`
`APPROVAL PACKAGE FOR:
`
`- APPLICATION NUMBER
`
`19-386/5—021
`
`Medical Review(s)
`
`
`
`To:
`
`NDA #191386, 8-019, 5-020, 8-021
`
`- From:
`
`Shari Targum, MD
`
`Correspondence Date: 9/30/02, 10/24/02
`
`Date of Review: 1/9/03
`
`, Re: Labeling changes
`
`The sponsor has submitted three labeling supplements for Brevibloc (esmolol HCl) Injection. These
`labeling supplements involve the addition of a Breviblock Double Strength Premixed Injection
`containing 20 mg/ml concentration of esmolol HCl (S-20) as well as completion of prior Phase 4
`commitment (to reduce overage of esmolol HCl added to the formulation).
`
`Under Dosage and Administration, this reviewer noted the following additional language
`(underlined):
`‘
`“The Brevibloc Premixed Injection contains Esmolol Hydrochloride at a concentration of 10
`milligrams/mL. When using a 10 milligrams/mL concentration, a loading dose of 0.5 milligrams/kg
`infiised over 1 minute period of time, for a 70 kg patient, is 3.5 mL...
`The Breviblock Premixed Injection DOUBLE STRENGTH contains Esmolol Hydrochloride at a
`concentration of 20 milli ms/mL. When usin a 20 milli
`mL concentration a loadin dose
`
`of 0.5 milliga_ms/kg infused over 1 minute period of time, for a 70 kg patient, is 1.75 ml...”
`
`Reviewer: Given the two-fold higher concentration in the Double-Strength formulation, the reviewer
`concurs with administration of half the loading dose volume.
`The reviewer has no objection to the color change proposed in the supplements, so long as these
`changes serve to clarify and not cause confusion.
`
`
`
`
`
`This is a representation of an electronic record that was signed electronically and
`this page is the manifestation of the electronic signature.
`
`Shari Targum
`1/13/03 04:35:09 PM
`MEDICAL OFFICER
`
`