Transplantation drug manual

151 Pages·2003·0.509 MB·English

by  John Pirsch, William D Simmons, Hans Sollinger

Transplantation
Drug Manual
Fourth Edition
John Pirsch, MD
Professor of Medicine and Surgery
Director of Medical Transplantation
University of Wisconsin
Madison, Wisconsin, USA
William D. Simmons, RPH
Senior Clinical Pharmacist
School of Pharmacy Instructor
Transplantation Specialist
University of Wisconsin
Madison, Wisconsin, USA
Hans Sollinger, MD, PhD
Folkert O. Belzer Professor of Surgery
Chairman, Division of Organ Transplantation
University of Wisconsin
Madison, Wisconsin, USA
LANDES
BIOSCIENCE
AUSTIN, TEXAS
U.S.A.
TRANSPLANTATION DRUG MANUAL, 4TH EDITION
LANDES BIOSCIENCE
Austin, Texas, U.S.A.
U.S. and World Copyright © 2003 Landes Bioscience
All rights reserved.
No part of this book may be reproduced or transmitted in any form or by any means,
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and retrieval system, without permission in writing from the publisher.
Printed in the U.S.A.
Please address all inquiries to the Publishers:
Landes Bioscience, 810 South Church Street, Georgetown, Texas, U.S.A. 78626
Phone: [phone]; FAX: [phone]
www.landesbioscience.com
International and U.S. ISBN 1-57059-678-6
Although this pocket reference guide summarizes pertinent drug information, full
Prescribing Information should be consulted before prescribing any product. The
contents of this publication are the sole responsibility of the medical editors and not of
Sangstat Medical Corporation or the Publisher.
While the authors, editors, and publisher believe that drug selection and dosage and the
specifications and usage of equipment and devices, as set forth in this book, are in accord
with current recommendations and practice at the time of publication, they make no
warranty, expressed or implied, with respect to material described in this book. In view of
the ongoing research, development, changes in governmental regulations and the rapid
accumulation of information relating to the biomedical sciences, the reader is urged to
carefully review and evaluate the information provided herein.
Library of Congress Cataloging-in-Publication Data
CIP applied for, but not available at time of publication.
Table of Contents
1. Working Guide to Immunosuppression................ 1
Current Agents Overview...................................................3
Antithymocyte Globulin (Equine).......................................5
Antithymocyte Globulin (Rabbit) .......................................6
Azathioprine......................................................................7
Cyclophosphamide............................................................8
Cyclosporine-A (Non-Modified).........................................9
Cyclosporine-A................................................................10
Cyclosporine Capsules and Oral Solution
(Modified)........................................................................11
Methylprednisolone.........................................................13
Muromonab-CD3............................................................15
Mycophenolate Mofetil....................................................17
Prednisone.......................................................................18
Tacrolimus.......................................................................19
Basiliximab......................................................................21
Daclizumab.....................................................................22
Sirolimus..........................................................................23
2. Antimicrobials .................................................... 25
Antivirals Overview.........................................................27
Acyclovir.........................................................................28
Valacyclovir.....................................................................31
Famciclovir......................................................................33
Ganciclovir......................................................................34
Valganciclovir..................................................................36
Immunoglobulin..............................................................37
CMV Hyperimmune Globulin..........................................38
Foscarnet Sodium............................................................39
Antibiotics Overview.......................................................41
Trimethoprim and Sulfamethoxazole (TMP-SMX).............43
Penicillins with Beta-Lactamase Inhibitor.........................45
Quinolones......................................................................47
Cephalosporins................................................................50
Aminoglycosides..............................................................53
Linezolid..........................................................................55
Antifungals Overview......................................................56
Nystatin Suspension.........................................................57
Clotrimazole Troche.........................................................58
Fluconazole.....................................................................59
Amphotericin B................................................................60
Amphotericin B Lipid Complex Injection.........................62
Miconazole Vaginal Cream 2%........................................63
Ketoconazole...................................................................64
Caspofungin.....................................................................65
3. Cardiovascular Agents......................................... 66
Cardiovascular Agents Overview.....................................68
Calcium Channel Blockers...............................................71
Alpha-Adrenergic Receptor Blockers................................74
Central Alpha-Adrenergic Agonist....................................75
Beta-Blockers...................................................................76
ACE Inhibitors..................................................................77
Angiotensin II Receptor Antagonists.................................79
Cholesterol-Lowering Agents ...........................................80
4. Antiosteoporosis Agents...................................... 83
Antiosteoporosis Agents Overview...................................85
Alendronate Sodium........................................................86
Etidronate Disodium........................................................87
Calcitonin-Salmon...........................................................88
5. Antiplatelets........................................................ 89
Antiplatelets Overview.....................................................91
Antiosteoporosis Agents Overview...................................91
Aspirin.............................................................................92
6. Diabetes Agents................................................... 93
Diabetes Agents Overview...............................................95
Insulin..............................................................................97
Glyburide......................................................................100
Glipizide........................................................................102
Metformin Hydrochloride..............................................103
Pioglitazone...................................................................104
Rosiglitazone.................................................................105
7. Ulcer Prophylaxis and Treatment...................... 107
Ulcer Prophylaxis and Treatment Overview...................109
Magnesium/Aluminum Hydroxide Suspension,
Aluminum Hydroxide Suspension,
Calcium Carbonate........................................................110
Histamine H2-Receptor Antagonists...............................112
Proton Pump Inhibitors..................................................114
Pantoprazole..................................................................116
Sucralfate.......................................................................117
8. Diuretics ........................................................... 119
Diuretics Overview........................................................121
Diuretics........................................................................122
9. Other Concomitant Agents............................... 125
Other Concomitant Agents Overview ............................127
Other Cardiovascular Agents .........................................131
Levothyroxine................................................................134
Sodium Bicarbonate.......................................................135
Aquaphor® Ointment....................................................136
Octreotide .....................................................................137
Metoclopramide ............................................................138
Bethanechol...................................................................140
Phenytoin......................................................................141
Warfarin.........................................................................142
Pentoxifylline.................................................................144
Fludrocortisone..............................................................145
Potassium......................................................................146
Introduction
The field of transplantation continues to evolve. In the
years since the first publication of the Transplantation
Drug Pocket Reference Guide, the therapeutic armamen-
tarium for transplantation has grown. The introduction
of new agents continues to enhance our ability to im-
prove the short- and long-term success of transplantation.
The third edition of the guide, now entitled Transplanta-
tion Drug Manual, includes information on agents
approved for use in transplant recipients. As in the first
and second editions, we compiled practical information
on the wide array of pharmaceutical agents currently
available—both those used for immunosuppression and
those used to minimize posttransplant complications. The
agents described here are the most frequently prescribed
drugs in the Transplant Service at the University of
Wisconsin. We hope you find this information to be
useful and practical in managing the transplant patient.
Chapter 1
Working Guide to Immunosuppression
Current Agents Overview
• Antithymocyte globulin (equine) - ATGAM
• Antithymocyte globulin (rabbit) -Thymoglobulin
• Azathioprine
• Cyclophosphamide
• Cyclosporine-A
• Cyclosporine Capsules and Oral Solution
(Modified)
• Methylprednisolone
• Muromonab-CD3
• Mycophenolate Mofetil
• Prednisone
• Tacrolimus
• Basiliximab
• Daclizumab
• Sirolimus

3
Current Agents Overview n
-o
nosi
ues
Agent Dosage mr
p
mp
Antithymocyte Delaying Onset of Allograft Rejection Iu
s
Globulin (ATGAM) •Fixed dose of 15 mg/kg for 14 days, then every other day for 14 days
s
for a total of 21 doses in 28 days al
•First dose should be administered within 24 hours before or after bi
o
transplantation cr
mi
Treatment of Rejection nti
A
•10-15 mg/kg/d IV for 8-14 days, then every other day up to 21 doses
Antithymocyte Treatment of Rejection ar
ul
Globulin (rabbit) • 1.5 mg/kg/d for 7 to 14 days IV cs
asnt
Azathioprine •3 mg/kg/d to 5 mg/kg/d single dose given at time of transplantation ve
og
•1 mg/kg/d to 3 mg/kg/d for maintenance diA
•Dose usually adjusted depending on WBCs Car
•Lower doses should be considered in presence of renal dysfunction
s
Cyclophosphamide •2 mg/kg/d to 3 mg/kg/d is initial recommended dose, but is rapidly o-ent
reduced due to toxicity ostes Ag
Cyclosporine-A Gelatin Capsules & Oral Solution ntiosi
•15 mg/kg single dose given 4 to 12 hours prior to transplantation Aor
•Usual starting dose in 4-10 mg/kg in bid dosing. Dose is titrated to p
achieve whole blood levels of 200-300 mg/ml s
et
el
IV Infusion at
•5 mg/kg to 6 mg/kg single dose given 4 to 12 hours prior to pl
transplantation nti
•Single daily IV dose continued postoperatively until patient can tolerate A
oral formulations
Cyclosporine NOTE: Neoral, Gengraf, and Sandimmune are not bioequivalent and ess
Capsules and Oral should not be used interchangeably. Neoral has increased etnt
be
Solution bioavailability and this should be taken into consideration ag
(Modified) when making dosing decisions. DiA
•Daily dose should be given as two divided doses on a consistent
schedule nt
re
em
Newly Transplanted Patients Ulcat
•Initial dose of Neoral should be the same as a Sandimmune dose. e
Suggested initial doses include: Tr
– 9 ± 3 mg/kg/day for kidney transplant patients
– 8 ± 4 mg/kg/day for liver transplant patients
s
•–Th e 7 d ±o s3e m isg t/hkgen/d sauyb fsoer qhueeanrttl ytr aandsjupslatendt ptoa taiecnhtiseve a predefined etic
r
cyclosporine blood concentration u
Di
Conversion from Sandimmune to Neoral
•Neoral should be started with the same daily dose as was previously
•uTsheed N weoitrha lS daonsdeim smhouunlde (th1e:1n dboes aed cjuosntveedr stoio nac)hieve preconversion herents
cyclosporine blood trough concentrations Otg
A
•Until cyclosporine blood trough concentrations reach preconversion
levels, monitoring should be undertaken every 4 to 7 days
Continued …
4
-on Current Agents Overview
nosi
ues
mpr Agent Dosage
mp
Isu Methylprednisolone Induction
•250 mg to 1000 mg at time of transplantation and for next 2 to 3 doses
s
al
obi Taper
cr •Start at 2 mg/kg/d, taper to a range of 0.15 mg/kg/d to 0.2 mg/kg/d after
mi
one year
nti
A
Attenuation of Cytokine Release Syndrome
ular •8 mg/kg given 1 to 4 hours prior to first injection of muromonab-CD3
ascnts Muromonab-CD3 •5 mg/d IV for 10 to 14 days
ve
dioAg Mycophenolate Initial dose should be given within 72 hours following transplantation
ar Mofetil •1.0 g twice a day used in combination with corticosteroids and
C cyclosporine
s
eo-gent Prednisone M•a0i.n1t emnga/nkcge/—d tAod 2u lmtsg/kg/d usually given once daily
osts A
ntiosi Maintenance—Pediatric
Aor •0.25 mg/kg/d to 2 mg/kg/d or 25 mg/m2 to 60 mg/m2 usually given
p daily or on alternate days
s
et Tacrolimus IV Infusion
el •0.03 to 0.05 mg/kg/d as a continuous infusion
at
pl
nti Capsules
A •0.15 mg/kg/d to 0.30 mg/kg/d administered in 2 divided daily doses
every 12 hours
s •First dose should be given 8 to 12 hours after discontinuing IV infusion
es
etnt Basiliximab • 20 mg within 2 hours of transplantation surgery and repeated 4 days
be
ag after transplantation
DiA
Daclizumab • 1 mg/kg/dose for 5 doses. The first dose within 24 hours of transplanta-
tion, then at intervals of 14 days for 4 doses
nt
re
em
c
Ulat
e
Tr
s
c
eti
r
u
Di
ernts
he
Otg
A
5
Antithymocyte Globulin (Equine) n
-o
nosi
ues
Brand Name ATGAM® mpr
mp
Company Pharmacia & Upjohn, Inc. Iu
s
Class •Immunosuppressant gamma globulin, primarily monomeric IgG, from
s
hyperimmune serum of horses immunized with human thymic al
lymphocytes bi
o
Mechanism of •Antibodies of multiple specificities interact with lymphocyte surface cr
mi
Action antigens, depleting numbers of circulating, thymus-dependent lympho-
cytes and interfering with cell-mediated and humoral immune responses nti
A
Indications •Management of renal allograft rejection
•Adjunct to other immunosuppressive therapy to delay the onset of the ular
first rejection episode cs
asnt
Contraindication •Hypersensitivity to ATGAM or any other equine gamma globulin ovge
preparation diA
ar
Warnings •Should be administered in facilities equipped and staffed with adequate C
laboratory and supportive medical resources s
•Immunosuppressive activity may vary from lot to lot o-ent
•Potential for the transmission of infectious agents eg
•Treatment should be discontinued if the following occur: osts A
• Symptoms of anaphylaxis • Thrombocytopenia • Leukopenia ntiosi
Special •Risk of infection, leukopenia, and thrombocytopenia Aor
p
Precautions •Safety and effectiveness demonstrated only in patients who received
s
concomitant immunosuppression et
•Pregnancy Category C el
at
Adverse Reactions •Fever (1 patient in 3) pl
•Chills (1 patient in 7) nti
•Leukopenia (1 patient in 7) A
•Dermatologic reactions (1 patient in 8)
•Thrombocytopenia (1 patient in 9)
s
Reported in >1%, but <5% of Patients etents
•Arthralgia •Chest and/or back pain be
•Clotted A/V fistula •Nausea and/or vomiting DiaAg
•Night sweats •Pain at infusion site
•Peripheral thrombophlebitis •Stomatitis
Drug Interaction •Dextrose Injection, USP nt
Formulation •5 mL ampule containing 50 mg/mL erme
c
Dosage Delaying Onset of Allograft Rejection Ulat
•Fixed dose of 15 mg/kg for 14 days, then every other day for 14 days for Tre
a total of 21 doses in 28 days
•First dose should be administered within 24 hours before or after
transplantation s
c
Treatment of Rejection eti
•10 mg/kg/d IV for 8-14 days, then every other day up to 21 doses r
u
Dose should be infused at least over 4 hours, through a 0.2-1 micron filter Di
Editors’ Notes:
ATGAM® and Thymoglobulin® are the only two polyclonal antilymphocyte preparations which are currently avail-
aAbTleG. AAMTG®A cMau®se si sle assn leimukmopuennoigal othbaunle T ahgyaminostg lloybmuplihno®cy. tBeos tphr eapgeanretds hinav eh obreseens; uTsehdy mtoo pgrleovbeunltin a®cu ties rperjeepctairoend aifnt erra tbrbanitss-. herents
plantation and to treat acute rejection episodes. Otg
A