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Plumb's V eterinary Drug Handbook Sixth Edition Donald C. Plumb, Pharm. D. distributed by Blackwell Publishing

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COPyri GHt © 2008 by d onald C. Plumb All rights reserved. No part of this book may be reproduced or transmitted in any form or any means, electronic or mechanical, including recording, photocopying, or by any information stor age and retrieval system, without the written permission of the copyright owner. worldwide print distribution by: Blackwell Publishing Professional 2121 s outh state Avenue Ames, i owa 50014-8300 (800) 862-6657www. blackwellpublishing. com/Vet/ published by Pharma V et Inc. stockholm, Wisconsin design and typesetting Peregrine Graphics s ervices st. Paul, Minnesota isb N: 978-0-8138-1097-3 Last digit is the print number 9 8 7 6 5 4 3 2 1

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For Shirley, Whose efforts, support, and love make this reference a reality * * *

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Contributors to the Sixth Edition C. A. t ony b uffington, d VM, Phd, d ACVN Professor of Veterinary Clinical sciences the Ohio state u niversity Veterinary Hospital Columbus, OH Dog and Cat Therapeutic Diets Andrea G. Cannon, d VM, d ACVd Animal d ermatology & Allergy rocklin, CA; Modesto, CA; b oise, id Dermatological Agents, Topical Gigi davidson, di CVP North Carolina state u niversity raleigh, NC Ophthalmology Products, Topical Principles of Compounding Ophthalmic Products Camille d e Clementi, VMd, d Abt As PCA Animal Poison Control Center urbana, i L Overdose and Toxin Exposure Decontamination Guidelines, ASPCA Animal Poison Control Center Data for Drug Monographs Michelle d u Mond, r Vt Nutrition s upport specialist the Ohio state u niversity Veterinary Hospital Columbus, OH Dog and Cat Therapeutic Diets dinah Jordan, Pharmd, di CVP Mississippi state u niversity Mississippi state, Ms Insulin, Maropitant, & Mirtazapine Monographs sandra Koch, d VM, Ms, d ACVd College of Veterinary Medicine, u niversity of Minnesota st. Paul, MNDermatological Agents, Topical elaine Lust, Pharmd, di CVP Creighton u niversity Omaha, Ne Ceftiofur (Free Acid, Sodium and HCl), Danofloxacin, Tulathromycin Monographs to sign up for e-mail notifi cation of updates and errata, or get information on ordering information for additional versions, visit Plumb's Veterinary Drug Handbook's web site at: www. vetdruginfo. com

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Preface to the Sixth Edition in this edition, Plumb's Veterinary Drug Handbook continues to evolve with the addition of more drugs, more types of drugs (topical dermatology drugs), and a new look; however, the basic premise remains to serve as a single volume reference to assist veterinarians, other health professionals, and animal caretakers in providing optimal drug therapy for veterinary patients. t he changes to this edition include a new design and layout; the addition of 75 new drug monographs; updates to the older monographs, with a listing for rapid-scanning for potential drug interactions and overdose information for 50 drugs from the As PCA Animal Poison Control Center; and new sections on topical dermatologic agents and products, Principles of Compounding Ophthalmic Products, and Overdose and t oxin exposure d econtamination Guidelines in the appendix. donald C. Plumb About the Author donald C. Plumb, Pharm. d., was formerly d irector of Pharmacy s ervices and Hospital d irector at the university of Minnesota's Veterinary Medical Center. Now retired from the u niversity of Minnesota, he focuses full-time on providing veterinary drug information to veterinarians, other health professionals, and animal caretakers.

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Notes and Cautions Dosages and Extra-Label Use of Medications dosages for the various species for the drugs listed in this reference come from a variety of sources and are referenced to their source in the appendix. While a sincere effort has been made to assure that the dosages and information in cluded in this book are accurate and reflect the original source's information, errors can occur; it is recommended that the reader refer to the original reference or the approved labeling information of the product for addi tional information and verification of all dosages. except for labeled dosages for veterinary-approved products (for a given species and indication,) dosages listed in this reference should be considered “extra-label” and are not necessarily endorsed by the manufacturer, the Food and drug Administration (Fd A) or this author. Veterinarians are responsible as per the Animal Medical drug u se Clarification Act (AMdu CA) for the appropriate use of medications. t he Animal Medicinal drug u se Clarification Act of 1994 (AMdu CA) allows veterinarians to prescribe extralabel uses of certain approved animal drugs and approved human drugs for animals under certain conditions. e xtralabel (or extra-label) use refers to the use of an approved drug in a manner that is not in accordance with the approved label directions. t he key constraints of AMdu CA are that any extralabel use must be by or on the order of a veterinarian within the context of a veterinarian-client-patient relationship, must not result in violative residues in food-producing animals, and the use must be in conformance with the implementing regulations published at 21 CFr Part 530. A list of drugs specifically prohibited from extra-label use appears in the Code of Federal r egulations. For additional information go to the Fd A-Center for Veterinary Medicine Website at: http://www. fda. gov/cvm/ Abbreviations: OTC & Rx in addition to the abbreviations used in writing prescriptions (e. g., tid, q8h, etc. —see the abbreviation list in the appendix), the terms O t C or rx are found in parentheses after a listed dosage form. i f rx, the drug is considered to be a prescription or legend product, and requires a prescription. O t C denotes that the item is available “over-the-counter” and does not require a prescription for purchase. Trade and Proprietary Names the notation used to signify trade names or proprietary names is an italicized, capitalized name followed by a ® (e. g., Amoxi-Tabs®). this notation may not accurately represent the drug's official registered copyright, trademark, or licensed status (e. g., ™, etc. ) Drug Interactions drug interaction identification and evaluation is in its infancy in veterinary medicine, as relatively little specific information is known on the subject for the variety of species treated. While drug interactions can be clinically significant and potentially life-threatening in veterinary patients, most of the interactions listed in the monographs are derived from human medicine (which is only slightly more informed than veterinary medicine on this topic) and are often included primarily to serve as cautions to the prescriber to be alert for unforeseen outcomes, or to enhance monitoring associated with the drug therapy. Additionally, it is likely there are potentially many other clinically significant interactions between drugs that are not listed; prescribers are reminded that the risk for adverse drug interactions occurring increases with the number of different drugs given to an individual patient. Disclaimer the author/publisher/distributor assume no responsibility for and make no warranty with respect to results that may be obtained from the uses, procedures, or dosages listed, and do not necessarily endorse such uses, procedures, or dosages. t he author/publisher shall not be liable to any person whatsoever for any dam ages, or equivalencies, or by reason of any misstatement or error, negligent or otherwise obtained in this work. should the pur chaser not wish to be bound by the above, he/she may return the reference to the distributor for a full refund.

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Contents Sy STEMIC MONOg RAPh S Acarbose 1 Acemannan 2 Acepromazine Maleate 3 Acetaminophen 6 Acetazolamide 7 Acetic Acid 9 Acetohydroxamic Acid 9 Acetylcysteine 10 Acitretin 12 Acyclovir 14 Aglepristone 15 Albendazole 17 Albuterol s ulfate 19 Alendronate s odium 21 Alfentanil HCl 22 Allopurinol 24 Alprazolam 26 Altrenogest 27 Aluminum Hydroxide 29 Amantadine HCl 30 Amikacin s ulfate 32 Aminocaproic Acid 35 Aminopentamide Hydrogen s ulfate 36 Aminophylline/t heophylline 37 Amiodarone HCl 40 Amitriptyline HCl 42 Amlodipine b esylate 44 Ammonium Chloride 46 Ammonium Molybdate 47 Ammonium t etrathiomolybdate 47 Amoxicillin 48 Amoxicillin/Clavulanate Potassium 51 Amphotericin b d esoxycholate 53 Amphotericin b Lipid-b ased 53 Ampicillin 57 Ampicillin s odium/s ulbactam s odium 60 Amprolium Hydrochloride 62 Antivenin (Crotalidae) Polyvalent (e quine Origin) 63 Antivenin (Crotalidae) Polyvalent i mmune Fab (Ovine Origin) 63 Antivenin (Micrurus Fulvias) eastern and t exas Coral s nake 65Antivenin (Latrodectus Mactans) b lack Widow spider 66 Apomorphine HCl 67 Apramycin s ulfate 69 Ascorbic Acid 70 Asparaginase 71 Aspirin 73 Atenolol 77 Atipamezole HCl 79 Atovaquone 80 Atracurium b esylate 81 Atropine s ulfate 83 Auranofin 86 Azaperone 87 Azathioprine 88 Azithromycin 91 Aztreonam 92 baclofen 94 barbiturate Pharmacology 95 benazepril HCl 96 betamethasone 97 bethanechol Chloride 99 bisacodyl 101 bismuth s ubsalicylate 102 bleomycin s ulfate 104 boldenone u ndecylenate 106 bromide, Potassium 107 bromide, s odium 107 bromocriptine Mesylate 109 budesonide 110 buprenorphine HCl 112 buspirone HCl 114 busulfan 115 butorphanol t artrate 116 Cabergoline 120 Calcitonin s almon 121 Calcitriol 122 Calcium Acetate 124 Calcium s alts 125 Captopril 129 Carbenicillin i ndanyl s odium 130 Carbimazole 132 Carboplatin 133 Carnitine 135 Carprofen 136 Carvedilol 139 Caspofungin Acetate 140

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Cefaclor 141 Cefadroxil 143 Cefazolin s odium 144 Cefepime HCl 147 Cefixime 148 Cefoperazone s odium 149 Cefotaxime s odium 151 Cefotetan d isodium 153 Cefoxitin s odium 154 Cefpodoxime Proxetil 156 Ceftazidime 157 Ceftiofur Crystalline Free Acid 159 Ceftiofur HCl 161 Ceftiofur s odium 164 Ceftriaxone s odium 166 Cefuroxime 168 Cephalexin 170 Cephapirin 172 Cetirizine HCl 173 Charcoal, Activated 174 Chlorambucil 176 Chloramphenicol 178 Chlordiazepoxide ± Clidinium b r 181 Chlorothiazide 183 Chlorpheniramine Maleate 185 Chlorpromazine HCl 186 Chlorpropamide 188 Chlortetracycline 190 Chorionic Gonadotropin (HCG) 191 Chromium 193 Cimetidine 194 Ciprofloxacin 197 Cisapride 199 Cisplatin 200 Citrate s alts 202 Clarithromycin 204 Clemastine Fumarate 206 Clenbuterol HCl 207 Clindamycin 209 Clofazimine 212 Clomipramine HCl 213 Clonazepam 215 Clonidine 217 Clopidogrel b isulfate 218 Cloprostenol s odium 219 Clorazepate d ipotassium 221 Clorsulon 223 Cloxacillin 224Codeine 225 Colchicine 227 Corticotropin (ACt H) 229 Cosyntropin 230 Cromolyn s odium 232 Cyanocobalamin (Vitamin b-12) 233 Cyclophosphamide 234 Cyclosporine 237 Cyproheptadine HCl 240 Cytarabine 241 dacarbazine (dti C) 243 dactinomycin 245 dalteparin s odium 246 danazol 248 danofloxacin Mesylate 249 dantrolene s odium 250 dapsone 252 darbepoetin Alfa 254 decoquinate 255 deferoxamine Mesylate 256 deracoxib 257 deslorelin Acetate 259 desmopressin Acetate 260 desoxycorticosterone Pivalate 262 detomidine HCl 263 dexamethasone 265 dexmedetomidine 270 dexpanthenol 271 dexrazoxane 272 dextran-70 273 diazepam 275 diazoxide, Oral 278 dichlorphenamide 280 dichlorvos 281 diclazuril 282 diclofenac s odium 283 dicloxacillin 284 diethylcarbamazine Citrate 286 diethylstilbestrol 287 difloxacin HCl 289 digoxin 291 dihydrotachysterol 294 diltiazem HCl 296 diminazene Aceturate 298 dimenhydrinate 299 dimercaprol 301 dimethyl s ulfoxide 303 dinoprost t romethamine 305

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diphenhydramine HCl 308 diphenoxylate HCl + Atropine s ulfate 310 dirlotapide 312 disopyramide Phosphate 314 dobutamine HCl 316 docusate 317 dolasetron Mesylate 319 domperidone 320 dopamine HCl 321 doramectin 323 doxapram HCl 325 doxepin HCl 327 doxorubicin HCl 328 doxycycline 331 edetate Calcium d isodium 334 edrophonium Chloride 336 emodepside + Praziquantel 337 enalapril 338 enoxaparin s odium 340 enrofloxacin 342 ephedrine s ulfate 345 epinephrine 347 epoetin Alfa/erythropoietin 349 eprinomectin 351 epsiprantel 352 ergocalciferol 352 ertapenem s odium 354 erythromycin 355 esmolol HCl 358 estradiol Cypionate 360 ethacrynic Acid 362 ethambutol HCl 363 ethanol 365 etidronate d isodium 366 etodolac 367 etomidate 369 euthanasia Agents with Pentobarbital 370 Famciclovir 371 Famotidine 372 Fatty Acids, essential/Omega 374 Felbamate 375 Fenbendazole 376 Fentanyl 379 Fentanyl Citrate, i njectable 379 Ferrous s ulfate 382 Filgrastim 384 Finasteride 385 Firocoxib 386Flavoxate HCl 388 Florfenicol 389 Fluconazole 391 Flucytosine 393 Fludrocortisone Acetate 394 Flumazenil 396 Flumethasone 397 Flunixin Meglumine 400 Fluorouracil 402 Fluoxetine 404 Fluticasone Propionate 405 Fluvoxamine Maleate 407 Folic Acid 409 Fomepizole 410 Furazolidone 411 Furosemide 413 Gabapentin 415 Gemcitabine HCl 417 Gemfibrozil 418 Gentamicin s ulfate 419 Glimepiride 423 Glipizide 424 Glucagon 425 Glucocorticoid Agents, General i nformation 427 Glucosamine/Chondroitin s ulfate 429 Glutamine 431 Glyburide 432 Glycerin, Oral 433 Glycopyrrolate 434 Gold s alts, i njectable 436 Gonadorelin 438 Granisetron HCl 440 Griseofulvin 441 Guaifenesin 443 Halothane 445 Hemoglobin Glutamer-200 (b ovine) 446 Heparin 448 Hetastarch 451 Hyaluronate s odium 452 Hydralazine HCl 453 Hydrochlorothiazide 455 Hydrocodone b itartrate 458 Hydrocortisone 459 Hydrogen Peroxide 3% (Oral) 462 Hydromorphone 464 Hydroxyurea 466 Hydroxyzine 467 Hyoscyamine s ulfate 469

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ibafloxacin 470 ifosfamide 471 imidocarb d ipropinate 473 imipenem-Cilastatin s odium 474 imipramine 476 inamrinone Lactate 478 insulin 479 interferon Alfa, Human r ecombinant 484 interferon Omega, Feline 486 iodide, s odium 487 iodide, Potassium 487 ipecac s yrup 488 ipodate s odium 490 ipratropium b romide 491 irbesartan 492 iron d extran 493 isoflupredone Acetate 494 isoflurane 496 isoniazid (i NH) 497 isoproterenol HCl 499 isosorbide d initrate 500 isosorbide Mononitrate 500 isotretinoin 502 isoxsuprine HCl 504 itraconazole 505 ivermectin 508 Kaolin/Pectin 512 Ketamine HCl 513 Ketoconazole 517 Ketoprofen 521 Ketorolac t romethamine 523 Lactulose 524 Leflunomide 526 Leucovorin Calcium 527 Leuprolide 528 Levamisole 529 Levetiracetam 532 Levothyroxine s odium 534 Lidocaine HCl 536 Lincomycin HCl 539 Liothyronine s odium 541 Lisinopril 542 Lomustine 544 Loperamide HCl 545 Lorazepam 547 Lufenuron 548 Lysine 550 Magnesium Hydroxide 551Magnesium/Aluminum Antacids 551 Magnesium (Parenteral) 553 Mannitol 555 Marbofloxacin 557 Maropitant Citrate 558 Mechlorethamine HCl 560 Meclizine HCl 561 Medetomidine HCl 562 Medium Chain t riglycerides 564 Medroxyprogesterone Acetate 565 Megestrol Acetate 567 Meglumine Antimoniate 570 Melarsomine 571 Melatonin 572 Meloxicam 574 Melphalan 575 Meperidine HCl 577 Mercaptopurine 579 Meropenem 581 Metformin HCl 582 Methadone HCl 584 Methazolamide 585 Methenamine Mandelate 587 Methimazole 588 Methionine 589 Methocarbamol 591 Methohexital s odium 592 Methotrexate 594 Methoxyflurane 596 Methylene b lue 597 Methylphenidate 599 Methylprednisolone 600 Methyltestosterone 604 Metoclopramide HCl 606 Metoprolol 608 Metronidazole 610 Mexiletine HCl 613 Mibolerone 614 Midazolam HCl 616 Milbemycin Oxime 618 Mineral Oil 620 Minocycline HCl 621 Mirtazapine 623 Misoprostol 625 Mitotane 627 Mitoxantrone HCl 629 Morantel t artrate 631 Morphine s ulfate 632

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Moxidectin 635 Mycobacterial Cell Wall Fraction i mmunomodulator 637 Mycophenolate Mofetil 639 Naloxone HCl 641 Naltrexone HCl 642 Nandrolone d ecanoate 643 Naproxen 645 Narcotic (Opiate) Agonist Analgesics, Pharmacology of 647 N-butylscopolammonium b romide 647 Neomycin s ulfate 648 Neostigmine 651 Niacinamide 652 Nitazoxanide 653 Nitenpyram 655 Nitrofurantoin 656 Nitroglycerin 658 Nitroprusside s odium 659 Nizatidine 661 Novobiocin s odium 662 Nystatin 664 Octreotide Acetate 665 Olsalazine s odium 666 Omeprazole 667 Ondansetron 669 Orbifloxacin 670 Oseltamivir Phosphate 671 Oxacillin s odium 673 Oxazepam 675 Oxfendazole 676 Oxibendazole 677 Oxybutynin Chloride 678 Oxymorphone HCl 679 Oxytetracycline 682 Oxytocin 685 Pamidronate d isodium 688 Pancrelipase 689 Pancuronium b romide 690 Pantoprazole 692 Parapox Ovis Virus i mmunomodulator 693 Paregoric 694 Paromomycin s ulfate 695 Paroxetine HCl 696 Penicillamine 698 Penicillins, General i nformation 699 Penicillin G 701 Penicillin V Potassium 705 Pentazocine 707 Pentobarbital s odium 709Pentosan Polysulfate s odium 712 Pentoxifylline 714 Pergolide Mesylate 715 Phenobarbital 717 Phenoxybenzamine HCl 720 Phenylbutazone 722 Phenylephrine HCl 724 Phenylpropanolamine HCl 726 Phenytoin s odium 727 Pheromones 730 Phosphate, Parenteral 731 Physostigmine s alicylate 733 Phytonadione 734 Pimobendan 736 Piperacillin s odium 738 Piperacillin s odium + t azobactam 739 Piperazine 741 Pirlimycin HCl 743 Piroxicam 744 Polysulfated Glycosaminoglycan 746 Ponazuril 747 Potassium 748 Pralidoxime Chloride 750 Praziquantel 751 Prazosin HCl 754 Prednisolone 755 Prednisone 755 Primaquine Phosphate 762 Primidone 764 Probenecid 766 Procainamide HCl 767 Procarbazine HCl 770 Prochlorperazine 771 Promethazine HCl 773 Propantheline b romide 775 Propionibacterium Acnes i njection 777 Propofol 778 Propranolol HCl 780 Protamine s ulfate 783 Pseudoephedrine HCl 784 Psyllium Hydrophilic Mucilloid 785 Pyrantel Pamoate 786 Pyridostigmine b romide 788 Pyridoxine HCl (Vitamin b-6) 790 Pyrilamine Maleate 791 Pyrimethamine 792 Pyrimethamine + s ulfadiazine 794 Quinacrine HCl 796

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Quinidine 797 ramipril 800 ranitidine HCl 801 rifampin 803 romifidine HCl 805 ronidazole 807 s-Adenosyl-Methionine (s AMe) 809 saline/Hyperosmotic Laxatives 810 selamectin 812 selegiline HCl 814 sertraline HCl 815 sevelamer HCl 817 sevoflurane 818 sildenafil Citrate 820 silymarin; Milk t histle 821 sodium b icarbonate 822 sodium Polystyrene s ulfonate 825 sodium stibogluconate; s odium Antimony Gluconate 826 sodium s ulfate 827 sodium t hiosulfate 827 somatotropin 828 sotalol HCl 829 spectinomycin HCl 831 spinosad 1015 spironolactone 832 stanozolol 834 staphylococcal Phage Lysate 836 streptokinase 837 streptozocin 838 succimer 839 succinylcholine Chloride 841 sucralfate 843 sufentanil Citrate 844 sulfachlorpyridazine s odium 846 sulfadiazine/t rimethoprim 847 sulfamethoxazole/t rimethoprim 847 sulfadimethoxine 851 sulfadimethoxine/Ormetoprim 853 sulfasalazine 854 taurine 856 tepoxalin 857 terbinafine HCl 858 terbutaline s ulfate 859 testosterone 861 tetracycline HCl 863 theophylline 37 thiabendazole 867 thiamine HCl 869thioguanine 870 thiopental s odium 872 thiotepa 874 thyrotropin 875 tiamulin 876 ticarcillin d isodium 877 ticarcillin d isodium + Clavulanate Potassium 880 tiletamine HCl/Zolazepam HCl 882 tilmicosin 884 tiludronate d isodium 885 tiludronic Acid 885 tinidazole 887 tiopronin 888 tobramycin s ulfate 889 tocainide HCl 892 tolazoline HCl 893 tolfenamic Acid 895 toltrazuril 896 topiramate 897 torsemide 898 tramadol HCl 900 triamcinolone Acetonide 901 triamterene 905 trientine HCl 906 trilostane 907 trimeprazine t artrate With Prednisolone 909 tripelennamine HCl 910 tulathromycin 911 tylosin 913 ursodiol 915 Valproic Acid 916 Vanadium 918 Vancomycin HCl 919 Vasopressin 920 Vecuronium b romide 922 Verapamil HCl 923 Vinblastine s ulfate 925 Vincristine s ulfate 927 Vitamin e/s elenium 929 Voriconazole 931 Warfarin s odium 933 Xylazine HCl 935 yohimbine HCl 938 Zafirlukast 939 Zidovudine (AZt ) 940 Zinc 942 Zonisamide 943

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APPENDIx Ophthalmic Products, t opical 945 routes of Administration For Ophthalmic drugs 945 diagnostic Agents 946 Fluorescein s odium 946 Lissamine Green 946 Phenol r ed t hread 947 Proparacaine 947 rose b engal 947 schirmer t ear t est 947 tetracaine 948 Glaucoma, t opical Agents 948 Parasmpathomimetics (Miotics) 949 Pilocarpine 949 demecarium 949 echothiophate i odide 949 sympathomimetics 950 Apraclonidine 950 brimonidine 950 beta-Adrenergic Antagonists 950 betaxolol 950 Carteolol 951 Levobunolol 951 Metipranolol 951 timolol 951 Carbonic Anhydrase i nhibitors 952 brinzolamide 952 dorzolamide 952 Prostaglandins 952 Latanaprost 952 bimatoprost 952 travoprost 952 Miscellaneous Agents for t reatment of Glaucoma 953 epinephrine 953 Mydriatic-Cycloplegic Vasoconstrictors 953 Cyclopentolate 953 Phenylephrine 953 Atropine 954 tropicamide 954 Anti-inflammatory/Analgesic Ophthalmic Agents 955 Mast Cell stabilizers, Antihistamines, d econgestants 955 Cromolyn s odium 955 Lodoxamine 955 Olopatadine 955 Non-steroidal Antiinflammatory Agents 955 bromfenac 955 diclofenac 956 Flurbiprofen 956Ketorolac 956 Nepafenac 957 suprofen 957 steroidal Anti-inflammatory Agents 957 Prednisolone Acetate 957 dexamethasone 957 Loteprednol e tabonate 957 Corticosteroids, t opical 957 Ophthalmic Analgesics 959 Morphine s ulfate 959 Nalbuphine 959 Antimicrobial Ophthalmic t herapy 959 Antibiotics, s ingle & Combination Agents 959 Chloramphenicol 960 Ciprofloxacin 960 Gatifloxacin 960 Levofloxacin 960 Moxifloxacin 960 Norfloxacin 960 Ofloxacin 960 Gentamicin 961 tobramycin 961 sulfacetamide 961 tetracycline 961 Oxytetracycline 961 Antibiotic Combinations 962 Antibiotic and Corticosteroid Combinations 962 Antifungals 963 Amphotericin b 963 Povidone i odine 963 Natamycin 964 Miconazole 964 silver s ulfadiazine 964 itraconazole 965 Voriconazole 965 Antivirals 966 trifluridine 966 idoxuridine 967 interferon Alpha 967 Acyclovir 967 Valacyclovir 967 Famciclovir 967 Ganciclovir 967 Cidofovir 967 Penciclovir 967 Keratoconjunctivitis s icca 968 Cyclosporine 968 tacrolimus 969

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Artificial t ear Products/Ocular Lubricants 969 Ophthalmic i rrigants 969 topical Hyperosmotic Agents 970 Polysulfonated glycosaminoglycan 970 Hypertonic s odium Chloride 970 Viscoelastic s ubstances 970 Hyaluronic Acid 971 Cytotoxic Ophthalmic Agents 971 Cisplatin beads 971 5-Fluorouracil 971 Mitomycin-C 971 sympathomimetics 972 Hydroxyamphetamine 972 Cocaine 972 Anticollagenase Agent 972 Acetylcysteine 972 edetate d isodium 972 Principles of Compounding Ophthalmic Products 973 dermatological Agents, t opical 976 Non-Corticosteroid Antipruritics 976 Aluminum Acetate s olution 976 diphenhydramine HCl 977 Pramoxine HCl 977 Colloidal Oatmeal 978 Phenol/Menthol/Camphor 979 Lidocaine 979 Lidocaine/Prilocaine (e MLA Cream) 979 Antiinflammatory Agents 980 Corticosteroids 980 Hydrocortisone 980 triamcinolone Acetonide 982 betamethasone 983 isoflupredone Acetate 984 Antiinfectives, t opical 985 Antibacterial Agents 985 Gentamicin s ulfate 985 bacitracin and b acitracin Combinations 986 benzoyl Peroxide 987 Clindamycin 988 Mupirocin 988 Nitrofurazone 989 silver s ulfadiazine (ssd) 990 Antiseptics 990 Chlorhexidine 990 ethyl Lactate 992 Povidone i odine 992 triclosan 993Antifungal Agents 994 Clotrimazole 994 enilconazole 994 Ketoconazole 995 Lime s ulfur 995 Miconazole 996 Nystatin 997 selenium s ulfide 998 terbinafine HCl 999 Keratolytic Agents 1000 salicylic Acid 1000 sulfur, Precipitated 1001 Coal t ar 1002 Antiseborrheic Products 1003 Phytosphingosine 1003 immunomodulators, t opical 1003 imiquimod 1003 tacrolimus 1004 Pimecrolimus 1004 retinoids 1005 tretinoin 1005 Antiparasitic Agents, t opical 1006 Amitraz 1006 Crotamiton 1007 Fipronil ± (s)-Methoprene 1008 imidacloprid 1009 imidacloprid with Permethrin 1009 imidacloprid with Moxidectin 1009 Metaflumizone 1010 (s)-Methoprene Combinations 1010 Pyriproxyfen & Pyriproxyfen Combinations 1011 Permethrin 1012 Pyrethrins and Pyrethrin Combinations 1013 spinosad 1015 Oti C Preparations 1016 ear Cleaners/Flushes/Antiseptic/d isinfectants 1016 Corticosteroid/Antiinflammatory 1017 Antimicrobial (Antibacterial) 1018 Antimicrobial (Antifungal) 1018 Corticosteroid + Antimicrobial 1018 Antiparasitic Preparations 1019 small Animal t herapeutic d iets 1020 therapeutic d iets for d ogs 1021 Modified Fiber d iets for d ogs 1021 Novel Protein d iets for d ogs 1021 Nutrient d ense d iets for d ogs 1024 reduced Fat d iets for d ogs 1026 reduced s odium d iets for d ogs 1028

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reduced Protein/Phosphorus d iets for d ogs 1029 reduced energy d iets for d ogs 1030 restricted Mineral d iets for d ogs 1032 Geriatric d iets for d ogs 1032 dental d iets for d ogs 1034 Other t herapeutic d iets for d ogs 1034 therapeutic d iets for Cats 1035 Modified Fiber d iets for Cats 1035 Novel Protein d iets for Cats 1036 Nutrient d ense d iets for Cats 1037 reduced Fat d iets for Cats 1038 restricted Mineral d iets for Cats 1040 reduced energy d iets for Cats 1041 reduced Phosphorus/Protein for Cats 1043 reduced s odium for Cats 1044 Geriatric d iets for Cats 1045 Other t herapeutic and Hairball d iets for Cats 1046 Overdose and t oxin e xposure d econtamination Guidelines 1047 Ar Ci u CGFs Classifications 1049 Chemotherapy Protocols for t reatment of Neoplastic d iseases in small Animals 1050 Canine Lymphoma Protocols 1050 Prednisone ± Chlorambucil Protocol 1050 COP (Cyclophosphamide-Vincristine-Prednisone) Protocol 1050 doxorubicin Protocol 1050 Wisconsin-Madison Protocol—short 1051 Ve LCAP-s Protocol 1051 Other Canine Protocols 1051 Canine s arcoma & Carcinoma t reatment Protocol “AC” 1051 Canine Osteogenic s arcoma Adjuvant Protocol 1051 Mast Cell t umor Protocol 1052 Feline Lymphoma Protocols 1052 COPLA Protocol 1052 COP Protocol 1052 COAP Protocol 1052 Ferret Lymphoma Protocols 1052 Ferret Ls A Protocol 1052 Conversion t ables for Weight in Kilograms to b ody s urface Area (m2) 1052 tables of Parenteral Fluids 1053 Abbreviations u sed i n Prescription Writing 1054 solubility d efinitions 1055 Conversion: Weights; t emperature; Liquids 1055 Milliequivalents & Molecular Weights 1055 “Normal” Vital s igns 1055 estrus and Gestation Periods for d ogs & Cats 1056 Conversion of Conventional Chemistry u nits to si u nits 1056 reference Laboratory r anges 1057 Chemistry: Canine, Feline, b ovine, e quine 1057Hematology: Canine, Feline, b ovine, e quine 1057 Coagulation: Canine, Feline, b ovine, e quine 1058 urinalysis: Canine, Feline 1058 Cerebral spinal Fluid: Canine, Feline 1058 Ferret: Male Albino 1059 rabbit: Female New Zealand White 1059 Avian: Macaws 1059 Avian: Parrots, African Grey 1059 Hematology: sheep, Goats, s wine 1060 Chemistry: sheep, Goats, s wine 1060 Phone Numbers and Websites 1061 Food and drug Administration Center for Veterinary Medicine (Fd A-CVM) 1061 u. s. d epartment of Agriculture (usd A) 1061 u. s. environmental Protection Agency (e PA) 1061 Food Animal r esidue Avoidance databank (FAr Ad) 1061 drug enforcement Administration (de A) 1061 Animal Poison Centers 1061 Animal b lood b anks 1061 Veterinary Pharmaceutical Manufacturers & s uppliers 1062 Legally i mporting drugs for Compassionate u se into the us A 1065 references 1066 systemic drugs s orted by t herapeutic Class or Major i ndication 1099 Antihistamines 1099 Central Nervous s ystem drugs 1099 euthanasia Agents 1099 Cardiovascular Agents 1099 respiratory drugs 1100 renal And u rinary t ract Agents 1100 Gastrointestinal Agents 1100 Hormones/endocrine/r eproductive Agents 1100 Anti-i nfective drugs 1101 blood Modifying Agents 1102 Fluid & electrolyte Modifiers 1102 Antineoplastics 1102 immunomodulators 1102 Antidotes 1102 bone/Joint Agents 1102 dermatologic Agents (s ystemic) 1103 Vitamins And Minerals/Nutrients 1103 Cholinergic Muscle stimulants 1103 systemic Acidifiers 1103 systemic Alkalinizers 1103 unclassified 1103 index 1104

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Ac Arbose (ay-kar-bose) Precose® Oral antidiabetic Prescriber Highlights Antihyperglycemic agent that reduces the rate & amount T T of glucose absorbed from the gut after a meal; may be use ful for mild reductions in blood glucose in dogs or cats Contraindications: Underweight animals, known hyper-T T sensitivity, diabetic ketoacidosis, inflammatory bowel dis-ease, colonic ulceration, partial intestinal obstruction or predis position to obstruction, chronic intestinal disease with marked disorders of digestion or absorption & when excessive gas formation would be detrimental Dose-dependent diarrhea & flatulence are the adverse T T effects most likely to be noted Give with meals (preferably right before) T T Expense may be an issue T T Uses/Indications May be useful for mild reduc tions in blood glucose concentrations (250-350 mg/dl range) in dogs and cats with non-insulin-depen-dent diabetes mellitus and as adjunctive treat ment of insulin de-pendent diabetes mellitus. Pharmacology/Actions Acarbose competitively inhibits pancreatic alpha-amylase and alpha-glucosidases found in the small intestine. This delays the diges tion of complex carbohydrates and disaccharides to glucose and other monosaccharides. Glucose is absorbed lower in the GI tract in lesser amounts than is normal thereby reducing insulin re-quirements during the postprandial hyperglycemic phase. Acarbose has no effect on lactase. Pharmacokinetics In dogs about 4% of an oral dose is absorbed; in humans only about 2% of an oral dose is absorbed from the gut which is then ex creted by the kidneys. Practically all remaining drug in the gut is metabo-lized in the GI tract by intestinal bacteria. Patients with severe re-nal dys function attain serum levels approximately 5 times those of normal subjects. Contraindications/Precautions/Warnings Acarbose is contraindicated in patients with known hypersensitiv-ity to the drug, diabetic ketoacidosis, inflammatory bowel disease, colonic ul ceration, partial intestinal obstruction or predis position to obstruction, chronic intestinal disease with marked disorders of digestion or absorption, and when excessive gas formation would be detrimental. Acarbose is not indicated in patients of low body weight (some say normal body weight as well) as it may have delete-rious effects on nutrition status. Use caution in patients with re nal dysfunction or severe liver disease. Adverse Effects Adverse effects re ported in cats include flatulence, soft stools and diar rhea; in dogs, diarrhea and weight loss. Ad verse effects are more likely at higher doses. While acarbose alone does not cause hypo glycemia, it may con-tribute to it by reducing the rate and amount of glucose absorbed when the patient is receiving other hypoglycemic agents (insulin, oral hypoglycemics). Reproductive/Nursing Safety Safety in pregnancy has not been established; weigh any potential risks versus benefits in preg nant animals. In humans, the FDA cat-egorizes this drug as category B for use during pregnancy (Animal studies have not yet demonstrated risk to the fetus, but there are no adequate studies in pregnant women; or animal studies have shown an adverse effect, but adequate studies in pregnant women have not demonstrated a risk to the fetus in the first trimester of pregnancy, and there is no evidence of risk in later trimesters. ) Overdosage/Acute Toxicity Acute overdosages are likely to cause only diarrhea and flatulence. No treatment should be necessary. Should acute hypoglycemia occur secondary to other antihy po glycemics, parenteral glucose should be admin istered. If treating orally, use glucose (do not use sucrose). Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving acarbose and may be of significance in veterinary patients: CHARCOAl T! : Intestinal adsorbents may reduce the efficacy of acarbose DIg Ox INT! : Acarbose may reduce digoxin blood concentrations Hy PERgly CEm IC Ag ENTS T! (corticosteroids, thiazides, estrogens, phe­ nothiazines, thyroid hormones, and calcium chan nel blockers ): May negate the effects of acarbose PANCREATINT!, PANCREl IPASE, or Amyl ASE : Exogenous enzyme for-mulations may reduce the efficacy of acarbose laboratory Considerations Increased T! serum aminotransferase levels have been noted in some humans taking high dosages for a long period Doses DOg S:T! a) For dogs poorly controlled with insulin and dietary therapy when another reason for the poor control cannot be identi-fied: Initially 12. 5-25 mg total dose per dog PO with each meal. Give only at the time of feeding. May increase dose after two weeks to 50 mg per dog and then to 100 mg per dog (in large dogs, >25 kg) if response has been inadequate. Greater chance of diarrhea at the higher dosages. (Nelson 2005) b) 12. 5-20 mg (total dose) per meal PO (Daminet 2003) CATS:T! a) 12. 5-25 mg (total dose) PO with meals. When acarbose is used with a low carbohydrate diet it may improve glycemic control and reduce insulin dependence. (Scherk 2005c) 1

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b) 12. 5 mg per cat PO twice daily with meals. May be able to reduce insulin dosage and thereby reduce hypoglycemia oc-currence. (Greco 2002b) c) 12. 5-20 mg (total dose) per meal PO (Daminet 2003) monitoring Serum glucose T! Adverse effects (diarrhea)T! Client Information Give immedi ately prior to feeding for best results T! If diarrhea be comes a problem, contact veterinarian T! Acarbose does not cause low blood sugar, but it may contribute T! to it if the animal is receiving other hypoglycemic agents (insulin, oral hypoglycemics) May take up to two weeks for maximal effect T! Chemistry/Synonyms A complex oligosaccharide antihy perglycemic agent, acarbose oc-curs as white to off-white powder, is soluble in water and has a p Ka of 5. 1. Acarbose may also be known as: Bay-g-5421, Precose®, Asucrose ®, Glicobase®, Glucobay®, Glucor®, Glumida®, or Prandase®. Storage/Stability Do not store tablets above 25°C (77°F); protect from moisture. Dosage Forms/Regulatory Status VETERINAR y­l Ab El ED PRODUCTS: None HUm AN­l Ab El ED PRODUCTS: Acarbose Tablets: 25 mg, 50 mg & 100 mg; Precose® (Bayer); (Rx) Acem Ann An (ase-man-in) n On-specific immun Ostimulant/ antiviral Prescriber Highlights Non-specific injectable immunostimulant that has been T T tried in Fe LV-, FIV, or FIP-positive cats, & vaccine-induced fibrosarcomas (intralesional) Use is controversial; little, if any controlled study docu-T T mentation supporting efficacy in veterinary medicine Adverse effects include: Possible hypersensitivity reac-T T tions; bolus IV administration can cause salivation, weak-ness, collapse, tachycardia, tachypnea; intralesional in-jection can cause prolonged pain at site; intraperitoneal injection can cause monocyte infiltrates on peritoneal surfaces, liver, & spleen Topical products available; potentially can reduce wound T T healing time Uses/Indications Veterinary acemannan injection is labeled for use in dogs or cats as an aid in the treatment (i. e., surgery) and clinical management of fibrosarcoma. It has been used to treat Fe LV, FIV, and FIP infections in cats but clinical efficacy has not been adequately proven by con-trolled clinical studies. It reportedly has been used in horses, but no specific information on this was located. Pharmacology/Actions Acemannan's immunostimulant activity is thought as a result of in-ducing increases in TNF-alpha and IL-1. At injection sites, increased lymphocytic infiltration and accumulation have been noted. In tis-sue cultures, acemannan has suppressed HIV replication. Pharmacokinetics No information was located. Contraindications/Precautions/Warnings The manufacturer lists no contraindications to using acemannan, however, it should not be used in patients who have demonstrated past severe hypersensitivity reactions to it. Adverse Effects While the manufacturer does not list any specific adverse effects associated with use, hypersensitivity or localized injection re-actions are possible. Bolus IV administration can cause saliva-tion, weakness, collapse, hypotension, tachycardia and tachypnea. Intralesional injection can cause prolonged pain at the injection site. Intraperitoneal injection can cause monocyte infiltrates on peritoneal surfaces, liver, and spleen. Reproductive/Nursing Safety No specific information was located on reproductive or nursing safety. The product label states, “The effects of this compound have not been studied in pregnant animals” and, also, “... the chemical nature of acemannan and the absence of significant toxicity in sev-eral animal species suggest the compound is not a teratogen. ” Overdosage/Acute Toxicity Single IP injections of 50 mg/kg in dogs resulted in no significant signs of toxicity. Acemannan fed orally to dogs at rates of up to 1. 5 g/kg/day for 90 days showed no significant effects. Drug Interactions None were identified. laboratory Considerations None were identified. Doses DOg S/CATS:T! For labeled indications (aid in treatment and management of fibrosarcoma): a) Prior to use, reconstitute with 10 m L sterile diluent. Five to 10 minutes may be necessary for complete dissolution. Shake well before using. Use within 4 hours after rehydration. Ad-minister by concurrent intraperitoneal (IP) and intralesional injections weekly for a minimum of 6 treatments. Recom-mended IP dose is 1 mg/kg. Recommended intralesional dose is 2 mg injected deep into each tumor mass. When used as a prelude to surgery, give concurrent IP and intralesional injections weekly. Continue until delineation, necrosis or maximum tumor enlargement due to edema and immune cellular infiltration occur. Rapid necrosis, which accompa-nies this response, may happen within 2 to 4 weeks. Surgical excision is recommended immediately upon delineation, ne-crosis or maximum tumor enlargement. (Label Information; Acemannan Immunostimulant—VPL) monitoring Clinical efficacy T! Adverse effects (most likely local reactions)T!2 ACEm ANNAN

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Client Information This compound is recommended for use by veterinary profes-T! sionals only Clients should be made aware of the “investigational” nature of T! using acemannan systemically; adverse effects are possible Chemistry Acemannan is a complex carbohydrate polymer that is derived from Aloe vera. It is a long-chained polydispersed beta-(1,4)-acetylated polymannose with interspersed O-acetyl groups with a mannose: acetyl ratio of approximately 1:1. Storage/Stability Acemannan injection should be stored at temperatures less than 35°C (95°F); protect from extremes of heat or light. Dosage Forms/Regulatory Status VETERINAR y­l Ab El ED PRODUCTS: Acemannan 10 mg vial with 10 m L vial of diluent (sterile saline) in kits of two vials (one of each) or eight vials (4 of each): Acemannan Immunostimulant® (VPL); OTC Biologic. Labeled for use in dogs or cats. Note : This product is a USDA-licensed biologic and is not an FDA-approved product. Note : There are also topical products labeled for veterinary use that contain acemannan including a wound dressing and cleansing foam. Trade name is Carra Vet® (VPL). HUm AN­l Ab El ED PRODUCTS: No systemic products located Aceprom Azine m Ale A te (ase-pro-ma-zeen) Prom Ace®, Aceproject® phen O thiazine sedative/tranquilizer Prescriber Highlights Negligible analgesic effects T T Dosage may need to be reduced in debilitated or geri-T T atric animals, those with hepatic or cardiac disease, or when combined with other agents Inject IV slowly; do not inject into arteries T T Certain dog breeds (T T e. g., giant breeds, sight hounds) may be overly sensitive to effects May cause significant hypotension, cardiac rate abnor-T T malities, hypo-or hyperthermia May cause penis protrusion in large animals (esp. horses) T T Uses/Indications Acepromazine is approved for use in dogs, cats, and horses. Labeled indica tions for dogs and cats include: “... as an aid in controlling intractable animals... alleviate itching as a result of skin irritation; as an antiemetic to control vomiting associated with motion sick-ness” and as a preanesthetic agent. The use of acepromazine as a sedative/tranquilizer in the treatment of adverse behaviors in dogs or cats has largely been supplanted by newer, effective agents that have fewer adverse effects. Its use for sedation during travel is con-troversial and many no longer recommend drug therapy for this purpose. In horses, acepromazine is labeled “... as an aid in controlling fractious animals,” and in conjunction with local anesthesia for various procedures and treatments. It is also commonly used in horses as a pre-anesthetic agent at very small doses to help control behavior. Although not approved, it is used as a tranquilizer (see doses) in other species such as swine, cattle, rabbits, sheep and goats. Acepromazine has also been shown to reduce the incidence of ha-lothane-induced malignant hyperthermia in susceptible pigs. Pharmacology/Actions Acepromazine is a phenothiazine neuroleptic agent. While the exact mechanisms of action are not fully understood, the phenothiazines block post-synaptic dopamine receptors in the CNS and may also inhibit the release of, and increase the turnover rate of dopamine. They are thought to depress portions of the reticular activating sys-tem that assists in the control of body temperature, basal metabolic rate, emesis, vasomotor tone, hormonal balance, and alertness. Addi tionally, phenothiazines have varying degrees of anticholin-ergic, antihistaminic, antispasmodic, and alpha-adrenergic block-ing effects. The primary desired effect for the use of acepromazine in veteri-nary medicine is its tranquilizing ac tion. Additional pharmacologic actions that acepromazine possess, include antiemetic, antispas-modic, and hypothermic actions. Some researchers have reported that acepromazine has anticonvul sant activity, but in veterinary medicine it is generally felt that phenothiazines should not be used in epileptic animals or those susceptible to seizures (e. g., post-my-elography) as it may precipitate seizures. Acepromazine may decrease respiratory rates, but studies have demonstrated that little or no effect occurs with regard to the blood gas picture, p H or oxyhemoglobin saturation. A dose dependent de crease in hematocrit is seen within 30 minutes after dosing in horses and dogs. Hema tocrit values in horses may decrease up to 50% of pre-dose values; this is probably due to increased splenic sequestration of red cells. Besides lowering arterial blood pressure in dogs, acepromaz-ine causes increases in central venous pressure, a vagally induced bradycardic effect and transient sinoatrial arrest. The bradycardia may be negated by a reflex tachycardic effect secondary to decreases in blood pressure. Acepro mazine also has antidysrhythmic effects. Acepromazine has been demonstrated to inhibit the ar rhythmias induced by ultra-short acting barbiturates, and protect against the ventricular fibrilla tory actions of halothane and epinephrine. Other pharmacologic actions are discussed in the adverse effects section below. Pharmacokinetics The pharmacokinetics of acepromazine have been studied in the horse (Ballard et al. 1982). The drug has a fairly high volume of distribution (6. 6 L/kg), and is more than 99% pro tein bound. The onset of action is fairly slow, requiring up to 15 minutes following IV administra tion, with peak effects seen in 30-60 minutes. The elimination half-life in horses is approximately 3 hours. Acepromazine is metabolized in the liver with both conjugated and unconjugated metabolites eliminated in the urine. Metabolites may be found in equine urine up to 96 hours after dosing. Contraindications/Precautions/Warnings Animals may require lower dosages of general anesthetics follow-ing acepromazine. Use cautiously and in smaller doses in animals with hepatic dysfunction, cardiac disease, or general debilitation. Because of its hypotensive effects, ace promazine is relatively con-traindicated in patients with hypovolemia or shock. Phenothiazines are relatively contraindicated in patients with tetanus or strychnine intoxication due to effects on the ex trapyramidal system. Intravenous injections should be made slowly. Do not administer intra-arterially in horses since it may cause severe CNS excitement/ACEPROm Az INE m Al EATE 3

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depression, seizures and death. Because of its effects on thermoregu-lation, use cautiously in very young or debilitated animals. Acepromazine has no analgesic effects; treat animals with ap-propriate analgesics to control pain. The tranquilization effects of acepromazine can be overridden and it cannot always be counted upon when used as a restraining agent. Do not administer to racing animals within 4 days of a race. In dogs, acepromazine's effects may be individually variable and breed dependent. Dogs with MDR1 mutations (many Collies, Australian shepherds, etc. ) may develop a more pronounced seda-tion that persists longer than normal. It may be prudent to reduce initial doses by 25% to determine the reaction of a patient identified or suspected of having this mutation. Acepromazine should be used very cautiously as a restraining agent in aggressive dogs as it may make the animal more prone to startle and react to noises or other sensory inputs. In geriatric pa-tients, very low doses have been associated with prolonged effects of the drug. Giant breeds and greyhounds may be ex tremely sensitive to the drug while terrier breeds are somewhat resistant to its effects. Atropine may be used with ace promazine to help negate its brady-cardic effects. In addition to the legal aspects (not approved) of using acepro-mazine in cattle, the drug may cause regurgitation of ruminal con-tents when inducing general anesthesia. Adverse Effects Acepromazine's effect on blood pressure (hypotension) is well de-scribed and an important consideration in therapy. This effect is thought to be mediated by both cen tral mechanisms and through the alpha-adrenergic actions of the drug. Cardiovascular collapse (secondary to bradycardia and hypotension) has been described in all major species. Dogs may be more sensitive to these effects than other animals. In male large animals acepromazine may cause protrusion of the penis; in horses, this effect may last 2 hours. Stallions should be given acepromazine with caution as injury to the penis can occur with resultant swelling and permanent paralysis of the penis retrac-tor muscle. Other clinical signs that have been reported in horses include excitement, restlessness, sweating, trembling, tachypnea, tachy cardia and, rarely, seizures and recumbency. Its effects of causing penis extension in horses, and pro lapse of the membrana nictitans in horses and dogs, may make its use unsuitable for show animals. There are also ethical considerations regarding the use of tranquilizers prior to showing an animal or having the animal examined before sale. Occasionally an animal may develop the contradictory clinical signs of aggressiveness and generalized CNS stimulation after re-ceiving acepromazine. IM injections may cause transient pain at the injec tion site. Reproductive/Nursing Safety In humans, the FDA categorizes phenothiazines as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) In a separate system evaluating the safety of drugs in canine and feline pregnancy (Papich 1989), this drug is categorized as in class: B (Safe for use if used cautiously. Studies in laboratory animals may have uncovered some risk, but these drugs appear to be safe in dogs and cats or these drugs are safe if they are not administered when the animal is near term. ) Overdosage/Acute Toxicity The LD 50 in mice is 61 mg/kg after IV dosage and 257 mg/kg af-ter oral dose. Dogs receiving 20-40 mg/kg over 6 weeks apparently demonstrated no adverse effects. Dogs gradually receiving up to 220 mg/kg orally exhibited signs of pulmonary edema and hyperemia of internal or gans, but no fatalities were noted. There were 128 exposures to acepromazine maleate reported to the ASPCA Animal Poison Control Center (APCC; www. apcc. aspca. org) during 2005-2006. In these cases, 89 were dogs with 37 show-ing clinical signs and the remaining 39 reported cases were cats with 12 cats showing clinical signs. Common findings in dogs recorded in decreasing frequency included ataxia, lethargy, sedation, depression, and recumbency. Common findings in cats recorded in decreasing frequency included lethargy, hypothermia, ataxia, protrusion of the third eyelid, and anorexia. Because of the apparent relatively low toxicity of acepromaz-ine, most overdoses can be handled by monitoring the animal and treating clinical signs as they occur; massive oral overdoses should definitely be treated by emptying the gut if possible. Hypotension should not be treated with epinephrine; use either phenylephrine or norepinephrine (levarterenol). Seizures may be controlled with barbiturates or diazepam. Doxapram has been suggested as an an-tagonist to the CNS depressant effects of ace promazine. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving acepromazine or other phenothiazines and may be of significance in veterinary patients: ACETAm INOPHEN!! : Possible increased risk for hypothermia ANTACIDS!! : May cause reduced GI absorption of oral phenothiazines ANTIDIARRHEAl m Ix TURES!! (e. g., Kaolin/pectin, bismuth subsalicylate mixtures ): May cause reduced GI absorption of oral phenothiazines CNS DEPRESSANT Ag ENTS!! (barbiturates, narcotics, anesthetics, etc. ): May cause additive CNS depression if used with ace promazine EPINEPHRINE!! : Phenothiazines block alpha-adrenergic receptors; concomitant epinephrine can lead to unop posed beta-activity causing vasodilation and increased cardiac rate OPIATES:T! May enhance the hypotensive effects of acepromazine; dosages of acepromazine are generally reduced when used with an opiate ORg ANOPHOSPHATE Ag ENTS !! : Acepromazine should not be given within one month of worming with these agents as their effects may be potentiated PHENy TOIN!! : Metabolism may be decreased if given concurrently with phenothiazines PROCAINE!! : Activity may be enhanced by phenothiazines PROPRANOl Ol!! : Increased blood levels of both drugs may result if administered with phenothiazines QUINIDINE!! : With phenothiazines may cause additive cardiac depression Doses Note : The manufacturer's dose of 0. 5-2. 2 mg/kg for dogs and cats is considered by many clinicians to be 10 times greater than is nec-essary for most indications. Give IV doses slowly; allow at least 15 minutes for onset of action. DOg S:T! a) Premedication: 0. 03-0. 05 mg/kg IM or 1-3 mg/kg PO at least one hour prior to surgery (not as reliable) (Hall and Clarke 1983) b) Restraint/sedation: 0. 025-0. 2 mg/kg IV; maximum of 3 mg or 0. 1-0. 25 mg/kg IM; Preanesthetic: 0. 1-0. 2 mg/kg IV or IM; maximum of 3 mg; 0. 05-1 mg/kg IV, IM or SC (Morgan 1988)4 ACEPROm Az INE m Al EATE

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c) T o reduce anxiety in the painful patient (not a substitute for analgesia): 0. 05 mg/kg IM, IV or SC; do not exceed 1 mg total dose (Carroll 1999) d) 0. 55-2. 2 mg/kg PO or 0. 55-1. 1 mg/kg IV, IM or SC (Pack-age Insert; Prom Ace ® —Fort Dodge) e) As a premedicant with morphine: acepromazine 0. 05 mg/kg IM; morphine 0. 5 mg/kg IM (Pablo 2003b) CATS:T! a) Restraint/sedation: 0. 05-0. 1 mg/kg IV, maximum of 1 mg (Morgan 1988) b) T o reduce anxiety in the painful patient (not a substitute for analgesia): 0. 05 mg/kg IM, IV or SC; do not exceed 1 mg total dose (Carroll 1999) c) 1. 1-2. 2 mg/kg PO, IV, IM or SC (Package Insert; Prom Ace ® —Fort Dodge) d) 0. 11 mg/kg with atropine (0. 045-0. 067 mg/kg) 15-20 min-utes prior to ketamine (22 mg/kg IM). (Booth 1988a) FERRETS:T! a) As a tranquilizer: 0. 25-0. 75 mg/kg IM or SC; has been used safely in pregnant jills, use with caution in dehydrated ani-mals. (Finkler 1999) b) 0. 1-0. 25 mg/kg IM or SC; may cause hypotension/hypo-thermia (Williams 2000) RAbb ITS/RODENTS/Sm All m Amm Al S:T! a) Rabbits: As a tranquilizer: 1 mg/kg IM, effect should begin in 10 minutes and last for 1-2 hours (Booth 1988a) b) Rabbits: As a premed: 0. 1-0. 5 mg/kg SC; 0. 25-2 mg/kg IV, IM, SC 15 minutes prior to induction. No analgesia; may cause hypotension/hypothermia. (Ivey and Morrisey 2000) c) Mice, Rats, Hamsters, Guinea pigs, Chinchillas: 0. 5 mg/kg IM. Do not use in Ger bils. (Adamcak and Otten 2000) CATTl E:T! a) Sedation: 0. 01-0. 02 mg/kg IV or 0. 03-0. 1 mg/kg IM (Booth 1988a) b) 0. 05-0. 1 mg/kg IV, IM or SC (Howard 1986) c) Sedative one hour prior to local anesthesia: 0. 1 mg/kg IM (Hall and Clarke 1983) HORSES:T! (Note : ARCI UCGFS Class 3 Drug) a) For mild sedation: 0. 01-0. 05 mg/kg IV or IM. Onset of ac-tion is about 15 minutes for IV; 30 minutes for IM (Taylor 1999) b) 0. 044-0. 088 mg/kg (2-4 mg/100 lbs. body weight) IV, IM or SC (Package Insert; Pro m Ace ® —Fort Dodge) c) 0. 02-0. 05 mg/kg IM or IV as a preanesthetic (Booth 1988a) d) Neuroleptanalgesia: 0. 02 mg/kg given with buprenorphine (0. 004 mg/kg IV) or xylazine (0. 6 mg/kg IV) (Thurmon and Benson 1987) e) For adjunctive treatment of laminitis (developmental phase): 0. 066-0. 1 mg/kg 4-6 times per day (Brumbaugh, Lopez et al. 1999) SWINE:T! a) 0. 1-0. 2 mg/kg IV, IM, or SC (Howard 1986) b) 0. 03-0. 1 mg/kg (Hall and Clarke 1983) c) For brief periods of immobilization: acepromazine 0. 5 mg/kg IM followed in 30 minutes by ketamine 15 mg/kg IM. At-ropine (0. 044 mg/kg IM) will reduce salivation and bronchial secretions. (Lumb and Jones 1984) SHEEP & g OATS:T! a) 0. 05-0. 1 mg/kg IM (Hall and Clarke 1983)monitoring Cardiac rate/rhythm/blood pressure if indicated and possible to T! measure Degree of tranquilization T! Male horses should be checked to make sure penis retracts and T! is not injured Body temperature (especially if ambient temperature is very hot T! or cold) Client Information May discolor the urine to a pink or red-brown color; this is not T! abnormal Acepromazine is approved for use in dogs, cats, and horses not T! intended for food Chemistry/Synonyms Acepromazine maleate (formerly acetylpromazine) is a phenothi-azine derivative that occurs as a yellow, odorless, bitter tasting pow-der. One gram is soluble in 27 m L of water, 13 m L of alcohol, and 3 m L of chloroform. Acepromazine Maleate may also be known as: acetylpromazine maleate, “ACE”, ACP, Aceproject ®, Aceprotabs®, Prom Ace ®, Plegicil®, Noten sil®, and Atravet ®. Storage/Stability/Compatibility Store protected from light. Tablets should be stored in tight con-tainers. Acepromazine injection should be kept from freezing. Although controlled studies have not documented the compat-ibility of these combinations, acepro mazine has been mixed with atropine, buprenorphine, chloral hydrate, ketamine, meperidine, oxy morphone, and xylazine. Both glycopyrrolate and diazepam have been reported to be physically in compatible with phenothiaz-ines, however, glycopyrrolate has been demonstrated to be compat­ ible with promazine HCl for injection. Dosage Forms/Regulatory Status VETERINAR y­l Ab El ED PRODUCTS: Acepromazine Maleate for Injection: 10 mg/m L for injection in 50 m L vials; Aceproject ® (Butler), Prom Ace ® (Fort Dodge); generic; (Rx). Approved forms available for use in dogs, cats and horses not intended for food. Acepromazine Maleate Tablets: 5, 10 & 25 mg in bottles of 100 and 500 tablets; Prom Ace ® (Fort Dodge); Aceprotabs® (Butler) generic; (Rx). Approved forms available for use in dogs, cats and horses not intended for food. When used in an extra-label manner in food animals, it is recom-mended to use the withdrawal periods used in Canada: Meat: 7 days; Milk: 48 hours. Contact FARAD (see appendix) for further guidance. The ARCI (Racing Commissioners International) has designated this drug as a class 3 substance. See the appendix for more information. HUm AN­l Ab El ED PRODUCTS: None ACEPROm Az INE m Al EATE 5

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6 ACETAm INOPHEN Acet Aminophen (ah-seet-a-min-a-fen) Tylenol®, APAP, Paracetamol Oral analgesic, antipyretic Prescriber Highlights Contraindicated in cats at any dosage; ferrets may be as T T sensitive to acetaminophen as cats At recommended dosages, not overly toxic to dogs, ro-T T dents, or rabbits Often used in combined dosage forms with codeine; see T T codeine monograph for more information Uses/Indications Acetaminophen is occasionally used as an oral analgesic in dogs. In conditions of more severe pain, it may be used in combination with oral codeine phosphate. See the codeine monograph for more infor-mation on the use of acetaminophen-codeine combi nation prepara-tions. Pharmacology/Actions Acetaminophen produces analgesia and antipyresis via a weak, re-versible, isoform-nonspecific inhibition of cyclooxygenase. Unlike aspirin, it does not possess significant antiinflammatory activity nor inhibit platelet function. Pharmacokinetics Specific pharmacokinetic information in domestic animals was not located. In humans, acetaminophen is rapidly and nearly completely absorbed from the gut and is rapidly dis tributed into most tissues. Approximately 25% is plasma protein bound. Dogs apparently ex-hibit dose dependent metabolism (saturable). Contraindications/Precautions/Warnings Acetaminophen is contraindicated in cats at any dosage. Severe methemoglobinemia, hematuria, and icterus can be seen. Cats are un able to significantly glucuronidate acetaminophen leading to tox-ic metabolites being formed and re sultant toxicity. Acetaminophen should not be used in ferrets as they may be as sensitive to it as are cats. At this time, acetaminophen should not be used in Sugar Gliders or Hedgehogs as its safety has not been determined. Dogs do not metabolize acetaminophen as well as humans and its use must be judicious. In dogs, it is generally not recommended to use acetaminophen during the immediate post-operative phase (first 24 hours) due to an increased risk of hepatotoxicity. Adverse Effects Because acetaminophen is not routinely used in veterinary medi-cine, experience on its adverse effect profile is limited. At suggested dosages in dogs, there is some po tential for renal, hepatic, GI, and hematologic effects occurring. Reproductive/Nursing Safety Absolute reproductive safety has not been established, but acet-aminophen is apparently relatively safe for occasional use in preg-nancy (no documented problems in humans). Animal data was not located. In humans, the FDA categorizes this drug as category B for use during pregnancy (Animal studies have not yet demonstrated risk to the fetus, but there are no adequate studies in pregnant women; or animal studies have shown an adverse effect, but adequate studies in pregnant women have not demonstrated a risk to the fetus in the first trimester of pregnancy, and there is no evidence of risk in later trimes-ters. ) In a separate system evaluating the safety of drugs in canine and feline pregnancy (Papich 1989), this drug is categorized as in class: C (These drugs may have potential risks. Studies in people or laboratory animals have uncovered risks, and these drugs should be used cautiously as a last resort when the benefit of therapy clearly out-weighs the risks. ) Acetaminophen is excreted in milk in low concentrations with reported milk:plasma ratios of 0. 91 to 1. 42 at 1 and 12 hours, re-spectively. In nursing human infants, no adverse effects have been reported. Overdosage/Acute Toxicity Because of the potentially severe toxicity associated with acetamino-phen, consultation with an animal poison control center is recom-mended (see appendix). For overdosage in dogs or cats, stan dard gut emptying techniques and supportive care should be administered when applicable. Further treatment with acetylcysteine may be war-ranted (see acetylcysteine monograph for more informa tion). Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving acetaminophen and may be of significance in veterinary patients: OTHER ANAlg ESICS!! : Chronic use with acetaminophen may lead to renal pathologies b ARb ITURATES!! : Increased conversion of acetaminophen to hepato-toxic metabolites; potentially increased risk for hepatotoxicity DOx ORUb ICIN!! : May deplete hepatic glutathione, thereby leading to increased hepatic toxicity HAl OTHANE!! : Acetaminophen is not recommended for use for post-operative analgesia in animals that received halothane anesthesia ISONIAz ID!! : Possible increased risk of hepatotoxicity PHENOTHIAz INES!! : Possible increased risk for hypothermia WARFARIN!! : While acetaminophen is relatively safe to use, large doses may potentiate anticoagulant effects laboratory Considerations False positive results may occur for urinary T! 5­hydroxyindoleacetic acid Doses Note : For dosages of acetaminophen/codeine combination products refer to the codeine monograph. DOg S:T! As an analgesic: a) 15 mg/kg PO q8h (Dodman 1992); (Mc Laughlin 2000) b) 10 mg/kg PO q12h (Kelly 1995) c) In the treatment of degenerative myelopathy (in German Shepherds): 5 mg/kg PO (not to exceed 20 mg/kg per day) (Clemmons 1991) RAbb ITS/RODENTS/Sm All m Amm Al S:T! As an analgesic: a) Using Children's Tylenol ®: 1-2 mg/m L in drinking water. Effective for controlling low-grade nociception. (Huerkamp 1995) b) Mice, Rats, Gerbils, Hamsters, Guinea pigs, Chinchillas: 1-2 mg/m L in drinking wa ter (Adamcak and Otten 2000) monitoring When used at recommended doses for pain control in otherwise T! healthy patients, little monitoring should be necessary. Howev-er, with chronic therapy, occasional liver, renal and hematologic

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ACETAz Ol Am IDE 7 monitoring may be warranted, particularly when clinical signs occur. Client Information Follow directions carefully; do not exceed dosage or increase dos-T! ing fre quency. Do not administer to cats or ferrets for any reason. Keep out of reach of children. Chemistry/Synonyms A synthetic non-opiate analgesic, acetaminophen (also known as paracetamol) oc curs as a crystalline, white powder with a slightly bitter taste. It is soluble in boiling water and freely soluble in alco-hol. Acetaminophen is known in the U. K. as paracetamol. Acetaminophen may also be known as: paracetamol, MAPAP or APAP; many trade names are available. Storage/Stability Acetaminophen products should be stored at temperatures less than 40°C. Do not freeze oral solution or suspension. Dosage Forms/Regulatory Status VETERINAR y­l Ab El ED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 4 substance. See the appendix for more information. HUm AN­l Ab El ED PRODUCTS: There are many different trade names and products of acetamino-phen available. The most com monly known trade name is Tylenol®. Acetaminophen is commonly available in, 325 mg, 500 mg, 650 mg tablets; 80 mg chewable tablets; 650 mg extended release tablets; 160mg, 500 mg, & 650 mg caplets; 500 mg gelcaps; 325 mg, & 500 mg capsules, 80 mg and 160 mg sprin kle capsules; 80 mg/0. 8 m L drops; 80 mg/2. 5 m L, 80 mg/5 m L, 120 mg/5 m L, & 160 mg/5 m L elixirs; 160 mg/5 m L, 500 mg/15 m L, and 100 mg/m L liquids and solutions; 80 mg, 120 mg, 125 mg 300 mg, 325 mg and 650 mg sup-positories. Combinations with other analgesics (aspirin, codeine phosphate, oxycodone or propoxyphene) are also available. Acet Azol Amide Acet Azol Amide sodium (ah-seet-a-zole-a-mide) Diamox®, Dazamide® carb Onic anhydrase inhibit Or diuretic; antiglauc Oma agent Prescriber Highlights Used primarily for metabolic alkalosis or glaucoma in T T small animals; HYPP in horses Contraindicated in patients with significant hepatic, T T renal, pulmonary or adrenocortical in sufficiency, hypona-tremia, hypokalemia, hyperchloremic acidosis or electro-lyte imbal ance Give oral doses with food if GI upset occurs T T Electrolytes & acid/base status should be monitored with T T chronic or high dose therapy Monitor with tonometry if using for glaucoma T TUses/Indications Acetazolamide has been used principally in veterinary medicine for its effects on aque ous humor production in the treatment of glaucoma, metabolic alkalosis, and for its diuretic action. It may be useful as an adjunctive treatment for syringomyelia in dogs. Acetazolamide's use in small animals is complicated by a relatively high occurrence of adverse effects. In horses, acetazolamide is used as an adjunctive treatment for hyperkalemic periodic paralysis (HYPP). In humans, the drug has been used as adjunctive therapy for epi-lepsy and for acute high-altitude sickness. Pharmacology/Actions The carbonic anhydrase inhibitors act by a noncompetitive, revers-ible inhibition of the enzyme carbonic anhydrase. This reduces the formation of hydrogen and bicarbonate ions from carbon dioxide thereby reducing the availability of these ions for active transport into body secretions. Pharmacologic effects of the carbonic anhydrase inhibitors in-clude: decreased formation of aqueous humor, thus reducing in-traocular pressure, increased renal tubular secretion of sodium and potas sium and, to a greater extent, bicarbonate, leading to increased urine alkalinity and volume. Acetazolamide has some anticon-vulsant activity, which is independent of its diuretic effects (mecha-nism is not fully understood, but may be due to carbonic anhydrase or a metabolic acidosis effect). Pharmacokinetics The pharmacokinetics of this agent have apparently not been stud-ied in domes tic animals. One report (Roberts 1985) states that after a dose of 22 mg/kg, the onset of action is 30 minutes; maximal ef-fects occur in 2-4 hours; duration of action is about 4-6 hours in small animals. In humans, the drug is well absorbed after oral administra-tion with peak levels occurring within 1-3 hours. It is distributed throughout the body with highest levels found in the kidneys, plas-ma and erythrocytes. Acetazolamide has been detected in the milk of lactating dogs and it crosses the pla centa (in unknown quanti-ties). Within 24 hours of administration, an average of 90% of the drug is ex creted unchanged into the urine by tubular secretion and passive reabsorption processes. Contraindications/Precautions/Warnings Carbonic anhydrase inhibitors are contraindicated in patients with significant hepatic disease (may precipitate hepatic coma), renal or adrenocortical insufficiency, hy ponatremia, hypokalemia, hyper-chloremic acidosis, or electrolyte imbalance. They should not be used in patients with severe pulmonary obstruction that are unable to increase alveolar ventilation or in those who are hypersensitive to them. Long-term use of carbonic anhydrase inhibitors is con-traindicated in patients with chronic, noncongestive, angle-closure glaucoma as angle closure may occur and the drug may mask the condition by lowering intraocular pressures. Acetazolamide should be used with caution in patients with se-vere respiratory acidosis or having preexisting hematologic abnor-malities. Cross sensitivity between acetazolamide and antibacterial sulfonamides may occur. Adverse Effects Potential adverse effects that may be encountered include: GI distur-bances, CNS effects (sedation, depression, weakness, excitement, etc. ), hematologic effects (bone marrow de pression), renal effects (crystalluria, dysuria, renal colic, polyuria), hypokalemia, hypergly-cemia, hyponatremia, hyperuricemia, hepatic insufficiency, derma-tologic effects (rash, etc. ), and hyper sensitivity reactions.

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8 ACETAz Ol Am IDE At the dosages used for HYPP in horses adverse effects are report-edly uncommon. Reproductive/Nursing Safety Acetazolamide has been implicated in fetal abnormalities in mice and rats when used at high (10X) dosages) and fetal toxicity has been noted when the drug has been used in pregnant humans. In humans, the FDA categorizes this drug as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) In humans, the manufacturer states that either nursing or the drug must be discontinued if the mother is receiving acetazolamide. Veterinary significance is not clear. Overdosage/Acute Toxicity Information regarding overdosage of this drug was not locat-ed. Monitor serum electrolytes, blood gases, volume status, and CNS status during an acute overdose; treat symptomatically and supportively. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving acetazolamide and may be of significance in veterinary patients: Al KAl INE!! URINE : Drugs where acetazolamide-caused alkaline urine may affect their excretion rate: Decreased urinary excretion of quinidine, procainamide, tricyclic antidepressants; Increased urinary excretion of salicylates, phenobarbital ASPIRIN!! (or other salicylates ): Increased risk of acetazolamide ac-cumulation and toxicity; increased risk for metabolic acidosis DIg Ox IN!! : As acetazolamide may cause hypokalemia, increased risk for toxicity INSUl IN:T! Rarely, carbonic anhydrase inhibitors interfere with the hypoglycemic effects of insulin m ETHENAm INE COm POUNDS !! : Acetazolamide may negate methe-namine effects in the urine DRUg S AFFECTINg !! POTASSIUm (corticosteroids, amphotericin b, corti­ cotropin, or other diuretics ): Concomitant use may exacerbate po-tassium depletion PRIm IDONE!! : Decreased primidone concentrations laboratory Considerations By alkalinizing the urine, carbonic anhydrase inhibitors may T! cause false positive results in determining urine protein when us-ing bromphenol blue reagent (Albustix®, Albutest®, Labstix®), sul-fosalicylic acid (Bumintest®, Exton's Test Reagent), nitric acid ring test, or heat and acetic acid test methods Carbonic anhydrase inhibitors may T! decrease iodine uptake by the thyroid gland in hyperthyroid or euthyroid patients Doses Directions for reconstitution of injection: Reconstitute 500 mg vial with at least 5 m L of Sterile Water for Injection; use within 24 hours after reconstitution. DOg S:T! For adjunctive treatment of metabolic alkalosis: a) 10 mg/kg four times daily (may aggravate volume contraction and hypokalemia) (Hardy and Robin son 1986) For adjunctive therapy of glaucoma:a) 10-25 mg/kg divided 2-3 times daily (Brooks 2002a) b) 50-75 mg/kg PO 2-3 times a day (Bedford 2003) c) 50 mg/kg IV one time; 7 mg/kg, PO three times daily (Vestre 1985) For adjunctive therapy of hydrocephalus in pediatric patients: a) 0. 1 mg/kg PO q8h (Coates 2002) CATS:T! For adjunctive therapy of glaucoma: a) 50 mg/kg IV once; 7 mg/kg, PO three times daily (Vestre 1985) HORSES:T! (Note : ARCI UCGFS Class 4 Drug) For adjunctive therapy of hyperkalemic periodic paralysis (HYPP): a) 2. 2-4. 4 mg/kg PO twice daily (Schott II 2004) b) 0. 5-2. 2 mg/kg PO twice daily (Mayhew 2005a) c) 3 mg/kg PO (dosing interval not specified) (Harris and May-hew 1998) RUm INANTS:T! a) 6-8 mg/kg IV, IM, or SC (Howard 1986) SWINE:T! a) 6-8 mg/kg IV, IM, or SC (Howard 1986) monitoring Intraocular pressure tonometry (if used for glaucoma)T! Blood gases if used for alkalosis T! Serum electrolytes T! Baseline CBC with differential and periodic retests if using chron-T! ically Other adverse effects T! Client Information Give with food if using oral preparation and GI upset occurs T! Notify veterinar ian if abnormal bleeding or bruising occurs or if T! animal develops tremors or a rash Chemistry/Synonyms A carbonic anhydrase inhibitor, acetazolamide occurs as a white to faintly yellowish-white, odorless, crystalline powder with p K as of 7. 4 and 9. 1. It is very slightly soluble in water, sparingly soluble in hot water (90-100°C) and alcohol. Acetazolamide sodium occurs as a white lyophilized solid and is freely soluble in water. The injection has a p H of 9. 2 after reconstitution with Sterile Water for Injection. Acetazolamide may also known as: acetazolam, acetazolamidum, or sodium acetazolamide; many trade names are available. Storage/Stability/Compatibility Acetazolamide products should be stored at room temperature. T o prepare parenteral solution: reconstitute with at least 5 m L of Sterile Water for Injection. After reconstitution, the injection is stable for one week when refrigerated, but as it contains no preserva-tives, it should be used within 24 hours. Acetazolamide sodium for injection is reportedly physically com­ patible with all commonly used IV solutions and cimetidine HCl for injection. Dosage Forms/Regulatory Status VETERINAR y­l Ab El ED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 4 substance. See the appendix for more information. HUm AN­l Ab El ED PRODUCTS: Acetazolamide Tablets: 125 mg, 250 mg; generic; (Rx) Acetazolamide Sustained-Release Capsules: 500 mg; Diamox Se-quels® (Barr); (Rx)

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ACETIC ACID, ACETOHy DROx Am IC ACID 9 Acetazolamide Injection: 500 mg per vial; Diamox® (Wyeth-Ayerst); (Rx) Acetazolamide Powder for Injection (lyophilized): 500 mg for re-constitution; generic; (Rx) Acetic Acid (ah-see-tick ass-id) Vinegar gi acidifier Prescriber Highlights Used primarily for treatment of non-protein nitrogen-in-T T duced ammonia toxicosis (secondary to urea poisoning, etc. ) in ruminants or enterolith prevention in horses Contraindicated if potential lactic acidosis (grain over-T T load, rumen acidosis) is possible Given via stomach tube T T Uses/Indications Acetic acid is used via its acidifying qualities in ruminants to treat non-protein nitrogen-induced (e. g., urea poisoning) ammonia tox-icosis. It is also used as a potential treatment to prevent enterolith formation in horses by reducing colonic p H. Pharmacology/Actions Acetic acid in the rumen lowers p H due to shifting ammonia to ammonium ions and reducing absorption. It may also slow the hy-drolysis of urea. Pharmacokinetics No information was noted. Contraindications/Precautions/Warnings Should not be administered to ruminants until potential lactic aci-dosis (grain overload, rumen acidosis) is ruled out. Adverse Effects Because of the unpleasant taste and potential for causing mucous membrane irritation, acetic acid is generally recommended for ad-ministration via stomach tube. Overdosage/Acute Toxicity When used for appropriate indications there is little likelihood of se rious toxicity occurring after minor overdoses. Due to its poten-tial corrosiveness, the greatest concern would occur if a concentrat-ed form of acetic acid was mistakenly used. However, one human pa tient who had glacial acetic acid used instead of 5% acetic acid during colposcopy (cervix) demon strated no detectable harm. Drug Interactions There are no documented drug interactions with oral acetic acid, but because of its acidic qualities it could, potentially, affect the degradation of several drugs in the gut. Doses CATTl E/RUm INANTS:T! For cattle with putrefaction of rumen associated with a high ru-men p H: a) 4-10 liters of vinegar (Constable 1993)For treatment of urea poisoning: a) Using 5% acetic acid (vinegar) infuse 2-6 liters (for cattle) into rumen; may be repeated as necessary if clinical signs reoccur. Recovery ranges from 8-24 hours. A post-recovery pro-biotic rumen inoculation may enhance the gain and productivity of urea poisoned animals. (Hall 2006) HORSES:T! For enterolith prevention: a) Using vinegar: 250 m L/450 kg body weight PO once daily (Robinson 1992) Chemistry/Synonyms Glacial acetic acid is C 2H4O2. Acetic acid has a distinctive odor and a sharp acid taste. It is miscible with water, alcohol or glycerin. Much confusion can occur with the percentages of C 2H4O2 con-tained in various acetic acid solutions. Acetic Acid USP is defined as having a concen tration of 36-37% C 2H4O2. Diluted Acetic Acid NF contains 5. 7-6. 3% w/v of C 2H4O2. Solutions containing ap-proximately 3-5% w/v of C 2H4O2 are commonly known as vin-egar. Be certain of the concentration of the product you are using and your dilutions. Acetic acid may also be known as: E260, eisessig (glacial acetic acid), essigsaure, etanoico, or ethanoic acid. Storage/Stability Acetic acid solutions should be stored in airtight containers. Dosage Forms/Regulatory Status VETERINAR y­l Ab El ED PRODUCTS: None HUm AN­l Ab El ED PRODUCTS: None There are no systemic products commercially available. Acetic acid (in various concentrations) may be purchased from chemical sup-ply houses. Distilled white vinegar is available in gallon sizes from grocery stores. Acetohydrox Amic Acid (ah-seet-oh-hy-drox-am-ik) Lithostat®, AHA urease inhibit Or Prescriber Highlights Used occasionally in dogs for persistent struvite uroliths T T & persistent urease-producing bacteriuria Contraindicated in patients with renal impairment & dur-T T ing pregnancy; do not use in cats Adverse effects are common & can include GI effects T T (anorexia, vomiting, mouth/esophageal ulcers), hemolytic anemia, hyperbilirubinemia & bilirubinuria Monitor renal function (incl. urinalysis), CBC's, & bilirubin T T levels Uses/Indications Acetohydroxamic acid can be used in dogs as adjunctive therapy in some cases of recurrent urolithiasis or in the treatment of per-sistent urinary tract infections caused by the following bacteria: E. coli, Klebsiella, Morganella morganii, Staphylococci spp., and Pseudomonas aeruginosa. Adverse effects limit its usefulness. Pharmacology/Actions AHA inhibits urease thereby reducing production of urea and subsequent urinary concentrations of ammonia, bicarbonate and

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10 ACETyl Cy STEINE carbonate. While the drug does not directly reduce urine p H, by re-ducing ammonia and bicarbonate production by urease-producing bacteria, it prevents in creases in urine p H. The drug may act syner-gistically with several antimicrobial agents (e. g., car benicillin, gen-tamicin, clindamycin, trimethoprim-sulfa or chloramphenicol) in treating some urinary tract infections. The drug's effects on urinary p H and infection also indirectly inhibit the formation of urinary calculi (struvite, carbonate-apatite). Pharmacokinetics No canine specific data was located. In humans, the drug is rapidly absorbed after PO administration. Absolute bioavailability “in ani-mals” is reported to be 50-60%. AHA is well distributed throughout body fluids. It is partially metabolized to acetamide, which is active; 36-65% of a dose is excreted in the urine unchanged, and 9-14% excreted in the urine as acetamide. The re mainder is reportedly ex-creted as CO 2 via the respiratory tract. Contraindications/Precautions/Warnings AHA is contraindicated in patients with poor renal function (e. g., serum creatinine >2. 5 mg/dl) or when it is not specifically indicated (see Indications). Acetohydroxamic acid is reportedly very toxic in cats and should not be used in felines. Adverse Effects In dogs, GI effects (anorexia, vomiting, mouth/esophageal ulcers), hemolytic anemia, hyperbilirubinemia and bilirubinuria have been reported. Other potential adverse effects include: CNS disturbances (anxiety, depres sion, tremulousness), hematologic effects (reticulo-cytosis, bone marrow depression), phlebitis, and skin rashes/alope-cia. Effects on bilirubin metabolism have also been reported. Reproductive/Nursing Safety AHA use is considered contraindicated during pregnancy. In preg-nant beagles, doses of 25 mg/kg/day caused cardiac, coccygeal, and abdominal wall abnormalities in puppies. At high doses (>750 mg/kg) leg deformities have been noted in test animals. Higher doses (1500 mg/kg) caused significant encephalopathologies. In humans, the FDA categorizes this drug as category X for use during preg-nancy (Studies in animals or humans demonstrate fetal abnormalities or adverse reaction; reports indicate evidence of fetal risk. The risk of use in pregnant women clearly outweighs any possible benefit. ) Overdosage/Acute Toxicity In humans, mild overdoses have resulted in hemolysis after several weeks of treatment, particularly in patients with reduced renal func-tion. Acute overdoses are ex pected to cause clinical signs such as an-orexia, tremors, lethargy, vomiting and anxiety. Increased reticulo-cyte counts and a severe hemolytic reac tion are laboratory findings that would be expected. Treatment for an acute overdose may in-clude intensive hematologic monitoring with adjunctive supportive therapy, including possible transfusions. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving acetohydroxamic acid (AHA) and may be of significance in veterinary patients: IRON!! : AHA may chelate iron salts in the gut if given concomitantly m ETHENAm INE!! : AHA may have a synergistic effect with meth-enamine in inhibiting the urine p H increases caused by urease-produc ing Proteus spp. ; AHA may also potentiate the antibacterial effect of methenamine against these bac teria Al COHOl!! : In humans, AHA with alcohol has resulted in rasheslaboratory Considerations Although AHA is a true urease inhibitor, it apparently does not T! inter fere with urea nitrogen determination using one of the fol-lowing: urease-Berthelot, urease-glutamate dehydroge nase or di-acetyl monoxime methods. Doses DOg S:T! For adjunctive therapy of persistent struvite uroliths and persis-tent urease-producing bacteria after treating with antibiotics and calculolytic diets: a) 12. 5 mg/kg twice daily PO (Osborne, Lulich et al. 1993); (Lu-lich, Osborne et al. 2000) monitoring CBCT! Renal/Hepatic (bilirubin) function T! Efficacy T! Client Information This medication can cause several adverse effects in dogs; contact T! veterinarian if dog develops persistent or severe vomiting, has a lack of appetite, a change in urine color, develops yellowing of the whites of the eyes, or has decreased energy/activity. Chemistry/Synonyms An inhibitor of urease, acetohydroxamic acid occurs as a white crys-tal having a p Ka of 9. 32-9. 4 and a p H of about 9. 4. 850 mg are soluble in one m L of water, and 400 mg are soluble in one m L of al cohol. Acetohydroxamic acid may also be known as: AHA, Acetic acid oxime, N-Acetylhydroxylamide, N-Hydroxyacetamide, Lithostat® or Uronefrex®. Storage/Stability Tablets should be stored in tight containers. Dosage Forms/Regulatory Status VETERINAR y­l Ab El ED PRODUCTS: None HUm AN­l Ab El ED PRODUCTS: Acetohydroxamic Acid Tablets: 250 mg; Lithostat® (Mission); (Rx) Acetylcysteine (assah-teel-sis-tay-een) N-acetylcysteine, Mucomyst®, NAC antid Ote; muc Olytic Prescriber Highlights Used primarily as a treatment for acetaminophen or phe-T T nol toxicity & for its mucolytic effect; used anecdotally for treating degenerative myelopathy Also used as a topical ophthalmic (see the Topical Oph-T T thalmic section in the appendix)Has caused hypersensitivity & bronchospasm when used T T in pulmonary tree Administer via gastric-or duodenal tube for acetamino-T T phen poisoning in animals

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ACETyl Cy STEINE 11 Uses/Indications Acetylcysteine is used in veterinary medicine as both a mucolytic agent in the pulmonary tree and as a treatment for acetaminophen or phenol toxicity in small animals. It has been used anecdotally with aminocaproic acid to treat degenerative myelopathy in dogs. In horses with strangles, acetylcysteine instilled into the gutteral pouch has been used to help break up chondroids and avoid the need for surgical removal. Acetylcysteine enemas have been used in neonatal foals to break up meconium refractory to repeated en-emas. Pharmacology/Actions When administered into the pulmonary tree, acetylcysteine reduces the viscosity of both purulent and nonpurulent secretions and ex-pedites the removal of these secretions via coughing, suction, or postural drainage. The free sulfhydryl group on the drug is believed to reduce disulfide linkages in mucoproteins; this effect is most pro-nounced at a p H from 7-9. The drug has no effect on living tissue or fibrin. Acetylcysteine can reduce the extent of liver injury or methemo-globinemia after ingestion of acetaminophen or phenol, by provid-ing an alternate substrate for conjugation with the reactive metabo-lite of acetaminophen, thus maintaining or restoring glutathione levels. Pharmacokinetics When given orally, acetylcysteine is absorbed from the GI tract. When adminis tered via nebulization or intratracheally into the pulmonary tract, most of the drug is involved in the sulfhydryl-disulfide reaction and the remainder is absorbed. Absorbed drug is converted (deacetylated) into cysteine in the liver and then further metabolized. Contraindications/Precautions/Warnings Acetylcysteine is contraindicated (for pul monary indications) in animals hypersensitive to it. There are no contraindications for its use as an antidote. Because acetylcysteine may cause bronchospasm in some pa-tients when used in the pulmonary sys tem, animals with bron-chospastic diseases should be monitored carefully when using this agent. Adverse Effects When given orally for acetaminophen toxicity, acetylcysteine can cause GI effects (nausea, vomiting) and rarely, urticaria. Because the taste of the solution is very bad, use of taste masking agents (e. g., colas, juices) have been used. Since oral dosing of these drugs may be very difficult in animals, gastric or duodenal tubes may be necessary. Rare adverse effects reported when acetylcysteine is administered into the pulmonary tract, include: hypersensitivity, chest tightness, bronchoconstriction, and bronchial or tracheal irritation. Reproductive/Nursing Safety Reproduction studies in rabbits and rats have not demonstrated any evidence of teratogenic or em bryotoxic effects when used in doses up to 17 times normal. In humans, the FDA categorizes this drug as category B for use during pregnancy (Animal studies have not yet demonstrated risk to the fetus, but there are no adequate studies in pregnant women; or animal studies have shown an adverse effect, but adequate studies in pregnant women have not demonstrated a risk to the fetus in the first trimester of pregnancy, and there is no evidence of risk in later trimesters. ) It is unknown if acetylcysteine enters milk. Use caution when administering to a nursing dam. Overdosage/Acute Toxicity The LD50 of acetylcysteine in dogs is 1 g/kg (PO) and 700 mg/kg (IV). It is believed that acetylcysteine is quite safe (with the excep-tion of the adverse effects listed above) in most overdose situations. Drug Interactions ACTIVATED CHARCOAl:T! The use of activated charcoal as a gut adsor-bent of acetaminophen is controversial, as charcoal may also ad-sorb acetylcysteine. Be cause cats can develop methemoglobin-emia very rapidly after ingestion of acetaminophen, do not delay acetylcysteine treatment and preferably give the first dose intra-venously. If using the solution (not labeled for injectable use), it is preferable to use a 0. 2 micron in-line filter. Doses DOg S:T! For acetaminophen toxicity:a) A 2-3 hour wait between activated charcoal and PO admin-istration of acetylcysteine (NAC) is necessary. Give NAC as an initial oral loading dose of 140 mg/kg (dilute to 5% in dextrose or sterile water), followed by 70 mg/kg PO four times daily (q6h) for 7 treatments. With ingestion of massive quantities, some authors suggest using a 280 mg/kg loading dose and continuing treatment for 12-17 doses. May also be given IV after diluting to 5% and given via slow IV over 15-20 minutes. Additional therapy may include IV fluids, blood or Oxyglobin®, ascorbic acid and SAMe. (Wismer 2006a) b) 150 mg/kg PO or IV initially, then 50 mg/kg q4h for 17 ad-ditional doses (Bailey 1986a) c) Loading dose of 140 mg/kg PO, then 70 mg/kg PO every 6 hours for 7 treatments (Grauer and Hjelle 1988a) For phenol toxicity: a) 140 mg/kg PO or IV initially, then 50 mg/kg q4h for 3 days. May be partially effective to reduce hepatic and renal injury. Resultant methemoglobinemia should be treated with ascor-bic acid or methylene blue. (Dorman and Dye 2005) For respiratory use: a) 50 m L/hr for 30-60 minutes every 12 hours by nebulization (Kirk 1986) For degenerative myelopathy:a) 25 mg/kg PO q8h for 2 weeks, then q8h every other day. The 20% solution should be diluted to 5% with chicken broth or suitable diluent. Used in conjunction with aminocaproic acid (500 mg per dog PO q8h indefinitely). Other treatments may include prednisone (0. 25-0. 5 mg/kg PO daily for 10 days then every other day), Vitamin C (1000 mg PO q12h) and Vitamin E (1000 Int. Units PO q12h). Note : No treatment has been shown to be effective in published trials. (Shell 2003a) CATS:T! For acetaminophen toxicity:a) A 2-3 hour wait between activated charcoal and PO admin-istration of acetylcysteine (NAC) is necessary. Give NAC as an initial oral loading dose of 140 mg/kg (dilute to 5% in dextrose or sterile water), followed by 70 mg/kg PO four times daily (q6h) for 7 treatments. With ingestion of massive quantities, some authors suggest using a 280 mg/kg loading dose and continuing treatment for 12-17 doses. May also be given IV after diluting to 5% and given via slow IV over 15-20 minutes. Additional therapy may include IV fluids, blood or Oxyglobin®, ascorbic acid and SAMe. (Wismer 2006a)

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12 ACITRETIN b) 150 mg/kg PO or IV initially, then 50 mg/kg q4h for 17 ad-ditional doses (Bailey 1986a) For phenol toxicity: a) 140 mg/kg PO or IV initially, then 50 mg/kg q4h for 3 days. May be partially effective to reduce hepatic and renal injury. Resultant methemoglobinemia should be treated with ascor-bic acid or methylene blue. (Dorman and Dye 2005) For respiratory use: a) 50 m L/hr for 30-60 minutes every 12 hours by nebulization (Kirk 1986) For adjunctive treatment of hepatic lipidosis (see also Carnitine): a) Identify underlying cause of anorexia and provide a protein replete feline diet, give acetylcysteine (NAC) at 140 mg/kg IV over 20 minutes, then 70 mg/kg IV q12h; dilute 10% NAC with saline 1:4 and administer IV using a 0. 25 micron filter; correct hypokalemia and hypophosphatemia, beware of elec-trolyte changes with re-feeding phenomenon (Center 2006c) HORSES:T! T o help break up chondroids in the gutteral pouch: a) Instill 20% solution (Foreman 1999) In neonatal foals to break up meconium refractory to repeated enemas: a) 8 grams in 20 g sodium bicarbonate in 200 m L water (p H of 7. 6), give as enema as needed to effect (Freeman 1999) b) With foal in lateral recumbency, insert a 30 french foley cath-eter with a 30 cc bulb for a retention enema. Using gravity flow, infuse slowly 100-200 m L of 4% acetylcysteine solution and retain for 30-45 minutes. IV fluids and pain medication should be considered. Monitor for possible bladder disten-tion. (Pusterla, Magdesian et al. 2003) monitoring When used for acetaminophen poisoning: Hepatic enzymes (particularly in dogs) T! Acetaminophen level, if available (particularly in dogs) T! Hemogram, with methemoglobin value (particularly in cats) T! Serum electrolytes, hydration status T! Client Information This agent should be used in a clinically supervised setting only T! Chemistry/Synonyms The N-acetyl derivative of L-cysteine, acetylcysteine occurs as a white, crystalline powder with a slight acetic odor. It is freely soluble in water or alcohol. Acetylcysteine may also be known as: N-acetylcysteine or N-acetyl-L-cysteine, NAC, 5052 acetylcysteinum, NSC-111180, Acetadote®, Mucomyst® or ACC ®. Storage/Stability/Compatibility When unopened, vials of sodium acetylcysteine should be stored at room temperature (15-30°C). After opening, vials should be kept refrigerated and used within 96 hours. The product labeled for IV use states to use within 24 hours. Acetylcysteine is incompatible with oxidizing agents; solutions can become discolored and lib erate hydrogen sulfide when exposed to rubber, copper, iron, and during autoclaving. It does not re act to aluminum, stainless steel, glass or plastic. If the solution becomes light purple in color, po tency is not appreciably affected, but it is best to use non-reactive materials when giving the drug via nebu-lization. Acetylcysteine solutions are incompatible with amphoteri-cin B, ampicillin sodium, erythromycin lactobionate, tetracycline, oxytetracycline, iodized oil, hydrogen peroxide and trypsin. Dosage Forms/Regulatory Status VETERINAR y­l Ab El ED PRODUCTS: None HUm AN­l Ab El ED PRODUCTS: Acetylcysteine injection: 20% (200 mg/m L), (0. 5 mg/m L EDTA in 30 m L single-dose vials, preservative free; Acetadote® (Cumberland); (Rx) Acetylcysteine Solution: 10% & 20% (as sodium) in 4 m L, 10 m L, 30 m L & 100 m L (20% only) vials; Mucomyst® (Apothecon); (Rx) Note: If using this product for dilution and then intravenous dosing, it is preferable to use a 0. 2 micron in-line filter. Acetylsalicylic Acid — See Aspirin Acitretin (ase-a-tre-tin) Soriatane® retin Oid Note : Originally etretinate was used for certain dermatologic indications in small animals (primarily dogs). It has been withdrawn from the mar-ket and replaced with acitretin, an active metabolite of etretinate with the same indications, but a much shorter half-life. Much of the information below is extrapolated from etretinate data. Prescriber Highlights Retinoid that may be useful for certain dermatologic con-T T ditions in small animals Contraindications: Pregnancy; Caution: Cardiovascular T T disease, hypertriglyceridemia or sensitivity to retinoids Adverse Effects: Limited experience; appears to be fairly T T well tolerated in small animals Potentially: anorexia/ vomiting/diarrhea, cracking of foot pads, pruritus, ventral abdomi nal erythema, polydipsia, lassitude, joint pain/ stiffness, eyelid abnormalities & con junctivitis (KCS), swollen tongue, & behavioral changes Known teratogen; do not use in households with preg-T T nant women present (Plumb's rec ommendation) May be very expensive; may need to compound smaller T T capsules for small dogs or cats Drug-drug; drug-lab interactions T T Uses/Indications Acitretin may be useful in the treatment of canine lamellar ich-thyosis, solar-in duced precancerous lesions in Dalmatians or bull T erriers, actinic keratoses, squamous cell carci nomas, and intracuta-neous cornifying epitheliomas (multiple keratoacanthomas). While the drug has provided effective treatment of idiopathic seborrhea (particularly in cocker spaniels), it is not effective in treat-ing the ceruminous otitis that may also be present. Results have been disap pointing in treating idiopathic seborrheas seen in basset hounds and West Highland terriers. Acitretin's usage in cats is very limited, but etretinate has shown some usefulness in treating para neoplastic actinic keratosis, solar-induced squamous cell carcinoma and Bowen's Disease in this species. Pharmacology/Actions Acitretin is a synthetic retinoid agent potentially useful in the treat-ment of several disorders related to abnormal keratinization and/

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ACITRETIN 13 or sebaceous gland abnormalities in small animals. The drug has some antiinflammatory activity, but its exact mechanism of action is not known. Pharmacokinetics Acitretin absorption is enhanced by food in the gut. Acitretin is highly bound to plasma proteins. The drug is metabolized to conju-gate forms that are excreted in the bile and urine. T erminal half-life averages 50 hours in humans. Contraindications/Precautions/Warnings Acitretin use should not be considered when the following condi-tions exist: cardiovascular disease, hy pertriglyceridemia or known sensitivity to acitretin. Use with caution in patients with renal or hepatic failure. Adverse Effects Veterinary experience with this medication is lim ited, but the in-cidence of adverse effects appears to be less in companion animals than in people. Most ani mals treated (thus far) do not exhibit ad-verse effects. Potential adverse effects include: anorexia/vomiting/diarrhea, cracking of foot pads, pruritus, ventral abdominal erythe-ma, polydipsia, lassitude, joint pain/stiffness, eyelid abnormalities and conjunctivitis (KCS), swollen tongue, and be havioral changes. The most common adverse effect seen in cats is anorexia with resultant weight loss. If cats develop adverse effects, the time be-tween doses may be prolonged (e. g., Every other week give ev ery other day) to reduce the total dose given. Reproductive/Nursing Safety Acitretin is a known teratogen. Major anomalies have been reported in children of women receiving acitretin. It should not be handled by pregnant women nor used in a household where women are pregnant or planning to become pregnant. It should be considered absolutely contraindi cated in pregnant veterinary patients. In hu-mans, the FDA categorizes this drug as category X for use during pregnancy (Studies in animals or humans demonstrate fetal abnor-malities or adverse reaction; reports indicate evidence of fetal risk. The risk of use in pregnant women clearly outweighs any possible benefit. ) Acitretin is excreted in rat milk. At this time, it cannot be recom-mended for use in nursing dams. Overdosage/Acute Toxicity Information on overdoses with this agent remains limited. One oral overdose (525 mg) in a human patient resulted only in vomiting. The oral LD50 in rats and mice is >4 grams/kg. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving acitretin and may be of significance in veterinary patients: Al COHOl!! : Acitretin can form etretinate in the presence of alcohol; etretinate is a teratogen with an extremely long terminal half-life and (can persist in adipose tissue for years) HEPATOTOx IC DRUg S!! (especially methotrexate and potentially an­ abolic steroids, androgens, asparaginase, erythromycins, estrogens, fluconazole, halothane, keto conazole, sulfonamides or valproic acid ): May be increased potential for hepatotoxicity OTHER RETINOIDS !! (isotretinoin, tretinoin, or vitamin A): May cause additive toxic effects. TETRACy Cl INES!! : Acitretin with tetracyclines may increase the po-tential for the occurrence of pseudotumor cerebri (cerebral ede-ma and increased CSF pressure) laboratory Considerations In humans, acitretin may cause significant increases in T! plasma trig­ lycerides, serum cholesterol, serum Al T (Sg PT ), serum AST (Sg OT ), and serum l DH con centrations. Serum HDl (high density lipopro-tein) concentrations may be decreased. Veterinary significance of these effects is unclear. Doses DOg S:T! For dermatologic conditions where retinoids may be useful:a) 0. 5-1 mg/kg PO once daily (Kwochka 2003b) b) 0. 5-2 mg/kg PO once daily (Merchant 2000) c) For sebaceous adenitis: 0. 5-1 mg/kg once daily PO (Bloom 2006c) CATS:T! For actinic keratosis/solar-induced squamous cell carcinoma; or Bowen's Disease: a) 10 mg per cat once daily PO. (Power and Ihrke 1995) Note : this dose is for etretinate, but as the smallest cap sule is 10 mg, this dose may need to suffice as well for cats. b) For Bowen's Disease: 3 mg/kg/day (Hnilica 2003d) monitoring Efficacy T! Liver function tests (baseline and if clinical signs appear) T! Schirmer tear tests (monthly—especially in older dogs)T! Client Information Acitretin should not be handled by pregnant women in the house-T! hold; veterinarians must take responsibility to educate clients of the potential risk of in gestion by pregnant females Food will increase the absorption of acitretin. T o reduce variabil-T! ity of absorption, either have clients consistently give with meals or when fasted Long-term therapy can be quite expensive T! Chemistry/Synonyms Acitretin, a synthetic retinoid occurs as a yellow to greenish-yellow powder. Acitretin may also be known as: acitretinum, etretin, Ro-10-1670, Ro-10-1670/000, Soriatane®, Acetrizoic Acid®, or Iodophil Viscous®. Storage/Stability Store at room temperature and protected from light. After bottle is opened, protect from high temperature and humidity. Dosage Forms/Regulatory Status VETERINAR y­l Ab El ED PRODUCTS: None HUm AN­l Ab El ED PRODUCTS: Acitretin Capsules: 10 mg & 25 mg; Soriatane® (Connetics); (Rx) ACTH — See Corticotropin Activated Charcoal — See Charcoal, Activated

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14 ACy Cl OVIR Acyclovir (ay-sye-kloe-vir) Zovirax® antiviral (herpes) Prescriber Highlights Used primarily in birds for Pacheco's disease; may be use-T T ful in cats for Herpes infection If given rapidly IV, may be nephrotoxic T T Oral use may cause GI distress T T Reduce dosage with renal insufficiency T T May be fetotoxic at high dosages T T Uses/Indications Acyclovir may be useful in treating herpes infections in a variety of avian species and in cats with corneal or conjunctival herpes infec-tions. Its use in veterinary medicine is not well established, however, and it should be used with caution. Acyclovir has relatively mild ac-tivity against Feline Herpesvirus-1 when compared to some of the newer antiviral agents (e. g., ganciclovir, cidofovir, or penciclovir). Acyclovir is being investigated as a treatment for equine herpes virus type-1 myeloencephalopathy in horses, but clinical efficacy has not yet been proven and the drug's poor oral bioavailability is problematic. There continues to be interest in finding a dosing regi-men that can achieve therapeutic levels and be economically viable, particularly since the drug's use during a recent outbreak appeared to have some efficacy in reducing morbidity and mortality (not sta-tistically proven). Also, intravenous acyclovir may be economically feasible to treat some neonatal foals. Pharmacology/Actions Acyclovir has antiviral activity against a variety of viruses includ-ing herpes sim plex (types I and II), cytomegalovirus, Epstein-Barr, and varicella-Zoster. It is preferentially taken up by these viruses, and converted into the active triphosphate form where it inhibits viral DNA replica tion. Pharmacokinetics In dogs, acyclovir bioavailability varies with the dose. At doses of 20 mg/kg and below, bioavailability is about 80%, but declines to about 50% at 50 mg/kg. Bioavailability in horses after oral administration is very low (<4%) and oral doses of up to 20 mg/kg may not yield sufficient levels to treat equine herpes virus. Elimination half-lives in dogs, cats and horses are approximately 3 hours, 2. 6 hours, and 10 hours, respectively. In humans, acyclovir is poorly absorbed after oral administration (approx. 20%) and ab sorption is not significantly affected by the presence of food. It is widely distributed throughout body tissues and fluids including the brain, semen, and CSF. It has low protein binding and crosses the placenta. Acyclovir is primarily hepatically metabolized and has a half-life of about 3 hours in hu mans. Renal disease does not significantly alter half-life unless anuria is present. Contraindications/Precautions/Warnings Acyclovir is potentially contraindicated (assess risk vs. benefit) during dehydrated states, pre-existing renal function impairment, hypersensitiv ity to it or other related antivirals, neurologic deficits, or previous neurologic reactions to other cyto toxic drugs. Adverse Effects With parenteral therapy potential adverse effects include throm-bophlebitis, acute renal failure, and ecephalopathologic changes (rare). GI disturbances may occur with either oral or parenteral therapy. Preliminary effects noted in cats, include leukopenia and anemias, which are apparently reversible with discontinuation of therapy. Reproductive/Nursing Safety Acyclovir crosses the placenta, but rodent studies have not demon-strated any teratogenic effects thus far. Acyclovir crosses into ma-ternal milk but associated adverse effects have not been noted. In humans, the FDA categorizes this drug as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) Acyclovir concentrations in milk of women following oral admin-istration have ranged from 0. 6 to 4. 1 times those found in plasma. These concentrations would potentially expose the breastfeeding in-fant to a dose of acyclovir up to 0. 3 mg/kg/day. Data for animals was not located. Use caution when administering to a nursing patient. Overdosage/Acute Toxicity Oral overdose is unlikely to cause significant toxicity. In a review of 105 dogs ingesting acyclovir (Richardson 2000), 10 animals were considered cases of acyclovir toxicosis. Adverse effects included vom-iting, anorexia, diarrhea and lethargy. One dog developed polyuria/polydipsia and another dog developed a mildly elevated BUN and serum creatinine 24 hours after ingesting 2068 mg/kg of acyclovir. Per the APCC database, acute renal injury was reported in one dog at a dose of 250 mg/kg. Treatment consists of standard decontami-nation procedures and supportive therapy. Contact an animal poi-son control center for further information, if necessary. There were 92 exposures to acyclovir reported to the ASPCA Animal Poison Control Center (APCC; www. apcc. aspca. org) dur-ing 2005-2006. In these cases 90 were dogs with 7 showing clinical signs; the remaining 2 cases were cats that showed no clinical signs. Common findings recorded in decreasing frequency included vom-iting, diarrhea, lethargy, anorexia, and crystalluria. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving acyclovir and may be of significance in veterinary patients: NEPHROTOx IC m EDICATIONS !! : Concomitant administration of IV acyclovir with nephrotoxic medications may increase the poten-tial for nephrotoxicity occurring. Amphotericin B may potentiate the antiviral effects of acyclovir but it also increases chances for development of nephrotoxicity. z IDOVUDINE!! : Concomitant use with zidovudine may cause addi-tional CNS depression. Doses b IRDS:T! For treatment of Pacheco's Disease:a) 80 mg/kg PO q8h or 40 mg/kg q8h IM (do not use parenter-ally for more than 72 hours as it can cause tissue necrosis at site of injection) (Oglesbee and Bishop 1994) b) 80 mg/kg in oral suspension once daily PO; mix suspension with peanut butter or add to drinking water 50 mg in 4 oz of water for 7-14 days (Jenkins 1993) c) When birds are being individually treated: 80 mg/kg PO or IM twice daily (Speer 1999)

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Agl EPRISTONE 15 d) For prophylaxis: Exposed birds are given 25 mg/kg IM once (give IM with caution as it is very irritating), and then acy-clovir is added to drinking water at 1 mg/m L and to the food at 400 mg/quart of seed for a minimum of 7 days. Quaker parrots have been treated with a gavage of acyclovir at 80 mg/kg q8h for 7 days. (Johnson-Delaney 2005b) CATS:T! For Herpesvirus-1 infections: a) 10-25 mg/kg PO twice daily. Never begin therapy until diag-nostic evaluation is completed. May be toxic in cats; monitor CBC every 2-3 weeks. (Lappin 2003b) HORSES:T! a) Although efficacy is undetermined, anecdotal use of acyclovir orally at 10 mg/kg PO 5 times daily or 20 mg/kg PO q8h may have had some efficacy in preventing or treating horses dur-ing EHV-1 outbreaks. Additional studies may further clarify the usefulness of such dosing regimens—Plumb 2007; based upon (Wilkins 2004a) & (Henninger, Reed et al. 2007) monitoring Renal function tests (BUN, Serum Cr) with prolonged or IV T! therapy Cats: CBCT! Chemistry/Synonyms An antiviral agent, acyclovir (also known as ACV or acycloguanos-ine), occurs as a white, crystalline powder. 1. 3 mg are soluble in one m L of water. Acyclovir sodium has a solubility of greater than 100 mg/m L in water. However, at a p H of 7. 4 at 37°C it is practically all unionized and has a solubility of only 2. 5 mg/m L in water. There is 4. 2 m Eq of sodium in each gram of acy clovir sodium. Acyclovir may be known as: aciclovirum, acycloguanosine, acy-clovir, BW-248U, Zovirax®, Acic®, Aciclobene®, Aciclotyrol®, Acivir ®, Acyrax®, Cicloviral®, Geavir®, Geavir®, Herpotern ®, Isavir®, Nycovir ®, Supraviran®, Viclovir®, Virherpes®, Viroxy ®, Xorox®, or Zovirax®. Storage/Stability/Compatibility Acyclovir capsules and tablets should be stored in tight, light re-sistant containers at room temperature. Acyclovir suspension and sodium sterile powder should be stored at room temperature. When reconstituting acyclovir sodium do not use bacteriostatic water with parabens as precipitation may occur. The manufacturer does not recommend using bacteriostatic water for injection with ben zyl alcohol because of the potential toxicity in neonates. After reconstitution with 50-100 m L of a standard electrolyte or dex-trose solution, the resulting solution is stable at 25°C for 24 hours. Acy clovir is reportedly incompatible with biologic or colloidial prod-ucts (e. g., blood products or protein containing solutions). It is also incompatible with dopamine HCl, dobutamine, fludarabine phos-phate, foscarnet sodium, meperidine and morphine sulfate. Many other drugs have been shown to be compatible in specific situations. Compatibility is dependent upon factors such as p H, concentra-tion, temperature and diluent used; consult specialized references or a hospital pharmacist for more specific in formation. Dosage Forms/Regulatory Status VETERINAR y­l Ab El ED PRODUCTS: None HUm AN­l Ab El ED PRODUCTS: Acyclovir Tablets: 400 mg & 800 mg; Zovirax® (Glaxo Wellcome); generic; (Rx) Acyclovir Capsules: 200 mg; Zovirax® (Glaxo Wellcome); generic; (Rx)Acyclovir Suspension: 200 mg/5 m L in 473 m L; Zovirax® (Glaxo W-ellcome); generic; (Rx)Acyclovir Sodium Injection (for IV infusion only): 50 mg/m L (as sodium): generic; (Rx) Acyclovir Powder for Injection: 500 mg/vial (as sodium) in 10 m L vials; 1000 mg/vial (as sodium) in 20 m L vials; 500 mg/vial Lyo-philized in 10 m L vials; Zovirax® (Glaxo Wellcome); generic; (Rx) Acyclovir Ointment: 5% (50 mg/g) in 15 g; Zovirax® (Biovail); (Rx) Acyclovir Cream: 5% (50 mg/g) in 2g tubes; Zovirax® (Biovail); (Rx) Aglepristone (a-gle-pris-tone) Alizin®, Alizine® injectable pr Ogester One bl Ocker Prescriber Highlights Injectable progesterone blocker indicated for pregnancy T T termination in bitches; may also be of benefit in inducing parturition or in treating pyometra complex in dogs & progesterone-dependent mammary hyperplasia in cats Not currently available in USA; marketed for use in dogs T T in Europe, South America, etc. Localized injection site reactions are most commonly T T noted adverse effect; other adverse effects reported in >5% of patients include: anorexia (25%), excitation (23%), depression (21%), & diarrhea (13%) Uses/Indications Aglepristone is labeled (in the U. K. and elsewhere) for pregnancy termination in bitches up to 45 days after mating. In dogs, aglepristone may prove useful in inducing parturition or treating pyometra complex (often in combination with a prosta-glandin F analog such as cloprostenol). In cats, it may be of benefit for pregnancy termination (one study documented 87% efficacy when administered at the recom-mended dog dose at day 25) or in treating mammary hyperplasias or pyometras. Pharmacology/Actions Aglepristone is a synthetic steroid that binds to the progesterone (P4) receptors thereby preventing biological effects from progesterone. It has an affinity for uterine progesterone receptors approximately three times that of progesterone. As progesterone is necessary for maintaining pregnancy, pregnancy can be terminated or parturition induced. Abortion occurs within 7 days of administration. Benign feline mammary hyperplasias (fibroadenomatous hy-perplasia; FAHs) are usually under the influence of progesterone and aglepristone can be used to medically treat this condition. When used for treating pyometra in dogs, aglepristone can cause opening of the cervix and resumption of miometral contractility. Within 24 hours of administration, aglepristone does not ap-preciably affect circulating plasma levels of progesterone, cortisol, prostaglandins or oxytocin. Plasma levels of prolactin are increased within 12 hours when used in dogs during mid-pregnancy which is probably the cause of mammary gland congestion often seen in these dogs.

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16 Agl EPRISTONE Aglepristone also binds to glucocorticoid receptors but has no glucocorticoid activity; it can prevent endogenous or exogenously administered glucocorticoids from binding and acting at these sites. Pharmacokinetics In dogs, after injecting two doses of 10mg/kg 24 hours apart, peak serum levels occur about 2. 5 days later and mean residence time is about 6 days. The majority (90%) of the drug is excreted via the feces. Contraindications/Precautions/Warnings Aglepristone is contraindicated in patients who have documented hypersensitivity to it and during pregnancy, unless used for preg-nancy termination or inducing parturition. Because of its antagonistic effects on glucocorticoid receptors, the drug should not be used in patients with hypoadrenocorticism or in dogs with a genetic predisposition to hypoadrenocorticism. The manufacturer does not recommend using the product in patients in poor health, with diabetes, or with impaired hepatic or renal function as there is no data documenting its safety with these conditions. Adverse Effects As the product is in an oil-alcohol base, localized pain and inflam-matory reactions (edema, skin thickening, ulceration, and local-ized lymph node enlargement) can be noted at the injection site. Resolution of pain generally occurs shortly after injection; other in-jection site reactions usually resolve within 2-4 weeks. The manu-facturer recommends light massage of the injection site after admin-istration. Larger dogs should not receive more than 5 m L at any one subcutaneous injection site. One source states that severe injection reactions can be avoided if the drug is administered into the scruff of the neck. Systemic adverse effects reported from field trials include: an-orexia (25%), excitation (23%), depression (21%), vomiting (2%), diarrhea (13%) and uterine infections (3. 4%). Transient changes in hematologic (RBC, WBC indices) or biochemical (BUN, creatinine, chloride, potassium, sodium, liver enzymes) laboratory parameters were seen in <5% of dogs treated. When used for pregnancy termination, a brown mucoid vaginal discharge can be seen approximately 24 hours before fetal expul-sion. This discharge can persist for an additional 3-5 days. If used in bitches after the 20 th day of gestation, abortion may be accompanied with other signs associated with parturition (e. g., inappetance, rest-lessness, mammary congestion). Bitches may return to estrus in as little as 45 days after pregnancy termination. Reproductive/Nursing Safety Unless used for pregnancy termination or at term to induce parturi-tion, aglepristone is contraindicated during pregnancy. One study (Baan, Taverne et al. 2005) using aglepristone to in-duce parturition (day 58) demonstrated no significant differences in weight gain between those puppies in the treatment group versus the control group suggesting that aglepristone did not have effect on milk production of treated bitches. Overdosage/Acute Toxicity When administered at 3X (30mg/kg) recommended doses, bitches demonstrated no untoward systemic effects. Localized reactions were noted at the injection site, presumably due to the larger vol-umes injected. Drug Interactions No documented drug interactions were noted. Theoretically, the fol-lowing interactions may occur with aglepristone: PROg ESTINS!! (natural or synthetic ): Could reduce the efficacy of aglepristone gl UCOCORTICOIDS!! : Aglepristone could reduce the efficacy of gluco-corticoid treatment KETOCONAz Ol E, ITRACONAz Ol E, ER y THROmy CIN !! : The manufacturer states that although there is no data, these drugs may interact with aglepristone laboratory Considerations None were noted Doses WARNINg: As accidental injection of this product can induce abor-tion; it should not be administered or handled by pregnant women. Accidental injection can also cause severe pain, intense swelling and ischemic necrosis that can lead to serious sequelae, including loss of a digit. In cases of accidental injection, prompt medical attention must be sought. DOg S:T! T o terminate pregnancy (up to day 45): a) 10 mg/kg (0. 33 m L/kg) subcutaneous injection only. Repeat one time, 24 hours after the first injection. A maximum of 5 m L should be injected at any one site. Light massage of the injection site is recommended after administration. (Label information; Alizin®—Virbac U. K. ) T o induce parturition: a) After day 58 of pregnancy: 15 mg/kg subcutaneously one time. 24 hours after aglepristone injection, give oxytocin 0. 15 Units/kg every 2 hours until the end of parturition. (Fieni, Bruyas et al. 2001) b) On or after day 58 of pregnancy: 15 mg/kg subcutaneously; repeat in 9 hours. In treated group, expulsion of first pup oc-curred between 32 and 56 hours after treatment. Use standard protocols to assist with birth (including oxytocin to assist in pup expulsion if necessary) or to intervene if parturition does not proceed. (Baan, Taverne et al. 2005) As an adjunct to treating pyometra/metritis: a) For closed cervix: 6 mg/kg twice daily on the first day followed by the same dose once daily on days 2, 3, and 4. Some pre-fer using larger doses (10mg/kg) once daily on days 1, 3,and 8, then follow up also on days 15 and 28 depending on the bitch's condition. (Romagnoli 2003a) b) For metritis: 10 mg/kg subcutaneously once daily on days 1, 2 and 8. For open or closed pyometra: aglepristone 10 mg/kg subcuta-neously once daily on days 1, 2 and 8 and cloprostenol 1 mcg/kg subcutaneously on days 3 to 7. Bitches with closed pyo-metra or with elevated temperature or dehydration should also receive intravenous fluids and antibiotics (e. g., amoxicil-lin/clavulanate at 24 mg/kg/day on days 1-5). If pyometra has not resolved, additional aglepristone doses should be given on days 14 and 28. (Fieni 2006) CATS:T! For treating mammary fibroadenomatous hyperplasia:a) 20 mg/kg aglepristone subcutaneously once weekly until reso-lution of signs. Cats who present with heart rates greater than 200 BPM should receive atenolol at 6. 25 mg (total dose) until heart rate is less than 200 BPM with regression in size of the mammary glands. (Gorlinger, Kooistra et al. 2002)

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Alb ENDAz Ol E 17 monitoring Clinical efficacy T! For pregnancy termination: ultrasound 10 days after treatment T! and at least 30 days after mating Adverse effects (see above)T! Client Information Only veterinary professionals should handle and administer this T! product When used for pregnancy termination in the bitch, clients should T! understand that aglepristone might only be 95% effective in ter-minating pregnancy when used between days 26-45 A brown mucoid vaginal discharge can be seen approximately 24 T! hours before fetal expulsion Bitch may exhibit the following after treatment: lack of appetite, T! excitement, restlessness or depression, vomiting, or diarrhea Clients should be instructed to contact veterinarian if bitch ex-T! hibits a purulent or hemorrhagic discharge after treatment or if vaginal discharge persists 3 weeks after treatment Chemistry/Synonyms Aglepristone is a synthetic steroid. The manufactured injectable dosage form is in a clear, yellow, oily, non-aqueous vehicle that con-tains arachis oil and ethanol. No additional antimicrobial agent is added to the injection. Aglepristone may also be known as RU-534, Alizine®, or Alizin®. Storage/Stability/Compatibility Aglepristone injection should be stored below 25°C and protected from light. The manufacturer recommends using the product with-in 28 days of withdrawing the first dose. Although no incompatibilities have been reported, due to the product's oil/alcohol vehicle formulation it should not be mixed with any other medication. Dosage Forms/Regulatory Status VETERINAR y­l Ab El ED PRODUCTS: Note : Not presently available or approved for use in the USA. In several countries: Aglepristone 30 mg/m L in 5 m L and 10 m L vials; Alizine® or Al-izin® (Virbac); (Rx)The FDA may allow legal importation of this medication for com-passionate use in animals; for more information, see the Instruc-tions for Legally Importing Drugs for Compassionate Use in the USA found in the appendix. HUm AN­l Ab El ED PRODUCTS: None Albend Azole (al-ben-da-zole) Albenza®, Valbazen® antiparasitic Prescriber Highlights Broad spectrum against a variety of nematodes, cestodes T T & protozoa; labeled for cattle & sheep (suspension only) Contraindicated with hepatic failure, pregnancy, lactating T T dairy cattle May cause GI effects (including hepatic dysfunction) & T T rarely blood dyscrasias (aplastic anemia)Do not use in pigeons, doves or crias T T Uses/Indications Albendazole is labeled for the following endoparasites of cattle (not lactating): Ostertagia ostertagi, Haemonchus spp., Trichostrongylus spp., Nematodius spp., Cooperia spp., Bunostomum phlebotomum, Oesphagostomum spp., Dictacaulus vivaparus (adult and 4th stage larva), Fasciola hepatica (adults), and Moniezia spp. In sheep, albendazole is approved for treating the following endoparasites: Ostertagia circumcincta, Marshallagia marshalli, Haemonchus contortus, Trichostrongylus spp., Nematodius spp., Cooperia spp., Oesphagostomum spp., Chibertia ovina, Dictacaulus filaria, Fasciola hepatica, Fascioides magna, Moniezia expansa, and Thysanosoma actinoides. Albendazole is also used (extra-label) in small mammals, goats and swine for endoparasite control. In cats, albendazole has been used to treat Paragonimus kelli-cotti infections. In dogs and cats, al bendazole has been used to treat capillariasis. In dogs, albendazole has been used to treat Filaroides infections. It has been used for treating giardia infections in small animals, but concerns about bone marrow toxicity have diminished enthusiasm for the drug's use. Pharmacology/Actions Benzimidazole antiparasitic agents have a broad spectrum of activ-ity against a variety of pathogenic internal parasites. In susceptible parasites, their mechanism of action is believed due to disrupting intracellular microtubular transport systems by binding selectively and damaging tubulin, preventing tubulin polymerization, and in-hibiting microtubule formation. Benzimidazoles also act at higher concentrations to disrupt metabolic pathways within the helminth, and inhibit metabolic enzymes, including malate dehydrogenase and fumarate reductase. Pharmacokinetics Pharmacokinetic data for albendazole in cattle, dogs and cats was not located. The drug is thought better absorbed orally than other benzimidazoles. Approximately 47% of an oral dose was recovered (as metabolites) in the urine over a 9-day period. After oral dosing in sheep, the parent compound was either not detectable or only transiently de tectable in plasma due to a very rapid first-pass effect. The active metabolites, albendazole sulphox-ide and albendazole sulfone, reached peak plasma concentrations 20 hours after dosing.

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18 Alb ENDAz Ol E Contraindications/Precautions/Warnings The drug is not approved for use in lactating dairy cattle. The manu-facturer recommends not administering to female cattle during the first 45 days of pregnancy or for 45 days after removal of bulls. In sheep, it should not be administered to ewes during the first 30 days of pregnancy or for 30 days after removal of rams. Pigeons and doves may be susceptible to albendazole and fen-bendazole toxicity (intestinal crypt epithelial necrosis and bone marrow hypoplasia). Nine alpaca crias receiving albendazole at dosages from 33-100 mg/kg/day once daily for 4 consecutive days developed neutropenia and severe watery diarrhea. All required treatment and 7 of 9 ani-mals treated died or were euthanized secondary to sepsis or multiple organ failure. (Gruntman and Nolen-Walston 2006) In humans, caution is recommended for use in patients with liver or hemato logic diseases. Albendazole was implicated as being an oncogen in 1984, but subsequent studies were unable to demonstrate any oncogenic or carcinogenic activity of the drug. Adverse Effects Albendazole is tolerated without significant adverse effects when dosed in cattle or sheep at recommended dosages. Dogs treated at 50 mg/kg twice daily may develop anorexia. Cats may exhibit clinical signs of mild lethargy, depression, anorexia, and resistance to receiving the medication when albendazole is used to treat Paragonimus. Albendazole has been implicated in causing aplastic anemia in dogs, cats, and humans. Reproductive/Nursing Safety Albendazole has been associated with teratogenic and embry otoxic effects in rats, rabbits and sheep when given early in pregnancy. The manufacturer recommends not administering to female cattle dur-ing the first 45 days of pregnancy or for 45 days after removal of bulls. In sheep, it should not be administered to ewes during the first 30 days of pregnancy or for 30 days after removal of rams. In humans, the FDA categorizes this drug as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) Safety during nursing has not been established. Overdosage/Toxicity Doses of 300 mg/kg (30X recommended) and 200 mg/kg (20X) have caused death in cattle and sheep, respectively. Doses of 45 mg/kg (4. 5X those recommended) did not cause any adverse effects in cattle tested. Cats receiving 100 mg/kg/day for 14-21 days showed signs of weight loss, neutropenia and mental dullness. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving albendazole and may be of significance in veterinary patients: CIm ETIDINE!! : Increased albendazole levels in bile and cystic fluid DEx Am ETHASONE!! : May increase albendazole serum levels PRAz IQUANTEl!! : May increase albendazole serum levels Doses DOg S:T! For Filaroides hirthi infections: a) 50 mg/kg q12h PO for 5 days; repeat in 21 days. Clinical signs may suddenly worsen during therapy, presumably due to a reaction to worm death. (Hawkins, Ettinger, and Suter 1989)b) 25 mg/kg PO q12h for 5 days; may repeat in 2 weeks (also for Oslerus osleri) (Reinemeyer 1995) For Filaroides osleri (also known as Oslerus osleri) infections: a) 9. 5 mg/kg for 55 days or 25 mg/kg PO twice daily for 5 days. Repeat therapy in 2 weeks. (T odd, Paul, and Di Pietro 1985) For Capillaria plica: a) 50 mg/kg q12h for 10-14 days. May cause anorexia. (Brown and Barsanti 1989) For Paragonimus kellicotti: a) 50 mg/kg PO per day for 21 days (Roberson 1988b) b) 30 mg/kg once daily for 12 days (T odd, Paul, and Di Pietro 1985) c) 25 mg/kg PO q12h for 14 days (Reinemeyer 1995) For Giardia:a) 25 mg/kg PO q12h for 4 doses (Barr, Bowman et al. ) b) 25 mg/kg PO twice daily for 5 days (Barr and Bowman 1994) c) 25 mg/kg PO twice daily for 2-5 days (Lappin 2000) For Leishmaniasis: a) 10 mg/kg PO once daily for 30 days or 5 mg/kg PO q6h for 60 days (Greene and Watson 1998) CATS:T! For Paragonimus kellicotti: a) 50 mg/kg PO per day for 21 days (Roberson 1988b) b) 25 mg/kg PO q12h for 10-21 days (Hawkins, Ettinger, and Suter 1989) c) 30 mg/kg once a day for 6 days (T odd, Paul, and Di Pietro 1985) ] d) 25 mg/kg PO q12h for 14 days (Reinemeyer 1995) For Giardia:a) 25 mg/kg PO twice daily for 5 days (Barr and Bowman 1994) b) 25 mg/kg PO q12h for 3-5 days; may cause bone marrow suppression in dogs and cats. (Vasilopulos 2006) For treatment of liver flukes (Platynosum or Opisthorchiidae families): a) 50 mg/kg PO once daily until ova are gone (Taboada 1999) RAbb ITS/RODENTS/Sm All m Amm Al S:T! a) Rabbits: For Encephalitozoon phacoclastic uveitis: 30 mg/kg PO once daily for 30 days, then 15 mg/kg PO once daily for 30 days (Ivey and Morrisey 2000) b) Chinchillas: For Giardia: 50-100 mg/kg PO once a day for 3 days (Hayes 2000) CATTl E:T! For susceptible parasites:a) 10 mg/kg PO (Labeled directions; Valbazen® —Pfizer) b) 7. 5 mg/kg PO; 15 mg/kg PO for adult liver flukes (Roberson 1988b) c) For adult liver flukes: 10 mg/kg PO; best used in fall when the majority are adults (little or no efficacy against immature forms). A second treatment in winter may be beneficial. (Herd 1986b) d) For gastrointestinal cestodes: 10 mg/kg PO (Herd 1986a) SWINE:T! For susceptible parasites: a) 5-10 mg/kg PO (Roberson 1988b) SHEEP & g OATS:T! For susceptible parasites:a) 7. 5 mg/kg PO (0. 75 m L of the suspension per 25 lb. body weight). (Labeled directions; Valbazen® Suspension—Pfizer) b) 7. 5 mg/kg PO; 15 mg/kg PO for adult liver flukes (Roberson 1988b)

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Alb UTEROl SUl FATE 19 c) For adult liver flukes in sheep: 7. 6 mg/kg (Paul 1986) d) For treatment of nematodes in sheep: 3 m L of suspension per 100 lbs of body weight PO (Bulgin 2003) b IRDS:T! a) Ratites: Using the suspension: 1 m L/22 kg of body weight twice daily for 3 days; repeat in 2 weeks. Has efficacy against flagellate parasites and tapeworms. (Jenson 1998) monitoring Efficacy T! Adverse effects if used in non-approved species or at dosages T! higher than recommended Consider monitoring CBC's and liver enzymes (q4-6 weeks) if T! treating long-term (>1 month) Client Information Shake well before administering T! Contact veterinarian if adverse effects occur (T! e. g., vomiting, diar-rhea, yellowish sclera/mucous membranes or skin) Chemistry/Synonyms A benzimidazole anthelmintic structurally related to mebendazole, albendazole has a molecular weight of 265. It is insoluble in water and soluble in alcohol. Albendazole may also be known as. Albendazole may also be known by these synonyms: albendazolum, SKF-62979, Valbazen® or Albenza®; many other trade names are available. Storage/Stability Albendazole suspension should be stored at room tempera-ture (15-30°C); protect from freezing. Shake well before using. Albendazole paste should be stored at controlled room temperature (15-30°C); protect from freezing. Dosage Forms/ Regulatory Status VETERINAR y­l Ab El ED PRODUCTS: Albendazole Suspension: 113. 6 mg/m L (11. 36%) in 500 m L, 1 liter, 5 liters; Valbazen® Suspension (Pfizer); (OTC). Approved for use in cattle (not female cattle during first 45 days of pregnancy or for 45 days after removal of bulls, or of breeding age) and sheep (do not administer to ewes during the first 30 days of pregnancy or for 30 days after removal of rams). Slaughter withdrawal for cattle = 27 days at la beled doses. Slaughter withdrawal for sheep = 7 days at labeled dose. Since milk withdrawal time has not been established, do not use in female dairy cattle of breeding age. ) Albendazole Paste: 30% in 205 g (7. 2 oz); Valbazen® (Pfizer); (OTC). Approved for use in cattle (not female cattle during first 45 days of pregnancy or for 45 days after removal of bulls or of breed-ing age). Slaughter withdrawal = 27 days at labeled doses. Since withdrawal time in milk has not been established, do not use in female dairy cattle of breeding age. HUm AN­l Ab El ED PRODUCTS: Albendazole Tablets: 200 mg; Albenza® (Smith Kline Beecham); (Rx) Albuterol sulf Ate (al-byoo-ter-ole) Salbutamol, Proventil®, Ventolin® beta-adrenergic ag Onist Prescriber Highlights Used primarily as a bronchodilator after PO or inhaled T T dosing Use with caution in patients with cardiac dysrhythmias T T or dysfunction, seizure disorders, hyper tension or hyperthyroidism May be teratogenic (high doses) or delay labor T T Uses/Indications Albuterol is used principally in dogs and cats for its effects on bron-chial smooth muscle to alleviate bronchospasm or cough. It is also used in horses as a bron chodilator. Pharmacology/Actions Like other beta-agonists, albuterol is believed to act by stimulat-ing production of cyclic AMP through activation of adenyl cyclase. Albuterol is considered to be predominantly a beta 2 agonist (relax-ation of bronchial, uterine, and vascular smooth muscles). At usual doses, al buterol possesses minimal beta 1 agonist (heart) activity. Beta-adrenergics can promote a shift of potassium away from the serum and into the cell, perhaps via stimulation of Na +-K+-ATPase. T em porary decreases in either normal or high serum potassium levels are possible. Pharmacokinetics The specific pharmacokinetics of this agent have apparently not been thor oughly studied in domestic animals. In general, albuterol is absorbed rapidly and well after oral ad ministration. Effects oc-cur within 5 minutes after oral inhalation; 30 minutes after oral adminis tration (e. g., tablets). It does not cross the blood-brain bar-rier but does cross the placenta. Duration of effect generally per-sists for 3-6 hours after inhalation and up to 12 hours (depending on dosage form) after oral administration. The drug is extensively metabolized in the liver principally to the inactive metabolite, al-buterol 4'-O-sulfate. After oral administration the serum half-life in humans has been reported as 2. 7-5 hours. Contraindications/Precautions/Warnings Albuterol is contraindicated in patients hy persensitive to it. It should be used with caution in patients with diabetes, hyperthy-roidism, hypertension, seizure disorders, or cardiac disease (espe-cially with concurrent arrhythmias). Use during the late stages of pregnancy may inhibit uterine contractions. Adverse Effects Most adverse effects are dose-related and those that would be ex-pected with sympathomimetic agents including increased heart rate, tremors, CNS excitement (nervousness) and dizziness. These effects are generally transient and mild and usually do not re quire discontinuation of therapy. Decreased serum potassium values may be noted; rarely is potas sium supplementation required. Some cats don't like the “hiss” occurring during actuation of the metered-dose inhaler or the taste of the drug/vehicle.

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20 Alb UTEROl SUl FATE Reproductive/Nursing Safety In very large doses, albuterol is teratogenic in rodents. It should be used (particularly the oral dosage forms) during pregnancy only when the potential benefits outweigh the risks. Like some other beta agonists, it may delay pre-term labor after oral administration. In humans, the FDA categorizes this drug as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) Overdosage/Acute Toxicity Clinical signs of significant overdose after systemic administration (including when dogs bite an aerosol canister) may include: arrhyth-mias (bradycardia, tachycardia, heart block, extrasystoles), hyperten-sion, fever, vomiting, mydriasis, and CNS stimulation. Hypokalemia may also be noted. If recently orally ingested, and if the animal does not have significant cardiac or CNS effects, it should be handled like other overdoses (empty gut, give activated charcoal and a cathartic). If cardiac arrhythmias require treatment, a beta-blocking agent (e. g., atenolol, metoprolol) can be used. The oral LD 50 of albuterol in rats is reported to be greater than 2 g/kg. Contact an animal poison control center for further information. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving albuterol (primarily when albuterol is given orally and not via inhalation) and may be of significance in veterinary patients: b ETA­ADRENERg IC bl OCKINg Ag ENTS !! (e. g., propranolol ): May antago-nize the actions of albuterol DIg Ox IN!! : Albuterol may increase the risk of cardiac arrhythmias INHAl ATION ANESTHETICS !! (e. g., halothane, isoflurane, methoxyflurane ): Albuterol may predispose the patient to ventricular arrhythmias, particularly in patients with preexisting cardiac disease—use cau-tiously OTHER Sym PATHOm Im ETIC Am INES !! : Used with albuterol may increase the risk of developing adverse cardiovascular effects TRICy Cl IC ANTIDEPRESSANTS OR m ONOAm INE Ox IDASE INHIb ITORS !! : May potentiate the vascular effects of albuterol Doses DOg S:T! WARNINg: There are several older references that state that the oral dose is 50 mg/kg q8h. This is an obvious overdose and should not be followed. A more reasonable dose orally in dogs is: 0. 05 mg/kg (50 micrograms/kg) PO q8-12h. a) 0. 05 mg/kg (50 micrograms/kg) PO q8h (Johnson 2000) b) 0. 02 mg/kg PO q12h for 5 days; if no improvement and no adverse effects may increase to 0. 05 mg/kg PO q8-12h. If patient responds, reduce to lowest effective dose. (Church 2003) c) For inhalation, based on a 60 lb dog: 0. 5 m L of the 0. 5% so-lution for nebulization in 4 m L of saline nebulized every 6 hours (Mc Connell and Hughey 1992) CATS:T! a) For bronchodilation in feline asthma using the 90 mcg/puff aerosol albuterol inhaler and an appropriate spacer and mask: For mild symptoms give one puff albuterol as needed with one puff of 110 mcg fluticasone twice daily. Moderate symptoms may be treated with albuterol one puff as needed with a 5 day course of prednisone at 1 mg/kg PO daily, and 220 mcg of fluticasone twice daily. Severely affected cats should be treated on an emergency basis with oxygen, an intravenous dose of a glucocorticoid, 90 mcg (one puff) albuterol every 30 minutes as needed. Chronic therapy should include fluticasone 220 mcg twice daily, 90 mcg albuterol as needed and 1 mg/kg prednisone ev-ery other day. (Dowling 2003b) b) For intermittent (not daily) signs (e. g., wheeze, increased cough or respiratory rate and effort at rest) of feline asthma: two puffs into an appropriate spacer (e. g., Aerokat) twice dai-ly; cat should breathe through the mask and spacer for 7-10 seconds. Positive clinical effect should be seen within 5-10 minutes. Can be used every H hour for 2-4 hours in crisis. (Padrid 2006) HORSES:T! (Note : ARCI UCGFS Class 3 Drug) a) 8 micrograms/kg PO q12h (Enos 1993) b) 2-3 mcg/kg via inhalation using a specially designed mask and spacer (Aeromask® and Aerovent ®) (Foreman 1999) c) For heaves: 0. 8-2 mcg/kg in a metered dose inhaler (Lavoie 2003) d) For short-acting bronchodilation: 450-900 mcg (5-10 puffs) as needed, not to exceed 4 times per week unless in conjunc-tion with a corticosteroid (Mazan 2003) e) For heaves: 360 mcg (4 puffs) inhaled as needed. T olerance develops rapidly if used as a sole therapy. (Rush 2006a) monitoring Clinical symptom improvement; auscultation, blood gases (if T! indi cated) Cardiac rate, rhythm (if warranted) T! Serum potassium, early in therapy if animal is sus ceptible to hy-T! pokalemia Client Information Contact veterinarian if animal's condition deteriorates or it be-T! comes acutely ill. If using the aerosol, shake well before using. Be certain how to ap-T! propriately administer the product to maximize effectiveness. Do not puncture or use near an open flame; do not allow exposure to temperatures greater than 120°F. Keep out of reach of children and pets. Chemistry/Synonyms A synthetic sympathomimetic amine, albuterol sulfate occurs as a white, almost taste less crystalline powder. It is soluble in water and slightly soluble in alcohol. One mg of albuterol is equivalent to 1. 2 mg of albuterol sulfate. Albuterol sulfate may also be known as: salbutamol hemisul-phate, salbutamol sulphate, or salbutamoli sulfas; many trade names are available. Storage/Stability Oral albuterol sulfate products should be stored at 2-30°C. The in-haled aerosol should be stored at room temperature; do not allow exposure to temperatures above 120°F or the canister may burst. The 0. 5% nebs should be stored at room temperature; the 0. 083% nebs should be stored in the refrigerator. Discard solutions if they become colored. Dosage Forms/Regulatory Status VETERINAR y­l Ab El ED PRODUCTS: T! None The ARCI (Racing Commissioners International) has designated this drug as a class 3 substance. See the appendix for more information.

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Al ENDRONATE SODIUm 21 HUm AN­l Ab El ED PRODUCTS: Albuterol Tablets: 2 mg & 4 mg; Proventil ® (Schering); generic; (Rx) Albuterol Extended Release Tablets: 4 mg & 8 mg; Vo Spire® ER (Od-yssey); (Rx) Albuterol Syrup: 2 mg (as sulfate) per 5 m L in 473 m L & 480 m L; Proventil ® (Schering); generic; (Rx) Albuterol Aerosol: Each actualization delivers 90 mcg albuterol in 6. 7g, 6. 8g, 8. 5g, 17g and 18g; Proven til® (Schering); Albuterol HFA ® & Pro Air HFA® (Ivax); Proventil HFA® (Key); Ventolin HFA® (Glaxo Smith Kline); generic; (Rx). Note : At the time or writing (2007), manufacturers of albuterol aerosols are transitioning their products from CFC propellants to ozone-friendly HFA propellants. While these new dosage forms have been shown to be effective, they are not considered generically equivalent to the CFC-containing products. Dosage adjustments may be required. Albuterol Solution for Inhalation (“Nebs”): 0. 021% preservative-free (0. 63 mg (as sulfate)/3m L), 0. 042% preservative-free (1. 25 mg (as sulfate)/3 m L), 0. 083% (2. 5 mg (as sulfate)/3 m L) and 0. 5% (5 mg (as sulfate)/m L) in 0. 5 m L vials, 3 m L UD vials or 20 m L; Proventil ® (Schering); Accu Neb® (Dey); generic; (Rx) Also available: 14. 7 g aerosol metered dose inhaler containing 18 mcg ipratropium bromide (an inhaled anticholinergic) and 103 mcg albuterol sulfate per puff; Combivent® (B-I); (Rx) and 3 m L unit dose solution for inhalation (neb) containing 0. 5 mg ipratro-pium bromide and 3 mg albuterol, Duo Neb® (Dey); (Rx) Alendron A te sodium (a-len-droe-nate) Fosamax® Oral bisph Osph Onate b One res Orpti On inhibit Or Prescriber Highlights Orally dosed bisphosphonate that reduces osteoclastic T T bone resorption Potentially useful for refractory hypercalcemia, FORLs, T T osteosarcoma Very limited clinical experience with use of this drug in T T animals; adverse effect profile, dosages, etc. may signifi-cantly change with more experience & clinical research Potentially can cause esophageal erosions; risks are not T T clear for dogs or cats Accurate dosing may be difficult & bioavailability is ad-T T versely affected by food, etc. Cost may be an issue T T Uses/Indications Alendronate use in small animals has been limited, but it may prove useful for treating refractory hypercalcemia in dogs or cats, feline odontoclastic resorptive lesions (FORLs), and as an osteosarcoma treatment adjuvant. Pharmacology/Actions Alendronate, like other bisphosphonates, inhibits osteoclastic bone resorption by inhibiting osteoclast function after binding to bone hydroxyapatite. Secondary actions that may contribute to therapeu-tic usefulness in osteogenic neoplasms include promoting apopto-sis and inhibiting osteoclastogenesis, angiogenesis and cancer cell proliferation. Pharmacokinetics Specific pharmacokinetic values are limited for dogs and appar-ently unavailable for cats. Oral bioavailability in all species studied is less than 2%. In humans, alendronate sodium has very low oral bioavailability (<1%) and the presence of food can reduce bioavail-ability further to negligible amounts. In women, taking the medi-cation with coffee or orange juice reduced bioavailability by 60% when compared to plain water. Absorbed drug is rapidly distributed to bone or excreted into the urine. The drug is reportedly not highly plasma protein bound in dogs, but it is in rats. Alendronate apparently accumulates on sub-gingival tooth surfaces and bordering alveolar bone. Plasma con-centrations are virtually undetectable after therapeutic dosing. Alendronate is not metabolized and drug taken up by bone is very slowly eliminated. It is estimated that the terminal elimination half-life in dogs is approximately 1000 days and, in humans, ap-proximately 10 years, however once incorporated into bone, alen-dronate is no longer active. Contraindications/Precautions/Warnings Alendronate is contraindicated in human patients with esopha-geal abnormalities (e. g., strictures, achalasia) that cause delayed esophageal emptying and those who cannot stand or sit upright for 30 minutes after administration. At present, it is not believed that small animal patients need to remain upright after administration. Because of a lack of experience, the drug is not recommended for use in human patients with severe renal dysfunction (Cr Cl <35 m L/min). Alendronate should not be used in patients who have demon-strated hypersensitivity reactions to it. Alendronate use in small animals should be considered inves-tigational at this point. Limited research and experience, dosing questions, risks of esophageal irritation or ulcers, and medication expense all are potential hindrances to its therapeutic usefulness. Adverse Effects Little information on the specific adverse effect profile for dogs or cats is published. In humans, alendronate can cause upper GI ir-ritation and erosions. Anecdotal reports of GI upset, vomiting and inappetance have been reported in dogs receiving the drug. It has been suggested that after administration, walking or playing with the dog for 30 minutes may reduce the incidence of esophageal problems. In cats, buttering the lips after administration to induce salivation and reduce esophageal transit time has been suggested. Other potential adverse effects of concern include jaw osteone-crosis and musculoskeletal pain. Reproductive/Nursing Safety Alendronate at dosages of 2 mg/kg in rats caused decreased post-implantation survival rates and at 1 mg/kg caused decreased weight gain in healthy pups. Higher dosages (10 mg/kg) caused incomplete fetal ossification of several bone types. In humans, the FDA catego-rizes alendronate as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no ad-equate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) While it is unknown if alendronate enters maternal milk, it would be unexpected that measurable quantities would be found in milk or enough would be absorbed in clinically significant amounts in nursing offspring.

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22 Al FENTANIl HCl Overdosage/Acute Toxicity No lethality was observed in dogs receiving doses of up to 200 mg/ kg. Lethality in mice and rats was seen at dosages starting at 966 mg/kg and 552 mg/kg, respectively. Observed adverse effects associated with overdoses included hypocalcemia, hypophosphatemia, and up-per GI reactions. A recently ingested overdose should be treated with orally ad-ministered antacids or milk to bind the drug and reduce absorption. Do not induce vomiting. Monitor serum calcium and phosphorus and treat supportively. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving alendronate and may be of significance in veterinary patients: ASPIRIN!! : Increased risk of upper GI adverse effects CAl CIUm­CONTAININg ORAl PRODUCTS !! or FOOD : Likely to significantly decrease oral bioavailability of alendronate RANITIDINE !! (IV): increased oral alendronate bioavailability two-fold in a human study NSAIDS!! : Humans taking NSAIDs with alendronate had no higher rates of GI adverse reactions than when NSAIDs were used with placebo laboratory Considerations No specific laboratory concerns or interactions have been noted. Doses DOg S:T! a) For refractory hypercalcemia: 0. 5-1 mg/kg PO once daily (Davies 2005) CATS:T! a) For feline odontoclastic resorptive lesions (FORLs): 3 mg/kg PO q12h (Gores 2004) Note : Use for this indication in cats is at present very controversial. (Plumb 2006) b) For idiopathic hypercalcemia (after dietary change has been attempted): Initially 2 mg/kg PO once weekly. Most cats re-spond to 10 mg (total dose). Administer at least 6 m L of water after administration and butter the lips to increase salivation and increase transit. If efficacious, effects usually seen in 3-4 weeks. Monitor via serum ionized calcium. (Chew and Green 2006) monitoring Serum calcium (ionized)T! GI adverse effects. T! Note : Depending on diagnosis (e. g., hypercalce-mia, adjunctive treatment of osteogenic sarcomas, or FORLs) oth-er monitoring of serum electrolytes (total calcium, phosphorus, potassium sodium) or disease-associated signs may be required Client Information Inform clients of the “investigational” nature with using this drug T! in small animals Potentially can cause esophageal erosions; risks are not clear for T! dogs or cats. Be sure adequate liquid is consumed after dosage and, ideally, do not feed for at least 30 minutes after dosing. See Adverse Effects for suggestions to minimize risks in dogs and cats. Chemistry/Synonyms Alendronate sodium is a synthetic analog of pyrophosphonate with the chemical name: (4-amino-1-hydroxy-1-phosphono-butyl) phosphonic acid. One mg is soluble in one liter of water. Alendronate may also be known as: Alendronic acid, Acide Alendronique, Acido Alendronico, Acidum Alendronicum, Adronat®, Alendros®, Arendal®, Onclast® or Fosamax®. Storage/Stability Alendronate tablets should be stored in well-closed containers at room temperature. The oral solution should be stored at room tem-perature; do not freeze. Dosage Forms/Regulatory Status VETERINAR y PRODUCTS: None HUm AN PRODUCTS: Alendronate Sodium Tablets: 5 mg, 10 mg, 35 mg, 40 mg, & 70 mg (as base): Fosamax® (Merck); (Rx) Alendronate Oral Solution: 70 mg (as base) in 75 m L; raspberry fla-vor; Fosamax® (Merck); (Rx) Alfent Anil hcl (al-fen-ta-nil) Alfenta® Opiate anesthetic adjunct Prescriber Highlights Injectable, potent opiate that may be useful for adjunc-T T tive anesthesia, particularly in cats Marginal veterinary experience & little published data T T available to draw conclusions on appropriate usage in veterinary species Dose-related respiratory & CNS depression are the most T T likely adverse effects seen Dose may need adjustment in geriatric patients & those T T with liver disease Class-II controlled substance; relatively expensive T T Uses/Indications An opioid analgesic, alfentanil may be useful for anesthesia, analge-sia, or sedation similar to fentanyl; fentanyl is generally preferred be-cause of the additional experience with its use in veterinary patients and cost. Alfentanil may be particularly useful in cats as adjunctive therapy during anesthesia to reduce other anesthetic (i. e., propofol or isoflurane) concentrations. Pharmacology/Actions Alfentanil is a potent mu opioid with the expected sedative, analge-sic, and anesthetic properties. When comparing analgesic potencies after IM injection, 0. 4-0. 8 mg of alfentanil is equivalent to 0. 1-0. 2 mg of fentanyl and approximately 10 mg of morphine. Pharmacokinetics The pharmacokinetics of alfentanil have been studied in the dog. The drug's steady state volume of distribution is about 0. 56 L/kg, clearance is approximately 30 m L/kg/minute, and the terminal half-life is approximately 20 minutes. In humans, onset of anesthetic action occurs within 2 minutes after intravenous dosing, and within 5 minutes of intramuscular in-jection. Peak effects occur approximately 15 minutes after IM injec-tion. The drug has a volume of distribution of 0. 4-1 L/kg. About 90% of the drug is bound to plasma proteins. Alfentanil is primarily metabolized in the liver to inactive metabolites that are excreted by

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Al FENTANIl HCl 23 the kidneys into the urine; only about 1% of the drug is excreted unchanged into the urine. T otal body clearance in humans ranges from 1. 6-17. 6 m L/minute/kg. Clearance is decreased by about 50% in patients with alcoholic cirrhosis or in those that are obese. Clearance is reduced by approximately 30% in geriatric patients. Elimination half-life in humans is about 100 minutes. Contraindications/Precautions/Warnings Alfentanil is contraindicated in patients hypersensitive to opioids. Because of the drug's potency and potential for significant adverse effects, it should only be used in situations where patient vital signs can be continuously monitored. Initial dosage reduction may be required in geriatric or debilitated patients, particularly those with diminished cardiopulmonary function. Adverse Effects Adverse effects are generally dose related and consistent with other opiate agonists. Respiratory depression, and CNS depression are most likely to be encountered. In humans, bradycardia that is usu-ally responsive to anticholinergic agents can occur. Dose-related skeletal muscle rigidity is not uncommon and neuromuscular blockers are routinely used. Alfentanil has rarely been associated with asystole, hypercarbia and hypersensitivity reactions. Respiratory or CNS depression may be exacerbated if alfentanil is given with other drugs that can cause those effects. Reproductive/Nursing Safety In humans, the FDA categorizes alfentanil as a category C drug for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans). If alfentanil is administered systemically to the mother close to giv-ing birth, offspring may show behavioral alterations (hypotonia, depression) associated with opioids. Although high dosages given for 10-30 days to laboratory animals have been associated with embryotoxicity, it is unclear if this is a result of direct effects of the drug or as a result of maternal toxicity secondary to reduced food and water intake. The effects of alfentanil on lactation or its safety for nursing off-spring is not well defined, but it is unlikely to cause significant ef-fects when used during anesthetic procedures in the mother. Overdosage/Acute Toxicity Intravenous, severe overdosages may cause circulatory collapse, pulmonary edema, seizures, cardiac arrest and death. Less severe overdoses may cause CNS and respiratory depression, coma, hy-potension, muscle flaccidity and miosis. Treatment is a combina-tion of supportive therapy, as necessary, and the administration of an opiate antagonist such as naloxone. Although alfentanil has a relatively rapid half-life, multiple doses of naloxone may be neces-sary. Because of the drug's potency, the use of a tuberculin syringe to measure dosages less than 1 m L with a dosage calculation and measurement double-check system, are recommended. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving alfentanil and may be of significance in veterinary patients: DRUg S THAT INHIb IT HEPATIC ISOENzym E Cy P3A4 !!, such as erythromy­ cin, cimetidine, ketoconazole, itraconazole, fluconazole or diltiazem : May increase the half-life and decrease the clearance of alfentanil leading to prolonged effect and an increased risk of respiratory depression D!!RUg S THAT DEPRESS CARDIAC FUNCTION OR REDUCE VAg Al TONE, such as beta­blockers or other anesthetic agents : May produce bra-dycardia or hypotension if used concurrently with alfentanil laboratory Considerations Patients receiving opiates may T! have increased plasma levels of amy­ lase or lipase secondary to increased biliary tract pressure. Values may be unreliable for 24 hours after administration of alfentanil. Doses (Note : in very obese patients, figure dosages based upon lean body weight. ) DOg S:T! As a premed: a) 5 mcg/kg alfentanil with 0. 3-0. 6 mg of atropine IV 30 sec-onds before injecting propofol can reduce the dose of propo-fol needed to induce anesthesia to 2 mg/kg, but apnea may still occur. (Hall, Clarke et al. 2001b) As an analgesic supplement to anesthesia: a) 2-5 mcg/kg IV q20 minutes. (Hall, Clarke et al. 2001b), (Hall, Clarke et al. 2001a) b) For intra-operative analgesia in patients with intracranial disease: 0. 2 mcg/kg/minute (Raisis 2005) monitoring Anesthetic and/or analgesic efficacy T! Cardiac and respiratory rate T! Pulse oximetry or other methods to measure blood oxygenation T! when used for anesthesia Client Information Alfentanil is a potent opiate that should only be used by pro-T! fessionals in a setting where adequate patient monitoring is available Chemistry/Synonyms A phenylpiperidine opioid anesthetic-analgesic related to fenta-nyl, alfentanil HCl occurs as a white to almost white powder. It is freely soluble in alcohol, water, chloroform or methanol. The com-mercially available injection has a p H of 4-6 and contains sodium chloride for isotonicity. Alfentanil is more lipid soluble than mor-phine, but less so than fentanyl. Alfentanil may also be known as: alfentanyl, Alfenta®, Fanaxal®, Fentalim®, Limifen®, or Rapifen®. Storage/Stability/Compatibility Alfentanil injection should be stored protected from light at room temperature. In concentrations of up to 80 mcg/m L, alfentanil in-jection has been shown to be compatible with Normal Saline, D5 in Normal Saline, D5W, and Lactated Ringers. Dosage Forms/Regulatory Status VETERINAR y­l Ab El ED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 1 substance. See the appendix for more information. HUm AN­l Ab El ED PRODUCTS: Alfentanil HCl for injection: 500 mcg/m L in 2 m L, 5 m L, 10 m L, and 20 m L amps; preservative free; Alfenta® (Akorn); Alfentanil HCl (Abbott); (Rx, C-II).

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24 All OPURINOl Allopurinol (al-oh-pyoor-i-nol) Zyloprim® Xanthine O Xidase inhibit Or; purine anal Og Prescriber Highlights Used as a uric acid reducer in dogs, cats, reptiles & birds T T & as an alternative treatment Leishmaniasis & Trypano-somiasis in dogs Use with caution (dosage adjustment may be required) in T T patients with renal or hepatic dysfunc tion Contraindicated in red-tailed hawks & should be used T T with caution, if at all, in other raptors Diet may need to be adjusted to lower purine T T GI effects are most likely adverse effects, but hypersensi-T T tivity, hepatic & renal effects can occur Many potential drug interactions T T Uses/Indications The principle veterinary uses for allopurinol are for the prophylactic treatment of recurrent uric acid uroliths and hyperuricosuric cal-cium oxalate uroliths in small animals. It has also been used in an attempt to treat gout in pet birds and reptiles. Allopurinol has been recommended as an alternative treatment for canine Leishmaniasis. Al though it appears to have clinical efficacy, it does not apparently clear the parasite in most dogs at usual dosag-es. Allopurinol may also be useful for American Trypanosomiasis. Pharmacology/Actions Allopurinol and its metabolite, oxypurinol, inhibit the enzyme xan-thine oxidase. Xanthine oxidase is responsible for the conversion of oxypurines (e. g., hypoxanthine, xanthine) to uric acid. Hepatic microsomal enzymes may also be inhibited by allopurinol. It does not increase the renal excretion of uric acid nor does it possess any antiinflammatory or analgesic activity. Allopurinol is metabolized by Leishmania into an inactive form of inosine that is incorporated into the organism's RNA leading to faulty protein and RNA synthesis. Allopurinol, by inhibiting xanthine oxidase, can inhibit the for-mation of superoxide anion radi cals, thereby providing protection against hemorrhagic shock and myocardial ischemia in laboratory conditions. The clinical use of the drug for these indications requires further study. Pharmacokinetics In Dalmatians, absorption rates were variable between subjects. Peak levels occur within 1-3 hours after oral dosing. Elimination half-life is about 2. 7 hours. In dogs (not necessarily Dalmatians), the serum half-life of allopurinol is approximately 2 hours and for oxipurinol, 4 hours. Food does not appear to alter the absorption of allopurinol in dogs. In horses, oral bioavailability of allopurinol is low (approximate-ly 15%). Allopurinol is rapidly converted to oxypurinol in the horse as the elimination half-life of allopurinol is approximately 5-6 min-utes. Oxypurinol has an elimination half-life of about 1. 1 hours in the horse. In humans, allopurinol is approximately 90% absorbed from the GI tract after oral dosing. Peak levels after oral allopurinol adminis-tration occur 1. 5 and 4. 5 hours later, for allopurinol and oxypurinol, respectively. Allopurinol is distributed in total body tissue water but levels in the CNS are only about 50% of those found elsewhere. Neither al-lopurinol nor oxypurinol are bound to plasma proteins, but both drugs are excreted into milk. Xanthine oxidase metabolizes allopurinol to oxypurinol. In humans, the serum half-life for allopurinol is 1-3 hours and for oxypurinol, 18-30 hours. Half-lives are in creased in patients with diminished renal function. Both allopurinol and oxypurinol are dia-lyzable. Contraindications/Precautions/Warnings Allopurinol is contraindicated in patients who are hypersensitive to it or have previously developed a severe reaction to it. It should be used cautiously and with intensified monitoring in patients with impaired hepatic or renal function. When used in patients with re-nal in sufficiency, dosage reductions and increased monitoring are usually warranted. Red-tailed hawks appear to be sensitive to the effects of al-lopurinol. Doses at 50 mg/kg PO once daily caused clinical signs of vomiting and hyperuricemia with renal dysfunction. Doses of 25 mg/kg PO once daily were safe but not effective in reducing plasma uric acid. Adverse Effects Adverse effects in dogs are apparently uncommon with allopurinol when fed low purine diets. There has been one report of a dog de-veloping hemolytic anemia and trigeminal neuropathy while receiv-ing allopurinol. Xanthine coatings have formed around ammonium urate uroliths in dogs that have been fed diets containing purine. If the drug is required for chronic therapy, reduction of purine precur-sors in the diet with dosage reduction should be considered. Several adverse effects have been reported in humans including GI dis tress, bone marrow suppression, skin rashes, hepatitis, and vasculitis. Human patients with renal dys function are at risk for fur-ther decreases in renal function and other severe adverse effects un-less dosages are reduced. Until further studies are performed in dogs with decreased renal function, the drug should be used with caution and at reduced dosages. Reproductive/Nursing Safety While the safe use of allopurinol during pregnancy has not been established, dosages of up to 20 times normal in rodents have not demonstrated decreases in fertility. Infertility in males (humans) has been reported with the drug, but a causal effect has not been firmly established. In humans, the FDA categorizes this drug as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) Allopurinol and oxypurinol may be excreted into milk; use cau-tion when allopurinol is administered to a nursing dam. Overdosage/Acute Toxicity Vomiting is common in dogs at doses >100 mg/kg per the APCC database. A human ingesting 22. 5 grams did not develop serious toxicity. The oral LD50 in mice is 78 mg/kg. There were 27 exposures to allopurinol reported to the ASPCA Animal Poison Control Center (APCC; www. apcc. aspca. org) dur-ing 2005-2006. In these cases 25 were dogs with 2 showing clini-cal signs; the remaining 2 reported cases were cats that showed no clinical signs. Common findings recorded in decreasing frequency included vomiting and tachycardia.

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All OPURINOl 25 Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving allopurinol and may be of significance in veterinary patients: Am INOPHyll INE !! or THEOPHyll INE : Large doses of allopurinol may decrease metabolism thereby increasing their serum levels Am Ox ICIll IN !! or Am PICIll IN : In humans, concomitant use with al-lopurinol has been im plicated in increased occurrences of skin rashes; the veterinary significance of this interaction is un known Az ATHIOPRINE !! or m ERCAPTOPURINE : Allopurinol may inhibit me-tabolism and increase toxicity; if concurrent use is necessary, dosages of the antineoplastic/immunosuppressive agent should be reduced initially to 25-33% of their usual dose and then ad-justed, dependent upon patient's response CHl ORPROPAm IDE!! : Allopurinol may increase risks for hypoglyce-mia and hepato-renal reactions Cy Cl OPHOSPHAm IDE!! : Increased bone marrow depression may oc-cur in patients receiving both allop urinol and cyclophosphamide Cy Cl OSPORINE!! : Allopurinol may increase cyclosporine levels DIURETICS!! (Furosemide, Thiazides, Diazoxide, and Alcohol ): Can in-crease uric acid levels ORAl ANTICOAg Ul ANTS!! (e. g., Warfarin ): Allopurinol may reduce the metabolism of warfarin thereby increasing effect TRIm ETHOPRIm/SUl FAm ETHOx Az Ol E!! : In a few human patients, thrombocytopenia has occurred when used with allopurinol URICOSURIC Ag ENTS!! (e. g., Probenecid, Sulfinpyrazone ): May increase the renal excretion of oxypuri nol and thereby reduce xanthine oxidase inhibition; in treating hyperuricemia the additive effects on blood uric acid may, in fact, be beneficial to the patient URINAR y ACIDIFIERS!! (e. g., methionine, Ammonium Chloride ) May re-duce the solubility of uric acid in the urine and induce urolithiasis Doses DOg S:T! For urate uroliths:a) 7-10 mg/kg PO three times daily for both dissolution and prevention. Goal is to reduce urine urate:creatinine ratio by 50%. (Senior 1989) b) For dissolution: 15 mg/kg PO q12h; only in conjunction with low purine foods. For prevention: 10-20 mg/kg/day; because prolonged high doses of allopurinol may result in xanthine uroliths, it may be preferable to minimize recurrence with dietary therapy, with the option of treating infrequent episodes of urate uro-lith formation with dissolution protocols. (Osborne, Lulich et al. 2003a) c) Alkalinize urine to a p H of 6. 5-7 (see sodium bicarbonate monograph), give low purine diet and eliminate any UTI. Al-lopurinol at 10 mg/kg three times daily for the first month, then 10 mg/kg once daily thereafter. Reduce dose in patients with renal failure. (Polzin and Os borne 1985), (Lage, Polzin, and Zenoble 1988) For Leishmaniasis: a) 15 mg/kg PO twice daily for months (Lappin 2000) b) If possible use with meglumine antimoniate, if not, use al-lopurinol alone at 10 mg/kg PO twice daily. If animal has re-nal insufficiency, use at 5 mg/kg PO twice daily. (Font 1999) c) Meglumine antimoniate (100 mg/kg/day SQ) until resolu-tion, with allopurinol at 20 mg/kg PO q12h for 9 months. An alternate protocol using allopurinol alone: allopurinol 10 mg/kg PO q8h or 10-20 mg/kg PO q12h for 1-4 months. (Brosey 2005) CATS:T! For urate uroliths: a) 9 mg/kg PO per day (Schultz 1986) b IRDS:T! For gout:a) In budgies and cockatiels: Crush one 100 mg tablet into 10 m L of water. Add 20 drops of this solution to one ounce of drinking water. (Mc Donald 1989) b) For parakeets: Crush one 100 mg tablet into 10 m L of water. Add 20 drops of this solution to one ounce of drinking water or give 1 drop 4 times daily. (Clubb 1986) REPTIl ES:T! a) For elevated uric acid levels in renal disease in lizards: 20 mg/kg PO once daily (de la Navarre 2003a) b) For gout: 20 mg/kg PO once daily. Suggested dosage based upon human data as dose is not established for reptiles. (Johnson-Delaney 2005d) monitoring Urine uric acid (for urolithiasis) T! Adverse effects T! Periodic CBC, liver and renal function tests (T! e. g., BUN, Creati-nine, liver enzymes); espe cially early in therapy Client Information Unless otherwise directed, administer after meals (usually 1 hour T! or so). No tify veterinarian if animal develops a rash, becomes le-thargic or ill. Chemistry/Synonyms A xanthine oxidase inhibitor, allopurinol occurs as a tasteless, fluffy white to off-white powder with a slight odor. It melts above 300° with decomposition and has an apparent p K a of 9. 4. Oxypurinol (aka oxipurinol, alloxanthine), its active metabolite, has a p K a of 7. 7. Allopuri nol is only very slightly soluble in both water and alcohol. Allopurinol may also be known as: allopurinolum, BW-56-158, HPP, or NSC-1390; many trade names are available. Storage/Stability/Compatibility Allopurinol tablets should be stored at room temperature in well-closed containers. The drug is stated to be stable in both light and air. The powder for injection should be stored at 25°C; may be ex-posed to 15-30°C. Once diluted to a concentration ≤ 6 mg/m L, store at room temperature and use within 10 hours; do not refriger-ate. Compatible IV solutions include D5W and normal saline. An extemporaneously prepared suspension containing 20 mg/ m L allopurinol for oral use can be prepared from the commercially available tablets. Tablets are crushed and mixed with an amount of Cologel® suspending agent equal to N the final volume. A mixture of simple syrup and wild cherry syrup at a ratio of 2:1 is added to produce the final volume. This preparation has been reported to be stable for at least 14 days when stored in an amber bottle at either room temperature or when refrigerated. Dosage Forms/Regulatory Status VETERINAR y­l Ab El ED PRODUCTS: None HUm AN­l Ab El ED PRODUCTS: Allopurinol Tablets: 100 mg & 300 mg; Zyloprim® (Glaxo Well-come); generic; (Rx) Allopurinol Powder for Injection: 500 mg preservative-free in 30 m L vials; Aloprim® (Nabi); Allopurinol Sodium (Bedford Labs); (Rx)

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26 Al PRAz Ol Am Alpr Azol Am (al-prah-zoe-lam) Xanax® benz Odiazepine sedative/tranquilizer Prescriber Highlights Oral benzodiazepine that may be useful for unwanted T T behaviors in dogs or cats Contraindications: Aggressive animals (controversial), T T benzodiazepine hypersensitivity Caution: Hepatic or renal disease T T Adverse Effects: Sedation, behavior changes, & contradic-T T tory responses; physical depen dence is a possibility; may impede training C-IV controlled substance T T Uses/Indications Alprazolam may be useful for adjunctive therapy in anxious, aggres-sive dogs or in those demonstrating panic reactions. ( Note : Some cli-nicians believe that benzodiazepines are contraindicated in aggres-sive dogs as anxiety may actually restrain the animal from aggressive tendencies). It may be useful in cats to treat anxiety disorders. Alprazolam may have less effect on motor function at low doses than does diazepam. Pharmacology/Actions Subcortical levels (primarily limbic, thalamic, and hypothalamic) of the CNS are depressed by alprazolam and other benzodiazepines thus producing the anxiolytic, sedative, skeletal muscle relaxant, and anticonvulsant effects seen. The exact mechanism of action is un known, but postulated mechanisms include: antagonism of se-rotonin, increased release of and/or fa cilitation of gamma-amin-obutyric acid (GABA) activity, and diminished release or turnover of acetylcholine in the CNS. Benzodiazepine specific receptors have been located in the mammalian brain, kidney, liver, lung, and heart. In all species studied, receptors are lacking in the white matter. Pharmacokinetics The pharmacokinetics of alprazolam have not been described for either dogs or cats. In humans, alprazolam is well absorbed and is characterized as having an inter mediate onset of action. Peak plasma levels occur in 1-2 hours. Alprazolam is highly lipid soluble and widely distributed throughout the body. It readily crosses the blood-brain barrier and is somewhat bound to plasma proteins (80%). Alprazolam is metabolized in the liver to at least two metabolites, including alpha-hydroxy-alprazo lam which is pharmacologically active. Elimination half-lives range from 6-27 hours in people. Contraindications/Precautions/Warnings Some clinicians believe that benzodi azepines are contraindicated in aggressive dogs as anxiety may actually restrain the animal from ag-gressive tendencies. This remains controversial. Alprazolam is con-traindicated in patients with known hy persensitivity to the drug. Use cautiously in patients with hepatic or renal disease, narrow an-gle glaucoma and debilitated or geriatric patients. Benzodiazepines may impair the abilities of working animals. Adverse Effects Benzodiazepines can cause sedation, increased appetite, and tran-sient ataxia. Cats may exhibit changes in be havior (irritability, in-creased affection, depression, aberrant demeanor) after receiving benzodi azepines. Dogs may rarely exhibit a contradictory response (CNS excite-ment) following administration of benzodiazepines. Chronic usage of benzodiazepines may induce physical depen-dence. Animals appear to be less likely than humans to develop physical dependence. Benzodiazepines may impede the ability of the animal to learn and may retard training. Reproductive/Nursing Safety Diazepam and other benzodiazepines have been implicated in caus-ing congenital abnormalities in humans if administered during the first trimester of pregnancy. Infants born of mothers receiving large doses of benzodiazepines shortly before delivery have been reported to suffer from apnea, im paired metabolic response to cold stress, dif-ficulty in feeding, hyperbilirubinemia, hypotonia, etc. Withdrawal symptoms have occurred in infants whose mothers chronically took benzodiazepines during pregnancy. The veterinary significance of these effects is unclear, but the use of these agents during the first trimester of pregnancy should only occur when the benefits clearly outweigh the risks associated with their use. In humans, the FDA categorizes this drug as category D for use during pregnancy (There is evidence of human fetal risk, but the potential benefits from the use of the drug in pregnant women may be acceptable despite its potential risks. ) Overdosage/Acute Toxicity When administered alone, alprazolam overdoses are generally lim-ited to significant CNS depression (confusion, coma, decreased re-flexes, etc. ). Hypotension, respiratory depression, and cardiac arrest have been reported in human patients but apparently, are quite rare. The reported LD50 in rats for alprazolam is >330 mg/kg, but cardiac arrest occurred at doses as low as 195 mg/kg. There were 935 exposures to alprazolam reported to the ASPCA Animal Poison Control Center (APCC; www. apcc. aspca. org) during 2005-2006. In these cases 863 were dogs with 208 showing clinical signs, 63 were cats with 20 showing clinical signs, 3 were rodents with 1 reported as having clinical signs, and 2 cases were rabbits with 1 reported as having clinical signs. Common findings in dogs recorded in decreasing frequency included ataxia, lethargy, hyperac-tivity, disorientation, depression. Common findings in cats recorded in decreasing frequency included ataxia disorientation, sedation, hy-peractivity and restlessness. Common findings in rodents recorded in decreasing frequency included ataxia, somnolence and vomiting. Common findings in lagomorphs recorded in decreasing frequency included ataxia and lethargy. Treatment of acute toxicity consists of standard protocols for re-moving and/or binding the drug in the gut if taken orally and sup-portive systemic measures. Flumazenil (see separate monograph) may be employed to reverse the sedative effects of alprazolam, but only if the patient has significant CNS or respiratory depression. Seizures may be precipitated in patients physically dependent. The use of analeptic agents (CNS stimulants such as caffeine) is generally not recommended. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving alprazolam and may be of significance in veterinary patients:

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Al TRENOg EST 27 ANTACIDS!! : May slow the rate, but not the extent of oral absorption of alprazolam; administer 2 hours apart to avoid this potential interaction CNS DEPRESSANT Ag ENTS !! (barbiturates, narcotics, anesthetics, etc. ): Additive effects may occur DIg Ox IN!! : Serum levels may be increased; monitor serum digoxin levels or clinical signs of toxicity Fl UOx ETINE, Fl UVOx Am INE!! : Increased alprazolam levels HEPATICAlly m ETAb Ol Iz ED DRUg S !! (e. g., cimetidine, erythromycin, iso­ niazid, ketoconazole, itracona zole): Metabolism of alprazolam may be decreased and excessive sedation may occur RIFAm PIN:!! May induce hepatic microsomal enzymes and decrease the pharmacologic effects of ben zodiazepines TRICy Cl IC ANTIDEPRESSANTS!! (e. g., amitriptyline, clomipramine, imip­ ramine ): Alprazolam may increase levels of these drugs; clinical significance is not known and some state that clomipramine and alprazolam together may improve efficacy for phobias (e. g., thunderstorm phobia) Doses DOg S:T! a) For treatment of canine anxiety disorders: 0. 01-0. 1 mg/kg PO as needed for panic, not to exceed 4 mg/dog/day. Start with 1-2 mg (total dose) for a medium-sized dog. (Overall 1997) b) For separation anxiety: 0. 25 mg-2 mg (total dose) once daily to three times daily PO. (Hunthausen 2006) c) For storm phobias: 0. 02-0. 4 mg/kg PO q4h as needed; helps to minimize impact of experiencing a severe storm (Crowell-Davis 2003c); 0. 02 mg/kg PO as needed one hour before anticipated storm and every 4 hours as needed; used as an adjunct after behav-ior modification and prior clomipramine treatment (see clo-mipramine monograph for further information) (Crowell-Davis 2003d) d) For phobias, night waking: 0. 01-0. 1 mg/kg or 0. 25-2 mg (total dose) per dog PO q6-12h PO (Siebert 2003c) CATS:T! a) For treatment of feline anxiety disorders: 0. 125-0. 25 mg/kg PO q12h (Start at 0. 125 mg/kg PO) (Overall 1997) b) For refractory house soiling: 0. 1 mg/kg or 0. 125-0. 25 mg (total dose) per cat PO q8-12h (Siebert 2003c) c) For urine marking: 0. 05-0. 2 mg/kg PO q12-24h (Virga 2002) d) For fears/phobias/anxieties: 0. 125-0. 25 mg (total dose) PO once to three times a day. (Landsberg 2005a) monitoring Efficacy T! Adverse Effects T! Consider monitoring hepatic enzymes particularly when treating T! cats chronically Client Information Try to dose approximately one hour in advance of storms or oth-T! er anticipated stimuli that evokes negative responses If difficulty with pilling the medication occurs, consider using the T! orally-disintegrating tablets; hands must be dry before handling If excessive sedation or yellowing of the whites of eyes (especially T! in cats) occurs, contact veterinarian Chemistry/Synonyms A benzodiazepine, alprazolam occurs as a white to off-white, crys-talline powder. It is soluble in alcohol and insoluble in water. Alprazolam may also be known as D65 MT, U 31889, or alprazo-lamum; many trade names available internationally. Storage/Stability Alprazolam tablets should be stored at room temperature in tight, light-resistant containers. The orally disintegrating tablets should be stored at room temperature and protected from moisture. Dosage Forms/Regulatory Status VETERINAR y­l Ab El ED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 2 substance. See the appendix for more information. HUm AN­l Ab El ED PRODUCTS: Alprazolam Tablets: 0. 25 mg, 0. 5 mg, 1 mg & 2 mg; Xanax® (Pfizer); generic; (Rx; C-IV) Alprazolam Extended-release Tablets: 0. 5 mg, 1 mg, 2 mg, & 3 mg; Xanax XR® (Pfizer); generic; (Rx; C-IV) Alprazolam Orally Disintegrating Tablets: 0. 25 mg, 0. 5 mg, 1 mg, & 2 mg; Niravam® (Pfizer); (Rx; C-IV) Alprazolam Oral Solution: 1 mg/m L in 30 m L; Alprazolam Inten-sol® (Roxane); (Rx; C-IV) Altrenogest (al-tre-noe-jest) Regu-Mate®, Matrix® Oral pr Ogestin Prescriber Highlights Progestational drug used in horses to suppress estrus T T or maintain pregnancy when progestin deficient; used in swine to synchronize estrus May be used in dogs for luteal deficiency or as a treat-T T ment to prevent premature delivery Many “handling” warnings for humans (see below) T T Very sensitive to light T T Uses/Indications Altrenogest (Regu-Mate®) is indicated (labeled) to suppress estrus in mares to allow a more predictable occurrence of estrus following withdrawal of the drug. It is used clinically to assist mares to es-tablish normal cycles during the transitional period from anestrus to the normal breeding season often in conjunction with an artifi-cial photoperiod. It is more effective in assisting in pregnancy at-tainment later in the transition period. Some authors (Squires et al. 1983) suggest selecting mares with considerable follicular activ-ity (mares with one or more follicles 20 mm or greater in size) for treatment during the transitional phase. Mares that have been in estrus for 10 days or more and have active ovaries are also consid-ered excellent candidates for progestin treatment. Altrenogest is effective in normally cycling mares for minimizing the necessity for estrus detection, for the synchronization of estrus, and permitting scheduled breeding. Estrus will ensue 2-5 days af-ter treatment is completed and most mares ovulate between 8-15 days after withdrawal. Altrenogest is also effective in suppressing

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28 Al TRENOg EST estrus expression in show mares or mares to be raced. Although the drug is labeled as contraindicated during pregnancy, it has been demonstrated to maintain pregnancy in oophorectomized mares and may be of benefit in mares that abort due to sub-therapeutic pro gestin levels. The product Matrix® is labeled for synchronization of estrus in sexually mature gilts that have had at least one estrous cycle. Treatment with altrenogest results in estrus (standing heat) 4-9 days after completion of the 14-day treatment period. Altrenogest has been used in dogs for luteal insufficiency and as a treatment to prevent premature delivery. Pharmacology/Actions Progestins are primarily produced endogenously by the corpus lu-teum. They trans form proliferative endometrium to secretory en-dometrium, enhance myometrium hypertrophy and inhibit spon-taneous uterine contraction. Progestins have a dose-dependent inhibitory effect on the secretion of pituitary gonadotropins and have some degree of estrogenic, anabolic and andro genic activity. Pharmacokinetics In horses, the pharmacokinetics of altrenogest have been studied (Machnik, Hegger et al. 2007). After oral dosing of 44 mg/kg PO, peak levels usually occur within 15-30 minutes post-dose; 24 hours post-dose, levels were below the level of quantification. Elimination half-lives are approximately 2. 5-4 hours. Altrenogest appears to be primarily eliminated in the urine. Peak urine levels occur 3-6 hours after oral dosing. Urine levels were detectable up to 12 days post-administration. Contraindications/Precautions/Warnings The manufacturer (Regu-Mate®—Intervet) lists pregnancy as a con-traindication to the use of altrenogest, however it has been used clin-ically to maintain pregnancy in certain mares (see Dosages below). Altrenogest should also not be used in horses intended for food pur-poses. Adverse Effects Adverse effects of altrenogest appear to be minimal when used at la beled dosages. One study (Shideler et al. 1983) found negligible changes in hematologic and most “standard” laboratory tests after administering altrenogest to 4 groups of horses (3 dosages, 1 con-trol) over 86 days. Occasionally, slight changes in Ca ++, K+, alkaline phosphatase and AST were noted in the treatment group, but values were only slightly elevated and only noted sporadically. No pattern or definite changes could be attributed to altrenogest. No outward adverse effects were noted in the treatment group during the trial. Use of progestational agents in mares with chronic uterine infec-tions should be avoided as the in fection process may be enhanced. Overdosage/Acute Toxicity The LD 50 of altrenogest is 175-177 mg/kg in rats. No information was located re garding the effects of an accidental acute overdose in horses or other species. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving altrenogest and may be of significance in veterinary patients: RIFAm PIN!! : May decrease progestin activity if administered con-comitantly. This is presumably due to microsomal enzyme induc-tion with resultant increase in progestin metabolism. The clinical significance of this potential interaction is unknown. laboratory Considerations Unlike exogenously administered progesterone, altrenogest does T! not interfere or cross-react with progesterone assays Doses DOg S:T! For luteal insufficiency: a) Document luteal insufficiency and rule out infectious causes of pregnancy loss. Best to avoid during first trimester. Give equine product (Regumate®) at 2 m L per 100 lbs of body weight PO once daily. Monitor pregnancy with ultrasound. Re member that exogenous progesterone is the experimental model for pyometra in the bitch, so monitor carefully. (Pur-swell 1999) b) For luteal insufficiency, pre-term labor: 0. 1 m L per 10 lb body weight PO once daily. (Barber 2006) c) T o maintain pregnancy if tocolytics (e. g., terbutaline) do not control myometrial contractility: 0. 088 mg/kg once dai-ly (q24h). Must be withdrawn 2-3 days prior to predicted whelp date. (Davidson 2006) HORSES:T! T o suppress estrus for synchronization:a) Administer 1 m L per 110 pounds body weight (0. 044 mg/kg) PO once daily for 15 con secutive days. May administer directly on tongue using a dose syringe or on the usual grain ration. (Package insert; Regu-Mate®—Intervet) b) 0. 044 mg/kg PO for 8-12 days (Bristol 1987) T o maintain pregnancy in mares with deficient progesterone levels: a) 22-44 mg daily PO (Squires et al. 1983) b) 0. 044 mg/kg PO once daily. Three options for treatment: 1) treatment until day 60 of pregnancy or greater AND measure-ment of endogenous progesterone level of >4 ng/m L; 2) treat-ment until day 120 of pregnancy; or 3) treatment until end of pregnancy. (Mc Cue 2003b) T o maintain pregnancy in mares with placentitis: a) 10-20 m L (22-44 mg) daily PO (Vaala 2003a) T o suppress estrus (long-term): a) 0. 044 mg/kg PO daily (Squires et al. 1983) SWINE:T! For synchronization of estrous in sexually mature gilts that have had at least one estrous cycle: a) Follow label directions for safe use. Administer 6. 8 m L (15 mg) per gilt for 14 consecutive days. Apply as a top-dressing on a portion of gilt's daily feed allowance. Estrous should oc-cur 4-9 days after completing treatment. (Package insert; Matrix®—Intervet) Client Information The manufacturer (T! Regu-Mate®, Matrix®—Intervet) lists the fol-lowing people as those who should not handle the product: 1. Women who are or suspect that they are pregnant 2. Anyone with thrombophlebitis or thromboembolic disorders or with a history of these events 3. Anyone having cerebrovascular or coronary artery disease 4. Women with known or suspected carcinoma of the breast 5. People with known or suspected estrogen-dependent neoplasias 6. Women with undiagnosed vaginal bleeding 7. People with benign or malignant tumor that developed dur-ing the use of oral contracep tives or other estrogen contain-ing products

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Al Um INUm Hy DROx IDE 29 Altrenogest can be absorbed after skin contact and absorption T! can be enhanced if the drug is covered by occlusive materials (e. g., under latex gloves, etc. ). If exposed to the skin, wash off im-mediately with soap and water. If the eyes are exposed, flush with water for 15 minutes and get medical atten tion. If the product is swallowed, do not induce vomiting and contact a physician or poison control center. This medication is prohibited from use in an extra-label manner T! to enhance food and/or fiber production in animals Chemistry/Synonyms An orally administered synthetic progestational agent, altrenogest has a chemical name of 17 alpha-Allyl-17beta-hydroxyestra-4,9,11-trien-3-one. Altrenogest may also be known as: allyl tren bolone, A-35957, A-41300, RH-2267, or RU-2267, Regu-Mate®, or Matrix®. Storage/Stability Altrenogest oral solution should be stored at room temperature. Altrenogest is extremely sensitive to light; dispense in light-resistant containers. Dosage Forms/Regulatory Status VETERINAR y­l Ab El ED PRODUCTS: Altrenogest 0. 22% (2. 2 mg/m L) in oil solution in 150 m L and 1000 m L bottles; Regu-Mate® (Intervet); (Rx). Approved for use in horses not intended for food. This medication is banned in racing animals in some countries. Altrenogest 0. 22% (2. 2 mg/m L) in 1000 m L bottles; Matrix® (In-tervet); (OTC, but extra-label use prohibited). Approved for use in sexually mature gilts that have had at least one estrous cycle. Gilts must not be slaughtered for human consumption for 21 days af-ter the last treatment. The FDA prohibits the extra-label use of this medication to enhance food and/or fiber production in animals. HUm AN­l Ab El ED PRODUCTS: None Aluminum hydroxide (ah-loo-min-um hye-droks-ide) Amphogel® Oral antacid/ph Osphate binder Prescriber Highlights Used to treat hyperphosphatemia in small animal pa-T T tients & sometimes as a gastric antacid for ulcers Chronic use may lead to electrolyte abnormalities; pos-T T sible aluminum toxicity Many potential drug interactions T T Availability has been an issue T T Uses/Indications Orally administered aluminum hydroxide is used to reduce hyper-phosphatemia in patients with renal failure. Pharmacology/Actions Aluminum salts reduce the amount of phosphorus absorbed from the intestine by physically binding to dietary phosphorus. Contraindications/Precautions/Warnings Aluminum-containing antacids may inhibit gastric emptying; use cautiously in patients with gastric outlet ob struction. Adverse Effects In small animals, the most likely side effect of aluminum hydrox-ide is constipation. If the patient is receiving a low phosphate diet and the patient chronically receives aluminum antacids, hypophos-phatemia can develop. Potentially, aluminum toxicity could occur with prolonged use but is thought unlikely to occur in small animal patients. Reproductive/Nursing Safety In a system evaluating the safety of drugs in canine and feline pregnancy (Papich 1989), these drugs are categorized as in class: A (Probably safe. Although specific studies may not have proved the safety of all drugs in dogs and cats, there are no reports of adverse ef-fects in laboratory animals or women. ) Overdosage/Acute Toxicity Acute toxicity is unlikely with an oral overdose. If necessary, GI and electrolyte imbalances that occur with chronic or acute overdose should be treated symptomatically. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving oral aluminum salts and may be of significance in veterinary patients: Aluminum salts can decrease the amount absorbed or the pharma-cologic effect of: All OPURINOl!! CHl OROQUINE!! CORTICOSTEROIDS!! DIg Ox IN!! ETHAmb UTOl!! Fl UOROQUINOl ONES!! H­2 ANTAg ONISTS !! (RANITIDINE, FAm OTIDINE, etc. ) IRON SAl TS !! ISONIAz ID!! PENICIll Am INE!! PHENOTHIAz INES!! TETRACy Cl INES!! THy ROID HORm ONES!! Separate oral doses of aluminum hydroxide and these drugs by two hours to help reduce this interaction. Doses DOg S:T! For hyperphosphatemia:a) Aluminum hydroxide: Initially at 30-90 mg/kg per day. Dos-age must be individualized. Capsules or suspension are pre-ferred as they are more easily mixed with food and dispersed throughout ingesta. Evaluate serum phosphate levels at 10-14 day intervals to determine optimum dosage. (Polzin and Osborne 1985) b) Aluminum hydroxide: 30-90 mg/kg PO once a day to three times a day with meals (Morgan 1988) c) 15-45 mg/kg PO q12h (Bartges 2002c) For adjunctive therapy for gastric ulcers:a) Aluminum hydroxide suspension or aluminum hydroxide/magnesium hydroxide suspen sion: 2-10 m L PO q2-4h (Hall and Twedt 1988) b) Aluminum hydroxide tablets: 0. 5-1 tablet PO q6h (Matz 1995)

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