I .
`
`I
`
`I
`
`on
`
`I 3TH EDITION
`
`Lawrence A. Trissel
`
`American Society of Health-System Pharmacists®
`Bethesda, Maryland
`
`Sandoz Exhibit 1013 Page 1
`
`

`

`LAWRENCE A. TRISSEL, F.A.S.H.P., the author of the Handbook on Injectable Drugs,
`is Director, Clinical Pharmaceutics Research, Division of Pharmacy, The University of
`Texas, M. D. Anderson Cancer Center, Houston, Texas.
`
`Any correspondence regarding this publication should be sent to the publisher, American
`Society of Health-System Pharmacists®, 7272 Wisconsin Avenue, Bethesda, MD 20814,
`attn: Special Publishing.
`
`The information presented herein reflects the opinions of the author and reviewers. It
`should not be interpreted as an official policy of ASHP or as an endorsement of any
`product.
`
`Drug information and its applications are constantly evolving because of
`ongoing research and clinical experience and are often subject to professional
`judgment and interpretation by the practitioner due to the uniqueness of a
`clinical situation. The author, reviewers, and ASHP have made every effort to
`ensure the accuracy and completeness of the information presented in this
`book. However, the reader is advised that the publisher, author, contributors,
`editors, and reviewers cannot be responsible for the continued cul'l'ency of the
`information, for any el'l'ors or omissions, and/or for any consequences arising
`from the use of the information in the clinical setting.
`
`The reader is cautioned that ASHP makes no representation, guarantee, or
`wananty, express or implied, that the use of the information contained in this
`book will p•·event problems with insurers and will bear no responsibility or
`liability for the results or consequences of its use.
`
`i i
`
`,!
`
`'
`
`Produced by Special Publishing and the Publications Production Center of the American
`Society of Health-System Pharmacists
`Director, Acquisitions and Product Development: Cynthia Conner
`Acquisitions Editor: Hal Pollard
`Director, ei-lealth Solutions Division: Jefti'ey Shick
`eHealth Data Manager and Clinical Informaticist: Edward D. Millikan
`Production Manager: Johnna Hershey
`Project Assistants: Leah Carter, Kristin Eckles, Karen Thomson
`
`Cover Design: David A. Wade
`
`©2005, American Society of Health-System Pharmacists, Inc. All rights reserved.
`
`No part of this publication may be reproduced or transmitted in any form or by any means,
`electronic or mechanical, including photocopying, microfilming, and recording, or by any
`information storage and retrieval system, without written permission from the American
`Society of Health-System Pharmacists.
`
`ASHP® is a service mark of the American Society of Health-System Pharmacists, Inc.;.
`registered in the U.S. Patent and Trademark Office.
`
`ISBN: 1-58528-107-7
`
`Sandoz Exhibit 1013 Page 2
`
`

`

`NICARDIPINB HYDROCHLORIDE/1109
`
`NICARDIPINE HYDROCHLORIDE
`AHFS 24:28.08
`
`should be changed every 12 hours to avoid venous irritation. (1-11/
`27/96; 4)
`
`Products - Nicardipine hydrochloride is available as a 2.S.mg/ml con(cid:173)
`centrate in 1 0-ml ampuls. Each milliliter also contains sorbitol48 mg,
`citric acid monohydrate 0.525 mg, and sodium hydroxide 0.09 mg in
`water fpr injection. Additional citric acid and/or sodium hydroxide
`may have been added to adjust solution pH. (1-11/27 /96)
`
`pH -Buffered to pH 3.5. (1-11/27/96)
`
`Trade N arne( s) - Cardene I. V.
`
`Administration - Nicardipine hydrochloride must be diluted for use.
`It is administered as a slow continuous intravenous infusion at a con(cid:173)
`centration of 0.1 mg/ml. The infusion is prepared by adding 10 ml of
`nicardipjne hydrochloride (25 mg) to 240 ml of compatible infusion
`solution, making 250 ml of a 0.1-mg/ml solution. If nicardipine hy(cid:173)
`drochloride is administered via a peripheral vein, the infusion site
`
`Stability -Intact ampuls of the clear, yellow solution should be stored
`at controlled room temperature and protected from light. Freezing
`does not adversely affect the product, but exposure to elevated tem(cid:173)
`peratures should be avoided. ( 1-11/27 /96)
`
`Light Effects- Deliberate exposure of a 0.1-mg/ml nicardipine hydro(cid:173)
`chloride solution to daylight resulted in about 8% loss in seven hours
`and 21% loss in 14 hours by HPLC analysis. The authors recom(cid:173)
`mended that protection from light be considered for pharmaceutical
`dosage forms. (2193)
`
`Sorption- Nicardipine hydrochloride (Dupont Merck) 50 and 500 mg/
`L in a variety of infusion solutions in PVC containers showed a de(cid:173)
`cline in concentration due to sorption to the plastic. Losses were rapid
`in Ringer's injection, lactated with nearly 50% lost in 24 hours. The
`drug concentrations were stable when prepared in glass containers.
`(1380)
`
`Solution Compatibility
`
`Compatibility Information
`
`Nicardipine HCI
`
`Solution
`
`Remarks
`
`Dextrose 5% in Ringer's injection, lactated
`
`MGa
`
`DME
`
`TRb
`
`DME
`
`TRb
`
`DME
`
`Dextrose 5% in sodium chloride 0.45%
`
`MGa
`
`DME
`
`TRb
`
`DME
`
`Dextrose 5% in sodium chloride 0.9%
`
`MGa
`
`DME
`
`TRb
`
`DME
`
`Dextrose 5% in water
`
`MGa
`
`DME
`
`TRb
`
`DME
`
`TRb
`
`DME
`
`50 and
`500mg
`
`Physically compatible with not more than 7% ni-
`cardipine loss by HPLC in 7 days at room tem-
`perature under fluorescent light
`500mg Physically compatible with about 7% nicardipine
`loss by HPLC in 24 hr at room temperature un-
`der fluorescent light
`Physically compatible with about 10 to 12% nicar-
`dipine loss by HPLC in 24 hr at room tempera-
`ture under fluorescent light
`
`50mg
`
`50 ;md
`500mg
`
`50 and
`500mg
`
`50 and
`500mg
`
`50 and
`500mg
`
`Physically compatible with little or no nicardipine
`loss by HPLC in 7 days at room temperature
`under fluorescent light
`Physically compatible with up to 9% nicardipine
`loss by HPLC in 72 hr at room temperature un-
`der fluorescent light
`
`Physically compatible with little or no nicardipine
`loss by HPLC in 7 clays at room temperature
`under fluorescent light
`Physically compatible with up to 7% nicardipine
`loss by HPLC in 7 days at room temperature
`under fluorescent light
`
`50 and
`500mg
`
`Physically compatible with little or no nicardipine
`loss by HPLC in 7 days at room temperature
`under fluorescent light
`500mg Physically compatible with up to 6% nicardipine
`loss by HPLC in 7 days at room temperature
`under fluorescent light
`Physically compatible with up to 13% nicardipine
`loss by HPLC in 24 hr at room temperature un-
`der fluorescent light
`
`50 mg
`
`C/1
`c
`
`c
`
`1380
`
`1380
`
`1380
`
`I
`
`1380
`
`1380
`
`1380
`
`1380
`
`1380
`
`1380
`
`1380
`(I
`
`c
`
`c
`
`c
`
`c
`
`c
`
`c
`
`I
`
`Sandoz Exhibit 1013 Page 3
`
`

`

`1110 /NICARDIPINE HYDROCHLORIDE
`
`Solution Compatibility (Cont.)
`
`Nicardipine HCI
`
`Solution
`
`Remarks
`
`Dextrose 5% in water with potassium chloride MG"
`0.3%
`
`DME
`
`c
`
`TRb
`
`DME
`
`50 and
`500mg
`
`50 and
`500mg
`
`Physically compatible with little or no nicardipine
`loss by HPLC in 7 days at room temperature
`under fluorescent light
`Physically compatible with up to 12% nicardipine
`loss by HPLC in 48 hr at room temperature un-
`der fluorescent light
`
`Ringer's injection, lactated
`
`MG"
`
`DME
`
`TRb
`
`DME
`
`TRb
`
`DME
`
`50 and
`500mg
`
`Physically compatible with little or no nicardipine
`loss by HPLC in 7 days at room temperature
`under fluorescent light
`500mg Physically compatible with up to 15% nicardipine
`loss by HPLC in 24 hr at room temperature un-
`der fluorescent light
`Physically compatible with up to 42% nicardipine
`loss by HPLC in 24 hr at room temperature un-
`der fluorescent light
`
`50mg
`
`Sodium bicarbonate 5%
`
`TR"
`
`DME
`
`50 and
`500mg
`
`Precipitate forms immediately
`
`Sodium chloride 0.45%
`
`MG"
`
`DME
`
`TRb
`
`DME
`
`TRb
`
`DME
`
`50 and
`500mg
`
`Physically compatible with little or no nicardipine
`loss by HPLC in 7 days at room temperature
`under fluorescent light
`500mg Physically compatible with up to 3% nicardipine
`loss by HPLC in 7 days at room temperature
`under fluorescent light
`Physically compatible with up to 11% nicardipine
`loss by HPLC in 241n· at room temperature un-
`der fluorescent light
`
`50mg
`
`Sodium chloride 0.9%
`
`MG•
`
`DME
`
`TRb
`
`DME
`
`50 and
`500mg
`
`50 and
`500mg
`
`Physically compatible with little or no nicardipine
`loss by HPLC in 7 days at room temperature
`under fluorescent light
`Physically compatible with up to 8% nicardipine
`loss by HPLC in 72 hr at room temperature un- ·
`der fluorescent light
`
`C/1
`c
`
`c
`
`c
`
`I
`
`I
`
`I
`
`c
`
`c
`
`1380
`
`1380
`
`1380
`
`1380
`
`1380
`
`1380
`
`1380
`
`1380
`
`1380
`
`I
`
`1380
`
`1380
`
`c
`
`c
`
`"Tested in glass containers.
`"Tested in PVC containers.
`
`Additive Compatibility
`
`Nicardipine HCI
`
`Drug
`
`Mfr
`
`Co neiL
`
`Mfr
`
`Conc!L
`
`Potassmm chlonde
`
`"Tested in glass containers.
`"Tested in PVC containers.
`
`ES
`
`ES
`
`40mEq
`
`DME
`
`40mEq
`
`DME
`
`50 and
`500mg
`
`50 and
`500mg
`
`Test
`Soln
`
`D5W•
`
`D5Wh
`
`Remarks
`
`Physically compatible with little or no ni-
`cardipine loss by HPLC in 7 days at
`room temperature under fluorescent light
`Physically compatible with up to 12% ni-
`cardipine loss by HPLC in 48 hr at room
`temperature under fluorescent light
`
`Ref
`
`1380
`
`1380
`
`C/1
`c
`
`c
`
`Sandoz Exhibit 1013 Page 4
`
`

`

`P'jl(
`
`NICARDIPINE HYDROCHLORIDE/1111
`
`I
`
`Y-Site Injection Compatibility (I :1 Mixture)
`
`Nicardipine HCI
`
`Drug
`
`Cone
`
`Cone
`
`Remarks
`
`Amikacin sulfate
`
`BR
`
`2 mg/ml"
`
`DCC
`
`0.1 mg/ml"
`
`Aminophylline
`
`ES
`
`1 mg/mla
`
`DCC
`
`0.1 mg/ml"
`
`Visually compatible for 24 hr at room tern-
`perature
`
`Visually compatible for 24 hr at room tern-
`perature
`
`Ampicillin sodium
`
`Ampicillin sodium-sulbactam
`sodium
`
`BR
`
`PF
`
`10 mg/ml•·b
`DCC
`10 + 5 mg/ DCC
`ml"·b
`
`0.1 mg/ml•·b
`
`Turbidity forms immediately
`
`0.1 mg/mla,b
`
`Turbidity forms immediately
`
`Aztreonam
`
`SQ
`
`10 mg/mla
`
`DCC
`
`0.1 mg/ml•
`
`Butorphan,.ol tartrate
`
`BR
`
`0,4 mg/mla
`
`DCC
`
`0.1 mg/ml•
`
`Visually compatible for 24 hr at room tern-
`perature
`
`Visually compatible for 24 hr at room tern-
`perature
`
`Calcium gluconate
`
`ES
`
`0.092 mEq/ DCC
`ml•
`
`0, 1 mg/ml a
`
`Visually compatible for 24 hr at room tern-
`perature
`
`Cefazolin sodium
`
`SKF
`
`20 mg/mla
`
`DCC
`
`O.lmg/mla
`
`Visually compatible for 24 hr at room tern-
`perature
`
`0.1 mg/ml a White precipitate in 4 hr
`
`Visually compatible for 24 hr at room tem-
`perature
`Precipitate forms immediately
`
`Cefoperazone
`
`Ceft.azidime
`
`RR
`
`GL"
`
`10 mg/ml•
`
`DCC
`
`DCC
`
`0.1 mg/mJa
`
`Ceftizoxime
`
`SKF
`
`10 mg/ml"
`
`DCC
`
`0.1 mg/ml a
`
`SKBC
`
`125 mg/ml
`
`1mg/ml
`
`C/1
`c
`
`c
`
`I
`
`I
`
`c
`
`c
`
`c
`
`c
`
`I
`c
`
`235
`
`235
`
`235
`
`235
`
`235
`
`235
`
`235
`
`235
`
`235
`
`235
`
`2434
`
`235
`
`Chloramphenicol sodium
`succinate
`
`PD
`
`10 mg/ml•
`
`DCC
`
`0.1mg/mla
`
`Cimetidine HCl
`
`SKF
`
`3 mg/ml•
`
`DCC
`
`0.1mg/ml•
`
`Clindamycin phosphate
`
`UP
`
`9 mg/ml"
`
`DCC
`
`0.1 mg/ml a
`
`Dextran 40 in.dextrose 5%
`
`TR
`
`10%
`
`DCC
`
`0.1 mg/ml"
`
`Diltiazem HCl
`
`Dobutamine HCl
`
`Dopamine HCl
`
`MMD
`
`1 mg/ml•
`
`LI
`LI
`
`4mg/ml"
`1 mg/mla
`
`WY
`
`WY
`DCC
`
`1 mg/ml•
`
`1 mg/mla
`0.1 mg/mla
`
`AB
`IMS
`
`3.2mg/ml• WY
`1.6 mg/ml•
`DCC
`
`1 mg/ml•
`0 .1mg/ml a
`
`Enalaprilat
`
`MSD
`
`0.5 mg/ml"
`
`DCC
`
`0.1 mg/ml•
`
`Visually compatible for 24 hr at room tern-
`perature
`
`Visually compatible for 24 hr at room tern-
`perature
`
`Visually compatible for 24 hr at room tem-
`perature
`
`Visually compatible for 24 hr at room tem-
`perature
`
`Visually compatible for 24 hr at room tern-
`perature
`Visually compatible for 4 hr at 27 oc
`Visually compatible for 4 hr at 27 oc
`Visually compatible for 24 hr at room tern-
`perature
`
`Visually compatible for 4 hr at 27 °C
`Visually compatible for 24 hr at room tem-
`perature
`
`Visually compatible for 24 hr at room tern-
`perature
`
`0.02 mg/ml• WY
`
`1 mg/ml•
`
`Visually compatible for 4 hr at 27 °C
`
`Visually compatible for 24 hr at room tem-
`perature
`
`Visually compatible for 24 lu· at room tem-
`perature
`
`Visually compatible for 24 hr at room tern-
`perature
`
`Epinephrine HCl
`
`Erythromycin lactobionate
`
`AB
`
`AB
`
`5 mg/ml"
`
`DCC
`
`0.1 mg/ml•
`
`Esmolol HCl
`
`DU
`
`10 mg/ml•
`
`DCC
`
`0.1 mg/mla
`
`Famotidine
`
`MSD
`
`0.2 mg/mla
`
`DCC
`
`0.1 mg/ml"
`
`I
`c
`
`c
`
`c
`
`c
`
`c
`
`c
`c
`c
`
`c
`c
`
`c
`
`c
`c
`
`c
`
`c
`
`235
`
`235
`
`235
`
`235
`
`2062
`
`2062
`235
`
`2062
`235
`
`235
`
`2062
`
`235
`
`235
`
`235
`
`Sandoz Exhibit 1013 Page 5
`
`

`

`I 1112 /NICARDIPINE HYDROCHLORIDE
`
`Y-Site Injection Compatibility (1 :1 Mixture) (Cont.)
`
`Nicardipine HCI
`
`Drug
`
`Cone
`
`Cone
`
`Remarks
`
`Fenoldopam mesylate
`
`AB
`
`80 mcg/mlb WAY
`
`1 mg/mlb
`
`Fentanyl citrate
`
`Furosemide
`
`Gatifioxacin
`
`Gentamicin sulfate
`
`Heparin sodium
`
`ES
`ES
`
`0.05 mg/ml WY
`2 mcg/ml•
`DCC
`
`1 mg/ml•
`0.1 mg/ml"
`
`AMR
`
`10mg/ml
`
`BMS
`
`2mg/ml"
`
`WY
`
`WY
`
`1 mg/ml•
`
`1 mg/ml"
`
`ES
`
`ES
`IX
`
`0.8 mg/ml"
`
`DCC
`
`0.1 mg/ml•
`
`100 units/ml• WY
`40 units/ml" DCC
`
`1 mg/ml•
`0.1 mg/ml"
`
`Hetastarch in sodium chloride
`0.9%
`
`DU
`
`6%
`
`DCC
`
`0.1 mg/ml"
`
`Hydrocortisone sodium succinate UP
`
`2 mg/ml•
`
`DCC
`
`0.1 mg/ml•
`
`liydromorphone HCl
`
`Labetalol HCl
`
`Lidocaine HCl
`
`KN
`
`AH
`GL
`
`1 mg/ml
`
`2 mg/ml•
`1 mg/ml•
`
`WY
`
`WY
`DCC
`
`1 mg/ml"
`
`1 mg/ml•
`0.1 mg/ml•
`
`Physically compatible with no increase in
`measured haze or particle content in
`4 hr at 23 °C under fluorescent light
`
`Visually compatible for 4 hr at 27 °C
`Visually compatible for 24 hr at room tem-
`perature
`
`Precipitate forms immediately
`
`Physically compatible with no change in
`measured haze or increase in particle
`content in 4 hr at 23 oc
`Visually compatible for 24 hr at room tem-
`perature
`
`Precipitate forms immediately
`Visually compatible for 24 hr at room tem-
`perature
`
`Visually compatible for 24 hr at room tem-
`perature
`
`Visually compatible for 24 hr at room tem-
`perature
`Visually compatible for 4 hr at 27 oc
`Visually compatible for 4 hr at 27 °C
`Visually compatible for 24 hr at room tem-
`perature
`
`C/1
`c
`
`c
`c
`
`I
`c
`
`c
`
`I
`c
`
`c
`
`c
`
`c
`c
`c
`
`2467
`
`2062
`235
`
`2062
`
`2234
`
`235
`
`2062
`235
`
`235
`
`235
`
`2062
`
`2062
`235
`
`235
`
`AST
`
`4 mg/ml"
`
`DCC
`
`0.1 mg/ml"
`
`Linezolid
`
`PHU
`
`2 mg/ml
`
`WAY
`
`1 mg/ml•
`
`Lorazepam
`
`Magnesium sulfate
`
`WY
`
`LY
`
`0.5 mg/ml" WY
`
`1 mg/ml"
`
`10 mg/ml•
`
`DCC
`
`0.1 mg/ml•
`
`Methylprednisolone sodium
`succinate
`
`Metronidazole
`
`Midazolam HCl
`
`Milrinone lactate
`
`Morphine sulfate
`
`UP
`
`0.8 mg/ml"
`
`DCC
`
`0.1 mg/ml•
`
`SE
`
`5 mg/ml
`
`DCC
`
`0.1 mg/ml"
`
`RC
`sw
`SCN
`WY
`
`2 mg/ml"
`
`WY
`
`0.2 mg/ml" WY
`
`1 mg/ml"
`
`1 mg/ml•
`
`2 mg/ml•
`0.2 mg/ml•
`
`WY
`DCC
`
`1 mg/ml"
`0.1 mg/ml"
`
`Nafcillin sodium
`
`BR
`
`10 mg/ml•
`
`DCC
`
`0.1 mg/ml•
`
`1, Nitroglycerin
`
`\Norepln<phdn< bltmtmt<
`· Normosol R
`
`AB
`
`AB.
`
`AB
`
`0.4 mg/ml" WY
`0.128 mg/ml• WY
`
`1 mg/ml•
`
`1 mg/ml"
`
`DCC
`
`0,1 mg/ml•
`
`Visually compatible for 24 hr at room tem-
`perature
`
`Physically compatible with no change in
`measmed turbidity or increase in parti-
`cle content in 4 hr at 23 °C
`Visually compatible for 4 hr at 27 oc
`Visually compatible for 24 hr at room tem-
`perature
`
`Visually compatible for 24 hr at room tem-
`perature
`
`Visually compatible for 24 hr at room tem-
`perature
`Visually compatible for 4 hr at 27 oc
`Visually compatible for 4 hr at 27 °C
`
`Visually compatible for 4 hr at 27 °C
`Visually compatible for 24 hr at room tem-
`perature
`
`Visually compatible for 24 hr at room tem-
`perature
`Visually compatible for 4 hr at 27 oc
`Visually compatible for 4 hr at 27 °C
`
`Visually compatible for 24 hr at room tem-
`perature
`
`l···
`,~.
`
`c
`
`C·
`
`c
`c
`
`c
`
`c
`
`2264
`
`2062
`
`235
`
`235
`
`235
`
`2062
`
`2062
`
`2062
`235
`
`c
`c
`c
`c
`235 . c
`c
`c
`c
`
`2062
`
`2062
`
`235
`
`Sandoz Exhibit 1013 Page 6
`
`

`

`NICARDIPINE HYDROCHLORIDE/1113
`
`'
`
`Y-Site Injection Compatibility (1:1 Mixture) (Cont.)
`
`Nicardipine HCI
`
`Drug
`
`Cone
`
`Penicillin G potassium
`
`PF
`
`50,000 units/ DCC
`ml•
`
`Cone
`
`0.1 mg/ml"
`
`Piperacillin sodium
`
`LE
`
`12 mg/ml•
`
`DCC
`
`0.1 mg/ml"
`
`Plasma-Lyte A
`
`TR
`
`DCC
`
`0.1 mg/ml•
`
`Potassium chloride
`
`LY
`
`0.4 mEq/ml• DCC
`
`0.1 mg/ml•
`
`Potassium phosphates
`
`LY
`
`0.44 mEq/ml" DCC
`
`0.1 mg/ml"
`
`Ranitidine HCl
`
`GL
`GL
`
`1 mg/ml•
`0.5 mg/ml•
`
`WY
`DCC
`
`1 mg/ml•
`0.1 mg/ml•
`
`Sodium acetate
`
`LY
`
`0.4 mEq/ml• DCC
`
`Remarks
`
`Visually compatible for 24 hr at room tern-
`perature
`
`Visually compatible for 24 hr at room tern-
`perature
`
`Visually compatible for 24 hr at room tern-
`perature
`
`Visually compatible for 24 hr at room tern-
`perature
`
`Visually compatible for 24 hr at room tem-
`perature
`Visually compatible for 4 hr at 27 oc
`Visually compatible for 24 hr at room tern-
`perature
`
`C/1
`c
`
`c
`
`c
`
`c
`
`c
`
`c
`c
`
`235
`
`235
`
`235
`
`235
`
`235
`
`2062
`235
`
`235
`
`Sodium nitroprusside
`
`LY
`
`0.2mg/ml"
`
`DCC
`
`0.1 mg/ml•
`
`Visually compatible for 24 hr at room tern-
`perature
`
`0.1 mg/ml"
`
`Visually compatible for 24 hr at room tern-
`perature
`
`25 mg/mlb
`
`WY
`
`1 mg/ml"
`
`Precipitate forms immediately
`
`Thiopental sodium
`
`Tobramycin sulfate
`
`AB
`
`LI
`
`Trimethoprim--sulfamethoxazole QU
`
`Vancomycin HCl
`
`LE
`
`5 mg/ml•
`
`DCC
`
`0.1 mg/ml•
`
`0.8 mg/ml•
`
`DCC
`
`0.1 mg/m1•
`
`0.16 +
`0.8 mg/ml•
`
`DCC
`
`0.1 mg/ml"
`
`Visually compatible for 24 hr at room tern-
`perature
`
`Visually compatible for 24 hr at room tern-
`perature
`
`Visually compatible for 24 hr at room tern-
`perature
`
`235
`
`2062
`
`235
`
`235
`
`235
`
`c
`
`c
`
`I
`c
`
`c
`
`c
`
`c
`
`Vecuronium bromide
`
`OR
`
`1 mg/ml
`
`WY
`
`1 mg/ml"
`
`Visually compatible for 4 hr at 27 °C
`
`2062
`
`"Tested in dextrose 5% in water.
`~>Tested in sterile water for injection.
`'Sodium carbonate-containing formulation tested.
`
`Additional Compatibility Information
`
`Infusion Solutions -The manufacturer states that nicardipine hydro(cid:173)
`chloride is stable for 24 hours at room temperature diluted to a 0.1-
`mg/ml concentration in glass and PVC containers in the following
`infusion solutions (1-11/27 /96):
`
`Dextrose 5% with potassium chloride 40 mEq
`Dextrose 5% in sodium chloride 0.45%
`Dextrose 5% in sodium chloride 0.9%
`Dextrose 5% in water
`Sodium chloride 0.45%
`Sodium chloride 0.9%
`
`Nicardipine hydrochloride is incompatible with Ringer's injection,
`lactated, and sodium bicarbonate 5%. (1-11/27/96)
`
`Sandoz Exhibit 1013 Page 7
`
`

`

`1604 /REFERENCES
`
`216. Shils ME, Wright WL, Turnbull A, et a!. Long-tenn parenteral nutrition
`through an external arteriovenous shunt. N Eng/ J Med. 1970; 283:341-4.
`217. Zia H, Tehrani M. Kinetics of carbenicillin degradation in aqueous solutions.
`Can J Pharm Sci. 1974; 9:112-7.
`218. Riff LJ, Jackson GG. Laboratory and clinical conditions for gentamicin inac(cid:173)
`tivation by carbenicillin. Arch Intern Med. 1972; 130:887-91.
`219. McLaughlin JE, Reeves DS. Clinical and laboratory evidence for inactivation
`of gentamicin by carbenicillin. Lancet. 1971; 1:261-4.
`220. Klastersky J. Carbenicillin plus gentamicin. Lancet. 1971; 1:653-4.
`221. Levison ME, Kaye D. Carbenicillin plus gentamicin. Lancet. 1971; 2:45-6.
`222. Eykyn S, Phillips I. Gentamicin plus carbenicillin. Lancet. 1971; 1:545-6.
`223. Riff L, Jackson GG. Gentamicin plus carbenicillin. Lancet. 1971; 1:592.
`224. Zost ED, Yanchick VA. Stability of gentamicin in combination with carben(cid:173)
`icillin. Am J Hosp Pharm. 1972; 29:388-90.
`Jacoby GA. Carbenicillin and gentamicin. N Eng/ J Med. 1971; 284:1096-8.
`225.
`226. Kleinberg ML (Professional Services, Immunex, Seattle, WA): Personal C01ll(cid:173)
`munication; 1993 Jun 14.
`227. Baldini JT (P.rofessional Services, Schering Laboratories, Kenilworth, NJ):
`Personal communication; 1972 Feb 11.
`228. Koup JR, Gerbracht L. Combined use of heparin and gentamicin in peritoneal
`dialysis solutions. Drug Intel/ Clin Pharm. 1975; 9:388.
`229. Reeves DS, Bywater MJ, WiseR, et al. Availability of three antibiotics after
`intramuscular injection into thigh and buttock. Lancet. 1974; 2:1421-2.
`Jackson GG. Gentamicin. Practitioner. 1967; 198:855-66.
`230.
`231. Preskey D, Kayes JB. Stability of sulfadiazine sodium as used in admixture
`with intravenous infusion fluids. J Clin Pharm. 1976; 1:39-48.
`232. Physicians' desk reference. 49th ed. Oradell, NJ: Medical Economics Com(cid:173)
`pany; 1995.
`233. Larsen SS, Jensen VG. Studies on stability of drugs in frozen systems. II. The
`stabilities of hexobarbital sodium and phenobarbital sodium in frozen aqueous
`solutions. Dan Tidsskr Farm. 1970; 44:21-31.
`234. NCI investigational drugs phmmaceutical data. Bethesda, MD: National Can(cid:173)
`cer Institute; 1988, 1990, 1994.
`235. Halpern NA, Colucci RD, Alicea M, et a!. The compatibility of nicardipine
`hydrochloride injection with various ICU medications during simulated Y-site
`injectimi.. Int J Clin Pharmacal Ther Toxico/. 1989; 27:250-4.
`236. Anon. Kidney toxicity-main source of methotrexate complications. J Am
`Med Assoc. 1975; 223:1036-7.
`237, Baker MBC Hospital Products Division, Abbott Laboratories, Abbott Park,
`Illinois: Personal Communication; 2003 Aug 27.
`238. Hoeprich PD, Huston AC. Stability of foup antifungal antimicrobics in vitro.
`J Infect Dis. 1978; 137:87-93.
`239. Selam JL, Lord P, van Antwerp WP, et a!. Heparin addition to insulin in
`implantable pumps to prevent catheter:obstruction. Diabetes Care. 1989; 12:
`38-9.
`240. Wang DP. Stability of procaine in aqueous systems. Analyst. 1983; 108:
`851-6.
`241. Lapidas B. Cautions regarding the preparation of high-dose methotrexate in(cid:173)
`fusions. Am J Hosp Pharm. 1976; 33:760.
`242. Pelsor FR. Cautions regarding the preparation of high-dose methotrexate in(cid:173)
`fusions. Am J Hosp Pharm. 1976; 33:760.
`243. Pritchard J. Stability of heparin solutions. J Pharm Pharmacal. 1964; 16:
`487-9.
`244. Turco SJ. LV. drug incompatibilities-heparin sodium USP. Am J IV Ther.
`1976; 3:16-9.
`.
`245. Kakkar VV, Coni gail TP. Prevention of fatal postoperative pulmonary em(cid:173)
`bolism by low doses of heparin: an international multicentre trial. Lancet.
`1975; 2:45-51.
`246. Sherry S. Low-dose heparin prophylaxis for postoperative venous thrombo(cid:173)
`embolism. N Eng/ J Med. 1975; 293:300-2.
`247. Gallus AS, Hirsch J, O'Brien SE, et al, Prevention of venous thrombosis with
`small, subcutaneous doses of heparin. JAMA. 1976; 235:1980-2.
`248. Hopefl A W. Low-dose heparin for the prevention of venous thromboembo(cid:173)
`lism. Hosp Pharm. 1976; 11:223.
`249. Wessler S. Heparin as an antithrombotic agent. Low-dose prophylaxis. JAMA.
`1976; 236:389-91.
`.
`250. Erdi A, Kakkar VV, Thomas DP, et al. Effect of low-dose subcutaneous hep-
`arin on whole-blood viscosity. Lancet. 1976; 2:342-4.
`251. Hadgraft JW. Adding drugs to intravenous infusions. Lancet. 1970; 2:1254.
`252. Stock SL, Warner N. Heparin in acid solutions. /3r Med J. 1971; 3:307.
`253. Chessells JM, Braithwaite T A. Dextrose and sorbitol as diluents for continuous
`intravenous heparin infusion. Br Med J. 1972; 2:81-2.
`254. Mitchell JF, Barger RC. Hepal'in stability in 5% dextrose and 0.9% sodium
`chloride. Am J Hosp Pharm. 1976; 33:540-2.
`
`255. Thomas RB, Salter FJ. Heparin locks: their advantages and disadvantages.
`Hosp Formul. 1975; 10:536-8.
`256. Deeb EN, DiMattia PE. The key question: how much heparin in the lock?. Am
`J IVTher. 1976; 3:22-6.
`257. DeFina E. How we use hepm·in locks. Am J IV Ther. 33 (Dec-Jan) 1976; 3:
`27.
`258. Hanson RL, Grant AM, Heparin-lock maintenance with ten units of sodium
`heparin in one milliliter of nonnal saline solution. Surg Gynecol Obstet. 1976;
`142:373-6.
`259. Rebagay ;r, DeLuca PP. Residues in antibiotic preparations, ii: effect of pH
`on the nature and level of particulate matter in sodium cephalothin intravenous
`solutions. Am J Hosp Pharm. 1976; 33:443-8.
`260. Albano D (Manager Drug Information, Wyeth-Ayerst). Personal Communi(cid:173)
`cation; 1994 Jan 5.
`261. Hopefl AW. Room temperature stability of drug products. Am J Hosp Pharm.
`1975; 32:1084.
`262. Barger RC. Room temperature stability of drug products. Am J Hosp Pharm.
`1975; 32:1089.
`263. Rosenbloom AL. Advances in commercial insulin preparations. Am J Dis
`Child. 1974; 128:631-3.
`264. Rosenberg JM, Simon W A, Sangkachand P, et al. Mixing insulin preparations.
`. Hosp Pharm. 1976; 11:186.
`265. Shainfeld FJ. Errors in insulin doses due to the design of insulin syringes.
`Pediatrics. 1975; 56:302-3.
`266. Weisenfeld S, Podolsky S, Goldsmith L, eta!. Adsorption of insulin to infusion
`bottles and tubing. Diabetes. 1968; 17:766-71.
`267. Petty C; Cunningham NL. fusulin adsorption by glass infusion bottles, poly(cid:173)
`vinylchloride infusion containers, and intravenous tubing. Anesthesiology.
`1974; 40:400-4.
`268. Kraegen EW, Lazarus L, Meier H, et a!. Canier solutions for low-level intra(cid:173)
`venous insulin infusion. Br Med J. 1975; 3:464-6.
`269. Semple P, Ratcliffe JG. Canier solutions for low-level intravenous insulin
`infusion. Br Med J. 1975; 4:228-9.
`270. Hays DP, Mehl B. LV. drug incompatibilities-insulin. Ami IV Ther. 1976;
`3:30-2.
`271. Owen JA. The insulin revolution. Hosp Formul. 1976; 11:343.
`272. Galloway JA (Medical Research Division, Eli Lilly and Company, fudianap(cid:173)
`olis, IN): Personal communication; 1967 Aug 29.
`273. Rubin J, Humphries J, Smith G, eta!. Antibiotic activity in peritoneal dialysate.
`Am J Kidney Dis. 1983; 3:205-8.
`274. De Vroe C, De Muynck C, Remon JP, et a!. The availability of diltiazem: a
`study on the smptimt by intravenous delivery systems and on the stability of
`the drug. J Pharm Pharmacal. 1989; 41:273-5.
`275. Kochevar M, Fry LK. fusulin and dead space volume. Drug Intel/ Clin Pharm.
`1974; 8:33-4.
`276. Bornstein M, Thomas PN, Coleman DL, eta!. Stability of parenteral solutions
`of cefazolin sodium. Am J Hasp Pharm. 1974; 31:296-98.
`277. Carone SM, Bomstein M, Coleman DL, et al. Stability of frozen solutions of
`cefazolin sodium. Am J Hosp Pharm, .1976; 33:639-41.
`278. Royston DA (Consumer Technical Services, Eli Lilly and Company, India(cid:173)
`napolis, IN): Personal communication; 1976 Feb 19.
`279. Brudney N, Eustace BT. Some fo'rmulations and compatibility problems with
`dimenhydrinate (Gravol). Can PharmJ. 1963; 96:470-1.
`280. Acred P, Brown DM, Knudsen ET~ eta!. New semi-synthetic penicillin active
`against pseudomonas pyocyanea. Nature (London). 1967; 215:25-30.
`281. Schwartz MA, Buckwalter FH. Pharmaceutics of penicillin.! Ph arm Sci. 1962;
`51:1119-28.
`.
`282. Thur MP (Parenteral Products, Travenol Laboratories, Deerfield, IL): Personal
`communication; 1976 Sep ·20.
`.
`283. Ziemba LJ (Medical Infoimation·, ICI Pharmaceuticals Group, Wilmington,
`DE): Personal communication; 1990 Mar 15.
`284. Yamana T, Tsuji A. Comparative stability of cephalosporins in aqueous so(cid:173)
`lution: kinetics and mechanisms of degradation. J Pharm Sci. 1976; 65:
`1563-74.
`285. Kleinman LM, Davignon JP, Cradock JC, et al. Investigational drug infor(cid:173)
`mation. Drug Intel/ Clin Pharm. 1976; 10:48-9.
`286. Chang SY, Evans TL. The stability of melphalan ·In the presence of chloride
`ion. J Pharm Pharmacal. 1979; 31:853-4.
`287. Mitenko PA, Ogilvie RI. Rational intravenous doses of theophylline. N Eng/
`J Med. 1973; 289:600-3.
`288. Simons FER, Pierson WE. Current status of the use of intravenously admin(cid:173)
`istered aminophylline. South Med J. 1975; 68:802-4.
`289. Weinberger MW, Mattlmy RA, Ginchansky EJ, eta!. Intravenous aminophyl(cid:173)
`line dosage. Use of serum theophylline measurement for guidance. JAMA.
`1976; 235:2110-3.
`
`Sandoz Exhibit 1013 Page 8
`
`

`

`1346. Messerschmidt W. Kompatibilitat von ciprofloxacin.und metronidazol in mis(cid:173)
`chinfusionen. Pharm Ztg. 1988; 133:26.
`1347. Murdoch JM, Garner ST. Calcium gluconate compatibility. Pharm J. 1989;
`242:634.
`1348. Stoberski P, Zakrzewski Z. Bandanie stabilnosci furosemidu i soli sodowej
`hemibursztynianu hydrokortyzonu metoda RP-HPLC w wybranych plynach
`infuzyjnych. Farm Pol. 1988; 44:398-401.
`1349. Veechio M, Walker SE, Iazzetta J, eta!. The stability of morphine intravenous
`infusion solutions. Can J·Hosp Pharm. 1988; 41:5-9.
`1350. Walker SE, Kirby K. Stability' of ranitidine hydrochloride admixtures refrig(cid:173)
`erated in polyvinyl chloride minibags. Can J Hosp Pharm. 1988; 41:105-8.
`1351. Gupta VD, Parasrampuria J, Bethea C, et at: Stability of clindamycin phos(cid:173)
`phate in dextrose and saline solutions. Can J Hosp Pharm. 1989; 42:109-12.
`1352. Walker SE, Iazzetta J, Lau DWC, eta!. Famotidine stability in total parenteral
`nutrient solutions. Can J Hosp Pharm. 1989; 42:97-103.
`1353. Walker SE, Dranitsaris G. Ceftazidime stability in normal saline·and dextrose
`5% in water. Can J Hosp Pharm. 1988; 41:65-71.
`1354. Walker SE, Birkhans B. Stability of intravenous vancomycin. Can J Hosp
`Pharm. 1988; 41:233-8.
`1355. Halpern NA, Colucci RD, Alicea M, et a!. Visual compatibility of enalaprilat
`with commonly used critical care medications during simulated Y-site injec(cid:173)
`tion. Int J Clin Pharmacal Ther Toxicol. 1989; 27:294-7.
`1356. Allen LV Jr, Stiles ML. Stability of fentanyl citrate in 0.9% sodium chloride
`solution in portable infusion pumps. Am J Hosp Pharm. 1990; 47:1572-4.
`1357. Kowalski SR, Gourlay GK. Stability of fentanyl citrate in glass and plastic
`containers and in a patient-controlled delivery system. Am J Hosp Pharm.
`1990; 47:1584-7.
`1358. Schaaf LJ, Robinson DH, Vogel GJ, eta!. Stability of esmolol hydrochloride
`in the presence of aminophylline, bretylium tosylate, heparin sodium, and pro(cid:173)
`cainamide hydrochloride. Am J Hosp Pharm. 1990; 47:1567-71.
`1359. Rosenberg LS, Hostetler CK, Wagenknecht DM, eta!. An accurate prediction
`of the pH change due to degradation: correction for a "produced" secondary
`buffering system. Pharm Res. 1988; 5:514-7.
`1360. Williams MF, Hak LJ. In vitro evaluation of the stability of·ranitidine hydro(cid:173)
`chloride in total parenteral nutrient mixtures. Am J Hosp Pharm. 1990; 47:
`1574-9.
`1361. Galante LJ, Stewart JT, Warren FW, eta!. Stability of ranitidine hydrochloride
`with eight medications in intravenous admixtures. Am J Hosp Pharm. 1990;
`47:1606-10.
`· 1362. Galante LJ, Stewart JT, Warren FW, eta!. Stability ofranitidine hydrochloride
`at dilute concentration in intravenous infusion fluids at room temperature. Am
`J Hosp Pharm. 1990; 47:1580-4.
`1363. Marquardt ED. Visual compatibility of tolazoline hydrochloride with various
`medications during simulated Y-site injection. Am J Hosp Pharm.1990; 47:
`1802-3.
`1364. Chandler SW, Folstad J. Aztreonam-vancomycin incompatibility. Am J Hosp
`Pharm. 1990; 47:1970.
`1365. Trissel LA, Tramonte SM. Visual compatibility of ondansetron hydrochloride
`with other selected drugs dJ!ring simulated Y-site injection. Am J Hosp Pharm.
`1991; 48:988-92.
`1366. Leak RE, Woodford JD. Pharmaceutical development of on(!ansetron injec(cid:173)
`tion. Eur J Cancer Clin Oneal. 1989; 25 (Suppl l);S67-S69. ·
`1367. Mackinnon JW, Collin DT. The chemistry of ondansetron. Eur J Cancer Clin
`Oneal. 1989; 25 (Suppl l):S61.
`1368. Adria Laboratories. Idamycin-hospital formulary product infmmation f9rm.
`Columbus, OH; 1990 Oct 19.
`·
`1369. Allwood M, Stanley A, Wright P. The cytotoxics handbook. 3rd ed, Oxford,
`England: Radcliffe Medical Press; 1997.
`1370. Gari~ot 0, Vitzling C, Mottu R, et a!. Sandostatine: compatibility of sandos(cid:173)
`tatine 100 f.Lg/ml and 500 f.Lg/ml infusions with various plastic syringes and
`infusion apparatus: Baste, Switzerland: Sandoz Pha1maceutical Research Cen(cid:173)
`ter; 1988 Sep.
`1371. Sandoz Laboratories. Sandostatin---compatibility between octreotide in the in(cid:173)
`fusion and the giving set/container. Basle, Switzerla~d; 1986 Apr 3.
`1372. Sandoz Laboratories. Sandostatin-stability in physio'!ogical salt solutions.
`Baste, Switzerland; 1986 Mar 26.
`1373. Marchiarullo M. Stability of octreotide in various infusion suppiies. East Han(cid:173)
`over, NJ: Sandoz Pharmaceuticals Corporation; 1990 Mar 20.
`1374. Beijnen JH, Beijnen-Bandhoe AU, Dubbelman AC, eta!. Chemical and phys(cid:173)
`ical stability of etoposide and teniposide in commonly used infusion fluids. J
`Parenter Sci Tee/mol. 1991; 45:108-12.
`1375. Santiero ML, Sagraves R. Osmolality of small-volume i.v. admixtures for pe(cid:173)
`diatric patients. Am J Hosp Pharm. 1990; 47:1359-64.
`1376. Messerschmidt W. Kompatibilitat von cefuroxim mit metronidazole. Kran(cid:173)
`ken/wuspharmazie. 1987; 8:45-7.
`
`REFERENCES/1621
`
`1377. Rosen GH. Potential incompatibility of insulin and octreotide in total paren(cid:173)
`teral nutrient solutions. Am J Hosp Pharm. 1989; 46:1128.
`1378. McElnay JC, Elliott DS, Cartwright-Shamoon J, eta!. Stability of methotrexate
`and vinblastine in burette administration sets. Int J Pharm. 1988; 47:
`239-47.
`1379. Williams DA. Stability and compatibility of admixtures of antineoplastic
`drngs. In: Lokich JJ, ed. Cancer chemotherapy by infusion. 2nd ed. Chicago,
`IL: Precept Press; 1990:52-73.
`1380. Baaske DM, DeMay JF, Latona CA, et al. Stability