide local anesthetic, chemically designated as 4-methyl-3-[2-(propylamino)-propionamido]-2-thiophene-carboxylic acid, methyl ester hydrochloride and is a racemic mixture. Articaine HCl has a molecular weight of 320.84 and the following structural formula: Articaine HCl has a partition coefficient in n-octanol/Soerensen buffer (pH 7.35) of 17 and a pKa of 7.8. Epinephrine bitartrate, (-)-1-(3,4-Dihydroxyphenyl)-2-methylamino-ethanol (+) tartrate (1:1) salt, is a vasoconstrictor with a concentration of 1:200,000 or 1:100,000 (expressed as free base). It has a molecular weight of 333.3 and the following structural formula: Articaine HCl and Epinephrine contains the following inactive ingredients: sodium chloride (1.6 mg/mL) and sodium metabisulfite (0.5 mg/mL). The product is formulated with a 15% overage of epinephrine. The pH is adjusted with sodium hydroxide. structural formula structural formula

Articaine HCl and Epinephrine, for intraoral submucosal infiltration use, is a sterile, aqueous solution that contains articaine HCl 4% (40 mg/mL) and epinephrine bitartrate in an epinephrine 1:200,000 or epinephrine 1:100,000 strength. Articaine HCl is an amino amide local anesthetic, chemically designated as 4-methyl-3-[2-(propylamino)-propionamido]-2-thiophene-carboxylic acid, methyl ester hydrochloride and is a racemic mixture. Articaine HCl has a molecular weight of 320.84 and the following structural formula: Articaine HCl has a partition coefficient in n-octanol/Soerensen buffer (pH 7.35) of 17 and a pKa of 7.8. Epinephrine bitartrate, (-)-1-(3,4-Dihydroxyphenyl)-2-methylamino-ethanol (+) tartrate (1:1) salt, is a vasoconstrictor with a concentration of 1:200,000 or 1:100,000 (expressed as free base). It has a molecular weight of 333.3 and the following structural formula: Articaine HCl and Epinephrine contains the following inactive ingredients: sodium chloride (1.6 mg/mL) and sodium metabisulfite (0.5 mg/mL). The product is formulated with a 15% overage of epinephrine. The pH is adjusted with sodium hydroxide. structural formula structural formula

Articaine HCl and Epinephrine, for intraoral submucosal infiltration use, is a sterile, aqueous solution that contains articaine HCl 4% (40 mg/mL) and epinephrine bitartrate in an epinephrine 1:200,000 or epinephrine 1:100,000 strength. Articaine HCl is an amino amide local anesthetic, chemically designated as 4-methyl-3-[2-(propylamino)-propionamido]-2-thiophene-carboxylic acid, methyl ester hydrochloride and is a racemic mixture. Articaine HCl has a molecular weight of 320.84 and the following structural formula: Articaine HCl has a partition coefficient in n-octanol/Soerensen buffer (pH 7.35) of 17 and a pKa of 7.8. Epinephrine bitartrate, (-)-1-(3,4-Dihydroxyphenyl)-2-methylamino-ethanol (+) tartrate (1:1) salt, is a vasoconstrictor with a concentration of 1:200,000 or 1:100,000 (expressed as free base). It has a molecular weight of 333.3 and the following structural formula: Articaine HCl and Epinephrine contains the following inactive ingredients: sodium chloride (1.6 mg/mL) and sodium metabisulfite (0.5 mg/mL). The product is formulated with a 15% overage of epinephrine. The pH is adjusted with sodium hydroxide. structural formula structural formula

Articaine HCl and Epinephrine, for intraoral submucosal infiltration use, is a sterile, aqueous solution that contains articaine HCl 4% (40 mg/mL) and epinephrine bitartrate in an epinephrine 1:200,000 or epinephrine 1:100,000 strength. Articaine HCl is an amino amide local anesthetic, chemically designated as 4-methyl-3-[2-(propylamino)-propionamido]-2-thiophene-carboxylic acid, methyl ester hydrochloride and is a racemic mixture. Articaine HCl has a molecular weight of 320.84 and the following structural formula: Articaine HCl has a partition coefficient in n-octanol/Soerensen buffer (pH 7.35) of 17 and a pKa of 7.8. Epinephrine bitartrate, (-)-1-(3,4-Dihydroxyphenyl)-2-methylamino-ethanol (+) tartrate (1:1) salt, is a vasoconstrictor with a concentration of 1:200,000 or 1:100,000 (expressed as free base). It has a molecular weight of 333.3 and the following structural formula: Articaine HCl and Epinephrine contains the following inactive ingredients: sodium chloride (1.6 mg/mL) and sodium metabisulfite (0.5 mg/mL). The product is formulated with a 15% overage of epinephrine. The pH is adjusted with sodium hydroxide. structural formula structural formula

Articaine HCl and Epinephrine, for intraoral submucosal infiltration use, is a sterile, aqueous solution that contains articaine HCl 4% (40 mg/mL) and epinephrine bitartrate in an epinephrine 1:200,000 or epinephrine 1:100,000 strength. Articaine HCl is an amino amide local anesthetic, chemically designated as 4-methyl-3-[2-(propylamino)-propionamido]-2-thiophene-carboxylic acid, methyl ester hydrochloride and is a racemic mixture. Articaine HCl has a molecular weight of 320.84 and the following structural formula: Articaine HCl has a partition coefficient in n-octanol/Soerensen buffer (pH 7.35) of 17 and a pKa of 7.8. Epinephrine bitartrate, (-)-1-(3,4-Dihydroxyphenyl)-2-methylamino-ethanol (+) tartrate (1:1) salt, is a vasoconstrictor with a concentration of 1:200,000 or 1:100,000 (expressed as free base). It has a molecular weight of 333.3 and the following structural formula: Articaine HCl and Epinephrine contains the following inactive ingredients: sodium chloride (1.6 mg/mL) and sodium metabisulfite (0.5 mg/mL). The product is formulated with a 15% overage of epinephrine. The pH is adjusted with sodium hydroxide. structural formula structural formula

Articaine HCl and Epinephrine (articaine hydrochloride and epinephrine injection), for intraoral submucosal infiltration use, is a sterile, aqueous solution that contains articaine HCl 4% (40mg/mL) and epinephrine bitartrate in an epinephrine 1:200,000 or epinephrine 1:100,000 strength. Articaine HCl is an amino amide local anesthetic, chemically designated as 4-methyl-3-[2-(propylamino)- propionamido]-2-thiophene-carboxylic acid, methyl ester hydrochloride and is a racemic mixture. Articaine HCl has a molecular weight of 320.84 and the following structural formula: Articaine HCl has a partition coefficient in n-octanol/Soerensen buffer (pH 7.35) of 17 and a pKa of 7.8. Epinephrine bitartrate, (-)-1-(3,4-dihydroxyphenyl)-2-methylamino-ethanol (+) tartrate (1:1) salt, is a vasoconstrictor with a concentration of 1:200,000 or 1:100,000 (expressed as free base). It has a molecular weight of 333.3 and the following structural formula: Articaine HCl and Epinephrine contains the following inactive ingredients: sodium chloride (1.0 mg/mL), sodium metabisulfite (0.5 mg/mL), and water for injection. The product is formulated with a 10% overage of epinephrine. The pH is adjusted to 3.6 with hydrochloric acid. Articaine HCl structural formula Epinephrine bitartrate structural formula

Articaine HCl and Epinephrine, for intraoral submucosal infiltration use, is a sterile, aqueous solution that contains articaine HCl 4% (40 mg/mL) and epinephrine bitartrate in an epinephrine 1:200,000 or epinephrine 1:100,000 strength. Articaine HCl is an amino amide local anesthetic, chemically designated as 4-methyl-3-[2-(propylamino)-propionamido]-2-thiophene-carboxylic acid, methyl ester hydrochloride and is a racemic mixture. Articaine HCl has a molecular weight of 320.84 and the following structural formula: Articaine HCl has a partition coefficient in n-octanol/Soerensen buffer (pH 7.35) of 17 and a pKa of 7.8. Epinephrine bitartrate, (-)-1-(3,4-Dihydroxyphenyl)-2-methylamino-ethanol (+) tartrate (1:1) salt, is a vasoconstrictor with a concentration of 1:200,000 or 1:100,000 (expressed as free base). It has a molecular weight of 333.3 and the following structural formula: Articaine HCl and Epinephrine contains the following inactive ingredients: sodium chloride (1.6 mg/mL) and sodium metabisulfite (0.5 mg/mL). The product is formulated with a 15% overage of epinephrine. The pH is adjusted with sodium hydroxide. articaine structural formula epinephrine structural formula

Articaine HCl and Epinephrine Injection, for intraoral submucosal infiltration use, is a sterile, aqueous solution that contains articaine HCl 4% (40mg/mL) and epinephrine bitartrate in an epinephrine 1:200,000 or epinephrine 1:100,000 strength. Articaine HCl is an amino amide local anesthetic, chemically designated as 4-methyl-3-[2-(propylamino)- propionamido]-2-thiophene-carboxylic acid, methyl ester hydrochloride and is a racemic mixture. Articaine HCl has a molecular weight of 320.84 and the following structural formula: Articaine HCl has a partition coefficient in n-octanol/Soerensen buffer (pH 7.35) of 17 and a pKa of 7.8. Epinephrine bitartrate, (-)-1-(3,4-dihydroxyphenyl)-2-methylamino-ethanol (+) tartrate (1:1) salt, is a vasoconstrictor with a concentration of 1:200,000 or 1:100,000 (expressed as free base). It has a molecular weight of 333.3 and the following structural formula: Articaine HCl and Epinephrine contains the following inactive ingredients: sodium chloride (1.0 mg/mL), sodium metabisulfite (0.5 mg/mL), and water for injection. The product is formulated with a 10% overage of epinephrine. The pH is adjusted to 3.6 with hydrochloric acid. Structure Structure2

Sensorcaine ® (bupivacaine HCl) injections are sterile isotonic solutions that contain a local anesthetic agent with and without epinephrine (as bitartrate) 1:200,000 and are administered parenterally by injection. See INDICATIONS & USAGE for specific uses. Solutions of bupivacaine HCl may be autoclaved if they do not contain epinephrine. Sensorcaine injections contain bupivacaine HCl which is chemically designated as 2- piperidinecarboxamide, 1-butyl- N-(2,6-dimethylphenyl)-, monohydrochloride, monohydrate and has the following structure: Epinephrine is (-)-3,4-Dihydroxy-α [(methylamino)methyl] benzyl alcohol. It has the following structural formula: The pK a of bupivacaine (8.1) is similar to that of lidocaine (7.86). However, bupivacaine possesses a greater degree of lipid solubility and is protein bound to a greater extent than lidocaine. Bupivacaine is related chemically and pharmacologically to the aminoacyl local anesthetics. It is a homologue of mepivacaine and is chemically related to lidocaine. All three of these anesthetics contain an amide linkage between the aromatic nucleus and the amino, or piperidine group. They differ in this respect from the procaine-type local anesthetics, which have an ester linkage. Dosage forms listed as Sensorcaine-MPF indicates s ingle dose solutions that are Methyl Paraben Free (MPF). Sensorcaine-MPF is a sterile isotonic solution containing sodium chloride. Sensorcaine in multiple dose vials, each mL also contains 1 mg methylparaben as antiseptic preservative. The pH of these solutions is adjusted to between 4.0 and 6.5 with sodium hydroxide and/or hydrochloric acid. Sensorcaine-MPF with Epinephrine 1:200,000 (as bitartrate) is a sterile isotonic solution containing sodium chloride. Each mL contains bupivacaine hydrochloride and 0.005 mg epinephrine, with 0.5 mg sodium metabisulfite as an antioxidant and 0.2 mg citric acid (anhydrous) as stabilizer. Sensorcaine with Epinephrine 1:200,000 (as bitartrate) in multiple dose vials, each mL also contains 1 mg methylparaben as antiseptic preservative. The pH of these solutions is adjusted to between 3.3 to 5.5 with sodium hydroxide and/or hydrochloric acid. Filled under nitrogen. Note: The user should have an appreciation and awareness of the formulations and their intended uses (see DOSAGE AND ADMINISTRATION ). STRUCTURE 1 STRUCTURE 2

Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection contains bupivacaine hydrochloride, an amide local anesthetic, as the active pharmaceutical ingredient. The route of administration for Bupivacaine Hydrochloride Injection (without epinephrine) is by injection, for infiltration, perineural, caudal, epidural, or retrobulbar use. The route of administration for Bupivacaine Hydrochloride and Epinephrine Injection is by injection, for infiltration, perineural, caudal, or epidural use. Multiple-dose vials contain methylparaben [see Warnings and Precautions (5.4) ] . Bupivacaine hydrochloride is 2-piperidinecarboxamide, 1-butyl- N -(2,6-dimethylphenyl)-, monohydrochloride, monohydrate. It is a white crystalline powder that is freely soluble in 95 percent ethanol, soluble in water, and slightly soluble in chloroform or acetone. It has the following structural formula: Bupivacaine hydrochloride with 1:200,000 epinephrine, contains bupivacaine hydrochloride and epinephrine (an alpha and beta-adrenergic agonist) as active pharmaceutical ingredients. This product is for injection via local infiltration, peripheral nerve block, and caudal and lumbar epidural blocks. Multiple-dose vials contain methylparaben and they should not be used for caudal and lumbar epidural blocks. Epinephrine is (-)-3,4-Dihydroxy-α-[(methylamino)methyl] benzyl alcohol. Epinephrine is a vasoconstrictor. It has the following structural formula: Bupivacaine Hydrochloride Injection, USP is a clear and colorless sterile isotonic solution. Each mL of single-dose vial contains 2.5 mg, 5 mg, or 7.5 mg of bupivacaine hydrochloride (equivalent to 2.22 mg, 4.44 mg, or 6.66 mg of bupivacaine, respectively), sodium chloride for isotonicity, sodium hydroxide or hydrochloric acid to adjust the pH between 4 and 6.5, in water for injection. For the multiple-dose vials, each mL also contains 1 mg methylparaben as preservative. Bupivacaine Hydrochloride and Epinephrine Injection, USP is a clear and colorless sterile isotonic solution. Each mL contains 2.5 mg or 5 mg bupivacaine hydrochloride (equivalent to 2.22 mg or 4.44 mg of bupivacaine, respectively), and 0.005 mg of epinephrine, with sodium chloride for isotonicity, 0.1 mg sodium metabisulfite as antioxidant, and 0.1 mg edetate calcium disodium anhydrous as stabilizer. The pH of these solutions is adjusted to between 3.3 and 5.5 with sodium hydroxide or hydrochloric acid. For the multiple-dose vials, each mL also contains 1 mg methylparaben as preservative. The specific gravity of Bupivacaine Hydrochloride and Epinephrine Injection [0.5% (5 mg/mL) of bupivacaine] at 25 ºC is 1.007. Chemical Structure Chemical Structure

Bupivacaine Hydrochloride is 2-Piperidinecarboxamide, 1-butyl-N-(2,6-dimethylphenyl)-, monohydrochloride, monohydrate, a white crystalline powder that is freely soluble in 95 percent ethanol, soluble in water, and slightly soluble in chloroform or acetone. It has the following structural formula: Epinephrine is (-)-3,4-Dihydroxy-a-[(methylamino)methyl] benzyl alcohol. It has the following structural formula: Bupivacaine Hydrochloride is available in sterile isotonic solutions with and without epinephrine (as bitartrate) 1:200,000 for injection via local infiltration, peripheral nerve block, and caudal and lumbar epidural blocks. Solutions of Bupivacaine Hydrochloride may be autoclaved if they do not contain epinephrine. Solutions are clear and colorless. Bupivacaine is related chemically and pharmacologically to the aminoacyl local anesthetics. It is a homologue of mepivacaine and is chemically related to lidocaine. All three of these anesthetics contain an amide linkage between the aromatic nucleus and the amino, or piperidine group. They differ in this respect from the procaine-type local anesthetics, which have an ester linkage. Bupivacaine Hydrochloride Injection, USP is available in sterile, isotonic solutions containing bupivacaine hydrochloride in water for injection with characteristics as follows: May contain sodium hydroxide and/or hydrochloric acid for pH adjustment. (See HOW SUPPLIED section for pH information.) Multiple-dose vials contain methylparaben 1 mg/mL added as a preservative. Bupivacaine and Epinephrine Injection, USP is available in sterile, isotonic solutions containing bupivacaine hydrochloride and epinephrine 1:200,000 with characteristics as follows: Sodium metabisulfite 0.1 mg/mL added as antioxidant and edetate calcium disodium, anhydrous 0.1 mg/mL added as stabilizer. May contain sodium hydroxide and/or hydrochloric acid for pH adjustment. (See HOW SUPPLIED section for pH information.) Multipledose vials contain methylparaben 1 mg/mL added as a preservative. Single-dose solutions contain no added bacteriostat or anti-microbial agent and unused portions should be discarded after use. Formula1.jpg Formula2.jpg Image1.jpg Image2.jpg

4% Citanest ® Forte DENTAL with Epinephrine 1:200,000 (Citanest Forte), Prilocaine HCl 4% (72 mg/1.8 mL) (40 mg/mL) with Epinephrine 1:200,000 Injection, is a sterile, non-pyrogenic isotonic solution that contains a local anesthetic agent with epinephrine (as bitartrate) and is administered parenterally by injection. See INDICATIONS AND USAGE for specific uses. The quantitative composition is shown in Table 1. Citanest Forte contains prilocaine HCl, which is chemically designated as propanamide, N-(2-methyl-phenyl) -2- (propylamino)-, monohydrochloride and has the following structural formula: C 13 H 20 N 2 O ∙ HCl molecular wt = 256.77 and epinephrine, which is (-) -3, 4-Dihydroxy- ∝ -[(methylamino) methyl] benzyl alcohol and has the following structural formula: C 9 H 13 NO 3 molecular wt = 183.21 Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. The specific quantitative composition is shown in Table 1. Table 1. COMPOSITION Product Identification Formula (mg/mL) Prilocaine HCl Epinephrine (as bitartrate) Citric Acid Sodium Metabisulfite pH Note: Sodium hydroxide and/or hydrochloric acid may be used to adjust the pH of Citanest Forte. 4% Citanest ® Forte DENTAL with Epinephrine 1:200,000 (Prilocaine HCl 4% (72 mg/1.8 mL) (40 mg/mL) with Epinephrine 1:200,000 Injection) 40.0 0.005 0.2 0.5 3.3 to 5.5 Chemical Structure Chemical Structure

Epinephrine in 0.9% Sodium Chloride Injection is a clear, colorless sterile solution containing 16 mg (64 mcg epinephrine base per mL which is equivalent to 116.4 mcg epinephrine bitartrate) epinephrine, USP in 250 mL VIAFLO bag. In 250 ml VIAFLO bag, each 1 mL of Epinephrine in 0.9% Sodium Chloride Injection solution contains 0.032 mg edetate disodium, 9 mg sodium chloride, 0.05 mg sodium metabisulfite, water for injection. Hydrochloric acid and/or sodium hydroxide to adjust pH range of 3.4 to 4.5. This sterile solution is to be administered by the intravenous route. Epinephrine Bitartrate, USP is a sympathomimetic catecholamine (adrenergic agent) designated chemically as 1,2-Benzenediol, 4-[1-hydroxy-2-(methylamino)ethyl]-, (R) -,[ R -( R *, R *)]-2,3-dihydroxybutanedioate (1:1) (salt), a white or greyish-white or light brownish-grey, odourless, crystalline powder. Slowly darkens on exposure to air and light. It has the following structural formula: The molecular weight of epinephrine bitartrate is 333.3 and molecular formula is C 9 H 13 NO 3 • C 4 H 6 O 6 . Epinephrine solution deteriorates rapidly on exposure to air or light, turning pink from oxidation to adrenochrome and brown from the formation of melanin. VIAFLO container is a flexible plastic container fabricated from a multilayer sheeting composed of Polypropylene (PP), Polyamide (PA) and Polyethylene (PE). The amount of water that can permeate from the container into the overpouch is insufficient to affect the solution significantly. Solutions in contact with the flexible container can leach out certain of the container’s chemical components in very small amounts within the expiration period. The suitability of the container material has been confirmed by tests in animals according to USP biological tests for plastic containers. image-01-structural-formula-epinephrine

Lidocaine Hydrochloride and Epinephrine, USP is a sterile isotonic solution containing a local anesthetic agent, Lidocaine Hydrochloride, and a vasoconstrictor, Epinephrine (as bitartrate) and are administered parenterally by injection. Both solutions are available in single dose cartridges of 1.7 mL (See INDICATIONS AND USAGE for specific uses). The solutions contain lidocaine hydrochloride which is chemically designated as acetamide, 2-(diethylamino)-N-(2,6-dimethylphenyl)-monohydrochloride, and has the following structural formula: C 14 H 22 N 2 0 • HCl • H 2 0 M.W. 288.8 Epinephrine is ( - )-3,4-Dihydroxy- α -[(Methylamino) methyl] benzyl alcohol and has the following structural formula: C 9 H 13 NO 3 M.W. 183.21 COMPOSITION OF AVAILABLE SOLUTIONS BRAND NAME PRODUCT IDENTIFICATION FORMULA SINGLE DOSE CARTRIDGE Lidocaine hydrochloride Epinephrine (as the bitartrate) Sodium Chloride Potassium metabisulfite Edetate Disodium Concentration % Dilution (mg/mL) (mg/mL) (mg/mL) 2 1:50,000 6.5 1.2 0.25 2 1:100,000 6.5 1.2 0.25 The pH of all solutions are adjusted to USP limits with sodium hydroxide. lidocaine hydrochloride Epinephrine

Lidocaine Hydrochloride and Epinephrine, USP is a sterile isotonic solution containing a local anesthetic agent, Lidocaine Hydrochloride, and a vasoconstrictor, Epinephrine (as bitartrate) and are administered parenterally by injection. Both solutions are available in single dose cartridges of 1.7 mL (See INDICATIONS AND USAGE for specific uses). The solutions contain lidocaine hydrochloride which is chemically designated as acetamide, 2-(diethylamino)-N-(2,6-dimethylphenyl)-monohydrochloride, and has the following structural formula: C 14 H 22 N 2 0 • HCl • H 2 0 M.W. 288.8 Epinephrine is ( - )-3,4-Dihydroxy- α -[(Methylamino) methyl] benzyl alcohol and has the following structural formula: C 9 H 13 NO 3 M.W. 183.21 COMPOSITION OF AVAILABLE SOLUTIONS PRODUCT IDENTIFICATION FORMULA SINGLE DOSE CARTRIDGE Lidocaine hydrochloride Epinephrine (as the bitartrate) Sodium Chloride Potassium metabisulfite Edetate Disodium Concentration % Dilution (mg/mL) (mg/mL) (mg/mL) The pH of all solutions are adjusted to USP limits with sodium hydroxide. 2 1:50,000 6.5 1.2 0.25 2 1:100,000 6.5 1.2 0.25 lidocaine hydrochloride Epinephrine

Lidocaine Hydrochloride and Epinephrine, USP is a sterile isotonic solution containing a local anesthetic agent, Lidocaine Hydrochloride, and a vasoconstrictor, Epinephrine (as bitartrate) and are administered parenterally by injection. Both solutions are available in single dose cartridges of 1.7 mL (See INDICATIONS AND USAGE for specific uses). The solutions contain lidocaine hydrochloride which is chemically designated as acetamide, 2-(diethylamino)-N-(2,6-dimethylphenyl)-monohydrochloride, and has the following structural formula: C 14 H 22 N 2 0 • HCl • H 2 0 M.W. 288.8 Epinephrine is ( - )-3,4-Dihydroxy- α -[(Methylamino) methyl] benzyl alcohol and has the following structural formula: C 9 H 13 NO 3 M.W. 183.21 COMPOSITION OF AVAILABLE SOLUTIONS BRAND NAME PRODUCT IDENTIFICATION FORMULA SINGLE DOSE CARTRIDGE Lidocaine hydrochloride Epinephrine (as the bitartrate) Sodium Chloride Potassium metabisulfite Edetate Disodium Concentration % Dilution (mg/mL) (mg/mL) (mg/mL) 2 1:50,000 6.5 1.2 0.25 2 1:100,000 6.5 1.2 0.25 The pH of all solutions are adjusted to USP limits with sodium hydroxide. lidocaine hydrochloride Epinephrine

Lidocaine Hydrochloride and Epinephrine, USP is a sterile isotonic solution containing a local anesthetic agent, Lidocaine Hydrochloride, and a vasoconstrictor, Epinephrine (as bitartrate) and are administered parenterally by injection. Both solutions are available in single dose cartridges of 1.7 mL (See INDICATIONS AND USAGE for specific uses). The solutions contain lidocaine hydrochloride which is chemically designated as acetamide, 2-(diethylamino)-N-(2,6-dimethylphenyl)-monohydrochloride, and has the following structural formula C 14 H 22 N 2 0HCl H 2 0 M.W. 288.8 Epinephrine is ( - )-3,4-Dihydroxy-α-[(Methylamino) methyl] benzyl alcohol and has the following structural formula: C 9 H 13 NO 3 M.W. 183.21 PRODUCT IDENTIFICATION COMPOSITION OF AVAILABLE SOLUTIONS BRAND NAME PRODUCT IDENTIFICATION FORMULA SINGLE DOSE CARTRIDGE Lidocaine hydrochloride Epinephrine (as the bitartrate) Sodium Chloride Potassium metabisulfite Edetate Disodium Concentration % Dilution (mg/mL) (mg/mL) (mg/mL) 2 1:50,000 6.5 1.2 0.25 2 1:100,000 6.5 1.2 0.25 The pH of all solutions are adjusted to USP limits with sodium hydroxide. lidocaine hydrochloride Epinephrine

Lidocaine Hydrochloride and Epinephrine, USP is a sterile isotonic solution containing a local anesthetic agent, Lidocaine Hydrochloride, and a vasoconstrictor, Epinephrine (as bitartrate) and are administered parenterally by injection. Both solutions are available in single dose cartridges of 1.7 mL (See INDICATIONS AND USAGE for specific uses). The solutions contain lidocaine hydrochloride which is chemically designated as acetamide, 2-(diethylamino)-N-(2,6-dimethylphenyl)-monohydrochloride, and has the following structural formula C 14 H 22 N 2 0•HCl• H 2 0 M.W. 288.8 Epinephrine is ( - )-3,4-Dihydroxy-α-[(Methylamino) methyl] benzyl alcohol and has the following structural formula: C 9 H 13 NO 3 M.W. 183.21 COMPOSITION OF AVAILABLE SOLUTIONS PRODUCT IDENTIFICATION FORMULA SINGLE DOSE CARTRIDGE Lidocaine hydrochloride Epinephrine (as the bitartrate) Sodium Chloride Potassium metabisulfite Edetate Disodium Concentration % Dilution (mg/mL) (mg/mL) (mg/mL) The pH of all solutions are adjusted to USP limits with sodium hydroxide. 2 1:50,000 6.5 1.2 0.25 2 1:100,000 6.5 1.2 0.25 lidocaine hydrochloride epinephrine

Lidocaine Hydrochloride and Epinephrine, USP is a sterile isotonic solution containing a local anesthetic agent, Lidocaine Hydrochloride, and a vasoconstrictor, Epinephrine (as bitartrate) and are administered parenterally by injection. Both solutions are available in single dose cartridges of 1.7 mL (See INDICATIONS AND USAGE for specific uses). The solutions contain lidocaine hydrochloride which is chemically designated as acetamide, 2-(diethylamino)-N-(2,6-dimethylphenyl)-monohydrochloride, and has the following structural formula C 14 H 22 N 2 0 HCl H 2 0 M.W. 288.8 Epinephrine is ( - )-3,4-Dihydroxy- -[(Methylamino) methyl] benzyl alcohol and has the following structural formula: C 9 H 13 NO 3 M.W. 183.21 COMPOSITION OF AVAILABLE SOLUTIONS BRAND NAME PRODUCT IDENTIFICATION FORMULA SINGLE DOSE CARTRIDGE Lidocaine hydrochloride Epinephrine (as the bitartrate) Sodium Chloride Potassium metabisulfite Edetate Disodium Concentration % Dilution (mg/mL) (mg/mL) (mg/mL) 2 1:50,000 6.5 1.2 0.25 2 1:100,000 6.5 1.2 0.25 The pH of all solutions are adjusted to USP limits with sodium hydroxide. Lidocaine Hydrochloride Epinephrine

Lidocaine Hydrochloride and Epinephrine, USP is a sterile isotonic solution containing a local anesthetic agent, Lidocaine Hydrochloride, and a vasoconstrictor, Epinephrine (as bitartrate) and are administered parenterally by injection. Both solutions are available in single dose cartridges of 1.7 mL (See INDICATIONS AND USAGE for specific uses). The solutions contain lidocaine hydrochloride which is chemically designated as acetamide, 2-(diethylamino)-N-(2,6-dimethylphenyl)-monohydrochloride, and has the following structural formula : C 14 H 22 N 2 0 • HCl • H 2 0 M.W. 288.8 Epinephrine is ( - )-3,4-Dihydroxy-α-[(Methylamino) methyl] benzyl alcohol and has the following structural formula : C 9 H 13 NO 3 M.W. 183.21 COMPOSITION OF AVAILABLE SOLUTIONS PRODUCT IDENTIFICATION FORMULA SINGLE DOSE CARTRIDGE Lidocaine hydrochloride Epinephrine (as the bitartrate) Sodium Chloride Potassium metabisulfite Edetate Disodium Concentration % Dilution (mg/mL) (mg/mL) (mg/mL) The pH of all solutions are adjusted to USP limits with sodium hydroxide. 2 1:50,000 6.5 1.2 0.25 2 1:100,000 6.5 1.2 0.25 Chemical Structure Chemical Structure

Lidocaine Hydrochloride and Epinephrine, USP is a sterile isotonic solution containing a local anesthetic agent, Lidocaine Hydrochloride, and a vasoconstrictor, Epinephrine (as bitartrate) and are administered parenterally by injection. Both solutions are available in single dose cartridges of 1.7 mL (See INDICATIONS AND USAGE for specific uses). The solutions contain lidocaine hydrochloride which is chemically designated as acetamide, 2-(diethylamino)-N-(2,6-dimethylphenyl)-monohydrochloride, and has the following structural formula: C 14 H 22 N 2 0 • HCl • H 2 0 M.W. 288.8 Epinephrine is ( - )-3,4-Dihydroxy-α-[(Methylamino) methyl] benzyl alcohol and has the following structural formula: C 9 H 13 NO 3 M.W. 183.21 COMPOSITION OF AVAILABLE SOLUTIONS BRAND NAME PRODUCT IDENTIFICATION FORMULA SINGLE DOSE CARTRIDGE Lidocaine hydrochloride Epinephrine (as the bitartrate) Sodium Chloride Potassium metabisulfite Edetate Disodium Concentration % Dilution (mg/mL) (mg/mL) (mg/mL) 2 1:50,000 6.5 1.2 0.25 2 1:100,000 6.5 1.2 0.25 The pH of all solutions are adjusted to USP limits with sodium hydroxide. lidocaine hydrochloride Epinephrine

Lidocaine Hydrochloride and Epinephrine, USP is a sterile isotonic solution containing a local anesthetic agent, Lidocaine Hydrochloride, and a vasoconstrictor, Epinephrine (as bitartrate) and are administered parenterally by injection. Both solutions are available in single dose cartridges of 1.7 mL (See INDICATIONS AND USAGE for specific uses). The solutions contain lidocaine hydrochloride which is chemically designated as acetamide, 2-(diethylamino)-N-(2,6-dimethylphenyl)-monohydrochloride, and has the following structural formula C 14 H 22 N 2 0 HCl H 2 0 M.W. 288.8 Epinephrine is ( - )-3,4-Dihydroxy-α-[(Methylamino) methyl] benzyl alcohol and has the following structural formula: C 9 H 13 NO 3 M.W. 183.21 COMPOSITION OF AVAILABLE SOLUTIONS BRAND NAME PRODUCT IDENTIFICATION FORMULA SINGLE DOSE CARTRIDGE Lidocaine hydrochloride Epinephrine (as the bitartrate) Sodium Chloride Potassium metabisulfite Edetate Disodium Concentration % Dilution (mg/mL) (mg/mL) (mg/mL) 2 1:50,000 6.5 1.2 0.25 2 1:100,000 6.5 1.2 0.25 The pH of all solutions are adjusted to USP limits with sodium hydroxide. Lidocaine Hydrochloride Epinephrine

Sterile isotonic solutions containing a local anesthetic agent, Lidocaine Hydrochloride, and a vasoconstrictor, epinephrine (as bitartrate) and are administered parenterally by injection. Both solutions are available in single dose cartridges of 1.7 mL (See INDICATIONS AND USAGE for specific uses). Solutions contain lidocaine hydrochloride which is chemically designated as acetamide, 2-(diethylamino)-N-(2,6-dimethylphenyl)-monohydrochloride, and has the following structural formula: C 14 H 22 N 2 0 • HCl • H 2 0 M.W. 288.8 Epinephrine is ( - )-3, 4-Dihydroxy-α-[(Methylamino) methyl] benzyl alcohol and has the following structural formula: C 9 H 13 N0 3 M.W. 183.21 COMPOSITION OF LIDOCAINE HYDROCHLORIDE AND EPINEPHRINE INJECTION, USP BRAND NAME PRODUCT IDENTIFICATION FORMULA SINGLE DOSE CARTRIDGE Lidocaine hydrochloride Epinephrine (as the bitartrate) Sodium Chloride Potassium metabisulfite Edetate Disodium Concentration % Dilution (mg/mL) (mg/mL) (mg/mL) LIDOCAINE HCl 2% and EPINEPHRINE 1:50,000 2 1:50,000 6.5 1.2 0.25 LIDOCAINE HCl 2% and EPINEPHRINE 1:100,000 2 1:100,000 6.5 1.2 0.25 The pH of the lidocaine hydrochloride and epinephrine injection, USP solutions are adjusted to USP limits with sodium hydroxide. lidocaine hydrochloride Epinephrine

Sterile isotonic solutions containing a local anesthetic agent, Lidocaine Hydrochloride, and a vasoconstrictor, epinephrine (as bitartrate) and are administered parenterally by injection. Both solutions are available in single dose cartridges of 1.7 mL (See INDICATIONS AND USAGE for specific uses). Solutions contain lidocaine hydrochloride which is chemically designated as acetamide, 2-(diethylamino)-N-(2,6-dimethylphenyl)-monohydrochloride, and has the following structural formula: C 14 H 22 N 2 0 HCl H 2 0 M.W. 288.8 Epinephrine is ( - )-3, 4-Dihydroxy-α-[(Methylamino) methyl] benzyl alcohol and has the following structural formula: C 9 H 13 NO 3 M.W. 183.21 COMPOSITION OF LIDOCAINE HYDROCHLORIDE AND EPINEPHRINE INJECTION, USP BRAND NAME PRODUCT IDENTIFICATION FORMULA SINGLE DOSE CARTRIDGE Lidocaine hydrochloride Epinephrine (as the bitartrate) Sodium Chloride Potassium metabisulfite Edetate Disodium Concentration % Dilution (mg/mL) (mg/mL) (mg/mL) LIDOCAINE HCl 2% and EPINEPHRINE 1:50,000 2 1:50,000 6.5 1.2 0.25 LIDOCAINE HCl 2% and EPINEPHRINE 1:100,000 2 1:100,000 6.5 1.2 0.25 The pH of the lidocaine hydrochloride and epinephrine injection, USP solutions are adjusted to USP limits with sodium hydroxide. lidocaine hydrochloride epinephrine

Lidocaine Hydrochloride and Epinephrine, USP is a sterile isotonic solution containing a local anesthetic agent, Lidocaine Hydrochloride, and a vasoconstrictor, Epinephrine (as bitartrate) and are administered parenterally by injection. Both solutions are available in single dose cartridges of 1.7 mL (See INDICATIONS AND USAGE for specific uses). The solutions contain lidocaine hydrochloride which is chemically designated as acetamide, 2-(diethylamino)-N-(2,6-dimethylphenyl)-monohydrochloride, and has the following structural formula : C 14 H 22 N 2 0•HCl• H 2 0 M.W. 288.8 Epinephrine is ( - )-3,4-Dihydroxy-α-[(Methylamino) methyl] benzyl alcohol and has the following structural formula : C 9 H 13 NO 3 M.W. 183.21 COMPOSITION OF AVAILABLE SOLUTIONS PRODUCT IDENTIFICATION FORMULA SINGLE DOSE CARTRIDGE Lidocaine hydrochloride Epinephrine (as the bitartrate) Sodium Chloride Potassium metabisulfite Edetate Disodium Concentration % Dilution (mg/mL) (mg/mL) (mg/mL) The pH of all solutions are adjusted to USP limits with sodium hydroxide. 2 1:50,000 6.5 1.2 0.25 2 1:100,000 6.5 1.2 0.25 Chemical Structure Chemical Structure

Lidocaine Hydrochloride and Epinephrine, USP is a sterile isotonic solution containing a local anesthetic agent, Lidocaine Hydrochloride, and a vasoconstrictor, Epinephrine (as bitartrate) and are administered parenterally by injection. Both solutions are available in single dose cartridges of 1.7 mL (See INDICATIONS AND USAGE for specific uses). The solutions contain lidocaine hydrochloride which is chemically designated as acetamide, 2-(diethylamino)-N-(2,6-dimethylphenyl)-monohydrochloride, and has the following structural formula: C 14 H 22 N 2 0 • HCl • H 2 0 M.W. 288.8 Epinephrine is ( - )-3,4-Dihydroxy- -[(Methylamino) methyl] benzyl alcohol and has the following structural formula: C 9 H 13 NO 3 M.W. 183.21 COMPOSITION OF AVAILABLE SOLUTIONS BRAND NAME PRODUCT IDENTIFICATION FORMULA SINGLE DOSE CARTRIDGE Lidocaine hydrochloride Epinephrine (as the bitartrate) Sodium Chloride Potassium metabisulfite Edetate Disodium Concentration % Dilution (mg/mL) (mg/mL) (mg/mL) 2 1:50,000 6.5 1.2 0.25 2 1:100,000 6.5 1.2 0.25 The pH of all solutions are adjusted to USP limits with sodium hydroxide. lidocaine hydrochloride symbol Epinephrine

Xylocaine (lidocaine HCl) Injections are sterile, nonpyrogenic, aqueous solutions that contain a local anesthetic agent with or without epinephrine and are administered parenterally by injection. See INDICATIONS AND USAGE section for specific uses. Xylocaine solutions contain lidocaine HCl, which is chemically designated as acetamide, 2-(diethylamino)-N-(2,6-dimethylphenyl)-, monohydrochloride and has the molecular wt. 270.8. Lidocaine HCl (C 14H 22N 2O • HCl) has the following structural formula: Epinephrine is (-) -3, 4-Dihydroxy-α-[(methylamino) methyl] benzyl alcohol and has the molecular wt. 183.21. Epinephrine (C 9H 13NO 3) has the following structural formula: Dosage forms listed as Xylocaine-MPF indicate single dose solutions that are Methyl Paraben Free (MPF). Xylocaine MPF is a sterile, nonpyrogenic, isotonic solution containing sodium chloride. Xylocaine in multiple dose vials: Each mL also contains 1 mg methyl­paraben as antiseptic preservative. The pH of these solutions is adjusted to approximately 6.5 (5.0 to 7.0) with sodium hydroxide and/or hydrochloric acid. Xylocaine MPF with Epinephrine is a sterile, nonpyrogenic, isotonic solution containing sodium chloride. Each mL contains lidocaine hydrochloride and epinephrine, with 0.5 mg sodium metabisulfite as an antioxidant and 0.2 mg citric acid as a stabilizer. Xylocaine with Epinephrine in multiple dose vials: Each mL also contains 1 mg methylparaben as antiseptic preservative. The pH of these solutions is adjusted to approximately 4.5 (3.3 to 5.5) with sodium hydroxide and/or hydrochloric acid. Filled under nitrogen. STRUCTURE 1 STRUCTURE 2

Xylocaine (lidocaine HCl) Injections are sterile, nonpyrogenic, aqueous solutions that contain a local anesthetic agent with or without epinephrine and are administered parenterally by injection. See INDICATIONS AND USAGE uses. Xylocaine solutions contain lidocaine HCl, which is chemically designated as acetamide, 2-(diethylamino)-N-(2,6-dimethylphenyl)-, monohydrochloride and has the molecular wt. 270.8. Lidocaine HCl (C 14H 22N 2O • HCl) has the following structural formula: Epinephrine is (-) -3, 4-Dihydroxy-α-[(methylamino) methyl] benzyl alcohol and has the molecular wt. 183.21. Epinephrine (C 9H 13NO 3) has the following structural formula: Dosage forms listed as Xylocaine-MPF indicate single dose solutions that are Methyl Paraben Free (MPF). Xylocaine MPF is a sterile, nonpyrogenic, isotonic solution containing sodium chloride. Xylocaine in multiple dose vials: Each mL also contains 1 mg methyl­paraben as antiseptic preservative. The pH of these solutions is adjusted to approximately 6.5 (5.0 to 7.0) with sodium hydroxide and/or hydrochloric acid. Xylocaine MPF with Epinephrine is a sterile, nonpyrogenic, isotonic solution containing sodium chloride. Each mL contains lidocaine hydrochloride and epinephrine, with 0.5 mg sodium metabisulfite as an antioxidant and 0.2 mg citric acid as a stabilizer. Xylocaine with Epinephrine in multiple dose vials: Each mL also contains 1 mg methylparaben as antiseptic preservative. The pH of these solutions is adjusted to approximately 4.5 (3.3 to 5.5) with sodium hydroxide and/or hydrochloric acid. Filled under nitrogen. STRUCTURE 1 STRUCTURE 2

Xylocaine (lidocaine HCl) Injections are sterile, nonpyrogenic, aqueous solutions that contain a local anesthetic agent with or without epinephrine and are administered parenterally by injection. See INDICATIONS & USAGE section for specific uses. Xylocaine solutions contain lidocaine HCl, which is chemically designated as acetamide, 2-(diethylamino)-N-(2,6-dimethylphenyl)-, monohydrochloride and has the molecular wt. 270.8. Lidocaine HCl (C 14H 22N 2O • HCl) has the following structural formula: Epinephrine is (-) -3, 4-Dihydroxy-α-[(methylamino) methyl] benzyl alcohol and has the molecular wt. 183.21. Epinephrine (C 9H 13NO 3) has the following structural formula: Dosage forms listed as Xylocaine-MPF indicate single dose solutions that are Methyl Paraben Free (MPF). Xylocaine MPF is a sterile, nonpyrogenic, isotonic solution containing sodium chloride. Xylocaine in multiple dose vials: Each mL also contains 1 mg methyl­paraben as antiseptic preservative. The pH of these solutions is adjusted to approximately 6.5 (5.0 to 7.0) with sodium hydroxide and/or hydrochloric acid. Xylocaine MPF with Epinephrine is a sterile, nonpyrogenic, isotonic solution containing sodium chloride. Each mL contains lidocaine hydrochloride and epinephrine, with 0.5 mg sodium metabisulfite as an antioxidant and 0.2 mg citric acid as a stabilizer. Xylocaine with Epinephrine in multiple dose vials: Each mL also contains 1 mg methylparaben as antiseptic preservative. The pH of these solutions is adjusted to approximately 4.5 (3.3 to 5.5) with sodium hydroxide and/or hydrochloric acid. Filled under nitrogen. STRUCTURE 1 STRUCTURE 2

Lidocaine Hydrochloride and Epinephrine Injection, USP is a sterile, nonpyrogenic, aqueous solution that contains a local anesthetic agent with epinephrine and is administered parenterally by injection. See INDICATIONS AND USAGE section for specific uses. Lidocaine Hydrochloride and Epinephrine Injection, USP solution contains lidocaine HCl, which is chemically designated as acetamide, 2-(diethylamino)-N-(2,6-dimethylphenyl)-, monohydrochloride and has the molecular wt. 270.8. Lidocaine HCl (C 14 H 22 N 2 O • HCl) has the following structural formula: Epinephrine is (-) -3, 4-Dihydroxy-α-[(methylamino) methyl] benzyl alcohol and has the molecular wt. 183.21. Epinephrine (C 9 H 13 NO 3 ) has the following structural formula: Lidocaine Hydrochloride and Epinephrine Injection, USP is a single-dose solution that is M ethyl P araben (Preservative) F ree (MPF). Lidocaine Hydrochloride and Epinephrine Injection, USP is a sterile, nonpyrogenic, isotonic solution containing sodium chloride. Each mL contains lidocaine hydrochloride and epinephrine, with 0.5 mg sodium metabisulfite as an antioxidant and 0.2 mg citric acid as a stabilizer. The pH of these solutions is adjusted to approximately 4.5 (3.3 to 5.5) with sodium hydroxide and/or hydrochloric acid. Filled under nitrogen. structure 1 Epinephrine Chemical Structure

Lidocaine Hydrochloride and Epinephrine, USP is a sterile isotonic solution containing a local anesthetic agent, Lidocaine Hydrochloride, and a vasoconstrictor, Epinephrine (as bitartrate) and are administered parenterally by injection. Both solutions are available in single dose cartridges of 1.7 mL (See INDICATIONS AND USAGE for specific uses). The solutions contain lidocaine hydrochloride which is chemically designated as acetamide, 2-(diethylamino)-N-(2,6-dimethylphenyl)-monohydrochloride, and has the following structural formula : C 14 H 22 N 2 0•HCl• H 2 0 M.W. 288.8 Epinephrine is ( - )-3,4-Dihydroxy- -[(Methylamino) methyl] benzyl alcohol and has the following structural formula : C 9 H 13 NO 3 M.W. 183.21 COMPOSITION OF AVAILABLE SOLUTIONS PRODUCT IDENTIFICATION FORMULA SINGLE DOSE CARTRIDGE Lidocaine hydrochloride Epinephrine (as the bitartrate) Sodium Chloride Potassium metabisulfite Edetate Disodium Concentration % Dilution (mg/mL) (mg/mL) (mg/mL) The pH of all solutions are adjusted to USP limits with sodium hydroxide. 2 1:50,000 6.5 1.2 0.25 2 1:100,000 6.5 1.2 0.25 Chemical Structure Chemical Structure

LIGNOSPAN FORTE and LIGNOSPAN STANDARD are sterile isotonic solutions containing a local anesthetic agent, Lidocaine Hydrochloride, and a vasoconstrictor, Epinephrine (as bitartrate) and are administered parenterally by injection. Both solutions are available in single dose cartridges of 1.7 mL (See INDICATIONS AND USAGE for specific uses). LIGNOSPAN Solutions contain lidocaine hydrochloride which is chemically designated as acetamide, 2-(diethylamino)-N-(2,6-dimethylphenyl)-monohydrochloride, and has the following structural formula: C 14 H 22 N 2 O • HCl • H 2 0 M.W. 288.8 Epinephrine is ( - )-3,4-Dihydroxy-α-[(Methylamino) methyl] benzyl alcohol and has the following structural formula: C 9 H 13 NO 3 M.W. 183.21 COMPOSITION OF THE LIGNOSPAN INJECTIONS BRAND NAME PRODUCT IDENTIFICATION FORMULA SINGLE DOSE CARTRIDGE Lidocaine hydrochloride Epinephrine (as the bitartrate) Sodium Chloride Potassium metabisulfite Edetate Disodium USP (as dihydrate) Concentration % Dilution (mg/mL) (mg/mL) (mg/mL) LIGNOSPAN FORTE 2 1:50,000 6.5 1.2 0.25 LlGNOSPAN STANDARD 2 1:100,000 6.5 1.2 0.25 The pH of the LIGNOSPAN FORTE and the LIGNOSPAN STANDARD solutions are adjusted to USP limits with Sodium Hydroxide or Hydrochloric Acid q.s. to adjust pH. Chemical Structure Chemical Structure

LIGNOSPAN FORTE and LIGNOSPAN STANDARD are sterile isotonic solutions containing a local anesthetic agent, Lidocaine Hydrochloride, and a vasoconstrictor, Epinephrine (as bitartrate) and are administered parenterally by injection. Both solutions are available in single dose cartridges of 1.7 mL (See INDICATIONS AND USAGE for specific uses). LIGNOSPAN Solutions contain lidocaine hydrochloride which is chemically designated as acetamide, 2-(diethylamino)-N-(2,6-dimethylphenyl)-monohydrochloride, and has the following structural formula: C 14 H 22 N 2 O • HCl • H 2 0 M.W. 288.8 Epinephrine is ( - )-3,4-Dihydroxy-α-[(Methylamino) methyl] benzyl alcohol and has the following structural formula: C 9 H 13 NO 3 M.W. 183.21 COMPOSITION OF THE LIGNOSPAN INJECTIONS BRAND NAME PRODUCT IDENTIFICATION FORMULA SINGLE DOSE CARTRIDGE Lidocaine hydrochloride Epinephrine (as the bitartrate) Sodium Chloride Potassium metabisulfite Edetate Disodium USP (as dihydrate) Concentration % Dilution (mg/mL) (mg/mL) (mg/mL) LIGNOSPAN FORTE 2 1:50,000 6.5 1.2 0.25 LlGNOSPAN STANDARD 2 1:100,000 6.5 1.2 0.25 The pH of the LIGNOSPAN FORTE and the LIGNOSPAN STANDARD solutions are adjusted to USP limits with Sodium Hydroxide or Hydrochloric Acid q.s. to adjust pH. Chemical Structure Chemical Structure

Bupivacaine hydrochloride is (±) -1-Butyl-2´, 6´-pipecoloxylidide monohydrochloride, monohydrate, a white crystalline powder that is freely soluble in 95 percent ethanol, soluble in water, and slightly soluble in chloroform or acetone. It has the following structural formula: Molecular Weight - 342.90 C 18 H 28 N 2 O • HCl • H 2 O Epinephrine bitartrate is (-)-1-(3,4-Dihydroxyphenyl)-2-methylamino-ethanol (+) tartrate (1:1) salt. It has the following structural formula: Molecular Weight - 333.29 C 13 H 19 NO 9 Bupivacaine is available in a sterile isotonic solution with epinephrine 1:200,000 (as bitartrate). Solutions of bupivacaine containing epinephrine may not be autoclaved. Bupivacaine is related chemically and pharmacologically to the aminoacyl local anesthetics. It is a homologue of mepivacaine and is chemically related to lidocaine. All three of these anesthetics contain an amide linkage between the aromatic nucleus and the amino or piperidine group. They differ in this respect from the procaine-type local anesthetics, which have an ester linkage. molecular structure molecular structure

MARCAINE / MARCAINE WITH EPINEPHRINE contains bupivacaine hydrochloride, an amide local anesthetic, as the active pharmaceutical ingredient. The route of administration for MARCAINE (without epinephrine) is by injection, for infiltration, perineural, caudal, epidural, or retrobulbar use. The route of administration for MARCAINE WITH EPINEPHRINE is by injection, for infiltration, perineural, caudal, or epidural use. Multiple-dose vials contain methylparaben [see Warnings and Precautions (5.4) ] . Bupivacaine hydrochloride is 2-piperidinecarboxamide, 1-butyl- N -(2,6-dimethylphenyl)-, monohydrochloride, monohydrate. It is a white crystalline powder that is freely soluble in 95 percent ethanol, soluble in water, and slightly soluble in chloroform or acetone. It has the following structural formula: MARCAINE with 1:200,000 epinephrine, contains bupivacaine hydrochloride and epinephrine bitartrate (an alpha and beta-adrenergic agonist) as active pharmaceutical ingredients. This product is for injection via local infiltration, peripheral nerve block, and caudal and lumbar epidural blocks. Multiple dose vials contain methylparaben and they should not be used for caudal and lumbar epidural blocks. Epinephrine bitartrate is (–) - 3,4-Dihydroxy-α-[(methylamino)methyl] benzyl alcohol (+)-tartrate (1:1) salt. Epinephrine is a vasoconstrictor. It has the following structural formula: MARCAINE (bupivacaine hydrochloride) is a clear and colorless sterile isotonic solution. Each mL of single-dose vial contains 2.5 mg, 5 mg or 7.5 mg of bupivacaine hydrochloride (equivalent to 2.22 mg, 4.44 mg or 6.66 mg of bupivacaine, respectively), sodium chloride for isotonicity, sodium hydroxide or hydrochloric acid to adjust the pH between 4 and 6.5, in water for injection. For the Multiple-dose vials, each mL also contains 1 mg methylparaben as preservative. MARCAINE with epinephrine 1:200,000 (as bitartrate) is a clear and colorless sterile isotonic solution. Each mL contains 2.5 mg or 5 mg bupivacaine hydrochloride (equivalent to 2.22 mg or 4.44 mg of bupivacaine, respectively), and 0.0091 mg epinephrine bitartrate (equivalent to 0.005 mg of epinephrine), with sodium chloride for isotonicity, 0.5 mg sodium metabisulfite, 0.001 mL monothioglycerol, and 2 mg ascorbic acid as antioxidants, 0.0017 mL 60% sodium lactate buffer, and 0.1 mg edetate calcium disodium as stabilizer. The pH of these solutions is adjusted to between 3.4 and 4.5 with sodium hydroxide or hydrochloric acid. For the Multiple-dose vials, each mL also contains 1 mg methylparaben as preservative. The specific gravity of MARCAINE 0.5% with epinephrine 1:200,000 (as bitartrate) at 25°C is 1.008 and at 37°C is 1.008. Chemical Structure Chemical Structure

MARCAINE / MARCAINE WITH EPINEPHRINE contains bupivacaine hydrochloride, an amide local anesthetic, as the active pharmaceutical ingredient. The route of administration for MARCAINE (without epinephrine) is by injection, for infiltration, perineural, caudal, epidural, or retrobulbar use. The route of administration for MARCAINE WITH EPINEPHRINE is by injection, for infiltration, perineural, caudal, or epidural use. Multiple-dose vials contain methylparaben [see Warnings and Precautions (5.4)]. Bupivacaine hydrochloride is 2-piperidinecarboxamide, 1-butyl-N-(2,6-dimethylphenyl)-, monohydrochloride, monohydrate. It is a white crystalline powder that is freely soluble in 95 percent ethanol, soluble in water, and slightly soluble in chloroform or acetone. It has the following structural formula: MARCAINE with 1:200,000 epinephrine, contains bupivacaine hydrochloride and epinephrine bitartrate (an alpha and beta-adrenergic agonist) as active pharmaceutical ingredients. This product is for injection via local infiltration, peripheral nerve block, and caudal and lumbar epidural blocks. Multiple dose vials contain methylparaben and they should not be used for caudal and lumbar epidural blocks. Epinephrine bitartrate is (–) - 3,4-Dihydroxy-α-[(methylamino)methyl] benzyl alcohol (+)-tartrate (1:1) salt. Epinephrine is a vasoconstrictor. It has the following structural formula: MARCAINE (bupivacaine hydrochloride) is a clear and colorless sterile isotonic solution. Each mL of single-dose vial contains 2.5 mg, 5 mg or 7.5 mg of bupivacaine hydrochloride (equivalent to 2.22 mg, 4.44 mg or 6.66 mg of bupivacaine, respectively), sodium chloride for isotonicity, sodium hydroxide or hydrochloric acid to adjust the pH between 4 and 6.5, in water for injection. For the Multiple-dose vials, each mL also contains 1 mg methylparaben as preservative. MARCAINE with epinephrine 1:200,000 (as bitartrate) is a clear and colorless sterile isotonic solution. Each mL contains 2.5 mg or 5 mg bupivacaine hydrochloride (equivalent to 2.22 mg or 4.44 mg of bupivacaine, respectively), and 0.0091 mg epinephrine bitartrate (equivalent to 0.005 mg of epinephrine), with sodium chloride for isotonicity, 0.5 mg sodium metabisulfite, 0.001 mL monothioglycerol, and 2 mg ascorbic acid as antioxidants, 0.0017 mL 60% sodium lactate buffer, and 0.1 mg edetate calcium disodium as stabilizer. The pH of these solutions is adjusted to between 3.4 and 4.5 with sodium hydroxide or hydrochloric acid. For the Multiple-dose vials, each mL also contains 1 mg methylparaben as preservative. The specific gravity of MARCAINE 0.5% with epinephrine 1:200,000 (as bitartrate) at 25°C is 1.008 and at 37°C is 1.008. Formula1.jpg Formula2.jpg

MARCAINE / MARCAINE WITH EPINEPHRINE contains bupivacaine hydrochloride, an amide local anesthetic, as the active pharmaceutical ingredient. The route of administration for MARCAINE (without epinephrine) is by injection, for infiltration, perineural, caudal, epidural, or retrobulbar use. The route of administration for MARCAINE WITH EPINEPHRINE is by injection, for infiltration, perineural, caudal, or epidural use. Multiple-dose vials contain methylparaben [see Warnings and Precautions (5.4) ] . Bupivacaine hydrochloride is 2-piperidinecarboxamide, 1-butyl- N -(2,6-dimethylphenyl)-, monohydrochloride, monohydrate. It is a white crystalline powder that is freely soluble in 95 percent ethanol, soluble in water, and slightly soluble in chloroform or acetone. It has the following structural formula: MARCAINE with 1:200,000 epinephrine, contains bupivacaine hydrochloride and epinephrine bitartrate (an alpha and beta-adrenergic agonist) as active pharmaceutical ingredients. This product is for injection via local infiltration, peripheral nerve block, and caudal and lumbar epidural blocks. Multiple dose vials contain methylparaben and they should not be used for caudal and lumbar epidural blocks. Epinephrine bitartrate is (–) - 3,4-Dihydroxy-α-[(methylamino)methyl] benzyl alcohol (+)-tartrate (1:1) salt. Epinephrine is a vasoconstrictor. It has the following structural formula: MARCAINE (bupivacaine hydrochloride) is a clear and colorless sterile isotonic solution. Each mL of single-dose vial contains 2.5 mg, 5 mg or 7.5 mg of bupivacaine hydrochloride (equivalent to 2.22 mg, 4.44 mg or 6.66 mg of bupivacaine, respectively), sodium chloride for isotonicity, sodium hydroxide or hydrochloric acid to adjust the pH between 4 and 6.5, in water for injection. For the Multiple-dose vials, each mL also contains 1 mg methylparaben as preservative. MARCAINE with epinephrine 1:200,000 (as bitartrate) is a clear and colorless sterile isotonic solution. Each mL contains 2.5 mg or 5 mg bupivacaine hydrochloride (equivalent to 2.22 mg or 4.44 mg of bupivacaine, respectively), and 0.0091 mg epinephrine bitartrate (equivalent to 0.005 mg of epinephrine), with sodium chloride for isotonicity, 0.5 mg sodium metabisulfite, 0.001 mL monothioglycerol, and 2 mg ascorbic acid as antioxidants, 0.0017 mL 60% sodium lactate buffer, and 0.1 mg edetate calcium disodium as stabilizer. The pH of these solutions is adjusted to between 3.4 and 4.5 with sodium hydroxide or hydrochloric acid. For the Multiple-dose vials, each mL also contains 1 mg methylparaben as preservative. The specific gravity of MARCAINE 0.5% with epinephrine 1:200,000 (as bitartrate) at 25 °C is 1.008 and at 37 °C is 1.008. Chemical Structure Chemical Structure

ORABLOC® (articaine hydrochloride and epinephrine injection), for intraoral submucosal infiltration use, is a sterile, aqueous solution that contains articaine HCl 4% (40mg/mL) and epinephrine bitartrate in an epinephrine 1:200,000 or epinephrine 1:100,000 strength. Articaine HCl is an amino amide local anesthetic, chemically designated as 4-methyl-3-[2-(propylamino)- propionamido]-2-thiophene-carboxylic acid, methyl ester hydrochloride and is a racemic mixture. Articaine HCl has a molecular weight of 320.84 and the following structural formula: Articaine HCl has a partition coefficient in n-octanol/Soerensen buffer (pH 7.35) of 17 and a pKa of 7.8. Epinephrine bitartrate, (-)-1-(3,4-dihydroxyphenyl)-2-methylamino-ethanol (+) tartrate (1:1) salt, is a vasoconstrictor with a concentration of 1:200,000 or 1:100,000 (expressed as free base). It has a molecular weight of 333.3 and the following structural formula: ORABLOC® contains the following inactive ingredients: sodium chloride (1.0 mg/mL), sodium metabisulfite (0.5 mg/mL), and water for injection. The product is formulated with a 10% overage of epinephrine. The pH is adjusted to 3.6 with hydrochloric acid. Articaine HCl structural formula Epinephrine bitartrate structural formula

SENSORCAINE-MPF / SENSORCAINE-MPF WITH EPINEPHRINE injections contains bupivacaine hydrochloride, a local anesthetic agent with and without epinephrine (as bitartrate) 1:200,000. The route of administration for SENSORCAINE-MPF / SENSORCAINE-MPF WITH EPINEPHRINE is parenterally by injection, for infiltration, perineural, caudal, epidural, or retrobulbar use. SENSORCAINE-MPF / SENSORCAINE-MPF WITH EPINEPHRINE injections are Methyl Paraben Free (MPF). SENSORCAINE/SENSORCAINE WITH EPINEPHRINE injections contains bupivacaine hydrochloride, a local anesthetic agent with and without epinephrine (as bitartrate) 1:200,000. The route of administration for SENSORCAINE / SENSORCAINE WITH EPINEPHRINE is parenterally by injection, for infiltration and perineural use. Bupivacaine hydrochloride is a white or almost white, crystalline powder or colorless crystals, soluble in water, freely soluble in alcohol. Bupivacaine is related chemically and pharmacologically to the aminoacyl local anesthetics. It is a homologue of mepivacaine and is chemically related to lidocaine. All three of these anesthetics contain an amide linkage between the aromatic nucleus and the amino, or piperidine group. They differ in this respect from the procaine-type local anesthetics, which have an ester linkage. Bupivacaine hydrochloride chemical name is 2-piperidinecarboxamide, 1-butyl- N -(2,6-dimethylphenyl)-, monohydrochloride, monohydrate. The molecular formula is C 18 H 28 N 2 O·HCl·H 2 O, with a molecular weight of 342.9 g/mol. Bupivacaine hydrochloride monohydrate has the following chemical structure: The pK a of bupivacaine (8.1) is similar to that of lidocaine (7.86). However, bupivacaine possesses a greater degree of lipid solubility and is protein bound to a greater extent than lidocaine. Epinephrine bitartrate is a white to greyish white or light brownish-grey, odorless, crystalline powder, freely soluble in water, slightly soluble in 96% ethanol and methanol, practically insoluble in chloroform, methylene chloride and ether. Epinephrine bitartrate chemical name is (-)-3,4-Dihydroxy- α [(methylamino)methyl] benzyl alcohol (+) tartrate (1:1) salt. The molecular formula is C 9 H 13 NO 3 ·C 4 H 6 O 6 , with a molecular weight of 333.29 g/mol. Epinephrine bitartrate has the following chemical structure: Bupivacaine Hydrochloride Monohydrate Chemical Structure Epinephrine Bitartrate Chemical Structure SENSORCAINE-MPF in single dose vials is a sterile, isotonic, clear, colorless, and preservative-free solution. Each mL contains 2.64 mg, 5.27 mg, or 7.92 mg of bupivacaine hydrochloride monohydrate (equivalent to 2.22 mg, 4.44 mg or 6.66 mg of bupivacaine, and also equivalent to 2.5 mg, 5.0 mg, or 7.5 mg of bupivacaine hydrochloride anhydrous; respectively), 8.0 mg sodium chloride for isotonicity, and sodium hydroxide and/or hydrochloric acid as pH adjusters. The pH of these solutions is adjusted to between 4.0 and 6.5. SENSORCAINE-MPF WITH EPINEPHRINE 1:200,000 (as bitartrate) in single dose vials is a sterile, isotonic, clear, colorless to slightly yellow and preservative-free solution. Each mL contains 2.64 mg, 5.27 mg, or 7.92 mg of bupivacaine hydrochloride monohydrate (equivalent to 2.22 mg, 4.44 mg or 6.66 mg of bupivacaine, and also equivalent to 2.5 mg, 5.0 mg or 7.5 mg bupivacaine hydrochloride anhydrous; respectively), 0.0091 mg or 9.09 mcg of epinephrine bitartrate (equivalent to 0.005 mg of epinephrine base), 0.5 mg sodium metabisulfite as an antioxidant, 0.2 mg citric acid (anhydrous) as a stabilizer, 8.0 mg sodium chloride for isotonicity, and sodium hydroxide and/or hydrochloric acid as pH adjusters. The pH of these solutions is adjusted to between 3.3 to 5.5. SENSORCAINE in multiple dose vials is a sterile, isotonic, clear, colorless solution. Each mL contains 2.64 mg, or 5.27 mg, of bupivacaine hydrochloride monohydrate (equivalent to 2.22 mg, or 4.44 mg of bupivacaine, and also equivalent to 2.5 mg and 5.0 mg of bupivacaine hydrochloride anhydrous; respectively), 8.0 g sodium chloride for isotonicity, 1 mg of methyl paraben as an antiseptic preservative and sodium hydroxide and/or hydrochloric acid as pH adjusters. The pH of these solutions is adjusted to between 4.0 and 6.5. SENSORCAINE WITH EPINEPHRINE 1:200,000 (as bitartrate) in multiple dose vials is a sterile, isotonic, clear, colorless to slightly yellow solution. Each mL contains 2.64 mg, or 5.27 mg, of bupivacaine hydrochloride monohydrate (equivalent to 2.22 mg, or 4.44 mg of bupivacaine, and also equivalent to 2.5 mg and 5.0 mg of bupivacaine hydrochloride anhydrous; respectively), 8.0 mg sodium chloride for isotonicity, 0.0091 mg or 9.09 mcg of epinephrine bitartrate (equivalent to 0.005 mg of epinephrine base), 1 mg methylparaben as an antiseptic preservative, 0.5 mg sodium metabisulfite as an antioxidant, 0.2 mg citric acid (anhydrous) as a stabilizer, and sodium hydroxide and/or hydrochloric acid as pH adjusters. The pH of these solutions is adjusted to between 3.3 to 5.5.

Sensorcaine ® (bupivacaine HCl) injections are sterile isotonic solutions that contain a local anesthetic agent with and without epinephrine (as bitartrate) 1:200,000 and are administered parenterally by injection. See INDICATIONS AND USAGE for specific uses. Solutions of bupivacaine HCl may be autoclaved if they do not contain epinephrine. Sensorcaine injections contain bupivacaine HCl which is chemically designated as 2- piperidinecarboxamide, 1-butyl- N -(2,6-dimethylphenyl)-, monohydrochloride, monohydrate and has the following structure: Epinephrine is (-)-3,4-Dihydroxy-α [(methylamino)methyl] benzyl alcohol. It has the following structural formula: The pK a of bupivacaine (8.1) is similar to that of lidocaine (7.86). However, bupivacaine possesses a greater degree of lipid solubility and is protein bound to a greater extent than lidocaine. Bupivacaine is related chemically and pharmacologically to the aminoacyl local anesthetics. It is a homologue of mepivacaine and is chemically related to lidocaine. All three of these anesthetics contain an amide linkage between the aromatic nucleus and the amino, or piperidine group. They differ in this respect from the procaine-type local anesthetics, which have an ester linkage. Figure Figure Dosage forms listed as Sensorcaine-MPF indicates s ingle dose solutions that are M ethyl P araben F ree (MPF). Sensorcaine-MPF is a sterile isotonic solution containing sodium chloride. Sensorcaine in multiple dose vials, each mL also contains 1 mg methylparaben as antiseptic preservative. The pH of these solutions is adjusted to between 4.0 and 6.5 with sodium hydroxide and/or hydrochloric acid. Sensorcaine-MPF with Epinephrine 1:200,000 (as bitartrate) is a sterile isotonic solution containing sodium chloride. Each mL contains bupivacaine hydrochloride and 0.005 mg epinephrine, with 0.5 mg sodium metabisulfite as an antioxidant and 0.2 mg citric acid (anhydrous) as stabilizer. Sensorcaine with Epinephrine 1:200,000 (as bitartrate) in multiple dose vials, each mL also contains 1 mg methylparaben as antiseptic preservative. The pH of these solutions is adjusted to between 3.3 to 5.5 with sodium hydroxide and/or hydrochloric acid. Filled under nitrogen. Note: The user should have an appreciation and awareness of the formulations and their intended uses (see DOSAGE AND ADMINISTRATION ).

Sensorcaine ® (bupivacaine HCl) injections are sterile isotonic solutions that contain a local anesthetic agent with and without epinephrine (as bitartrate) 1:200,000 and are administered parenterally by injection. See INDICATIONS AND USAGE for specific uses. Solutions of bupivacaine HCl may be autoclaved if they do not contain epinephrine. Sensorcaine injections contain bupivacaine HCl which is chemically designated as 2-piperidinecarboxamide, 1-butyl- N -(2,6-dimethylphenyl)-, monohydrochloride, monohydrate and has the following structure: Epinephrine is (-)-3,4-Dihydroxy-α [(methylamino)methyl] benzyl alcohol. It has the following structural formula: The pK a of bupivacaine (8.1) is similar to that of lidocaine (7.86). However, bupivacaine possesses a greater degree of lipid solubility and is protein bound to a greater extent than lidocaine. Bupivacaine is related chemically and pharmacologically to the aminoacyl local anesthetics. It is a homologue of mepivacaine and is chemically related to lidocaine. All three of these anesthetics contain an amide linkage between the aromatic nucleus and the amino, or piperidine group. They differ in this respect from the procaine-type local anesthetics, which have an ester linkage. Figure Figure Dosage forms listed as Sensorcaine-MPF indicates single dose solutions that are M ethyl P araben F ree (MPF). Sensorcaine-MPF is a sterile isotonic solution containing sodium chloride. The pH of this solution is adjusted to between 4.0 and 6.5 with sodium hydroxide and/or hydrochloric acid. Sensorcaine-MPF with Epinephrine 1:200,000 (as bitartrate) is a sterile isotonic solution containing sodium chloride. Each mL contains bupivacaine hydrochloride and 0.005 mg epinephrine, with 0.5 mg sodium metabisulfite as an antioxidant and 0.2 mg citric acid (anhydrous) as stabilizer. The pH of this solution is adjusted to between 3.3 to 5.5 with sodium hydroxide and/or hydrochloric acid. Filled under nitrogen. Note: The user should have an appreciation and awareness of the formulations and their intended uses (see DOSAGE AND ADMINISTRATION ).

Sensorcaine ® (bupivacaine HCl) injections are sterile isotonic solutions that contain a local anesthetic agent with and without epinephrine (as bitartrate) 1:200,000 and are administered parenterally by injection. See INDICATIONS AND USAGE for specific uses. Solutions of bupivacaine HCl may be autoclaved if they do not contain epinephrine. Sensorcaine injections contain bupivacaine HCl which is chemically designated as 2-piperidinecarboxamide, 1-butyl- N -(2,6-dimethylphenyl)-, monohydrochloride, monohydrate and has the following structure: Epinephrine is (-)-3,4-Dihydroxy-α [(methylamino)methyl] benzyl alcohol. It has the following structural formula: The pK a of bupivacaine (8.1) is similar to that of lidocaine (7.86). However, bupivacaine possesses a greater degree of lipid solubility and is protein bound to a greater extent than lidocaine. Bupivacaine is related chemically and pharmacologically to the aminoacyl local anesthetics. It is a homologue of mepivacaine and is chemically related to lidocaine. All three of these anesthetics contain an amide linkage between the aromatic nucleus and the amino, or piperidine group. They differ in this respect from the procaine-type local anesthetics, which have an ester linkage. Dosage forms listed as Sensorcaine-MPF indicates single dose solutions that are M ethyl P araben F ree (MPF). Sensorcaine-MPF is a sterile isotonic solution containing sodium chloride. The pH of this solution is adjusted to between 4.0 and 6.5 with sodium hydroxide and/or hydrochloric acid. Sensorcaine-MPF with Epinephrine 1:200,000 (as bitartrate) is a sterile isotonic solution containing sodium chloride. Each mL contains bupivacaine hydrochloride and 0.005 mg epinephrine, with 0.5 mg sodium metabisulfite as an antioxidant and 0.2 mg citric acid (anhydrous) as stabilizer. The pH of this solution is adjusted to between 3.3 to 5.5 with sodium hydroxide and/or hydrochloric acid. Filled under nitrogen. Note: The user should have an appreciation and awareness of the formulations and their intended uses (see DOSAGE AND ADMINISTRATION ). senso-struc-01.jpg senso-struc-02.jpg

Sensorcaine ® (bupivacaine HCl) injections are sterile isotonic solutions that contain a local anesthetic agent with and without epinephrine (as bitartrate) 1:200,000 and are administered parenterally by injection. See INDICATIONS & USAGE for specific uses. Solutions of bupivacaine HCl may be autoclaved if they do not contain epinephrine. Sensorcaine injections contain bupivacaine HCl which is chemically designated as 2- piperidinecarboxamide, 1-butyl- N-(2,6-dimethylphenyl)-, monohydrochloride, monohydrate and has the following structure: Epinephrine is (-)-3,4-Dihydroxy-α [(methylamino)methyl] benzyl alcohol. It has the following structural formula: The pK a of bupivacaine (8.1) is similar to that of lidocaine (7.86). However, bupivacaine possesses a greater degree of lipid solubility and is protein bound to a greater extent than lidocaine. Bupivacaine is related chemically and pharmacologically to the aminoacyl local anesthetics. It is a homologue of mepivacaine and is chemically related to lidocaine. All three of these anesthetics contain an amide linkage between the aromatic nucleus and the amino, or piperidine group. They differ in this respect from the procaine-type local anesthetics, which have an ester linkage. Dosage forms listed as Sensorcaine-MPF indicates s ingle dose solutions that are Methyl Paraben Free (MPF). Sensorcaine-MPF is a sterile isotonic solution containing sodium chloride. Sensorcaine in multiple dose vials, each mL also contains 1 mg methylparaben as antiseptic preservative. The pH of these solutions is adjusted to between 4.0 and 6.5 with sodium hydroxide and/or hydrochloric acid. Sensorcaine-MPF with Epinephrine 1:200,000 (as bitartrate) is a sterile isotonic solution containing sodium chloride. Each mL contains bupivacaine hydrochloride and 0.005 mg epinephrine, with 0.5 mg sodium metabisulfite as an antioxidant and 0.2 mg citric acid (anhydrous) as stabilizer. Sensorcaine with Epinephrine 1:200,000 (as bitartrate) in multiple dose vials, each mL also contains 1 mg methylparaben as antiseptic preservative. The pH of these solutions is adjusted to between 3.3 to 5.5 with sodium hydroxide and/or hydrochloric acid. Filled under nitrogen. Note: The user should have an appreciation and awareness of the formulations and their intended uses (see DOSAGE & ADMINISTRATION DOSAGE AND ADMINISTRATION). STRUCTURE 1 STRUCTURE 2

SEPTOCAINE (articaine hydrochloride and epinephrine injection), for intraoral submucosal infiltration use, is a sterile, aqueous solution that contains articaine HCl 4% (68 mg/1.7mL) (40 mg/mL) and epinephrine bitartrate in an epinephrine 1:200,000 or epinephrine 1:100,000 strength. Articaine HCl is an amino amide local anesthetic, chemically designated as 4-methyl-3-[2-(propylamino)-propionamido]-2-thiophene-carboxylic acid, methyl ester hydrochloride and is a racemic mixture. Articaine HCl has a molecular weight of 320.84 and the following structural formula: Articaine HCl has a partition coefficient in n-octanol/Soerensen buffer (pH 7.35) of 17 and a pKa of 7.8. Epinephrine bitartrate, (-)-1-(3,4-Dihydroxyphenyl)-2-methylamino-ethanol (+) tartrate (1:1) salt, is a vasoconstrictor with a concentration of 1:200,000 or 1:100,000 (expressed as free base). It has a molecular weight of 333.3 and the following structural formula: SEPTOCAINE contains the following inactive ingredients: sodium chloride (1.6 mg/mL) and sodium metabisulfite (0.5 mg/mL). The product is formulated with a 15% overage of epinephrine. The pH is adjusted with sodium hydroxide. articaine structural formula epinephrine structural formula

Bupivacaine hydrochloride is (±) -1-Butyl-2´, 6´-pipecoloxylidide monohydrochloride, monohydrate, a white crystalline powder that is freely soluble in 95 percent ethanol, soluble in water, and slightly soluble in chloroform or acetone. It has the following structural formula: Molecular Weight - 342.90 C 18 H 28 N 2 O • HCl • H 2 O Epinephrine bitartrate is (-)-1-(3,4-Dihydroxyphenyl)-2-methylamino-ethanol (+) tartrate (1:1) salt. It has the following structural formula: Molecular Weight - 333.29 C 13 H 19 NO 9 Bupivacaine is available in a sterile isotonic solution with epinephrine 1:200,000 (as bitartrate). Solutions of bupivacaine containing epinephrine may not be autoclaved. Bupivacaine is related chemically and pharmacologically to the aminoacyl local anesthetics. It is a homologue of mepivacaine and is chemically related to lidocaine. All three of these anesthetics contain an amide linkage between the aromatic nucleus and the amino or piperidine group. They differ in this respect from the procaine-type local anesthetics, which have an ester linkage. Chemical Structure Chemical Structure

Xylocaine (lidocaine HCl) Injections are sterile, nonpyrogenic, aqueous solutions that contain a local anesthetic agent with or without epinephrine and are administered parenterally by injection. See INDICATIONS AND USAGE section for specific uses. Xylocaine solutions contain lidocaine HCl, which is chemically designated as acetamide, 2-(diethylamino)-N-(2,6-dimethylphenyl)-, monohydrochloride and has the molecular wt. 270.8. Lidocaine HCl (C14H22N2O • HCl) has the following structural formula: Epinephrine is (-) -3, 4-Dihydroxy-α-[(methylamino) methyl] benzyl alcohol and has the molecular wt. 183.21. Epinephrine (C9H13NO3) has the following structural formula: Dosage forms listed as Xylocaine-MPF indicate single dose solutions that are Methyl Paraben Free (MPF). Xylocaine MPF is a sterile, nonpyrogenic, isotonic solution containing sodium chloride. Xylocaine in multiple dose vials: Each mL also contains 1 mg methyl­paraben as antiseptic preservative. The pH of these solutions is adjusted to approximately 6.5 (5.0 to 7.0) with sodium hydroxide and/or hydrochloric acid. Xylocaine MPF with Epinephrine is a sterile, nonpyrogenic, isotonic solution containing sodium chloride. Each mL contains lidocaine hydrochloride and epinephrine, with 0.5 mg sodium metabisulfite as an antioxidant and 0.2 mg citric acid as a stabilizer. Xylocaine with Epinephrine in multiple dose vials: Each mL also contains 1 mg methylparaben as antiseptic preservative. The pH of these solutions is adjusted to approximately 4.5 (3.3 to 5.5) with sodium hydroxide and/or hydrochloric acid. Filled under nitrogen. Formula1.jpg Formula2.jpg

Xylocaine (lidocaine HCl) Injections are sterile, nonpyrogenic, aqueous solutions that contain a local anesthetic agent with or without epinephrine and are administered parenterally by injection. See INDICATIONS AND USAGE section for specific uses. Xylocaine solutions contain lidocaine HCl, which is chemically designated as acetamide, 2-(diethylamino)-N-(2,6-dimethylphenyl)-, monohydrochloride and has the molecular wt. 270.8. Lidocaine HCl (C 14 H 22 N 2 O • HCl) has the following structural formula: Epinephrine is (-) -3, 4-Dihydroxy-α-[(methylamino) methyl] benzyl alcohol and has the molecular wt. 183.21. Epinephrine (C 9 H 13 NO 3 ) has the following structural formula: Dosage forms listed as Xylocaine-MPF indicate single dose solutions that are M ethyl P araben F ree (MPF). Xylocaine MPF is a sterile, nonpyrogenic, isotonic solution containing sodium chloride. Xylocaine in multiple dose vials: Each mL also contains 1 mg methyl­paraben as antiseptic preservative. The pH of these solutions is adjusted to approximately 6.5 (5.0 to 7.0) with sodium hydroxide and/or hydrochloric acid. Xylocaine MPF with Epinephrine is a sterile, nonpyrogenic, isotonic solution containing sodium chloride. Each mL contains lidocaine hydrochloride and epinephrine, with 0.5 mg sodium metabisulfite as an antioxidant and 0.2 mg citric acid as a stabilizer. Xylocaine with Epinephrine in multiple dose vials: Each mL also contains 1 mg methylparaben as antiseptic preservative. The pH of these solutions is adjusted to approximately 4.5 (3.3 to 5.5) with sodium hydroxide and/or hydrochloric acid. Filled under nitrogen. structure 1 structure 2

Xylocaine (lidocaine HCl) Injections are sterile, nonpyrogenic, aqueous solutions that contain a local anesthetic agent with or without epinephrine and are administered parenterally by injection. See INDICATIONS AND USAGE section for specific uses. Xylocaine solutions contain lidocaine HCl, which is chemically designated as acetamide, 2-(diethylamino)-N-(2,6-dimethylphenyl)-, monohydrochloride and has the molecular wt. 270.8. Lidocaine HCl (C 14 H 22 N 2 O • HCl) has the following structural formula: Epinephrine is (-) -3, 4-Dihydroxy-α-[(methylamino) methyl] benzyl alcohol and has the molecular wt. 183.21. Epinephrine (C 9 H 13 NO 3 ) has the following structural formula: Dosage forms listed as Xylocaine-MPF indicate single dose solutions that are M ethyl P araben F ree (MPF). Xylocaine MPF is a sterile, nonpyrogenic, isotonic solution containing sodium chloride. Xylocaine in multiple dose vials: Each mL also contains 1 mg methyl­paraben as antiseptic preservative. The pH of these solutions is adjusted to approximately 6.5 (5.0 to 7.0) with sodium hydroxide and/or hydrochloric acid. Xylocaine MPF with Epinephrine is a sterile, nonpyrogenic, isotonic solution containing sodium chloride. Each mL contains lidocaine hydrochloride and epinephrine, with 0.5 mg sodium metabisulfite as an antioxidant and 0.2 mg citric acid as a stabilizer. Xylocaine with Epinephrine in multiple dose vials: Each mL also contains 1 mg methylparaben as antiseptic preservative. The pH of these solutions is adjusted to approximately 4.5 (3.3 to 5.5) with sodium hydroxide and/or hydrochloric acid. Filled under nitrogen. structure 1 structure 2