BSAVA Small Animal Formulary, Notas de estudo de Medicina Veterinária

Baixe BSAVA Small Animal Formulary e outras Notas de estudo em PDF para Medicina Veterinária, somente na Docsity! BSAVA Joc RA Vain mo gaba ban = BSAVA Small Animal Formulary 6th edition | iii Contents Editorial Panel iv Preface to the sixth edition vi Foreword viii Introduction How to use the Formulary ix Distribution categories x The cascade xii “Off-label' use of medicines xii Drug storage and dispensing xiv Health and safety in dispensing xv Drug listings and monographs 1 (listed A-Z by generic name) Appendix Abbreviations 358 Writing a prescription 359 Body weight to body surface area conversion tables 360 Percentage solutions 361 Dosing small and exotic animals 361 Antibacterial selection 362 Radiographic contrast agents Barium contrast media 364 lodinated contrast media 365 MRI contrast media 367 Composition of intravenous fluids 370 Pancreatic enzyme supplements 371 Polypharmaceuticals 372 Sedative protocols Sedative combinations for dogs 372 Sedative combinations for cats 374 Sedative combinations for exotic pets 376 Chemotherapy protocols for Iymphoma 378 Drugs usage in renal and hepatic insufficiency 379 Further reading 382 Suspected Adverse Reaction Form 383 Index sorted by therapeutic class 385 Index (alphabetical by generic and trade names) 392 Errata 405 iv BSAVA Small Animal Formulary 6th edition Editorial Panel Sally Anne Argyle MVB CertSAC PhD MRCVS Royal (Dick) School of Veterinary Studies, University of Edinburgh, Hospital for Small Animals, Easter Bush Veterinary Centre, Roslin, Midlothian EH25 9RG John Chitty BvetMed CeriZooMed MRCVS Strathmore Veterinary Clinic, London Road, Andover, Hants SP10 2PH Jane Dobson MA DVetMed DipECVIM-CA(Oncology) MRCVS Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 0ES Clive M. Elwood MA VetMB MSc PhD CertSAC DipACVIM DipECVIM-CA MRCVS Davies Veterinary Specialists, Manor Farm Business Park, Higham Gobion, Hitchin, Herts SG5 3HR Heidi Featherstone BVetMed DVOphthal DipECVO MRCVS Willows Referral Service, 78 Tanworth Lane, Shirley, Solihull, West Midlands B90 4DF Simon Girling BVMS (Hons) DZooMed CBiol MIBiol MRCVS Muirfield, Glenfarg, Perthshire PH2 90D Edward J. Hall MA VetMB PhD DipECVIM-CA MRCVS Department of Clinical Veterinary Science, University of Bristol, Langford House, Langford, Bristol BS40 5DU Hilary A. Jackson BVM&S DVD DipaCVD MRCVS Dermatology Referral Practice, 528 Paisley Road West, Glasgow G64 4JG Mark W. Jackson BSc DVM PhD DipACVIM MRCVS Small Animal Hospital, University of Glasgow, Bearsden Road, Bearsden, Glasgow G61 1QH Mike Stafford Johnson MvB CeriSAM MACVS DVC MRCVS 43 Waverley Road, Kenilworth, Warwickshire CV8 1JL Fraser McConnell BVvM&S DVR DipECVDI CertSAM MRCVS Small Animal Teaching Hospital, University of Liverpool, Leahurst, Chester High Road, Neston, Wirral CH64 7TE Anna Meredith MA VetMB CeriLAS DZooMed MRCVS Royal (Dick) School of Veterinary Studies, University of Edinburgh, Hospital for Small Animals, Easter Bush Veterinary Centre, Roslin, Midlothian EH25 9RG BSAVA Small Animal Formulary 6th edition v Daniel S. Mills BVSc PhD CBiol MiBiol ILTM CCAB DipECVBM-CA MRCVS Biological Sciences Department, University of Lincoln, Riseholme Park, Lincoln LN2 2LG Jo Murrell BVSc (Hons) PhD DipECVAA MRCVS Department of Clinical Veterinary Science, University of Bristol, Langford House, Langford, Bristol BS40 5DU Jacques Penderis BVSc MVM PhD CeriVR DipECVN MRCVS Small Animal Hospital, University of Glasgow, Bearsden Road, Bearsden, Glasgow G61 1QH lan Ramsey BVSc PhD DSAM DipECVIM-CA FHEA MRCVS Small Animal Hospital, University of Glasgow, Bearsden Road, Bearsden, Glasgow G61 1QH Richard Saunders Bsc BVSc CertZooMed CIBiol MiBiol MRCVS Veterinary Department, Bristol Zoo Gardens, Bristol BS8 3HA BSAVA Small Animal Formulary 6th edition Foreword The BSAVA Small Animal Formulary has become established as one of the most useful books on the practice shelf. It contains a wealth of vital information on available drugs and how to use them to best effect — but remains a manageable size and exceptionally user- friendly. As such, it is one of the most valued of the benefits of BSAVA membership; each BSAVA member is sent a free copy of each new edition as it is published. The first edition of the formulary was published in 1994, and subsequent editions have been published at 3-yearly intervals since then. lan Ramsey has taken over the role of Editor-in-Chief for this 6th edition from Bryn Tennant. Bryn is a hard act to follow; his hard work and expertise over the years has allowed each edition of the Formulary to surpass the preceding one, and the BSAVA is indebted to him for his long-term commitment to the project. However, lan is a worthy successor who has tackled the task of updating the information contained within the Formulary with enthusiasm, energy and undoubted knowledge. The appropriate and responsible use of medicines is a vital issue for the profession, both in the context of ensuring the best possible treatment for each individual patient, and in the wider context of human and animal health. The BSAVA Small Animal Formulary contributes in no small part by ensuring that veterinary surgeons remain well informed about drugs and their usage. Frances Barr MA VetMB DVR PhD DipECVDI MRCVS BSAVA President 2007-8 Introduction ix Introduction How to use the Formulary For information on a drug, look up the generic name in the A-Z section, where you will find each drug listed in a standard format. Example monograph Generic name (other generic names) (trade names) LEGAL CATEGORY Formulations Action Use Safety and handling Contraindications Adverse reactions Drug interactions Doses: Dogs, cats and others Notes on the monographs * Name. The rINN generic name is used. The list of trade names is not necessarily comprehensive, and the mention or exclusion of any particular commercial product is not a recommendation or otherwise as to its value. Any omission of a product that is authorized for a particular small animal indication is purely accidental. All monographs were updated in the period July— December 2007. Products that are not authorized for veterinary use are marked with an asterisk. Note that an indication that a product is authorized does not necessarily mean thatit is authorized for all species listed in the monograph; users should check individual data sheets. * Action and Use. Veterinary surgeons using this publication are warned that many of the drugs and doses listed are not currently authorized by the Veterinary Medicines Directorate (VMD) or the European Agency for the Evaluation of Medicinal Products (EMEA) (either at all or for a particular species), or manufacturers' recommendations may be limited to particular indications. The decision, and therefore the responsibility, for prescribing any drug for an animal lies solely with the veterinary surgeon. Expert assistance should be obtained when necessary. The 'cascade' and its implications are discussed below. * Safety and handling. This section only outlines specific risks and precautions for a particular drug that are different to the general advice given below in the 'Health and safety in prescribing' section. x Introduction * Contraindications and Adverse reactions: Cautionary notes are included in the section on contraindications. Cautionary notes usually imply that increased monitoring and decreased doses should be used. The list of adverse reactions is not intended to be comprehensive and is limited to those effects that may be of clinical significance. The information for both of these sections is taken from published veterinary and human references and not just from product literature. * Druginteractions. A listing of those interactions which may be of clinical significance. * Doses. These are based on those recommended by the manufacturers in their data sheets and package inserts, or are based on those given in published articles or textbooks, or are based on clinical experience. These recommendations should be used only as guidelines and should not be considered appropriate for every case. Clinical judgement must take precedence. Where possible, doses have been given for individual species; however, sometimes generalizations are used. 'Birds' includes psittacines, raptors, pigeons and others. 'Reptiles' includes chelonians, lizards and snakes. 'Small mammals' includes ferrets, lagomorphs and rodents. Distribution categories Authorized small animal medicines now fall within the first four categories below and all packaging supplied by drug manufacturers and distributors has to be changed by 1st November 2008. Medical products not authorized for veterinary use retain their former classification (e.g. P, POM). AVM-GSL: Authorized veterinary medicine — general sales list (formerly GSL). This may be sold by anyone. NFA-VPS: Non-food animal medicine — veterinarian, pharmacist, Suitably Qualified Person (SQP) (formerly PML companion animal products and a few P products). These medicines for companion animals must be supplied by a veterinary surgeon, pharmacist or SQP. An SQP has to be registered with the Animal Medicines Training Regulatory Authority (AMTRA). Veterinary nurses can become SQPs but it is not automatic. POM-VPS: Prescription-only medicine — veterinarian, pharmacist, SQP (formerly PML livestock products, MFSX products and a few P products). These medicines for food-producing animals (including horses) can only be supplied on an oral or written veterinary prescription from a veterinary surgeon, pharmacist or SQP and can only be supplied by one of those groups of people in accordance with the prescription. POM-V: Prescription-only medicine — veterinarian (formerly POM products and a few P products). These medicines can only be supplied against a veterinary prescription that has been prepared (either orally or in writing) by a veterinary surgeon to animals under Introduction xiii * Discuss all therapeutic options with the owner * Use the cascade to determine your choice of medicine * —Obtain signed informed consent if an unauthorized product is to be used, ensuring that all potential problems are explained to the client *—Administer unauthorized medicines against a patient-specific prescription. Do not administer to a group of animals if at all possible. An 'off-label' medicine must show a comparative clinical advantage to the authorized product in the specific circumstances presented (where applicable). Medicines may be used 'off-label' in the following ways (this is not an exhaustive list): Authorized product at an unauthorized dose Authorized product for an unauthorized indication Authorized product used outwith the authorized age range Authorized product administered by an unauthorized route Authorized product used to treat an animal in an unauthorized physiological state, e.g. pregnancy (i.e. an unauthorized indication) * Product authorized for use in humans or a different animal species to that being treated. Adverse effects may or may not be specific for a species, and idiosyncratic reactions are always a possibility. If no adverse effects are listed, consider data from different species. When using novel or unfamiliar drugs, consider pharmaceutical and pharmacological interactions. In some species, and with some diseases, the ability to metabolize/excrete a drug may be impaired/enhanced. Use the lowest dose that might be effective and the safest route of administration. Ensure that you are aware of the clinical signs that may suggest toxicity. Information on “off-label' use may be available from a wide variety of sources (see Appendix). Drug storage and dispensing Acode of practice on the storage and dispensing of medicines is available (BVA Good Practice Guide on Veterinary Medicines). Itis recommended that, in general, medications are kept in and dispensed in the manufacturer's original packaging. Medicines can be adversely affected by adverse temperatures, excessive light, humidity and rough handling. Loose tablets or capsules that are repackaged from bulk containers should be dispensed in child-resistant containers and supplied with a package insert (if one exists). Tablets and capsules in foil strips should be sold in their original packaging or in a similar cardboard box for smaller quantities. Preparations for external application should be dispensed in coloured fluted bottles. Oral liquids should be dispensed in plain glass bottles with child-resistant closures. xiv Introduction All medicines should be labelled. The label should include: The owner's name and address Date Product name (and strength) Total quantity of the product supplied in the container Instructions for dosage Practice name and address The wording “Keep out of reach of children" and 'For animal treatment only” The words 'For external use only' should be included on labels for products for topical use. All labels should be typed. In order to comply with the new Veterinary Medicines Regulations (2005), records of all products supplied on prescription must be kept for 5 years. When a batch is brought into use in a practice, the batch number and date should be recorded. Itis not necessary to record the batch number of each medication used for a given animal. Health and safety in dispensing All drugs are potentially poisonous to humans as well as animals. Toxicity may be mild or severe and includes carcinogenic and teratogenic effects. Warnings are given in the monographs. However, risks to humans dispensing medicines are not always well characterized and idiosyncratic reactions may occur. Itis good practice for everyone to wear prote: clothing (including gloves) when directly handling medicines, not to eat or drink (or store food or drink) near medicines, and to wash their hands frequently when working with medicines. Gloves, masks and safety glasses should be worn if handling potentially toxic liquids, powders or broken tablets. Avoid breaking tablets of antineoplastic oytotoxic drugs and use laminar flow cabinets for the preparation and dispensing of these medications. Many prescribers and users of medicines are not aware of the carcinogenic potential of the drugs they are handling. Below are lists of medicines included in the BSAVA Formulary that are known or potential carcinogens or teratogens. The lists are not all-inclusive: they include only those substances that have been evaluated. Most of the drugs are connected only with certain kinds of cancer. The relative carcinogenicity of the agents varies considerably and some do not cause cancer at all times or under all circumstances. Some may only be carcinogenic or teratogenic if a person is exposed in a certain way (for example, ingesting as opposed to touching the drug). For more detailed information refer to the International Agency for Research on Cancer (IARC) or the National Toxicology Program (NTP) (information is available on their respective websites). Introduction xv Examples of drugs known or suspected to be human carcinogens (c) or teratogens (t): ACE inhibitors (t), e.g. benazepril, enalapril, ramipril Androgenic (anabolic) steroids (t, o) Antibiotics (0), e.g. metronidazole, chloramphenicol Antibiotics (t) e.g. aminoglycosides, doxycycline, trimethoprim, sulphonamides Antifungals (c), e.g. ketoconazole, fluconazole, itraconazole, flucytosine Antineoplastic drugs (c, t) - all Antithyroid drugs (t), e.g. carbimazole/methimazole Beta-blockers (t) Dantron (c) Desferrioxamine (t) Diltiazem (t) Finasteride (t) Immunosuppressives (c), e.g. azathioprine, ciclosporin Lithium (t) Methotrexate (t) Misoprostol (t) NSAIDS (t) Penicillamine (t) Phenoxybenzamine (c) Phenytoin (c) Phenytoin (t) Progesterone (c) and some oestrogens (c) Vitamin A (t) Warfarin (t) Note that most carcinogens are also likely to be teratogens. 2 BSAVA Small Animal Formulary 6th edition dosed on a mg/kg basis; use the lowest end of the dose range in these breeds. In Boxers spontaneous fainting and syncope can occur due to sinoatrial block caused by excessive vagal tone; use low doses (0.01 mg/kg i.m.) or avoid ACP in this breed. Adverse reactions: Rarely, healthy animals may develop profound hypotension following administration of phenothiazines. Supportive therapy to maintain body temperature and fluid balance is indicated until the animal is fully recovered. Can lead to seizures in gerbils. Drug interactions: Administration of ACP in combination with alpha-2 agonists is not advised due to the excessive hypotension that may result. Other CNS depressant agents (e.g. barbiturates, propofol, volatile anaesthetics) will cause additive CNS depression if used with ACP. Doses of other anaesthetic drugs should be reduced when ACP has been used for premedication. Quinidine given with phenothiazines may cause additional cardiac depression. Increased levels of both drugs may result if propanolol is administered with phenothiazines. As phenothiazines block alpha-adrenergic receptors, concomitant use with adrenaline may lead to unopposed beta activity, thereby causing vasodilation and tachycardia. Antidiarrhoeal mixtures (e.g. kaolin/pectin, bismuth salicylate) and antacids may cause reduced GI absorption of oral phenothiazines. DOSES Dogs, Cats: 0.01-0.02 mg/kg slowly i.v.; 0.01-0.05 mg/kg im., s.c.; 1-3 mg/kg p.o. Small mammals: Ferrets: 0.2-0.5 mg/kg i.m., s.c., p.o.; Rabbits: 0.1-1.0 mg/kg i.m., s.c.; Guinea pigs: 2.5-5 mg/kg im., s.c., p. Hamsters: 5 mg/kg i.m., s.c., p.o.; Gerbils: 3 mg/kg im., s.c., p. Rats: 2.5 mg/kg i.m., s.c., p.o.; Mice: 1-5 mg/kg im., s.c., p.o. Birds: Not recommended. Reptiles: 0.1-0.5 mg/kg im. Acetaminophen see Paracetamol Acetazolamide (Diamox, Diamox SR*) POM Formulations: Injectable: 500 mg vial (powder for reconstitution). Oral: 250 mg tablets, capsules. Action: Systemic carbonic anhydrase inhibitor that reduces intraocular pressure by reducing aqueous humour production by inhibiting bicarbonate ion formation within the ciliary body epithelium. Use: Treatment of acute glaucoma. However, it is not considered as the treatment of choice for long-term control of glaucoma. Topical carbonic anhydrase inhibitors are preferred for chronic glaucoma in dogs and cats. The concurrent use of a topical or systemic carbonic BSAVA Small Animal Formulary 6th edition 3 anhydrase inhibitor is not beneficial as there is no additional decrease in intraocular pressure compared with the sole use of either topical or systemic treatment. Safety and handling: Normal precautions should be observed. Contraindications: Avoid in anorexic dogs, those with hepatic or renal dysfunction and those with sulphonamide hypersensitivity. Cats are particularly susceptible to the adverse effects of systemic carbonic anhydrase inhibitors, avoid in this species. Adverse reactions: Weakness, Gi disturbances (anorexia, vomiting, diarrhoea), panting, metabolic acidosis, diuresis, electrolyte disturbances in particular potassium depletion. Drug interactions: Primidone absorption may be inhibited by oral acetazolamide. Acetazolamide alkalinizes urine; thus, excretion rate of weak bases may be decreased but weak acid excretion increased. Concomitant use of corticosteroids may exacerbate potassium depletion, causing hypokalaemia. DOSES Dogs: 5-10 mg/kg i.v. single dose, 4-8 mg/kg p.o. g8-12h. Cats: Do not use. Small mammais, Birds, Reptiles: No information available. Acetylcysteine (llube*, Parvolex*) POM Formulations: Injectable: 200 mg/ml solution. Topical: 5% ophthalmic solution in combination with 0.35% hypromellose ophthalmic drops in 10 ml bottle. Action: Decreases the viscosity of bronchial secretions, maintains glutathione levels in the liver and has some anticollagenase activity. Use: Reduces the extent of liver injury in cases of paracetamol (acetaminophen) poisoning and can also be used as a mucolytic in respiratory disease. Oral solution should be diluted to a 5% solution and given via a stomach tube as it tastes unpleasant. Acetylcysteine may be useful in the treatment of keratoconjunctivitis sicca (KCS) (dry eye), or in 'melting' corneal ulcers although there is limited in vivo work to confirm this. In the eye it may be used in conjunction with hypromellose. In rabbits direct application into the ear has been reported as beneficial in cases of secretory otitis media, reducing inflammation and preventing long-term fibrotic changes. Safety and handling: Normal precautions should be observed. Contiraindications: No information available. Adverse reactions: Acetylcysteine has caused hypersensitivity and bronchospasm when used in the pulmonary tree. When given orally for paracetamol! poisoning it may cause Gl effects (nausea, vomiting) and, rarely, urticaria. Drug interactions: No information available. 4 BSAVA Small Animal Formulary 6th edition DOSES Dogs, Cats: * Mucolytic: Either nebulize 50 mg as a 2% (dilute with saline) solution over 30-60 min or instil directly into the trachea 1-2 ml of a 20% solution. * Paracetamol poisoning: After inducing emesis, use immediately if ingestion occurred within 24 hours. Either give 150 mg/kg by i.v. infusion in 200 ml 5% glucose over 15 min, followed by 50 mg/kg iv. infusion in 500 ml over 4 hours, then 100 mg/kg i.v. infusion in 1000 ml over 16 hours or give 140 mg/kg loading dose p.o., then 70 mg/kg p.o. q4h for 17 doses unless initial serum paracetamol levels indicate a non-toxic level. * KCS:1 drop of the ophthalmic solution topically to the eye q6-8h. Rarely used now for this indication. * Melting corneal ulcers: 1 drop of the ophthalmic solution q1-4h in the affected eye for 24-48 hours. Topical autologous serum is more effective for the treatment of a melting corneal ulcer and is preferred. Small mammals: Rabbits: Mucolytic: either nebulize 50 mg as a 2% (dilute with saline) solution over 30-60 min or instil directly into the trachea; Otic lavage: 1-2 ml of a 20% solution. Birds: Mucolytic: as Rabbits (2-5 drops in 15 ml saline for nebulization). Reptiles: 2% solution (dilute with saline) nebulized for 15 min. Acetylsalicyclic acid see Aspirin Aciclovir (Zovirax') PoM Formulations: Ophthalmic: 5% ointmentin 2 g, 10 g tubes. Action: Inhibits viral replication (viral DNA polymerase); depends on viral thymidine kinase for phosphorylation. Use: Management of ocular feline herpesvirus (FHV-1) infections. In vitro studies suggest the combination of aciclovir and recombinant human interferon to be more effective against FHV-1 than aciclovir on its own; in vivo efficacy of the combination is not known. The clinical use of aciclovir on its own is questionable. Aciclovir is virostatic and is unable to eradicate latent viral infection. In refractory and severe cases of FHV-1 ulceration, combined therapy including topical antiviral medication, human recombinant IFN-alpha and oral Iysine, can be used. Also used to treat herpesvirus infections of other species (e.g. Pacheco's disease in psittacid birds). Safety and handling: Normal precautions should be observed. Contraindications: No information available. BSAVA Small Animal Formulary 6th edition 7 accompanied by the physiological signs of parturition, i.e. fetal expulsion, slight anorexia, mammary congestion. After induced abortion an early retum to oestrus is frequently observed (the oestrus-to-oestrus interval may be shortened by 1-3 months). Safety and handling: Use with care. Accidental injection may be a hazard to women who are pregnant or intending to become pregnant. Contiraindications: No information available. Adverse reactions: Transient pain at the injection site; any local inflammation produced resolves uneventfully. Drug interactions: No information available. DOSES Dogs: 10 mg/kg s.c. q24h for two doses. Cats: Not used. Small mammais, Birds, Reptiles: No information available. Alfaxalone (Alfaxan CD) PoM-v Formulations: Injectable: 10 mg/ml solution; the alfaxalone is solubilized in a cyclodextrin. Action: Anaesthesia induced by the CNS depressant effect of the alfaxalone. Use: Induction agent used before inhalational anaesthesia, or as a sole anaesthetic agent for examination or surgical procedures. As with all i.v. anaesthetic drugs, premedication will reduce the dose required for induction and maintenance of anaesthesia. The drug should be given slowly and to effect in order to prevent inadvertent overdose. The dose recommended by the manufacturer for induction of anaesthesia can usually be reduced in all animals. Analgesia is insufficient for surgery: other analgesic drugs such as opioids should be incorporated into the anaesthetic protocol. Alfaxalone is shorter acting and causes less excitement during recovery than the alfaxalone/alfadalone combination previously available. The oyclodextrin carrier does not cause histamine release in dogs (cf. the cremaphor EL of the combination). Safety and handling: Does not contain an antimicrobial preservative; thus it is recommended that the remainder of an opened bottle is discarded after single use. Contiraindications: Do not use in combination with other i.v. anaesthetic agents. Safety in animals <12 weeks old has not been demonstrated. Adverse reactions: A slight increase in heart rate can occur immediately after i.v. injection as a compensatory response to maintain blood pressure in the face of mild hypotension. This effect can be minimized by slow i.v. injection. As with all anaesthetic drugs, respiratory depression can occur with overdoses. Longer recoveries from anaesthesia are likely to occur when alfaxalone is used for maintenance of anaesthesia. 8 BSAVA Small Animal Formulary 6th edition Drug interactions: No information available. DOSES Dogs: 3 mg/kg i.v. in unpremedicated dogs; 2 mg/kg i.v. in premedicated dogs for induction of anaesthesia, although commontly lower doses can be used. 6-9 mg/kg/h is recommended as a continuous rate infusion for maintenance of anaesthesia or top-up boluses of 1-1.5 mg/kg every 10 min. Cats: 2-5 mg/kg i.v. for induction of anesthesia; the lower end of the dose range is often adequate. 7-10 mg/kg/h is recommended as a continuous rate infusion for maintenance of anaesthesia or top-up boluses of 1-1.5 mg/kg q1Omin. Small mammals: Ferrets: 9-12 mg (0.5-0.75 ml)/kg i.v., i.m.; Rabbits: 6-9 mg/kg i.v. or 9 mg/kg i.m.; Guinea pigs: 40 mg/kg i.m. or i Other rodents: 20 mg/kg i.m. or 120 mg/kg i.p. Birds: No information available. Reptiles: 6-9 mg/kg i.v. or 15 mg/kg im. Alfentanil (Rapifen*) PoM CD Scneouce 2 Formulations: Injectable: 0.5 mg/ml solution, available in 2 ml or 10 ml vials; 5 mg/ml solution. Action: Pure OP3 agonist of the phenylpiperidine series. Use: Very potent opioid analgesic (10-20 times more potent than morphine) used to provide intraoperative analgesia during anaesthesia in dogs and cats. Use of such potent opioids during anaesthesia contributes to a balanced anaesthesia technique but they must be administered accurately. It has a rapid onset (15-30 seconds) and short duration of action. It is best given using continuous rate infusions. The drug is not suited to provision of analgesia in the postoperative period. Safety and handling: Normal precautions should be observed. Contraindications: Animals with pre-existing respiratory compromise. Adverse reactions: A reduction in heart rate is likely whenever alfentanil is given; atropine can be administered to counter bradycardia if necessary. Respiratory depression leading to cessation of spontaneous respiration is likely following administration. Do not use unless facilities for positive pressure ventilation are available (either manual or automatic). Rapid i.v. injection can cause a severe bradycardia, even asystole. Drug interactions: Alfentanil reduces the dose requirements of concurrently administered anaesthetics, including inhaled anaesthetics, by at least 50%. DOSES Dogs: 0.001-0.005 mg/kgi.v. as a single bolus or 0.001-0.0025 mg/kg/ min continuous rate infusion. BSAVA Small Animal Formulary 6th edition 9 Cats: 0.001 mg/kg i.v. as a single bolus or 0.001 mg/kg/min continuous rate infusion. Clinical evaluation of alfentanil in cats is very limited. Small mammais, Birds, Reptiles: No information available. Allopurino! (Zyloric*) PoM Formulations: Oral: 100 mg, 300 mg tablets. Action: Xanthine oxidase inhibition decreases formation of uric acid by blocking the conversion of hypoxanthine to xanthine, and of xanthine to uric acid. Use: In dogs, the treatment and prevention of recurrent uric acid uroliths and hyperuricosuric calcium oxalate urolithiasis and, in combination with meglumine antimonate, to treat leishmaniasis. In birds and reptiles it is used in the treatment of hyperuricaemia and gout, and in the management of renal disease. Safety and handling: Normal precautions should be observed. Contraindications: Use with caution in patients with impaired renal function. Adverse reactions: In humans, allopurinol may enhance the effects of azathioprine and theophylline. Drug interactions: No information available. DOSES Dogs: * Uri acid urolithiasis: 10 mg/kg p.o. q8h for 1 month, then 10 mg/kg p.o. q24h. * Leishmaniasis: 30 mg/kg p.o. q24h with meglumine antimonate for up to 3 months, then 20 mg/kg p.o. q24h for one week each month. Cats, Small mammals: No information available. Birds: 10 mg/kg p.o. q12h (all species); Pigeons: 830 mg/l drinking water, Psittacids: 10 mg/30 ml drinking water. Reptiles: 10-20 mg/kg p.o. q24h (most species); Chelonians: 50 mg/kg p.o. q24h for 30 days then q72h. Alphaxalone see Alfaxalone Alprazolam (Alprazolam*, Xanax*) POM Formulations: Oral: 0.25 mg, 0.5 mg tablets. Action: Increases GABA activity within the CNS, resulting in anxiolysis and a range of cognitive effects including the inhibition of memory. 12 BSAVA Small Animal Formulary 6th edition DOSES Dogs: 3.0 mg/kg q24h. The dose is based on anecdotal discussion and may not be appropriate for all animals. Cats: 1.0-4.0 mg/kg q24h; start at the lowest dose and increase slowly. Small mammais, Birds, Reptiles: No information available. Amethocaine see Tetracaine Amikacin (Amikacin*, Amikin*) POM Formulations: Injectable: 50 mg/ml, 250 mg/ml solutions. Action: Aminoglycosides inhibit bacterial protein synthesis. They are bactericidal and their mechanism of killing is concentration- dependent, leading to a marked post-antibiotic effect, allowing pulse-dosing regimens (which may reduce toxicity). Use: Active against many Gram-negative bacteria including some that may be resistant to gentamicin. lts use is generally only indicated when sensitivity testing has been performed. Activity at low oxygen sites may be limited. Movement across biological membranes may also be limited, hence systemic levels require parenteral administration, and access to sites such as the CNS and ocular fluids is very limited. Monitoring serum amikacin levels should be considered to ensure therapeutic levels and minimize toxicity, particularly in neonates, geriatric patients and those with reduced renal function. Monitoring renal function is also advisable during treatment of any animal. Intravenous doses should be given slowly, generally over 30-60 min. Concurrent fluid therapy is advised. Safety and handling: Normal precautions should be observed. Contraindications: Can potentiate neuromuscular blockade so avoid use in combination with neuromuscular blocking agents. If possible avoid use in animals with reduced renal function. Use with caution in birds, as it is toxic. Adverse reactions: Nephrotoxic and ototoxic. Drug interactions: Synergism may occur in vivo when aminoglycosides are combined with beta-lactam antimicrobials. Avoid the concurrent use of other nephrotoxic, ototoxic or neurotoxic agents (e.g. amphotericin B, cisplatin, furosemide). Aminoglycosides may be inactivated in vitro by beta-lactam antibiotics (e.g. penicillins, cephalosporins) or heparin; do not give these drugs in the same syringe. DOSES Dogs, Cats: 5-10 mg/kgi.v., im., s.c. q8h or 10-15 mg/kgi.v., im., s.c. q24h (possibly less nephrotoxic and more in-line with BSAVA Small Animal Formulary 6th edition 13 concentration-dependent effect). Doses up to 30 mg/kg i.v., im., s.c. q24h have been recommended by some authors for managing septic shock, although there is an increased risk of adverse effects with such high doses. Small mammals: Ferrets: 8-16 mg/kg i.v., im., s.c. q8-24h; Rabbits: 2-10 mg/kg i.v., im., s.c. q8-12h; Rodents: 5-15 mg/kg i.v. ., 8.0. q8-12h. Concurrent fluid therapy advised, especially if hydration status poor or uncertain. Birds: 10-20 mg/kg im., s.c., i.v. q8-12h. Reptiles: 5 mg/kg im. once, then 2.5 mg/kg i.m. q72h O 25ºC. Amiloride (Amiloride Hydrochloride*) PoM Formulations: Oral: 5 mg tablets, 1 mg/ml solution. Also present in compound preparations with hydrochlorothiazide (Moduret, Moduretic) and furosemide (Frumil, Lasoride). Action: Potassium-sparing weak diuretic which inhibits sodium absorption in the distal tubule and collecting duct. This leads to a failure of the normal renal concentration gradient. Use: Oedema or ascites due to liver or heart failure. Often added to more potent diuretics such as furosemide in cases of refractory heart failure. Doses have not been widely reported in the veterinary literature. Safety and handling: Normal precautions should be observed. Contraindications: Avoid in renal insufficiency, diabetes mellitus or hyperkalaemia. Adverse reactions: Hypotension, hyperkalaemia and hyponatraemia may develop. Drug interactions: Avoid the concomitant administration of potassium. DOSES Dogs, Cats: 0.1 mg/kg p.o. q12h is used in humans and has been suggested for dogs and cats. Small mammais, Birds, Reptiles: No information available. Amino acid solutions (Duphalyte, Aminoplasmal”, Aminoven*, Glamin*, Intrafusin*) POM Formulations: Injectable: synthetic crystalline L-amino acid solutions for iv. use only. Numerous human products are available, varying in concentration of essential amino acids. Some products also contain electrolytes. Action: Support protein anabolism, arrest protein and muscle wasting, and maintain intermediary metabolism. 14 BSAVA Small Animal Formulary 6th edition Use: Amino acid solutions supply essential and non-essential amino acids for protein production. They are used parenterally in patients requiring nutritional support. The authorized veterinary preparation contains insufficient amino acids to meet basal requirements for protein production and is intended as an aid for i.v. fluid support. None of the human formulations contains taurine, which is essential for cats and in specific conditions in dogs. Most products are hyperosmolar. The use of concentrated amino acid solutions for parenteral nutrition support should not be undertaken without specific training and requires central venous access and intensive care monitoring. Parenteral nutrition also needs to supply the patient's requirements for fluids, essential electrolytes (sodium, potassium, magnesium, bicarbonate, calcium) and phosphate. Additionally if treatment is prolonged, vitamins and trace elements must also be given. Safety and handling: Normal precautions should be observed. Contraindications: Dehydration, shock, electrolyte imbalances and inadequate oxygenation. Adverse reactions: The main complications of parenteral nutrition are catheter-associated thrombophlebitis, bacterial colonization of the catheter and resulting bacteraemia and septicaemia. Potentially life-threatening electrolyte imbalances including hypophosphataemia may also be seen. Other metabolic complications associated with parenteral nutrition include hyperglycaemia, hypoglycaemia, hyperlipidaemia, hypercapnia, acid-base disturbances, and 'refeeding syndrome”. Additionally, because solutions are hyperosmolar severe tissue damage can occur if they are extravasated. Drug interactions: Consult specific product data sheet(s). Intravenous lines for amino acid solutions should be dedicated for that use alone and should not be used for other medications. DOSES Dogs: 2-4 g protein/100 kcal (418 kJ) energy requirements. Cats: 3-6 g protein/100 kcal (418 kJ) energy requirements. Small mammais, Birds, Reptiles: No information available. Aminophylline (Aminophyiline*) PoM Formulations: Injectable: 25 mg/ml solution. Oral: 100 mg tablet. For modified-release preparations see Theophylline (100 mg of aminophylline is equivalent to 79 mg of theophylline). Action: Thought to include: inhibition of phosphodiesterase enzyme, alteration of intracellular calcium, catecholamine release, and adenosine and prostaglandin antagonism. Use: Spasmolytic agent and has a mild diuretic action. It is used to dilate bronchi and in the management of pulmonary ocedema. Aminophylline is a stable mixture of theophylline and ethylenediamine. Theophylline has a low therapeutic index and should be dosed on a lean body weight basis. BSAVA Small Animal Formulary 6th edition 17 DOSES Dogs: * Generalized demodicosis: 0.05% solution (1 ml concentrated liquid in 100 ml water) q5-7d until two negative skin scrapings/hair plucks are achieved 2 weeks apart. * Sarcoptic acariasis: 0.025% solution (1 ml concentrated liquid in 200 ml water) weekly for 2-6 weeks. Cats: Do not use. Small mammals: Rodents: 0.007% solution: 1.4 ml concentrated liquid in 1000 ml water. Apply with a cotton bud q14d for 3-6 treatments. Birds, Reptiles: No information available. Amitriptyline (Amitriptyline*) PoM Formulations: Oral: 10 mg, 25 mg, 50 mg tablets; 5 mg/ml, 10 mg/ml solutions. Action: Blocks noradrenaline and serotonin re-uptake in the brain, resulting in antidepressive activity. Use: Management of chronic anxiety problems, including 'compulsive disorders", separation anxiety in dogs and 'compulsive disorders", psychogenic alopecia, hypervocalization and idiopathic cystitis in cats. The atypical tricyclic antidepressant clomipramine exists as an authorized preparation for use in dogs. Safety and handling: Normal precautions should be observed. Contraindications: Hypersensitivity to tricyclic antidepressants, glaucoma, history of seizures or urinary retention, severe liver disease. Some caution and careful monitoring is warranted in patients with cardiac or renal disease. Adverse reactions: Sedation, dry mouth, diarrhoea, vomiting, excitability, arrhythmias, hypotension, syncope, increased appetite, weight gain and, less commontly, seizures and bone marrow disorders have been reported in humans. Drug interactions: Should not be used with monoamine oxidase inhibitors or drugs metabolized by cytochrome P450 2D6, e.g. chlorpheniramine, cimetidine. DOSES Dogs: 1-2 mg/kg p.o. q12-24h. Cats: 0.5-1 mg/kg p.o. q24h. Small mammais, Birds, Reptiles: No information available. Amlodipine (Amiodipine*, Istin*) PoM Formulations: Oral: 5 mg, 10 mg tablets. Action: Calcium-channel blocker, with predominant effects in the peripheral vasculature, which produces mild negative inotropic and chronotropic effects. 18 BSAVA Small Animal Formulary 6th edition Use: Treatment of systemic hypertension in cats and appears to be safe even when there is concurrent renal failure. Has been used in dogs with systemic hypertension and in normotensive dogs with refractory cardiac failure, to reduce cardiac afterload. As an antihypertensive agent amlodipine is the first choice in cats but is less effective in dogs, where it is more commontly used in advanced heart failure. Safety and handling: Normal precautions should be observed. Contraindications: Amlodipine is metabolized in the liver and dosage should be reduced when there is hepatic dysfunction. Avoid in cardiogenic shock and pregnancy. Adverse reactions: Lethargy, hypertension or inappetence are rare side effects. Drug interactions: Little is known in animals. Hepatic metabolism may be impaired by drugs such as cimetidine. Hypotension is a risk if combined with other antihypertensives, e.g. ACE inhibitors, diuretios, beta-blockers. DOSES Dogs: Initial dose 0.05-0.1 mg/kg p.o. q12-24h. The dose may be titrated upwards weekly if necessary, monitoring blood pressure regularly. Cats: 0.625-1.25 mg/cat p.o. q24h. The dose may be increased slowly or the frequency increased to q 12h if necessary. Blood pressure monitoring is essential. Small mammais, Birds, Reptiles: No information available. Amoxicillin (Amoxycillin) (Amoxinsol, Amoxycare, Amoxival, Amoxypen, Bimoxyl, Clamoxyl, Duphamox, Vetremox) POM-V Formulations: Injectable: 150 mg/ml suspension. Oral: 40 mg, 200 mg, 250 mg tablets; suspension which when reconstituted provides 50 mg/ml. Action: Binds to penicillin-binding proteins involved in bacterial cell wall synthesis, thereby decreasing cell wall strength and rigidity, affecting cell division, growth and septum formation. These antimicrobials act in a time-dependent bactericidal fashion. Use: Active against certain Gram-positive and Gram-negative aerobic organisms and many obligate anaerobes but not against those that produce penicilinases (beta-lactamases), e.g. Escherichia coli, Staphylococcus aureus. The more difficult Gram-negative organisms (Pseudomonas spp., Klebsiella spp.) are usually resistant. Amoxicillin is excreted well in bile and urine. Oral amoxicillin may be given with or without food. Since amoxicillin works in a time-dependent fashion, itis important to maintain levels above the MIC for a high percentage of the time. In practical terms this means that dosing interval is critical and missing doses can seriously compromise efficacy. In ferrets is used in combination with bismuth subsalicylate, ranitidine or omeparazole and metronidazole (triple therapy") for treatment of Helicobacter mustelae infection. BSAVA Small Animal Formulary 6th edition 19 Safety and handling: Refrigerate oral suspension after reconstitution; discard if solution becomes dark or after 7 days. Contraindications: Avoid oral antibiotics in critically ill patients, as absorption from the Gl tract may be unreliable. Do not administer penicillins to hamsters, guinea pigs, gerbils, chinchillas or rabbits. Adverse reactions: Nausea, diarrhoea and skin rashes are the commonest adverse effects. Drug interactions: Avoid concurrent use with bacteriostatic antibiotios (e.g. tetracycline, erythromycin, chloramphenicol). Do not mix in the same syringe as aminoglycosides. A synergistic effect is seen when beta-lactam and aminoglycoside antimicrobials are used concurrently. DOSES Dogs, Cats: Parenteral: 7 mg/kg im. q24h; 15 mg/kg i.m. q48h for depot preparations. Oral: 10 mg/kg p.o. q8-12h. (Doses of 16-33 mg/kg i.v. q8h are used in humans to treat serious infections.) Dose chosen will depend on site of infection, causal organism and severity of the disease. Small mammals: Ferrets: 10-30 mg/kg s.c., p.o. q12h; Rats, Mice: 100-150 mg/kg i.m., s.c. q12h. Birds: 150-175 mg/kg i.m., s.c. q8-12h (g24h for long-acting preparations); Parrots, Raptors: 150-175 mg/kg p.o. q12h; Pigeons: 1-1.5 g/ drinking water (Vetremox pigeon) q24h for 3-5 days or 100-200 mg/kg p.o. q6-8h; Waterfowl: 1 g/ drinking water (Amoxinsol soluble powder) alternate days for 3-5 days, 300-500 mg/kg soft food for 3-5 days; Passerines 1.5g/I drinking water (Vetremox pigeon). Reptiles: 5-10 mg/kg i.m., p.o. q12-24h (most species); Chelonians: 5-50 mg/kg im., p.o. q12h. Amoxicillin/Clavulanate (Amoxycilin/Clavulanic acid) (Augmentin, Clavaseptin, Nisamox, Synulox) POM-V, POM Formulations: Injectable: 175 mg/ml suspension (140 mg amoxicillin, 35 mg clavulanate); 600 mg powder (500 mg amoxicillin, 100 mg clavulanate); 1.2 g powder (1 g amoxicilin, 200 mg clavulanate) for reconstitution (Augmentin). Oral: 50 mg, 250 mg, 500 mg tablets each containing amoxicillin and clavulanate in a ratio of 4:1. Palatable drops which when reconstituted with water provide 40 mg amoxicillin and 10 mg clavulanic acid per ml. Action: Amoxicillin binds to penicillin-binding proteins involved in bacterial cell wall synthesis, thereby decreasing cell wall strength and rigidity, affecting cell division, growth and septum formation. The addition of the beta-lactamase inhibitor clavulanate increases the antimicrobial spectrum against those organisms that produce beta- lactamase, such as Staphylococcus spp. Use: Active against Gram-positive and Gram-negative aerobic organisms and many obligate anaerobes. Penicillinase-producing Escherichia coliand Staphylococcus spp. are susceptible, but difficult 22 BSAVA Small Animal Formulary 6th edition Birds: Systemic fungal infections: 1-1.5 mg/kg i.v. q8-12h for 3-5 days (give with 10-15 ml/kg saline) or 1 mg/kg in 2 ml sterile water intratracheally q8-12h for 12 days then q48h for 5 weeks; Parrots: 100-300 mg/kg mg/kg p.o. q12-24h for Macrorhabdus infection; Passerines: 100,000 IU/kg p.o. q8-12h or 1-5 g/ drinking water) or 1 mg/ml in saline nebulized for 15 mins q12h. Reptiles: 0.5-1 mg/kg i.v., intracoelomically q24-72h for 2-4 weeks; for respiratory infections nebulize 5 mg in 150 ml saline for 30-60 min; may also use topically on lesions q12h. Ampicillin (Amfipen, Ampicaps, Ampicare, Duphacillin) POM-V Formulations: Injectable: Ampicillin sodium 250 mg, 500 mg powders for reconstitution (human licensed product only); 150 mg/ml suspension, 100 mg/ml long acting preparation. Oral: 50 mg, 125 mg, 500 mg tablets; 250 mg capsule. Action: Binds to penicillin-binding proteins involved in bacterial cell wall synthesis, thereby decreasing cell wall strength and rigidity, affecting cell division, growth and septum formation. It acts in a time-dependent bactericidal fashion. Use: Active against many Gram-positive and Gram-negative aerobic organisms and obligate anaerobes, but not against those that produce penicilinases (beta-lactamases), e.g. Escherichia coli, Staphylococcus aureus. The difficult Gram-negative organisms such as Pseudomonas aeruginosa and Klebsiella spp. are usually resistant. Ampicillin is excreted well in bile and urine. Maintaining levels above the MIC is critical for efficacy and thereby prolonged dosage intervals or missed doses can compromise therapeutic response. Dose and dosing interval is determined by infection site, severity and organism. Oral bioavailability is reduced in the presence of food. Safety and handling: After reconstitution the sodium salt will retain adequate potency for up to 8 hours if refrigerated, but use within 2 hours if kept at room temperature. Contraindications: Avoid the use of oral antibiotic agents in critically ill patients, as absorption from the GI tract may be unreliable. Do not administer penicillins to hamsters, guinea pigs, chinchillas or rabbits. Use with caution in gerbils and only when indicated by sensitivity testing. Adverse reactions: Nausea, diarrhoea and skin rashes are the commonest adverse effects. Drug interactions: Avoid the concurrent use of ampicillin with bacteriostatic antibiotics (e.g. tetracycline, erythromycin, chloramphenicol). Do not mix in the same syringe as aminoglycosides. A synergistic effect is seen when beta-lactam and aminoglycoside antimicrobials are used concurrently. BSAVA Small Animal Formulary 6th edition 23 DOSES Dogs: Routine infections: 10-20 mg/kg i.v., im., s.c., p.o. q6-8h. CNS or serious bacterial infections: up to 40 mg/kg i.v. q6h has been recommended. Cats: 10-20 mg/kg i.v., im., s.c., p.o. q6-8h. Small mammals: Ferrets: 5-30 mg/kg i.m., s.c. q12h; Rabbits, Chinchillas, Guinea pigs, Hamsters: do not use; Gerbils: 20-100 mg/kg s.c. q8h, 6-30 mg/kg p.o. q8h; Rats, Mice: 25 mg/kg i.m., s.c. qt2h, 50-200 mg/kg p.o. qt2h. Birds: 50-100 mg/kg i.v., i.m. q8-12h, 150-200 mg/kg p.o. q8-12h, 1-2 g/l drinking water, 2-3 g/kg soft feed. Reptiles: 20 mg/kg s.c., im. q24h O 26ºC. Amprolium (Coxoid) avm-gsL Formulations: Oral: 3.84% solution for dilution in water. Action: Thiamine analogue that disrupts protozoal metabolism. Use: Coccidiosis in homing/racing pigeons. Has been used for coccidiosis in dogs and cats. Limit duration of therapy to 2 weeks. Safety and handling: Normal precautions should be observed. Contiraindications: No information available. Adverse reactions: Anorexia, diarrhoea and depression in dogs. Prolonged high doses can cause thiamine deficiency. Drug interactions: No information available. DOSES Dogs: 300-400 mg/dog p.o. q24h for 5 days. Use lower end of dose in puppies. Cats: 300-400 mg/cat p.o. q24h. Birds: Pigeons: 28 ml of the concentrate in 4.5 | of drinking water for 7 days; in severe outbreaks continue with half-strength solution for a further 7 days; medicated water should be discarded after 24 hours. Passerines: 50-100 mg/l drinking water for 5 days or longer. Small mammais, Reptiles: No information available. Antivenom (European Adder) pom Formulations: Injectable: 10 ml vial for injection. Action: Immunoglobulin raised against venom inhibits toxic effects. Use: Used in the management of snake bites by the European Adder (Viper). The current supplier can be found on the internet. The value of antivenom decreases with time following the bite. There are no published studies on efficacy in small animals. This antivenom is unlikely to work for other snake bites and specialist help should be urgently sought for such bites. 24 BSAVA Small Animal Formulary 6th edition Safety and handling: Normal precautions should be observed. Contraindications: No information available. Adverse reactions: Anaphylactic reactions may develop. Drug interactions: No information available. DOSES Dogs, Cats: 10 ml concentrated antivenom per animal, diluted in 5 ml of 0.9% NaCl per kg body weight. Administer by i.v. infusion over 30 min or i.v. injection over 10-15 min. Repeat after 1-2 hours if signs persist. Small mammais, Birds, Reptiles: No information available. Apomorphine (APO-go*) Pom Formulations: Injectable: 10 mg/ml solution in 2 ml or 5 ml ampoules; 5 mg/ml, 10 mg/ml solutions in 10 ml pre-filled syringes. Action: Stimulates emesis through D2 dopamine receptors in the chemoreceptor trigger zone. Use: Induction of self-limiting emesis within a few minutes of administration in dogs where vomiting is desirable, e.g. following the ingestion of toxic, non-caustic foreign material. Emesis generally occurs rapidly and within a maximum of 10 min. Further doses depress the vomiting centre and may not result in any further vomiting. Must not be administered i.v. Safety and handling: Normal precautions should be observed. Contraindications: Induction of emesis is contraindicated if strong acid or alkali has been ingested, due to the risk of further damage to the oesophagus. Induction of vomiting is contraindicated if the dog is unconscious, fitting, or has a reduced cough reflex, or if the poison has been ingested for >2 hours, or if the ingesta contains paraffin, petroleum products or other oily or volatile organic products, due to the risk of inhalation. Adverse reactions: Apomorphine may induce excessive vomiting, respiratory depression and sedation. Drug interactions: In the absence of compatibility studies, apomorphine must not be mixed with other products. DOSES Dogs: 40-100 ug/kg s.c., im. (s.c. route is more effective). Cats: Not recommended; xylazine is a potent emetic in cats and at least as safe. Small mammais, Birds, Reptiles: No information available. Appeasines see Dog appeasing pheromone BSAVA Small Animal Formulary 6th edition 27 Cats: Doses of 10-25 mg/kg q48h have been suggested for the prevention of thromboembolism; this equates to !/, of a 300 mg tablet for an average sized cat p.o. 3 days a week. Some authors suggest a very low dose (0.5 mg/kg q24h) to inhibit platelet COX without preventing the beneficial effects of prostacyclin production. The safety and efficacy of these different doses have not been evaluated in clinical or experimental studies. Small mammals: Rodents: 50-150 mg/kg p.o. q4-8h. Birds: Parrots: 5 mg/kg p.o. q8h, 325 mg/250 ml drinking water. Reptiles: No information available. Atenolo! (Atenolo!*, Tenormin*) POM Formulations: Oral: 25 mg, 50 mg, 100 mg tablets; 5 mg/ml syrup. Action: Blocks the chronotropic and inotropic effects of beta- adrenergic stimulation, thereby slowing the heart. lts bronchoconstrictor, vasodilatory and hypoglycaemic effects are less marked. At levels in excess of therapeutic doses atenolol has a quinidine-like stabilizing effect on the heart. Use: Cardiac arrhythmias (atrial fibrillation, supraventricular tachycardia), hyperthyroidism, hypertrophic cardiomyopathy (cats), obstructive cardiac disease (severe aortic or pulmonic stenosis) and systemic hypertension. For supraventricular or ventricular arrhythmias, often added to other antiarrhythmic drugs, especially mexilitene. Unlikely to be effective for ventricular arrhythmias when used alone. Itis recommended to withdraw therapy gradually in patients who have been receiving the drug chronically. Safety and handling: Normal precautions should be observed. Contraindications: Patients with supraventricular bradycardia and atrioventricular (AV) block and relatively contraindicated in animals with congestive heart failure. Adverse reactions: Most frequently seen in geriatric patients with chronic heart disease or in patients with rapidly decompensating cardiac failure. Include bradycardia, impaired AV conduction, myocardial depression, heart failure, syncope, glucose intolerance, bronchospasm, diarrhoea and peripheral vasoconstriction. Depression and lethargy may occur as a result of atenolol's high lipid solubility and its penetration into the CNS. Drug interactions: As the beta effects of sympathomimetics (e.g. adrenaline, phenylpropanolamine, terbutaline) may be blocked by atenolol, the unopposed alpha effects may result in severe hypertension and a decreased heart rate. The hypotensive effect of atenolol is enhanced by anaesthetic agents that depress myocardial activity, phenothiazines, antihypertensive drugs (e.g. hydralazine, prazosin), diazepam, diuretics and other antiarrhythmics. There is an increased risk of severe hypotension, heart failure and AV block if atenolol is used with calcium-channel blockers (e.g. diltiazem, 28 BSAVA Small Animal Formulary 6th edition verapamil). Concurrent digoxin administration potentiates bradycardia. The metabolism of atenolol is accelerated by thyroid hormones; thus the dose of atenolol may need to be decreased when initiating carbimazole therapy. Atenolol enhances the effects of muscle relaxants (e.g. suxamethonium, tubocurarine). Hepatic enzyme induction by phenobarbital may increase the rate of metabolism of atenolol. The bronchodilatory effects of theophylline may be blocked by atenolol. In patients with diabetes mellitus, insulin requirements should be monitored as atenolol may enhance the hypoglycaemic effect of insulin. DOSES Dogs: 0.5-2 mg/kg p.o. q12h; the lower dose is often used initially with gradual titration upwards if necessary. Cats: 6.25-12.5 mg/cat p.o. q24h initially, increasing to q12h after a week if necessary. Small mammais, Birds, Reptiles: No information available. Atipamezole (Antisedan) POM-v Formulations: Injectable: 5 mg/ml solution. Action: Selective alpha-2 adrenoreceptor antagonist. Use: Reverses the sedative effects of medetomidine; will also reverse other alpha-2 agonists to provide a quick recovery from anaesthesia and sedation. It also reverses other effects such as the analgesic, cardiovascular and respiratory effects of alpha-2 agonists. Atipamezole does not alter the metabolism of medetomidine but occupies the alpha-2 receptor preventing binding of medetomidine. The duration of action of atipamezole and medetomidine are similar, so re-sedation is uncommon. However, re-sedation may occur when atipamezole is given after romifidine (longer action). Atipamezole should not be administered until at least 45 min after medetomidine/ ketamine combinations have been given to cats, to avoid CNS excitation in recovery. Note: When alpha-2-mediated cardiovascular collapse is imminent, atipamezole may be given i.v. See Sedation protocols in Appendix. Safety and handling: Normal precautions should be observed. Contraindications: Atipamezole has been administered to a limited number of pregnant dogs and cats and therefore cannot be recommended in pregnancy. Routine administration of atipamezole i.v. is not recommended because the rapid recovery from sedation is usually associated with excitation, though i.v. administration may be indicated in an emergency (e.g. excessive sedation from medetomidine or cardiovascular complications). Adverse reactions: Transient over-alertness and tachycardia may be observed after overdosage. This is best handled by minimizing external stimuli and allowing the animal to recover quietly. Drug interactions: No information available. BSAVA Small Animal Formulary 6th edition 29 DOSES Dogs: Five times the previous medetomidine dose (in mg/kg) i.m.; i.e. equal volume to medetomidine. When medetomidine has been administered at least an hour before, dose of atipamezole can be reduced by half (i.e. half the volume of medetomidine), and repeated if recovery is slow. Cats: Two and a half times the previous medetomidine dose (in mg/kg) im.; i.e. half the volume of medetomidine given. Small mammals: Rodents: 1 mogi im., i.p., s.c.; Mice 1-2.5 mg/kg ip.; Other: 1 mg/kg i.m. Birds: 0.065 -0.25 mg/kg im. Reptiles: Five times the previous medetomidine dose (mg/kg) i.m., i.v. Atracurium (Tracrium*) POM Formulations: Injectable: 10 mg/ml solution. Action: Inhibits the actions of acetylcholine at the neuromuscular junction by binding competitively to the nicotinic acetylcholine receptor on the post-junctional membrane. Use: Neuromuscular blockade during anaesthesia. This may be to improve surgical access through muscle relaxation, to facilitate positive pressure ventilation or for intraocular surgery. Atracurium has an intermediate duration of action (15-35 min) and is non-cumulative due to non-enzymatic (Hofmann) elimination). It is therefore suitable for administration to animals with renal or hepatic disease. Monitoring (using a nerve stimulator) and reversal of the neuromuscular blockade is recommended to ensure complete recovery before the end of anaesthesia. Hypothermia, acidosis and hypokalaemia will prolong the duration of action of neuromuscular blockade. Safety and handling: Store in refrigerator. Contraindications: Do not administer unless the animal is adequately anaesthetized and facilities to provide positive pressure ventilation are available. Adverse reactions: Can precipitate the release of histamine after rapid i.v. administration, resulting in bronchospasm and hypotension. Diluting the drug in normal saline and giving the drug slowly i.v. minimizes these effects. Drug interactions: Neuromuscular blockade is more prolonged when atracurium is given in combination with volatile anaesthetics, aminoglycosides, clindamycin or lincomycin. DOSES Dogs, Cats: 0.5 mg/kg initially, followed by increments of 0.2 mg/kg iv. Small mammais, Birds, Reptiles: No information available. 32 BSAVA Small Animal Formulary 6th edition Azidothymidine see Zidovudine Azithromycin (Zithromax*) PoM Formulations: Oral: 250 mg capsule; 200 mg/5 ml suspension (reconstitute with water). Action: Binds to the 50S bacterial ribosome (like erythromycin), inhibiting peptide bond formation and has bactericidal or bacteriostatic activity depending on the susceptibility of the organism. Azithromycin has a longer tissue half-life than erythromycin, shows better oral absorption and is better tolerated in humans. Use: Alternative to penicillin in allergic individuals as it has a similar, although not identical, antibacterial spectrum. It is active against Gram-positive cocci (some Staphylococcus spp. are resistant), Gram-positive bacilli, some Gram-negative bacilli (Haemophilus and Pasteurella spp.), mycobacteria, obligate anaerobes, Chlamydophila spp., Mycoplasma spp. and Toxoplasma. Some strains of Actinomyces, Nocardia and Rickettsia are also inhibited. Most strains of the Enterobacteriaceae (Pseudomonas spp., Escherichia coli, Klebsiella spp.) are resistant. Useful in the management of respiratory tract, mild to moderate skin and soft tissue, and non-tubercular mycobacterial infections. It has not proved possible to eliminate C. felis from chronically infected cats using azithromycin, even with once daily administration. Little information is available on the use of this drug in animals and drug pharmacokinetics have not been studied closely in the dog and cat. Doses are empirical and subject to change as experience with the drug is gained. More work is needed to optimize the clinically effective dose rate. Azithromycin activity is enhanced in an alkaline pH; administer on an empty stomach. Safety and handling: Normal precautions should be observed. Contraindications: Use with great care in animals with hepatic dysfunction. Reduce dose in animals with renal impairment. Adverse reactions: In humans similar adverse effects to those of erythromycin are seen, i.e. vomiting, cholestatic hepatitis, stomatitis and glossitis, but the effects are generally less marked than with erythromycin. Drug interactions: Azithromycin may increase the serum levels of methylprednisolone, theophylline and terfenadine. The absorption of digoxin may be enhanced. DOSES Dogs: 5-10 mg/kg p.o. q12-24h. Cats: 5 mg/kg p.o. q48h. Small mammals: Rats: 10-20 mg/kg p.o. q12h for 14 days. Birds: 50 mg/kg p.o. q24h. Chlamydophilosis requires therapy for 45 days. Reptiles: 10 mg/kg p.o. q3d for skin infections; q5d for respiratory tract infections; q7d for liver and kidney infections. BSAVA Small Animal Formulary 6th edition 33 AZT see Zidovudine Benazepril (Fortekor) Pom-v Formulations: Oral: 2.5 mg, 5 mg, 20 mg tablets. Action: Inhibits conversion of angiotensin | to angiotensin Il, which results in veno- and arteriodilation and decreased salt and water retention (reduced aldosterone production). In the kidney, due to efferent arteriolar dilation resulting in a reduced glomerular filtration pressure, proteinuria may be reduced. Use: Reduce afterload on the heart when there is cardiac insufficiency and to reduce blood pressure in hypertension. It may be of benefit in certain cases of renal disease, particularly protein-losing glomerulopathies. Often used in conjunction with diuretics and other drugs in cases of heart failure. Less potent in reducing blood pressure compared with amlodipine in cats but sometimes used together as antihypertensives. Benazepril is rapidly converted by the liver to the active drug benazeprilat. Unlike enalapril, benazepril has significant hepatic metabolism and may not need dose adjustment in renal failure. Safety and handling: Normal precautions should be observed. Contraindications: Monitor blood pressure carefully when used in cases of severe heart failure. Use cautiously if sodium depletion is present. Adverse reactions: Potential adverse effects include hypotension, hyperkalaemia and renal impairment. Anorexia, vomiting and diarrhoea are rare. Dosage should be reduced if there are signs of hypotension (weakness, disorientation). Although no teratogenic effects have been reported, it is not recommended for breeding dogs, or pregnant or lactating bitches, as it apparently crosses the placenta and enters milk. Drug interactions: Concomitant usage with potassium-sparing diuretics, e.g. spironolactone, or potassium supplements could result in hyperkalaemia. There may be an increased risk of nephrotoxicity when used with NSAIDs. Concomitant administration of other antihypertensives can cause hypotension. DOSES Dogs: Heart failure: 0.25-0.5 mg/kg p.o. q24h. Cats: Chronic renal insufficiency: 0.5-1.0 mg/kg p.o. q24h. Small mammals: Rabbits: 0.25-0.5 mg/kg p.o. q24h. Birds, Reptiles: No information available. Benzoyl peroxide (Paxcutol) Pom-v Formulations: Topical: 2.5% shampoo. Action: Antimicrobial and keratolytic. 34 BSAVA Small Animal Formulary 6th edition Use: Topical treatment of bacterial skin infections in dogs. Concurrent systemic antibacterial therapy is generally advised. Leave in contact with the skin for 5-10 min prior to washing off. Safety and handling: Normal precautions should be observed. Contraindications: No information available. Adverse reactions: May irritate mucous membranes. Can bleach some fabrics. Drug interactions: No information available. DOSES Dogs: To be used as a shampoo 2-3 times weekly. May be used less frequently once infection is controlled. Cats, Small mammails, Birds, Reptiles: No information available. Benzyl penicillin see Penicillin G Betamethasone (Betnesol”, Betsolan, Fuciderm, Maxidex”, Norbet, Oterna, Vetsovate) POM-V, POM Formulations: Injectable: 2 mg/ml suspension for i.m. use; 2 mg/ml solution for i.v. use. Oral: 0.25 mg tablet. Ophthalmic/Otic: 0.1%. betamethasone solution. Betamethasone is also present in varying concentrations in several topical preparations with or without antibacterials. Action: Alters the transcription of DNA, leading to alterations in cellular metabolism which causes reduction in inflammatory responses. Has high glucocorticoid but low mineralocorticoid activity. Betamethasone also antagonizes insulin and ADH. Use: Short-term relief of many inflammatory but non-infectious conditions. Betamethasone has a long duration of activity and therefore is not suitable for long-term daily or alternate-day use. It has an anti-inflammatory potency 8.75 times greater than prednisolone. On a dose basis, 0.12 mg betamethasone is equivalent to 1 mg prednisolone. Prolonged use of glucocorticoids suppresses the hypothalamic-pituitary axis, resulting in adrenal atrophy. Animals on chronic corticosteroid therapy should be given tapered decreasing doses when discontinuing the drug. Safety and handling: Wear gloves when applying cream. Contraindications: Do not use in pregnant animals. Systemic corticosteroids are generally contraindicated in patients with renal disease and diabetes mellitus. Impaired wound healing and delayed recovery from infections may be seen. Topical corticosteroids are contraindicated in ulcerative Keratitis. Use glucocorticoids with care in rabbits as they are a corticosteroid-sensitive species and even small single doses can cause severe pathological changes. BSAVA Small Animal Formulary 6th edition 37 Adverse reactions: Abdominal discomfort and diarrhoea . Drug interactions: No information available. DOSES Dogs: 5-20 mg/dog prn. Cats: 2-5 mg/cat prn. Small mammais, Birds, Reptiles: No information available. Bismuth salts (Bismuth carbonate, subnitrate and subsalicylate: tri-potassium di-citrato bismuthate (bismuth chelate)) (BCK granules, De-Noltab*, Pepto-Bismol*) AVM-GSL, P Formulations: Oral: BCK, granules containing 39.2 mg/g bismuth subnitrate + 49 mg/g calcium phosphate + 400 mg/g charcoal + 422 mg/g kaolin. De-Noltab: tablets containing the equivalent of 120 mg bismuth oxide. Pepto-Bismol: bismuth subsalicylate suspension. Action: Bismuth is a gastric cytoprotectant with activity against spiral bacteria. Bismuth chelate is effective in healing gastric and duodenal ulcers in humans, due to its direct toxic effects on gastric Helicobacter pylori and by stimulating mucosal prostaglandin and bicarbonate secretion. It is often used in conjunction with an H2 receptor antagonist. Bismuth subsalicylate has a mild anti-inflammatory effect. Use: Acute oral poisoning, gastric ulceration and flatulent diarrhoea. Doses for products oher than BCK are empirical; none have been defined in dogs and cats. Safety and handling: Normal precautions should be observed. Contraindications: Do not use where specific oral antidotes are being administered in cases of poisoning. Do not use if the patient is unconscious, fitting, or has a reduced cough reflex, or in cases of intestinal obstruction, or where enterotomy or enterectomy is to be performed. Pepto-Bismol should be used with caution in cats due to its subsalicylate content. Adverse reactions: Avoid long-term use (except chelates) as absorbed bismuth is neurotoxic. Bismuth chelate is contraindicated in renal impairment. Nausea and vomiting reported in humans. Drug interactions: Absorption of tetracyclines is reduced by bismuth and specific antidotes may also be affected. DOSES Dogs: BCK: 1-3 heaped teaspoons (--5 ml, 69) p.o. q8-12h. De-Noltab: !/, tab p.o. q6h (dogs up to 30 kg), 1 tab p.o. q6h (>30 kg). Pepto-Bismol: 1 ml/kg p.o. q4-6h. Cats: BCK: 1-3 heaped teaspoons (5 ml, 6 9) p.o. q8-12h. De-Noltab: !/> tab p.o. q6h. Pepto-Bismol: 1 ml/kg p.o. q4-6h — use with caution. Small mammals: Ferrets: Pepto-Bismol: 0.25-1.0 ml/kg p.o. q4-Bh. Birds, Reptiles: No information available. 38 BSAVA Small Animal Formulary 6th edition Bowel cleansing solutions (Polyethylene glycol, Macrogol) (Klean-Prep*, Moviprep*) P Formulations: Oral: Powder for reconstitution. Action: Bowel cleansing solutions contain polyethylene glycol as an osmotic laxative and balanced electrolytes to maintain isotonicity and prevent net fluid loss or gain. When administered orally they rapidly empty the bowel. Use: Bowel preparation before colonoscopy or radiographic examination. May also be used for constipation. Powder may take several minutes to dissolve, and reconstitution is best performed by adding warm water to the powder. Safety and handling: Normal precautions should be observed. Contraindications: Gl obstruction or perforation. Do not administer to heavily sedated patients or animals with a reduced gag reflex. Adverse reactions: Diarrhoea is an expected outcome. Occasional vomiting is seen, especially if the maximum volume is administered. Inhalation can cause severe, and even fatal, aspiration pneumonia. Drug interactions: Oral medication should not be taken within 1 hour of administration as itmay be flushed from the Gl tract and not absorbed. DOSES Dogs: Prior to lower Gl examination: 22-33 ml/kg p.o. by stomach tube, two or three times, at least 4h apart. Cats: Prior to lower GI examination: 22-33 ml/kg p.o. by naso- oesophageal tube. Small mammais, Birds, Reptiles: No information available. Brinzolamide (Azopt') Pom Formulations: Ophthalmic: 10 mg/ml (1%) in 5 ml bottle. Action: Reduces intraocular pressure by reducing the rate of aqueous humour production by inhibition of the formation of bicarbonate ions within the ciliary body epithelium. Use: In the control of all types of cainine glaucoma in dogs, either alone or in combination with other topicals. It may be better tolerated than dorzolamide due to a more physiological pH of 7.5. The concurrent use of a topical or systemic carbonic anhydrase inhibitor is not beneficial as there is no additional decrease in intraocular pressure compared with the sole use of either topical or systemic treatment. Brinzolamide is ineffective in normal cats; by contrast dorzolamide is effective in both dogs and cats. Safety and handling: Normal precautions should be observed. Contraindications: Severe hepatic or renal impairment. Adverse reactions: Local irritation. Brinzolamide may cause less ocular irritation than dorzolamide. Drug interactions: No information available. BSAVA Small Animal Formulary 6th edition 39 DOSES Dogs: 1 drop per eye g8-12h. Cats: Not applicable. Small mammais, Birds, Reptiles: No information available. British anti-lewisite see Dimercaprol Bromhexine (Bisolvon) Pom-v Formulations: Injectable: 3 mg/ml solution. Oral: 10 mg/g powder. Action: A bronchial secretolytic that disrupts the structure of acid mucopolysaccharide fibres in mucoid sputum and produces a less viscous mucus, which is easier to expectorate. Use: To aid the management of respiratory diseases. Safety and handling: Normal precautions should be observed. Contiraindications: No information available. Adverse reactions: No information available Drug interactions: No information available. DOSES Dogs: 3-15 mg/dog i.m. q12h; 2-2.5 mg/kg p.o. q12h. Cats: 3 mg/cat im. q24h; 1 mg/kg p.o. q24h. Small mammals: 0.3 mg/animal p.o. q24h. Birds: 1.5 mg/kg i.m., p.o. q12-24h. Reptiles: 0.1-0.2 mg/kg q24h. Bromocriptine (Bromocriptine*, Parlodel*) PoM Formulations: Oral: 1 mg, 2.5 mg tablets; 5 mg, 10 mg capsules. Action: Bromocriptine stimulates dopamine receptors in the CNS and inhibits release of prolactin by the pituitary. Use: Management of false pregnancy. Safety and handling: Normal precautions should be observed. Contiraindications: No information available. Adverse reactions: Vomiting, anorexia, depression and behavioural changes may be seen. Drug interactions: Metoclopramide may antagonize the hypoprolactinaemic effect of bromocriptine. DOSES Dogs: False pregnancy: 0.01 mg/kg p.o. q12h for 10 days or 0.03 mg/kg q24h for 16 days. Cats: Not used. Small mammais, Birds, Reptiles: No information available. 42 BSAVA Small Animal Formulary 6th edition Safety and handling: Normal precautions should be observed. Contraindications: Combination with full OP3 agonists is not recommended for analgesia; therefore, do not use for premedication when administration of potent opioids during surgery is anticipated. Adverse reactions: As a partial agonist, side effects are rare after clinical doses. Drug interactions: In common with other opioids, buprenorphine will reduce the doses of other drugs required for induction and maintenance of anaesthesia. DOSES Dogs: 20 ug/kgi.v., i-m., s.c. q6h. Cats: Doses as for dogs. Also well tolerated and effective when given sublingually. Small mammals: Ferrets: 0.05 mg/kg s.c. q6-12h; Rabbits: 0.05-0.1 mg/kg i.m., s.c. q6-12h; Guinea pigs, Gerbils, Hamsters, Rats: 0.01-0.05 mg/kg i.m., s.c. q6-12h; Mice: 0.05-0.1 mg/kg i.m., s.c. q6-12h. Birds: 0.01-0.05 mg/kg i.v., im g8-12h. Reptiles: 0.01 mg/kg i.m. q24-48h. Buserelin (Receptal) POM-v Formulations: Injectable: 4 ug/ml solution. Action: Synthetic GnRH (gonadotropin releasing hormone) analogue that stimulates LH and FSH production, thus causing oestrus to develop and progress. Use: To supplement natural LH in cases of ovulation failure or delay. Will also induce lactation postpartum. In males, it may stimulate testosterone secretion and is indicated in the management of genital hypoplasia and reduced libido. In ferrets it may be used in the management of signs of oestrus. In rabbits it is used to induce ovulation postpartum for insemination and to improve conception rates. Used in birds for chronic egg laying (must be combined with husbandry changes). Safety and handling: Normal precautions should be observed. Contraindications: No information available. Adverse reactions: Anaphylactic reactions may occasionally occur. Drug interactions: No information available. DOSES Dogs: 4 ug/dog im. q24-48h. Cats: 2 ug/cat im. once. Small mammals: Ferrets: 1.5 ug/ferret im. q24h for 2 days; Rabbits: 0.8 ug/rabbit s.c. at time of insemination or mating; Guinea pigs: 25 ug/guinea pig, repeat in 2 weeks. Birds: 0.5-1.0 ug/kg q48h, up to 3 times. Reptiles: No information available. BSAVA Small Animal Formulary 6th edition 43 Buspirone (Buspar*, Buspirone Hydrocloride*) POM Formulations: Oral: 5 mg, 10 mg tablets. Action: Blocks presynaptic and partially postsynaptic serotonin 1A receptors and downregulates serotonin 2 receptors. It is metabolized to a pharmacologically active metabolite. Use: Management of mild to moderate anxiety-related behaviour problems, including urine spraying in cats when associated with mild anxiety. Repeat dosing results in an exponential increase in blood levels, so caution is required in its use. Itis suggested that it has less sedative effect than benzodiazepines and less anticholinergic effect than the tricyclic antidepressants. Cats may often become more affectionate upon medication, but caution is advised if buspirone is to be used in multi-cat households due to reports of paradoxical increases in intraspecific aggression in association with buspirone medication. Safety and handling: Normal precautions should be observed. Contraindications: Renal or hepatic compromise, history of seizures. Adverse reactions: Paradoxical increase in anxiety may occur in some cases. Drug interactions: Plasma levels are elevated in the presence of erythromycin. DOSES Dogs: 1-2 mg/kg p.o. q8-12h. Cats: 0.5-1.0 mg/kg p.o. 98-12h. Urine spraying: dose for an initial 2-week period, then evaluate response. Small mammals: Rabbits: 0.25-1.0 mg/kg q12h p.o. Birds, Reptiles: No information available. Busulfan (Busulphan) (Myleran*) POM Formulations: Oral: 2 mg tablet. (Available in other countries as Busulfex, 6 mg/ml solution for i.v. administration, but use not been reported in animals.) Action: Interacts with cellular thio groups and nucleic acid to form DNA-DNA and DNA-protein crosslinks, resulting in inhibition of DNA synthesis and function. Use: Management of chronic granulocytic leukaemia and polycythaemia vera. See Appendix for conversion of body weight to body surface area. Safety and handling: Busulfan is listed as a Group 1 carcinogen. Disposable gloves should be worn to handle or administer tablets. Staff and clients should be warned that excreta (including saliva) may contain traces of the parent drug or its metabolites, and should be handled with due care. 44 BSAVA Small Animal Formulary 6th edition Contraindications: Bone marrow suppression, animals at high risk of infection. Adverse reactions: Frequent haematological assessment is required as excessive myelosuppression may result in irreversible bone marrow aplasia. Hyperpigmentation of the skin, progressive pulmonary fibrosis and hepatotoxicity may occur. Drug interactions: Phenytoin increases busulfan metabolism in the liver. DOSES Dogs, Cats: 2-6 mg/m? p.o. q24h initially until remission achieved, then at a reduced dosage/frequenoy as required to maintain remission. Small mammais, Birds, Reptiles: No information available. Butorphanol! (Dolorex, Torbugesic, Torbutrol) POM-V Formulations: Injectable: 10 mg/ml solution. Oral: 5 mg, 10 mg tablets. Action: Analgesia resulting from affinity for the OP2 opioid receptor. Also has OP3 receptor antagonist properties and an antitussive action resulting from central depression of the cough mechanism. Use: Management of mild perioperative pain. Provision of sedation through combination with acepromazine or alpha-2 agonists. Potent antitussive agent indicated for the relief of acute or chronic non- productive cough associated with tracheobronchitis, tracheitis, tonsillitis or laryngitis resulting from inflammatory conditions of the upper respiratory tract. Butorphanol has a very rapid and relatively short duration of action; in different models analgesia has been shown to last between 45 minutes and 4 hours. Butorphanol is metabolized in the liver and some prolongation of effect may be seen with impaired liver function. Butorphanol crosses the placenta and may exert sedative effects in neonates born to bitches treated prior to parturition. Butorphanol! is unlikely to be adequate for the management of severe pain. Higher doses of full OP3 agonists may be needed to provide additional analgesia after butorphanol but it is not necessary to wait 4h after butorphanol administration to give other opioids. Response to all opioids appears to be very variable between individuals; therefore assessment of pain after administration is imperative. Be careful of species differences in effect in birds. See Appendix for sedation protocols. Safety and handling: Protect from light Contraindications: Animals with diseases of the lower respiratory tract associated with copious mucous production. Premedication when administration of potent opioids during surgery is anticipated. Adverse reactions: As an OP2 agonist/OP3 antagonist, side effects such as respiratory depression, bradycardia and vomiting are rare after clinical doses. Cough suppression following torbugesic tablets may be associated with mild sedation. BSAVA Small Animal Formulary 6th edition 47 * Injectable: 200 mg/ml calcium borogluconate solution equivalent to 15 mg/ml calcium formed from 168 mg/ml of calcium gluconate and 34 mg/ml boric acid (Calcibor 20); 100 mg/ml (10%) calcium chloride solution containing 27.3 mg/ml elemental calcium (= 1.36 mEgq calcium/ml = 680 umol/ml); 100 mg/ml calcium gluconate solution 10 ml ampoules containing 9 mg elemental calcium/ml (= mEgq calcium/ml). * Oral: 600 mg calcium gluconate tablets (= 53.4 mg elemental calcium). Note on other formulations: 11.2 mg calcium gluconate, 13.3 mg calcium borogluconate, 3.6 mg calcium chloride; each contains 1 mg elemental calcium = 0.5 mEq calcium. Action: Calcium is an essential element involved in maintenance of numerous homeostatic roles and key reactions including activation of key enzymes, cell membrane potentials and nerve and musculoskeletal function. Use: Management of hypocalcaemia. Calcium gluconate and borogluconate are preferred for this. Calcium chloride is used as a positive inotrope in the management of cardiac arrest. Serum calcium levels and renal function tests should be assessed before starting therapy. ECG monitoring during i.v. infusions is advised. Avoid using mixed electrolyte solutions intended for cattle use if possible. Safety and handling: Normal precautions should be observed. Contraindications: Ventricular fibrillation or hypercalcaemia. Parenteral calcium should be used very cautiously in patients receiving digitalis glycosides or those with cardiac or renal disease. Calcium should be avoided in pregnancy unless there is a deficient state. Adverse reactions: Hypercalcaemia can occur, especially in renal impairment or cardiac disease. Tissue irritation is common and can occur with injectable preparation regardless of route. Rapid injection may cause hypotension, cardiac arrhythmias and cardiac arrest. Perivascular administration is treated by stopping the infusion, infiltrating the tissue with normal saline and topical application of corticosteroids. Use i.v. in dehydrated reptiles and birds may precipitate gout. Drug interactions: Patients on digitalis glycosides are more prone to develop arrhythmias if given i.v. calcium. All calcium salts may antogonize verapamil and other calcium-channel blockers. Calcium borogluconate is compatible with most i.v. fluids except those containing other divalent cations or phosphorus. Calcium borogluconate is reportedly compatible with lidocaine, adrenaline and hydrocortisone. Calcium chloride is incompatible with amphotericin B, cephalothin sodium and chlorphenamine. Calcium gluconate is incompatible with many drugs, including lipid emulsions, propofol, amphotericin B, cefamandole, naftate, cephalothin sodium, dobutamine, methyprednisolone sodium succinate and metoclopramide. Consult manufacturers' data sheets for incompatibilities with other solutions. 48 BSAVA Small Animal Formulary 6th edition DOSES Dogs: * Hypocalcaemia: 50-150 mg/kg calcium (boro)gluconate = 0.5-1.5 ml/kg of a 10% solution i.v. over 20-30 min (equivalent to 3.8-11.4 mg/kg calcium borogluconate or 4.5-14 mg/kg calcium gluconate). Alternatively 5-10 mg/kg calcium chloride or 0.05-0.1 mi/kg of a 10% solution i.v. (equivalent to 0.068-0.136 mEq/kg). Additional doses to a maximum of 1-1.5 g/kg calcium boro(gluconate) may need to be administered i.v. over the next 24 hours. Adjust dose by monitoring serum calcium and phosphorus levels. * Oral treatment of hypocalcaemia: 50-250 mg/kg calcium gluconate p.o. q8h; adjust dose by monitoring serum calcium and phosphorus levels. * Cardiac arrest: 1-2 ml of a 10% calcium chloride solution i.v. to effect, monitor the ECG. * Hyperkalaemia and hyperkalaemic cardiotoxicity: 0.5-1.5 ml/kg of a 10% solution of calcium gluconate i.v. slowly over 10-20 min, once. Monitor ECG. Rapidly corrects arrhythmias but effects are short-lived (5-10 min to effect) and i.v. glucose 0.5-1 g/kg with or without insulin may be needed. Cats: Parenteral: 95-140 mg calcium gluconate/kg slowly i.v. to effect. Using 10% calcium gluconate this is equivalent to 1-1.5 ml/kg slowly i.v. over 10-20 min. Monitor ECG if possible. If bradycardia, or Q-T interval shortening occurs, slow rate or temporarily discontinue. Once life-threatening signs are resolved, add calcium gluconate to i.v. fluids and administer slowly at 60-90 mg/kg/day elemental calcium. This converts to 2.5 ml/kg of 10% calcium gluconate q6-8h or the equivalent as a constant rate infusion over 24h. Monitor serum calcium and adjust as needed. Oral: Begin oral therapy at 50-100 mg elemental calcium/kg/day divided in 3-4 doses, equivalent to 560-1120 mg oral calcium gluconate. Small mammals: Chinchillas, Guinea pigs: 100 mg/kg i.m., ip. Birds: Egg retention, hypocalcaemia: 150-200 mg/kg calcium borogluconate i.m., s.c.; Hypocalcaemia: 5-10 mg/kg calcium gluconate im. q12h. Reptiles: Egg retention, hypocalcaemia: 100 mg/kg calcium borogluconate i.v., i.m. s.c. or 50-100 mg/kg calcium gluconate mg/kg im., s.c. Use with oxytocin for egg retention. Dilute both 1 in 10 with water for injection or dextrose-saline before use. Carbamazepine (Epimaz*, Tegretol*) POM Formulations: Oral: 100 mg, 200 mg tablets, 20 mg/ml liquid. Slow release formulations for oral use also available. Action: Stabilizes sodium ion channels in their inactive state, reducing the capacity to generate an action potential within the neurons. BSAVA Small Animal Formulary 6th edition 49 Use: Limbic or partial seizure activity, which can present as an apparent compulsive disorder in the form of tail chasing or spinning. Carbamazepine may also be used to manage neuralgic pain. Response may be temporary and may require supplementary therapy with other anticonvulsants. Contraindications: Atrioventricular abnormalities or history of bone marrow suppression. Adverse reactions: May cause nausea, vomiting, lethargy, irritability, GI disturbance and anxiety. An erythematous rash is not uncommon in humans. Drug interactions: Induces cytochrome P450 activity and so may alter the efficacy of drugs metabolized by this cytochrome. Valproic acid inhibits the breakdown of carbamazepine. DOSES Dogs: 4-8 mg/kg p.o. q12h. Cats: Often not tolerated well and so not recommended. Small mammais, Birds, Reptiles: No information available. Carbimazole (Vidalta) Pom-v Formulations: Oral: 10 mg, 15 mg tablets. Action: Carbimazole is metabolized to the active drug methimazole, which interferes with the synthesis of thyroid hormones. Use: Control of thyroid hormone levels in cats with hyperthyroidism. Has also been used in canine hyperthyroidism. A new formulation authorized for use in cats has recently been released. There are no data on its use in dogs. The dose is therefore empirically derived by extrapolation from the formulation authorized for use in humans. Consult specialist advice before administering to dogs. Safety and handling: Normal precautions should be observed. Contiraindications: No information available. Adverse reactions: Vomiting, rashes, alopecia, jaundice, anorexia, lymphopenia and leucopenia are reported but are rarely seen. Animals that have an adverse reaction to methimazole are likely also to have an adverse reaction to carbimazole. Drug interactions: Carbimazole must be discontinued for at least 2 weeks prior to iodine-131 treatment. DOSES Dogs, Cats: Starting dose 15 mg/animal p.o. q24h unless total thyroxine concentrations are <100 nmol/l in which case starting dose is 10 mg p.o. q24h. Adjust dose in 5 mg increments but do not break tablets. Small mammais, Birds, Reptiles: No information available. 52 BSAVA Small Animal Formulary 6th edition potential for drug accumulation and overdose with repeated dosing. Prolonged long-term treatment should be under veterinary supervision. In cats, due to the longer half-life and narrower therapeutic index, particular care should be taken not to exceed the recommended dose and the use of a 1 ml graduated syringe is recommended to measure the dose accurately. Tablets are not authorized for use in cats. Safety and handling: Rimadyl palatable tablets are extremely palatable. Animals have been reported to eat tablets spontaneously, resulting in overdose. Ensure that tablets are stored out of animal reach. Store injectable solution in the refrigerator; once broached the product is stable for use at temperatures up to 25ºC for 28 days. Contraindications: Do not give to dehydrated, hypovolaemic or hypotensive patients or those with GI disease or blood clotting abnormalities. Administration of carprofen to animals with renal disease must be carefully evaluated and is not advisable in the perioperative period. Do not give to pregnant animals or animals <6 weeks old. Use with caution in birds with dehydration, shock and renal dysfunction. Adverse reactions: Gl signs may occur in all animals after NSAID administration. Stop therapy if this persists beyond 1-2 days. Some animals develop signs with one NSAID drug and not another. A 1-2 wk wash-out period should be allowed before starting another NSAID after cessation of therapy. Stop therapy immediately if GI bleeding is suspected. There is a small risk that NSAIDs may precipitate cardiac failure in animals with cardiovascular disease. Drug interactions: Different NSAIDs should not be administered within 24 hours of each other or glucocorticoids as they are more ulcerogenic when used concurrently. The nephrotoxic tendencies of all NSAIDs are significantly increased when administered concurrently with other nephrotoxic agents, e.g. aminoglycosides. DOSES Dogs: 4 mg/kg i.v., s.c. preoperatively or at time of anaesthetic induction; single dose should provide analgesia for up to 24h. Continued analgesia can be provided orally at 4 mg/kg/day, in single or divided dose. Subject to clinical response the dose MAY be reduced to 2 mg/kg/day, single dose, after 7 days. Cats: 4 mg/kgi.v., s.c., single dose preoperatively or at time of anaesthetic induction. Small mammals: Ferrets: 1 mg/kg p.o; Rabbits: 1.5 mg/kg p.o., 1-2mgkgs.c., iv. q24h; Rodents: 2-5 mg/kg total daily dose i.v., im., s.c., p.o., in single or two divided doses; Others: 4 mg/kg i.v., im., s.c. Birds: 1-5 mg/kgi.m., s.c., p.o. q12-24h (higher rate appears effective for 24 hours). Reptiles: 4 mg/kg s.c., i.m., p.o. once, then 2 mg/kg s.c., im., p.o. q24h. BSAVA Small Animal Formulary 6th edition 53 Carvedilo! (Cardevidol*, Eucardic*) POM Formulations: Oral: 3.125 mg, 6.25 mg, 12.5 mg, 25 mg tablets. Action: Non-selective beta-blocker with the afterload reduction properties of an alpha-1 blocker. Additional antioxidant properties may decrease the oxidant stress associated with progressive heart failure. Use: Adjunct to diuretics, ACE inhibitors and digoxin/pimobendan in management of symptomatic chronic heart failure whether due to valvular disease or DCM in dogs. Limited data on pharmacokinetics and pharmacodynamics in dogs. Treatment should not be started until congestive heart failure has been stabilized for at least 2 weeks initially. Safety and handling: Normal precautions should be observed. Contraindications: Patients with supraventricular bradycardia, AV block and acute or decompensated heart failure. Adverse reactions: Likely to be similar to those of propranolol, i.e. bradycardia, impaired AV conduction, myocardial depression, heart failure, syncope, bronchospasm, diarrhoea and peripheral vasoconstriction. A reduction in the glomerular filtration rate may exacerbate pre-existing renal impairment. Drug interactions: Severe hypertension may develop when given with sympathomimetios (e.g. adrenaline, noradrenaline). Asystole, severe hypotension and heart failure develop in humans when given with verapamil. Enhanced hypotensive effects may develop when given with phenothiazines, nitroprusside, calcium-channel blockers and alpha-blockers. Hypotensive effect antagonized by NSAIDs. Carvedilol may enhance the hypoglycaemic effect of insulin. Systemic vascular resistance may develop when given with dobutamine. Increased risk of AV block and bradycardia when beta-blockers given with diltiazem or cardiac glycosides. Carvedilol increases plasma concentration of ciclosporin. DOSES Dogs: Start at 0.1-0.2 mg/kg q12h and gradually increase at 2-week intervals to target dose of 0.4 mg/kg p.o. q12h, if tolerated. Cats, Small mammais, Birds, Reptiles: No information available. CCNU see Lomustine Cefalexin (Cephalexin) (Cefaseptin, Ceporex, Rilexine) POMV Formulations: Injectable: 180 mg/ml (18%) suspension. Oral: 50 mg, 75 mg, 120 mg, 250 mg, 300 mg, 500 mg, 600 mg tablets; granules which, when reconstituted, provide a 100 mg/ml oral syrup. 54 BSAVA Small Animal Formulary 6th edition Action: Binds to proteins involved in bacterial cell wall synthesis, thereby decreasing cell wall strength and rigidity, and affecting cell division. Resistant to some bacterial beta-lactamases, particularly those produced by staphylococci. As for other beta-lactam antibacterials, works in a time-dependent fashion. Use: Active against several Gram-positive and Gram-negative organisms (e.g. Staphylococcus, Pasteurella and Escherichia coli). Pseudomonas and Proteus are often resistant. Maintaining levels above the MIC is critical for efficacy and prolonged dosage intervals or missed doses can compromise therapeutic response. Dose and dosing interval is determined by infection site, severity and organism. In severe or acute conditions, doses may be doubled or given at more frequent intervals. Safety and handling: Reconstituted oral drops should be stored in the refrigerator and discarded after 10 days. Contraindications: Patients hypersensitive to penicillins may also be sensitive to cephalosporins (cross-hypersensitivity in <10% of human patients); avoid use in animals with reported sensitivity to other beta-lactam antimicrobials. Adverse reactions: Vomiting and diarrhoea most commonesst; administration with food may reduce these. Cefalexin may cause enterotoxaemia in rodents and lagomorphs, although it is used in rabbits. Oral administration in particular carries a significant risk of fatal enterotoxaemia. Injection may be painful. Drug interactions: Bactericidal activity may be affected by concomitant use of bacteriostatic agents (e.g. erythromycin, oxytetracycline). May be an increased risk of nephrotoxicity if cephalosporins are used with amphotericin or loop diuretics (e.g. furosemide); monitor renal function. Do not mix in the same syringe as aminoglycosides. DOSES Dogs, Cats: 10-25 mg/kg p.o. q8-12h; im, s.c q24h. Small mammals: Ferrets: 15-30 mg/kg p.o. q8-12h; Rabbits: 15-20 mg/kg s.c q12-24h; Guinea pigs 25 mg/kg p.o., im. q12-24h; Others:15-30 mg/kg im. q8-12h. Birds: 35-100 mg/kg p.o., i.m. q6-8h. Reptiles: 20-40 mg/kg p.o. q24h at 30ºC. Cefotaxime (Cefotaxime*, Claforan*) POM Formulations: Injectable: 500 mg, 1 g, 2g powders for reconstitution. Action: Binds to proteins involved in bacterial cell wall synthesis, thereby decreasing cell wall strength and rigidity, and affecting cell division. Resistant to many bacterial beta-lactamases, particularly those produced by staphylococci. As other beta-lactam antibacterials, works in a time-dependent fashion. BSAVA Small Animal Formulary 6th edition 57 Adverse reactions: Gl disturbances associated with drug use in humans. Drug interactions: Bactericidal activity may be affected by concomitant use of bacteriostatic agents (e.g. oxytetracycline, erythromycin). May be an increased risk of nephrotoxicity if cephalosporins are used with amphotericin or loop diuretios (e.g. furosemide); monitor renal function. Do not mix in the same syringe as aminoglycosides. Ceftazidime is synergistic with the aminoglycoside antimicrobials in vivo (often used in humans for pseudomonal infection in neutropenic patients). DOSES Dogs, Cats: 20-50 mg/kg i.v. q8-12h. Small mammals: No information available. Birds: Birds: 75-200 mg/kg i.v., im. q6-12h. Reptiles: Most species: 20 mg/kg i.m., s.c., i.v. q72h; Chameleons: 20 mg/kg i.m., s.c. q24-48h. Ceftiofur (Excenel) Pom-v Formulations: Injectable: 1 g, 4g powder for reconstitution; 50 mg/ml suspension. Action: Binds to proteins involved in bacterial cell wall synthesis, thereby decreasing cell wall strength and rigidity and affecting cell division. Resistant to many bacterial beta-lactamases, particularly those produced by staphylococci. Uniquely among the cephalosporins, ceftiofur is metabolized to desfuroylceftiofur which is an active metabolite. Action is time-dependent. Use: Higher activity against many Gram-negative organisms, especially Enterobacteriaceae (not Pseudomonas) but lower activity against many Gram-positives than 1st and 2nd generation cephalosporins. Particularly useful for tortoises with bacterial respiratory tract infections (e.g. Pasteurella or Gram-negative bacteria). Use should be reserved for patients suffering from acute sepsis or serious infections where cultures are pending, other licensed preparations are not appropriate and the animal is not a good candidate for intensive aminoglycoside therapy (pre-existing renal dysfunction). Important to maintain tissue concentrations above the MIC. Authorized for use in dogs in other countries where the main indication for use is in the treatment of urinary tract infections. Safety and handling: Store powder in the refrigerator; once reconstituted store in the refrigerator and discard after 24h. Contraindications: Patients hypersensitive to penicillins may also be sensitive to cephalosporins (cross-hypersensitivity in <10% of human patients), avoid use in animals with reported sensitivity to other beta-lactam antimicrobials.Use with care in patients with renal disease and consider increasing dose interval. 58 BSAVA Small Animal Formulary 6th edition Adverse reactions: May produce pain on injection. Gl disturbance and superinfection with resistant microorganisms is a potential risk. May be an increased risk of nephrotoxicity if cephalosporins are used with amphotericin or loop diuretics (e.g. furosemide); monitor renal function. In dogs a dose- and duration-dependent anaemia and thrombocytopenia has been recorded, although this should not occur with recommended doses. Drug interactions: Bactericidal activity may be affected by concomitant use of bacteriostatic agents (e.g. oxytetracycline, erythromycin). The cephalosporins are synergistic with the aminoglycosides, but should not be mixed in the same syringe. DOSES Dogs: 2.2 mg/kg s.c. q24h. Cats, Small mammalis, Birds: No information available. Reptiles: Chelonians: 4 mg/kg i.m. q24h; Snakes: 2.2 mg/kg im. q24h. Cefuroxime (Zinacef*, Zinnat') PoM Formulations: Injectable: 250 mg, 750mg 1.5 g powders for reconstitution (sodium salt). Oral (as cefuroxime axetil): 125 mg, 250 mg tablets; 125 mg/5ml suspension. Action: Binds to proteins involved in bacterial cell wall synthesis, thereby decreasing cell wall strength and rigidity, and affecting cell division. Resistant to some bacterial beta-lactamases. As other beta-lactam antibacterials, works in a time-dependent fashion. Cefuroxime axetil is hydrolysed in intestinal mucosa and liver to yield active drug giving oral bioavailability. Use: Higher activity against many Gram-negative organisms but lower activity against many Gram-positive organisms when compared to fst generation cephalosporins. Good activity against a wider spectrum of Enterobacteriaceae (not Pseudomonas). Many obligate anaerobes also susceptible. Many uses but may be particularly indicated for surgical prophylaxis in prolonged and difficult orthopaedic procedures. Important to maintain tissue concentrations above the MIC. Safety and handling: Normal precautions should be observed. Contraindications: Patients hypersensitive to penicillins may also be sensitive to cephalosporins (cross-hypersensitivity in <10% of human patients); avoid use in animals with reported sensitivity to other beta-lactam antimicrobials. Adverse reactions: May cause pain on im. and s.c. injection. GI disturbance has been reported in humans, particularly associated with the oral axetil formulation. Drug interactions: Bactericidal activity may be affected by concomitant use of bacteriostatic agents (e.g. oxytetracycline, erythromycin). May be an increased risk of nephrotoxicity if BSAVA Small Animal Formulary 6th edition 59 cephalosporins are used with amphotericin or loop diuretios (e.g. furosemide); monitor renal function. Synergistic with aminoglycosides, do not mix in the same syringe. DOSES Dogs, Cats: 10-15 mg/kg iv. q8-12h. Small mammals: No information available. Birds: No information available. Reptiles: 100 mg/kg im. q24h for 10 days at 30ºC. Cephalexin see Cefalexin Charcoal (Activated charcoal) (BCK, Actidose-Aqua*, Charcodote*, Liqui-Char*) AVM-GSL Formulations: Oral: granules containing 39.2 mg/g bismuth subnitrate + 49 mg/g calcium phosphate + 400 mg/g charcoal + 422 mg/g kaolin (BCK); 50 g activated charcoal powder or premixed slurry (200 mg/ml). Action: Absorbs toxins, fluids and gases in the Gl tract. Activated charcoal has increased porosity and enhanced absorptive capacity. Use: Acute poisoning with with organophosphates, carbamates, chlorinated hydrocarbons, strychnine, ethylene glycol, inorganic and organic arsenical and mercurial compounds, polycyclic organic compounds (most pesticides), and dermal toxicants that may be ingested following grooming. As a general rule administer at a dose of at least 10 times the volume of intoxicant ingested. Safety and handling: Activated charcoal powder floats, covering everything in the area; prepare very carefully as it will stain permanently. Contraindications: Activated charcoal should not be used prior to the use of emetics. Adverse reactions: Charcoal colours stools black, which is medically insignificant but may be alarming to the owner. Drug interactions: Activated charcoal reduces the absorption and therefore efficacy of orally administered drugs. DOSES Dogs, Cats: 0.5-4 g p.o. of activated charcoal/kg as a slurry in water by stomach tube; usually followed by a saline cathartic 20-30 min later. Repeat dosing prn if emesis or massive toxin ingestion occurs. Small mammais, Birds, Reptiles: No information available. 62 BSAVA Small Animal Formulary 6th edition Chlorhexidine (Savion , Malaseb, Hibiscrub, Chlorohex*, Viatop*) POM-V, AVM-GSL Formulations: Topical shampoo 2% chlorhexidine + 2% miconazole (Malaseb); Cleansing solution 1.5% chlorhexidine + cetrimide (Savlon); Surgical scrub solution 4% chlorhexidine + isopropyl alcohol (Hibiscrub); Chlorhexidine (0.12%) mouthwash (Chlorohex) Topical gel: 0.06% chlorhexidine, aqua, raffinose, propylene glycol, saponins, triethanolamine, acrylates, phenoxyethanol, benzoic acid esters, allantoin (Viatop). Action: Chemical antiseptic that disrupts bacterial cell membrane. Use: Topical treatment of bacterial, dermatophyte and Malassezia skin infections in dogs as a shampoo (Malaseb). Washing surgical instruments, routine antisepsis for surgical operations (Savlon, Hibiscrub). Dental hygiene (Chlorohex). Topical treatment of mild pruritus (Viatop). Concurrent systemic antibacterial therapy is generally advised when treating bacterial skin infections. Leave in contact with the skin for 5-10min prior to washing off. Chlorhexidine as a single agent is not consistently effective as an antifungal. Safety and handling: Normal precautions should be observed. Contraindications: Ototoxic; should not be instilled in ears where the integrity of the tympanum is unknown. Adverse reactions: May irritate mucous membranes. Drug interactions: Not known. DOSES Dogs, cats: Shampoo 2-3 times weekly. May be used less frequently once infection is controlled. Small mammals: Apply to affected area q8h at 0.5-2.0% concentrations. 0.05% solution in water can be used as a safe wound flush. When treating dermatophytosis continue treatment for 2 weeks after apparent clinical cure and negative fungal culture results. Otic: Dilute topical products to a 1.0% concentration and apply topically q8-12h. Birds, Reptiles: No information available. Chlorphenamine (Chiorpheniramine) (Piriton*) Pom, GsL Formulations: Injectable: 10 mg/ml solution. Oral: 4 mg tablet, 0.4 mg/ml syrup. Action: Binds to H1 histamine receptors to prevent histamine binding. Use: Management of allergic disease and early treatment of anaphylaxis. Specific doses for dogs and cats have not been determined by pharmokinetic studies. Safety and handling: Normal precautions should be observed. Contraindications: Use with caution in cases with urinary retention, angle-closure glaucoma and pyloroduodenal obstruction. May reduce seizure threshold. BSAVA Small Animal Formulary 6th edition 63 Adverse reactions: May cause mild sedation. Drug interactions: No information available. DOSES Dogs: 4-8 mg q8h. Cats: 2-4 mg q8-12h. Small mammals: Ferrets: 1-2 mg/kg p.o. q8-12h; Rodents: 0.6 mg/kg p.o. q24h. Birds, Reptiles: No information available. Chlorpheniramine see Chlorphenamine Chlortetracycline (Aureomycin) Pom-v Formulations: Topical: 1% chlortetracycline hydrochloride ophthalmic ointment, wound powder containing 2% chlortetracycline hydrochioride (with 1% benzocaine); soluble powder 5.5% (w/w) for oral administration. Action: Bacteriostatic antibiotic which inhibits bacterial protein synthesis. Use: Inhibits growth of many Gram-positive and Gram-negative bacteria, rickettsiae, mycoplasmas, spirochaetes and other microbes. Used topically to treat ocular infections (including chlamydophilosis) and the wound powder is used topically to reduce infections. Also, soluble powder is used to make a solution suitable for oral administration (however, clean drinking water must also be available); because of the taste of the medication in the water this method is best avoided. Safety and handling: Normal precautions should be observed. Contiraindications: No information available. Adverse reactions: No information available. Drug interactions: Avoid combined use with bactericidal antimicrobials such as aminoglycosides and beta-lactams. DOSES Dogs, Cats: Ophthalmic: Apply at least three times daily to the affected eye. Use a separate tube for each animal to avoid contamination. Small mammals: Chinchillas: 50 mg/kg p.o. q12h; Hamsters: 20 mg/kg p.o. q12h; Mice: 25 mg/kg p.o. q12h. Birds: Pigeons: 40-50 mg/kg p.o. q8h or 130-400 mg/l drinking water; others: 2500-5000 mg per kg of feed for 45 days for chlamydophilosis. Reptiles: No information available. 64 BSAVA Small Animal Formulary 6th edition Cholestyramine see Colestyramine Chorionic gonadotrophin (Human chorionic gonadotrophin, ACG) (Chorulon) POM-v Formulations: Injectable: 1500 IU powder for reconstitution. Action: In females induces follicular maturation, ovulation and development of the corpus luteum. In males stimulates testosterone secretion. Use: Used to supplement or replace LH in cases of ovulation failure or delay, to induce lactation post-partum, or in bitches who fail to hold to mating. Used in ferrets to treat persistent oestrus. In male animals it may increase libido; may also assist the treatment of cryptorchidism before surgical castration, provided inguinal canal remains patent and therapy is started early. Safety and handling: Reconstituted vials do not contain any preservative and so should be discarded within 24 hours. Contraindications: No information available. Adverse reactions: Anaphylactic reactions may occasionally occur. Drug interactions: No information available. DOSES Dogs: * Delayed ovulation: 22 IU/kg i.m. q24-48h or 44 IU/kg i.m. once; mate on behavioural oestrus. * Anoestrus: 500 IU im. followed by 20 IU/kg q24h for 10 days. * Deficient male libido, cryptorchidism: 100-500 IU im. twice weekly for up to 6 weeks. Cats: Not authorized for use in cats. Doses as for dogs. Small mammals: Ferrets: 100 IU s.c., im. once; use 10-14 days after onset of oestrus; Guinea pigs: 100 IU/kg weekly for 3 doses. Birds, Reptiles: No information available. Ciclosporin (Cyclosporin(e)) (Atopica, Neoral*, Optimmune, Sandimmun*) POM Formulations: Ophthalmic: 0.2% ointment (Optimmune). Oral: 10 mg, 25 mg, 50 mg, 100 mg capsules; 100 mg/ml solution. Injectable: 50 mg/ml solution. Action: T lymphocyte inhibition. Use: Authorized for veterinary use as topical ophthalmic preparation for keratoconjunctivitis sicca in dogs and as oral preparation for atopic dermatitis in dogs. May also be useful as an immunosuppressant in chronic superficial keratoconjunctivitis (pannus), perianal fistula, sebaceous adenitis and immune-mediated diseases. No evidence of systemic or ocular toxicity following ocular BSAVA Small Animal Formulary 6th edition 67 Drug interactions: Retards oxidative hepatic drug metabolism by binding to the microsomal cytochrome P450. May increase plasma levels of beta-blockers (e.g. propranolol), calcium-channel blockers (e.g. verapamil), diazepam, lidocaine, metronidazole, pethidine and theophylline. When used with other agents that cause leucopenia may exacerbate the problem. Sucralfate may decrease bioavailability; although there is little evidence to suggest this is of clinical importance it may be a wise precaution to administer sucralfate at least 2 hours before cimetidine. Stagger oral doses by 2 hours when used with other antacids, digoxin, ketoconazole or maropitant. DOSES Dogs: 5-10 mg/kg i.v., im., p.o. q8h. Cats: 2.5-5 mg/kg iv., im., p.o. q12h. Small mammals: Ferrets: 5-10 mg/kg i.m., s.c.,p.o. q8h; Rodents: 5-10 mg/kg p.o. s.c., im., i.v. q6-12h. Birds: No information available. Reptiles: 4 mg/kg im., p.o. q8h. Cinchophen (PLT tablets) Pom-v Formulations: Oral: 200 mg tablets in combination with prednisolone img. Action: Anti-inflammatory agent via non-steroidal action. Use: Management of osteoarthritis pain in dogs. Animals should be monitored for signs of GI ulceration and deterioration in liver function. At the end of treatment the dose should be reduced gradually as with any glucocorticoid. Safety and handling: Normal precautions should be observed. Contraindications: Only commercially available in tablets combined with prednisolone, therefore do not administer to animals that are receiving therapy with other steroids or with NSAIDs. Do not give in perioperative period or to animals that are shocked, hypotensive or have renal insufficiency. Do not give to animals with hepatic disease or with pre-existing GI ulceration. Do not use in cats or small mammals. Adverse reactions: GI ulceration and irritation are common side effects of all NSAIDs and particularly so with cinchophen. Advisable to stop therapy if diarrhoea or nausea persists beyond 1-2 days. Stop therapy immediately if GI bleeding suspected and begin symptomatic treatment. There is a small risk that NSAIDs may precipitate cardiac failure in animals with cardiovascular disease. Cinchophen has been associated with liver damage in dogs after prolonged oral administration (6 weeks). Drug interactions: Increased risk of Gl ulceration if administered concurrently or within 24 hours of other NSAIDs and glucocorticoids. Increased risk of nephrotoxicity if administered with other potentially nephrotoxic agents, e.g. aminoglycosides. 68 BSAVA Small Animal Formulary 6th edition DOSES Dogs: 25 mg/kg p/o q12h. Cats, Small mammalis: Do not use. Birds, Reptiles: No information available. Ciprofloxacin (Ciloxan*, Ciproxin*) PoM Formulations: Oral: 100 mg, 250 mg and 500 mg tablets; 50 mg/ml suspension. Injectable: 2 mg/ml for i.v. infusion. Ophthalmic: 0.3% solution in 5 ml bottle; 0.3% ointment in 3.5 g tube. Action: Bactericidal through inhibition of bacterial DNA gyrase. Use: Broad-spectrum activity against wide range of Gram-negative and some Gram-positive aerobes; some activity against Mycoplasma and Chlamydophila. Active against many ocular pathogens, including Staphylococcus and Pseudomonas aeruginosa, although there is increasing resistance amongst staphylococci and streptococci. Use should be reserved for serious corneal infections due to sensitive organisms, particularly aminoglycoside-resistant Pseudomonas when other antibacterials are ineffective, and should ideally be dictated by sensitivity testing. The eyedrop formulation is also used in reptiles for the topical management of wounds. Safety and handling: Normal precautions should be observed. Contraindications: No information available. Adverse reactions: May cause local irritation after application. In humans the following are reported: local burning and itching; lid margin crusting; hyperaemia; taste disturbances; corneal staining, keratitis, lid oedema, lacrimation, photophobia, corneal infiltrates; nausea; and visual disturbances. Drug interactions: No information available. DOSES Dogs, Cats: 1 drop to affected eye q6h; loading dose can be used 1 drop to affected eye q15min for 4 doses. Small mammals: Rabbits: 1 drop to affected eye q6h; loading dose can be used 1 drop to affected eye q15min for 4 doses; Chinchillas, Guinea pigs: 5-25 mg/kg p.o. q12h; Hamsters: 10-20 mg/kg p.o. qt2h; Other rodents: 7-25 mg/kg p.o. q12h. Birds: No information available. Reptiles: Topical: 1 drop to affected eyes or in wounds. Systemic: 5-10 mg/kg p.o., s.c., im. q24h. Cisatracurium (Nimbex') PoM Formulations: Injectable: 2 mg/ml, 10 mg/ml solutions. BSAVA Small Animal Formulary 6th edition 69 Action: Inhibits actions of acetylcholine at neuromuscular junction by binding competitively to nicotinic acetylcholine receptor on post- junctional membrane. Use: Provision of neuromuscular blockade during anaesthesia. This may be to improve surgical access through muscle relaxation, to facilitate positive pressure ventilation or for intraocular surgery. Cisatracurium is one of the isomers that comprise atracurium; it is 3-5 times more potent than atracurium in dogs. This means that the plasma concentrations of the epileptogenic byproduct laudanosine are lower and there is less histamine release. Monitoring (using a nerve stimulator) and reversal of the neuromuscular blockade is recommended to ensure complete recovery before the end of anaesthesia. Hypothermia, acidosis and hypokalaemia will prolong the duration of action of neuromuscular blockade. Safety and handling: Store in refrigerator. Contraindications: Do not administer unless the animal is adequately anaesthetized and facilities to provide positive pressure ventilation are available. Adverse reactions: Can precipitate the release of histamine after rapid i.v. administration, resulting in bronchospasm and hypotension. Diluting the drug in normal saline and giving the drug slowly i.v. minimizes these effects. Drug interactions: Neuromuscular blockade is more prolonged when given in combination with volatile anaesthetics, aminoglycosides, oclindamycin and lincomycin. DOSES Dogs: 0.1 mg/kg i.v. followed by additional doses of 0.03 mg/kg as required (based on monitoring of neuromuscular blockade) Cats, Small mammais, Birds, Reptiles: No information available. Cisplatin (Cisplatin*) PoM Formulations: Injectable: 1 mg/ml solution; 10 mg, 50 mg and 150 mg powders for reconstitution. Action: Binds to DNA to form intra- and interstrand crosslinks and DNA-protein crosslinks, resulting in inhibition of DNA synthesis and function. Use: Most commontly in management of canine osteosarcoma but has been described against various sarcomas and carcinomas. The drug is irritant and must be administered via a preplaced i.v. catheter. Do not use needles or i.v. sets containing aluminium; plastic catheters, plastic hub needles and stainless steel are compatible. Pre- and post-treatment hydration is important to ensure adequate renal clearance and reduce nephrotoxicity. Patients should be observed carefully during administration because of adverse effects. See Appendix for conversion of body weight to surface area. 72 BSAVA Small Animal Formulary 6th edition DOSES Birds: Raptors: 30 mg/kg once; Pigeons: 5-10 mg/kg once (treat all birds in loft simultaneously); Psittacines: 7 mg/kg p.o q2d for 2 doses. Dogs, Cats, Small mammals, Reptiles: No information available. Clemastine (Tavegil") GsL Formulations: Oral: 1 mg tablet. Action: Binds to H1 histamine receptors and prevents histamine from binding. Use: Management of allergic disease. Specific doses for cats have not been determined by pharmokinetic studies and in dogs therapeutic levels are not usually achieved by oral administration. Safety and handling: Normal precautions should be observed. Contraindications: Use with caution in cases with urinary retention, angle-closure glaucoma and pyloroduodenal obstruction. Adverse reactions: May cause mild sedation. May reduce seizure threshold. Drug interactions: No information available. DOSES Dogs: 0.05-0. img/kg p.o. q12h. Cats: 0.1 mg/kg p.o. q12h. Small mammais, Birds, Reptiles: No information available. Clindamycin (Antirobe, Clinacin) PoM-v Formulations: Oral: 25 mg, 75 mg, 150 mg, 300 mg capsules. Action: Lincosamide antibiotic that binds to the 508 ribosomal subunit, inhibiting peptide bond formation. May be bactericidal or bacteriostatic depending on susceptibility. Use: Bone and joint infections associated with Gram-positive bacteria; pyoderma; toxoplasmosis; and infections associated with the oral cavity. Active against Gram-positive cocci (including penicillin- resistant staphylococci), many obligate anaerobes, mycoplasmas and Toxoplasma gondii. Attains high concentrations in bone and bile. Being a weak base, it becomes ion-trapped (and therefore concentrated) in fluids that are more acidic than plasma, such as prostatic fluid, milk and intracelular fluid. There is complete cross resistance between lincomycin and clindamycin, and partial cross resistance with erythromycin. Use with care in individuals with hepatic or renal impairment. Safety and handling: Normal precautions should be observed. Contraindications: Lincosamides cause a potentially fatal clostridial enterotoxaemia in rabbits, guinea pigs, chinchillas and hamsters and should be avoided in these species. BSAVA Small Animal Formulary 6th edition 73 Adverse reactions: Colitis, vomiting and diarrhoea are reported. Although not a major problem in dogs and cats, discontinue drug if diarrhoea develops. In cats may be associated with oesophagitis and oesophageal stricture; therefore consider following tablet administration with a small water or food bolus. Drug interactions: May enhance the effect of non-depolarizing muscle relaxants (e.g. tubocurarine) and may antagonize the effects of neostigmine and pyridostigmine. Do not administer with macrolide, chloramphenicol or other lincosamide antimicrobials as these combinations are antagonistic. DOSES Dogs: 5.5 mg/kg p.o. q12h or 11 mg/kg q24h; in severe infection can increase to 11 mg/kg q12h. Toxoplasmosis: 25 mg/kg p.o. daily in divided doses. Cats: 5.5 mg/kg p.o. q12h or 1timg/kg q24h. Toxoplasmosis: 25 mg/kg p.o. daily in divided doses. Small mammals: Ferrets: 5.5-11 mg/kg p.o. q12h (toxoplasmosis: 12.5-25 mg/kg p.o. q12h). Rabbits, Rodents: Do not use. Birds: 25 mg/kg p.o. q8h or 50 mg/kg p.o. qt2h or 100 mg/kg p.o. q24h. Reptiles: 2.5-5 mg/kg p.o. q24h. Clodronate (Bonefos*, Loron*) PoM Formulations: Injectable: 30 mg/ml, 60 mg/ml solutions. Oral: 400 mg capsule. Action: Adsorbed on to hydroxyapatite crystals and ingested by osteoclasts. Metabolized in the cell to compounds that compete with ATP, leading to apoptosis of the cell and thus slowing the rate of bone destruction. Use: Treatment of acute moderate to severe hypercalcaemia when other therapies are ineffective, or in the long-term therapy of chronic hypercalcaemia. Few reports of use in dogs and no reports of use in cats or other veterinary species. Excretion reduced in chronic renal failure; dose adjustment may be required. Safety and handling: Normal precautions should be observed. Contiraindications: No information available. Adverse reactions: Nausea, diarrhoea, hypocalcaemia, hypophosphataemia, hypomagnesaemia and hypersensitivity reactions. Drug interactions: Reduced absorption if administered with antacids, calcium and iron salts, administer 2 hours apart. Concurrent use of aminoglycosides may result in severe hypocalcaemia. DOSES Dogs: 5-14 mg/kg i.v. q24h; 10-30 mg/kg p.o. q8-12h. Cats, Small mammais, Birds, Reptiles: No information available. 74 BSAVA Small Animal Formulary 6th edition Clofazimine (Clofazimine*) PoM Formulations: Oral: 100 mg capsule Action: Not entirely clear but appears to be bactericidal and has membrane disrupting properties. Use: Mycobacterial infections including feline leprosy. Limited information available, most derived from human medicine. For feline mycobaterial infection long-term treatment is required and combination therapy is utilized, e.g. with clarithromycin and doxycycline. Monitor hepatic and renal function during treatment. Safety and handling: Normal precautions should be observed. Contraindications: Use with caution in hepatic and renal impairment. Adverse reactions: In humans the major adverse effects are nausea, diarrhoea and renal and hepatic impairment (monitor functions during therapy). Skin discoloration has been reported in the cat. Drug interactions: No information available. DOSES Dogs, Cats: 2-12 mg/kg p.o. q24h for 2-6 months. Small mammais, Birds, Reptiles: No information available. Clomipramine (Clomicalm) Pom Formulations: Oral: 5, 20, 80 mg tablets. Action: Both clomipramine and its primary metabolite desmethylclomipramine are active in blocking serotonin and noradrenaline re-uptake in the brain, with resultant anxiolytic, antidepressant and compulsive effects. Use: Licensed for use in association with a behaviour modification plan for the management of separation-related disorders in dogs. Also used in management of a wider range of anxiety-related disorders in dogs and cats, including 'compulsive behaviours', noise fears and urine spraying. Used in birds for feather plucking, especially if due to separation anxiety, should be used in association with a behaviour modification plan. Can be used with benzodiazepines. Safety and handling: Normal precautions should be observed. Contraindications: Patients sensitive to tricyclic antidepressants. Noto be given in association with monoamine oxidase inhibitors (e.g. selegiline). Not recommended for use in male breeding animals, as testicular hypoplasia may occur. Care required before use in animals with a history of constipation, epilepsy, glaucoma, urinary retention or arrhythmias. Do not give with, or within 2 weeks of, monoamine oxidase inhibitors. Adverse reactions: May cause sporadic vomiting, changes in appetite or lethargy. Vomiting may be reduced by co-administration with a small quantity of food. BSAVA Small Animal Formulary 6th edition 77 Action: Topical imidazole with an inhibitory action on the growth of pathogenic dermatophytes, Aspergillus and yeasts by inhibiting cytochrome P450-dependent ergosterol synthesis. Use: Superficial fungal infections. Naso-sinal infections including aspergillosis. Safety and handling: Normal precautions should be observed. Contiraindications: No information available. Adverse reactions: No information available. Drug interactions: No information available. DOSES Dogs, Cats: Otic: Instil 3-5 drops in ear q12h. Topical: Apply to affected area and massage in gently q12h; if no improvement in 4 weeks re-evaluate therapy or diagnosis. Nasal: Instil 10 g (dogs up to 10 kg) or 20 g (dogs >10 kg) of 1% cream in each frontal sinus via trephine holes. Alternatively, instil 30 ml (in dogs up to 10 kg) or 60 ml (in dogs >10 kg) of a 1% solution in polyethylene glycol into each nasal cavity, with nares and nasopharynx sealed by Foley catheters and turning every 15 min. A combination of both aproaches may be used. Small mammals: Rabbits: Otic: Instil 3-5 drops in ear q12h; Topical: Apply to affected area and massage in gently q12h; if no improvement in 4 weeks re-evaluate therapy or diagnosis. Birds: Endoscopic: 10 mg/kg applied directly to fungal lesions. Nasal flush: 10 mg/ml (flush volume 20 ml/kg). Intratracheal: 2-3 ml of a 1% solution nebulized for periods of 1 hour q24h or topically. Reptiles: Apply topically to lesion q12h. Cloxacillin (Orbenin) Pom-v Formulations: Ophthalmic: Cloxacillin benzathine ester 16.7% suspension. Action: Beta-lactamase-resistant penicillin which is bactericidal and works in a time-dependent fashion. Binds to penicillin-binding proteins involved in cell wall synthesis, thereby decreasing bacterial cell wall strength and rigidity, and affecting cell division, growth and septum formation. Use: Narrow spectrum antimicrobial. Less active than penicillin G or V against Streptococcus. Specifically indicated for ocular infections by beta-lactamase-producing Staphylococcus. Avoid contamination of the tube during use. Safety and handling: Normal precautions should be observed. Contraindications: Do not administer penicillins to hamsters, gerbils, guinea pigs, chinchillas or rabbits. Adverse reactions: No information available. Drug interactions: Avoid the concomitant use of bacteriostatic antibiotics (chloramphenicol, erythromycin, tetracycline). 78 BSAVA Small Animal Formulary 6th edition DOSES Dog, Cats, Birds: Apply 1/10th of a tube (0.3 9) q24h. Small mammals: Rabbits, Chinchillas, Hamsters, Gerbils, Guinea pigs: do not use. Reptiles: No information available. Co-danthramer, Co-danthrusate see Dantron Codeine (Codeine*, Pardale-V) POM Formulations: Oral: 3 mg/ml, 3 mg/5 ml linctus. Action: Opioid analgesic. Use: Cough suppression, analgesia and diarrhoea. Pardale-V is a veterinary formulation with 400 mg paracetamol! + 9 mg codeine. However, to deliver the dose of codeine listed below would result in a very high dose of paracetamol and therefore Pardale-V tablets cannot be recommended as a source of codeine for general usage. Never administer Pardale-V to cats. Safety and handling: Normal precautions should be observed. Contraindications: Renal insufficiency, hypoadrenocorticism, increased intracranial pressure, hypothyroidism. Adverse reactions: Sedation, ataxia, respiratory depression and constipation. Drug interactions: No information available. DOSES Dogs: 0.5-2 mg/kg p.o. q12h. Cats: Do not use formulation with paracetamol. Small mammais, Birds, Reptiles: No information available. Colchicine (Colchicine*) PoM Formulations: Oral: 0.5 mg tablet. Action: Colchicine inhibits collagen synthesis, may enhance collagenase activity and blocks the synthesis and secretion of serum amyloid A. Use: Management of fibrotic hepatic and pulmonary diseases, oesophageal stricture and renal amyloidosis (including that caused by 'Shar pei fever”. In birds, used for gout and hepatic cirrhosis/ fibrosis. Only anecdotal evidence of efficacy against fibrosis in dogs. Prophylactic use in Shar pei fever cannot be recommended at this time. Safety and handling: Protect from light. Contraindications: Pregnanoy. BSAVA Small Animal Formulary 6th edition 79 Adverse reactions: The commoner adverse effects include vomiting, abdominal pain and diarrhoea. Rarely, renal damage, bone marrow suppression, myopathy and peripheral neuropathy may develop. Colchicine may cause elevated serum ALP and ALT, decreased platelet counts and false-positive results when testing urine for RBCs and haemoglobin. Overdoses can be fatal. Drug interactions: Possible increased risk of nephrotoxicity and myotoxicity when colchicine given with ciclosporin. DOSES Dogs: 0.03 mg/kg p.o. q8-72h in conjunction with appropriate specific/dietary therapy. Cats, Small mammalis: No information available. Birds: 0.04 mg/kg q12h. Reptiles: No information available. Colestyramine (Cholestyramine) (Questran*) POM Formulations: Oral: 4 g powder/sachet. Action: lon exchange resin. Use: In rabbits for absorbing toxins produced in the Gl tract following the development of overgrowth of Clostridium. In dogs for the reduction of serum cholesterol in idiopathic hypercholesterolaemia. May be used in digoxin overdose in dogs. Safety and handling: Normal precautions should be observed. Contiraindications: No information available. Adverse reactions: Constipation may develop. Drug interactions: Colestyramine reduces the absorption of digoxin, anticoagulants, diuretics and thyroxine. DOSES Dogs: 1-2 g/dog p.o. q12h. Cats: No information available. Small mammals: Rabbits: 2 g/rabbit p.o. syringed gently with 20 ml water. Birds, Reptiles: No information available. Cordycepic acid see Mannitol Crisantaspase (Asparaginase, L-Asparginase) (Asparginase”, Erwinase*, Elspar*) POM Formulations: Injectable: vials of 10,000 IU powder for reconstitution.