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PSy LLium Hy DRo PHi Lic muci LLoi D 785 monitoring Efficacy T! Adverse effects (heart rate, CNS stimulation, appetite)T! client information For this drug to be effective, it must be administered as directed T! by the veterinarian; missed doses will negate its effect. It may take several days for the full benefit of the drug to take place. Contact veterinarian if the animal demonstrates ongoing changes T! in behavior (restlessness, irritability) or if incontinence persists or increases. chemistry/Synonyms A sympathomimetic, pseudoephedrine HCl is the stereoisomer of ephedrine. It occurs as a fine, white to off-white powder or crystals. Approximately 2 grams are soluble in one m L of water. Pseudoephedrine may also be known as: pseudoephedrini, pseudoephedrina, Equi-Phar Equi-Hist 1200 Granules®, Drixoral®, Equiphed®, Histgranules®, Sudafed®, and Tri-Hist®. Storage/Stability Oral pseudoephedrine products should be stored at room tempera-ture in tight containers. Oral liquid preparations should be pro-tected from light and freezing. Dosage Forms/Regulatory Status In the USA, pseudoephedrine is classified as a list 1 chemical (drugs that can be used as precursors to manufacture methamphetamine) and in some states it may be a controlled substance or have other restrictions placed upon its sale. Be alert to persons desiring to pur-chase this medication. Vete Rina R y-Labe Le D PRo Duct S: Pseudoephedrine HCl 600 mg/oz and Pyrilamine maleate 600 mg/oz Granules in 20 oz, 5 lb and 10 lb containers; Equiphed® (AHC), Equi-Phar Equi-Hist 1200 Granules® (Vedco); Tri-Hist® Granules (Neogen); Histgranules® (Butler); (Rx). Approved for use in horses not intended for food. Do not use at least 72 hours before sporting events. The ARCI (Racing Commissioners International) has designated this drug as a class 3 substance. See the appendix for more information. Human-Labe Le D PRo Duct S: Pseudoephedrine HCl Tablets and Capsules: 15 mg (chewable), 30 mg (regular & softgel), and 60 mg; 120 mg and 250 mg extended/controlled-release. A common trade name is Sudafed®, but there are many others and generically labeled pseudoephedrine is available. All are OTC, but sales are now restricted to “behind-the-counter” status. Pseudonephedrine Sulfate Tables (Extended-Release): 120 mg; Drix-oral 12 Hour Non-Drowsy Formula® (Schering-Plough Healthcare); (OTC, restricted)Pseudoephedrine Liquid: 3 mg/m L and 6 mg/m L in 118 m L, 120 m L, 237 m L, 480 m L and 3. 8 L. A common trade name is Sudafed®, but there are many others, including generically labeled pseudoephedrine available. All are OTC, restricted. Pseudoephedrine Oral Drops: 7. 5 mg/0. 8 m L in 15 m L and 30 m L; (OTC, restricted)p Sylliu M Hydrop Hilic Mucilloid (sill-i-yum hye-droe-fill-ik myoo-sill-oid) Metamucil®, Equi-Psyllium® bulk forming gi l axative/antidiarrheal Prescriber Highlights Bulk-forming agent used for treatment & prevention of T T sand colic in horses, as a laxative, & to increase stool consistency in patients with chronic, watery diarrhea Contraindications: Rabbits. Where prompt intestinal T T evacuation is required, & when fecal impaction or intesti-nal obstruction is present. Adverse Effects: Flatulence; if insufficient liquid is given, T T increased possibility of esophageal or bowel obstruction uses/indications Bulk forming laxatives are used in patients where constipation is a result a too little fiber in their diets or when straining to defecate may be deleterious. Psyllium is considered the laxative of choice in the treatment and prevention of sand colic in horses. Psyllium has also been used to increase stool consistency in pa-tients with chronic, watery diarrhea. The total amount of water in the stool remains unchanged. Pharmacology/actions By swelling after absorbing water, psyllium increases bulk in the intestine and is believed to induce peristalsis and decrease intes-tinal transit time. In the treatment of sand colic in horses, psyl-lium is thought to help collect sand and to help lubricate its passage through the GI tract. Pharmacokinetics Psyllium is not absorbed when administered orally. Laxative action may take up to 72 hours to occur. contraindications/Precautions/Warnings Bulk-forming laxatives should not be used in cases where prompt intestinal evacuation is required, or when fecal impaction (no feces being passed) or intestinal obstruction is present. Psyllium prod-ucts are not recommended for use in rabbits as they may damage intestinal mucosa and cause blockage. adverse effects With the exception of increased flatulence, psyllium very rarely pro-duces any adverse reactions if adequate water is given or is available to the patient. If insufficient liquid is given, there is an increased possibility of esophageal or bowel obstruction occurring. Reproductive/nursing Safety Because there is no appreciable absorption of psyllium from the gut, it should be safe to use in pregnant animals. In humans, the FDA categorizes this drug as category B for use during pregnancy (Animal studies have not yet demonstrated risk to the fetus, but there are no adequate studies in pregnant women; or animal studies have shown an adverse effect, but adequate studies in pregnant women have not demonstrated a risk to the fetus in the first trimester of pregnancy, and there is no evidence of risk in later trimesters. ) Psyllium should be safe to administer to lactating animals.	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
786 Py Rante L P amoate overdosage/acute t oxicity If administered with sufficient liquid, psyllium overdose should cause only an increased amount of soft or loose stools. Drug interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving psyllium and may be of significance in veterinary patients: a SPi Rin T! (and other Sa Licy Late S ): Potential exists for psyllium to bind and reduce absorption if given at the same time; if possible, separate doses by 3 hours or more Di Goxin T! : Potential exists for psyllium to bind and reduce absorp-tion if given at the same time; if possible, separate doses by 3 hours or more nit Ro Fu Rantoin T! : Potential exists for psyllium to bind and reduce absorption if given at the same time; if possible, separate doses by 3 hours or more Doses Do GS:T! a) For a trial to treat chronic idiopathic large bowel diarrhea using Metamucil®: Median dose is 2 tablespoonsful (1. 33 g/ kg/day; range: 0. 32-4. 9 g/kg/day) per day added to a highly digestible diet such as Hill's i/d® (Leib 2004a), (Leib 2005) b) T o increase fiber in dogs with chronic colitis: Add 1-2 table-spoonsful (15-30 m L) per 25 kg body weight to animal's regular diet. (Jergens 2007) c) 1 teaspoonful-2 tablespoonsful mixed with food every 12 hours (Mc Connell and Hughey 1987) cat S:T! a) For chronic constipation: 1-4 teaspoonsful per meal added to canned cat food. Be sure cat is properly hydrated. (Washa-bau 2001) b) For adjunctive treatment of feline megacolon: 1-4 tea-spoonsful mixed with food PO q12-24h (Scherk 2003b) Ho RSe S:T! a) For treatment of sand colic: 0. 5 kg in 6-8 L (1 pound in 1. 5-2 gallons) of water via stomach tube. Mix with water just before administration; simultaneously mixing water with psyllium as mixture is being pumped is ideal. May re-peat as necessary as long as horse continues to pass feces and fluid does not accumulate in stomach. After initial treatment, may add up to 125 gm with each feeding; best if mixed with grain or sweet feed. Water must be available. (Calahan 1987) b) For sand impactions: 8 ounces in water via NG tube q24h. (Blikslager 2006a) monitoring Stool consistency, frequency T! client information Contact veterinarian if patient begins vomiting T! Be sure animal has free access to water T! chemistry/Synonyms Psyllium is obtained from the ripe seeds of varieties of Plantago species. The seed coating is high in content of hemicellulose muci-lage that absorbs and swells in the presence of water. Psyllium may also be known as Metamucil®; many other trade names are available. Storage/Stability Store psyllium products in tightly closed containers; protect from excess moisture or humidity. Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: Equine Enteric Colloid® (T echmix); Equi-Phar® Sweet Psyllium ( Ve-dco); (not for horses intended for food); Sandclear® (Farnam), An-ipsyll® Powder (AHC), Purepsyll® Powder (AHC), Vita-Flex Sand Re-lief® (Vita-lex), Equa Aid Psyllium® (Equi Aid); (OTC). Products may be available in 28 oz, 56 oz, 1 lb, 10 lb and 30 lb pails and are labeled for use in horses. Vetasyl Fiber Tablets for Cats® 500 mg, & 1000 mg tablets in bottles of 60 or 180; (Virbac) (OTC); Labeled for use in cats. Also contains barley malt extract powder, acacia and thiamine. Human-Labe Le D PRo Duct S: There are many human-approved products containing psyllium, most products contain approximately 3. 4 grams of psyllium per rounded teaspoonful. Dosages of sugar-free products may be different from those containing sugar. pyrantel p a Moate (pi-ran-tel) Strongid T®, Nemex® anti P ara Sitic Prescriber Highlights Pyrimidine anthelmintic used primarily for ascarids in a T T variety of species Contraindications: Severely debilitated animals T T Adverse Effects: Unlikely, emesis possible in small T T animals uses/indications Pyrantel has been used for the removal of the following para-sites in dogs: ascarids (Toxocara canis, T. leonina), hookworms (Ancylostoma caninum, Uncinaria stenocephala), and stomach worm (Physaloptera). Although not approved for use in cats, it is useful for similar parasites and is considered safe to use. Pyrantel is indicated (labeled) for the removal of the follow-ing parasites in horses: Strongylus vulgaris and equinus, Parasacaris equorum, and Probstymayria vivapara. It has variable activity against Oxyuris equi, S. edentatus, and small strongyles. Pyrantel is active against ileocecal tapeworm (A. perfoliata) when used at twice the recommended dose, although resistance has been reported. Although there are apparently no pyrantel products approved for use in cattle, sheep, or goats, the drug is effective (as the tar-trate) for the removal of the following parasites: Haemonchus spp., Ostertagia spp., Trichostrongylus spp., Nematodirus spp., Chabertia spp., Cooperia spp. and Oesophagostomum spp. Pyrantel tartrate is indicated (labeled) for the removal or preven-tion of the following parasites in swine: large roundworms (Ascaris suum) and Oesophagostomum spp. The drug has activity against the swine stomach worm (Hyostrongylus rubidus). Although not approved, pyrantel has been used in pet birds and llamas. See the Dosage section for more information.	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
Py Rante L P amoate 787 Pharmacology/actions Pyrantel acts as a depolarizing, neuromuscular-blocking agent in susceptible parasites, which paralyzes the organism. The drug pos-sesses nicotine-like properties and acts similarly to acetylcholine. It also inhibits cholinesterase. Pharmacokinetics Pyrantel pamoate is poorly absorbed from the GI tract, thus al-lowing it to reach the lower GI in dogs, cats and equines. Pyrantel tartrate is absorbed more readily than the pamoate salt. Pigs and dogs absorb pyrantel tartrate more so than do ruminants, with peak plasma levels occurring 2-3 hours after administration. Peak plasma levels occur at highly variable times in ruminants. Absorbed drug is rapidly metabolized and excreted into the urine and feces. contraindications/Precautions/Warnings Use with caution in severely debilitated animals. The manufactur-ers usually recommend not administering the drug to severely de-bilitated animals. adverse effects When administered at recommended doses, adverse effects are un-likely. Emesis may possibly occur in small animals receiving pyran-tel pamoate. Reproductive/nursing Safety In humans, the FDA categorizes this drug as category C for use dur-ing pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) In a separate system evaluating the safety of drugs in canine and fe-line pregnancy (Papich 1989), this drug is categorized as class: A (Probably safe. Although specific studies may not have proved he safety of all drugs in dogs and cats, there are no reports of adverse effects in laboratory animals or women. ) Pyrantel is considered safe to use in nursing veterinary patients. overdosage/acute t oxicity Pyrantel has a moderate margin of safety. Dosages up to approxi-mately 7 times recommended generally result in no toxic reactions. In horses, doses of 20X yielded no adverse effects. The LD 50 in mice and rats for pyrantel tartrate is 170 mg/kg; >690 mg/kg for pyrantel pamoate in dogs. Chronic dosing of pyrantel pamoate in dogs resulted in clinical signs when given at 50 mg/kg/day, but not at 20 mg/kg/day over 3 months. Clinical signs of toxicity that may be seen include in-creased respiratory rates, profuse sweating (in species with sweat glands), ataxia or other cholinergic effects. Drug interactions Diet Hy Lca Rbamazine T! : Increased risk for adverse effects Le Vami So Le T! : Because of similar mechanisms of action (and toxic-ity), do not use concurrently with pyrantel mo Rante LT! : Because of similar mechanisms of action (and toxic-ity), do not use concurrently with pyrantel o RGano PHo SPHate ST! : Increased risk for adverse effects Pi Pe Razine T! : Pyrantel and piperazine have antagonistic mecha-nisms of action; do not use together Doses All doses are for pyrantel pamoate unless otherwise noted. caution: Listed dosages are often not specified as to whether using the salt or base. Do GS:T! For susceptible parasites:a) For hookworms, or roundworms: 5 mg/kg PO after meals; repeat in 7-10 days (Willard 2003a) b) 15 mg/kg PO 30 minutes after a light meal. Re-treatment recommendations: For hooks: 2 weeks; every other week for 5-6 weeks (beginning at 1 week old) if bitch previously lost pups due to hookworm anemia. For Ascarids: Every other week for 3-4 treatments beginning at 2 weeks old if pups have heavy infestation; retreatment usually not necessary for mature animals. (Cornelius and Roberson 1986) c) Puppies: Can be treated as early as 2-3 weeks of age at 5-10 mg/kg PO; can be repeated every 2-3 weeks until at least 12 weeks of age. (Hoskins 2005d) d) For dogs weighing <5 lb: 10 mg/kg (as base) PO; for dogs weighing >5 lbs: 5 mg/kg (as base) PO. Treat puppies at 2, 3, 4, 6, 8, and 10 weeks of age. Treat lactating bitches 2-3 weeks after whelping. Do follow-up fecal 2-4 weeks after treating to determine need for retreatment. (Label directions; Nem-ex® Tabs—Pfizer) e) 20 mg/kg PO; be sure that liquid is well mixed before using; tablets may be broken for accurate dosing. Not approved for cats but very safe and effective. (Blagburn 2005b) cat S:T! For susceptible parasites:a) Ascarids, Hookworms, Physaloptera: 5 mg/kg, PO; repeat in 2 weeks (one time only for Physaloptera) (Dimski 1989) b) 10 mg/kg PO, repeat in 3 weeks (Kirk 1989) c) Kittens: Can be treated as early as 2-3 weeks of age at 5-10 mg/kg PO; can be repeated every 2-3 weeks until at least 12 weeks of age. (Hoskins 2005d) Rabbit S, Ro Dent S, Sma LL mamma LS:T! a) Rabbits: 15-10 mg/kg PO, repeat in 2-3 weeks (Ivey and Morrisey 2000) Ho RSe S:T! For susceptible parasites:a) 6. 6 mg (as base)/kg PO; 13. 2 mg (as base)/kg for cestodes (Robinson 1987), (Roberson 1988b) b) 19 mg/kg, PO (Brander, Pugh, and Bywater 1982) c) Pyrantel tartrate: 12. 5 mg/kg, PO (Roberson 1988b) SWine:T! For susceptible parasites:a) T o remove Ascaris suum or Oesophagostomum spp. : Pyrantel tartrate: 22 mg/kg PO (or in feed at a rate of 800 g/ton) as a single treatment. For Ascaris suum only: in feed at a rate of 96 g/ton (2. 6 mg/kg) for 3 days (Paul 1986) (Label instructions from several pyrantel tartrate premix products) b) Pyrantel tartrate: 22 mg/kg, PO; maximum of 2 grams per animal (Roberson 1988b) c) For ascarids and nodular worms in potbellied pigs: 6. 6 mg/kg PO (Braun 1995) catt Le, SHee P & Goat S:T! For susceptible parasites: a) Pyrantel tartrate: 25 mg/kg, PO (Roberson 1988b)	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
788 Py Ri Do Sti Gmine b Romi De LLama S:T! For susceptible parasites: a) 18 mg/kg, PO for one day (Cheney and Allen 1989), (Fowler 1989) bi RDS:T! For intestinal nematodes:a) 4. 5 mg/kg PO once. Repeat in 14 days. Suspension is non-toxic and palatable. (Clubb 1986) b) For nematodes: 100 mg/kg, PO as a single dose in psittacines and passerines (Marshall 1993) client information Shake suspensions well before administering. T! chemistry/Synonyms A pyrimidine-derivative anthelmintic, pyrantel pamoate occurs as yellow to tan solid and is practically insoluble in water and alcohol. Each gram of pyrantel pamoate is approximately equivalent to 347 mg (34. 7%) of the base. Pyrantel may also be known as: CP-10423-16, pyrantel embonate, pirantel pamoate, Anthel®, Antiminth®, Ascarical®, Aut ®, Bantel®, Cobantril®, Combantrin®, Combantrin®, Early Bird®, Helmex®, Helmintox®, Jaa Pyral®, Lombriareu®, Nemex ®, Nemocid®, Pin-X®, Pirantrim®, Pyrantin®, Pyrantrin®, Pyrapam®, Reese's® Pinworm, Strongid®, Trilombrin®, or Vertel ®. Storage/Stability/compatibility Pyrantel pamoate products should be stored in tight, light-resistant containers at room temperature (15-30°C) unless otherwise di-rected by the manufacturer. Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: note : Many products available; a partial listing of products follows: Pyrantel Pamoate Tablets: 22. 7 mg (of base), 113. 5 mg (of base); (OTC). Approved for use in dogs. A commonly known product is Nemex ® Tabs (Pfizer). Pyrantel Pamoate Oral Suspension: 4. 54 mg/m L (as base) (for dogs only); in 60 m L, 120 m L 280 m L and 473 m L bottles;) Many products are available; a commonly known trade name is Nemex-2® (Pfizer); (OTC) Pyrantel Pamoate Oral Suspension: 50 mg/m L (of base); Many prod-ucts are available; a commonly known trade name is Strongid® T (Pfizer); (OTC). Approved for use in horses not intended for food. Pyrantel Pamoate Oral Paste: 43. 9% w/w pyrantel base in 23. 6 g (20 m L) paste (180 mg pyrantel base/m L); Several products are available; a commonly known trade name is Strongid® Paste (Pfizer); (OTC). Approved for use in horses not intended for food. Pyrantel Tartrate 1. 06% (4. 8 g/lb) T op Dress: in 25 lb pails: Strongid C® (Pfizer); (OTC). Labeled for use in horses (not intended for food). Combination Products: Praziquantel 18. 2 mg/pyrantel pamoate 72. 6 mg (as base); Drontal® Tablets (Bayer); (OTC). Approved for use in cats and kittens that are 4 weeks of age or older and weigh 1. 5 lb. or greater. Praziquantel 30 mg/pyrantel pamoate 30 mg; & Praziquantel 114 mg/pyrantel pamoate 114 mg Chewable Tablets: Virbantel Flavored Chewables® (Virbac); (OTC). Approved for use in dogs. Praziquantel/pyrantel pamoate plus febantel Tablets: Small, medium and large dog sizes. Drontal® Plus Tablets (Bayer); (Rx); Approved for dogs and puppies 3 weeks of age or older and weighing 2 lb. or greater. Ivermectin/Pyrantel Oral Chewable Tablets: 68 mcg/57 mg, 136 mcg/114mg, 272 mcg/228 mg; Heartgard® Plus Chewables (Merial); Tri-Heart® Plus Chewable Tablets (Schering); (Rx). Approved for use in dogs. Human-Labe Le D PRo Duct S: Pyrantel Pamoate Oral Suspension or Liquid: 50 mg/m L pyrantel (as pamoate) in 30 m L and 60 m L; Antiminth® (Pfizer Labs); Reese's® Pinworm (Reese); Pin-X® (Effcon); (OTC) Pyrantel Soft-gel Capsules: 180 mg (equivalent to 62. 5 mg pyrantel base); Pin-Rid® (Apothecary); Reese's® Pinworm (Reese); (OTC) pyrido Stig Mine bro Mide (peer-i-oh-stig-meen) Mestinon® anticholine Stera Se agent Prescriber Highlights Anticholinesterase used for treatment of myasthenia T T gravis Contraindications: hypersensitivity to this class of com-T T pounds or bromides, patients with mechanical or physi-cal obstructions of the urinary or GI tract Caution: bronchospastic disease, epilepsy, hyperthyroid-T T ism, bradycardia or other arrhythmias, vagotonia, or GI ulcer diseases Adverse Effects: Usually dose related cholinergic effects T T GI (nausea, vomiting, diarrhea), salivation, sweating, re-spiratory (increased bronchial secretions, bronchospasm, pulmonary edema, respiratory paralysis), ophthalmic (miosis, blurred vision, lacrimation), cardiovascular (bra-dycardia or tachycardia, cardiospasm, hypotension, car-diac arrest), muscle cramps, & weakness uses/indications Pyridostigmine is used in the treatment of myasthenia gravis (MG) in dogs (and rarely in cats). It is considered to be much more effec-tive in acquired MG, than in congenital MG. Pharmacology/actions Pyridostigmine inhibits the hydrolysis of acetylcholine by directly competing with acetylcholine for attachment to acetylcholinest-erase. Because the pyridostigmine-acetylcholinesterase complex is hydrolyzed at a much slower rate than the acetylcholine-acetylcho-linesterase complex, acetylcholine tends to accumulate at cholin-ergic synapses with resultant cholinergic activity. At usual doses, pyridostigmine does not cross into the CNS (quaternary ammonium structure), but overdoses can cause CNS effects. Pharmacokinetics Pyridostigmine is only marginally absorbed from the GI tract and absorption may be more erratic with the sustained-release tablets than the regular tablets. The onset of action after oral dosing is gen-erally within one hour.	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
Py Ri Do Sti Gmine b Romi De 789 At usual doses, pyridostigmine is apparently distributed to most tissues, but not to the brain, intestinal wall, fat or thymus. The drug crosses the placenta. Pyridostigmine is metabolized by both the liver and hydrolyzed by cholinesterases. contraindications/Precautions/Warnings Pyridostigmine is contraindicated in patients hypersensitive to this class of compounds or bromides, or in those who have mechanical or physical obstructions of the urinary or GI tract. The drug should be used with caution in patients with bron-chospastic disease, epilepsy, hyperthyroidism, bradycardia or other arrhythmias, vagotonia, or GI ulcer diseases. adverse effects Adverse effects associated with pyridostigmine are generally dose related and cholinergic in nature. Although usually mild and easily treatable with dosage reduction, severe adverse effects are possible (see Overdosage below). Reproductive/nursing Safety In humans, the FDA categorizes this drug as category C for use dur-ing pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) Pyridostigmine is excreted in maternal milk; use with caution in nursing patients. overdosage/acute t oxicity Overdosage of pyridostigmine may induce a cholinergic crisis. Clinical signs of cholinergic toxicity can include: GI effects (nau-sea, vomiting, diarrhea), salivation, sweating (species with sweat glands), respiratory effects (increased bronchial secretions, bron-chospasm, pulmonary edema, respiratory paralysis), ophthalmic effects (miosis, blurred vision, lacrimation), cardiovascular effects (bradycardia or tachycardia, cardiospasm, hypotension, cardiac ar-rest), muscle cramps, and weakness. Overdoses in myasthenic patients can be very difficult to distin-guish from the effects associated with a myasthenic crisis. The time of onset of clinical signs or an edrophonium challenge may help to distinguish between the two. Treatment of pyridostigmine overdosage consists of both respi-ratory and cardiac supportive therapy and atropine if necessary. Refer to the atropine monograph for more information on its use for cholinergic toxicity. Drug interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving pyridostigmine and may be of significance in veterinary patients: at Ro Pine T! : Atropine will antagonize the muscarinic effects of pyri-dostigmine but concurrent use should be used cautiously as atro-pine can mask the early clinical signs of cholinergic crisis co Rtico Ste Roi DST! : May decrease the anticholinesterase activity of pyridostigmine. After stopping corticosteroid therapy, drugs like pyridostigmine may cause increased anticholinesterase activity Dex P ant Heno LT! : Theoretically, dexpan thenol may have additive ef-fects when used with pyridostigmine DRu GS Wit H neu Romu Scu La R b Lockin G abi Lity T! (e. g., aminoglyco-side antibiotics ): May necessitate increased dosages of pyridostig-mine in treating or diagnosing myasthenic patients ma Gne Sium T! : Anticholinesterase therapy may be antagonized by administration of parenteral magnesium therapy, as it can have a direct depressant effect on skeletal musclemu Sc Le Re Laxant ST! : Pyridostigmine may prolong the Phase I block of depolarizing muscle relaxants (e. g., succinylcholine, decametho nium ) and edrophonium antagonizes the actions of non-depolarizing neuromuscular blocking agents (e. g., pancuro-nium, tubocurarine, gallamine, vecuronium, atracurium, etc. ) Doses Do GS:T! For myasthenia gravis (MG):a) 0. 5-3 mg/kg (either PO or stomach tube) q8-12h. Start at low end of dose and increase as necessary to avoid a cholin-ergic crisis. (Dewey 1999) b) 1-3 mg/kg PO q8-12h (Inzana 2000) c) For acquired MG: After oral regurgitation is abolished with parenteral therapy (neostigmine), may begin oral therapy with pyridostigmine at 7. 5-30 mg PO two times a day. Once patient is stable and infections have resolved, begin corticos-teroid therapy (antiinflammatory doses of prednisone) and continue concurrently with anticholinesterase drugs for 2 weeks, then pyridostigmine may be gradually reduced. (Pe-droia 1989) d) 0. 5-3 mg/kg PO two to three times a day. If no response, add prednisone (0. 5-1 mg/kg day; increase to 1-2 mg/kg after a few days). (Kornegay 2006) e) 0. 5-1 mg/kg PO two to three times a day with or without prednisone (2 mg/kg PO twice daily). Not uncommon for dogs to fully recover without treatment (spontaneous remis-sion). (Le Couteur 2005) cat S:T! For myasthenia gravis (MG):a) For acquired MG: Cats are sensitive to anticholinesterase agents. Do not exceed 0. 25 mg/kg/day, PO initially in cats (Fenner 1989) b) 1-3 mg/kg PO q8-12h (Inzana 2000) c) 0. 5-3 mg/kg PO per day with corticosteroids (Wheeler 2006) monitoring Animals should be routinely monitored for clinical signs of cho-T! linergic toxicity (see Overdosage section above) and efficacy of the therapy client information Clients should be instructed to report to the veterinarian clinical T! signs of excessive salivation, GI disturbances, weakness, or dif-ficulty breathing chemistry/Synonyms An anticholinesterase agent, pyridostigmine bromide is a synthet-ic quaternary ammonium compound that occurs as an agreeable smelling, bitter tasting, hydroscopic, white or practically white, crystalline powder. It is freely soluble in water and in alcohol. The p H of the commercially available injection is approximately 5. Pyridostigmine Bromide may also be known as: pyridostigmini bromidum, Distinon®, Kalymin®, Mestinon®, or Regonol®. Storage/Stability/compatibility Unless otherwise instructed by the manufacturer, store pyridostig-mine products at room temperature. The oral solution and injec-tion should be protected from light and freezing. Pyridostigmine tablets should be kept in tight containers. The extended-release tablets may become mottled with time, but this does not affect their potency.	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
790 Py Ri Doxine Hc L Pyridostigmine injection is unstable in alkaline solutions. It is reportedly physically compatible with glycopyrrolate, hepa-rin sodium, hydrocortisone sodium succinate, potassium chloride, and vitamin B-complex with C. Compatibility is dependent upon factors such as p H, concentration, temperature and diluent used; consult specialized references or a hospital pharmacist for more specific information. Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: None The ARCI (Racing Commissioners International) has designated this drug as a class 3 substance. See the appendix for more information. Human-Labe Le D PRo Duct S: Pyridostigmine Bromide Tablets: 60 mg; Mestinon® (ICN); generic, (Rx) Pyridostigmine Bromide Extended-Release Tablets: 180 mg; Mesti-non® (ICN); (Rx)Pyridostigmine Bromide Syrup: 12 mg/m L in 480 m L; Mestinon® (ICN); (Rx)Pyridostigmine Bromide Injection: 5 mg/m L in 2 m L amps; Mesti-non® (ICN); (Rx) pyridoxine Hcl (vita Min b-6) (peer-ih-dox-een) nutritional b vitamin, antidote Prescriber Highlights Pyridoxine may be beneficial in the treatment of isoni-T T azid or crimidine toxicity, or delaying cutaneous toxicity of Doxil® (liposomal doxorubicin) Overdoses may cause peripheral neuropathy T T uses/indications Pyridoxine use in veterinary medicine is relatively infrequent. It may be of benefit in the treatment of isoniazid (INH) or crimidine (an older rodenticide) toxicity. Pyridoxine deficiency is apparently extremely rare in dogs or cats able to ingest food. Cats with severe intestinal disease may have a greater requirement for pyridoxine in their diet. Experimentally, pyridoxine has been successfully used in dogs to reduce the cutaneous toxicity associated with doxorubi-cin containing pegylated liposomes (Doxil ®). Pyridoxine has been demonstrated to suppress the growth of feline mammary tumors (cell line FRM) in vitro. In humans, labeled uses for pyridoxine include pyridoxine de-ficiency and intractable neonatal seizures secondary to pyridoxine dependency syndrome. Unlabeled uses include premenstrual syn-drome (PMS), carpal tunnel syndrome, tardive dyskinesia second-ary to antipsychotic drugs, nausea and vomiting in pregnancy, hy-peroxaluria type 1 and oxalate kidney stones, and for the treatment of isoniazid (INH), cycloserine, hydrazine or Gyometra mushroom poisonings. Pharmacology/actions In erythrocytes, pyridoxine is converted to pyridoxal phosphate and, to a lesser extent, pyridoxamine, which serve as coenzymes for metabolic functions affecting protein, lipid and carbohydrate utilization. Pyridoxine is necessary for tryptophan conversion to serotonin or niacin, glycogen breakdown, heme synthesis, synthesis of GABA in the CNS, and oxalate conversion to glycine. Pyridoxine can act as an antidote by enhancing the excretion of cycloserine or isoniazid. Pyridoxine requirements increase as protein ingestion increases. Pharmacokinetics Pyridoxine is absorbed from the GI tract primarily in the jejunum. Malabsorption syndromes can significantly impair pyridoxine ab-sorption. Pyridoxine is not bound to plasma proteins, but pyridoxal phosphate is completely bound to plasma proteins. Pyridoxine is stored primarily in the liver with smaller amounts stored in the brain and muscle. It is biotransformed in the liver and various tis-sues, and excreted almost entirely as metabolites into the urine. Elimination half-life in humans is approximately 15-20 days. contraindications/Precautions/Warnings Weigh potential risks versus benefits in patients with documented sensitivity to pyridoxine. adverse effects Pyridoxine is generally well tolerated unless doses are large (see Overdosage). In humans, paresthesias and somnolence have been reported. Reduced serum folic acid levels have occurred. Reproductive/nursing Safety While pyridoxine is a nutritional agent and very safe at recom-mended doses during pregnancy, very large doses during pregnancy can cause a pyridoxine dependency syndrome in neonates. Pyridoxine administration at low dosages should be safe dur-ing nursing. Pyridoxine requirements of the dam may be increased during nursing. overdosage/acute t oxicity Single overdoses are not considered overly problematic, unless they are massive. Laboratory animals given 3-4 g/kg developed seizures and died. Dogs (Beagles) repeatedly given 3 gram oral daily doses developed uncoordinated gait and neurologic signs. Neuronal le-sions were noted in sensory, dorsal root ganglia, and trigeminal ganglia. Signs generally resolved over a 2-month drug free period. Drug interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving pyridoxine and may be of significance in veterinary patients: c HLo Ram PHenico LT! : May cause increased pyridoxine requirements e St Ro Gen ST! : May cause increased pyridoxine requirements Hy DRa Lazine T! : May cause increased pyridoxine requirements immuno Su PPRe SSant ST! (e. g., azathioprine, chlorambucil, cyclo-phosphamide, corticosteroids ): May cause increased pyridoxine requirements i Soniazi DT! : May cause increased pyridoxine requirements Penici LLamine T! : May cause increased pyridoxine requirements Le Vo Do P a T! : Pyridoxine may reduce levodopa efficacy (no interac-tion when levodopa is used with carbidopa) PHenoba Rbita LT! : High dose pyridoxine may decrease phenobarbi-tal serum levels PHenytoin T! : High dose pyridoxine may decrease phenytoin serum concentration	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
Py Ri Lamine ma Leate 791 Laboratory considerations The following laboratory alterations have been reported in humans with pyridoxine and may be of significance in veterinary patients: urobilinogen in the spot test using ehrlich's reagent T! : Pyridoxine may cause false-positive results a St T! : Excessive dosages of pyridoxine may elevate AST Doses Do GS /cat S:T! a) Dogs: For isoniazid (INH) toxicity: If quantity of INH in-gested is known, give pyridoxine on a mg for mg (1:1) basis. If it is not known, give pyridoxine initially at 71 mg/kg as a 5-10% IV infusion over 30-60 minutes (some sources say it can be given as an IV bolus). Pyridoxine injection can usually be obtained from human hospital pharmacies. Do not use injectable B-complex vitamins. (Gwaltney-Brant 2003) b) T o replace pyridoxine antagonized by crimidine ingestion: 20 mg/kg IV (Dalefield and Oehme 2006) c) Dogs: T o delay the development of cutaneous toxicity (PPES; palmer-plantar-dyerythrodysesthesia) associated with doxo-rubicin containing pegylated liposomes (Doxil ®): 50 mg PO three times daily during chemotherapy protocol period. (Vail, Chun et al. 1998) monitoring Other than evaluating efficacy for its intended use, no significant T! monitoring is required client information Do not give more than prescribed by the veterinarian T! Contact veterinarian if animal develops any abnormal signs such T! as difficulty walking, using stairs, etc. chemistry/Synonyms Pyridoxine (vitamin B6) is a water-soluble vitamin present in many foods (liver, meat, eggs, cereals, legumes, and vegetables). The com-mercially available form (pyridoxine HCl) found in medications is obtained synthetically. Pyridoxine HCl occurs as white or practi-cally white, crystals or crystalline powder with a slightly bitter, salty taste. It is freely soluble in water and slightly soluble in alcohol. Pyridoxine or Vitamin B6 may also be known by the following synonyms or analogs: adermine, pyridoxal, pyridoxal-5-phosphate, pyridoxamine, pirodoxamina, piridossima, piridoxolum, piridos-sina, Aminoxin®, and Vitelle Nestrex®. Storage/Stability/compatibility Unless otherwise specified by the manufacturer, pyridoxine tablets should be stored below 40°C (104°F), preferably between 15-30°C (59-86°F), in well-closed containers protected from light. Pyridoxine HCl injection should be stored below 40°C (104°F), preferably between 15-30°C (59-86°F), protected from light and freezing. Pyridoxine HCl injection can be administered undiluted or add-ed to commonly used IV solutions. It is reportedly compatible with doxapram when mixed in a syringe and with fat emulsion 10%. It is reportedly incompatible with alkaline or oxidizing solutions, and iron salts. Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: No single ingredient pyridoxine products were located. There are a multitude of various veterinary-labeled products that contain pyri-doxine as one of several ingredients. Human-Labe Le D PRo Duct S: Pyridoxine Tablets: 25 mg, 50 mg, 100 mg, 250 mg, & 500 mg; Vitelle Nestrex® (Fielding), generic; (OTC) Pyridoxine (as pyridoxal-5'-phosphate) Tablets (enteric-coated): 20 mg; Aminoxin® (Tyson); (OTC) Pyridoxine HCl Injection: 100 mg/m L in 1 m L vials; generic; (Rx)Pyridoxine is also an ingredient in many combination products (e. g., B-Complex, multivitamins). pyrila Mine Maleate (pye-ril-a-meen) Histall®, Equiphed® antihi Stamine Prescriber Highlights Injectable antihistamine T T Contraindications: None noted T T Adverse Effects: T T HORSES: CNS stimulation (nervousness, insomnia, convulsions, tremors, ataxia), palpitation, GI disturbances, CNS depression (sedation), muscular weak-ness, anorexia, lassitude & incoordination Drug Interactions T T uses/indications Antihistamines are used in veterinary medicine to reduce or help prevent histamine mediated adverse effects; predominantly used in horses. Pharmacology/actions Antihistamines (H 1-receptor antagonists) competitively inhibit his-tamine at H 1 receptor sites. They do not inactivate, nor prevent the release of histamine, but can prevent histamine's action on the cell. Besides their antihistaminic activity, these agents also have varying degrees of anticholinergic and CNS activity (sedation). Pyrilamine is considered to be less sedating and have fewer anticholinergic ef-fects when compared to most other antihistamines. Pharmacokinetics The pharmacokinetics of this agent have apparently not been ex-tensively studied. contraindications/Precautions/Warnings The manufacturer indicates that the use of this product “... should not supersede the use of other emergency drugs and procedures. ” adverse effects Adverse effects in horses can include CNS stimulation (nervous-ness, insomnia, convulsions, tremors, ataxia), palpitation, GI dis-turbances, CNS depression (sedation), muscular weakness, anorex-ia, lassitude and incoordination. Reproductive/nursing Safety At usual doses, pyrilamine is probably safe to use during pregnancy. Rats and mice treated with 10-20 times the human dose had an increased frequency of embryonic, fetal or perinatal death, but a study in pregnant women, showed no increase in teratogenic or fe-tocidal rates. It is unknown if pyrilamine enters milk.	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
792 Py Rimet Hamine overdosage/acute t oxicity Treatment of overdosage is supportive and symptomatic. One man-ufacturer (Histavet-P®—Schering) suggests using “careful titra-tion” of barbiturates to treat convulsions, and analeptics (caffeine, ephedrine, or amphetamines) to treat CNS depression. Most toxi-cologists however, recommend avoiding the use of CNS stimulants in the treatment of CNS depressant overdoses. Phenytoin (IV) is recommended in the treatment of seizures caused by antihistamine overdose in humans; barbiturates and diazepam are to be avoided. Drug interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving pyrilamine and may be of significance in veterinary patients: anticoa Gu Lant ST! (heparin, warfarin ): Antihistamines may partially counteract the anticoagulation effects of heparin or warfarin cn S De PRe SSant DRu GST! : Increased sedation can occur if pyril-amine is combined with other CNS depressant drugs e Pine PHRine T! : Pyrilamine may enhance the effects of epinephrine Laboratory considerations Antihistamines can decrease the wheal and flare response to anti-T! gen skin testing. In humans, it is suggested that antihistamines be discontinued at least 4 days before testing. Doses Do GS: T! a) 12. 5-25 mg PO four times a day; 25-125 mg IM (Swinyard 1975) catt Le:T! a) 0. 5-1. 5 grams IM (Swinyard 1975) b) For adjunctive treatment of aseptic laminitis: 55-110 mg/100 kg IV or IM (Berg 1986) Ho RSe S:T! (Note: ARCI UCGFS Class 3 Drug) a) 0. 88-1. 32 mg/kg (2-3 m L of 20 mg/m L solution per 100 lbs body weight) IV (slowly), IM or SC; may repeat in 6-12 hours if necessary. Foals: 0. 44 mg/kg (1 m L of 20 mg/m L so-lution per 100 lbs. body weight) IV (slowly), IM or SC; may repeat in 6-12 hours if necessary. (Package Insert; Histavet-P®—Schering) b) 1 mg/kg IV, IM or SC (Robinson 1987) c) 0. 5-1. 5 grams IM (Swinyard 1975) SHee P, SWine: T! a) 0. 25-0. 5 gram IM (Swinyard 1975) monitoring Clinical efficacy T! Adverse effects T! chemistry/Synonyms An ethylenediamine antihistamine, pyrilamine maleate occurs as a white, crystalline powder with a melting range of 99-103°. One gram is soluble in approximately 0. 5 m L of water or 3 m L alcohol. Pyrilamine Maleate may also be known as: pyranisamine hydro-chloride, pyrilamine hydrochloride, mepyramine hydrochloride, mepyramini maleas, myranisamine maleate, myrilamine maleate, mepyramine maleate, Anihist®, Alergitanil®, Antemesyl®, Anthisan®, Anthisan®, Equi-Phar® Equi-Hist®, Equiphed®, Fluidasa®, Histall®, Histagranules®, Histamed®, Mepyraderm®, Mepyrimal, Pyramine®, Pyriped ®, Relaxa-Tabs®, and Tri-Hist®. Storage/Stability Avoid freezing the injectable product. Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: Pyrilamine Granules: 600 mg/oz in 20 oz containers; Histall® (AHC); (OTC). Labeled for use in horses. Do not use at least 72 hours before sporting events. Pseudoephedrine HCl 600 mg/oz and Pyrilamine maleate 600 mg/ oz Granules: in 20 oz, 5 lb and 10 lb containers; Equiphed® (AHC), Equi-Phar Equi-Hist 1200 Granules® (Vedco), Tri-Hist Granules® (Neogen), Histagranules® (Butler); (Rx). Labeled for use in horses. Do not use at least 72 hours before sporting events. Pyrilamine 600 mg/oz and Guaifenesin 2400 mg/oz Granules: in 20 oz, 5 lb and 25 lb containers; Anihist® (AHC), Hist-EQ® (Butler); (OTC). Labeled for use in horses. Do not use at least 72 hours before sporting events. There are also combination cough syrups containing pyrilamine la-beled for use in small animals. The ARCI (Racing Commissioners International) has designated this drug as a class 3 substance. See the appendix for more information. Human-Labe Le D PRo Duct S: None pyri Met Ha Mine (pye-ri-meth-a-meen) Daraprim® anti Protozoal note : Also see the Pyrimethamine/Sulfadiazine, and Sulfadiazine/ Trimethoprim monographs Prescriber Highlights Folic acid inhibitor used primarily (in combination) for T T toxoplasmosis, H. americanum, neosporosis, & equine protozoal encephalomyelitis Contraindications: Hypersensitive to pyrimethamine T T Caution: Hematologic disorders; cats T T Adverse Effects: T T SMALL ANIMALS: Anorexia, malaise, vomiting, depression, & bone marrow depression (ane-mia, thrombocytopenia, leukopenia). Cats may be more likely to develop adverse reactions. HORSES: Leukope-nias, thrombocytopenia, & anemias; Baker's yeast or foli-nic acid may treat/prevent. Potentially teratogenic; avoid use in pregnancy T T Dosage form (25 mg tab only) may be inconvenient; un-T T palatable to cats uses/indications In veterinary medicine, pyrimethamine is used to treat Hepatozoon americanum infections, and toxoplasmosis in small animals (often in combination with sulfonamides). In horses, it is used to treat equine protozoal myeloencephalitis, sometimes called equine toxo-plasmosis. In humans, pyrimethamine is used for the treatment of toxo-plasmosis and as a prophylactic agent for malaria.	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
Py Rimet Hamine 793 Pharmacology/actions Pyrimethamine is a folic acid antagonist similar to trimethoprim. It acts by inhibiting the enzyme, dihydrofolate reductase, that cata-lyzes the conversion of dihydrofolic acid to tetrahydrofolic acid. Pharmacokinetics No pharmacokinetic data was located for veterinary species. In hu-mans, pyrimethamine is well absorbed from the gut after oral ad-ministration. It is distributed primarily to the kidneys, liver, spleen, and lungs, but does cross the blood-brain barrier. It has a volume of distribution of about 3 L/kg and is 80% bound to plasma proteins. Pyrimethamine enters milk in levels greater than those found in serum and can be detected in milk up to 48 hours after dosing. In humans, plasma half-life is approximately 3-5 days. It is un-known how or where the drug is metabolized, but metabolites are found in the urine. contraindications/Precautions/Warnings Pyrimethamine is contraindicated in patients hypersensitive to it and should be used cautiously in patients with preexisting hemato-logic disorders. Some clinicians recommend avoiding its use in cats because of its adverse effect profile. adverse effects In small animals, anorexia, malaise, vomiting, depression, and bone marrow depression (anemia, thrombocytopenia, leukopenia) have been seen. Adverse effects may be more prominent in cats and not-ed 4-6 days after starting combination therapy. Some clinicians recommend avoiding its use in this species. Hematologic effects can develop rapidly and frequent monitoring is recommended, particu-larly if therapy persists longer than 2 weeks. Oral administration of folinic acid at 1 mg/kg PO, folic acid 5 mg/day, or Brewer's yeast 100 mg/kg/day have been suggested to alleviate adverse effects. The drug is unpalatable to cats when mixed with food and the 25 mg tablet dosage size makes successful dosing a challenge. In horses, pyrimethamine has caused leukopenias, thrombocy-topenia and anemias when used in combination with sulfonamides. Baker's yeast and folinic acid have been suggested to antagonize these adverse effects. Alternatively, folic acid supplement may be used (an example is Folic Acid and Vitamin E Pak from Buckeye Feed Mills in Dalton, Ohio). Reproductive/nursing Safety Pyrimethamine has been demonstrated to be teratogenic in rats. Fetal abnormalities have been seen in foals after mares have been treated, however, it has been used in treating women with toxoplas-mosis during pregnancy. Clearly, the risks associated with therapy must be weighed against the potential for toxicity, the severity of the disease, and any alternative therapies available (e. g., clindamy-cin in small animals). Concomitant administration of folinic acid has been recommended if the drug is to be used during pregnancy by some, but others state that pregnant mares should not receive folic acid during therapy as it may exacerbate fetal abnormalities or mortality. In humans, the FDA categorizes this drug as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) Pyrimethamine is excreted in maternal milk; consider using milk replacer. overdosage/acute t oxicity Reports of acute overdosage of pyrimethamine in animals were not located. In humans, vomiting, nausea, anorexia, CNS stimu-lation (including seizures), and hematologic effects can be seen. Recommendations for treatment include: standard procedures in emptying the gut or preventing absorption, parenteral barbiturates for seizures, folinic acid for hematologic effects, and long-term monitoring (at least 1 month) of renal and hematopoietic systems. Drug interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving pyrimethamine and may be of significance in veterinary patients: p-T!aminobenzoic aci D (Paba): PABA is reportedly antagonistic towards the activity of pyrimethamine; clinical significance is unclear Su LFonami De ST! : Pyrimethamine is synergistic with sulfonamides in activity against toxoplasmosis (and malaria) t Rimet Ho PRim T! : Use with pyrimethamine/sulfa is not recom-mended in humans as adverse effects may be additive, however, this combination has been used clinically in horses Doses Do GS:T! For protozoal diseases:a) For toxoplasmosis: 0. 5-1 mg/kg PO once daily for 2 days, then 0. 25 mg/kg PO once daily for 2 weeks. Given with sulfa-diazine at 30-50 mg/kg PO divided two to four times a day for 1-2 weeks (Murtaugh 1988) b) For T oxoplasmosis: 0. 25-0. 5 mg/kg once daily for 28 days; For Neospora (with trimethoprim sulfa): 1 mg/kg once daily for 28 days; For Hepatazoon canis (with trimethoprim sulfa and clindamycin): 0. 25-0. 5 mg/kg once daily for 2-4 weeks (Lappin 2000) c) For Hepatazoon americanum: Trimethoprim/sulfa (15 mg/kg PO q12h), pyrimethamine (0. 25 mg/kg PO q24h), and clin-damycin (10 mg/kg q8h). Once remission attained, decoqui-nate (see monograph) can maintain. (Baneth 2007) d) For Hepatazoon americanum: Trimethoprim/sulfa (15 mg/kg PO q12h for 14 days), pyrimethamine (0. 25 mg/kg PO q24h for 14 days), and clindamycin (10 mg/kg q8h for 14 days). Once remission attained, decoquinate (see monograph) can maintain. For neosporosis: pyrimethamine (1 mg/kg PO daily) with trimethoprim/sulfa (15-30 mg/kg PO twice daily. (Blagburn 2005a) cat S:T! See warnings above. For toxoplasmosis:a) 0. 5-1 mg/kg PO once daily for 2 days, then 0. 25 mg/kg PO once daily for 2 weeks. Given with sulfadiazine at 30-50 mg/ kg PO divided two to four times a day for 1-2 weeks (Mur-taugh 1988) b) For enteroepithelial cycle: 2 mg/kg, PO once daily. For ex-traintestinal cycle: 0. 5-1 mg/kg PO divided two to three times daily combined with sulfonamides (e. g., triple sulfa, sulfadiazine) at 60 mg/kg PO or IM divided two to three times daily (Lappin 1989) c) For protozoal myocarditis: Pyrimethamine 1 mg/kg PO once daily for 3 days, then decrease dose to 0. 5 mg/kg PO once a day, with sulfadimethoxine 25 mg/kg PO, IV, or IM once a day (Ogburn 1988) d) Pyrimethamine: 0. 5 mg/kg PO per day with sulfadiazine at 30 mg/kg, PO q12h for 7-10 days. Do not use continuously for longer than 2 weeks. Supplementation with folic acid 5 mg/day or folinic acid 1 mg/kg/day may alleviate toxicity. (Swango, Bankemper, and Kong 1989)	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
794 Py Rimet Hamine + Su LF a Diazine Ho RSe S:T! See also the next monograph (Pyrimethamine + Sulfadiazine) For equine protozoal myeloencephalitis: a) Pyrimethamine 1 mg/kg PO once a day for 90-120 days (or longer). Given with a sulfa or potentiated sulfa (sulfadiazine 20 mg/kg PO once or twice a day). Monitor: CBC's (Moore 1999); (Mac Kay, Granstrom et al. 2000) bi RDS: T! For Coccidian organisms in raptors: a) 0. 5 mg/kg PO twice daily for 14-28 days (especially effec-tive against T oxoplasmosis, Atoxoplasmosis and Sarcocystis). (Jones 2007b) monitoring See adverse effects; CBC with platelet count T! Clinical efficacy T! client information Clients should he instructed to monitor for clinical signs of ab-T! normal bleeding, lassitude, etc. that may signal development of hematologic disorders. Accurate dosing of the tablets in cats may be very difficult as T! only 25 mg tablets are commercially available. Preferably, cus-tom prepared capsules containing the accurate dosage should be prepared. chemistry/Synonyms An aminopyrimidine agent structurally related to trimethoprim, pyrimethamine occurs as an odorless, white, or almost white, crys-talline powder or crystals. It is practically insoluble in water and slightly soluble in alcohol. Pyrimethamine may also be known as: BW-50-63, pirimet-amina, pyrimethaminum, RP-4753, Daraprim®, Malocide®, or Pirimecidan®. Storage/Stability/compatibility Pyrimethamine tablets should be stored in tight, light-resistant containers. Pyrimethamine tablets may be crushed to make oral suspensions of the drug. Although stable in an aqueous solution, sugars tend to adversely affect the stability of pyrimethamine. If cherry syrup, corn syrup, or sucrose-containing liquids are used in the prepara-tion of the suspension, it is recommended to store the suspension at room temperature and discard after 7 days. Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: None Human-Labe Le D PRo Duct S: Pyrimethamine Tablets: 25 mg; Daraprim® (Glaxo Smith Kline); (Rx)pyri Met Ha Mine + Sulfadiazine (pye-ri-meth-a-meen + sul-fa-dye-a-zeen) Re Balance® anti Protozoal note : Also see the Pyrimethamine, and Sulfadiazine/Trimethoprim monographs Prescriber Highlights Tetrahydrofolic acid inhibitor suspension labeled for the T T treatment of horses with equine protozoal myeloenceph-alitis (EPM) caused by Sarcocystis neurona May cause bone marrow suppression, GI effects, & T T “treatment crisis” (patient's signs worsen after beginning therapy) Daily treatment may be required for 3-9 months T T uses/indications Re Balance® (pyrimethamine/sulfadiazine suspension in a 1:20 concentration) is labeled for the treatment of horses with equine protozoal myeloencephalitis (EPM) caused by Sarcocystis neurona. Although not labeled for use in small animals it potentially could be useful for treating protozoal infections such as T oxoplasmosis in cats or Neosporosis in dogs. Pharmacology/actions Sulfonamides inhibit the conversion of para-aminobenzoic acid (PABA) to dihydrofolic acid (DFA) by competing with PABA for dihydropteroate synthase. Pyrimethamine blocks the conversion of DFA to tetrahydrofolic acid by inhibiting dihydrofolate re-ductase. When sulfas and dihydrofolate reductase inhibitors (e. g., trimethoprim, pyrimethamine) are used together, synergistic ef-fects can occur. When comparing pyrimethamine and trimethop-rim, pyrimethamine is more active against protozoal dihydrofolate reductase and trimethoprim is more active against bacterial dihy-drofolate reductase. Pharmacokinetics No specific information was located for the pharmacokinetics of this drug combination and dosage form (oral suspension) in horses. Previous reports in horses using other dosage forms reported py-rimethamine oral bioavailability of approximately 56% and elimi-nation half-life of about 12 hours. CNS levels are approximately 25-50% of those found in plasma. Sulfadiazine is apparently well absorbed after oral administration to horses and enters the CSF. Volume of distribution is approximately 0. 58 L/kg; elimination half-life is about 3-4 hours. contraindications/Precautions/Warnings This drug combination is contraindicated in horses hypersensitive to either pyrimethamine or sulfadiazine. It should not be used in horses intended for human consumption. Because it may cause bone marrow suppression, use with caution in horses with preexist-ing hematologic abnormalities or those receiving other drugs that may cause bone marrow suppression. adverse effects Adverse effects in horses reported during field trials for py-rimethamine/sulfadiazine suspension include bone marrow sup-pression (anemia, leukopenia, neutropenia, thrombocytopenia),	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
Py Rimet Hamine + Su LF a Diazine 795 reduced appetite/anorexia, loose stools/diarrhea, and urticaria. CNS effects may be noted (seizures, depression), but are probably a result of the disease (EPM). Baker's yeast or folinic acid have been suggested to antagonize the drug combination's bone marrow depressive effects, but efficacy has not been proven. During the initial period (first few days) of treatment, neurolog-ic signs may worsen—so-called treatment crisis—and may persist up to 5 weeks. It is thought this may be the result of an inflamma-tory reaction secondary to dying parasites in the central nervous system. Reproductive/nursing Safety The label for Re Balance® (pyrimethamine/sulfadiazine suspension) states that the safe use of this product in horses for breeding pur-poses, during pregnancy, or in lactating mares has not been evalu-ated. Pyrimethamine has been demonstrated to be teratogenic in rats. Fetal abnormalities have been seen in foals after mares have been treated; however, it has been used in treating women with toxoplasmosis during pregnancy. Risks associated with therapy must be weighed against the potential for toxicity, the severity of the disease, and any alternative therapies available. Some have rec-ommended concomitant administration of folinic acid if the drug is to be used during pregnancy, but others state that pregnant mares should not receive folic acid during therapy as it may exacerbate fetal abnormalities or mortality. In humans, the FDA categorizes pyrimethamine as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no ad-equate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) Sulfas cross the placenta and fetal serum levels may be up to 50% of that found in maternal serum. T eratogenicity has been reported in some laboratory animals when given at very high doses. Sulfas should be used in pregnant animals only when the benefits clearly outweigh the risks of therapy. Sulfonamides are distributed into milk. Pyrimethamine is ex-creted in maternal milk and safety for nursing offspring has not been established; consider using milk replacer. overdosage/acute t oxicity Acute overdosage information for pyrimethamine/sulfadiaz-ine in horses (greater than 2X) was not located. Re Balance® (py-rimethamine/sulfadiazine suspension) was administered at 2X the labeled dose for 92 days to 49 horses. Signs noted included loose stools, slight increases in ALP in some horses, declines in RBC, HCT, Hgb, and PCV, and depressed appetite. Drug interactions The label for Re Balance® (pyrimethamine/sulfadiazine suspension) states that the safety of this product with concomitant therapies in horses has not been evaluated. In humans, the following drug interactions with sulfas and/or py-rimethamine have been reported or are theoretical and may be of significance in veterinary patients: antaci DST! : May decrease the bioavailability of sulfonamides if ad-ministered concurrently Hi GHL y PRotein-boun D DRu GS T! (e. g., methotrexate, phenylbutazone, thiazide diuretics, salicylates, probenecid, phenytoin, warfarin ): Sul-fonamides may displace other highly bound drugs p-T!aminobenzoic aci D (Paba): PABA is reportedly antagonistic towards the activity of pyrimethamine; clinical significance is unclear t Rimet Ho PRim T! : Use with pyrimethamine/sulfa is not recom-mended in humans as adverse effects may be additive, however, this combination has been used clinically in horses Laboratory considerations The following laboratory alterations have been reported in hu-mans taking sulfonamides and may be of significance in veterinary patients: urine glucose T! : Sulfonamides may give false-positive results when using the Benedict's method Doses Ho RSe S:T! For treatment of EPM: a) 20 mg/kg sulfadiazine with 1 mg/kg pyrimethamine; equiva-lent to 4 m L of Re Balance® suspension per 50 kg (110 lb) body weight PO once daily at least 1 hour before feeding with hay or grain. Administer using a suitable oral dosing syringe; insert nozzle through the interdental space and de-posit the dose on the back of the tongue by depressing the plunger. Treatment duration is based upon clinical response, but usually ranges from 90-270 days. (Label information; Re Balance®—Phoenix) monitoring CBC (including platelets): baseline and at least monthly during T! therapy GI adverse effects T! Clinical Efficacy: Improvement in neuro signs, CSF Western Blot T! test negative client information Shake well before using and store at room temperature; see dos-T! age information for instructions on proper administration Horse may develop worsening signs after beginning treatment, T! probably due to local inflammation from dying parasites Watch for signs that may indicate toxicity including depression, T! bleeding, bruising, bloody diarrhea, etc. ; contact veterinarian if these occur chemistry/Synonyms Pyrimethamine is an aminopyrimidine agent structurally related to trimethoprim. It occurs as an odorless, white, or almost white, crystalline powder or crystals. It is practically insoluble in water and slightly soluble in alcohol. Sulfadiazine occurs as an odorless or nearly odorless, white to slightly yellow powder. It is practically insoluble in water and spar-ingly soluble in alcohol. Sulfadoxine and Pyrimethamine may also be known as Fansidar® and Re Balance®. Storage/Stability Re Balance® suspension should be stored at controlled room tem-perature (15-30°C) and protected from freezing. Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: Sulfadiazine (as the sodium salt) 250 mg/m L and Pyrimethamine 12. 5 mg/m L Oral Suspension in quart (946. 4 m L) bottles; Re Balance® Antiprotozoal Oral Suspension (Phoenix); (Rx) Approved for use in horses; not for use in horses intended for human consumption.	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
796 quinac Rine Hc L Human-Labe Le D PRo Duct S: A related compound for humans is: Sulfadoxine & Pyrimethamine Tablets: 500 mg sulfadoxine & 25 mg pyrimethamine; Fansidar® (Roche); (Rx) quinacrine Hcl (qwin-a-krin) anti Protozoal Prescriber Highlights Antiprotozoal that may be useful for treatment of Giardia, T T Leishmania, & coccidia. May improve clinical signs asso-ciated with giardial infection, but not eliminate infection Contraindications: Potentially, if hepatic dysfunction or T T pregnancy Adverse Effects: Yellowing of skin & urine color, (not of T T clinical importance); GI (anorexia, nausea, vomiting, diar-rhea), abnormal behaviors (“fly biting”, agitation), pru-ritus, & fever. Potentially: Hypersensitivity, hepatopathy, aplastic anemia, corneal edema, & retinopathy. Availability an issue T T Potential teratogen T T Give with meals; have liquid available T T uses/indications While quinacrine has activity against a variety of protozoans and helminths, its use against all but Giardia and Trichomonas has been superseded by safer or more effective agents. In humans, quinacrine may be used for treatment of mild to moderate discoid lupus eryth-romatosis, transcervically as a sterilizing agent, or in powder form as an intrapleural sclerosing agent. Pharmacology/actions Quinacrine's mechanism of action for its antiprotozoal activity against Giardia is not understood, however, it does bind to DNA by intercalation to adjacent base pairs thereby inhibiting RNA transcription and translocation. Additionally, quinacrine interferes with electron transport and inhibits succinate oxidation and cho-linesterase. Quinacrine binds to nucleoproteins that (in humans at least) can suppress lupus erythromatosis (LE) cell factor. Pharmacokinetics Quinacrine is absorbed well from the GI tract or after intrapleural administration. It is distributed throughout the body, but CSF lev-els are only 1-5% of those found in plasma. Drug is concentrated in the liver, spleen, lungs, and adrenals. It is relatively highly bound to plasma proteins in humans (80-90%). Quinacrine crosses the placenta, but only small amounts enter maternal milk. Quinacrine is eliminated very slowly (half life in humans: 5-14 days). Quinacrine is slowly metabolized, but primarily eliminated by the kidneys; acidifying the urine will increase renal excretion somewhat. Significant amounts may be detected in urine up to 2 months after drug discontinuation. contraindications/Precautions/Warnings In humans, quinacrine is relatively contraindicated in patients with psychotic disorders, psoriasis, or porphyria as it may exacerbate these conditions. Veterinary relevance is unknown. The drug should be used with extreme caution in patients with hepatic dysfunction. adverse effects In small animals, a yellowing of skin and urine color can occur, but is not of clinical importance (does not indicate jaundice). Additionally, gastrointestinal disturbances (anorexia, nausea, vom-iting, diarrhea), abnormal behaviors (“fly biting”, agitation), pruri-tus, and fever have been noted. Potentially hypersensitivity reactions, hepatopathy, aplastic anemia, corneal edema, and retinopathy could occur (all reported rarely in humans, primarily with high dose long-term use). Reproductive/nursing Safety Quinacrine crosses the placenta and has been implicated in causing a case of renal agenesis and hydrocephalus in a human infant. In high doses, it has caused increased fetal death rates in rats. Weigh the potential benefits with the risks when considering use in preg-nant animals. In humans, the FDA categorizes this drug as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) overdosage/acute t oxicity Overdosage may be serious depending on the dose. In humans, a dose as low as 6. 8 grams (administered intraduodenally) caused death. Clinical signs associated with acute toxicity include CNS ex-citation (including seizures), GI disturbances, vascular collapse, and cardiac arrhythmias. Treatment consists of gut emptying protocols, and supportive and symptomatic therapies. Urinary acidification with ammonium chloride and forced diuresis (with adequate fluid therapy) may be beneficial in enhancing urinary excretion of the drug. Drug interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving quinacrine HCl and may be of significance in veterinary patients: a Lco Ho LT! : Quinacrine may cause a “disulfiram-reaction” if used with alcohol. He Patotoxic DRu GST! : Quinacrine concentrates in the liver and should be used with caution with hepatotoxic drugs (clinical sig-nificance unknown). PRimaquine T! : Quinacrine increases the toxicity of primaquine (generally not used in veterinary medicine), and the two should not be used simultaneously. Laboratory considerations When urine is acidic, quinacrine can cause it to turn a deep yel-T! low color. By causing an interfering fluorescence, quinacrine can cause falsely elevated values of plasma and urine cortisol values.	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
quini Dine 797 Doses Do GS:T! As a drug of second-choice in the treatment of Giardia or other susceptible protozoa:a) 6. 6 mg/kg PO q12h for 5 days (Papich 1992), (Sherding and Johnson 1994), (Blagburn 2003b), (Blagburn 2005a) b) 9 mg/kg PO q24h for 6 days. (Lappin 2006b) cat S:T! a) Giardia: 9 mg/kg PO once daily for 6 days; Coccidiosis: 10 mg/kg PO once daily for 5 days (Blagburn 2003b), (Blagburn 2005a) b) Giardia: 11 mg/kg PO q24h for 12 days (Lappin 2006b) c) Coccidiosis: 10 mg/kg PO once daily for 5 days (Greene and Watson 1998) Re Pti Le S:T! a) For hemoprotozoal infections: 19-100 mg/kg PO q48h (ev-ery other day) for 2-3 weeks (de la Navarre 2003b) monitoring Efficacy (fecal exams, reduction in diarrhea)T! Adverse effects T! client information Quinacrine should preferably be given after meals with plenty of T! liquids available. Make sure clients understand the importance of compliance with T! directions and to watch for signs of adverse effects. chemistry/Synonyms A synthetic acridine derivative anthelmintic, quinacrine HCl oc-curs as a bright yellow, odorless, crystalline powder having a bitter taste. It is sparingly soluble in water. Quinacrine HCl may also be known as mepacrine HCl. Storage/Stability Tablets should be stored in tight, light-resistant containers at room temperature. Quinacrine is not stable in solution for any length of time; however, it may be crushed and mixed with foods to mask its very bitter taste. Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: None Human-Labe Le D PRo Duct S: None There currently are no quinacrine products being marketed in the USA. It may be available from compounding pharmacies. quinidine gluconate quinidine polygalacturonate quinidine Sulfate (qwin-i-deen) Quinidex® antiarrhythmic Prescriber Highlights Antiarrhythmic agent used in small animals & horses T T Contraindications: Hypersensitivity, myasthenia gravis; T T complete AV block with an AV junctional or idioven-tricular pacemaker; intraventricular conduction defects; digitalis intoxication with associated arrhythmias or AV conduction disorders; aberrant ectopic impulses; or ab-normal rhythms secondary to escape mechanisms Extreme Caution: Any form of AV block or if any clinical T T signs of digoxin toxicity are exhibited Caution: Uncorrected hypokalemia, hypoxia, & disorders T T or acid-base balance; hepatic or renal insufficiency Adverse Effects: T T DOGS: GI effects, weakness, hypotension (especially with too rapid IV administration), negative inotropism, widened QRS complex & QT intervals, AV block, & multiform ventricular tachycardias hypotension. HORSES: inappetence, depression, swelling of the nasal mucosa, ataxia, diarrhea, colic, hypotension & rarely, laminitis, paraphimosis & the development of urticarial wheals; cardiac arrhythmias including AV block, circula-tory collapse & sudden death Consider monitoring blood levels T T Administer at evenly spaced intervals throughout the T T day/night GI upset may be decreased if administered with food T T Do not allow animal to chew or crush sustained-release T T oral dosage forms Many drug Interactions T T uses/indications Quinidine is used in small animal or equine medicine for the treat-ment of ventricular arrhythmias (VPCs, ventricular tachycardia), refractory supraventricular tachycardias, and supraventricular arrhythmias associated with anomalous conduction in Wolff-Parkinson-White (WPW) syndrome. Chronic use of quinidine for controlling ventricular arrhythmias and supraventricular tachy-cardia in dogs has diminished over the years as other drugs appear to be more effective. It is still used in dogs and horses to convert atrial fibrillation to sinus rhythm. Oral therapy is generally not used in cats. Pharmacology/actions A class IA antiarrhythmic, quinidine has effects similar to that of procainamide. It depresses myocardial excitability, conduction ve-locity, and contractility. Quinidine will prolong the effective refrac-tory period, which prevents the reentry phenomenon and increases conduction times. Quinidine also possesses anticholinergic activity which decreases vagal tone and may facilitate A V conduction.	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
798 quini Dine Pharmacokinetics After oral administration, quinidine salts are nearly completely ab-sorbed from the GI, however, the actual amount that reaches the systemic circulation will be reduced due to the hepatic first-pass effect. The extended-release formulations of quinidine sulfate and gluconate, as well as the polygalacturonate tablets, are more slowly absorbed than the conventional tablets or capsules. Quinidine is distributed rapidly to all body tissues except the brain. Protein binding varies from 82-92%. The reported volumes of distribution in various species are: horses ≈ 15. 1 L/kg; cattle ≈ 3. 8 L/kg; dogs ≈ 2. 9 L/kg; cats ≈ 2. 2 L/kg. Quinidine is distributed into milk and crosses the placenta. Quinidine is metabolized in the liver, primarily by hydroxyla-tion. Approximately 20% of a dose may be excreted unchanged in the urine within 24 hours after dosing. Serum half-lives reported in various species are: horses ≈ 8. 1 hours; cattle ≈ 2. 3 hours; dogs ≈ 5. 6 hours; cats ≈ 1. 9 hours; swine ≈ 5. 5 hours; goats ≈ 0. 9 hours. Acidic urine (p H <6) can increase renal excretion of quinidine and decrease its serum half-life. contraindications/Precautions/Warnings Quinidine is generally contraindicated in patients who have dem-onstrated previous hypersensitivity reactions to it; myasthenia gravis; complete A V block with an A V junctional or idioventricu-lar pacemaker; intraventricular conduction defects (especially with pronounced QRS widening); digitalis intoxication with associated arrhythmias or A V conduction disorders; aberrant ectopic impulses; or abnormal rhythms secondary to escape mechanisms. It should be used with extreme caution, if at all, in any form of A V block or if any clinical signs of digitalis toxicity are exhibited. Quinidine should be used with caution in patients with uncor-rected hypokalemia, hypoxia, and disorders or acid-base balance. Use cautiously in patients with hepatic or renal insufficiency as ac-cumulation of the drug may result. adverse effects In dogs, gastrointestinal effects may include anorexia, vomiting, or diarrhea. Effects related to the cardiovascular system can include weakness, hypotension (especially with too rapid IV administra-tion), negative inotropism, widened QRS complex and QT inter-vals, A V block, and multiform ventricular tachycardias. Horses may exhibit inappetence and depression commonly af-ter quinidine therapy but this does not necessarily indicate toxicity. Signs of toxicity include swelling of the nasal mucosa, ataxia, di-arrhea, colic, hypotension and, rarely, laminitis, paraphimosis and the development of urticarial wheals. Urticaria or upper respira-tory tract obstruction may be treated by discontinuing the drug and administering corticosteroids if necessary. If obstruction persists, nasotracheal tube placement or tracheostomy may be required. Horses may develop cardiac arrhythmias including A V block, circu-latory collapse, and sudden death. Patients exhibiting signs of toxicity or lack of response may be candidates for therapeutic serum monitoring. The therapeutic range is thought to be 2. 5-5 mcg/m L in dogs. T oxic effects usually are not seen unless levels are >10 mcg/m L. Reproductive/nursing Safety In humans, the FDA categorizes this drug as category C for use dur-ing pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) In a separate system evaluating the safety of drugs in canine and feline pregnancy (Papich 1989), this drug is categorized as class: B (Safe for use if used cautiously. Studies in laboratory animals may have un-covered some risk, but these drugs appear to be safe in dogs and cats or these drugs are safe if they are not administered when the animal is near term. ) Quinidine is excreted into maternal milk with a milk:serum ratio of approximately 0. 71. Use caution when quinidine is administered to nursing patients. The American Academy of Pediatrics considers quinidine compatible with breastfeeding. overdosage/acute t oxicity Clinical signs of overdosage can include depression, hypotension, lethargy, confusion, seizures, vomiting, diarrhea, and oliguria. Cardiac signs may include depressed automaticity and conduction, or tachyarrhythmias. The CNS effects are often delayed after the onset of cardiovascular effects but may persist after the cardiovas-cular effects have begun to resolve. If a recent oral ingestion, emptying of the gut and charcoal ad-ministration may be beneficial to remove any unabsorbed drug. IV fluids, plus metaraminol or norepinephrine, can be considered to treat hypotensive effects. A 1/6 molar intravenous infusion of so-dium lactate may be used in an attempt to reduce the cardiotoxic effects of quinidine. Forced diuresis using fluids and diuretics along with reduction of urinary p H may enhance the renal excretion of the drug. T emporary cardiac pacing may be necessary should severe A V block occur. Hemodialysis will effectively remove quinidine, but peritoneal dialysis will not. Drug interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving quinidine and may be of significance in veterinary patients: amio Da Rone T! : May increase quinidine levels (significantly) antaci DST! : May delay oral absorption; separate dosages antia RRHyt Hmic a Gent S T! : Use with caution with other antidys-rhythmic agents, as additive cardiotoxic or other toxic effects may result antic Ho Line Ste Ra Se ST! (e. g., pyridostigmine, neostigmine ): Quini-dine may antagonize the effects of anticholinesterases in patients with myasthenia gravis cimeti Dine T! : Cimetidine may increase the levels of quinidine by inhibiting hepatic microsomal enzymes c La Rit HRomycin T! : Increased risk for torsade de pointes Di Goxin T! : Digoxin levels may increase considerably in patients stabilized on digoxin who receive quinidine. Some cardiologists recommend decreasing the digoxin dosage by 1/2 when adding quinidine. Therapeutic drug monitoring of both quinidine and digoxin may be warranted in these cases. Di Ltiazem T! : Possible decreased clearance; increased elimination half-life of quinidine Hy Poten Si Ve a Gent S T! : Quinidine may potentiate the effects of other drugs having hypotensive effects ketoconazo Le T! : May reduce the metabolism of quinidine neu Romu Scu La R b Lockin G a Gent S T! : Quinidine may increase the neuromuscular blocking effects of drugs like succinylcholine, tubocurarine, or atracurium PHenoba Rbita L, PHenytoin T! : May induce hepatic enzymes that metabolize quinidine thus reducing quinidine serum half-life by 50% PHenot Hiazine ST! : Additive cardiac depressant effects may be seen Re Se RPine T! : Additive cardiac depressant effects may be seen Ri Fam Pin T! : May induce hepatic enzymes that metabolize quinidine thus reducing quinidine serum half-life by 50%	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
quini Dine 799 u Rina R y aci Di Fie RS T! (e. g., methionine, ammonium chloride ): Drugs that acidify the urine (may increase the excretion of quinidine and decrease serum level u Rina R y a Lka Linize RS T! (carbonic anhydrase inhibitors, thiazide diuret-ics, sodium bicarbonate, antacids, etc. ): Drugs that alkalinize the urine may decrease the excretion of quinidine, prolonging its half-life Ve Ra P ami LT! : Possible decreased clearance; increased elimination half-life of quinidine; increased risk for hypotension Wa RFa Rin T! : Coumarin anticoagulants with quinidine may increase the likelihood of bleeding problems Doses Do GS:T! a) For VPC's or ventricular tachycardia: Quinidine gluconate: 6. 6-22 mg/kg IM q2-4h or q8-12h PO (delayed dosage forms). Quinidine Sulfate: 6. 6-22 mg/kg PO q6-8h; may be given initially q2h as a loading dose until arrhythmia is controlled or toxicity is induced (Ettinger 1989) b) 6-20 mg/kg IM q6h (loading dose 14-20 mg/kg); 6-16 mg/ kg PO q6h; Sustained action oral preparations: 8-20 mg/kg PO q8h (Ware 2000) c) 6-16 mg/kg PO or IM q6h (q8h with sustained release prod-ucts) (Fox 2003a) d) For conversion of atrial fib to sinus rhythm: Initially at-tempted with quinidine gluconate at 6-11 mg/kg IM q6h. Most dogs will convert in the first 24 hours of therapy. If rapid ventricular response occurs, may give either digoxin or a beta-blocker to slow rate of conduction across A V node. (Russell and Rush 1995) cat S:T! a) 6-16 mg/kg IM or PO q8h (Ware 2000) Ho RSe S:T! (note : ARCI UCGFS Class 4 Drug) a) For atrial fib without signs of heart failure: Keep horse quiet during dosing stage. Monitor ECG either continuously or be-fore each dose. Horses with recent onset (<7 days) or whom develop atrial fib during anesthesia: Quinidine gluconate 1. 1-2. 2 mg/kg IV every 10 minutes to a total dose of 8. 8-11 mg/kg (or until conversion or toxicity develop). For horses who have had atrial fib for >7 days: Give quinidine sulfate 22 mg/kg via NG tube every 2 hours for a total dose of 88-132 mg/kg (or until conversion or toxicity develop). If this fails to convert and no signs of toxicity are evident may continue at 22 mg/kg, PO q6h for an additional 2-4 or more days. Discontinue if QRS duration is >125% of base-line. Rapid SVT's (>100 BPM) or ventricular arrhythmias may necessitate specific antiarrhythmic therapy. For V-Tach: Quinidine gluconate 0. 5-2. 2 mg/kg IV bolus-es every 10 minutes up to a total of 8. 8-11 mg/kg (Mogg 1999) b) For atrial fibrillation in a horse without heart failure: Oral (via NG tube) Dosing: give quinidine sulfate 22 mg/kg PO via nasogastric tube every two hours until cardioversion, toxic effects, or six doses have been given. If AF remains con-tinue administration every 6 hours until cardioversion or adverse effects. Alternate IV dosing method: 0. 5-2. 2 mg/kg IV bolus every 5-10 minutes to effect or until adverse effects seen. Maxi-mum IV dose is 12mg/kg. Conversion of ventricular tachy-cardia has occurred with a single 0. 5 mg/kg dose. Monitor ECG throughout treatment. Heart rate in excess of 80 bpm, widening QRS complex >125% of baseline, or ab-normal complexes are indicators to discontinue treatment. T oxic effects are variable. Mild signs include nasal edema, and mild depression. More severe signs include marked atax-ia, hypotension, colic, diarrhea, seizures, sustained tachycar-dia, syncope and sudden death. Adverse effects not necessar-ily dose dependent. Hypokalemia increases risk for torsades de pointes. Therapeutic levels 3-5 mcg/m L. (Kimberly and Mc Gurrin 2006) c) For atrial fibrillation: Oral (via NG tube) Dosing: give quinidine sulfate 22 mg/kg PO via nasogastric tube every two hours for 4-6 doses, fol-lowed by dosing q6h if needed for conversion. Withhold food for 12 hours prior to starting treatment to ensure maximum oral absorption. Quinidine dissolves poorly so 1-2 liters of water may be needed per dose. Oral ulcers can occur if at-tempting to administer by mouth. If nasal edema or urticaria occur, discontinue immediately. Heart rate in excess of 100 bpm, widening QRS complex >125% of baseline, ventricu-lar arrhythmias or abnormal complexes are indicators to discontinue treatment or prolong dosing interval. Suggest monitoring levels. (Risberg 2005) monitoring ECG, continuous if possible T! Blood pressure, during IV administration T! Clinical signs of toxicity (see Adverse Reactions/Overdosage)T! Serum levels. Therapeutic serum levels are believed to range from T! 2-7 micrograms/m L. Levels >10 mcg/m L are considered toxic. client information Oral products should be administered at evenly spaced intervals T! throughout the day/night. GI upset may be decreased if admin-istered with food. Do not allow animal to chew or crush sustained-release oral dos-T! age forms. Notify veterinarian if animal's condition deteriorates or signs of T! toxicity (e. g., vomiting, diarrhea, weakness, etc. ) occur. chemistry/Synonyms Used as an antiarrhythmic agent, quinidine is an alkaloid obtained from cinchona or related plants, or is prepared from quinine. It is available commercially in three separate salts: gluconate, polygalac-turonate, or sulfate. Quinidine gluconate occurs as a very bitter tasting, odorless, white powder. It is freely soluble in water and slightly soluble in alcohol. The injectable form has a p H of 5. 5 - 7. Quinidine polygalacturonate occurs as a bitter tasting, creamy white, amorphous powder. It is sparingly soluble in water and freely soluble in hot 40% alcohol. Quinidine sulfate occurs as very bitter tasting, odorless, fine, needle-like, white crystals that may cohere in masses. One gram is soluble in approximately 100 m L of water or 10 m L of alcohol. Quinidine Gluconate may also be known as: quinidinium glu-conate, Duraquin®, Quinaglute®, Quinalan®, and Quinate®. Quinidine Sulfate may also be known as: chinidini sulfas, chini-dinsulfate, chinidinum sulfuricum, or quinidini sulfas; many trade names are available. Quinidine Polygalacturonate may also be known as: Cardioquin®, Cardioquin®, Cardioquine®, Galactoquin®, Naticardina®, or Neochinidin Ritmocor®.	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
800 Rami PRi L Storage/Stability/compatibility All quinidine salts darken upon exposure to light (acquire a brown-ish tint) and should be stored in light-resistant, well-closed con-tainers. Use only colorless, clear solutions of quinidine gluconate for injection. Quinidine gluconate injection is usually administered intramus-cularly, but may be given very slowly (1 m L/minute) intravenously. It may be diluted by adding 10 to 40 m L of D 5W. Quinidine glu-conate is reported to be physically compatible with bretylium tosy-late, cimetidine HCl, and verapamil HCl. It is reportedly physically incompatible with alkalies and iodides. Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: None The ARCI (Racing Commissioners International) has designated this drug as a class 4 substance. See the appendix for more information. Human-Labe Le D PRo Duct S: Quinidine Sulfate (contains 83% anhydrous quinidine alkaloid) Tab-lets: 200 mg & 300 mg; generic; (Rx) Quinidine Sulfate (contains 83% anhydrous quinidine alkaloid) Sus-tained-Release Tablets: 300 mg; generic; (Rx) Quinidine Gluconate Sustained-release Tablets: 324 mg; generic; (Rx) Quinidine Gluconate Injection: 80 mg/m L (50 mg/m L of quinidine base) in 10 m L multi-dose vials; generic (Lilly); (Rx) ra Mipril (ram-ih-prill) Altace®, Vasotop® angioten Sin c onverting enzyme (ace) inhibitor Prescriber Highlights ACE inhibitor used primarily as a vasodilator in the treat-T T ment of heart failure or hypertension; may be of benefit in the treatment of chronic renal failure or protein losing nephropathies Not as much information or experience available as T T some other ACE inhibitors (e. g., enalapril) in dogs or cats Contraindications: Hypersensitivity to ACE inhibitors T T Caution: Pregnancy, patients with hyponatremia, coronary T T or cerebrovascular insuffi ciency, preexisting hematologic abnormalities, or a collagen vascular disease (e. g., SLE)Adverse Effects: Appears well tolerated in both dogs & T T cats. GI effects (anorexia, vomiting, diarrhea) possible; potentially: weakness, hy potension, & hyperkalemia uses/indications Ramipril is a long-acting angiotensin converting enzyme (ACE) in-hibitor that may be useful in treating heart failure or hypertension in dogs or cats. It is an approved product in the UK for treating heart failure in dogs. In cats, ramipril has been used for treating arterial hypertension. A recent study (Mac Donald, Kittleson et al. 2006) did not show any significant benefit using ramipril in treat-ing Maine Coon cats with hypertrophic cardiomyopathy without heart failure. Like other ACE inhibitors, it may potentially be useful as adjunc-tive treatment in chronic renal failure and protein losing nephropa-thies. In dogs with moderate renal impairment (such as might be found with CHF), there is apparently no need to adjust ramipril dosage. Pharmacology/actions Ramipril is a pro-drug that has little pharmacologic activity un-til converted into ramiprilat. Ramiprilat prevents the formation of angiotensin-II (a potent vasoconstrictor) by competing with angio-tensin-I for the enzyme angiotensin-converting enzyme (ACE). ACE has a much higher affinity for ramiprilat than for angiotensin-I. Because angiotensin-II concentrations are decreased, aldos terone secretion is reduced and plasma renin activity is increased. The cardiovascular effects of ramiprilat in patients with CHF include decreased total peripheral resis tance, pulmonary vascular resistance, mean arterial and right atrial pressures, and pulmonary capillary wedge pressure with no change or decrease in heart rate. Increased cardiac index and output, stroke volume, and exercise tolerance also occur. Renal blood flow can be increased with little change in hepatic blood flow. In animals with glomerular disease, ACE inhibitors probably decrease proteinuria and help to preserve renal function. Pharmacokinetics After oral administration to dogs, ramipril is rapidly converted via de-esterification into ramiprilat. Bioavailability of ramiprilat after a dose of 0. 25 mg/kg per day of ramipril is about 6. 7%. At this dose, ACE activity never exceeded 60% in either healthy dogs or those with experimentally induced renal dysfunction (GFR reduced 58%) (Lefebvre, Jeunesse et al. 2006). After oral administration to cats with ramipril doses ranging from 0. 125 mg/kg to 1 mg/kg once daily for 9 days, ramipril peak concentrations occurred in about 0. 5 hours. Ramipril is rapidly converted into its active metabolite ramiprilat, which peaks at 1 hour post-administration. Repeated doses of 0. 125 mg/kg inhibited serum ACE activity by 94% at maximum to 55% 24 hours post-dose. At a dose of 1 mg/kg, ACE activity was 97% inhibited at maxi-mum, and 83% inhibited 24 hours post-dose (Coulet and Burgaud 2002). When cats were administered radio-labeled ramipril orally, 85-89% of the radioactivity was recovered in the feces. It is unclear how much of this represents unabsorbed drug or absorbed parent compound/metabolites eliminated in the feces. Approximately 10% of administered drug was recovered in the urine. Excretion of ra-dio-labeled compounds was complete by 168 hours after dosing. contraindications/Precautions/Warnings The labeling for the UK product approved for dogs (Vasotop®) states that it should not be used in clinical cases of vascular stenosis (e. g., aortic stenosis), obstructive hypertrophic cardiomyopathy, or with potassium-sparing diuretics (see Drug Interactions). adverse effects While information is limited, ramipril appears to be well tolerat-ed in dogs and cats. Gastrointestinal effects are probably the most likely adverse effects to be noted. Weakness, hypotension, or hyper-kalemia are possible. Reproductive/nursing Safety The labeling for the product approved in the UK (Vasotop®) sug-gests not using in bitches during pregnancy or lactation. Weigh the potential risks associated with using this medication (see human data below) in veterinary patients with the potential benefits of therapy. Dosages of up to 500 mg/kg/day did not impair fertility in	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
Raniti Dine Hc L 801 rats. While no teratogenic effects have been detected with ramipril in studies performed in mice, rats, rabbits, and cynomolgus mon-keys, fetal risk is increased in humans. If used in humans during the 2nd and 3rd trimesters increased rates of fetal death, neonatal hypotension, skull hypoplasia, anuria, renal failure, oligohydramnios leading to fetal limb contractures, craniofacial deformation, and hypoplastic lung development were noted. In humans, ramipril has a “black box” warning regarding its use in pregnancy that states “When used in pregnancy during the second and third trimesters, angiotensin-converting enzyme (ACE) inhibitors can cause injury and even death to the developing fe-tus. When pregnancy is detected, ramipril should be discontinued as soon as possible. ” For humans, the FDA categorizes ramipril as category D for use during the 2nd and 3rd trimesters of pregnancy (There is evidence of human fetal risk, but the potential benefits from the use of the drug in pregnant women may be acceptable despite its potential risks) and as category C for use during the first trimester of pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) It is unknown whether ramipril (or ramiprilat) enters milk. Both the veterinary label (UK) and human label recommended not using the drug during nursing. overdosage/acute t oxicity In dogs, ramipril appears quite safe; dosages as high as 1 gram/kg induced only mild GI distress. Lethal doses in rats and mice were noted at 10-11 g/kg. No information was located on overdoses in cats. In overdose situations, the primary concern is hypotension; support ive treatment with volume expansion with normal saline is recommended to correct blood pressure. Because of the drug's long duration of action, prolonged monitoring and treatment may be required. Drug interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving ramipril and may be of significance in veterinary patients: a SPi Rin T! : Aspirin may potentially negate the decrease in systemic vascular resistance induced by ACE inhibitors. However, in one study in dogs using low-dose aspirin, hemodynamic effects of enalaprilat (active metabolite of enalapril, a related drug) were not affected. anti Diabetic a Gent ST! (insulin, oral agents ): Possible increased risk for hypoglycemia; enhanced monitoring recommended Diu Retic ST! (e. g., furosemide, hydrochlorothiazide ): Potential for in-creased hypotensive effects Diu Retic S, Pota SSium SPa Rin G T! (e. g., spironolactone, triamterene ): Increased hyperkalemic effects, enhanced monitoring of serum potassium n Sai DST! : Potential for increased risk of renal dysfunction or hy-perkalemia Pota SSium Su PPLement ST! : Increased risk for hyperkalemia Laboratory considerations ACE inhibitors may cause a reversible decrease in localization T! and excretion of iodohippurate sodium i123/i134, or tech netium tc99 pententate renal imaging in the affected kidney in patients with renal artery stenosis, which could lead to confusion in test inter-pretation Doses Do GS: a) For treatment of heart failure: Initially, 0. 125 mg/kg PO once daily; depending on the severity of pulmonary congestion, dose may be increased to 0. 25 mg/kg PO once daily (Label information; Vasotop®—Intervet UK) cat S: a) For treatment of arterial hypertension: 0. 125 mg/kg PO once daily (Graff and Herve 2003) monitoring Clinical signs of CHFT! Serum electrolytes, creatinine, BUN, urine protein T! CBC with differential, periodic T! Blood pressure (if treating hypertension or clinical signs associ-T! ated with hypotension arise) client information For this drug to be maximally effective it must be given once daily T! at about the same time each day Do not abruptly stop or reduce therapy without veterinarian's T! approval Con tact veterinarian if vomiting or diarrhea persist, are severe, or T! if animal's condition deteriorates chemistry/Synonyms Ramipril occurs as a white to almost white, crystalline powder that is sparingly soluble in water and freely soluble in methyl alcohol. Ramipril may also be known as Hoe-498, ramiprilis, or ramipril-ium. There are many international trade names, including: Altace®, Cardase®, Delix®, Ramase®, Triatec®, and Tritace®. Storage/Stability Capsules should be stored at room temperature (15-30°C) pro-tected from light in tight containers. Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: None in the USA; in the UK and in other European countries: Ramipril Tablets: 0. 625 mg, 1. 25 mg, 2. 5 mg, & 5 mg; Vasotop® (In-tervet); (Rx). Approved for use in dogs. Human-Labe Le D PRo Duct S: Ramipril Capsules: 1. 25 mg, 2. 5 mg, 5 mg, & 10 mg; Altace® (Mon-arch); (Rx) ranitidine Hcl (rah-nit-a-deen) Zantac® h2 rece Ptor antagoni St; Prokinetic Prescriber Highlights HT T2 receptor antagonist similar to cimetidine, but fewer drug interactions; used to reduce acid output in stomach; also has prokinetic activity Contraindications: Hypersensitivity. Caution: Geriatric pa-T T tients, hepatic or renal insufficiency Adverse Effects: Rare. IV boluses may cause vomiting. T T Potentially: Mental confusion, agranulocytosis, & tran-sient cardiac arrhythmias (too rapid IV injection). Pain at the injection site after IM administration.	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
802 Raniti Dine Hc L uses/indications In veterinary medicine, ranitidine has been used for the treatment and/or prophylaxis of gastric, abomasal, and duodenal ulcers, uremic gastritis, stress-related or drug-induced erosive gastritis, esophagitis, duodenal gastric reflux and esophageal reflux. It has also been employed to treat hypersecretory conditions associated with gastrinomas and systemic mastocytosis. Because of its effects on gastric motility, ranitidine may be useful in increasing gastric emptying, particularly when delayed gastric emptying is associated with gastric ulcer disease. Ranitidine may also be useful to stimulate colonic activity in cats via its prokinetic effects. Pharmacology/actions At the H 2 receptors of the parietal cells, ranitidine competitively in-hibits histamine, thereby reducing gastric acid output both during basal conditions and when stimulated by food, amino acids, penta-gastrin, histamine, or insulin. Ranitidine is between 3-13 times more potent (on a molar basis) as cimetidine. While ranitidine may cause gastric emptying times to be de-layed, it more likely will stimulate GI motility by inhibiting ace-tylcholinesterase (thereby increasing acetylcholine at muscarinic receptors). Lower esophageal sphincter pressures may be increased by ranitidine. By decreasing the amount of gastric juice produced, ranitidine decreases the amount of pepsin secreted. Ranitidine, unlike cimetidine, does not appear to have any ap-preciable effect on serum prolactin levels, although it may inhibit the release of vasopressin. Pharmacokinetics In dogs, the oral bioavailability is approximately 81%, serum half-life is 2. 2 hours and volume of distribution 2. 6 L/kg. In horses, oral ranitidine has a bioavailability of about 27% in adults and 38% in foals. Peak levels after oral dosing occur in about 100 minutes in adults and 60 minutes in foals. Apparent volume of distribution is approximately 1. 1 L/kg and 1. 5 L/kg in adults and foals, respectively. Clearance in adults is approximately 10 m L/min/kg and 13. 3 m L/min/kg in foals. In humans, ranitidine is absorbed rapidly after oral adminis-tration, but undergoes extensive first-pass metabolism with a net systemic bioavailability of approximately 50%. Peak levels occur at about 2-3 hours after oral dosing. Food does not appreciably alter the extent of absorption or the peak serum levels attained. Ranitidine is distributed widely throughout the body and is only 10-19% bound to plasma proteins. Ranitidine is distributed into human milk at levels 25-100% of those found in plasma. Ranitidine is both excreted in the urine by the kidneys (via glomerular filtration and tubular secretion) and metabolized in the liver to inactive metabolites; accumulation of the drug can occur in patients with renal insufficiency. The serum half-life of ranitidine in humans averages 2-3 hours. The duration of action at usual doses is from 8-12 hours. contraindications/Precautions/Warnings Ranitidine is contraindicated in patients who are hypersensitive to it. It should be used cautiously and possibly at reduced dosage in patients with diminished renal function. Ranitidine has caused increased serum ALT levels in humans receiving high, IV doses for longer than 5 days. The manufacturer recommends that with high dose, chronic therapy, serum ALT values be considered for monitoring. adverse effects Adverse effects appear to be very rare in animals at the dosages generally used. Potential adverse effects (documented in humans) that might be seen include mental confusion and headache. Rarely, agranulocytosis may develop and, if given rapidly IV, transient car-diac arrhythmias may be seen. Pain at the injection site may be not-ed after IM administration. IV boluses have been associated with vomiting in small animals. Reproductive/nursing Safety In humans, the FDA categorizes this drug as category B for use dur-ing pregnancy (Animal studies have not yet demonstrated risk to the fetus, but there are no adequate studies in pregnant women; or animal studies have shown an adverse effect, but adequate studies in pregnant women have not demonstrated a risk to the fetus in the first trimester of pregnancy, and there is no evidence of risk in later trimesters. ) In a separate system evaluating the safety of drugs in canine and feline pregnancy (Papich 1989), this drug is categorized as class: B (Safe for use if used cautiously. Studies in laboratory animals may have un-covered some risk, but these drugs appear to be safe in dogs and cats or these drugs are safe if they are not administered when the animal is near term. ) Ranitidine is excreted in human breast milk with milk:plasma ratios of approximately 5:1 to 12:1. The drug is not recommended to be used in nursing humans; use with caution in nursing veteri-nary patients. overdosage/acute t oxicity Clinical experience with ranitidine overdosage is limited. In labo-ratory animals, very high dosages (225 mg/kg/day) have been as-sociated with muscular tremors, vomiting and rapid respirations. Single doses of 1 gram/kg in rodents did not cause death. Treatment of overdoses in animals should be handled us-ing standard protocols for oral ingestions of drugs; clinical signs may be treated symptomatically and supportively if necessary. Hemodialysis and peritoneal dialysis have been noted to remove ranitidine from the body. Drug interactions Unlike cimetidine, ranitidine appears to have much less effect on the hepatic metabolism of drugs and is unlikely to cause clinically relevant drug interactions via this mechanism. The following drug interactions have either been reported or are theoretical in humans or animals receiving ranitidine and may be of significance in vet-erinary patients: acetamino PHen T! : Ranitidine (dose-dependent) may inhibit acet-aminophen metabolism antaci DST! (high doses): May decrease the absorption of ranitidine; give at separate times (2 hours apart) if used concurrently ketoconazo Le, it Raconazo Le T! : Absorption may be reduced sec-ondary to increased gastric p H meto PRo Lo LT! : Ranitidine may increase metoprolol half-life, and peak levels ni Fe Di Pine T! : Ranitidine may increase nifedipine AUC by 30% PRo P ant He Line T! : Delays the absorption but increases the peak se-rum level of ranitidine; relative bioavailability of ranitidine may be increased by 23% when propantheline is administered con-comitantly with ranitidine Vitamin b-12T! : Long-term ranitidine use may reduce oral absorp-tion of B-12 Laboratory considerations Ranitidine may cause a false-positive T! urine protein reading when using Multistix®. The sulfosalicylic acid reagent is recommended for determining urine protein when the patient is concomitantly receiving ranitidine.	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
Ri Fam Pin 803 Doses Do GS:T! For esophagitis: a) 1-2 mg/kg PO twice daily (Watrous 1988) For chronic gastritis: a) 0. 5 mg/kg PO twice daily (Hall and Twedt 1988) For ulcer disease:a) 0. 5-2 mg/kg PO, IV or IM q8-12h (Haskins 2000) b) 2 mg/kg PO, IV q8h (Matz 1995) c) 1-2 mg/kg PO, IV, SC q12h (also used for esophagitis) (Sell-on 2007b) d) 2 mg/kg PO, IV q12h (Waddell 2007a) For gastrinoma:a) 1-2 mg/kg PO, SC, IV q8-12h (Zerbe and Washabau 2000) b) 0. 5 mg/kg PO, IV or SC twice daily (Kay, Kruth, and Twedt 1988) T o treat hypergastrinemia secondary to chronic renal failure: a) 1-2 mg/kg PO twice daily (Morgan 1988) T o treat hyperhistaminemia secondary to mast cell tumors: a) 2 mg/kg q12h (Fox 1995) As a prokinetic agent to stimulate gastric contractions: a) 1-2 mg/kg PO q12h (Hall and Washabau 2000) cat S:T! For ulcer disease/esophagitis:: a) 2. 5 mg/kg IV q12h or 3. 5 mg/kg PO q12h (Matz 1995), (Johnson 1996) b) 1-2 mg/kg PO, IV, SC q12h (Sellon 2007b) c) 2 mg/kg PO, IV q12h (Waddell 2007a) As a prokinetic agent to stimulate colonic motility:a) 1-2 mg/kg PO q8-12h (Washabau and Holt 2000) b) 1-2 mg/kg PO q12h (Scherk 2003b) Ho RSe S:T! (note : ARCI UCGFS Class 5 Drug) a) 6. 6 mg/kg PO q8h (Andrews and Nadeau 1999) b) Foals: 6. 6 mg/kg IV q4h or 0. 8-2. 2 mg/kg IV four times a day; 5-10 mg/kg PO two to four times a day. (Wilkins 2004b) c) 1. 5-2 mg/kg IV or IM q6-8h; 6. 6 mg/kg PO q8h (Sanchez 2004a) monitoring Clinical efficacy (dependent on reason for use); monitored by de-T! crease in clinical signs, endoscopic examination, blood in feces, etc. client information T o maximize the benefit of this medication, it must be adminis-T! tered as prescribed by the veterinarian; symptoms may reoccur if dosages are missed. chemistry/Synonyms An H 2 receptor antagonist, ranitidine HCl occurs as a white to pale-yellow granular substance with a bitter taste and a sulfur-like odor. The drug has p K as of 8. 2 and 2. 7. One gram is approximately soluble in 1. 5 m L of water or 6 m L of alcohol. The commercially available injection has a p H of 6. 7-7. 3. Ranitidine HCl may also be known as: AH-19065, ranitidini hy-drochloridum; many trade names are available. Storage/Stability Ranitidine tablets should be stored in tight, light-resistant contain-ers at room temperature. The injectable product should be stored protected from light and at a temperature less than 30°C. A slight darkening of the injectable solution does not affect the potency of the drug. Ranitidine injection is reportedly stable up to 48 hours when mixed with the commonly used IV solutions (including 5% sodium bicarbonate). Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: None The ARCI (Racing Commissioners International) has designated this drug as a class 5 substance. See the appendix for more information. Human-Labe Le D PRo Duct S: Ranitidine HCl Tablets: 75 mg, 150 mg & 300 mg (as base); Zan-tac® (Glaxo Smith Kline); (Rx); Zantac® 75 &-150 (Pfizer Consumer Healthcare); generic; (Rx or OTC) Ranitidine HCl Effervescent Tablets: 25 mg & 150 mg (as base); Zan-tac® EFFERdose (Glaxo Smith Kline); (Rx)Ranitidine HCl Syrup: 15 mg/m L (as base) in 480 m L; Zantac® (Glaxo Smith Kline); (Rx)Ranitidine HCl Injection: 1 mg/m L (premixed) & 25 mg/m L in 50 m L (preservative free) plastic containers, 2 m L single-dose and 6 m L multi-dose vials; Zantac® (Glaxo Smith Kline); generic (Bedford); (Rx) rifa Mpin (rif-am-pin) Rifadin®, Rimactane® antimicrobial Prescriber Highlights Antimicrobial with activity against a variety of microbes T T (Rhodococcus, mycobacteria, staphylococci); has some antifungal & antiviral activity as well. Contraindications: Hypersensitivity to it or other T T rifamycins Caution: Preexisting hepatic dysfunction (may need to T T reduce dosage)Adverse Effects: Uncommon; potentially rashes, GI dis-T T tress, & increases in liver enzymes. Should not be used alone as resistance develops rapidly T T Preferably, give on an empty stomach T T May cause red/orange urine, tears, & sweat (harmless)T T Drug Interactions, lab interactions T T uses/indications The principle use of rifampin in veterinary medicine is in the treat-ment of Rhodococcus equi ( Corynebacterium equi) infections (usu-ally with erythromycin estolate) in young horses. It may also be useful to treat proliferative enteropathy caused by Lawsonia intra-cellularis in foals. In small animals, the drug is sometimes used in combination with other antifungal agents (amphotericin B and 5-FC) in the treatment of histoplasmosis or aspergillosis with CNS involvement.	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
804 Ri Fam Pin Pharmacology/actions Rifampin may act as either a bactericidal or bacteriostatic anti-microbial dependent upon the susceptibility of the organism and the concentration of the drug. Rifampin acts by inhibiting DNA-dependent RNA polymerase in susceptible organisms, thereby sup-pressing the initiation of chain formation for RNA synthesis. It does not inhibit the mammalian enzyme. Rifampin is active against a variety of mycobacterium species and Staphylococcus aureus, Neisseria, Haemophilus, and Rhodococcus equi ( C. equi). At very high levels, rifampin has activity against pox-viruses, adenoviruses, and Chlamydia trachomatis. Rifampin has antifungal activity when combined with other antifungal agents. Pharmacokinetics After oral administration, rifampin is relatively well absorbed from the GI tract. Oral bioavailability is reportedly about 40-70% in horses and 37% in adult sheep. If food is given concurrently, peak plasma levels may be delayed and slightly reduced. Rifampin is very lipophilic and readily penetrates most body tissues (including bone and prostate), cells and fluids (including CSF). It also penetrates abscesses and caseous material. Rifampin is 70-90% bound to serum proteins, is distributed into milk and crosses the placenta. Mean volume of distribution is approximately 0. 9 L/kg in horses, and 1. 3 L/kg in sheep. Rifampin is metabolized in the liver to a deacetylated form that also has antibacterial activity. Both this metabolite and unchanged drug are excreted primarily in the bile, but up to 30% may be ex-creted in the urine. The parent drug is substantially reabsorbed in the gut, but the metabolite is not. Reported elimination half-lives for various species are: 6-8 hours (horses), 8 hours (dogs), 3-5 hour's (sheep). Because rifampin can induce hepatic microsomal enzymes, elimination rates may increase with time. contraindications/Precautions/Warnings Rifampin is contraindicated in patients hypersensitive to it or to other rifamycins. It should be used with caution in patients with preexisting hepatic dysfunction. adverse effects Rifampin can cause red-orange colored urine, tears, sweat, and sa-liva. There are no harmful consequences from this effect. In some species (e. g., humans) rashes, GI distress, and increases in liver en-zymes may occur, particularly with long-term use. Because resistance develops rapidly when rifampin is used alone, it should be used in combination with other effective antibiotics. Adverse effects in horses are apparently rare, but when com-bined with erythromycin, mild diarrhea (self-limiting) to severe enterocolitis in foals and mares, hyperthermia, and acute respira-tory distress can occur. Although not commercially available, intra-venous rifampin has caused CNS depression, sweating, hemolysis, and anorexia in horses. Reproductive/nursing Safety Rodents given high doses of rifampin 150-250 mg/kg/day resulted in some congenital malformations in offspring, but the drug has been used in pregnant women with no reported increases in terato-genicity. In humans, the FDA categorizes this drug as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) Rifampin is excreted in maternal milk; use with caution in nurs-ing veterinary patients. overdosage/acute t oxicity Clinical signs associated with overdosage of oral rifampin generally are extensions of the adverse effects outlined above (GI, orange-red coloring of fluids, and skin), but massive overdoses may cause hepatotoxicity. There were 16 exposures to rifampin reported to the ASPCA Animal Poison Control Center (APCC; www. apcc. aspca. org) dur-ing 2005-2006. In these cases 6 were dogs with 1 showing clinical signs and 8 were cats with 1 showing clinical signs. The remaining 2 reported cases were both equine showing no clinical signs. Common findings in dogs recorded in decreasing frequency included ataxia, and central nervous system depression. Common findings in cats recorded in decreasing frequency included edema of the face, ery-thema, injected mucous membranes, mydriasis and tachypnea. Should a massive oral overdosage occur, the gut should be emp-tied following standard protocols. Liver enzymes should be moni-tored and supportive treatment initiated if necessary. Drug interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving rifampin and may be of significance in veterinary patients: FLuo Roquino Lone ST! : In vitro antagonism has been reported when rifampin is used concurrently with fluoroquinolone antibiotics and concurrent use should be avoided Because rifampin has been documented to induce hepatic mi-crosomal enzymes, drugs that are metabolized by these enzymes may have their elimination half-lives shortened and serum levels de-creased; drugs/classes that may be affected by this process include: ba Rbitu Rate S !! benzo Diaze Pine S !! (e. g., diazepam ) c HLo Ram PHenico L!! co Rtico Ste Roi DS!! Da PSone !! ketoconazo Le!! PRo PRano Lo L!! quini Dine T! Wa RFa Rin!! Laboratory considerations Microbiologic methods of assaying serum T! folate and vitamin b12 are interfered with by rifampin. Rifampin can cause false-positive T! b SP (bromosulfophthalein, sulfobromophthalein) test results by inhibiting the hepatic up-take of the drug Doses note : Because resistance develops rapidly when rifampin is used alone, it should be used in combination with other effective antibiotics. Do GS:T! a) For combination therapy of atypical Mycobacteria infec-tions; treatment of resistant Staph endocarditis (in combi-nation with amoxicillin/clavulanate or trimethoprim/sulfa): 10-20 mg/kg PO q8-12h (Trepanier 1999) b) For CNS fungal infections (aspergillosis/histoplasmosis): Ri-fampin 10-20 mg/kg PO three times daily with amphoteri-cin B and flucytosine (Schunk 1988) c) For actinomycosis: 10-20 mg/kg PO q12h PO (Hardie 1984)	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
Romi Fi Dine Hc L 805 cat S:T! a) For CNS fungal infections (aspergillosis/histoplasmosis): Ri-fampin 10-20 mg/kg PO three times daily with amphoteri-cin B and flucytosine (Schunk 1988) Ho RSe S:T! For treatment of Rhodococcus equi (C. equi) infections in foals:a) Rifampin 5 mg/kg PO two times daily with erythromycin 15-25 mg/kg, PO q12-24h. Conventional treatment, but erythromycin has numerous side effects including entero-colitis in foals and mares, hyperthermia, and acute respi-ratory distress. Clarithromycin may be superior. (Chaffin 2006b) b) Rifampin 5 mg/kg PO two times daily or 10 mg/kg PO once daily with erythromycin 25 mg/kg, PO q6-8h. Duration of therapy usually takes 4-9 weeks. (Giguere 2003b) For susceptible infections in foals: a) For treatment of proliferative enteropathy caused by Lawso-nia intracellularis in foals: Erythromycin estolate (25 mg/kg PO q6-8h) alone or in combination with rifampin: 10 mg/ kg PO once daily for a minimum of 21 days (Lavoie and Dro-let 2003) bi RDS:T! For treatment of mycobacteriosis: a) Rifampin (45 mg/kg PO once daily) in combination with ethambutol (30 mg/kg PO once daily) and one of the fol-lowing: clofazimine (6 mg/kg PO once daily) or isoniazid (30 mg/kg PO once daily). (Pollock 2007a) monitoring Clinical efficacy T! For monitoring T! C. equi infections in foals and response to ri-fampin/erythromycin: Chest radiographs and plasma fibrinogen levels have been suggested as prognostic indicators when done after 1 week of therapy. (Hillidge and Zertuche 1987) Adverse effects: may consider liver function monitoring with T! long-term therapy. client information Rifampin may cause urine and other secretions (tears, saliva, etc. ) T! to turn red-orange in color; this is not abnormal Preferably give on an empty stomach T! May cause softening of stools in horses/foals T! chemistry/Synonyms A semi-synthetic zwitterion derivative of rifamycin B, rifampin oc-curs as a red-brown, crystalline powder with a p K a of 7. 9. It is very slightly soluble in water and slightly soluble in alcohol. Rifampin may also be known as: Ba-41166/E, L-5103, NSC-113926, rifaldazine, rifampicinum, rifamycin AMP; many trade names are available. Storage/Stability Rifampin capsules should be stored in tight, light-resistant contain-ers, preferably at room temperature (15-30°C). Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: None Human-Labe Le D PRo Duct S: Rifampin Capsules: 150 mg & 300 mg; Rifadin® (Aventis); Rimac-tane® (Novartis); generic; (Rx) Rifampin Powder for Injection: 600 mg; Rifadin® (Aventis); (Rx)ro Mifidine Hcl (roe-mif-ih-deen) Sedivet® al Pha-2 agoni St Sedative analge Sic Prescriber Highlights Alpha-2 agonist with sedative, muscle relaxant & analge-T T sic effects Indicated in USA for adult horses as a sedative & anal-T T gesic to facilitate handling, clinical examinations & pro-cedures, minor surgical procedures, & as preanesthetic prior to the induction of general anesthesia Labeled in some European countries for use in dogs & T T cats; has been used extra-label in foals & cattle Adverse effects in T T HORSES include bradycardia (pos-sibly profound), first-& second-degree atrioventricular heart block, sinus arrhythmias (dose dependent), initial hypertension followed by hypotension, ataxia, sweating, piloerection, salivation, muscle tremors, penile-relaxation, urination, swelling of face, lips & upper airways, stridor, decreased GI motility, flatulence & mild colic; anaphylaxis possible In T TDOGS & CATS, romifidine may cause bradycardia, car-diac arrhythmias, hypotension, transient hyperglycemia, & alterations in thermoregulation. Dogs may pant, sali-vate, vomit (less likely than in cats), & develop muscle twitching. Vomiting in cats may be a problem Adjust dosage if used with other CNS depressant drugs T T uses/indications Romifidine is an alpha-2 agonist with sedative, muscle relaxant and analgesic effects. It is indicated (in the USA) for use in adult horses as a sedative and analgesic to facilitate handling, clinical examina-tions and procedures, minor surgical procedures, and as a preanes-thetic prior to the induction of general anesthesia. In certain European countries, it is approved for use in dogs and cats as a sedative/preanesthetic. Although not approved, romifidine has been used in cattle and foals. Pharmacology/actions A potent alpha 2-adrenergic agonist, romifidine is classified as a sed-ative/analgesic with muscle relaxant properties. Alpha-2 receptors are found in the CNS and several tissues peripherally; both presyn-aptically and postsynaptically. In the CNS, the primary action is a feedback inhibition of norepinephrine release. Opioids and alpha-2 agonists may have synergistic analgesic effects. Pharmacologic effects of romifidine include sedation, an-algesia, and reduced catecholamine release from the CNS. Thermoregulatory mechanisms may be altered. Peripherally, an initial vasoconstrictive response occurs with increases in blood pressure. Within minutes a hypotensive phase occurs. Heart rate can significantly decrease secondary to a vagal response to hyper-tension. A second-degree atrioventricular block may also occur. Antimuscarinic agents can prevent bradycardia, but their use is controversial as they can potentially cause hypertension, increased myocardial oxygen demand, and reduced GI motility. Alpha-2 ago-nists can transiently slow duodenal motility and increase mictura-tion in horses and can inhibit insulin release from pancreatic islet cells resulting in hyperglycemia. Other effects seen in horses in-	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
806 Romi Fi Dine Hc L clude sweating, mydriasis, decreases in hematocrit, and increased uterine pressure in non-pregnant mares. In horses, when compared with other alpha-2 agonists (xylazine, detomidine, medetomidine), romifidine does not appear to cause as much ataxia at sedative dosages and has the longest duration of sedation. Duration of analgesia is shorter than the duration of sedation. Pharmacokinetics Pharmacokinetic studies for romifidine in horses were not located. In dogs and cats, bioavailability after IM administration is 86% and 95%, respectively. Bioavailability after subcutaneous injection in dogs is 92%. Peak levels after IM injection occur in approximate-ly 50 minutes in dogs and 25 minutes in cats. After IV injection, volumes of distribution are about 3 L/kg in dogs, and 6 L/kg in cats. Romifidine is biotransformed in the liver. In dogs, about 80% of an administered dose is eliminated in the urine; 20% in the feces. Elimination half-lives are approximately 2 hours for dogs, 6 hours for cats. contraindications/Precautions/Warnings Romifidine should not be used in animals hypersensitive to it or in combination with intravenous potentiated sulfonamides. The label states that this medication should not be used in horses with respiratory disease, hepatic or renal disease, or other systemic con-ditions of compromised health. It also states that the effects of this medication have not been evaluated in horses with colic, or in foals. Because of its effects on heart rhythm and blood pressure, use very cautiously in horses with preexisting cardiac conditions. The manufacturer cautions that using with other sedatives, tran-quilizers, or opioids may potentiate the adverse effects of romifi-dine and to avoid using epinephrine as it may potentiate the effects of alpha-2 agonists. Although animals may appear to be deeply sedated, some may respond (kick, etc. ) to external stim uli; use appropriate caution. When used in dogs and cats, the label for Romydis® (Virbac— Ireland) states: “Animals should be restrained to prevent injury, ensure that animals have sufficient fluid intake, and if undergoing prolonged sedation, animals should be prevented from becoming hypothermic. Additionally, care should be taken when used in ani-mals in poor health, suffering from respiratory distress, or in cases of cardiovascular, renal, hepatic or pancreatic disease. ” Cats with pancreatitis should be closely monitored. Because dogs and, partic-ularly, cats may vomit after receiving romifidine, the manufacturer recommends not feeding for at least 12 hours prior to use. This medication can be absorbed through the skin and via oral routes. Persons administering the medication should handle it care-fully and avoid self-exposure. adverse effects In horses, romifidine may cause bradycardia (possibly profound), first-and second-degree atrioventricular heart block, and sinus arrhythmias (dose dependent). Initially, hypertension may occur followed by hypotension. Other adverse effects can include: ataxia, sweating, piloerection, salivation, muscle tremors, penile-relaxation, urination (occurs about one hour after dose), swelling of face, lips and upper airways, stridor, decreased GI motility, flatulence and mild colic. There is a possibility that horses may react paradoxically (excitation) to romifidine. Rarely, anaphylactic reactions to alpha-2 agonists have been reported in horses. In dogs and cats romifidine may cause bradycardia, cardiac ar-rhythmias, hypotension, transient hyperglycemia, and alterations in thermoregulation (body temperature may increase or decrease de-pending on ambient temperature). Dogs may pant, salivate, vomit (less likely than in cats), and develop muscle twitching. In cats, vomiting associated with romifidine use can be seen and persist up to 24 hours after dosing. Pancreatitis has been noted in some cats receiving the drug repeatedly every 2 days for 6 days; dose related increases in BUN have been observed. Localized injec-tion site reactions have occurred in cats receiving the medication intramuscularly. Reproductive/nursing Safety The label for the US product states that the effects of this medica-tion have not been evaluated in pregnant mares, horses intended for breeding, or foals. The labeling for the equine and small animal products approved in Europe states that the drug is contraindicated in pregnant horses during the last month of pregnancy and during pregnancy in dogs and cats. overdosage/acute t oxicity Horses have received up to 600 mcg/kg (5X) in experimental stud-ies. Signs exhibited included sinus bradycardia, 2nd degree heart block, occasional apnea and mild respiratory stridor, deep sedation, frequent urination, and sweating. No clinically significant altera-tions in blood gases, acid-base, hematological or chemical param-eters were noted. If necessary, a reversal agent such as atipamezole (at a dose of 30-80 mcg/kg) or yohimbine may be used to reduce the duration and extent of adverse effects associated with acute toxicity. Dogs have been administered doses of up to 1 mg/kg (approx 8-10X) IV daily for up to 4 weeks with no serious adverse effects reported. Drug interactions int Ra Venou S Potentiate D Su LFonami De S T! (e. g., trimethoprim/sulfa ): The manufacturer warns against using this agent with intrave-nous potentiated sulfonamides as fatal dysrhythmias may occur ot He R a LPHa-2 a Goni St ST! (e. g., xylazine, medetomidine, detomidine, clonidine and including epinephrine ): Not recommended to be used together with romifidine as effects may be additive PHenot Hiazine ST! (e. g., acepromazine ): Severe hypotension can result The following drug interactions have either been reported or are theoretical in humans receiving a similar alpha-2 agonist, dexmeto-midine and may be of significance in veterinary patients: ane St Hetic S, o Piate S, Se Dati Ve/Hy Pnotic S T! : Effects may be addi-tive; dosage reduction of one or both agents may be required; potential for increased risk for arrhythmias when used in combi-nation with thiopental, ketamine or halothane Laboratory considerations a DP-induced platelet aggregation T! : Can be inhibited in cats by me-detomidine (a related alpha-2 agonist); not known if romifidine can have this effect Doses Ho RSe S T! (adults): a) For sedation and analgesia : 40-120 mcg/kg IV slowly one time. This dose is equivalent to 0. 4-1. 2 m L per 100 kg (220 lb) body weight using the 1% (10 mg/m L) injection. Degree of sedation and analgesia is dose and time dependent. Onset of action occurs between 30 seconds to 5 minutes and gradu-ally subsides during the next 2-4 hours. Duration of analge-sia is shorter than the duration of sedation. See the package insert for expected onset and duration times for sedation and analgesia based upon dose.	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
Roni Dazo Le 807 as a preanesthetic : 100 mcg/kg as slow, single IV injection. In-duce anesthesia after maximal sedation is achieved. Mild to moderate sedation occurs in 2-4 minutes. Anesthetic doses may need to be decreased to prevent an overdose as romi-fidine has anesthesia-sparing effects. (Label information; Sedavet®—B-I Vetmedica) Do GS:T! a) For sedation : 40-120 mcg/kg IV, IM or SQ. IV administration causes sedation within approximately 5 minutes. With SC or IM injection sedation is delayed until about 30 minutes post-injection. Sedation depth is also lower than with IV injection. Atipamezole may be used to hasten recovery. A dose of 200 mcg/kg atipamezole IM will reverse a dose of 120 mcg/kg of romifidine. as a preanesthetic : 40-120 mcg/kg IV, IM or SQ. Induce anesthesia (with propofol or thiopental) approximately 10 minutes after IV injection and 10-15 minutes after IM or SC injection. Label states to maintain anesthesia with halothane. (Label information; Romydis®—Virbac-Ireland) b) as an analgesic adjunct: 10-20 mcg/kg IM, SQ. May combine with an anticholinergic agent in exercise-tolerant patients free from heart disease. (Lamont and Tranquilli 2002) cat S:T! a) For sedation : 200-400 mcg/kg IV or IM. An IM injection of 200 mcg/kg gives sedation in about 10 minutes and persists for about 60 minutes. IV administration gives a more rapid onset of action (5 minutes) and the duration is similar to IM. Atipamezole IM 30 minutes after IM romifidine injection may be used to hasten recovery. A dose of 400 mcg/kg atipa-mezole IM will reverse a dose of 400 mcg/kg of romifidine. as a preanesthetic : 200 mcg/kg IM 10-15 minutes prior to giving ketamine at 10 mg/kg IM will provide surgical anes-thesia for up to 30 minutes. Increasing the dose of romifidine to 400 mcg/kg will extend period of surgical anesthesia. A ”top-up dose” of 50% of the initial doses of romifidine and ketamine can be used to prolong anesthesia. (Label informa-tion; Romydis®—Virbac-Ireland) b) as an analgesic adjunct: 20-40 mcg/kg IM, IV. May combine with an anticholinergic agent in exercise-tolerant patients free from heart disease. (Lamont and Tranquilli 2002) catt Le:T! note : Romifidine is not approved for use in cattle or other food-producing animals in the USA. For guidance with determin-ing withdrawal times, contact FARAD (see Phone Numbers & Websites in the appendix for contact information). a) For epidural anesthesia for paralumbar analgesia or laparotomy : Romifidine 50 mcg/kg plus morphine 0. 1 mg/kg. Duration of analgesia is 12 hours maximum. (Anderson 2006b) monitoring Level of sedation/analgesia T! Respiratory rate T! Heart rate/rhythm; blood pressure (during general anesthesia) T! Body temperature for longer procedures using higher dosages T! client information This medication should only be administered by veterinary pro-T! fessionals If clients are involved with handling horses after they are dosed T! with romifidine, they should be warned that although the horse looks fully sedated it may respond defensively (e. g., kick) when stimulatedchemistry/Synonyms Romifidine HCl is an alpha-2 adrenoreceptor agonist that is struc-turally related to clonidine. It has a mo lecular weight of 258. 1 and occurs as a crystalline, white, odorless substance that is soluble in water. Its chemical name is 2-(2-Bromo-7-fluoroanilino-)-2-imi-dazoline or 2-Bromo-6-fluoro-N-(1-imida zolin-2yl)analine. Romifidine may also be known as: STH-2130, romi fidiini, romi-fidin, romifidina, romifidinum, Romidys®, Sedivet®, and Sedivan®. Storage/Stability Romifidine HCl injection should be stored at controlled room tem-perature (15-30°C). Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: Romifidine HCl 1% (10 mg/m L) Injection; Sedivet® (B-I Vetmedica); (Rx). In the USA: Approved for use in horses not intended for hu-man consumption. In the UK, slaughter withdrawal is 6 days for horses. A small animal product, Romidys® (Virbac) containing 1 mg/m L is approved for use in dogs and cats in some European countries. Human-Labe Le D PRo Duct S: None ronidazole (roe-nid-ah-zole) anti Protozoal Prescriber Highlights Nitroimidazole antibiotic/antiparasitic drug that appears T T to be useful in treating Tritrichomonas foetus infections in cats; also used for treating trichomonas infections in non-food birds Potentially carcinogenic; avoid human exposure T T Neurotoxicity (reversible): more likely at higher doses (50 T T mg/kg twice daily), but can occur at lower dosages as well; GI effects possible Many potential drug interactions T T Must be compounded from bulk powder (100%) & ide-T T ally, put in gelatin capsules uses/indications Ronidazole is a nitroimidazole antibiotic/antiparasitic drug that appears to be useful in treating Tritrichomonas foetus infections in cats. The drug is not commercially available in the USA and must be compounded from bulk powder by a compounding pharmacy. The drug is also used for treating Trichomonas infections in non-food animal birds. Pharmacology/actions Ronidazole, like other 5-nitroimidazoles such as metronidazole is converted by hydrogenosomes (an organelle found in trichomonads) into polar autotoxic anion radicals. T. foetus infections in cats have been resistant to treatment by metronidazole, but ronidazole ap-pears to have greater activity against the organism. Pharmacokinetics No information was located.	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
808 Roni Dazo Le contraindications/Precautions/Warnings Ronidazole should not be used in patients hypersensitive to it or other 5-nitroimidazoles (e. g., metronidazole). The compound has been demonstrated to be carcinogenic in mice but not rats. While humans should avoid contact with this compound or with animal waste from treated patients, it can be safely compounded using a biological safety cabinet. The FDA prohibits this drug for use in food animals. adverse effects Reversible neurotoxicity similar to that reported with metronida-zole, has been reported in cats with ronidazole. Initial signs may in-clude ataxia, nystagmus, or behavior changes. Should neurotoxicity be diagnosed, discontinue ronidazole, treat supportively, and if nec-essary, consider administering a benzodiazepine such as diazepam to competitively inhibit GABA receptors in the CNS. Incidence of neurotoxicity appears to be higher when using the 50 mg/kg twice daily dosage, but may occur at lower dosages as well. Potentially, gastrointestinal effects can occur (anorexia, vomiting). Ronidazole is very bitter and should be administered to cats in capsule form. Ronidazole has been shown to increase the rate of benign mam-mary tumors in rats and increase the rates of benign and malignant pulmonary tumors in mice at dosages at or above 20 mg/kg/day. Dogs given 30 mg/kg per day for two years (40 mg/kg/day the first month) showed some testicular toxicity (type not specified), but no tumors. Reproductive/nursing Safety Safety of this compound during pregnancy is not established. T eratology studies have been performed in mice, rats, and rabbits. In rabbits given 30 mg/kg/day, no embryotoxicity occurred, but fetal weights were significantly decreased. Mice demonstrated no teratogenic effects at dosages of up to 200 mg/kg/day. Rats given up to 150 mg/kg/day demonstrated no embryotoxic effects, but at dosages of 200 mg/kg/day both maternal and fetal weights were decreased. If this compound is to be used in pregnant cats, weigh the po-tential benefits of treating with the potential for adverse effects in the offspring and queen. It is not known if ronidazole is distributed into milk and safety cannot be assured. Consider using milk replacer if treating nursing queens. overdosage/acute t oxicity No specific information was located. Cats receiving doses of 50 mg/kg twice daily appear to have greater incidences of neurotoxicity (see Adverse Reactions). If overdoses cause neurotoxicity, discon-tinue further therapy and treat supportively. Consider administer-ing a GABA inhibitor such as diazepam, to competitively inhibit GABA receptors in the CNS. Drug interactions In humans, the following drug interactions with metronidazole, a compound similar to ronidazole, have been reported or are theo-retical and may be of significance in veterinary patients in patients receiving ronidazole: a Lco Ho LT! : May induce a disulfiram-like (nausea, vomiting, cramps, etc. ) reaction cimeti Dine, ketoconazo Le T! : May decrease the metabolism of ronidazole and increase the likelihood of dose-re lated side effects occurring cyc Lo SPo Rine, tac Ro Limu S T! (systemic ): Ronidazole may increase the serum levels of cyclosporine or tacrolimus FLuo Rou Raci LT! (systemic ): Ronidazole may increase the serum lev-els of fluorouracil and increase risk for toxicity Lit Hium T! : Ronidazole may increase lithium serum levels and in-crease risk for lithium toxicity oxytet Racyc Line T! : Reportedly may antagonize the therapeutic ef-fects of metronidazole (and presumably ronidazole) PHenoba Rbita LT!, Ri Fam Pin or PHenytoin : May increase the metabo-lism of ronidazole thereby decreasing blood levels Wa RF a Rin T! : Metronidazole (and potentially ronidazole), may pro-long INR/PT in patients taking coumarin anticoagulants; avoid concurrent use if possible; otherwise intensify monitoring Laboratory considerations a St, a Lt, LDH T! (lactic dehydrogenase ), triglycerides, Hexokinase glucose : A related compound, metronidazole can cause falsely decreased readings when determined using methods measur-ing decreases in ultraviolet absorbance when NADH is reduced to NAD. It is not known if ronidazole can also cause falsely de-creased values. Doses cat S:T! a) For treatment of T. foetus infections: 30 mg/kg PO twice daily for 14 days. (Gookin 2007) note : Based on results of a published study of experimental T. foetus infection (Gookin, Copple et al. 2006) the author suggested using 30-50 mg/kg twice daily for 14 days, but subsequent experience has dem-onstrated a higher incidence of neurotoxicity at the higher dose and she now recommends treating at 30 mg/kg PO twice daily. monitoring Clinical efficacy (diarrhea improvement)T! Adverse effects (neurotoxicity, vomiting, anorexia)T! PCR testing (can be used to confirm infection, but negative re-T! sults after treatment do not conclusively prove that infection has been eradicated) client information Ronidazole must be given by mouth twice daily (approximate-T! ly 12 hours apart) for 14 days for it to be effective. Do not skip doses. Store capsules in the freezer. T! This drug is considered a carcinogen. Do not open or crush cap-T! sules; give whole. It is recommended to wear disposable gloves when administering this medication. When cleaning litter box, wear disposable gloves; double bag fe-T! ces and dispose in trash. Contact veterinarian immediately if cat shows signs of behavior T! changes, eyes moving back and forth (nystagmus), or has diffi-culty walking, climbing stairs, etc. (ataxia). These could be signs that drug toxicity is occurring. chemistry/Synonyms Ronidazole is a 5-nitroimidazole compound that occurs as a white to yellowish-brown, odorless or almost odorless, bitter-tasting, powder. It is very slightly soluble in water or alcohol. Ronidazole may also be known as ronidazol, ronidazolum, Belga ®, Ridsol-S®, Ronida®, Ronivet®, Ronizol®, Turbosol®, Tricho Plus®, Trichocure®, or Trichorex®.	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
S-a Deno Sy L-met Hionine/a Demetionine 809 Storage/Stability Compounded capsules should be stored in child-resistant, tight containers protected from light. Until further stability studies can be performed, capsules should be stored in the freezer. Aqueous solutions are reportedly not very stable. It is recom-mended that fresh solutions using the 10% powder for addition to drinking water (used for pigeons) be freshly prepared every day. Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: None in the USA; a 10% ronidazole powder to be added to drink-ing water for treating Trichomonas infections in pigeons is available in some countries, but these products are unsuitable for use in cats due to the dosage required and the unpalatability (very bitter) of the powder and solution. Capsules prepared from 100% bulk powder for an individual feline patient should be obtained from a compounding pharmacy that can prepare the capsules in a bio-safety hood that will protect the compounder from drug exposure. The FDA prohibits this drug for use in food animals. Human-Labe Le D PRo Duct S: None S-adeno Syl-Met Hionine (Sa Me) ade Metionine (ess-ah-den-oh-seel meth-ie-oh-neen) he P ato Protectant Prescriber Highlights “Nutraceutical” that can be used as an adjunctive treat-T T ment for liver disease (chronic hepatitis), osteoarthritis, or treatment of acetaminophen toxicity in small animals Well tolerated T T Not a regulated drug; choose products carefully T T uses/indications In small animal medicine, SAMe is most commonly used as an ad-junctive treatment for liver disease (chronic hepatitis, hepatic lipi-dosis, cholangiohepatitis, feline triad disease, etc. ). It may also be of benefit in osteoarthritis, treatment of acute hepatotoxin-induced liver toxicity (e. g., acetaminophen toxicity), and at-risk patients on long-term therapy using drugs with hepatotoxic potential. In humans, SAMe is being used as a treatment for depression, osteoarthritis, AIDS-related myopathy, intrahepatic cholestasis, liver disease, alcoholic liver cirrhosis, fibromyalgia, adult ADHD, Alzheimer's, migraines, etc. Pharmacology/actions S-adenosyl-methionine (SAMe) is an endogenous molecule synthe-sized by cells throughout the body. SAMe is formed from the amino acid methionine and ATP, in conjunction with SAMe synthetase enzyme (an enzyme manufactured in the liver, a rate-limiting step in the presence of liver compromise). SAMe is an essential part of three major biochemical pathways: transmethylation, transsulfura-tion, and aminopropylation. Normal function of these pathways is especially vital to the liver as many metabolic reactions occur there. In the transmethylation pathway, SAMe serves as a methyl donor (necessary for many substances and drugs to be activated and/or eliminated). Transmethylation is essential in phospholipid synthesis important to cell membrane structure, fluidity, and func-tion. In aminopropylation, SAMe donates aminopropyl groups and is a source of polyamines. Aminopropylation is important in producing substances that have antiinflammatory effects, protein and DNA synthesis, and promoting cell replication and liver mass regeneration. In transulfuration, SAMe generates sulfur contain-ing compounds important for conjugation reactions used in de-toxification and as a precursor to glutathione (GSH). Glutathione is important in many metabolic processes and cell detoxification. The conversion of SAMe to glutathione requires the presence of folate, cyanocobalamin (B12), and pyridoxine (B6). Normally, the liver produces ample SAMe, but in liver disease or in the presence of hepatotoxic substances, endogenous conversion to glutathione may be deficient. Exogenous SAMe has been shown to increase liver and red cell glutathione levels and/or prevent its depletion. SAMe inhib-its apoptosis secondary to alcohol or bile acids in hepatocytes. In humans, the mechanism for its antidepressant effects are not well understood, but it apparently increases serotonin turnover and increases dopamine and norepinephrine levels. Neuroimaging studies in humans show that SAMe affects the brain similarly to other antidepressant medications. Pharmacokinetics Oral bioavailability is dependent on the salt used to stabilize SAMe. Oral bioavailability of the tosylate salt is reportedly 1% whereas the 1,4-butanedisulfonate form has a bioavailability of 5%. The pres-ence of food in the gut can substantially reduce the amount of drug absorbed. Peak levels occur in 1-6 hours after oral dosing. Once absorbed, SAMe enters the portal circulation and is primarily me-tabolized in the liver. In humans, 17% of a dose of radio-labeled SAMe was recovered in the urine within 48 hours of dosing; 27% in the feces. contraindications/Precautions/Warnings There are no apparent contraindications to the use of SAMe. adverse effects Adverse effects appear to be minimal or non-existent in treated ani-mals. Most studies in humans have shown adverse effects similar to that of placebo. Oral SAMe in humans may cause anorexia, nausea, vomiting, diarrhea, flatulence, constipation, dry mouth, insomnia/nervousness, headache, sweating, and dizziness. Reproductive/nursing Safety The safety of exogenous SAMe has not been proven in pregnan-cy; use with caution. Limited studies in laboratory animals and in pregnant women with liver disease have not demonstrated any ill effects to mother or fetus. It is unknown if SAMe enters maternal milk. overdosage/acute t oxicity SAMe appears to be quite safe. LD50 in rodents exceeds 4. 65 g/kg, and toxicity studies in dogs and cats at the usual prescribed dos-ages demonstrated no deleterious effects. In the case of an overdose, gastrointestinal effects may be observed, but unlikely to require treatment. Drug interactions No interactions have been documented, but theoretically, concur-rent use of SAMe with tramadol, meperidine, dextromethorphan, penta-zocine, monoamine oxidase inhibitors ( maois ) including selegiline, selective serotonin reuptake inhibitors ( SSRis ) such as fluoxetine, or other antidepressants (e. g., amitriptyline, clomipramine ) could cause additive serotonergic effects.	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
810 Sa Line/Hy Pe Ro Smotic Laxati Ve S/ma Gne Sium Sa L t S Laboratory considerations No specific laboratory interactions or considerations noted. Doses Do GS & cat S: T! Daily dose for animals with body weights of: up to 12 pounds (5. 5 kg): one 90 mg tablet; 12-25 pounds (5. 5-11 kg): two 90 mg tablets (or one 225 mg tablet, if more convenient); 25-35 pounds (11-16 kg): one 225 mg tablet; 35-65 pounds (16-29. 5 kg): two 225 mg tablets; 65-90 pounds (29. 5 kg-41 kg): three 225 mg tablets; over 90 pounds (41 kg+): four 225 mg tablets. Daily dosage may also be calculated based on 18 mg/kg of body weight and rounded to the closest tablet size or combination of sizes. Product should be given on an empty stomach, at least one hour before feeding. If giving more than one tablet, may divide total daily dosage and give twice daily. The number of tablets can be gradually reduced or may be increased at any time de-pending on the pet's needs. (Package information; Denosyl®— Nutramax) For Liver Disease: a) For adjunctive treatment of chronic hepatitis: Dogs: 17-20 mg/kg or higher per day given on an empty stomach Cats: 200 mg/day on an empty stomach. Recommend using a reliable product with proven research in dogs and cats such as Denosyl®. (Center 2002) b) 20 mg/kg once daily (Willard 2006b) monitoring Clinical signs (appetite, activity, attitude)T! Liver enzymes, bilirubin, bile acids T! Liver biopsies T! Hepatic and erythrocyte glutathione levels (available at research T! institutions only at this time); may require 1-4 months before any changes in lab values are noted client information Administer tablets to animal with an empty stomach, preferably T! at least one hour before feeding Keep tablets in original packaging until administration. Do not T! crush or split tablets chemistry/Synonyms S-adenosyl-methionine (SAMe) is a naturally occurring molecule found throughout the body. Because pure SAMe is highly reactive and unstable, commercially available forms of SAMe are salt forms; sulfate, sulfate-p-toluenesulfonate (also known as tosylate), and butanedisulfonate salts can all be procured. SAMe may also be known as: S-adenosyl-L-methionine, S-adenosylmethionine, SAM, SAM-e, adenosylmethionine, Sammy, methioninyl adenylate, Donamet®, Gumbaral®, Isimet®, Mood Lift®, S Amet®, Samyr®, Transmetil®, and Tunik®. Storage/Stability Unless otherwise labeled, SAMe tablets should be stored at room temperature. Avoid conditions of high temperature or humidity. SAMe is inherently unstable in acidic or aqueous environments; store in tightly sealed, moisture-resistant containers. Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: None as a pharmaceutical. SAMe is considered a nutritional supple-ment by the FDA. No standards have been accepted for potency, pu-rity, safety, or efficacy by regulatory bodies. Supplements are available from a wide variety of sources and dosage forms include tablets in a variety of concentrations. There are specific products marketed for use in animals, including Denosyl® (Nutramax) in 90 mg, 225 mg, & 425 mg enteric-coated, blister-packed tablets and Zentonil® (Vetoqui-nol) in 100 mg, 200 mg and 400 mg tablets. Bioequivalence between SAMe products is not assured. A combination product Denamarin® (Nutramax), containing SAMe and silybin (silymarin) is also labeled for use in dogs and cats. Human-Labe Le D PRo Duct S: None as a pharmaceutical. Saline/Hypero SMotic laxative S Magne Siu M Salt S peg 3350 product S Go LYTELY®, Epsom Salts laxative S Prescriber Highlights Saline/hyperosmotic agents for constipation, bowel T T “cleansing”, & to increase elimination of GI toxins Contraindications: PEG 3350 solutions are contraindi-T T cated in patients with GI obstruction, gastric retention, bowel perforation, toxic colitis, or megacolon. Saline ca-thartics should be used with extreme caution in patients with renal insufficiency, pre-existing water-balance or electrolyte abnormalities, or cardiac disease. Adverse Effects: Cramping, nausea possible T T If magnesium salts used chronically: Hypermagnesemia T T (muscle weakness, ECG changes & CNS effects)Drug Interactions T T uses/indications The saline laxatives are used for their cathartic action to relieve con-stipation. They are also used to reduce intestinal transit time thereby reducing the absorption of orally ingested toxicants. Polyethylene glycol 3350 balanced electrolyte solutions are used to evacuate the colon prior to intestinal examination or surgery. Pharmacology/actions Although unproven, it is commonly believed that the hyperosmotic effect of the poorly absorbed magnesium cation causes water re-tention, stimulates stretch receptors and enhances peristalsis in the small intestine and colon. Recent data, however, suggests that magnesium ions may directly decrease transit times and increase cholecystokinin release. Polyethylene glycol 3350 is a non-absorbable compound that acts as an osmotic agent. By adding sodium sulfate as the primary sodium source, sodium absorption is minimized. Other electrolytes (bicarbonate potassium and chloride) are also added so that no net	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
Sa Line/Hy Pe Ro Smotic Laxati Ve S/ma Gne Sium Sa L t S 811 change occurs with either absorption or secretion of electrolytes or water in the gut. Pharmacokinetics When magnesium salts are administered, up to 30% of the magne-sium dose of magnesium can be absorbed. Generally, the onset of action of saline cathartics (characterized by a loose, watery stool) occurs in 3-12 hours after dosing in mo-nogastric animals and within 18 hours in ruminants. contraindications/Precautions/Warnings Saline cathartics are contraindicated for long-term or chronic use. Sodium containing laxatives are contraindicated in patients with congestive heart failure or congenital megacolon. PEG 3350 solu-tions are contraindicated in patients with GI obstruction, gastric retention, bowel perforation, toxic colitis, or megacolon. Saline ca-thartics should be used with extreme caution in patients with renal insufficiency, pre-existing water-balance or electrolyte abnormali-ties, or cardiac disease. adverse effects Except for possible cramping and nausea, adverse effects in other-wise healthy patients generally occur only with the saline cathartics with chronic use or overdoses. Hypermagnesemia manifested by muscle weakness, ECG changes and CNS effects can occur. Reproductive/nursing Safety In humans, the FDA categorizes magnesium sulfate as category B for use during pregnancy (Animal studies have not yet demonstrated risk to the fetus, but there are no adequate studies in pregnant women; or animal studies have shown an adverse effect, but adequate studies in pregnant women have not demonstrated a risk to the fetus in the first trimester of pregnancy, and there is no evidence of risk in later trimesters. ) Other saline or hyperosmolar cathartics should be safe to use in pregnancy when used infrequently. Magnesium emulsions administered orally did not affect the stools of nursing infants, although magnesium content in breast milk was slightly elevated compared with untreated patients. In veterinary patients, it should be safe to use during nursing when used infrequently. overdosage/acute t oxicity Clinical signs of overdosage of magnesium containing laxatives are described above. Treatment should consist of monitoring and cor-recting any fluid imbalances that occur with parenteral fluids. If hypermagnesemia occurs, furosemide may be used to enhance the renal excretion of the excess magnesium. Calcium has been sug-gested to help antagonize the CNS effects of magnesium. Drug interactions All orally administered saline laxatives may alter the rate and ex-tent of absorption of other orally administered drugs by decreasing intestinal transit times. The extent of these effects has not been well characterized for individual drugs, however. tet Racyc Line ST! : Magnesium laxatives should not be administered with tetracycline products Doses Do GS:T! Magnesium hydroxide (Milk of Magnesia) as a cathartic: a) 5-10 m L (Davis 1985a) b) 1-20 m L PO (Rossoff 1974) Magnesium sulfate: a) 5-25 grams PO (Davis 1985a) b) 2-60 grams PO (Rossoff 1974)Polyethylene Glycol-Electrolyte Solution:a) For colonic cleansing prior to colonoscopy using Go-Lyte-ly®: Keep animal from food for 24-36 hours. On the eve-ning prior to a morning colonoscopy (or the morning for an afternoon colonoscopy), give 60 m L/kg via orogastric tube. Repeat in 2 hours. A warm water enema should follow each dose and a third enema given prior to anesthesia. (Leib 2003), (Leib 2006) b) For colonic cleansing prior to colonoscopy using Go-Lytely®: 12-18 hours prior to colonoscopy give 25 m L/kg via oro-gastric tube three to five times, one hour apart. Give enema shortly after last Go-Lytely® dose and one to two hours prior to endoscopy procedure. (Richter 2003) c) For colonic cleansing prior to colonoscopy using Go-Lytely®: Withhold food for 18-24 hours. Give two doses of 20 m L/ kg Go-Lytely® 4-6 hours apart the afternoon before an AM endoscopy. The morning of procedure, a warm-water enema is administered. (Jergens 2003) d) For mechanical bowel cleansing prior to (antibiotics and) colonic surgery: Go-Lytely® (or similar osmotic cathartic): 50-75 m L/kg by stomach tube or NE tube the evening prior to surgery. (Trepanier 2003) cat S:T! Magnesium hydroxide (Milk of Magnesia) as a cathartic: a) 2-6 m L (Davis 1985a) b) 1-5 m L PO (Rossoff 1974) Magnesium sulfate: a) 2-5 grams PO (Davis 1985a), (Rossoff 1974) Polyethylene Glycol-Electrolyte Solution: a) For colonic cleansing prior to colonoscopy using Go-Lytely®: Keep animal from food for 24-36 hours. On the evening prior to a morning colonoscopy (or the morning for an af-ternoon colonoscopy), give 60 m L/kg via nasogastric tube. Repeat in 2 hours. A warm water enema should follow each dose and a third enema given prior to anesthesia. Metoclo-pramide (0. 2 mg/kg SC 15-20 minutes before the first Go-Lytely ® dose is given to reduce vomiting. (Leib 2003), (Leib 2006) catt Le:T! Magnesium sulfate (as a cathartic): a) 0. 5-1 kg/500 kg orally (Whitlock 1986b) b) 1-2 gm/kg PO (Howard 1986) Magnesium oxide: a) 0. 5-1 kg/500 kg orally (Whitlock 1986b) Ho RSe S:T! Magnesium sulfate (Epsom salt): a) 0. 2 gm/kg diluted in 4 L of warm water administered via nasogastric tube. Administer only to well-hydrated animals (ideally in conjunction with IV fluid therapy). Do not treat longer than 3 days or there is an increased risk of enteritis or magnesium toxicity occurring. (Clark and Becht 1987) b) As a laxative: 1 g/kg PO every 1-2 days; in colic delay treat-ment until rehydrated (Moore 1999) c) T o reduce absorption of toxicants and GI transit time: 500 gm (as a 20% solution) PO. If mineral oil has been used ini-tially, give saline cathartic 30- 45 minutes after mineral oil. (Oehme 1987) d) For cecal impactions: 1 g/kg dissolved in water dissolved in water and given via NG tube. Give with a balanced electro-lyte solution IV to stimulate secretion into the dehydrated ingesta. (White 2005a)	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
812 Se Lamectin SWine:T! Magnesium sulfate (as a cathartic): a) 1-2 gm/kg PO (Howard 1986) T!bi RDS: Magnesium sulfate: a) T o act as a cathartic and reduce lead absorption: 0. 5-1 gm/ kg PO as a 5% solution in drinking water (Mc Donald 1986) monitoring Fluid and electrolyte status in susceptible patients, high doses, or T! chronic use Clinical efficacy T! client information Do not give dosages greater than, or for periods longer than rec-T! ommended by veterinarian Contact veterinarian if patient begins vomiting T! chemistry/Synonyms Magnesium cation containing solutions of magnesium citrate, magnesium hydroxide, or magnesium sulfate act as saline laxatives. Magnesium citrate solutions contain 4. 71 m Eq of magnesium per 5 m L. Magnesium hydroxide contains 34. 3 m Eq of magnesium per gram and milk of magnesia contains 13. 66 m Eq per 5 m L. One gram of magnesium sulfate (Epsom salt) contains approximately 8. 1 m Eq of magnesium. Polyethylene glycol 3350 is a non-absorbable compound that acts as an osmotic agent. Storage/Stability Magnesium citrate solutions should be stored at 2-30°C. Store milk of magnesia at temperatures less than 35°C, but do not freeze. PEG 3350 reconstituted (from powder by the pharmacy, client, clinic, etc. ) solutions should be kept refrigerated and used within 24 hours. Dosage Forms/Regulatory Status Saline cathartic products have apparently not been formally approved for use in domestic animals. They are available without prescription (OTC). PEG 3350 products are available only by prescription and are approved for use in humans. Vete Rina R y-Labe Le D PRo Duct S: None located Human-Labe Le D PRo Duct S: Saline Laxatives (not an inclusive list): Magnesium Hydroxide Suspension (Milk of Magnesia): equiv. to 30 m L milk of magnesia in 100 m L, 400 m L & UD 10 m L; magnesium hydroxide 160 mg/m L & 80 mg/m L in 180 m L, 240 m L, 360 m L, 400 m L, 480 m L, 780 m L, UD 30 m L; Milk of Magnesia Concentrated® (Roxane); Phillips'® Milk of Magnesia and Phillips'® Milk of Magnesia Concentrated (Bayer); generic; (OTC) Magnesium Sulfate (Epsom Salt) Granules: in 120 g, 1lb and 4lbs; generic; (OTC) Hyperosmotic Laxatives (not an inclusive list): Polyethylene Glycol-Electrolyte Solution: OCL® Solution (Abbott); (Rx) Oral Solution in 1500 m L: 146 mg so-dium chloride, 168 mg sodium bicarbonate, 1. 29 g sodium sulfate decahydrate, 75 mg potassium chloride, 6 grams PEG-3350 and 30 mg polysorbate-80/100 m L Co Lyte® (Schwartz Pharma); (Rx); 1 gallon of Powder for Oral So-lution in bottles: 227. 1 g PEG 3350, 5. 53 gm sodium chloride, 6. 36 gm sodium bicarbonate, 21. 5 gm sodium sulfate, 2. 82 gm potassium chloride; 4L of solution: 240 g PEG 3350, 22. 72 g sodium sulfate, 6. 72 g sodium bicarbonate, 5. 84 g Na Cl, 2. 98 g KCL Go LYTELY® (Braintree Labs); (Rx); Powder for Oral Solution in jugs: 5. 86 gm sodium chloride, 6. 74 gm sodium bicarbonate, 22. 74 gm so-dium sulfate, 2. 97 gm potassium chloride, 236 gm PEG 3350; Packets: 227. 1 g PEG 3350, 21. 5 g sodium sulfate, 6. 36 g sodium bicarbonate, 5. 53 g Na Cl, 2. 82 g KCl Nu Lytely® (Braintree Labs); Tri Lyte® (Schwarz Pharma); (Rx); Pow-der for Reconstitution in 4 L jugs: 420 g PEG 3350, 5. 72 g sodium bicarbonate, 11. 2 g Na Cl, 1. 48 g KCL Movi Prep® (Salix); (Rx); Powder for Reconstitution in pouches: 100 g PEG 3350, 7. 5 g sodium sulfate, 2. 691 g Na Cl, 1. 015 KCl. Sela Mectin (sell-a-mek-tin) Revolution® avermectin ( to Pical) anti P ara Sitic Prescriber Highlights Topical avermectin antiparasiticide approved for multiple T T indications in dogs & cats Applied monthly (usually; some indications one time T T dosing) Adverse effect profile appears minimal T T uses/indications T opical selamectin (Revolution®—Pfizer) is indicated for flea in-festations (Ctenocephalides felis), prevention of heartworm disease (Dirofilaria immitis), and for ear mites (Otodectes cynotis) in both dogs and cats. Additionally in dogs, it is indicated for sarcoptic mange (Sarcoptes scabeii), and tick infestations (Dermacentor vari-abilis). In cats: hookworm (Ancylostoma tubaeforme) and round-worm (Toxocara cati). The product (Revolution®) is labeled as not effective against ei-ther adult heartworms or clearing circulating microfilaria, but it possibly may have some efficacy with prolonged, continuous ad-ministration (Atkins 2007b). Pharmacology/actions Like other compounds in its class, selamectin is believed to act by enhancing chloride permeability or enhancing the release of gamma amino butyric acid (GABA) at presynaptic neurons. GABA acts as an inhibitory neurotransmitter and blocks the post-synaptic stimu-lation of the adjacent neuron in nematodes or the muscle fiber in arthropods. By stimulating the release of GABA, it causes paralysis of the parasite and eventual death. As liver flukes and tapeworms do not use GABA as a peripheral nerve transmitter, selamectin would probably be ineffective against these parasites. Pharmacokinetics After topical administration to dogs, about 5% of the drug is bio-available and peak plasma levels occur about 3 days later. Elimination half-life after topical administration is about 11 days. After topical administration to cats, about 75% of the drug is bioavailable and peak plasma levels occur about 15 hours later. Elimination half-life after topical administration is about 8 days. In cats, bioavailability is about 75% and peak levels may be 64 times those in dogs.	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
Se Lamectin 813 The persistence of the drug in the body is believed to be due to the drug forming reservoirs in skin sebaceous glands. It is secreted into the intestine to kill susceptible endoparasites in cats. contraindications/Precautions/Warnings The manufacturer recommends caution when using in sick, under-weight, or debilitated dogs or cats. It is not recommended for use in animals under 6 weeks of age. At labeled doses of selamectin, dogs at risk for MDR1-allele mutation (Collies, Australian Shepherds, Shelties, Long-haired Whippet, etc “white feet”) should tolerate the medication, but use cautiously. adverse effects In field trials (limited numbers of animals) adverse effects were rare. Approximately 1% of cats showed a transient, localized alopecia at the area of administration. Other effects reported (< or = 0. 5% incidence) include diarrhea, vomiting, muscle tremors, anorexia, pruritus/urticaria, erythema, lethargy, salivation and tachypnea. Very rarely, seizures and ataxia have been reported in dogs. Reproductive/nursing Safety Selamectin appears to be safe to use in pregnant or lactating dogs or cats. overdosage/acute t oxicity Dogs: Oral overdoses of up to 15 mg/kg did not cause adverse ef-fects (except for ataxia in one avermectin sensitive collie). T opical overdoses (10x) to puppies caused no adverse effects; topical over-doses to avermectin-sensitive Collies caused salivation. Cats: Oral ingestion may cause salivation and vomiting. T opical overdoses of up to 10x caused no observable adverse effects. There were 218 exposures to selamectin reported to the ASPCA Animal Poison Control Center (APCC; www. apcc. aspca. org) dur-ing 2005-2006. In these cases 125 were dogs with 4 showing clini-cal signs and 86 cases were cats with 15 showing clinical signs. The remaining 7 cases consisted of 5 ferrets and 2 lagomorphs none of which had clinical signs. Common findings in dogs recorded in decreasing frequency included hypersalivation, agitation, diar-rhea, edema of the face and hyperactivity. Common findings in cats recorded in decreasing frequency included vomiting, anorexia, hy-peresthesia, hyperthermia and mydriasis. Drug interactions None documented, but caution is advised if using other drugs that can inhibit p-glycoprotein. Those dogs at risk for MDR1-allele muta-tion (Collies, Australian Shepherds, Shelties, Long-haired Whippet, etc “white feet”) should probably not receive selamectin with the following drugs, unless tested “normal”: Drugs and drug classes in-volved include: amio Da Rone!! ca RVe Di Lo L!! c La Rit HRomycin!! cyc Lo SPo Rine!! Di Ltiazem!! e Ryt HRomycin!! it Raconazo Le!! ketoconazo Le!! quini Dine!! SPi Rono Lactone T! tamoxi Fen!! Ve Ra P ami L!!Laboratory considerations None reported. Doses Do GS: T! For prophylaxis and treatment of dirofilariasis, it is suggested to re-view the guidelines published by the American Heartworm Society at www. heartwormsociety. org for more information a) The recommended topical dose is 6 mg/kg. Dosing frequen-cy: Heartworm prevention, flea control = monthly; Ticks = monthly (if heavy infestations, may repeat 2 weeks after the first dose); Ear Mites, Sarcoptes = once, repeat in one month if necessary. See the package for specific instructions on ad-ministration technique. (Label information; Revolution®— Pfizer) cat S: T! a) The recommended topical dose is 6 mg/kg. Dosing fre-quency: Heartworm prevention, flea control = monthly; Ear Mites = once, repeat in one month if necessary. Hookworms, Roundworms = once. See the package for specific instruc-tions on administration technique. (Label information; Revolution®—Pfizer) Fe RRet S:T! a) For heartworm prevention: 18 mg/kg topically every 30 days. (Johnson 2006c) Rabbit S: T! a) For ear mites (P. Cunuculi): 6-18 mg/kg topically (Mc Tier, Hair et al. 2003) monitoring Clinical efficacy T! Owner compliance with treatment regimen T! client information Follow label directions for administration technique; do not T! massage into skin, and do not apply if hair coat is wet. Because the product contains alcohol, do not apply to broken skin. Avoid contact with animal while the application site is wet. T! Wait two hours or more after applying to bathe the animal (or T! allow to go swimming). Avoid getting the product on human skin; if contact occurs, wash T! off immediately. Dispose of tubes in regular household refuse. Do not expose to flame as the product is flammable. T! chemistry/Synonyms A semi-synthetic avermectin, selamectin is commercially available as a colorless to yellow solution (flammable). Selamectin may also be known as UK-124114, or Revolution®. Storage/Stability The commercially available solution should be stored below 30°C (86°F). Keep away from flame or other igniters. Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: Selamectin Topical Solution for Cats; Revolution® (Pfizer); (Rx): Up to 5 lbs in wt, Pkg. Color: mauve. 15 mg/tube. Tube volume: 0. 25 m L 5. 1-15 lbs in wt, Pkg. Color: blue. 45 mg/tube. Tube volume: 0. 75 m L	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
814 Se Le Gi Line Hc L Selamectin Topical Solution for Dogs; Revolution® (Pfizer); (Rx) Up to 5 lbs in wt, Pkg. Color: mauve. 15 mg/tube. Tube volume: 0. 25 m L 5. 1-10 lbs in wt, Pkg. Color: purple. 30 mg/tube. Tube volume: 0. 25 m L10. 1-20 lbs in wt, Pkg. Color: brown. 60 mg/tube. Tube volume: 0. 5 m L20. 1-40 lbs in wt, Pkg. Color: red. 120 mg/tube. Tube volume: 1 m L 40. 1-85 lbs in wt, Pkg. Color: teal. 240 mg/tube. Tube volume: 2 m L 85. 1-130 lbs in wt, Pkg. Color: plum. One 120 mg tube and one 240 mg tube. T otal volume: 3 m L Human-Labe Le D PRo Duct S: None Selegiline Hcl l-deprenyl (se-le-ji-leen) Anipryl®, Eldepryl® monamine o xida Se inhibitor Prescriber Highlights MAO-B inhibitor that may be useful for canine cognitive T T dysfunction syndrome or Cushing's (efficacy in doubt for Cushing's) Contraindications: Hypersensitivity to it. May be contrain-T T dicated in patients receiving opiates Adverse Effects: Vomiting & diarrhea; CNS effects mani-T T fested by restlessness, repetitive movements, or lethargy; salivation & anorexia. Diminished hearing/deafness, pru-ritus, licking, shivers/trembles/shakes possible Drug Interactions T T uses/indications Selegiline is approved for use in dogs for the treatment of Cushing's disease and for Canine Cognitive Dysfunction (so-called “old dog dementia”). Its use for Cushing's disease is somewhat controversial as clinical studies evaluating its efficacy have shown disappointing results. In humans, selegiline's primary indication is for the adjunc-tive treatment of Parkinson's disease. Pharmacology/actions Selegiline's mechanism of action for treatment of Cushing's disease (pituitary dependent hyperadrenocorticism—PDH) is complex; a somewhat simplified explanation follows: In the hypothalamus, corticotropin-releasing hormone (CRH) acts to stimulate the pro-duction of ACTH in the pituitary and dopamine acts to inhibit the release of ACTH. As dogs age, there is a tendency for a decrease in do-pamine production that can contribute to the development of PDH. As dopamine is metabolized by monamine oxidase-B (MAO-B) and selegiline inhibits MAO-B, dopamine levels can be increased at receptor sites after selegiline administration. In theory, this al-lows the levels of dopamine and CRH to be in balance in the hy-pothalamus, thereby reducing the amount of ACTH produced and ultimately, cortisol. While selegiline is labeled as a MAO-B inhibitor, at higher than labeled dosages, the drug loses its MAO-B specificity and also in-hibits MAO-A. Two of three metabolites of selegiline are amphet-amine and methamphetamine that may contribute to both the ef-ficacy and the adverse effects of the drug. Pharmacokinetics There is only limited information on the pharmacokinetics of selegiline in dogs. A study done in 4 dogs showed that selegiline was absorbed rapidly and had an absolute bioavailability of about 10%. The volume of distribution of the central compartment was measured at approximately 7 L/kg. T erminal half-life was about one hour. In humans, selegiline pharmacokinetics have wide interpatient variability. The drug has a high first pass effect where extensive metabolism to L-desmethylselegiline, methylamphetamine, and L-amphetamine occur. Each of these metabolites is active. While L-desmethylselegiline does inhibit MAO-B, the others do not, but thye are CNS stimulants. The drug is excreted in the urine, primar-ily as conjugated and unconjugated metabolites. contraindications/Precautions/Warnings Selegiline is contraindicated in patients known to be hypersensitive to it. In human patients, it is contraindicated in patients receiving meperidine and possibly with other opioids as well. The manufacturer cautions to perform appropriate diagnostic tests to confirm the diagnosis before starting therapy and not to at-tempt to treat hyperadrenocorticism not of pituitary origin. adverse effects Adverse reports reported thus far in dogs include, vomiting, diar-rhea, CNS effects manifested by restlessness, repetitive movements or lethargy, salivation, and anorexia. Should GI effects be a prob-lem, discontinue the drug for a few days and restart at a lower dose. Diminished hearing/deafness, pruritus, licking, shivers/trembles/shakes have also been reported. The manufacturer advises to ob-serve animals carefully for atypical responses. Adverse effects that have been reported in human patients in-clude nausea (10%), hallucinations, confusion, depression, loss of balance, insomnia, and hypersexuality. These effects are noted be-cause of their “subjective” nature and they could help explain un-toward behavioral changes in canine patients should they occur. Because selegiline could potentially be abused by humans, veter-inarians should be alert for drug “shoppers. ” Selegiline is classified by the Association of Racing Commissioners International (ARCI) as a class 2 agent (high abuse potential in racing horses). Reproductive/nursing Safety Safety of selegiline in pregnant, breeding or lactating animals has not been established. Rat studies have not demonstrated overt teratogenicity. In humans, the FDA categorizes this drug as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) It is not known whether selegiline is excreted in maternal milk. overdosage/acute t oxicity Oral LD 50 in laboratory animals was approximately 200-445 mg/ kg. In limited data, dogs receiving 3x dosages showed signs of de-creased weight, salivation, decreased pupillary response, panting, stereotypic behaviors and decreased skin elasticity (dehydration). Overdoses, if severe, should be treated with appropriate gut empty-ing and supportive treatments. Drug interactions Evaluating the potential for drug interactions for selegiline in dogs is problematic. There are a plethora of significant interactions with monamine oxidase inhibitors in humans for selegiline, but because there are significant species differences in quantities and locations of MOA-A and B and selegiline's effects at various dosages on these	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
Se Rt Ra Line Hc L 815 enzymes, they may not apply to dogs. However, the following drug interactions are some of the more significant interactions reported or are theoretical in humans or animals receiving selegiline and potentially could be of significance in veterinary patients; cau-tion is advised particularly if using selegiline at higher than labeled dosages: amit Raz T! : The manufacturer recommends not using selegiline concurrently with amitraz (Mitaban®) in dogs bu PRo Pion T! : Potential for serotonin syndrome e PHe DRine T! : The manufacturer recommends not using selegiline concurrently with ephedrine in dogs me Pe Ri Dine T! : In humans, severe agitation, hallucinations and death have occurred in some patients receiving meperidine and an MAO inhibitor. Until the data can be clarified, it is recommended not to use selegiline and meperidine together. A separation of two weeks has been recommended. Other opioids (e. g., morphine) should be safer, but use with extreme caution, if at all. PHeny LPRo P ano Lamine, PSeu Doe PHe DRine T! : Increased risk for hy-pertension, hyperpyrexia SSRi'ST! (e. g., fluoxetine ): Potentially, the so-called serotonin syn-drome could occur if selegiline is used concurrently with selec-tive serotonin reuptake inhibitors (SSRIs); t Rama Do LT! : Use contraindicated in humans; serotonin syndrome, nausea, vomiting, cardiovascular collapse t Ricyc Lic & tet Racyc Lic anti De PRe SSant S T! (clomipramine, amitrip-tyline, etc. ): Potentially, the so-called serotonin syndrome could occur if selegiline is used concurrently with these agents and use together is not advised at this time; a 2-week separation between these compounds and selegiline is recommended. Doses Do GS:T! For Cushing's disease: a) 1 mg/kg PO in the AM (with food as needed); Reevaluate clinically over next 2 mos. ; if no improvement, may increase to 2 mg/kg once daily; if no improvement or signs increase, reevaluate diagnosis or consider alternate treatment (Pack-age Insert; Anipryl®—Pfizer). For Canine Cognitive Dysfunction: a) 0. 5-1 mg/kg, PO once daily, preferably in the AM. Initially, dose to the nearest whole tablet; adjustments should then be made based upon response and tolerance to the drug (Pack-age Insert; Anipryl®—Pfizer). b) 0. 5-1 mg/kg PO once daily (give with food) (Hoskins 1999) monitoring Clinical efficacy T! Adverse effects. No correlation between low dose dexametha-T! sone suppression test results and clinical efficacy of the drug. The manufacturer recommends physical exam and history as the pri-mary methods to measure response to therapy. client information Keep this and all medications out of reach of children T! Have clients monitor closely for adverse effects T! Clients should be advised on the importance of complying with T! the dosing recommendations to adequately evaluate therapeutic response to the drug chemistry/Synonyms Selegiline HCl, also commonly called l-deprenyl, occurs as a white to off-white crystalline powder that is freely soluble in water. It has a p Ka of 7. 5. Selegiline HCl may also be known as: deprenyl, L-deprenyl, sele-gilini hydrochloridum; many trade names are available. Storage/Stability Commercially available veterinary tablets should be stored at con-trolled room temperature 20-25°C (68-77°F). The commercially available human-labeled tablets and capsules are recommended to be stored from 15-30°C. Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: Selegiline HCl Oral Tablets: 2 mg, 5 mg, 10 mg, 15 mg, 30 mg in blister-packs of 30 tablets; Anipryl® (Pfizer); (Rx). Approved for use in dogs. The ARCI (Racing Commissioners International) has designated this drug as a class 2 substance. See the appendix for more information. Human-Labe Le D PRo Duct S: Selegiline HCl Tablets and Capsules: 1. 25 mg (orally disintegrating) & 5 mg; Eldepryl® (Somerset); Carbex® (Du Pont Pharma); Zelapar® (Valeant Pharmaceuticals); generic tablets; (Rx) Selegiline HCl Transdermal System: 6 mg/24 h (20 mg/20 cm2); 9 mg/24 h (30 mg/30 cm2) & 12 mg/25 h (40 mg/40cm2); Emsam® (Bristol-Myers Squibb); (Rx) Sertraline Hcl (sir-trah-leen) Zoloft® Selective Serotonin reu Ptake inhibitor (SSri) Prescriber Highlights A selective serotonin reuptake inhibitor that may be use-T T ful in treating a variety of behavior-related diagnoses in dogs & cats, including aggression, anxiety-related behav-iors & other obsessive-compulsive behaviors Caution: geriatric patients or those with severe hepatic T T disease; dosages may need to be adjusted Adverse effect profile not well established. Potentially, T T DOGS: Anorexia, lethargy, GI effects, anxiety, irritability, insomnia/hyperactivity, or panting. Aggressive behavior in previously non-aggressive dogs possible. CATS: Seda-tion, decreased appetite/anorexia, vomiting, diarrhea, behavior changes (anxiety, irritability, sleep disturbances), & changes in elimination patterns Drug-drug interactions T T Relatively inexpensive generic forms now available T T uses/indications Sertraline may be considered for use in treating a variety of behav-ior-related diagnoses in dogs and cats, including aggression, and anxiety-related or other obsessive-compulsive behaviors. Pharmacology/actions Sertraline is a highly selective inhibitor of the reuptake of sero-tonin (5-hydroxytryptamine) in the CNS thus potentiating its pharmacologic activity. Sertraline apparently has little effect on dopamine or norepinephrine, and apparently no effect on other neurotransmitters.	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
816 Se Rt Ra Line Hc L Pharmacokinetics In dogs, sertraline's volume of distribution is 25 L/kg and is 97% bound to plasma proteins. High first-pass metabolism occurs; clearance is greater than 35 m L/min/kg. Bile is the major route of excretion in the dog. In humans, sertraline peak levels occur 30-45 minutes after oral dosing. It is 98% bound to plasma proteins. Sertraline appears to be highly metabolized primarily to N-desmethylsertraline, which is active. Elimination half-lives for sertraline and desmethylsertraline average 26 and 80 hours respectively. contraindications/Precautions/Warnings Sertraline is contraindicated in patients hypersensitive to it or any SSRI, or receiving a monoamine oxidase inhibitor (MAOI) or cisap-ride. Use with caution in geriatric patients and those with hepatic impairment; dosages may need to be decreased or dosing interval increased. adverse effects Limited use of sertraline in dogs or cats makes it difficult to com-pare its adverse effect profile with other SSRIs (e. g., fluoxetine, par-oxetine, fluvoxamine). In dogs, SSRIs can cause lethargy, GI effects, anxiety, irritability, insomnia/hyperactivity, or panting. Anorexia is a common side effect in dogs (usually transient and may be negat-ed by temporarily increasing the palatability of food and/or hand feeding). Some dogs have persistent anorexia that precludes further treatment. Aggressive behavior in previously non-aggressive dogs has been reported. SSRI's in cats can cause sedation, decreased ap-petite/anorexia, vomiting, diarrhea, behavior changes (anxiety, ir-ritability, sleep disturbances), and changes in elimination patterns. Reproductive/nursing Safety In humans, the FDA categorizes sertraline as a category C drug for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) In rats and rabbits, sertraline was implicated in causing delayed ossification. Sertraline decreased pup survival in rats exposed in utero. It is unknown if sertraline enters maternal milk. overdosage/acute t oxicity In overdoses, the SSRI's can cause vomiting, diarrhea, hypersaliva-tion, and lethargy. Serotonin syndrome may occur with signs that include muscle tremors, rigidity, agitation, hyperthermia, vocaliza-tion, hypertension or hypotension, tachycardia, seizures, coma, and death. Human overdoses of as little of 2. 5 grams have caused death, but one patient survived after taking 13. 5 grams. There were 469 exposures to sertraline reported to the ASPCA Animal Poison Control Center (APCC; www. apcc. aspca. org) during 2005-2006. In these cases 430 were dogs with 38 showing clinical signs and 37 were cats with 4 showing clinical signs. The remaining 2 cases were a bird and an unknown species that showed no clinical signs. Common findings in dogs recorded in decreasing frequency included lethargy, hyperactivity, tachycardia, agitation and mydria-sis. Common findings in cats recorded in decreasing frequency in-cluded mydriasis, agitation, anorexia and hallucinating. Management of sertraline overdoses should be handled aggres-sively with supportive and symptomatic treatment. Veterinarians are encouraged to contact an animal poison control center for fur-ther guidance. Drug interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving sertraline and may be of significance in veterinary patients: bu SPi Rone T! : Increased risk for serotonin syndrome cimeti Dine T! : May increase sertraline levels cy PRo He Pta Dine T! : May decrease or reverse the effects of SSRIs Diaze P am T! : Sertraline may decrease diazepam clearance i Soniazi DT! : Increased risk for serotonin syndrome mao in Hibito RST! (including amitraz and potentially, selegiline ): High risk for serotonin syndrome; use contraindicated; in hu-mans, a 5 week washout period is required after discontinuing sertraline and a 2 week washout period is required if first discon-tinuing the MAO inhibitor Pentazocine T! : Serotonin syndrome-like adverse effects possible t Ricyc Lic anti De PRe SSant S T! (e. g., clomipramine, amitriptyline ): Ser-traline may increase TCA blood levels and may increase the risk for serotonin syndrome Wa RFa Rin T! : Sertraline may increase the risk for bleeding Laboratory considerations No significant laboratory interactions or considerations were located. Doses Do GS:T! a) For treatment of compulsive disorders: 2-4 mg/kg PO once daily or divided twice daily (Landsberg 2004) b) 1-2 mg/kg PO q24h (once daily) (allow 6-8 weeks for initial trial) (Virga 2005b) c) 1-3 mg/kg PO once daily. Plan is to use the drug for a limited time (3-6 months) during which time behavioral modifica-tion is also employed. The animal should learn appropriate behavior in previously problematic situations. Then the ani-mal should be weaned off the medication over a 2 to 4 week period by halving the dose weekly (Neilson 2002) d) For treatment of behavioral diagnoses: 0. 25-0. 5 mg/kg PO q24h (once a day). note : must treat for 3-5 weeks minimum to assess effects; then treat until “well” until either has no signs associated with diagnosis or some low, consistent level (a minimum of another 1-2 months). Then treat for anoth-er 1-2 months (minimum), so that reliability of assessment is reasonably assured. If weaning off the drug do so over 3-5 weeks (or longer). Treatment should last for a minimum 4-6 months once initiating therapy. (Overall 2001) e) For compulsive disorder, anxiety: 1-4 mg/kg PO q24h (once daily) (Seibert 2003) cat S:T! a) For treatment of compulsive disorders: 0. 5 mg/kg PO once daily (Landsberg 2004) b) For urine marking (spraying), aggression, anxiety—includ-ing anxiogenic house soiling, phobias, fears: 0. 5-1 mg/kg PO q24h (once daily) (Virga 2002) c) For treatment of behavioral diagnoses: 1 mg/kg PO q24h (once a day). note : must treat for 3-5 weeks minimum to assess effects; then treat until “well” until either has no signs associated with diagnosis or some low, consistent level (a minimum of another 1 -2 months). Then treat for another 1-2 months (minimum), so that reliability of assessment is reasonably assured. If weaning off the drug do so over 3-5 weeks (or longer). Treatment should last for a minimum 4-6 months once initiating therapy. (Overall 2001)	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
Se Ve Lame R Hc L 817 d) For treatment of fear, affective or dominance aggression: 0. 5-1 mg/kg PO once daily (Crowell-Davis 2003b), (Crow-ell-Davis 2003a) e) For treatment of compulsive disorder, anxiety: 0. 5-1 mg/kg PO q24h (once daily) (Seibert 2003) monitoring Efficacy T! Adverse Effects; including appetite (weight) T! Consider doing baseline liver function tests and ECG; re-test as T! needed client information Because there has not as yet been widespread use of sertraline in T! dogs or cats, its adverse effect and efficacy profiles have not been yet fully determined; clients should report any significant abnor-mal findings to the veterinarian. Clients should understand that this drug is unlikely to have an T! immediate effect (or even in the short-term) and must commit to using the drug for months to determine efficacy chemistry/Synonyms A selective serotonin reuptake inhibitor, sertraline hydrochloride is a white crystalline powder that is slightly soluble in water and isopropyl alcohol; sparingly soluble in ethanol. The commercially available oral solution contains 12% ethanol and has a menthol scent. Sertraline may also be known as: CP-51974-01; CP-51974-1; Altruline®, Anilar®, Aremis®, Atenix®, Besitran®, Bicromil®, Gladem®, Insertec®, Irradial®, Lustral®, Novativ®, Sealdin®, Serad®, Sercerin®, Serlain®, Serta®, Tatig®, Tolrest®, Tresleen® or Zoloft®. Storage/Stability Store commercially available sertraline tablets and oral solution at controlled room temperature (25°C; 77°F); excursions permitted to 15-30°C (59-86°F). The manufacturer states to dilute the oral so-lution only in the following liquids: water, orange juice, ginger ale, lemonade or lemon/lime soda; use immediately after dilution. Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: None The ARCI (Racing Commissioners International) has designated this drug as a class 2 substance. See the appendix for more information. Human-Labe Le D PRo Duct S: Sertraline HCl Tablets: 25 mg, 50 mg & 100 mg (as base); Zoloft® (Pfizer); generic; (Rx) Sertraline HCl Oral Concentrate: 20 mg/m L in 60 m L; Zoloft® (Pfiz-er); (Rx)Sevela Mer Hcl (se-vel-a-mer) Renagel® Pho SPhoru S binding agent Prescriber Highlights Phosphorus binding agent (in the gut) for hyperphos-T T phatemia associated with chronic renal failure May be useful if patient cannot tolerate aluminum salts T T or aluminum salts are commercially unavailable Expensive when compared to aluminum hydroxide or cal-T T cium carbonate products Drug-drug interactions including nutrients T T uses/indications Sevalamer may be useful for treating hyperphosphatemia associ-ated with chronic renal failure, particularly when oral aluminum salts are not tolerated. Pharmacology/actions Sevelamer binds phosphorus in the gut; when combined with de-creased phosphorus in the diet it can substantially reduce serum phosphorus levels. It also reduces serum low-density lipoproteins and total cholesterol. Pharmacokinetics Sevelamer is administered orally, but is not absorbed systemically. contraindications/Precautions/Warnings Sevelamer is contraindicated in patients with hypophosphatemia, or bowel obstruction and in patients hypersensitive to it. adverse effects Adverse effects in humans are reported to be the same as placebo. Potentially some GI effects occur. As oral vitamin absorption may be reduced by sevalamer, con-sider the addition of vitamin supplementation during therapy. Reproductive/nursing Safety Safety during pregnancy is not established; because of the potential for binding vitamins, additional vitamins (both fat and water sol-uble) may be necessary. In humans, the FDA categorizes this drug as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) There are no adequate and well-controlled studies in nursing mothers. overdosage/acute t oxicity As sevalamer is not absorbed, acute toxicity potential appears to be negligible. Drug interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving sevalamer and may be of significance in veterinary patients: anticon Vu LSant ST! (oral): Sevelamer may reduce oral absorption; give at least one hour before or three hours after sevalamer capsules	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
818 Se Vo FLu Rane antia RRHyt Hmic ST! (oral): Sevelamer may reduce oral absorp-tion; give at least one hour before or three hours after sevalamer capsules ci PRo FLoxacin T! : Concurrent administration with sevelamer may decrease absorption by 50%; administer ciprofloxacin and other oral fluoroquinolones at least one hour before or 3 hours after, sevelamer o Ra L me Dication ST! : There are only a few medications having doc-umented reductions in oral administration when administered with sevelamer; consider dosing other oral drugs separately, par-ticularly for drugs with narrow therapeutic indexes Vitamin ST! : Sevelamer may reduce vitamin absorption from food; consider administering vitamin supplements separately from sevelamer dose Doses Do GS:T! a) For medium to large sized dog: 400 mg PO with meals (Vaden 2007) cat S:T! a) Has been used at 200 mg 2-3 times daily. Anecdotally ap-pears to be safe and effective. (Sparkes 2006a) monitoring Serum phosphorus (and other electrolytes calcium, bicarbonate, T! chloride) Consider a baseline coagulation screening test before and after T! sevalamer therapy implementation as vitamin K absorption may be impacted by the drug chemistry/Synonyms A phosphorus binding agent, sevalamer HCl is a complex chemical that is hydrophilic, but insoluble in water. Sevelamer may also be known as GT16-026A and Renagel®. Storage/Stability Sevelamer capsules should be stored at room temperature and pro-tected from moisture. Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: None Human-Labe Le D PRo Duct S: Sevalamer HCl Tablets: 400 mg and 800 mg (on an anhydrous basis); Renagel® (Genzyme); (Rx) Sevoflurane (see-voe-floo-rane) Sevo Flo®, Ultane® inhalational ane Sthetic Prescriber Highlights Inhalational anesthetic similar to isoflurane, but with T T more rapid induction & recovery Currently more expensive than isoflurane T T uses/indications Sevoflurane may be useful in a variety of species when rapid in-duction and/or rapid recoveries are desired with an inhalational anesthetic. Pharmacology/actions While the precise mechanism that inhalant anesthetics exert their general anesthetic effects is not precisely known, they may interfere with functioning of nerve cells in the brain by acting at the lipid matrix of the membrane. Sevoflurane has a very low blood:gas par-tition coefficient (0. 6) allowing very rapid anesthesia induction and recovery. Rapid mask induction is possible. Pharmacologic effects of sevoflurane are similar to isoflurane and include: CNS depression, depression of body temperature reg-ulating centers, increased cerebral blood flow, respiratory depres-sion, hypotension, vasodilatation, myocardial depression (less so than with halothane), and muscular relaxation. Minimal Alveolar Concentration (MAC; %) in oxygen reported for sevoflurane in various species: Dog = 2. 09-2. 4; Cat = 2. 58; Horse = 2. 31; Sheep = 3. 3; Swine = 1. 97-2. 66; Human (adult) = 1. 71-2. 05. Several factors may alter MAC (acid/base status, tem-perature, other CNS depressants on board, age, ongoing acute dis-ease, etc. ). Pharmacokinetics Because of its low solubility in blood, only small concentrations of sevoflurane in the blood are required to be dissolved in blood be-fore alveolar partial pressures are in equilibrium with arterial par-tial pressures. This low solubility means that sevoflurane is rapidly removed from the lungs. It is unknown what percent sevoflurane is bound to plasma proteins. The majority of sevoflurane is excreted via the lungs, but about 3% is metabolized in the liver via the cyto-chrome P450 2E1 isoenzyme system. contraindications/Precautions/Warnings Sevoflurane is contraindicated in patients with a history or predi-lection towards malignant hyperthermia. It should be used with caution (benefits vs. risks) in patients with increased CSF or head injury, or renal insufficiency. Because of its rapid action, use caution not to overdose during the induction phase. Because of the rapid recovery associated with sevoflurane use caution (and appropriate sedation during the re-covery phase), particularly with large animals. Geriatric animals may require less inhalation anesthetic. Sevoflurane does not appear to be a good inhalational anesthetic in rabbits (breath holding, struggling). adverse effects Sevoflurane seems to be well tolerated. Hypotension may occur and is considered dose related. Dose-dependent respiratory depression and GI effects (nausea, vomiting, ileus) have been reported. While cardiodepression generally is minimal at doses causing surgical planes of anesthesia, it may occur; bradycardia is possible. Malignant hyperthermia may be triggered by this agent (like other inhalational anesthetics). Sevoflurane can react with carbon dioxide absorbents to pro-duce “compound A ”, a nephrotoxin. After extensive clinical use in humans however, nephrotoxicity has not been demonstrated to be of clinical concern. Sevoflurane should be used in precision, agent-specific, out of circuit vaporizers. Reproductive/nursing Safety No overt fetotoxicity or teratogenicity has been demonstrated in lab animal studies, but definite safety has not been established for use during pregnancy.	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
Se Vo FLu Rane 819 overdosage/acute t oxicity In the event of an overdosage, discontinue sevoflurane; maintain airway and support respiratory and cardiac function as necessary. Drug interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving sevoflurane and may be of significance in veterinary patients: amino GL yco Si De S, Linco Sami De S T! : May enhance neuromuscular blockade ba Rbitu Rate ST! (phenobarbital, pentobarbital, etc. ): May increase concentrations of inorganic fluoride i Soniazi DT! : May increase concentrations of inorganic fluoride mi Dazo Lam T! : May potentiate sevoflurane effects; decrease MAC non-De Po La Rizin G neu Romu Scu La R b Lockin G a Gent ST! (atracurium, pancuronium, vecuronium ): Additive neuromuscular blockade may occur o Piate ST! : May potentiate sevoflurane effects; decrease MAC St. Jo Hn S Wo R t T! : Increased risk for anesthetic complications; recommend discontinuing St. John's Wort 5 days in advance of surgery Succiny Lc Ho Line T! : Sevoflurane may enhance effects Sym P at Homimetic ST! (dopamine, epinephrine, norepinephrine, ephed-rine, metaraminol, etc. ): While sevoflurane sensitizes the myocar-dium to the effects of sympathomimetics less so than halothane, arrhythmias may still result; caution and monitoring is advised Ve Ra P ami LT! : May cause cardiodepression Laboratory considerations Inhalational anesthetics may cause transient increases in T! liver function tests, Wbcs, and glucose Doses Minimal Alveolar Concentration (MAC; %) in oxygen reported for sevoflurane in various species: Dog = 2. 09-2. 4; Cat = 2. 58; Horse = 2. 31; Sheep = 3. 3; Swine = 1. 97-2. 66; Human (adult) = 1. 71-2. 05. Several factors may alter MAC (acid/base status, temperature, other CNS depressants on board, age, ongoing acute disease, etc. ) Do GS: T! Inspired Concentration: The delivered concentration of Sevo-Flo® (sevoflurane) should be known. Since the depth of an-esthesia may be altered easily and rapidly, only vaporizers producing predictable percentage concentrations of sevoflu-rane should be used. Sevoflurane should be vaporized using a precision vaporizer specifically calibrated for sevoflurane. Sevoflurane contains no stabilizer. Nothing in the drug prod-uct alters calibration or operation of these vaporizers. The administration of general anesthesia must be individualized based on the patient's response. When using sevoflurane, pa-tients should be continuously monitored and facilities for mainte-nance of patient airway, artificial ventilation, and oxygen supple-mentation must be immediately available. Replacement of Desiccated CO2 Absorbents: When a clinician suspects that the CO2 absorbent may be desiccated, it should be replaced. An exothermic reaction occurs when sevoflu-rane is exposed to CO2 absorbents. This reaction is increased when the CO2 absorbent becomes desiccated. Premedication : No specific premedication is either indicated or contraindicated with sevoflurane. The necessity for and choice of premedication is left to the discretion of the veteri-narian. Preanesthetic doses for premedicants may be lower than the label directions for their use as a single medication. induction : For mask induction using sevoflurane, inspired concentrations up to 7% sevoflurane with oxygen are em-ployed to induce surgical anesthesia in the healthy dog. These concentrations can be expected to produce surgical anesthesia in 3 to 14 minutes. Due to the rapid and dose depen-dent changes in anesthetic depth, care should be taken to prevent overdosing. Respiration must be monitored closely in the dog and supported when necessary with supplemental oxygen and/or as-sisted ventilation. maintenance : Sevo Flo® may be used for maintenance anes-thesia following mask induction using sevoflurane or fol-lowing injectable induction agents. The concentration of vapor necessary to maintain anesthesia is much less than that required to induce it. Surgical levels of anesthesia in the healthy dog may be maintained with inhaled concentrations of 3. 7-4% sevoflurane in oxygen in the absence of premedi-cation and 3. 3-3. 6% in the presence of premedication. The use of injectable induction agents without premedication has little effect on the concentrations of sevoflurane required for maintenance. Anesthetic regimens that include opioid, alpha2-agonist benzodiazepine or phenothiazine premedi-cation will allow the use of lower sevoflurane maintenance concentrations. (Label directions; Sevo Flo®—Abbott Animal Health) monitoring Respiratory and ventilatory status T! Cardiac rate/rhythm; blood pressure (particularly with “at risk” T! patients Level of anesthesia T! chemistry/Synonyms Sevoflurane is an isopropyl ether inhalational anesthetic with a mo-lecular wt. of 200, saturate vapor pressure at 20°C of 160 mm Hg and a boiling pt. of 58. 5°C. It is reported to have a pleasant odor and is not irritating to airways. It is non-flammable and non-explosive. Sevoflurane is a clear, colorless liquid that is miscible with ethanol or ether and slightly soluble in water. Sevoflurane may also be known as: BAX-3084, MR-654, Sevocris®, Sevo Flo®, Sevorane®, or Ultane®. Storage/Stability Sevoflurane should be stored at room temperature. Sevoflurane does not react with metal. Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: Sevoflurane in 250 m L btls; Sevo Flo® (Abbott); (Rx). Approved for use in dogs. Human-Labe Le D PRo Duct S: Sevoflurane in 250 m L btls; Ultane® (Abbott); (Rx)	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
820 Si LDena Fi L cit Rate Sildenafil citrate (sil-den-ah-fil) Viagra®, Revatio® va Sodilator; Pho SPhodie Stera Se ty Pe 5 inhibitor Prescriber Highlights Used in veterinary medicine for treating pulmonary T T hypertension Contraindicated if patients receiving organic nitrates T T Adverse effects not well-known; inguinal flushing, pos-T T sible GI effects reported Treatment may be very expensive T T uses/indications Sildenafil may be of benefit in the adjunctive treatment of pulmo-nary hypertension in small animals. In humans, sildenafil is indicated for erectile dysfunction or pul-monary hypertension. Pharmacology/actions Sildenafil inhibits cyclic guanosine monophosphate (c GMP) spe-cific phosphodiesterase type-5 (PDE5) found in the smooth muscle of the pulmonary vasculature, corpus cavernosum and elsewhere, where PDE5 is responsible for degradation of c GMP. Sildenafil in-creases c GMP thereby resulting in nitric oxide mediated vasodilata-tion within pulmonary vascular smooth muscle cells. Pharmacokinetics The pharmacokinetics of sildenafil has been reported in dogs (Walker, Ackland et al. 1999). Oral bioavailability is approximately 50% (higher than humans); volume of distribution is about 5. 2 L/kg (versus 1. 2 L/kg in humans); elimination half-life approximately 6 hours (significant interpatient variability; average human half life is about 4 hours). contraindications/Precautions/Warnings Sildenafil should not be used concurrently with nitrates (see drug interactions) or in patients documented hypersensitive to it. Pulmonary vasodilators may significantly worsen the cardio-vascular status of patients with pulmonary veno-occlusive disease (PVOD). Use with extreme caution in patients with resting hypotension, fluid depletion, severe left ventricular outflow obstruction, or auto-nomic dysfunction. adverse effects Because of limited use in dogs, the adverse effect profile is not fully known. Cutaneous flushing of the inguinal region has been report-ed and GI effects are possible. In humans, headache, visual distur-bances, dyspepsia, nasal congestion, myalgia, priapism, dizziness, and back pain have been reported. Reproductive/nursing Safety No evidence of teratogenicity, embryotoxicity or fetotoxicity was observed in pregnant rats or rabbits, dosed at 200 mg/kg/day dur-ing organogenesis. In a rat pre-and postnatal development study, the no-observed-adverse-effect dose was 30 mg/kg/day. In humans, the FDA categorizes this drug as category B for use during preg-nancy (Animal studies have not yet demonstrated risk to the fetus, but there are no adequate studies in pregnant women; or animal studies have shown an adverse effect, but adequate studies in pregnant women have not demonstrated a risk to the fetus in the first trimester of preg-nancy, and there is no evidence of risk in later trimesters. ) It is not known if sildenafil or its metabolites are excreted in milk. overdosage/acute t oxicity Little information is available. An adult women ingested 2000 mg and survived but developed tachycardia, nonspecific ST-T changes on ECG, headache, dizziness, and flushing. It is expected that overdoses in animals would mirror the drugs adverse effect profile; treat supportively. Drug interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving sildenafil and may be of significance in veterinary patients: a LPHa-a DRene RGic b Locke RS T! (e. g., phentolamine, phenothiazines, phenoxybenzamine ): May increase hypotensive effects am Lo Di Pine T! : Potential to increase hypotensive effects anti Hy Pe R ten Si Ve, Hy Poten Si Ve DRu GS T! : Potentially could increase hypotensive effects azo Le anti Fun Ga LS T! (ketoconazole, itraconazole ): May reduce sildenafil metabolism and increase AUC cimeti Dine T! : May reduce sildenafil metabolism and increase AUC e Ryt HRomycin, c La Rit HRomycin T! : May reduce sildenafil metabo-lism and increase AUC He Pa Rin T! : May increase bleeding risks nit Rate ST! (e. g., nt G, isosorbide ): Significant potentiation of vaso-dilatory effects; life-threatening hypotension possible nit Ro PRu SSi De So Dium T! : Significant potentiation of vasodilatory effects; life-threatening hypotension possible PHenoba Rbita LT! : May decrease sildenafil concentrations Ri Fam Pin T! : May decrease sildenafil concentrations Laboratory considerations None were noted. Doses Do GS/cat S:T! Dogs: From a retrospective study: median dose was 1. 9 mg/kg (range from 0. 5-2. 7 mg/kg) q8-24h. Dogs may have been also treated with oxygen, ACE inhibitors, furosemide, amlodipine, diltiazem, theophylline, phenobarbital and/or antibiotics. (Bach, Rozanski et al. 2006) For pulmonary hypertension documented by Doppler, chronic pulmonary disease, right-sided heart failure (HW disease; con-genital): 0. 5-1 mg/kg PO two times daily (higher dose of 2-3 mg/kg three times a day may be tolerated and needed) (Tilley 2007) monitoring Clinical efficacy (improved syncope, cough, respiratory effort)T! Pulmonary artery pressure, systemic blood pressure T! client information Brief clients on the experimental nature of using this medication T! in small animals and the costs of therapy chemistry/Synonyms Sildenafil citrate occurs as a white to off-white crystalline powder with a solubility of 3. 5 mg/m L in water and a molecular weight of 666. 7.	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
Si Lyma Rin; mi Lk t Hi St Le 821 Sildenafil may also be known as UK 92480, UK 92480-10, Aphrodil®, Revatio®, or Viagra®. Storage/Stability Sildenafil tablets should be stored at room temperature (25°C; 77°F); excursions permitted to 15-30°C (59-86°F). Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: None Human-Labe Le D PRo Duct S: Sildenafil Citrate Tablets: 20 mg (of sildenafil); Revatio® (Pfizer); (Rx) Sildenafil Citrate Tablets: 25 mg, 50 mg & 100 mg (of sildenafil); Via-gra® (Pfizer); (Rx) Sily Marin Mil K t Hi Stle (sill-e-mar-in) Marin® nutraceutical he P ato-Protectant Prescriber Highlights Nutraceutical that may be useful for treatment of chronic T T & acute liver disease, cirrhosis; as a hepato-protective agent when hepatotoxins (e. g., Aminita phalloide) in-gested Appears well-tolerated; potentially could cause GI effects T T Do not confuse Milk Thistle with Blessed Thistle T T Potential drug interactions T T uses/indications While controlled studies demonstrating efficacy and a standardized form and concentration of silymarin are lacking, it is being used to treat a variety of liver diseases in humans and domestic companion animals (birds, dogs, cats, horses, rabbits). It is mostly of interest in treating chronic and acute liver disease, cirrhosis, and as a hepato-protective agent when hepatotoxic agents are ingested (e. g., Aminita phalloide; “Death Cap Mushrooms”). Pharmacology/actions Silymarin has a variety of pharmacologic actions that may contrib-ute to its apparent effects in treating liver disease. It inhibits lipid peroxidase and beta-glucoronidase and acts as an anti-oxidant and free radical scavenger. Silymarin also inhibits the cytotoxic, inflam-matory, and apoptotic effects of tumor necrosis factor (TFN). It apparently can alter outer hepatocyte cell membranes that can pre-vent toxin penetration. Silymarin is thought to reduce hepatic col-lagen formation and increase hepatic glutathione content. Pharmacokinetics In humans, silymarin has an oral bioavailability of less than 50% and peak levels occur 2-4 hours post-dose. When silibinin (sily-bin, sylibin) is complexed with phosphatidylcholine, oral absorp-tion can be increased. The drug undergoes extensive enterohepatic circulation and has significantly higher concentrations in liver cells and bile than in plasma. Elimination half-life in humans averages 6 hours. The majority of the drug is eliminated unchanged in the feces, but 20-40% is converted into glucuronide and sulfate con-jugates which are eliminated in the feces; only about 8% is excreted in the urine. contraindications/Precautions/Warnings There are no reported absolute contraindications to silymarin in animals. Extracts from the plant parts of Milk Thistle (not the seeds which are used to make the extract silymarin), may possess estro-gen-like activity and should not be used in patients where exog-enous estrogens would be contraindicated. adverse effects Silymarin is apparently well tolerated when administered orally. In humans, GI disturbances have been reported on occasion (nausea to diarrhea). Patients who have allergies to other members of the Asteraceae/Compositae plant family (includes ragweed, marigolds, daisies, etc. ) may exhibit allergic reactions to Milk Thistle deriva-tives. Do not confuse Milk Thistle with Blessed Thistle. Reproductive/nursing Safety Data on the safety of silymarin use during pregnancy or nursing is not available; its potential benefit must be weighed against the uncertainty of its safety. overdosage/acute t oxicity Overdoses are unlikely to cause significant morbidity. Gastrointestinal effects may be seen and treated in a supportive manner. Drug interactions While no specific drug interactions have been reported, silymarin may inhibit cytochrome P450 isoenzyme 2C9 (CYP2C9). Drugs with narrow therapeutic indexes that are metabolized by this isoen-zyme should be used with caution when using silymarin. Drugs that could be affected include: warfarin, amitriptyline, verapamil, etc. Silymarin also may inhibit CYP3A4, but thus far this interaction does not appear to be clinically significant. Silymarin may increase the clearance of drugs that undergo hepatic glucuronidation (not cats), including: acetaminophen, diazepam, morphine, and lamotrigine. Clinical significance has not been determined for this interaction and the usefulness of silymarin for treating acetaminophen toxicity has not been determined. Laboratory considerations No interactions with laboratory tests are reported. Doses Do GS & cat S:T! a) Therapeutic dosage is unknown, but suggested doses range from 50-250 mg/day (Twedt 2004) b) For adjunctive therapy for chronic liver disease: 20-50 mg/ kg per day (extrapolated from human, monkey, rodent and dog research) (Center 2002) c) For chronic liver disease and ameliorating the effects of an-ticonvulsants: Dosages vary from 50-200 mg given every 12-24 hours (Tams 2001) d) For hepatotoxicity, hepatic recovery/regeneration, hepatic fi-brosis: 20-50 mg/kg/day. (Webb 2007b) e) Cats: 4-8 mg/kg/day (Zoran 2006b) monitoring Clinical efficacy T! client information Because silymarin experience in animals is limited, clients should T! understand the “investigational nature” of its use chemistry/Synonyms Milk Thistle, the common name for Silybum marianum, has been used as a medicinal agent for at least two thousand years. The me-	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
822 So Dium bica Rbonate dicinal extract from the seeds of the plant is silymarin that contains the four flavolignans: silichristin (sylichristin), isosilibinin, silydi-anin (silidianin), and the most biological active component, silibi-nin (sylibin, silybin, silibide). Milk Thistle extract contains approxi-mately 70% silymarin of which about 70% is silibinin. Silymarin is reportedly fairly insoluble in water. Silymarin or Milk thistle may also be known as Carduus mari-anus, Holy Thistle, Legalon, or Marian Thistle. Blessed Thistle is a different compound. Storage/Stability Unless otherwise labeled, commercially available products contain-ing silymarin should be stored at room temperature in tight con-tainers. Avoid storing the products in areas of high humidity. Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: Milk Thistle or silymarin is considered a nutritional supplement by the FDA. No standards have been accepted for potency, etc. by regula-tory bodies. Supplements are available from a wide variety of sources and dosage forms include tablets and capsules in a variety of concen-trations (150-1000 mg). When choosing a product it is recommend-ed to purchase ones that state the concentration (usually 70-80%) of silymarin contained in the product. Silybin A+B 9 mg (in a phosphatidylcholine complex) & Vitamin E 50 IU Tablets: Marin® for Cats (Nutramax); Not considered a drug by the FDA. Silybin A+B 24 mg (in a phosphatidylcholine complex), Vitamin E 105 IU, & Zinc 17 mg Chewable Tablets: Marin® for Dogs (Nutra-max); Not considered a drug by the FDA. Labeled for use in small to medium dogs. Silybin A+B 70 mg (in a phosphatidylcholine complex), Vitamin E 300 IU, & Zinc 45 mg Chewable Tablets: Marin® for Dogs (Nutra-max); not considered a drug by the FDA. Labeled for use in large dogs. A combination product (Denamarin®, Nutramax) containing SAMe and silybin (silymarin) is also labeled for use in dogs and cats. Human-Labe Le D PRo Duct S: None as pharmaceuticals Sodiu M bicarbonate (soe-dee-um bye-kar-boe-nate) Neut® alkalinizer Prescriber Highlights Alkalinizing agent used to treat metabolic acidosis & T T alkalinize urine; may be used adjunctively for hypercalce-mic or hyperkalemic crises Contraindications: Parenteral bicarbonate is generally T T contraindicated in patients with metabolic or respiratory alkalosis, excessive chloride loss secondary to vomiting or GI suction, at risk for development of diuretic-induced hypochloremic alkalosis, or with hypocalcemia where al-kalosis may induce tetany Extreme Caution: Hypocalcemia Caution: CHF, nephrotic T T syndrome, hypertension, oliguria or volume overload Adverse Effects: Especially with parenteral (high dose): T T metabolic alkalosis, hypokalemia, hypocalcemia, “over-shoot” alkalosis, hypernatremia, volume overload, con-gestive heart failure, shifts in the oxygen dissociation curve causing decreased tissue oxygenation, & paradoxi-cal CNS acidosis leading to respiratory arrest. If used dur-ing CPR: hypercapnia, if the patient is not well ventilated; patients may be predisposed to ventricular fibrillation. Drug Interactions T T uses/indications Sodium bicarbonate is indicated to treat metabolic acidosis and al-kalinize the urine. It is also used as adjunctive therapy in treating hypercalcemic or hyperkalemia crises. Pharmacology/actions Bicarbonate ion is the conjugate base component of bicar-bonate:carbonic acid buffer, the principal extracellular buffer in the body. contraindications/Precautions/Warnings Parenterally administered sodium bicarbonate is considered gener-ally contraindicated in patients with metabolic or respiratory alka-losis, excessive chloride loss secondary to vomiting or GI suction, at risk for development of diuretic-induced hypochloremic alkalosis, or with hypocalcemia where alkalosis may induce tetany. Use with extreme caution and give very slowly in patients with hypocalcemia. Because of the potential sodium load, use with cau-tion in patients with CHF, nephrotic syndrome, hypertension, olig-uria, or volume overload. adverse effects Sodium bicarbonate therapy (particularly high-dose parenteral use) can lead to metabolic alkalosis, hypokalemia, hypocalcemia, “overshoot” alkalosis, hypernatremia, volume overload, congestive heart failure, shifts in the oxygen dissociation curve causing de-creased tissue oxygenation, and paradoxical CNS acidosis leading to respiratory arrest. When sodium bicarbonate is used during cardiopulmonary re-suscitation, hypercapnia may result if the patient is not well venti-lated; patients may be predisposed to ventricular fibrillation. Oral and parenteral bicarbonate (especially at higher doses) may contribute significant amounts of sodium and result in hyper-	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
So Dium bica Rbonate 823 natremia and volume overload; use with caution in patients with CHF, or acute renal failure. Reproductive/nursing Safety Reproductive safety studies have not been performed. Assess risk versus benefit before using. overdosage/acute t oxicity Sodium bicarbonate can cause severe alkalosis, with irritability or tetany if overdosed or given too rapidly. Dosages should be thor-oughly checked and frequent monitoring of electrolyte and acid/base status performed. Treatment may consist of simply discontinuing bicarbonate if alkalosis is mild or by using a rebreathing mask. Severe alkalosis may require intravenous calcium therapy. Sodium chloride or po-tassium chloride may be necessary if hypokalemia is present. Drug interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving sodium bicarbonate and may be of significance in veterinary patients: antic Ho Line RGic a Gent ST! : Concomitant oral sodium bicarbonate may reduce absorption; administer separately azo Le anti Fun Ga LST! (ketoconazole, itraconazole ): Concomitant oral sodium bicarbonate may reduce absorption; administer separately ci PRo FLoxacin; en Ro FLoxacin T! : The solubility of ciprofloxacin and enrofloxacin is decreased in an alkaline environment; patients with alkaline urine should be monitored for signs of crystalluria co Rtico Ste Roi DST! : Patients receiving high dosages of sodium bicar-bonate and ACTH or glucocorticoids may develop hypernatremia Diu Retic ST! (e. g., thiazides, furosemide ): Concurrent use of sodium bicarbonate in patients receiving potassium-wasting diuretics may cause hypochloremic alkalosis e PHe DRine T! : When urine is alkalinized by sodium bicarbonate, ex-cretion may be decreased Hi Stamine T! 2 b Lockin G a Gent S (e. g., cimetidine, ranitidine ): Con-comitant oral sodium bicarbonate may reduce absorption; ad-minister separately i Ron PRo Duct ST! : Concomitant oral sodium bicarbonate may re-duce absorption; administer separately o Ra L me Dication ST! : Because oral sodium bicarbonate can either increase or reduce the rate and/or extent of absorption of many orally administered drugs, it is recommended to avoid giving other drugs within 1-2 hours of sodium bicarbonate quini Dine T! : When urine is alkalinized by sodium bicarbonate, ex-cretion may be decreased Sa Licy Late ST! : When urine is alkalinized by sodium bicarbonate, excretion of weakly acidic drugs may be increased Suc Ra LF ate T! : Oral sodium bicarbonate may reduce the efficacy of sucralfate if administered concurrently tet Racyc Line ST! : Concomitant oral sodium bicarbonate may re-duce absorption; administer separately Doses Do GS & cat S:T! For severe metabolic acidosis: a) Main therapeutic goal should be to eliminate the underly-ing cause of acidosis. If causes are not readily reversible, arte-rial p H is <7. 2 (7. 1 if diabetic ketoacidosis), and ventilatory procedures have not reduced acidemia, bicarbonate therapy should be considered. m Eq of bicarbonate required = 0. 5 x body weight in kgs. x (desired total CO 2 m Eq/L minus mea-sured total CO 2 m Eq/L). Give 1/2 of the calculated dose slowly over 3-4 hours IV. Recheck blood gases and assess the clinical status of the patient. Avoid over-alkalinization. (Schaer 1986) For adjunctive therapy of diabetic ketoacidosis: note: Use of bicarb for this indication is somewhat controversial a) If plasma bicarbonate is ≤11 m Eq/L give bicarbonate thera-py. Dose (in m Eq) = body weight in kgs. x 0. 4 x (12-patient's bicarbonate) x 0. 5. Give above dose over 6 hours in IV fluids and then recheck plasma bicarbonate or total venous CO2. If still ≤11 m Eq/L, recalculate dose and repeat therapy. (Nelson and Feldman 1988) For metabolic acidosis in acutely critical situations (cardiac ar-rest): a) 1 m Eq/kg IV initially, followed by 0. 5 m Eq/kg at 10-15 min-ute intervals during CPR (Moses 1988) b) Give none during the first 5-10 minutes of arrest, then 0. 5 m Eq/kg every 5 minutes of cardiac arrest thereafter (Haskins 1989) For adjunctive treatment of hypercalcemic crisis: a) The m Eq of bicarbonate required = 0. 3 x body weight in kgs. x (desired plasma bicarbonate m Eq/L-measured plasma bicarbonate m Eq/L); or 1 m Eq/kg IV every 10-15 minutes; maximum total dose: 4 m Eq/L (Kruger, Osborne, and Polzin 1986) For adjunctive therapy for hyperkalemic crises: a) If serum bicarbonate or total CO 2 is unavailable: 2- 3 m Eq/ kg IV over 30 minutes if patient has decreased tissue perfu-sion or renal failure and does not have diabetic ketoacidosis. Must be used judiciously. (Willard 1986) b) 1-2 m Eq/kg IV slowly (Macintire 2006a) Metabolic acidosis secondary to renal failure: a) Dogs: Initial dose: 8-12 mg/kg PO q8h; adjust dosage to at-tain blood total CO 2 concentrations to 18-24 m Eq/L for re-nal failure. Although, inferior to monitoring total CO 2; urine p H may be used as a guideline for adjusting dosage. Urine p H should be between 6. 5-7. (Polzin and Osborne 1985) b) Initial dose: 8-12 mg/kg q8h; adjust dosage to attain blood total CO 2 concentrations to 18-24 m Eq/L (Allen 1989) c) 8-12 mg/kg PO q8-12h (Vaden 2007) T o alkalinize the urine:a) Dosage must be individualized to the patient. Initially give 10-90 grains (650 mg-5. 85 grams) PO per day, depend-ing on the size of the patient and the pretreatment urine p H value. Goal of therapy is to maintain a urine p H of about 7; avoid p H >7. 5. (Osborne et al. 1989) b) For adjunctive therapy in dissolution and/or prevention of urate urolithiasis in dogs: 0. 5-1 gram (1/8-1/4 tsp. ) per 5 kg of body weight three times daily PO. Goal of therapy is to attain a urine p H of from 7-7. 5. (Senior 1989) Ho RSe S:T! For metabolic acidosis: a) Associated with colic; if p H is <7. 3 and base deficit is >10 m Eq/L estimate bicarbonate requirement using the formula: bicarbonate deficit (HCO-3 m Eq) = base deficit (m Eq/L) x 0. 4 x body weight (kg). May administer as a 5% sodium bi-carbonate solution. Each L of solution contains 600 m Eq of bicarbonate (hypertonic) and should not be administered any faster than 1-2 L/hr. Because acidotic horses with colic tend also to be dehydrated, may be preferable to give as iso-tonic sodium bicarbonate (150 m Eq/L). (Stover 1987)	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
824 So Dium bica Rbonate Ruminant S:T! For acidosis: a) 2-5 m Eq/kg IV for a 4-8 hour period (Howard 1986) b) For severely dehydrated (10-16% dehydrated) acidotic calves (usually comatose): Use isotonic sodium bicarbonate (156 m Eq/L). Most calves require about 2 liters of this so-lution given over 1-2 hours, then change to isotonic saline and sodium bicarbonate or a balanced electrolyte solution. Isotonic sodium bicarbonate may be made by dissolving 13 grams of sodium bicarbonate in 1 L of sterile water. Isotonic saline and sodium bicarbonate may be made by: mixing 1 L of isotonic saline with 1 L of isotonic sodium bicarbonate. (Radostits 1986) bi RDS: T! For metabolic acidosis: a) 1 m Eq/kg initially IV (then SC) for 15-30 minutes to a max-imum of 4 m Eq/kg (Clubb 1986) monitoring Acid/base status T! Serum electrolytes T! Urine p H (if being used to alkalinize urine)T! chemistry/Synonyms An alkalinizing agent, sodium bicarbonate occurs as a white, crys-talline powder having a slightly saline or alkaline taste. It is soluble in water and insoluble in alcohol. One gram of sodium bicarbonate contains about 12 m Eq each of sodium and bicarbonate; 84 mg of sodium bicarbonate contains 1 m Eq each of sodium and bicarbon-ate. A 1. 5% solution of sodium bicarbonate is approximately isoton-ic. An 8. 4% solution of sodium bicarbonate can be made isotonic by diluting each m L with 4. 6 m L of sterile water for injection. Sodium Bicarbonate may also be known as: baking soda, E500, monosodium carbonate, natrii bicarbonas, natrii hydrogenocarbo-nas, sal de vichy, sodium acid carbonate, Na HCO 3, sodium hydro-gen carbonate; many trade names are available. Storage/Stability/compatibility Sodium bicarbonate tablets should be stored in tight containers, preferably at room temperature (15-30°C). Sodium bicarbonate injection should be stored at temperatures less than 40°C and pref-erably at room temperature; avoid freezing. Sodium bicarbonate powder is stable in dry air, but will slowly decompose upon exposure to moist air. Sodium bicarbonate is reportedly physically compatible with the following intravenous solutions and drugs: Dextrose in water, dextrose/saline combinations, dextrose-Ringer's combinations, sodium chloride injections, amikacin sulfate, aminophylline, amo-barbital sodium, amphotericin B, atropine sulfate, bretylium tosy-late, carbenicillin disodium, cefoxitin sodium, cephalothin sodium, cephapirin sodium, chloramphenicol sodium succinate, chlorothi-azide sodium, cimetidine HCl, clindamycin phosphate, ergonovine maleate, erythromycin gluceptate/lactobionate, Innovar®, heparin sodium, hyaluronidase, hydrocortisone sodium succinate, kana-mycin sulfate, lidocaine HCl, metaraminol bitartrate, methotrex-ate sodium, methyldopate HCl, nafcillin sodium, netilmicin sulfate, oxacillin sodium, oxytocin, phenobarbital sodium, phenyleph-rine HCl, phenytoin sodium, phytonadione, potassium chloride, prochlorperazine edisylate, and sodium iodide. Sodium bicarbonate compatibility information conflicts or is depen-dent on diluent or concentration factors with the following drugs or solutions: lactated Ringer's injection, Ringer's injection, sodium lactate 1/6 M, ampicillin sodium, calcium chloride/gluconate, me-thicillin sodium, penicillin G potassium, pentobarbital sodium, promazine HCl, thiopental sodium, vancomycin HCl, verapamil HCl, and vitamin B-complex with C. Consult specialized references or a hospital pharmacist for more specific information. Sodium bicarbonate is reportedly physically incompatible with the following solutions or drugs: alcohol 5%/dextrose 5%, D 5 lac-tated Ringer's, amrinone lactate, ascorbic acid injection, carmus-tine, cisplatin, codeine phosphate, corticotropin, dobutamine HCl, epinephrine HCl, glycopyrrolate, hydromorphone HCl, imipenem-cilastatin, regular insulin, isoproterenol HCl, labetolol HCl, levor-phanol bitartrate, magnesium sulfate, meperidine HCl, methadone HCl, metoclopramide HCl, norepinephrine bitartrate, oxytetracy-cline HCl, pentazocine lactate, procaine HCl, secobarbital sodium, streptomycin sulfate, succinylcholine chloride, tetracycline HCl. Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: Sodium Bicarbonate Injection: 8. 4% (1 m Eq/m L) in 50 m L (50 m Eq/ vial), 100 m L (100 m Eq/vial) and 500 m L (500 m Eq/vial) vials; avail-able generically labeled; (Rx) Human-Labe Le D PRo Duct S: Injectable Products: Sodium Bicarbonate Neutralizing Additive Solution: 4% (0. 48 m Eq/m L) in 5 m L (2. 4 m Eq) vials; 4. 2% (0. 5 m Eq/m L) in 5 m L fill in 6 m L vials (2. 5 m Eq); Neut® (Abbott); Sodium Bicarbonate (American Pharmaceutical Partners); (Rx) Sodium Bicarbonate Injection: 4. 2% (0. 5 m Eq/m L) in 10 m L (5 m Eq) syringes, 10 m L (5 m Eq) Bristoject syringes; generic, (Hospira, American Pharmaceutical Partners); (Rx) Sodium Bicarbonate Injection: 5% (0. 6 m Eq/m L) in 500 m L vials (297. 5 m Eq); generic, (Hospira, Baxter, Mc Gaw); (Rx) Sodium Bicarbonate Injection: 7. 5% (0. 9 m Eq/m L) in 50 m L (44. 6 m Eq) amps, syringes, vials, Bristoject syringes and 200 m L (179 m Eq) Maxi Vials; generic (Hospira, American Regent, American Pharma-ceutical Partners); (Rx) Sodium Bicarbonate Injection: 8. 4% (1 m Eq/m L) in 10 m L (10 m Eq) and 50 m L (50 m Eq) syringes and 50 m L vials (50 m Eq/vial); generic (Hospira, American Regent, American Pharmaceutical Partners); (Rx) Oral Products: Tablets: 325 mg & 650 mg; (1 g sodium bicarbonate provides 11. 9 m Mol sodium and 11. 9 m Mol bicarbonate); generic; (OTC) Powder: 120 g, 300 g & 1 lb; generic; (OTC)Omeprazole/Sodium Bicarbonate Capsules (immediate re-lease): 20 mg omeprazole/1,100 mg sodium bicarbonate) & 40 mg omeprazole/1,100 mg sodium bicarbonate; Zegerid® (Santarus); (Rx) Omeprazole/Sodium Bicarbonate Powder for Oral Suspension: 20 mg omeprazole/1,680 mg sodium bicarbonate & 40 mg omeprazole/1,680 mg sodium bicarbonate; Zegerid® (Santarus); (Rx) Sodium Bromide — see Bromides Sodium Chloride Injections — see the Intravenous Fluids section in the appendix Sodium Citrate — see Citrate Salts Sodium Hyaluronate — see Hyaluronate Sodium Sodium Iodide — see Iodide, Sodium Sodium Nitroprusside — See Nitroprusside Sodium Sodium Phosphate — see Phosphate, Parenteral	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
So Dium Po L y Sty Rene Su LFonate 825 Sodiu M poly Styrene Sulfonate (soe-dee-um pol-ee-stye-reen sulf-foe-nate) Kayexalate®, SPS cationic exchange re Sin (hy Perkalemia) Prescriber Highlights Cation exchange resin used to treat hyperkalemia T T Contraindications: Patients who cannot tolerate a large T T sodium load Cause of hyperkalemia must be addressed T T Adverse Effects: Constipation, anorexia, vomiting, or T T nausea. Overdosage/overuse may lead to hypokalemia, hypocalcemia & hypomagnesemia. If given PO, often mixed with sorbitol to expedite removal T T of resin (& potassium)Drug Interactions T T uses/indications SPS is indicated as adjunctive treatment of hyperkalemia. The cause of the hyperkalemia should be elucidated and corrected if possible. Pharmacology/actions SPS is a resin that exchanges sodium for other cations. After be-ing given orally, hydrogen ions will be exchanged for sodium (in an acidic environment). As the resin travels through the intestinal tract, the hydrogen ions will be exchanged with other more concen-trated cations. Primary exchange with potassium occurs predomi-nantly in the large intestine. When given as a retention enema, SPS generally exchanges sodium for potassium directly in the colorec-tum. While theoretically, up to 3. 1 m Eq of potassium could be ex-changed per gram of SPS, it is unlikely that more than one m Eq will be exchanged per gram of resin administered. Pharmacokinetics SPS is not absorbed from the GI tract. Its onset of action may be from hours to days; so severe hyperkalemia may require other treat-ments (e. g., dialysis) in the interim. contraindications/Precautions/Warnings Because large quantities of sodium may be released and absorbed, patients on severely restricted sodium diets (severe CHF, hyperten-sion, oliguria) may benefit from alternative methods of treatment. Overdosage/overuse may lead to hypokalemia, hypocalcemia and hypomagnesemia. adverse effects Large doses may cause constipation (fecal impactions have been re-ported rarely), anorexia, vomiting or nausea. Dose related hypocal-cemia, hypokalemia and sodium retention have also been noted. T o hasten the drug's action and prevent constipation, SPS is generally mixed with 70% sorbitol (3-4 m L per one gram of resin) when dosed orally. Reproductive/nursing Safety While reproductive studies have apparently not been performed, it is unlikely the drug carries much teratogenic potential. In hu-mans, the FDA categorizes this drug as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) As SPS is not absorbed, it should be safe to use during nursing. overdosage/acute t oxicity Overdosage may cause the adverse effects noted (above); treat symptomatically. Drug interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving SPS and may be of sig-nificance in veterinary patients: antaci DS,T! Laxati Ve S (calcium-or magnesium-containing ): SPS may bind with magnesium or calcium found in laxatives (milk of magnesia, magnesium sulfate, etc. ) or antacids which can prevent bicarbonate ion neutralization and lead to metabolic alkalosis. Concurrent use is not recommended during SPS therapy. Doses If dosed orally, to hasten the drug's action and to prevent constipa-tion SPS is generally mixed with 70% sorbitol (3-4 m L per one gram of resin); shake well before using. Do GS:T! a) For hyperkalemia: 2 grams of resin/kg of body weight (each gram should be suspended in 3-4 m L of water; or use com-mercially prepared suspension products) divided into 3 daily doses. If given orally, give with a cathartic. Do not use a ca-thartic if using as a retention enema as it must be in the colon for at least 30 minutes. T o prepare a retention enema from the powder: add 15 grams per 100 m L of a 1% methylcel-lulose solution or 10% dextrose. If hyperkalemia is severe: 3-4 times the normal amount of resin may be given. (Wil-lard 1986) b) For mild hyperkalemia (<6 m Eq/L): 2 grams/kg PO in 3-4 divided doses with 20% sorbitol; may also be give as an en-ema without sorbitol. (Cowgill and Francey 2005) Ho RSe S:T! a) For life-threatening hyperkalemia in neonatal foals: 15 grams of resin in 100 m L of 10% dextrose via enema. Monitor se-rum potassium and sodium closely. (Madigan 2002b) monitoring Serum electrolytes (sodium potassium (at least once a day), cal-T! cium, magnesium Acid/base status, ECG, if warranted T! chemistry/Synonyms A sulfonated cation exchange resin, sodium polystyrene sulfonate (SPS) occurs as a golden brown, fine powder. It is odorless and tasteless. Each gram contains 4. 1 m Eq of sodium and has an in vitro exchange capacity of about 3. 1 m Eq of potassium (in actuality a maximum of 1 m Eq is usually exchanged). Sodium Polystyrene Sulfonate may also be known as: natrii poly-styrenesulfonas, sodium polystyrene sulphonate, Elutit-Natrium®, K-Exit®, Kayexalate®, Kexelate®, Kionex®, Resinsodio®, Resonium®, Resonium A®, or SPS®. Storage/Stability Store products in well-closed containers at room temperature; do not heat. Suspensions made from powder should be freshly pre-pared and used within 24 hours.	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
826 So Dium Stibo GLuconate Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: None Human-Labe Le D PRo Duct S: Sodium Polystyrene Sulfonate Powder: Sodium content is approxi-mately 100 mg (4. 1 m Eq) per g; in 1 lb. jars & 454 g; Kayexalate® (Sanofi Winthrop); Kionex® (Paddock); (Rx) Sodium Polystyrene Sulfonate Suspension: 15 g/60 m L (sodium 1. 5 g, 65 m Eq) in 60 m L, 120 m L, 200 m L, 480 m L, 500 m L and UD 60 m L; SPS® (Carolina Medical Products Co); generic; (Roxane); (Rx) Sodiu M Stibogluconate Sodiu M anti Mony gluconate (sti-boe-gloo-koe-nate; an-ti-moe-nee gloo-koe-nate) Pentostam® antilei Shmanial Prescriber Highlights Antimony compound for treatment of leishmaniasis in T T humans & dogs Not commercially available in USA (CDC distributes)T T Contraindicated in renal failure, pre-existing arrhythmias T T Many potential adverse effects, including some very T T serious uses/indications Sodium stibogluconate is used for the treatment of leishmaniasis in dogs. Pharmacology/actions Sodium stibogluconate's exact mode of action is unknown. It is believed that it may reduce ATP and GTP synthesis in susceptible amistigotes. Pharmacokinetics In dogs, stibogluconate's volume of distribution (steady-state) was 0. 25 L/kg, clearance 1. 71 L/kg/hr, and terminal half-life ranged from 0. 6-1. 5 hours. The main route of excretion is via the kidneys; glomerular filtration rate determines excretion rate. contraindications/Precautions/Warnings Stibogluconate is contraindicated in patients with pre-existing car-diac arrhythmias, or significantly impaired renal function. It should not be used in those that have had a serious adverse reaction to a previous dose. adverse effects Dogs given 40 mg/kg of stibogluconate developed increased AST levels. Other reported adverse effects (incidence unknown) include pain on injection, musculoskeletal pain, hemolytic anemia, leuko-penia, vomiting, diarrhea, pancreatitis, myocardial injury and ar-rhythmias, renal toxicity, shock and sudden death. Intravenous ad-ministration can cause thrombophlebitis. Reportedly, the incidence of adverse effects increases if the drug is administered for longer than 2 months. Reproductive/nursing Safety Sodium stibogluconate has not been shown to cause fetal harm, but the manufacturer states that the drug should be withheld during pregnancy unless the benefits outweigh the risks. The use of this drug during nursing is controversial. Some (e. g., The American Academy of Pediatrics) say that it is usually compat-ible with breast-feeding, but the manufacturer states that it should not be used in nursing mothers. overdosage/acute t oxicity In the unlikely event of a parenterally administered overdose, it is suggested to contact an animal poison control center. Potentially, antimony can be chelated with dimercaptosuccinic acid (DMSA) or d-penicillamine. Drug interactions No specific drug interactions were noted. Stibogluconate has re-portedly been used with allopurinol, paromomycin, or pentami-dine without problems. Laboratory considerations No specific laboratory interactions or considerations noted. Doses Do GS:T! a) For treatment of cutaneous leishmaniasis: 30-50 mg/kg IV or SC daily for 3-4 weeks (Anon 2004), (Brosey 2005) monitoring Laboratory and clinical signs associated with adverse effects T! (CBC, liver enzymes, renal function tests, ECG, etc. ) Bone marrow cultures for Leishmania T! Clinical efficacy T! client information Clients should understand the potential public health implica-T! tions of this disease (dependent on country) in dogs, the guarded prognosis (even with treatment), risks of treatment and associ-ated expenses. chemistry/Synonyms Sodium stibogluconate is a pentavalent antimony compound that contains between 30-34% antimony and is a colorless, odorless or almost odorless, amorphous powder. Sodium stibogluconate is very soluble in water and practically insoluble in alcohol or ether. The commercially available (not in the USA) injection has a p H between 5-5. 6. Sodium stibogluconate may also be known as: sodium anti-mony gluconate, stiboglucat-natrium, natriumstibogluconat-9-wasser, solusurmin, stibogluconat, sodio stibogluconato, and natrii stibogluconas. Storage/Stability The commercially available injection (Pentostam®) should be stored at temperatures below 25°C (76°F) and protected from freezing and exposure to light. After removing the first dose, the vial should not be used after one month. Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: None Human-Labe Le D PRo Duct S: None in the USA. Sodium Stibogluconate (sodium antimony gluconate) 100 mg (of antimony)/m L for injection in 6 m L and 100 m L (Pentostam®—Wellcome Foundation) is available from the Centers for Disease Con-trol (CDC). It may or may not be released for use in domestic ani-	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
So Dium Su LF ate/t Hio Su LF ate 827 mals. Contact the CDC at 404-639-3670 from 8 AM-4:30 PM Eastern Time, Monday-Friday for more information or go to their website: www. cdc. gov/ncidod/srp/drugs/drug-service. html Pentostam® is available commercially in several countries. Sodiu M Sulfate glauber'S Salt (soe-dee-um sul-fayte; glow-bers salt) Saline cathartic Prescriber Highlights Used primarily in food animals T T Contraindications: Dehydration T T Caution in patients with severe CHF or in patients other-T T wise susceptible to sodium retention Adverse Effects: Diarrhea, cramping, & flatulence may T T result; electrolyte abnormalities may occur with chronic use uses/indications Sodium sulfate is used as a saline cathartic, primarily in food animals. Pharmacology/actions When given orally, sodium sulfate acts as a saline cathartic (draws water into small intestine). Sodium sulfate is considered the most effective saline cathartic on a molar basis. Sulfates also react with a variety of cations to form non-absorbable compounds, which may explain their efficacy in reducing copper loads and reduce gut calcium. Pharmacokinetics Sodium sulfate is not appreciably absorbed from the GI tract and thereby acts a saline cathartic. Sodium may be absorbed however, after exchanging with other cations. contraindications/Precautions/Warnings Saline cathartics should not be used in dehydrated animals. Because of the drug's high sodium content, it should be used with caution in patients with severe CHF or otherwise susceptible to sodium retention. adverse effects Diarrhea, cramping, and flatulence may result. Electrolyte abnor-malities may occur with chronic use. Drug interactions/Laboratory considerations No specific drug or laboratory interactions or considerations were noted. Doses note : When used in food animals, FARAD states that this salt is rapid-ly excreted and is not considered a residue concern in animal tissues; therefore, a 24 hour preslaughter withdrawal interval (WDI) would be sufficient. (Haskell, Payne et al. 2005) catt Le:T! a) As a cathartic: 500-750 g PO as a 6% solution via stomach tube (Davis 1993)SHee P & Goat S:T! a) As a cathartic: 60 g PO as a 6% solution via stomach tube (Davis 1993) SWine:T! a) As a cathartic: 30-60 g PO as a 6% solution via stomach tube (Davis 1993) chemistry/Synonyms Sodium sulfate (hexahydrate form) occurs as large, colorless, odor-less, crystals or white crystalline powder. It will effloresce in dry air and partially dissolve in its own water of crystallization at about 33°C. 1 gram is soluble in about 2. 5 m L of water. Sodium sulfate may also be known as E514, Glauber's Salt, natrii sulphas, natrio sulfata, or natrium sulfuricum. Storage/Stability Store in tight containers at temperatures not exceeding 30°C. Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: None Human-Labe Le D PRo Duct S: None Sodium sulfate (hexahydrate) is available from chemical supply houses. Sodiu M t Hio Sulfate (soe-dee-um thye-oh-sul-fayte) Sodium Hyposulfite antidote (ar Senic, cyanide) Prescriber Highlights Used for cyanide or arsenic poisoning T T Contraindications: None T T Adverse Effects: Large doses by mouth may cause pro-T T fuse diarrhea Injectable forms should be given slowly IVT T uses/indications Sodium thiosulfate (alone or in combination with sodium nitrite) is useful in the treatment of cyanide toxicity. It has been touted for use in treating arsenic or other heavy metal poisonings, but its ef-ficacy is in question for these purposes. However, because sodium thiosulfate is relatively non-toxic and inexpensive, it may be tried to treat arsenic poisoning. When used in combination with sodium molybdate, sodium thiosulfate may be useful for the treatment of copper poisoning. Sodium thiosulfate may be useful for the topical treatment for some fungal infections (Tinea). In humans, sodium thiosulfate has been used to reduce the nephrotoxicity of cisplatin therapy. A 3 or 4% solution has been used to infiltrate the site of extravasations of cisplatin, carboplatin, or dactinomycin. In combination with ste-roids, sodium thiosulfate may reduce the healing time associated with doxorubicin extravasation. Pharmacology/actions By administering thiosulfate, an exogenous source of sulfur is avail-able to the body, thereby hastening the detoxification of cyanide using the enzyme rhodanese. Rhodanese (thiosulfate cyanide sul-furtransferase) converts cyanide to the relatively nontoxic thiocya-nate ion; thiocyanate is then excreted in the urine.	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
828 Somatot Ro Pin Sodium thiosulfate has been used in humans to treat extravasa-tion injuries secondary to carboplatin or cisplatin, for prophylaxis to prevent nephrotoxicity after cisplatin overdoses and ototoxicity with carboplatin overdoses. Sodium thiosulfate's topical antifungal activity is probably due to its slow release of colloidal sulfur. While sodium thiosulfate has been recommended for treating arsenic (and some other heavy metal) poisoning, the proposed mechanism of action is not known and its efficacy is in question. Presumably, the sulfate moiety may react with and chelate the metal allowing its removal. Pharmacokinetics Sodium thiosulfate is relatively poorly absorbed from the GI tract. When substantial doses are given PO, it acts a saline cathartic. When administered intravenously, it is distributed in the extracel-lular fluid and then rapidly excreted via the urine. contraindications/Precautions/Warnings There are no absolute contraindications to the use of the drug. adverse effects The drug is relatively non-toxic. Large doses by mouth may cause profuse diarrhea. Injectable forms should be given slowly IV. Reproductive/nursing Safety Safe use during pregnancy has not been established; use when ben-efits outweigh the potential risks. In humans, the FDA categorizes this drug as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) No lactation information was found. Drug interactions/Laboratory considerations No specific drug or laboratory interactions or considerations were noted. Doses Do GS, cat S:T! a) For cyanide toxicity: Contact an animal poison control cen-ter for guidance. b) For treating extravasation injuries secondary to doxorubicin, carboplatin, cisplatin infusions: note : These are recommen-dations for human patients. Doxorubicin: Subcutaneous sodium thiosulfate 2% added to therapy with subcutaneous hydrocortisone and topical be-tamethasone decreased the healing time by half for cytotoxic drug extravasation (including doxorubicin and epirubicin) when compared to therapy without sodium thiosulfate. Carboplatin: Prepare a 0. 17 moles/L solution by mixing 4 m L sodium thiosulfate 10% w/v with 6 m L sterile water for injec-tion. Inject 5 m L into extravasation site. Cisplatin: For extravasation of large amounts (greater than 20 m L) of highly concentrated (greater than 0. 5 mg/m L) solutions: Prepare a 0. 17 moles/L solution by mixing 4 m L sodium thiosulfate 10% w/v with 6 m L sterile water for in-jection. Inject into extravasation site. (DRUGDEX® Evalua-tions. Micromedex Healthcare Series; Thompson, 2007) Ho RSe S:T! a) For cyanide toxicity: First give sodium nitrite at a dose of 16 mg/kg IV followed with a 20% solution of sodium thiosulfate given at a dose of 30-40 mg/kg IV. If repeating treatment, use sodium thiosulfate only. (Bailey and Garland 1992)b) For cyanide toxicity: First give sodium nitrite in a 20% solu-tion at a dose of 10-20 mg/kg IV followed with a 20% solu-tion of sodium thiosulfate given at a dose of 30-40 mg/kg IV (Osweiler 2003) c) For arsenic toxicity: Sodium thiosulfate at 20-30 grams in 300 m L of water orally with dimercaprol (BAL) 3 mg/kg IM q4h (Jones 2004c) Ruminant S: T! note : When used in food animals, FARAD states that this salt is rapidly excreted and is not considered a residue concern in animal tissues; therefore, a 24 hour preslaughter withdrawal in-terval (WDI) would be sufficient. (Haskell, Payne et al. 2005) a) In combination with sodium molybdate for the treatment of copper poisoning: In conjunction with fluid replacement therapy, 500 mg sodium thiosulfate in combination with 200 mg ammonium or sodium molybdate PO daily for up to 3 weeks will help decrease total body burden of copper (Thompson and Buck 1993) b) For treatment of cyanide toxicity secondary to cyanogenic plants: 660 mg/kg IV sodium thiosulfate in a 30% solution given rapidly using a 12 or 14 gauge needle (Nicholson 1993), (Post and Keller 2000) c) For treatment of arsenic poisoning: 30-60 grams PO every 6 hours for 3-4 days and 30-60 grams as a 10-20% solution IV may be potentially useful in binding arsenic. Adjunctive fluid and electrolyte replacement is necessary. (Galey 1993) chemistry/Synonyms Sodium thiosulfate occurs as large, colorless crystals or coarse, crys-talline powder. It is very soluble in water, deliquescent in moist air and effloresces in dry air at temperatures >33°C. Sodium thiosulfate may also be known as: natrii thiosulfas, na-trium thiosulfuricum, sodium hyposulphite, sodium thiosulphate, Consept Step 2®, Hiposul®, Hyposulfene®, or S-hydril®. Storage/Stability/compatibility Unless otherwise stated by the manufacturer, store at room tem-perature. Crystals should be stored in tight containers. Sodium thiosulfate is not compatible mixed with cyanocobalamin. Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: None Human-Labe Le D PRo Duct S: Sodium Thiosulfate for Injection: 10% (100 mg/m L, as pentahydrate) & 25% (250 mg/m L) preservative-free in 10 m L & 50 m L single-use vials; generic, (American Regent); (Rx) So Matotropin (gro Wt H Hor Mone) (soe-ma-toe-troe-pin) hormone Prescriber Highlights Used for canine hypopituitary dwarfism or growth hor-T T mone-responsive dermatosis (in adult dogs). May cause diabetes mellitus T T Availability & expense issues T T	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
Sota Lo L Hc L 829 uses/indications Somatotropin may be useful in treating hypopituitary dwarfism or growth hormone-responsive dermatosis (in adult dogs). Pharmacology/actions Growth hormone (somatotropin) is responsible for, or contributes to, linear and skeletal growth, organ growth, and cell growth. It also is a factor in protein, carbohydrate, lipid, connective tissue, and mineral metabolism. Pharmacokinetics No canine information was located. Both the liver and kidney are major elimination organs for somatotropin. contraindications/Precautions/Warnings Growth hormone derived from other species is contraindicated in patients hypersensitive to it. adverse effects Growth hormone may cause diabetes mellitus in dogs. This may be transient or permanent even after discontinuing treatment. Blood and urine glucose should be routinely monitored. If blood glucose exceeds 150 mg/dl, therapy should be stopped. Hypersensitivity reactions are possible, but less so if using porcine origin prod-uct. Long-term treatment at high doses may cause acromegaly. Acromegaly in dogs can cause increased size of paws and head, in-creased skin folds around head and neck area, prognathism, and inspiratory stridor. Reproductive/nursing Safety In humans, the FDA categorizes this drug as category C for use dur-ing pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) overdosage/acute t oxicity Acute overdosage could cause hypoglycemia initially and then hy-perglycemia. Blood glucose should be monitored and supportive treatment (glucose/insulin) performed. Drug interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving somatotropin and may be of significance in veterinary patients: GLucoco R ticoi DS T! : May inhibit the growth promoting effect of so-matotropin. When concurrent adrenal insufficiency is diagnosed, adjust glucocorticoid dose carefully to avoid negative effects on growth. Doses Do GS:T! a) For treatment of hypopituitary dwarfism: 0. 1 IU (0. 05 mg)/kg SC three times per week for 4-6 weeks. note : May also re-quire life-long thyroid hormone supplementation and if sec-ondary adrenal insufficiency present, glucocorticoid treat-ment. If after successful treatment, dermatologic signs recur, may dose as above (0. 1 IU/kg three times weekly for one week). Repeat these weekly regimens at intervals determined by the time lapse between treatments and relapse. (Feldman and Nelson 1996) b) For treatment of growth hormone-responsive dermatosis in adult dogs: Dose as above (a), but thyroid and steroid supple-mentation not required (Feldman and Nelson 1996) c) For Alopecia X: 0. 15 IU/kg of porcine growth hormone SC 2 times weekly for 6 weeks. (Hillier 2006a)monitoring Clinical efficacy T! Blood glucose (weekly)T! Urine glucose (daily)T! Thyroid function, adrenal function initially and then periodically T! (pituitary dwarfism pts. ) client information Clients should be instructed on the methods for SC injection and T! testing urine glucose May be expensive to treat and diabetes (permanent) can occur T! Synonyms Somatotropin may also be known as: CB-311, HGH, human growth hormone, LY-137998, somatropinum; many trade names are available. Dosage Forms/Regulatory Status There are several manufacturers of human recombinant DNA origin somatotropin products, but these are expensive, can cause immuno-genicity reactions in dogs, and not sold for veterinary use. The bovine recombinant growth hormone product (Posilac®— Monsanto) is not suitable for canine use as it is a sustained release formulation and not easily diluted down to the smaller doses re-quired for dogs. Porcine growth hormone appears to have little immunogenicity in dogs and reportedly can be obtained via: Dr A. F. Partlow at: 310-222-3537 E-Mail: Partlow@HUMC. edu WEBSITE: www. humc. edu/hormones The ARCI (Racing Commissioners International) has designated this drug as a class 2 substance. See the appendix for more information. Sotalol Hcl (soh-ta-lole) Betapace® beta-adrenergic blocker Prescriber Highlights Non-selective beta blocker/Class III antiarrhythmic for T T ventricular tachycardia Adverse Effects: Most serious: negative inotropism & T T pro-arrhythmic but dyspnea/bronchospasm, fatigue/dizzi-ness, & nausea/vomiting possible Treatment is relatively expensive T T uses/indications Sotalol may be useful in the treatment of ventricular tachycardias and, possibly, supraventricular tachycardias in dogs. Pharmacology/actions Sotalol is a non-selective beta-blocker and Class III antiarrhythmic agent. The beta blocking activity of sotalol is about 30% that of propranolol. Its primary usage in veterinary medicine is associated with its antiarrhythmic activity. Like other Class III drugs, it pro-longs repolarization and refractoriness without affecting conduc-tion. The pharmacologic action is believed caused by selectively inhibiting potassium channels.	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
830 Sota Lo L Hc L Pharmacokinetics Unlike propranolol, sotalol does not have any appreciable first pass effect after oral administration. Food may reduce the bioavailability of sotalol by approximately 20% (human data) and, if given on an empty stomach, bioavailability is 90-100%. The drug has relatively low lipid solubility and virtually no protein binding. Elimination is almost all via the kidney and most of the drug is excreted un-changed. In dogs, sotalol's elimination half-life is 5 hours; in hu-mans about 12 hours. contraindications/Precautions/Warnings Sotalol is considered contraindicated in patients with asthma, si-nus bradycardia, 2nd or 3rd degree heart block (unless artificially paced), long Q-T syndromes, cardiogenic shock or uncontrolled CHF. Because of the potential for negative inotropic effects, use with caution in CHF. Also, use with caution in patients with diabe-tes mellitus, or hyperthyroidism (may mask signs). Use with cau-tion in patients with renal dysfunction; dosage intervals may need to be extended. adverse effects Primary concerns with sotalol in dogs are the potential for negative inotropic and proarrhythmic effects. These generally are not clini-cally important if dosage is not excessive. Other potential adverse effects include dyspnea/bronchospasm, fatigue/dizziness, and nau-sea/vomiting. Reproductive/nursing Safety Sotalol did not cause any fetotoxicity or teratogenicity when given to pregnant lab animals at high dosages, but clear safety in preg-nancy has not been established. Sotalol enters maternal milk in concentrations up to 5X found in the serum; consider using milk replacer in nursing animals. In humans, the FDA categorizes this drug as category B for use during pregnancy (Animal studies have not yet demonstrated risk to the fetus, but there are no adequate studies in pregnant women; or animal studies have shown an adverse effect, but adequate studies in pregnant women have not demonstrated a risk to the fetus in the first trimester of pregnancy, and there is no evidence of risk in later trimesters. ) Sotalol is excreted in milk; use with caution in nursing patients. It is not recommended for use in nursing humans. overdosage/acute t oxicity Overdoses may result in bradycardia, hypotension, CHF, broncho-spasm, and hypoglycemia. Use gut evacuation (if not contraindi-cated) when significant risk of morbidity is possible. Treat adverse effects symptomatically and supportively. Drug interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving sotalol and may be of significance in veterinary patients: amio Da Rone T! : May prolong refractory periods; concurrent use not recommended in human patients ane St Hetic S, Gene Ra LT! : Additive myocardial depression may oc-cur with the concurrent use of sotalol and myocardial depressant anesthetic agents antaci DST! : May reduce oral sotalol absorption; separate doses by at least 2 hours antia RRHyt Hmic S, c La SS ia T! (quinidine, procainamide, disopyramide ): May prolong refractory periods; concurrent use not recommend-ed in human patients; may also prolong QT intervalantia RRHyt Hmic S, c La SS ib, 1c T! (lidocaine, mexiletine, phenytoin, fle-cainide etc. ): May prolong QT interval ca Lcium c Hanne L b Locke RS T! (verapamil, diltiazem, etc. ): Potential to increase hypotensive effects; may have additive effects on A V conduction or ventricular function; use with caution, particu-larly in patients with preexisting cardiomyopathy or CHF ci Sa PRi De T! : May prolong QT interval c Loni Dine T! : If clonidine is discontinued after concomitant therapy with sotalol, there is an increased risk for rebound hypertension Di Goxin T! : Potential for increased risks for proarrhythmic events e Ryt HRomycin; c La Rit HRomycin T! : May prolong QT interval Li Docaine T! : Clearance may be impaired by sotalol PHenot Hiazine ST! : May prolong QT interval Re Se RPine T! : May have additive effects (hypotension, bradycardia) with sotalol Sym P at Homimetic S, beta 2 a Goni St S T! (e. g., metaproterenol, terbuta-line, albuterol ): May have their actions blocked by sotalol t Ricyc Lic anti De PRe SSant ST! : May prolong QT interval Laboratory considerations Beta-blockers may produce hypoglycemia and interfere with T! glu-cose or insulin tolerance tests Sotalol may falsely elevate urine T! metanephrine levels (pheochro-mocytoma screen) if using a fluorometric or photometric assay Doses Do GS:T! a) 1-2 mg/kg PO q12h (Fox 2003a), (Moise 2002) b) 2- 3 mg/kg PO q12h (Meurs 2002) c) For ventricular tachycardia: 1-2 mg/kg PO twice daily (At-kins 2007a) d) For ventricular tachycardias, supraventricular tachycardias: 1-2 mg/kg PO q12h (Smith 2007) e) For ventricular tachyarrhythmias in Boxers in combination with mexiletine: Sotalol 1. 5-3 mg/kg PO twice daily with mexiletine (5-7. 5 mg/kg PO three times daily). (Prosek, Es-trada et al. 2006) cat S:T! a) 2 mg/kg PO twice daily (Atkins 2003b) monitoring Efficacy (ECG)T! Adverse effects T! client information Relatively limited clinical experience; but appears safe T! Must be given as prescribed; do not stop drug suddenly or alter T! dosing without veterinarian guidance Report adverse effects to veterinarian immediately T! chemistry/Synonyms A non-selective beta-blocker and Class III antiarrhythmic agent, so-talol HCl is a racemic mixture of the d-and l-forms. Both isomers exhibit antiarrhythmic (Class II) activity, but only the Levo-form has beta blocking activity. Sotalol HCl occurs as white, crystalline solid that is soluble in water. Sotalol may also be known as: MJ-1999, d,l-sotalol hydrochlo-ride, or sotaloli hydrochloridum; many trade names are available. Storage/Stability Store tablets at room temperature.	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
SPectinomycin 831 Dosage Forms/approval Vete Rina R y-Labe Le D PRo Duct S: None The ARCI (Racing Commissioners International) has designated this drug as a class 3 substance. See the appendix for more information. Human-Labe Le D PRo Duct S: Sotalol HCl Tablets: 80 mg, 120 mg, 160 mg & 240 mg; Betapace® & Betapace® AF (Berlex); generic; (Rx) Spectino Mycin Hcl Spectino Mycin Sulfate (spek-ti-noe-mye-sin) Adspec®, Spectam® aminocyclitol antibiotic Prescriber Highlights Aminocyclitol antibiotic used primarily in food producing T T animals; relatively broad spectrum but minimal activity against anaerobes & most strains of Pseudomonas Contraindications: Hypersensitive to it T T Adverse Effects: Appears to have minimal adverse ef-T T fects at labeled dosages; probably less nephrotoxicity/ ototoxicity than other aminocyclitols. Can cause neuro-muscular blockade. May cause swelling at SC injection sites. uses/indications Although occasionally used in dogs, cats, and horses for susceptible infections, Spectinomycin only has approved dosage forms for cat-tle, chickens, turkeys, and swine. Refer to the Dosage section below for more information on approved uses. Pharmacology/actions Spectinomycin is primarily a bacteriostatic antibiotic that inhibits protein synthesis in susceptible bacteria by binding to the 30S ribo-somal subunit. Spectinomycin has activity against a wide variety of gram-positive and gram-negative bacteria, including E. coli, Klebsiella, Proteus, Enterobacter, Salmonella, Streptococci, Staphylococcus, and Mycoplasma. It has minimal activity against anaerobes, most strains of Pseudomonas, Chlamydia, or Treponema. In human medicine, spectinomycin is used principally for its ac-tivity against Neisseria gonorrhoeae. Pharmacokinetics After oral administration only about 7% of the dose is absorbed, but the drug that remains in the GI tract is active. When injected SC or IM, the drug is reportedly absorbed well with peak levels oc-curring in about 1 hour. Tissue levels of absorbed drug are lower than those found in the serum. Spectinomycin does not appreciably enter the CSF or the eye and is not bound significantly to plasma proteins. It is unknown whether spectinomycin crosses the placenta or enters milk. Absorbed drug is excreted via glomerular filtration into the urine mostly unchanged. In cattle, terminal half-life is about 2 hours. contraindications/Precautions/Warnings Spectinomycin is contraindicated in patients hypersensitive to it. adverse effects When used as labeled, adverse effects are unlikely with this drug. It is reported that parenteral use of this drug is much safer than with other aminocyclitol antibiotics, but little is known regarding its prolonged use. It is probably safe to say that spectinomycin is significantly less ototoxic and nephrotoxic than other commonly used aminocyclitol antibiotics, but can cause neuromuscular block-ade. Parenteral calcium administration will generally reverse the blockade. Adverse effects that have been reported in human patients re-ceiving the drug in single or multidose studies include soreness at injection site, increases in BUN, alkaline phosphatase and SGPT, and decreases in hemoglobin, hematocrit, and creatinine clearance. Although increases in BUN and decreases in creatinine clearance and urine output have been noted, overt renal toxicity has not been demonstrated with this drug. Cattle receiving the sulfate form subcutaneously have developed swelling at the injection site. Reproductive/nursing Safety In humans, the FDA categorizes this drug as category B for use dur-ing pregnancy (Animal studies have not yet demonstrated risk to the fetus, but there are no adequate studies in pregnant women; or animal studies have shown an adverse effect, but adequate studies in pregnant women have not demonstrated a risk to the fetus in the first trimester of pregnancy, and there is no evidence of risk in later trimesters. ) It is not known whether spectinomycin is excreted in milk; use caution when administering to nursing patients. overdosage/acute t oxicity No specific information was located on oral overdoses, but because the drug is negligibly absorbed after oral administration, significant toxicity is unlikely via this route. Injected doses of 90 mg produced transient ataxia in turkey poults. Drug interactions Antagonism has been reported when spectinomycin is used with T! chloramphenicol or tetracycline. Doses Do GS:T! For susceptible infections:a) 5. 5-11 mg/kg q12h IM or 22 mg/kg PO q12h (for enteric infections; not absorbed) (Kirk 1989) b) 5-10 mg/kg IM q12h (Davis 1985) c) For acute infectious gastroenteritis: 5-12 mg/kg IM q12h (De Novo 1986) cat S:T! For susceptible infections: a) For acute infectious gastroenteritis: 5-12 mg/kg IM q12h (De Novo 1986) catt Le:T! For susceptible infections:a) For bronchopneumonia and fibrinous pneumonia: 33 mg/kg SC q8h. Suggested withdrawal time is 60 days. (Hjerpe 1986) b) 22-39. 6 mg/kg/day IM divided three times daily (Upson 1988) c) For bovine respiratory disease: 10-15 mg/kg SC (in the neck; not more than 50 m L per site) once daily (q24h) for 3-5 consecutive days (Label directions; Adspec®)	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
832 SPi Rono Lactone Ho RSe S:T! For susceptible infections: a) 20 mg/kg, IM three times daily (Robinson 1987) b) For pneumonia: 20 mg/kg IM q8h; may cause local myositis. Insufficient data to comment on use. (Beech 1987b) SWine:T! For susceptible enteric infections:a) 10 mg/kg, PO q12h (Howard 1986) b) For bacterial enteritis (white scours) in baby pigs associated with E. coli susceptible to spectinomycin: 50 mg/10 lbs of body weight PO twice daily for 3-5 days (Label directions; Spectam Scour-Halt®—Ceva) c) 10 mg/kg, IM q12h (Baggot 1983) bi RDS:T! a) For airsacculitis associated with M. meleagridis or chronic re-spiratory disease associated with E. coli in turkey poults (1-3 days old): Inject 0. 1 m L (10 mg) SC in the base of the neck. For control and to lessen mortality due to infections from M. synoviae, S. typhimurium, S. infantis, and E. coli in newly hatched chicks: Dilute injection with normal saline to a con-centration of 2. 5-5 mg/0. 2 m L and inject SC. (Label direc-tions; Spectam® Injectable—Ceva) b) For prevention and control of chronic respiratory disease as-sociated with Mycoplasma gallisepticum in broilers: Add suf-ficient amount to drinking water to attain a final concentra-tion of 2 g/gallon. For infectious synovitis associated with Mycoplasma synoviae in broilers: Add sufficient amount to drinking water to attain a final concentration of 1 g/gallon. For improved weight gain/feed efficiency in floor-raised broilers: Add sufficient amount to drinking water to attain a final concentration of 0. 5 g/gallon. (Label directions; Spec-tam® Water-Soluble—Ceva) monitoring Clinical efficacy T! chemistry/Synonyms An aminocyclitol antibiotic obtained from Streptomyces spectabilis, spectinomycin is available as the dihydrochloride pentahydrate and hexahydrate sulfate salts. It occurs as a white to pale buff, crystal-line powder with p K as of 7 and 8. 7. It is freely soluble in water and practically insoluble in alcohol. Spectinomycin may also be known as: M-141, actinospectacin, spectinomycini, U-18409AE, Adspec®, Amtech Spectam®, Kempi®, Kirin®, Spectoguard Scour-Chek®, Stanilo®, Togamycin®, Trobicin®, Trobicine®, or Vabicin®. Storage/Stability Unless otherwise instructed by the manufacturer, spectinomycin products should be stored at room temperature (15-30°C). Protect from freezing. Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: Spectinomycin Sulfate Injection: 100 mg/m L in 500 m L vials; Ad-spec®; (Pharmacia & Upjohn); (Rx). When used as labeled, slaughter withdrawal in cattle = 11 days; not to be used in veal calves or in dairy cattle 20 months of age or older. Spectinomycin Injection: 100 mg/m L in 500 m L vials; Amtech Spec-tam® Injectable (IVX); (OTC). Approved for use in 1-3 days old tur-key poults and newly hatched chicks. Spectinomycin Water Soluble Concentrate: 0. 5 g of spectinomycin per gram Spectam® Water Soluble (Bimeda); (OTC). Approved for use in chickens (not layers). Slaughter withdrawal (at labeled doses) = 5 days. Spectinomycin Oral Solution: 50 mg/m L in 240 m L pump bottle and 500 and 1000 m L without pump; Amtech Spectam Scour-Halt®, (IVX), Spectoguard Scour-Chek® (Bimeda), Spectam Scour-Halt®, (Agri Pharm); (OTC). Approved for use in swine (Weighing less than 15 lbs and not older than 4 weeks of age). Slaughter withdrawal (at labeled doses) = 21 days. Spectinomycin/Lincomycin in a 2:1 ratio LS 50 Water Soluble Powder® (Pharmacia & Upjohn); Sepclinx-50® (Bimeda); generic (IVX, Agri Labs); in 2. 65 oz packets. Each packet contains lincomycin 16. 7 g and spectinomycin 33. 3 g. Approved for use in chickens up to 7 days of age. Lincomycin 50 mg/Spectinomycin 100 mg per m L in 20 m L vials; Linco-Spectin® Sterile Solution (Pharmacia & Upjohn); (OTC). Ap-proved for use in semen extenders only. Human-Labe Le D PRo Duct S: Spectinomycin Powder for Injection: 400 mg (as the HCl) per m L after reconstitution in 2 g vial with 3. 2 m L diluent; Trobicin® (Up-john); (Rx) Spironolactone (speer-on-oh-lak-tone) Aldactone® aldo Sterone antagoni St Prescriber Highlights Aldosterone antagonist used as a potassium sparing di-T T uretic or for adjunctive treatment for heart failure (use is somewhat controversial for CHF in dogs); should not be substituted for furosemide in CHF Contraindications: Hyperkalemia, Addison's disease, anu-T T ria, acute renal failure or significant renal impairment Caution: Any renal impairment or hepatic disease T T Adverse Effects: Hyperkalemia, hyponatremia, & dehy-T T dration; increased BUN & mild acidosis in patients with renal impairment. GI distress (vomiting, anorexia, etc. ), CNS effects (lethargy, ataxia, headache, etc. ), & endo-crine changes possible uses/indications Spironolactone may be used in patients with congestive heart failure who do not adequately respond to furosemide and ACE inhibitors, who develop hypokalemia on other diuretics, and are unwilling or unable to supplement with exogenous potassium sources. It may also be effective in treating ascites as it has less potential to increase ammonia levels than other diuretics. Pharmacology/actions Aldosterone is competitively inhibited by spironolactone in the dis-tal renal tubules with resultant increased excretion of sodium, chlo-ride, and water, and decreased excretion of potassium, ammonium, phosphate, and titratable acid. Spironolactone has no effect on car-bonic anhydrase or renal transport mechanisms and has its great-est effect in patients with hyperaldosteronism. When used alone in	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
SPi Rono Lactone 833 healthy dogs, spironolactone does not appear to cause significant diuresis (Jeunesse, Wohrle et al. 2004). Spironolactone is not commonly used alone as most sodium is reabsorbed at the proximal tubules. Combining it with a thiazide or loop diuretic will yield maximum diuretic effect. After cats received 2. 7 mg/kg spironolactone twice daily for 7-9 days, the following serum values increased (on average) significant-ly: potassium 0. 39 m Eq/L, calcium 0. 48 mg/d L, creatinine 0. 22 mg/d L, phosphorus 0. 63 mg/d L and total protein 0. 51 mg/d L. (Abbott and Saker 2006) In humans, spironolactone can have antifibrotic effects on car-diac muscle. Pharmacokinetics No information was found regarding the pharmacokinetics of spironolactone in veterinary species. In humans, spironolactone is >90% bioavailable and peak levels are reached within 1-2 hours. The diuretic action of spironolactone (when used alone) is gradu-ally attained and generally reaches its maximal effect on the third day of therapy. Spironolactone and its active metabolite, canrenone, are both about 98% bound to plasma proteins. Both spironolactone and its metabolites may cross the placenta. Canrenone has been detected in breast milk. Spironolactone is rapidly metabolized (half-life of 1-2 hours) to several metabolites, including canrenone, which has diuretic activity. Canrenone is more slowly eliminated, with an av-erage half-life of around 20 hours. contraindications/Precautions/Warnings Spironolactone is contraindicated in patients with hyperkalemia, Addison's disease, anuria, acute renal failure or significant renal im-pairment. It should be used cautiously in patients with any renal impairment or hepatic disease. adverse effects Adverse effects are usually considered mild and reversible upon dis-continuation of the drug. Electrolyte (hyperkalemia, hyponatremia) and water balance (dehydration) abnormalities are the most likely effects with spironolactone therapy, but electrolytes in dogs do not appear to be significantly affected. Transient increases in BUN and mild acidosis may occur in pa-tients with renal impairment. GI distress (vomiting, anorexia, etc. ), CNS effects (lethargy, ataxia, headache, etc. ), and endocrine chang-es (gynecomastia in human males) are all possible. Use of spironolactone in patients with renal impairment may lead to hyperkalemia. Spironolactone reportedly inhibits the syn-thesis of testosterone and may increase the peripheral conversion of testosterone to estradiol. Long-term toxicity studies in rats have demonstrated that spironolactone is tumorigenic in that species. Reproductive/nursing Safety Spironolactone or its metabolites may cross the placental barrier. Feminization occurs in male rat fetuses. In humans, the FDA cat-egorizes this drug as category D for use during pregnancy (There is evidence of human fetal risk, but the potential benefits from the use of the drug in pregnant women may be acceptable despite its potential risks. ) Canrenone, a metabolite of spironolactone, appears in maternal milk. In humans, the estimated maximum dose to the infant is ap-proximately 0. 2% of the mother's daily dose. Use with caution in nursing patients, but it is unlikely of clinical significance in veteri-nary patients. overdosage/acute t oxicity Information on overdosage of spironolactone is apparently un-available. Should an acute overdose occur, it is suggested to fol-low the guidelines outlined in the chlorothiazide and furosemide monographs. Contact an animal poison control center for further guidance. Drug interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving spironolactone and may be of significance in veterinary patients: Di Goxin T! : Spironolactone may increase the half-life of digoxin; en-hanced monitoring of digoxin serum levels and effects are war-ranted when spironolactone is used with these agents mitotane T! : Spironolactone may mute the effects of mitotane if given concurrently, but very limited information is available on this potential interaction; monitor carefully. neu Romu Scu La R b Locke RS, non-De Po La Rizin G T! : Increase in neuro-muscular blockade effects possible Pota SSium-SP a Rin G Diu Retic S, ot He R T! (e. g., triamterene ): Hyper-kalemia possible Pota SSium Su PPLement ST! : Hyperkalemia possible Sa Licy Late ST! : Spironolactone's diuretic effects may be decreased if aspirin or other salicylates are administered concomitantly Laboratory considerations Spironolactone may give falsely elevated T! digoxin values, if using a radioimmune assay (RIA) method. Fluorometric methods of determining plasma and urinary T! 17-hydroxycorticosteroids (cortisol) may be interfered with by spironolactone. Doses Do GS:T! As a diuretic in CHF: a) When furosemide and ACE inhibitors alone do not control fluid accumulation in refractory CHF: 1-2 mg/kg PO q12h (Ware and Keene 2000) b) With other diuretics when hypokalemia is an issue: 2-4 mg/ kg PO once daily (Kittleson 2000) c) T o allow further reduction of furosemide dose (target dose for furosemide during maintenance phase: 1-2 mg/kg PO q24-48h): Spironolactone dose varies between 0. 5 mg/kg PO once daily (aldosterone blockage, weak diuretic effect) to 2 mg/kg twice daily (stronger diuretic effect). (de Madron 2004) For treating ascites: a) 1-2 mg/kg PO twice daily; if no response in 4-5 days, dou-ble dose for an additional 4-5 days; if no response, may dou-ble again (4-8 mg/kg twice daily). Monitor (weigh) patients daily and do not allow patient to become dehydrated or to lose more than 0. 25-0. 5 kg/day. (Hardy 1985) b) Attempt at treating underlying abnormality. When ascites is caused by right-sided heart failure: Be sure owner is admin-istering medication properly and the prescription is correct. Increase furosemide to 4-6 mg/kg PO q8h (generally speak-ing dose should be increased until all the abnormal accumu-lated fluid is eliminated or unacceptable azotemia develops). Optimize ACE inhibitor dose. Restrict dietary sodium. Add spironolactone at 1-2 mg/kg PO q12h. Initially (3 times weekly) substitute one of the oral furosemide doses with a SC dose. Consider adding hydrochlorothiazide initially at 2 mg/kg PO every other day. (Connolly 2006)	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
834 Stanozo Lo L For adjunctive treatment of hypertension: a) 1-2 mg/kg PO q12h (Stepian 2006b) cat S:T! As a diuretic in CHF:a) When furosemide and ACE inhibitors alone do not control fluid accumulation in refractory CHF: 1-2 mg/kg PO q12h (Ware and Keene 2000) b) 1 mg/kg q12h PO when serum potassium is low (Bonagura 1989) For adjunctive treatment of hypertension: a) 1-2 mg/kg PO q12h (Stepian 2006b) monitoring Serum electrolytes, BUN, creatinine T! Hydration status T! Blood pressure, if indicated T! Clinical signs of edema/ascites; patient weight, if indicated T! client information Notify veterinarian if GI symptoms (T! e. g., vomiting, diarrhea, an-orexia), lethargy, or other CNS effects are severe or persist chemistry/Synonyms A synthetically produced aldosterone antagonist, spironolactone occurs as a cream-colored to light tan, crystalline powder with a faint mercaptan-like odor. It has a melting range of 198°-207°, with decomposition. Spironolactone is practically insoluble in wa-ter and soluble in alcohol. Spironolactone may also be known as: espironolactona, SC-9420, spirolactone, spironolactonum; many trade names are available. Storage/Stability Spironolactone tablets should be stored at room temperature in tight, light-resistant containers. An extemporaneously prepared oral suspension can be prepared by pulverizing commercially avail-able tablets and adding cherry syrup. This preparation is reportedly stable for at least one month when refrigerated. Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: None The ARCI (Racing Commissioners International) has designated this drug as a class 4 substance. See the appendix for more information. Human-Labe Le D PRo Duct S: Spironolactone Tablets: 25 mg, 50 mg & 100 mg; Aldactone® (Searle); generic; (Rx) Also available in combination with hydrochlorothiazide. Stanozolol (stah-no-zo-lahl) Winstrol®-V anabolic Steroid Prescriber Highlights Anabolic steroid; veterinary labeled products no longer T T marketed in USA Contraindications: Pregnant animals, breeding stallions, T T food animals. Extreme Caution: Cats, hepatic dysfunction, hypercalcemia, history of myocardial infarction, pituitary insufficiency, prostate carcinoma, mammary carcinoma, benign prostatic hypertrophy, & during the nephrotic stage of nephritis. Caution: Cardiac & renal dysfunction with enhanced fluid & electrolyte monitoring. Adverse Effects: Potentially high incidence of hepatotox-T T icity in cats. Other possible effects: sodium, calcium, po-tassium, water, chloride, & phosphate retention; hepato-toxicity, behavioral (androgenic) changes, & reproductive abnormalities (oligospermia, estrus suppression) Category “ T T X” for pregnancy; teratogenicity outweighs any possible benefit Controlled substance in the USA T T Drug Interactions; lab interactions T T uses/indications Labeled indications for the previously marketed veterinary sta-nozolol product Winstrol®-V (Winthrop/Upjohn) included “... to improve appetite, promote weight gain, and increase strength and vitality... ” in dogs, cats and horses. The manufacturer also stated that: “Anabolic therapy is intended primarily as an adjunct to other specific and supportive therapy, including nutritional therapy. ” Like nandrolone, stanozolol has been used to treat anemia of chronic disease. Because stanozolol has been demonstrated to en-hance fibrinolysis after parenteral injection, it may be efficacious in the treatment of feline aortic thromboembolism or thrombosis in nephrotic syndrome; however, clinical studies and/or experience are apparently lacking for this indication at present. Pharmacology/actions Stanozolol possesses the actions of other anabolic agents but it may be less androgenic than other anabolics that are used in veterinary medicine. Refer to the discussion in the boldenone monograph for more information. Pharmacokinetics No specific information was located for this agent. It is generally recommended that the injectable suspension be dosed on a weekly basis in both small animals and horses. contraindications/Precautions/Warnings Stanozolol is contraindicated in pregnant animals and in breeding stallions and should not be administered to horses intended for food purposes. Because of reported hepatotoxicity associated with this drug in cats, it should only be used in this species with extreme caution. The manufacturer recommends using stanozolol cautiously in patients with cardiac and renal dysfunction with enhanced fluid and electrolyte monitoring.	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
Stanozo Lo L 835 In humans, anabolic agents are contraindicated in patients with hepatic dysfunction, hypercalcemia, patients with a history of myo-cardial infarction (can cause hypercholesterolemia), pituitary in-sufficiency, prostate carcinoma, benign prostatic hypertrophy, dur-ing the nephrotic stage of nephritis, and in selected patients with breast carcinoma. adverse effects The manufacturer (Winthrop/Upjohn) lists as adverse effects in dogs, cats, and horses only “mild androgenic effects” and then only when used with excessively high doses for a prolonged period of time. One study in cats, demonstrated a very high incidence of hepa-totoxicity associated with stanozolol use and the authors recom-mended that this drug not be used in cats until further toxicological studies are performed. Potentially (from human data), adverse reactions of the ana-bolic agents in dogs and cats could include: sodium, calcium, po-tassium, water, chloride, and phosphate retention, hepatotoxicity, behavioral (androgenic) changes, and reproductive abnormalities (oligospermia, estrus suppression). Reproductive/nursing Safety In humans, the FDA categorizes this drug as category X for use during pregnancy (Studies in animals or humans demonstrate fetal abnormalities or adverse reaction; reports indicate evidence of fetal risk. The risk of use in pregnant women clearly outweighs any pos-sible benefit. ) In a separate system evaluating the safety of drugs in canine and feline pregnancy (Papich 1989), this drug is categorized as in class: D (Contraindicated. These drugs have been shown to cause congenital malformations or embryotoxicity. ) It is not known whether anabolic steroids are excreted in mater-nal milk. Because of the potential for serious adverse reactions in nursing offspring, use in nursing patients with extreme caution. overdosage/acute t oxicity No information was located for this specific agent. In humans, so-dium and water retention can occur after overdosage of anabolic steroids. It is suggested to treat supportively and monitor liver func-tion should an inadvertent overdose be administered. Drug interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving stanozolol and may be of significance in veterinary patients: anticoa Gu Lant S T! (heparin, warfarin ): Anabolic agents as a class may potentiate the effects of anticoagulants; monitoring of INR/PT's and dosage adjustment, if necessary, of the anticoagulant are recommended co Rtico Ste Roi DST! : Anabolics may enhance the edema that can be associated with ACTH or adrenal steroid therapy in Su Lin T! : Diabetic patients receiving insulin may need dosage ad-justments if anabolic therapy is added or discontinued; anabolics may decrease blood glucose and decrease insulin requirements Laboratory considerations Concentrations of protein bound iodine (PBI) can be decreased T! in patients receiving androgen/anabolic therapy, but the clinical significance of this is probably not important. Androgen/ana-bolic agents can decrease amounts of thyroxine-binding globulin and decrease total t4 concentrations and increase resin uptake of t3 and t4. Free thyroid hormones are unaltered and there is no evidence of dysfunction. Both T! creatinine and creatine excretion can be decreased by ana-bolic steroids. Anabolic steroids can increase the urinary excretion of T! 17-keto-steroids. Androgenic/anabolic steroids may alter T! blood glucose levels. Androgenic/anabolic steroids may suppress T! clotting factors II, V, VII, and X. Anabolic agents can affect T! liver function tests (BSP retention, SGOT, SGPT, bilirubin, and alkaline phosphatase). Doses Do GS:T! As an anabolic agent per labeled indications: a) Small Breeds: 1-2 mg PO twice daily; or 25 mg deep IM, may repeat weekly. Large Breeds: 2-4 mg PO twice daily; or 50 mg deep IM, may repeat weekly. Treatment should continue for several weeks, depend-ing on response and condition of animal. (Package Insert; Winstrol®-V —Winthrop/Upjohn) For anemia secondary to chronic renal failure:a) 1-4 mg PO once daily (Ross et al. 1988) b) For anemias secondary to uremia: 2-10 mg PO twice daily (Maggio-Price 1988) As an anabolic/appetite stimulant:a) 1-4 mg PO twice daily (Weller 1988) b) 1-2 mg PO twice daily or 25-50 mg IM weekly (Macy and Ralston 1989), (Bartges 2003b) For canine cognitive dysfunction: a) 2 mg/kg IM for 4-6 weeks with 1-2 mg (total dose) PO once daily for dogs less than 23 kg and 4 mg (total dose) PO once daily for dogs greater than 23 kg. If drug has some positive effect, maintain oral dosing and gradually reduce injections to every 3-4 weeks. (Hoskins 1999) cat S: T! note : See Warnings Above As an anabolic agent per labeled indications: a) 1-2 mg PO twice daily; or 25 mg deep IM, may repeat week-ly. Treatment should continue for several weeks, depend-ing on response and condition of animal. (Package Insert; Winstrol®-V —Winthrop/Upjohn) Fe RRet S:T! a) 0. 5 mg/kg PO or SC twice daily; use with caution in hepatic disease (Williams 2000) Rabbit S, Ro Dent S, Sma LL mamma LS:T! a) Rabbits: As an appetite stimulant: 0. 5-2 mg PO once (Ivey and Morrisey 2000) Ho RSe S:T! (note : ARCI UCGFS Class 4 Drug) As an anabolic agent per labeled indications: a) 0. 55 mg/kg (25 mg per 100 pounds of body weight) IM deep-ly. May repeat weekly for up to and including 4 weeks. (Pack-age Insert; Winstrol®-V—Winthrop/Upjohn) SHee P & Goat S:T! For acute or subacute aflatoxicosis in ruminants: a) Stanozolol 2 mg/kg IM (plus activated charcoal 6. 7 mg/kg as a 30% w/v slurry in M/15, p H 7 phosphate buffer). Do not combine with oxytetracycline therapy. (Hatch 1988) bi RDS:T! As an anabolic agent to promote weight gain and recovery from disease: a) 0. 5-1 m L/kg (25- 50 mg/kg) IM once or twice weekly. Use with caution in birds with renal disease. (Clubb 1986)	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
836 Sta PHy Lococca L PHa Ge L y Sate Re Pti Le S:T! For most species post-surgically and in very debilitated animals: a) 5 mg/kg IM once a week as needed (Gauvin 1993) monitoring Androgenic side effects T! Fluid and electrolyte status, if indicated T! Liver function tests if indicated T! RBC count, indices, if indicated T! Weight, appetite T! client information Tablets may be crushed and administered with food T! Because of the potential for abuse of anabolic steroids this agent T! is a controlled drug; it should be kept in a secure area and out of the reach of children chemistry/Synonyms An anabolic steroid, stanozolol occurs as an odorless, nearly color-less, crystalline powder that can exist in two forms: prisms that melt at approximately 235°C, and needles that melt at about 155°C. It is sparingly soluble in alcohol and insoluble in water. Stanozolol may also be known as: androstanazole, estanozolol, methylstanazole, NSC-43193, stanozololum, win-14833, Menabol®, Neurabol®, Stanol®, Stromba®, Strombaject® and Winstrol®. Storage/Stability Stanozolol tablets should be stored in tight, light-resistant packag-ing, preferably at room temperature. Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: None Winstrol®-V (Pfizer) tablets and injection were previously available. The ARCI (Racing Commissioners International) has designated this drug as a class 4 substance. See the appendix for more information. Human-Labe Le D PRo Duct S: Stanozolol Oral Tablets: 2 mg (scored); Winstrol® (Winthrop Pharm. ); (Rx, C-III) Stap Hylococcal p Hage l y Sate (staf-loe-kok-al faje lye-sate) Staphage Lysate (SP)®, SPL immune Stimulant Prescriber Highlights Injectable immune stimulant used to treat dogs with re-T T current, idiopathic, staphylococcal pyodermas May cause hypersensitivity (local or systemic)T T uses/indications Staphylococcal phage lysate (SPL) is labeled for treatment of ca-nine pyoderma and related staphylococcal hypersensitivity, or polymicrobial skin infections with a staphylococcal component. Veterinary dermatologists use SPL most commonly to treat recur-rent, idiopathic, staphylococcal pyodermas in combination (at least initially) with an appropriate antibiotic. Pharmacology/actions SPL apparently enhances cell-mediated immunity. It stimulates the production of tumor necrosis factor, interleukin-6, interleukin-γ, and γ-interferon. Pharmacokinetics No information was located. contraindications/Precautions/Warnings The label states that “there are no known contraindications to the use of SPL® except that in highly allergic patients, reduced desensi-tizing doses may be indicated. ” However, use with extreme caution, if at all, in patients with prior systemic hypersensitivity reactions to it or documented hypersensitivity reactions to beef products (con-tains unfiltered beef heart infusion broth). Avoid administering subsequent doses at the same injection site. The product contains no preservative so it must be handled aseptically. It is recommended to use the entire contents when the vial is opened. adverse effects Adverse effects reported for SPL include post vaccine-type reactions (fever, malaise, etc. ) and injection site reactions (redness, itching, swelling) that may occur in 2-3 hours after injection and persisting up to 3 days. If these effects are excessive, the manufacturer recom-mends dosage reduction. Systemic hypersensitivity reactions are thought to occur rarely. Signs could include weakness, vomiting, diarrhea, severe itching, rapid breathing, and/or fatigue/lassitude. Should an anaphylactic-type reaction occur, treat supportively; the manufacturer recom-mends epinephrine and atropine as antidotes. Reproductive/nursing Safety Studies performed in rats and rabbits demonstrated no impaired fertility or fetal harm. No information was located on safety during nursing, but it is unlikely to be of concern. overdosage/acute t oxicity No specific information was located. Other than an increased risk for local or systemic hypersensitivity reactions, significant morbid-ity appears unlikely. Drug interactions ce LL-me Diate D immuno Su PPRe SSi Ve DRu GS T! (e. g., corticosteroids, cyclosporine ): These drugs may reduce the efficacy of SPL Laboratory considerations No significant concerns noted. Doses Do GS:T! a) For labeled indications: Highly allergic patients: Skin test with 0. 05-0. 1 m L intradermally. Therapy: Initially, 0. 2 m L SC, then incremental increases of 0. 2 m L once a week to 1 m L (a total of 5 injections). Then continue at 1 m L SC weekly for approximately 10-12 weeks. For non-allergic patients: 0. 5 m L SC twice weekly for 10-12 weeks, then 0. 5-1 m L every 1-2 weeks. Concomitant antibiotic therapy is recommended for an ini-tial 4-6 week period. Maximum dose should be decreased in small dogs and can be increased cautiously, if necessary, in large dogs to 1. 5 m L. This dose is continued until improvement is demonstrated	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
St Re Ptokina Se 837 then the interval may be lengthened gradually to the longest interval that maintains adequate clinical control. (Label in-formation; Staphage Lysate (SPL)®—Delmont Labs) b) For idiopathic, recurrent pyoderma: Typically given 0. 5 m L SC twice weekly for 10-12 weeks, then tapered to effect. This agent is rarely needed, because in most cases, an underlying cause can be identified and treated. (Gram 2005) monitoring Clinical efficacy T! Local and systemic reactions (see adverse effects) T! client information This medication should ideally be administered at a veterinary T! practice where suitable treatment can be instituted should a seri-ous adverse effect (e. g., anaphylaxis) occur Report to veterinarian any adverse effects noted ( T! e. g., local effects at injection site, itching, change in behavior or activity level, dif-ficulty or unexplained rapid breathing, vomiting, diarrhea) chemistry/Synonyms SPL is prepared by lysing cultures of Staphylococcal aureas (Cowan serologic types I & III; human strains) by a staphylococcal bacte-riophage. Pre-lysed cell counts (120-180 CFU/m L) are used to standardize the product; ultrafiltration achieves bacteriologic ste-rility. The prepared solution contains Staphylococcal aureas compo-nents (protein A extracts), bacteriophage, and unfiltered beef heart infusion. Storage/Stability/compatibility SPL should be stored in the refrigerator (2-7°C); do not freeze. Unopened, properly stored vials and ampules have an average expiration date of one year past the shipment date. The product contains no preservative and must be handled aseptically. It is rec-ommended using the entire contents of the vial after opening. Do not use if contents are cloudy. Do not mix with other drugs or solutions prior to administration. Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: Staphylococcal Phage Lysate (serotypes I & III): in 1 m L ampules (box of 10) and 10 m L multi-dose vials (no preservative added and manufacturer recommends using entire contents when opened); Staphage Lysate (SPL)® (Delmont Labs); (Biologic OTC) note : This product is a USDA-licensed biologic and is not an FDA-approved product. Human-Labe Le D PRo Duct S: None Strepto Kina Se (strep-toe-kin-ase) Streptase® thrombolytic Prescriber Highlights Used for serious thromboembolic disease in dogs T T May be contraindicated in cats; use is controversial in T T this species Adverse Effects (most frequent/serious): Hemorrhage, T T hyperkalemia, fever, & allergic reactions Expensive T T Patient must be intensively monitored T T uses/indications Streptokinase may be useful for the adjunctive treatment of serious thromboses. The use of thrombolytics (streptokinase, t-PA) in cats is controversial. Pharmacology/actions Streptokinase promotes thrombolysis via a complex mechanism; put simply, streptokinase helps convert plasminogen into plasmin. Plasmin then degrades fibrin and fibrinogen to lyse thrombi. Pharmacokinetics After IV injection, streptokinase is cleared from the circula-tion rapidly via the reticuloendothelial system and by circulating antibodies. contraindications/Precautions/Warnings Streptokinase is contraindicated in severe hypertension, internal bleeding, trauma within the past month, or when the risks of hem-orrhage outweigh the benefits of therapy. Streptokinase use is controversial in cats and many clinicians be-lieve it is contraindicated in this species. While the drug has been used without mortality under research conditions, lack of efficacy in the laboratory and high rates of death in clinical settings have occurred. Streptokinase therapy in veterinary medicine should be reserved for those hospitals where adequate monitoring is available (Heme/coag lab) and having clinical experience in managing serious thrombotic and coagulation disorders. adverse effects The most severe and frequently reported adverse effects associated with streptokinase therapy in dogs are hemorrhage, fever, hyper-kalemia, and allergic reactions. Additionally, hypotension, arrhyth-mias, and phlebitis at the site of the injection have been noted. In cats, thrombolytic therapy has been associated with a high mortality and morbidity. Hyperkalemia, acidosis, mild hemor-rhage, and fever have been reported in cats. Streptokinase resistance has been reported in humans, particu-larly after a recent Streptococcal infection or if previous strepto-kinase therapy has been given. If thrombin time or other factors associated with lysis have not changed after 4 hours of therapy, it is recommended to discontinue therapy. Reproductive/nursing Safety It is unknown if streptokinase can cause fetal harm. The drug may cause premature separation of the placenta if administered during the first half of pregnancy. Streptokinase apparently does not cross	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
838 St Re Ptozocin the placenta, but antibodies to it do. In humans, the FDA categoriz-es this drug as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) overdosage/acute t oxicity See Adverse Effects above. Treating severe spontaneous bleeding may include: discontinuing streptokinase infusions and giving plas-ma volume expanders (dextrans, hetastarch, and packed RBC's). In an emergency situation, aminocaproic acid may be considered to reduce the fibrinolytic state. Doses for humans are: loading dose of 5 grams (IV or PO) followed by 1 gram per hour for 2-4 hours. Drug interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving streptokinase and may be of significance in veterinary patients: aminoca PRoic aci DT! : May reverse the fibrinolytic effects of streptokinase He Pa Rin, Wa RF a Rin T! : Other anticoagulants are often used in con-junction with streptokinase, but may increase the likelihood of bleeding; adequate monitoring is essential Laboratory considerations IV streptokinase will significantly decrease T! plasminogen and fibrin-ogen, and increase tt, a Ptt and Pt. Doses Do GS:T! For the treatment of serious thrombosis: a) 90,000 IU IV over 1/2 hour followed by a constant rate infu-sion of 45,000 IU per hour for 7-12 hours. Must also specifi-cally treat primary disease process and give supportive care to correct hypoxemia and loss of tissue perfusion. (Brooks 2000) b) 15,000-18,000 U/kg IV as a loading dose, followed by a maintenance dose of 45,000 U/hr for up to 12 hours. Use only if hemodynamically stable. (Kramer 2003b) c) For pulmonary thromboembolism: 90,000 IU IV over 30 minutes followed by a constant rate infusion of 45,000 IU per hour for 6-12 hours until respiration/hypoxemia improves. (Macintire 2006c) cat S: T! note : Thrombolytic therapy in cats is controversial. Use with ex-treme caution. For thrombolytic treatment of serious thrombosis: a) 90,000 IU IV over 20 minutes followed by a constant rate infusion of 45,000 IU for 2-24 hours (Fox 2003b), (Fox 2007a) monitoring Monitoring essential: Coagulation status: hemorrhage, serial fibrinogen, fibrin degra-T! dation products Blood pressure T! Serum potassium T! Clinical status (including temperature) T! chemistry/Synonyms Produced by group C Beta-hemolytic streptococci, streptokinase is commercially available as a lyophilized white powder. It is freely soluble in water. Streptokinase may also be known as: estreptoquinasa, plasminoki-nase, streptokinasum, Kabikinase®, Streptase®, Streptonase®, Uni-tinase®, or Zykinase®. Storage/Stability The powder should be stored at room temperature. Because they contain no preservatives, ideally, streptokinase solutions should be used immediately after reconstitution. If administration is delayed, refrigerate the solution and use within 24 hours. Do not mix with dextran solutions. Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: None Human-Labe Le D PRo Duct S: Streptokinase Powder for Injection lyophilized: 250,000 IU, 750,000 IU or 1. 5 million IU preservative-free in 6 m L vials and 50 m L infu-sion bottles; Streptase® (Aventis Behring); (Rx) Streptozocin (strep-toe-zoe-sin) Zanosar® antineo Pla Stic Prescriber Highlights Antineoplastic used primarily for treating recurrent insuli-T T noma in dogs May be nephrotoxic, myelotoxic, hepatotoxic T T Vomiting after treatment may occur T T To reduce nephrotoxicity, must give saline diuresis during T T administration uses/indications At present the primary purpose for streptozocin use in veterinary medicine is as a treatment for insulinomas in dogs, particularly those with refractory hypoglycemia and when tumors are non-resectable or have metastasized. Streptozocin potentially could be used for other oncologic conditions as well. Pharmacology/actions While streptozocin has activity against gram-positive and gram-negative bacteria, its cytotoxicity prevents it from clinical useful-ness for this purpose. While its antineoplastic activity is not well understood, streptozocin is considered an alkylating agent and it inhibits DNA synthesis, probably by inhibiting precursor incorpo-ration into DNA. Streptozocin also exhibits a species-specific (in dogs, not hu-mans) diabetogenic effect via reducing nicotinamide adenine di-nucleotide (NAD) concentration in pancreatic beta cells. This effect is usually irreversible in animals with preexisting normal beta cell function. Pharmacokinetics Streptozocin must be administered IV. Its distribution character-istics are not well known, but the drug does distribute to most tis-sues; concentrations in the pancreas are higher than those found in plasma. Streptozocin is metabolized, probably in the liver. Both unchanged and metabolized drug are excreted in the urine.	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
Succime R 839 contraindications/Precautions/Warnings Should be used for recurrent insulinoma only in dogs that have un-dergone previous surgery in which all of the tumor could not be resected. Confirmed histologic diagnosis is mandatory. Streptozocin must be used with extreme caution in patients with decreased renal, bone marrow, or hepatic function. adverse effects The primary concern when used for treating insulinomas in dogs is the potential for the development of serious, permanent renal tox-icity. Aggressive saline diuresis during drug administration appears to reduce this concern. Additionally, GI effects (vomiting/nausea) often occur and can be severe or protracted. Less commonly, hema-tologic changes (mild myelosuppression) and increases in liver en-zymes can occur. Injection site reactions (including severe necrosis) may occur if the drug extravasates. Reproductive/nursing Safety Streptozocin has been shown to be teratogenic in rats; use during pregnancy when the benefits outweigh the risks. In humans, the FDA categorizes this drug as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduc-tion studies and no adequate studies in humans. ) It is not known whether streptozocin is excreted in milk. Because of the potential for serious adverse reactions in nursing offspring, consider using milk replacer if used in nursing patients. overdosage/acute t oxicity Severe toxicity may result if acutely overdosed (see Adverse Effects); calculate dosages carefully. Drug interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving streptozocin and may be of significance in veterinary patients: Doxo Rubicin T! : Streptozocin may prolong the half-life of doxorubi-cin; dosage adjustment may be required mye Lo Su PPRe SSi Ve DRu GS, ot He R T! : When streptozocin is used with other myelosuppressive drugs (e. g., carmustine ) additive or syner-gistic myelosuppression may occur ne PHRotoxic DRu GS, ot He R T! (aminoglycosides, amphotericin b, cis-platin, etc. ): May cause additive nephrotoxicity when used with streptozocin niacinami De T! (nicotinamide ): Can block the diabetogenic effects of streptozocin without altering its antineoplastic activity; this may be beneficial or detrimental depending on the reason for use Doses Do GS:T! a) For “investigational” treatment of recurrent insulinoma after surgery: Begin saline diuresis: Give normal saline at 18-20 m L/kg/hour for 7-8 hours. Over the 4th-5th hour, give streptozocin in the saline solution at a dose of 500 mg/m2 IV. Give an antiemetic (e. g., butorphanol) at the end of the 7-hour period. (Meleo and Caplan 2000) b) Normal saline is given IV at 18. 3 m L/kg/hr for 3 hours, then streptozocin is administered at 500 mg/m2 over two hours with the saline diuresis continuing. After streptozocin infu-sion completed, continue saline diuresis for another 2 hours. Butorphanol is administered as an antiemetic immediately after streptozocin. May repeat at 3 week intervals until evi-dence of tumor progression, recurrence of hypoglycemia, or drug toxicity. Monitor for myelosuppression and nephrotox-icity. (Moore, Nelson et al. 2002)monitoring Blood glucose (efficacy)T! Baseline renal function tests (including urinalyses) and after T! treatment CBCT! Baseline liver function tests and before retreatment T! Hydration status (especially for the first few days after treatment T! or if vomiting a problem). client information Clients should understand the “experimental” nature of this T! treatment and the potential risks for serious adverse effects; fol-low-up monitoring is essential. chemistry/Synonyms Streptozocin is an antineoplastic antibiotic produced by Streptomyces achromogenes, although the commercial product is prepared syn-thetically. It occurs as an ivory colored, crystalline powder. It is very soluble in water and has a p Ka of 1. 35. Streptozocin may also be known as: NSC-85998, streptozotocin, U-9889 and Zanosar®. Storage/Stability The lyophilized powder for injection should be stored in the refrig-erator and protected from light. It is stable for at least 3 years after manufacture. If stored at room temperature, it is stable for at least one year after manufacture. After reconstitution, the lyophilized powder for injection has a p H of 3. 5-4. 5. Dextrose 5% or 0. 9% sodium chloride are used to reconstitute the solution. Citric acid is added to buffer the solu-tion at a concentration of 22 mg/m L. The solution is stable for 48 hours at room temperature and 96 hours if refrigerated, but as no preservative is added the manufacturer recommends using the drug within 12 hours of mixing. Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: None Human-Labe Le D PRo Duct S: Streptozocin Powder for Injection: 1 gram (100 mg/m L) in vials; Zanosar® (Genesia Sicor); (Rx) Succi Mer (sux-i-mer) Chemet®, DMSA, Dimercaptosuccinic acid antidote; chelator Prescriber Highlights Oral heavy metal chelator T T Appears to be safe & effective despite limited experience T T Most likely adverse effects noted are GI in nature; may T T also cause increased liver enzymes, rash High doses may be fatal in birds T T Unpleasant odor of capsules; may give feces, urine, sa-T T liva, etc. a very unpleasant smell Cost is an issue T T	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
840 Succime R uses/indications In veterinary medicine, succimer may be useful for the oral treatment of lead poisoning in small animals (including birds). Potentially, it also may be of benefit for the treatment of other toxic heavy metals such as arsenic or mercury, but more research must be done before this can be recommended. Pharmacology/actions Succimer physically chelates heavy metals such as lead, mercury, and arsenic. These water-soluble chelates are then excreted via the kidneys. Pharmacokinetics No veterinary information was located. In humans, the drug is rap-idly absorbed after oral ingestion, but only incompletely. Absorbed drug is excreted primarily through the kidneys into the urine. Half-life in humans is about 2 days. contraindications/Precautions/Warnings Succimer is contraindicated in patients hypersensitive to it. Chelation therapy should only be attempted if the source of lead is removed to prevent further exposure. adverse effects Most common adverse reactions reported in humans are GI relat-ed effects (vomiting, diarrhea, etc. ) or “flu-like” symptoms (body aches, fatigue, etc. ). Increases in liver enzymes and rashes have also been reported. Reproductive/nursing Safety It is unknown if succimer is safe to use during pregnancy. At high doses it was fetotoxic and teratogenic in mice. Mothers are discour-aged from nursing when taking succimer. In humans, the FDA cat-egorizes this drug as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no ad-equate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) It is not known whether this drug is excreted in breast milk. Discourage mothers requiring therapy from nursing their infants. overdosage/acute t oxicity In toxicology studies, doses of up to 200 mg/kg per day in dogs did not cause overt toxicity. Doses of 300 mg/day did cause fatalities in dogs; primarily kidney and GI tract lesions were seen. Doses of 80 mg/kg, PO q12h did cause a significant number of fatalities in Cockatiels (but 40 mg/kg q12h did not). If an overdose situation is encountered, standardized gut evacuation with subsequent acti-vated charcoal protocols are recommended. Drug interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving succimer and may be of significance in veterinary patients: c He Latin G a Gent S, ot He R T! (cae Dta, dimercaprol, trientine, pen-icillamine, etc. ): Concomitant use with other chelating agents is not recommended in humans Laboratory considerations False positive T! urine ketones can be reported when using nitrop-russide reagents (e. g., as in Ketostix®) Falsely low measurements of T! c Pk or serum uric acid can be caused by succimer Doses Do GS:T! For lead poisoning: a) 10 mg/kg, PO q8h for 10 days (Sisson 2000) b) 10 mg/kg PO three times daily for 5 days, followed by 10 mg/kg PO twice daily for 2 weeks (Poppenga 2002) cat S:T! For lead poisoning: a) 10 mg/kg PO three times daily for 5 days, followed by 10 mg/kg PO twice daily for 2 weeks (Poppenga 2002) bi RDS:T! For lead poisoning: a) 15-35 mg/kg PO twice daily for 5 days (Calvert and Mieurs 2000) b) 30 mg/kg PO twice daily for a minimum of 7 days. If severe neurologic signs, may supplement with one dose of Ca EDTA (edetate calcium disodium; <50 mg/kg of body weight IM) (Hoogesteijn, Raphael et al. 2003) monitoring Blood lead T! GI adverse effects T! Liver enzymes (AST, ALT)T! client information Capsules may have an unpleasant odor; this is no problem with T! the drug, but unpleasant odor may be transferred to saliva, urine, feces Contents of capsules may be sprinkled on soft food T! Animals must be adequately hydrated as the lead chelates are ex-T! creted in the urine chemistry/Synonyms A heavy metal chelating agent also known as meso-2,3 dimercapto-succinic acid (DMSA), succimer is an analog of dimercaprol. It has an unpleasant odor. Succimer may also be known as: meso-2,3 dimercaptosuc-cinic acid, dimercaptosuccinic acid, DIM-SA, DMSA, Chemet® or Succicaptal®. Storage/Stability Unless otherwise labeled, store succimer capsules in tight contain-ers at room temperature. Protect from light. Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: None Human-Labe Le D PRo Duct S: Succimer Capsules: 100 mg; Chemet® (Ovation); (Rx)	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
Succiny Lc Ho Line c HLo Ri De 841 Succinylc Holine c Hloride (suks-sin-i-nil-koe-leen) Anectine® neuromu Scular blocking agent Prescriber Highlights Depolarizing neuromuscular blocking agent T T Contraindications: Severe liver disease, chronic anemias, T T malnourishment, glaucoma or penetrating eye injuries, predisposition to malignant hyperthermia, & increased CPK values with resultant myopathies Extreme Caution: Traumatic wounds or burns, receiving T T quinidine or digoxin therapy, hyperkalemia or electrolyte imbalances Caution: Pulmonary, renal, cardiovascular, metabolic or T T hepatic dysfunction Adverse Effects: Muscle soreness, histamine release, ma-T T lignant hyperthermia, excessive salivation, hyperkalemia, rash, & myoglobinemia/myoglobinuria. Cardiovascular effects, (bradycardia, tachycardia, hypertension, hypoten-sion, or arrhythmias) Specific recommendations for use in horses (see Con-T T traindications below)No analgesic or anesthetic effects T T uses/indications Succinylcholine chloride is indicated for short-term muscle relax-ation needed for surgical or diagnostic procedures, to facilitate en-dotracheal intubation in some species, and reducing the intensity of muscle contractions associated with electro-or pharmacolog-ical-induced convulsions. Dogs, cats, and horses are the primary veterinary species where succinylcholine chloride has been used. Pharmacology/actions An ultrashort-acting depolarizing skeletal muscle relaxant, suc-cinylcholine bonds with motor endplate cholinergic receptors to produce depolarization (perceived as fasciculations). The neuro-muscular block remains as long as sufficient quantities of succinyl-choline remain, and is characterized by a flaccid paralysis. Other pharmacologic effects are discussed in the precautions and adverse effects sections. Pharmacokinetics The onset of action, with complete muscle relaxation, after IV ad-ministration is usually within 30-60 seconds. In humans, this ef-fect lasts for 2-3 minutes and then gradually diminishes within 10 minutes. The very short duration of action after a single IV dose is thought to occur because the drug diffuses away from the motor end plate. If multiple injections or a continuous infusion is per-formed, the brief activity is a result of rapid hydrolysis by pseudo-cholinesterases at the site of action. After IM injection, the onset of action is generally within 2-3 minutes and may persist for 10-30 minutes. Dogs exhibit a prolonged duration of action (≈ 20 min-utes); this species appears unique in this idiosyncratic response. Succinylcholine is metabolized by plasma pseudocholinesterases to succinylmonocholine and choline; 10% is excreted unchanged in the urine. Succinylmonocholine is partially excreted in the urine and may accumulate in patients with impaired renal function. Succinylmonocholine has approximately 1/20th the neuromuscu-lar blocking activity of succinylcholine, but if it accumulates, pro-longed periods of apnea may result. contraindications/Precautions/Warnings Succinylcholine is contraindicated in patients with severe liver dis-ease, chronic anemias, malnourishment (chronic), glaucoma or penetrating eye injuries, predisposition to malignant hypertherm-ia, and increased CPK values with resultant myopathies. As suc-cinylcholine can exacerbate the effects of hyperkalemia, it should be used with extreme caution in patients who have suffered trau-matic wounds or burns, are receiving quinidine or digoxin therapy, or have preexisting hyperkalemia or electrolyte imbalances as ar-rhythmias or cardiac arrest may occur. It should be used with cau-tion in patients with pulmonary, renal, cardiovascular, metabolic, or hepatic dysfunction. Succinylcholine should not be used if organophosphate agents have been given or applied recently. Succinylcholine chloride does not have analgesic effects; and should be used with appropriate analgesic, sedative, and anesthetic agents. In horses, The American Association of Equine Practitioners have made the following additional recommendations: 1) Inform the owner that succinylcholine chloride is to be used as a restraining agent, not as an anesthetic. 2) Obtain history before use; do not use in horses if within 30 days they have received, an antibiotic ending in “mycin”, or-ganophosphate insecticides or anthelmintics, any other cho-linesterase inhibitor, or procaine. 3) Do not use in debilitated, excited, or exhausted horses. 4) If possible, withhold food for 4-6 hours before use. 5) Dosage of 0. 088 mg/kg IV may be used to paralyze skeletal muscles without causing respiratory depression. Higher dos-es may cause apnea and death without respiratory support. Lower doses may be possible if used with a preanesthetic agent. 6) After administration, have someone hold the horse that is familiar with the actions of succinylcholine chloride so that the animal does not fall forward on its nose. Be prepared to administer oxygen and artificial respiration. 7) If death occurs, a necropsy should be performed. adverse effects Succinylcholine chloride can cause muscle soreness, histamine re-lease, malignant hyperthermia, excessive salivation, hyperkalemia, rash, and myoglobinemia/myoglobinuria. Cardiovascular effects can include bradycardia, tachycardia, hypertension, hypotension, or arrhythmias. Reproductive/nursing Safety It is unknown if succinylcholine can cause fetal harm. The drug does cross the placenta in low concentrations and a newly delivered neonate may show signs of neuromuscular blockade if the mother received high doses or prolonged administration of the drug prior to delivery. In humans, the FDA categorizes this drug as category C for use during pregnancy (Animal studies have shown an adverse ef-fect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in hu-mans. ) In a separate system evaluating the safety of drugs in canine and feline pregnancy (Papich 1989), this drug is categorized as in class: B (Safe for use if used cautiously. Studies in laboratory animals may have uncovered some risk, but these drugs appear to be safe in dogs and cats or these drugs are safe if they are not administered when the animal is near term. )	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
842 Succiny Lc Ho Line c HLo Ri De It is not known whether this drug is excreted into milk; exercise caution when succinylcholine is administered to a nursing patient. overdosage/acute t oxicity Inadvertent overdoses, or standard doses in patients deficient in pseudocholinesterase may result in prolonged apnea. Mechanical ventilation with O 2 should be used until recovery. Repeated or prolonged high dosages may cause patients to con-vert from a phase I to a phase II block. Drug interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving succinylcholine and may be of significance in veterinary patients: am PHote Ricin b T! : May increase succinylcholine's effects by causing electrolyte imbalances Di Goxin T! : Succinylcholine may cause a sudden outflux of potas-sium from muscle cells, thus causing arrhythmias in digitalized patients o Piate ST! : Potential for increased incidences of bradycardia and sinus arrest t Hiazi De Diu Retic S T! : May increase succinylcholine's effects by causing electrolyte imbalances The following drugs/drug classes may increase or prolong neuro-muscular blockade if used concurrently with succinylcholine: amino GL yco Si De S !! ane St Hetic S, in Ha Lation !! (isoflurane, desflurane ) antia RRHyt Hmic S !! (quinidine, lidocaine, procainamide ) beta-a DRene RGic b Locke RS!! c HLo Roquine!! c Lin Damycin!! co Rtico Ste Roi DS!! cyc Lo PHo SPHami De!! ma Gne Sium Sa L t S !! mao in Hibito RS!! metoc Lo PRami De!! neo Sti Gmine!! o RGano PHo SPHate S!! oxytocin!! Pancu Ronium!! PHenot Hiazine S!! PRocaine !! (i V) te Rbuta Line!! t Hiote P a T! Doses Do GS:T! a) 0. 07 mg/kg IV (Morgan 1988) b) 0. 22 mg/kg IV (M andsager 1988) cat S:T! a) 0. 06 mg/kg IV (Morgan 1988) b) 0. 11 mg/kg IV (Mandsager 1988) Ho RSe S: T! See Precautions above. ( note : ARCI UCGFS Class 2 Drug) a) 0. 088 mg/kg (Muir) b) 0. 088-0. 11 mg/kg IV, IM (Mandsager 1988) Re Pti Le S:T! a) T o relax an animal to allow intubation: 0. 5-1 mg/kg IM. Especially helpful with turtles and crocodilians. (Lewbart 2001)monitoring Level of muscle relaxation T! Cardiac rate/rhythm T! Respiratory depressant effect T! client information This drug should only be used by professionals familiar with its T! use chemistry/Synonyms A depolarizing neuromuscular blocking agent, succinylcholine chloride occurs as an odorless, white, crystalline powder. The di-hydrate form melts at 190°C and the anhydrous form at 160°C. Aqueous solutions are acidic with a p H of approximately 4. One gram is soluble in about 1 m L of water and about 350 m L of alco-hol. Commercially available injections have a p H from 3-4. 5. Succinylcholine chloride may also be known as: choline chloride succinate, succicurarium chloride, succinylcholine chloride, sux-amethonii chloridum, suxametonklorid, suxamethonium chloride; many trade names are available. Storage/Stability/compatibility Commercial injectable solutions should be stored refrigerated (2°-8°C). One manufacturer (Anectine®—Glaxo Wellcome) states that multiple dose vials are stable up to 2 weeks at room tempera-ture with no significant loss of potency. The powder forms of the drug are stable indefinitely when stored unopened at room temperature. After reconstitution with either D5W or normal saline, they are stable for 4 weeks at 5°C or 1 week at room temperature, but because they contain no preservative, it is recommended they be used within 24 hours. Succinylcholine chloride is physically compatible with all com-monly used IV solutions, amikacin sulfate, cephapirin sodium, iso-proterenol HCl, meperidine HCl, norepinephrine bitartrate, and scopolamine HBr. It may not be compatible with pentobarbital so-dium and is physically incompatible with sodium bicarbonate and thiopental sodium. Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: None The ARCI (Racing Commissioners International) has designated this drug as a class 2 substance. See the appendix for more information. Human-Labe Le D PRo Duct S: Succinylcholine Chloride Injection: 20 mg/m L & 50 mg/m L in 10 m L vials, amps and 5 m L Abboject syringes; Anectine® (Glaxo Wellcome); Quelicin® (Hospira); (Rx) Succinylcholine Chloride Powder for Infusion: 500 mg and 1 gram vials; Anectine® Flo-Pak (Glaxo Wellcome); (Rx)	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
Suc Ra LF ate 843 Sucralfate (soo-kral-fate) Carafate® ga Stro Protectant Prescriber Highlights Locally-acting treatment for GI ulcers; may also protect T T somewhat against GI ulceration. Potentially could be use-ful for lowering serum phosphorus in renal patients. Contraindications: None, use with caution where de-T T creased GI transit times may be harmful Adverse Effects: Unlikely; constipation possible T T Give on empty stomach if possible T T Drug Interactions T T uses/indications Sucralfate has been used in the treatment of oral, esophageal, gas-tric, and duodenal ulcers. It has also been employed to prevent drug-induced (e. g., aspirin) gastric erosions, but efficacy for this is somewhat sporadic. Sucralfate has been used in human patients with hyperphosphatemia secondary to renal failure and potentially could be useful for this in animals as well. Pharmacology/actions While the exact mechanism of action of sucralfate as an antiulcer agent is not known, the drug has a local effect rather than a systemic one. After oral administration, sucralfate reacts with hydrochloric acid in the stomach to form a paste-like complex that will bind to the proteinaceous exudates that generally are found at ulcer sites. This insoluble complex forms a barrier at the site and protects the ulcer from further damage caused by pepsin, acid, or bile. Sucralfate may have some cytoprotective effects, possibly by stim-ulation of prostaglandin E 2 and I 2. Sucralfate also has some antacid activity, but it is believed that this is not of clinical importance. Sucralfate does not significantly affect gastric acid output, or trypsin or pancreatic amylase activity. It may decrease the rate of gastric emptying. As an aluminum salt, sucralfate can bind to gastrointestinal phosphorus. Pharmacokinetics Animal studies have indicated that only 3-5% of an oral dose is absorbed which is excreted in the urine unchanged within 48 hours. By reacting with hydrochloric acid in the gut, the remainder of the drug is converted to sucrose sulfate which is excreted in the feces within 48 hours. The duration of action (binding to ulcer site) may persist up to 6 hours after oral dosing. contraindications/Precautions/Warnings There are no known contraindications to the use of sucralfate. Because it may cause constipation, it should be used with cau-tion in animals where decreased intestinal transit times might be deleterious. adverse effects Adverse effects are uncommon with sucralfate therapy. Constipation is the most prominent adverse effect reported in humans (2%) and dogs receiving the drug. Reproductive/nursing Safety It is unknown if sucralfate crosses the placenta and whether it may definitively be used safely during pregnancy. In rats, dosages up to 38 times those used in humans caused no impaired fertility and doses up to 50 times normal caused no symptoms of teratogenicity. In humans, the FDA categorizes this drug as category B for use dur-ing pregnancy (Animal studies have not yet demonstrated risk to the fetus, but there are no adequate studies in pregnant women; or animal studies have shown an adverse effect, but adequate studies in pregnant women have not demonstrated a risk to the fetus in the first trimester of pregnancy, and there is no evidence of risk in later trimesters. ) In a separate system evaluating the safety of drugs in canine and fe-line pregnancy (Papich 1989), this drug is categorized as in class: A (Probably safe. Although specific studies may not have proved he safety of all drugs in dogs and cats, there are no reports of adverse effects in laboratory animals or women. ) It is not known whether this drug is excreted in milk, but it is unlikely to be of concern. overdosage/acute t oxicity Overdosage is unlikely to cause any significant problems. Laboratory animals receiving up to 12 grams/kg orally demonstrated no inci-dence of mortality. Drug interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving sucralfate and may be of significance in veterinary patients: Sucralfate may impair the oral absorption of the following med-ications; separate dosing by at least 2 hours to minimize this effect: ci PRo FLoxacin!! (assume other oral fluoroquinolones as well) Dic Lo Fenac!! Di Goxin!! ketoconazo Le!! Le Vot Hy Roxine!! Penici LLamine!! tet Racyc Line S!! Vitamin S!! (fat soluble ) Wa RF a Rin T! Doses Do GS:T! a) For esophagitis: 0. 5-1 gram PO three times a day. Suspen-sions are more therapeutic than intact tablets. (Washabau 2000) b) For large dogs: 1 gram PO q8; for smaller dogs: 0. 5 gram PO q8h (Zerbe and Washabau 2000) c) 0. 5-1 gram PO 2-4 times a day; patients with severe GI blood loss give an initial loading dose of 3-6 grams and then resume lower dose. If also using an H2 blocker, administer sucralfate 30-60 minutes later. (Hall 2000) d) For eliminating Helicobacter gastritis infections: Using triple therapy: Metronidazole 33 mg/kg once daily, amoxicillin 11 mg/kg q12h and either sucralfate (0. 25-0. 5 grams q8h) or omeprazole 0. 66 mg/kg once daily (Hall 2000) e) In patients with severe hematemesis and anemia we some-times give a loading dose of 3-6 grams initially and then de-crease to 1 gram PO three to four times a day. May not always work in vomiting dogs. Suspensions may have less tendency to be vomited up in these patients. (Willard 2006d) f) For gastric ulcers, esophagitis: 0. 5-1 gram PO per dog q8-12h (Sellon 2007b)	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
844 Su Fentani L cit Rate g) For GI ulcers/esophagitis associated with acute renal failure: 1 gram per 30 kg body weight PO q6h (Waddell 2007a) cat S:T! a) 0. 25-0. 5 grams PO q8-12h (Zerbe and Washabau 2000) b) 0. 25 gram PO q8-12h (Matz 1995) c) For gastric ulcers, esophagitis: 0. 25-0. 5 grams PO per cat PO q8-12h (Sellon 2007b) Fe RRet S:T! a) 75 mg/kg PO q4-6h; give 10 minutes prior to feeding (Wil-liams 2000) Ho RSe S:T! a) For adjunctive treatment for preventing stress-induced ul-cers in foals: 10-20 mg/kg PO q6-8h (Sanchez 2004b) b) For treating equine gastric ulcer syndrome: 20-40 mg/kg PO q8h (Sanchez 2004b), (Nadeau and Andrews 2003) Re Pti Le S:T! a) For GI irritation in most species: 500-1,000 mg/kg PO q6-8h (Gauvin 1993) monitoring Clinical efficacy (dependent on reason for use); monitored by T! decrease in symptomatology, endoscopic examination, blood in feces, etc. client information T o maximize the benefit of this medication, it must be adminis-T! tered as prescribed by the veterinarian; clinical signs may reoccur if dosages are missed Unless otherwise instructed, give this medication to animal hav-T! ing an empty stomach (1 hour before feeding or 2 hours after) and at bedtime chemistry/Synonyms A basic, aluminum complex of sucrose sulfate, sucralfate occurs as a white, amorphous powder. It is practically insoluble in alcohol or water. Sucralfate is structurally related to heparin, but does not possess any appreciable anticoagulant activity. It is also structurally related to sucrose, but is not utilized as a sugar by the body. Sucralfate is also known as aluminum sucrose sulfate, basic and Carafate®. Storage/Stability Store sucralfate tablets in tight containers at room temperature. Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: None Human-Labe Le D PRo Duct S: Sucralfate Tablets: 1 gram (scored); Carafate® (Axcan Sandipharm); generic; (Rx) Sucralfate Suspension: 1 g/10 m L in 10 m L unit dose cups & 415 m L; Carafate® (Axcan Scandipharm); generic (Precision Dose); (Rx)Sufentanil citrate (soo-fen-ta-nil) Sufenta® o Piate agoni St Prescriber Highlights Injectable, extremely potent opiate that may be useful T T for adjunctive anesthesia or epidural analgesia Marginal veterinary experience & little published data T T available to draw conclusions on appropriate usage in veterinary species Dose-related respiratory & CNS depression most likely T T adverse effects Class-II controlled substance; expensive when compared T T to fentanyl uses/indications An opioid analgesic, sufentanil may be useful as an anesthesia ad-junct or as an epidural analgesic. In humans, it has been used as the primary anesthetic in intubated patients with assisted ventilation, and as a post-operative analgesic. Pharmacology/actions Sufentanil is a potent mu opioid with the expected sedative, an-algesic, and anesthetic properties. When comparing analgesic po-tencies, 0. 01-0. 04 mg of sufentanil is equivalent to 0. 4-0. 8 mg of alfentanil, 0. 1-0. 2 mg of fentanyl, and approximately 10 mg of morphine, when all are injected IM. Like fentanyl, sufentanil ap-pears to have less circulatory effects than does morphine. Sufentanil has a rapid onset of action (1-3 minutes) and a faster recovery time than fentanyl. Pharmacokinetics No information on the pharmacokinetics of sufentanil in domestic animals was located. In humans, the drug has rapid onset of ac-tion (1-3 minutes) after intravenous injection. The drug is highly lipid soluble and has volume of distribution in the central com-partment of 0. 1 L/kg. Approximately 93% is bound to plasma pro-teins; plasma concentrations rapidly decline due to redistribution. T erminal elimination half-life is about 2. 5 hours. Plasma clearance has been reported to be 11. 8 m L/min/kg. Sufentanil is metabolized primarily in the liver and small intestine via O-demethylation and N-dealkylation. The parent drug and these metabolites are excreted primarily in the urine. While the manufacturer states to use with caution in patients with impaired renal of hepatic function, limited pharmacokinetic studies in these patients, rarely showed any drug accumulation. contraindications/Precautions/Warnings Sufentanil is contraindicated in patients hypersensitive to it or other opioids. It should be used with caution in debilitated or ge-riatric patients and those with severely diminished renal or hepatic function. Because of the drug's potency and potential for significant ad-verse effects, it should only be used in situations where patient vital signs can be continuously monitored. Initial dosage reduction may be required in geriatric or debilitated patients, particularly those with diminished cardiopulmonary function.	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
Su Fentani L cit Rate 845 adverse effects Adverse effects are generally dose related and consistent with other opiate agonists. Respiratory depression and/or CNS depression are most likely to be encountered. In humans, bradycardia that is usually responsive to anticho-linergic agents can occur. Dose-related skeletal muscle rigidity is not uncommon, and neuromuscular blockers are routinely used. Sufentanil has rarely been associated with asystole, hypercarbia and hypersensitivity reactions. Respiratory or CNS depression may be exacerbated if sufentanil is given with other drugs that can cause those effects. Reproductive/nursing Safety In humans, the FDA categorizes sufentanil as a category C drug for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) While sufentanil is indicated for epidural use (mixed with bupi-vacaine ± epinephrine) in women for labor/delivery, it should not be administered systemically to a mother close to giving birth as offspring may show behavioral alterations (hypotonia, depression) associated with opioids. The effects of sufentanil on lactation or its safety for nursing offspring is not well-defined, but sufentanil milk levels approximate those found in serum. This coupled with its low oral bioavailability, make it unlikely to cause significant effects in nursing offspring. overdosage/acute t oxicity In dogs, the LD50 of intravenous sufentanil is 10. 1-19. 5 mg/kg. Intravenous severe overdoses may cause apnea, circulatory collapse, pulmonary edema, seizures, cardiac arrest and death. Treatment is a combination of supportive therapy and administration of an opiate antagonist such as naloxone. Although sufentanil has a fairly rapid half-life, multiple doses of naloxone may be necessary. Because of the drug's potency, the use of a tuberculin syringe to measure dos-ages less than 1 m L, with a dosage calculation and measurement double-check system is recommended. Drug interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving sufentanil and may be of significance in veterinary patients: beta-a DRene RGic b Locke RST! : May increase bradycardia and hypotension ca Lcium-c Hanne L b Locke RS T! : May increase bradycardia and hypotension cn S De PRe SSant S, ot He R T! : Additive effects can occur if sufentanil is used concurrently with other drugs that can depress CNS or respiratory function (e. g., barbiturates, etc. ) nit Rou S oxi De T! : Can cause cardiovascular depression if used with high dose sufentanil Laboratory considerations Because opiates can increase biliary tract pressure and raise se-T! rum amylase and lipase values, these values may be unreliable for 24 hours after sufentanil is administered. Doses (note : In very obese patients, figure dosages based upon lean body weight. ) Do GS:T! a) As a pre-med: 3 mcg/kg IV. As a combination for induction: Sufentanil 3 mcg/kg IV first, then diazepam or midazolam 0. 2-0. 5 mg IV. (Banyard 2004) b) For epidural analgesia: 0. 7-1 mcg/kg diluted to a volume of 0. 26 m L/kg with sterile saline. Onset of action in 10-15 min-utes; duration 1-4 hours. (Otero 2006b) c) Acute pain relief in an emergency: 0. 75-2 mcg/kg IV; con-stant rate infusion of 1-2 mcg/kg/hour. (Otero 2006a) d) For surgical pain: 5 mcg/kg IV prior to a CRI. Duration of effect: 2-6 hours. CRI (post-operative) of 0. 1 mcg/kg/hour. (Ogilvie 2004) cat S:T! a) Acute pain relief in an emergency: 0. 1-0. 5 mcg/kg IV; con-stant rate infusion of 0. 5-1 mcg/kg/hour. (Otero 2006a) monitoring Anesthetic and/or analgesic efficacy T! Cardiac and respiratory rate T! Pulse oximetry or other methods to measure blood oxygenation T! when used for anesthesia client information Sufentanil is a very potent opiate that should only be used by T! professionals in a setting where adequate patient monitoring is available. chemistry/Synonyms A phenylpiperidine derivative opioid related to fentanyl, sufenta-nil citrate occurs as a white or almost white powder that is soluble in water, sparingly soluble in alcohol, acetone, or chloroform. The commercially available injection has a p H (adjusted with citric acid) of 3. 5-6. Sufentanil citrate may also be known as: R-33800, sufentanili citras, fentathienel citrate, sufentanyl citrate, sulfentanil citrate, Fastfen®, Fentaientel® and Sufenta®. Storage/Stability/compatibility Unless otherwise labeled, sufentanil injection should be stored pro-tected from light at room temperature. Sufentanil citrate is hydro-lyzed in acidic solutions. Sufentanil citrate is reportedly compatible with D5W and bupiva-caine. For Y-site injection it is compatible with solutions containing: atropine, dexamethasone sodium phosphate, diazepam, diphen-hydramine, etomidate, metoclopramide, midazolam, phenobarbi-tal, and propofol. It is incompatible with lorazepam, phenytoin and thiopental. Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: None The ARCI (Racing Commissioners International) has designated this drug as a class 1 substance. See the appendix for more information. Human-Labe Le D PRo Duct S: Sufentanil Citrate Injection: 50 mcg/m L (as base) in 1 m L, 2 m L and 5 m L amps; Sufenta® (preservative free) (Taylor); generic (with pre-servatives); (Rx, C-II).	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
846 Su LFac HLo RPy Ri Dazine So Dium Sulfac Hlorpyridazine Sodiu M (sul-fa-klor-pye-rid-a-zeen) Vetisulid® Sulfonamide antibacterial Prescriber Highlights Contraindications: Hypersensitivity to sulfas, thiazides, or T T sulfonylurea agents; severe renal or hepatic impairment Caution: Diminished renal or hepatic function, or urinary T T obstruction Adverse Effects: Can precipitate in the urine (especially T T with high dosages for prolonged periods, acidic urine or highly concentrated urine); DOGS: Keratoconjunctivitis sicca, bone marrow depression, hypersensitivity reactions (rashes, dermatitis), focal retinitis, fever, vomiting, & non-septic polyarthritis possible Potentially teratogenic; weigh risk vs. benefit T T Too-rapid IV injection may cause muscle weakness, blind-T T ness, ataxia, & collapse; SC or IM injection may cause tissue irritation uses/indications Sulfachlorpyridazine is indicated for the treatment of diarrhea caused or complicated by E. coli in calves less than one month of age or colibacillosis in swine. It is also used parenterally as a general-purpose sulfonamide in adult cattle and other species. Pharmacology/actions Sulfonamides are usually bacteriostatic agents when used alone. They are thought to prevent bacterial replication by competing with para-aminobenzoic acid (PABA) in the biosynthesis of tetra-hydrofolic acid in the pathway to form folic acid. Only microorgan-isms that synthesize their own folic acid are affected by sulfas. Microorganisms that are usually affected by sulfonamides in-clude some gram-positive bacteria, including some strains of strep-tococci, staphylococcus, Bacillus anthracis, Clostridium tetani, C. perfringens, and many strains of Nocardia. Sulfas have in vitro ac-tivity against some gram-negative species, including some strains of Shigella, Salmonella, E. coli, Klebsiella, Enterobacter, Pasturella, and Proteus. Sulfas also have activity against some rickettsia and protozoa (T oxoplasma, Coccidia). Unfortunately, resistance to sul-fas is a progressing phenomenon and many strains of bacteria that were once susceptible to this class of antibacterial are now resistant. The sulfas are less efficacious in pus, necrotic tissue, or in areas with extensive cellular debris. Pharmacokinetics Very limited information is available on the specific pharmacoki-netics for this agent. In general, sulfonamides are readily absorbed from the GI tract of non-ruminants, but absorption can vary de-pending on the drug, species, disease process, etc. Food delays the rate, but usually not the extent of absorption. Peak levels occur within 1-2 hours in non-ruminant (and young pre-ruminant) ani-mals. Adult ruminants may have significant delays before the drug is absorbed orally. Sulfas are well distributed throughout the body and some reach significant levels in the CSF. Levels of the drugs tend to be highest in liver, kidney, and lung, and lower in muscle and bone. The sulfas can be highly bound to serum proteins, but the extent of binding is species and drug dependent. When bound to proteins the sulfa is not active. Sulfonamides are both renally excreted and metabolized. Renal excretion of unchanged drug occurs via both tubular secretion and glomerular filtration. Protein bound drug is not filtered by the glomeruli. Metabolism is performed principally in the liver, but extra-hepatic metabolism is also involved. Mechanisms of metabo-lism are usually acetylation and glucuronidation. The acetylated metabolites may be less soluble and crystallization in the urine can occur with some sulfonamides, particularly at lower p H. The se-rum half-life of sulfachlorpyridazine is approximately 1. 2 hours in cattle. contraindications/Precautions/Warnings Sulfonamides are contraindicated in patients hypersensitive to them, thiazides, or sulfonylurea agents. They are also considered contraindicated in patients with severe renal or hepatic impairment and should be used with caution in patients with diminished renal or hepatic function, or urinary obstruction. Oral sulfonamides can depress the normal cellulytic function of the ruminoreticulum, but this effect is generally temporary and the animal adapts. adverse effects Sulfonamides (or their metabolites) can precipitate in the urine, particularly when given at high dosages for prolonged periods. Acidic or highly concentrated urine may also contribute to in-creased risk of crystalluria, hematuria, and renal tubule obstruc-tion. Different sulfonamides have different solubilities at various p H's. Alkalinization of the urine using sodium bicarbonate may prevent crystalluria, but it also decreases the amount available for tubular reabsorption. Crystalluria can usually be avoided with most of the commercially available sulfonamides by maintaining an ad-equate urine flow. Normal urine p H in herbivores is usually 8 or more, so crystalluria is not frequently a problem. Sulfonamides can also cause various hypersensitivity reactions or diarrhea by altering the normal gut flora. T oo rapid intravenous injection of the sulfas can cause muscle weakness, blindness, ataxia, and collapse. In dogs, keratoconjunctivitis sicca has been reported with sul-fonamide therapy. In addition, bone marrow depression, hypersen-sitivity reactions (rashes, dermatitis), focal retinitis, fever, vomiting and nonseptic polyarthritis have been reported in dogs. Oral sulfonamides can depress the normal cellulytic function of the ruminoreticulum, but this effect is generally temporary and the animal adapts. Because solutions of sulfonamides are usually alkaline, they can cause tissue irritation and necrosis if injected intramuscularly or subcutaneously. Reproductive/nursing Safety Sulfas cross the placenta and may reach fetal levels of 50% or great-er those found in maternal serum; teratogenicity has been reported in some laboratory animals when given at very high doses. They should be used in pregnant animals only when the benefits clearly outweigh the risks of therapy. Sulfonamides are distributed into milk. Safe use during lactation cannot be assumed; use with caution. overdosage/acute t oxicity Acute toxicity secondary to overdoses apparently occurs only rarely in veterinary species. In addition to the adverse effects listed above, CNS stimulation and myelin degeneration have been noted after very high dosages.	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
Su LFa Diazine/t Rimet Ho PRim; Su LF amet Hoxazo Le/t Rimet Ho PRim 847 Drug interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving sulfachlorpyridazine and may be of significance in veterinary patients: antaci DST! : May decrease the oral bioavailability of sulfonamides if administered concurrently Laboratory considerations Sulfonamides may give false-positive results for T! urine glucose de-terminations when using the Benedict's method. Doses catt Le:T! In calves for labeled indications: 33-49. 5 mg/kg PO, or IV twice daily for 1-5 days; suggest initiating therapy with intravenous preparation and then changing to oral if possible (Package in-sert; Vetisulid®—Fort Dodge) SWine:T! For labeled indications: 44-77 mg/kg PO per day (divide dose and give twice daily if treating individual animals) for 1-5 days (Package insert; Vetisulid®—Fort Dodge) bi RDS:T! For enteric bacterial infections:a) Using the oral powder: Mix 1/4 teaspoonful per liter of water and use as only supply of drinking water for 5-10 days. May be effective for many E. coli enteric infections. (Clubb 1986) b) Using the oral powder: Mix 3/4 teaspoonsful per 2 quarts of water. Fairly effective for enteric infections, particularly E. coli. Reserved for clients who are unable to give other medi-cations by mouth or parenterally. (Mc Donald 1989) c) For pigeons: 1200 mg per gallon of drinking water. Very ef-fective for E. coli and it is a good coccidiostat. (Harlin 2006) monitoring Clinical efficacy T! Adverse effects T! client information T o help reduce the possibility of crystalluria occurring, animals T! should have free access to water; avoid dehydration. chemistry/Synonyms Sulfachlorpyridazine sodium is listed as a short to intermediate-acting, low lipid soluble sulfonamide antibacterial. It is reportedly very soluble in urine at usual p H's. Sulfachlorpyridazine may also be known as cluricol, sulphachlo-rpyridazine, or Vetisulid®. Storage/Stability/compatibility The injection should be stored at room temperature and protected from light; avoid freezing. The oral suspension should be stored at room temperature; avoid freezing. The oral boluses and powder should be stored at room temperature; avoid excessive heat (above 40°C/104°F). No information was located regarding the compatibility of sul-fachlorpyridazine with other fluids or agents. Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: Sulfachlorpyridazine Sodium Oral powder: 54 grams per bottle; Vetisulid® Powder (Fort Dodge); (OTC) Indicated for use in calves under one month of age and swine. Slaughter withdrawal (at labeled doses) = 7 days for cattle and 4 days for swine. Sulfachlorpyridazine Sodium Oral Suspension: 50 mg/m L in 180 m L bottles; Vetisulid® Oral Suspension (Fort Dodge); (OTC). Approved for use in swine. Slaughter withdrawal (at labeled doses) = 4 days for swine. Human-Labe Le D PRo Duct S: None Sulfadiazine/Pyrimethamine — See Pyrimethamine/ Sulfadiazine Sulfadiazine/tri Met Hopri M Sulfa Met Hoxazole/ tri Met Hopri M (sul-fa-dye-a-zeen; sul-fa-meth-ox-a-zole/trye-meth-ohe-prim) Co-trimoxazole, Tribrissen®, Bactrim®, Septra® Potentiated Sulfonamide antimicrobial note : In the practice of veterinary medicine in the USA, two sepa-rate combinations with trimethoprim are used clinically. There are trimethoprim/sulfadiazine products approved for use in dogs, cats, and horses in both parenteral and oral dosage forms. Many veterinarians also use the human approved, trimethoprim/sulfamethoxazole oral products. In Canada, sulfadoxine is available in combination with trimethoprim for veterinary use. Prescriber Highlights Potentiated sulfonamide antimicrobial agent T T Contraindications: Hypersensitivity to sulfas, thiazides, or T T sulfonylurea agents; severe renal or hepatic impairment Caution: Diminished renal or hepatic function, or urinary T T obstruction or urolithiasis Adverse Effects: T T DOGS: Keratoconjunctivitis sicca, hyper-sensitivity (type 1 or type 3), acute neutrophilic hepatitis with icterus, vomiting, anorexia, diarrhea, fever, hemolytic anemia, urticaria, polyarthritis, facial swelling, polydipsia, crystalluria, hematuria, polyuria, cholestasis, hypothy-roidism, anemias, agranulocytosis, idiosyncratic hepatic necrosis in dogs. CATS: Anorexia, crystalluria, hematuria, leukopenias & anemias. HORSES: Transient pruritic (after IV injection). Oral: diarrhea, hypersensitivity reactions & hematologic effects (anemias, thrombocytopenia, or leu-kopenias Local injection effects possible (check label for product T T recommendation for injection technique)Potentially teratogenic, weigh risk vs. benefit T T uses/indications Although only approved for use in dogs and horses, trimethoprim/ sulfadiazine etc. is used in many species to treat infections caused by susceptible organisms. See Dosage section for more information. Pharmacology/actions Alone, sulfonamides are bacteriostatic agents and trimethoprim is bactericidal, but when used in combination, the potentiated sul-fas are bactericidal. Potentiated sulfas sequentially inhibit enzymes in the folic acid pathway, inhibiting bacterial thymidine synthesis. The sulfonamide blocks the conversion of para-aminobenzoic acid (PABA) to dihydrofolic acid (DFA), and trimethoprim blocks the	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
848 Su LFa Diazine/t Rimet Ho PRim; Su LF amet Hoxazo Le/t Rimet Ho PRim conversion of DFA to tetrahydrofolic acid by inhibiting dihydrofo-late reductase. The in vitro optimal ratio for most susceptible bacteria is ap-proximately 1:20 (trimethoprim:sulfa), but synergistic activity can reportedly occur with ratios of 1:1-1:40. The serum concentration of the trimethoprim component is considered more important than the sulfa concentration. For most susceptible bacteria, the MIC's for TMP are generally above 0. 5 mcg/m L. The potentiated sulfas have a fairly broad spectrum of activ-ity. Gram-positive bacteria that are generally susceptible include most streptococci, many strains of staphylococcus, and Nocardia. In horses, approximately 30% of strains tested of Streptococcus zooepidemicus are resistant to TMP/Sulfa. Many gram-negative organisms of the family Enterobacteriaceae are susceptible to the potentiated sulfas, but not Pseudomonas aeruginosa. Some protozoa (Pneumocystis carinii, Coccidia, and T oxoplasma) are also inhibited by the combination. Potentiated sulfas reportedly have little activity against most anaerobes, but opinions on this vary. Resistance will develop more slowly to the combination of drugs than to either one alone. In gram-negative organisms, resistance is usually plasmid-mediated. Pharmacokinetics Trimethoprim/sulfa is well absorbed after oral administration, with peak levels occurring about 1-4 hours after dosing; the drug is more slowly absorbed after subcutaneous absorption, however. In ruminants, trimethoprim is apparently trapped in the ruminoretic-ulum after oral administration and undergoes some degradation. Trimethoprim/sulfa is well distributed in the body. When me-ninges are inflamed, the drugs enter the CSF in levels of about 50% those found in the serum. Both drugs cross the placenta and are distributed into milk. The volume of distribution for trimethoprim in various species are: 1. 49 L/kg (dogs); 0. 59-1. 51 L/kg (horses). The volume of distribution for sulfadiazine in dogs is 1. 02 L/kg. Trimethoprim/sulfa is both renally excreted unchanged via glomerular filtration and tubular secretion and metabolized by the liver. The sulfas are primarily acetylated and conjugated with glucuronic acid and trimethoprim is metabolized to oxide and hydroxylated metabolites. Trimethoprim may be more extensively metabolized in the liver in adult ruminants, than in other species. The serum elimination half-lives for trimethoprim in various spe-cies is: 2. 5 hours (dogs), 1. 91-3 hours (horses), 1. 5 hours (cattle). The serum elimination half-lives for sulfadiazine in various species is: 9. 84 hours (dogs), 2. 71 hours (horses), and 2. 5 hours (cattle). While trimethoprim is rapidly eliminated from the serum, the drug may persist for a longer period of time in tissues. Because of the number of variables involved, it is extremely diffi-cult to apply pharmacokinetic values in making dosage recommen-dations with these combinations. Each drug (trimethoprim and the sulfa) has different pharmacokinetic parameters (absorption, distri-bution, elimination) in each species. Since different organisms have different MIC values and the optimal ratio of trimethoprim to sulfa differs from organism to organism, this problem is exacerbated. There is considerable controversy regarding the frequency of administration of these combinations. The veterinary product, trimethoprim/sulfadiazine is labeled for once daily administration in dogs and horses, but many clinicians believe that the drug is more efficacious if given twice daily, regardless of which sulfa is used. contraindications/Precautions/Warnings The manufacturer states that trimethoprim/sulfadiazine should not be used in dogs or horses showing marked liver parenchymal damage, blood dyscrasias, or those with a history of sulfonamide sensitivity. It is not for use in horses (or approved for other ani-mals) intended for food. This combination should be used with caution in patients with pre-existing hepatic disease. Because of its potential for crystallization in the urine, it may be wise to avoid the use of sulfadiazine in dogs known to have uroliths, at increased risk for developing uroliths or known to have highly concentrated or acidic urine. adverse effects Adverse effects noted in dogs include: keratoconjunctivitis sicca (which may be irreversible), acute neutrophilic hepatitis with icter-us, vomiting, anorexia, diarrhea, fever, hemolytic anemia, urticaria, polyarthritis, facial swelling, polydipsia, polyuria and cholestasis. Potentiated sulfonamides may cause hypothyroidism in dogs, par-ticularly with extended therapy. Acute hypersensitivity reactions manifesting as Type I (anaphylaxis) or Type III reaction (serum sickness) can be seen. Hypersensitivity reactions appear to be more common in large breed dogs; Doberman Pinschers may possibly be more susceptible to this effect than other breeds. Other hemato-logic effects (anemias, agranulocytosis) are possible, but fairly rare. TMP/Sulfa has rarely been noted to cause an idiosyncratic, moder-ate to massive hepatic necrosis. TMP/Sulfa may be a risk factor for developing acute pancreatitis, but cause and effect have not been definitively shown. Adverse effects noted in cats may include anorexia, leukopenias and anemias. In horses, transient pruritus has been noted after intravenous injection. Oral therapy has resulted in diarrhea in some horses. Previous administration of potentiated sulfas has been implicated in increasing the mortality rate of associated with severe diarrhea. If the 48% injectable product is injected IM, SC, or extravasates af-ter IV administration, swelling, pain and minor tissue damage may result. Hypersensitivity reactions and hematologic effects (anemias, thrombocytopenia, or leukopenias) may also be seen; long-term therapy should include periodic hematologic monitoring. Sulfonamides (or their metabolites) can precipitate in the urine, particularly when given at high dosages for prolonged pe-riods. Acidic urine or highly concentrated urine may also contrib-ute to increased risk of crystalluria, hematuria, and renal tubule obstruction. Reproductive/nursing Safety Safety of trimethoprim/sulfa has not been clearly established in pregnant animals. Reports of teratogenicity (cleft palate) have been reported. Studies thus far in male animals have not dem-onstrated any decreases in reproductive performance. In humans, the FDA categorizes this drug as category C for use during preg-nancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no ani-mal reproduction studies and no adequate studies in humans. ) In a separate system evaluating the safety of drugs in canine and feline pregnancy (Papich 1989), this drug is categorized as in class: B (Safe for use if used cautiously. Studies in laboratory animals may have uncovered some risk, but these drugs appear to be safe in dogs and cats or these drugs are safe if they are not administered when the animal is near term. )	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
Su LFa Diazine/t Rimet Ho PRim; Su LF amet Hoxazo Le/t Rimet Ho PRim 849 Use TMP/sulfa products in nursing animals with caution. TMP-SMZ is not recommended for human use in the nursing period as sulfonamides are excreted in milk and may cause kernicterus. Premature infants and infants with hyperbilirubinemia or G-6-PD deficiency are also at risk for adverse effects. overdosage/acute t oxicity Manifestations of an acute overdosage can include clinical signs of GI distress (nausea, vomiting, diarrhea), CNS toxicity (depression, headache, and confusion), facial swelling, bone marrow depression and increases in serum aminotransferases. Oral overdoses can be treated by emptying the stomach, (following usual protocols), and initiating symptomatic and supportive therapy. Acidification of the urine may increase the renal elimination of trimethoprim, but could also cause sulfonamide crystalluria, particularly with sulfadiazine containing products. Complete blood counts (and other labora-tory parameters) should be monitored as necessary. Bone marrow suppression associated with chronic overdoses may be treated with folinic acid (leucovorin) if severe. Peritoneal dialysis is not effective in removing TMP or sulfas from the circulation. Drug interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving trimethoprim/sulfa and may be of significance in veterinary patients: amanta Dine T! : A human patient developed toxic delirium when re-ceiving amantadine with TMP/sulfa antaci DST! : May decrease the bioavailability of sulfonamides if ad-ministered concurrently cyc Lo SPo Rine T! : TMP/sulfa may increase the risk of nephrotoxicity Di Goxin T! : TMP/sulfa may increase digoxin levels Diu Retic S, t Hiazi De T! : May increase risk for thrombocytopenia Hy Po GL ycemic a Gent S, o Ra LT! : TMP/sulfa may potentiate effects met Hot Rexate T! : TMP/sulfa may displace from plasma proteins and increase risk for toxic effects; it can also interfere with MTX assays (competitive protein binding technique) PHenytoin T! : TMP/sulfa may increase half-life t Ricyc Lic anti De PRe SSant ST! : TMP/sulfa may decrease efficacy Wa RF a Rin T! : TMP/sulfa may prolong INR/PT Laboratory considerations When using the Jaffe alkaline picrate reaction assay for T! creatinine determination, trimethoprim/sulfa may cause an overestimation of approximately 10%. Sulfonamides may give false-positive results for T! urine glucose de-terminations when using the Benedict's method. Doses note : There is significant controversy regarding the frequency of dos-ing these drugs. See the pharmacokinetic section above for more infor-mation. Unless otherwise noted, doses are for combined amounts of trimethoprim/sulfa. Do GS:T! For susceptible infections: a) For UTI, pyoderma, soft tissue infections: 30 mg/kg PO q24h (not soft tissue infections) or 15 mg/kg PO q12h for 14 days. For chronic pyoderma, acanthamebiasis: 30 mg/kg PO q12h for 21-42 days. For systemic infections; bacteremia: 30-45 mg/kg PO q12h for 3-5 days. (Greene, Hartmannn et al. 2006) b) For bacterial UTI: 30 mg/kg q12h PO (Bartges 2007)c) For protozoal diseases: For toxoplasmosis: 15 mg/kg, PO q12h for 28 days. For Neospora: 15 mg/kg, PO q12h for 4 weeks. Used con-currently with clindamycin (10 mg/kg q12h for 4 weeks) or pyrimethamine (1 mg/kg PO once daily for 4 weeks). For Hepatazoon canis: 15 mg/kg, PO q12h for 2-4 weeks. Used concurrently with clindamycin (10 mg/kg PO q8h for 2-4 weeks) and pyrimethamine (0. 25 mg/kg PO once daily for 2-4 weeks) (Lappin 2000) d) For coccidiosis: 30 mg/kg PO once daily for 10 days (Matz 1995) e) For pneumocystosis (Pneumocystis carinii): 15 mg/kg PO q8h or 30 mg/kg PO q12h, both for 3 weeks. May be given with cimetidine and levamisole as potential immune stimulants. (Hawkins 2000) f) For Hepatazoon americanum: TMP/sulfa (15 mg/kg PO q12h), pyrimethamine (0. 25 mg/kg PO q24h), and clin-damycin (10 mg/kg q8h). Once remission attained decoqui-nate (see monograph) can maintain. (Baneth 2007) g) For Hepatazoon americanum: TMP/sulfa (15 mg/kg PO q12h for 14 days), pyrimethamine (0. 25 mg/kg PO q24h for 14 days), and clindamycin (10 mg/kg q8h for 14 days). Once remission attained decoquinate (see monograph) can maintain. For neosporosis: pyrimethamine (1 mg/kg PO daily) with TMP/sulfa (15-30 mg/kg PO twice daily. (Blagburn 2005a) cat ST! : For susceptible infections:a) For UTI: 30 mg/kg PO q24h for 7-14 days. For UTI, soft tissue infections: 15 mg/kg PO q12h for 7-14 days. (Greene, Hartmannn et al. 2006) b) 30 mg/kg q12h (if treating Nocardia, double dose) (Ford and Aronson 1985) c) For toxoplasmosis: 15 mg/kg PO q12h for 28 days (Lappin 2000) d) For bacterial UTI: 30 mg/kg q12h PO (Bartges 2007) Fe RRet S:T! For susceptible infections: a) 30 mg/kg PO twice daily (Williams 2000) b) For coccidiosis: 30 mg/kg PO once daily for 14 days. (John-son 2006c) Rabbit S, Ro Dent S, Sma LL mamma LS:T! a) Rabbits: 15-30 mg/kg, PO q12-24h; 30-48 mg/kg SC q12h. Sulfadiazine has a very short half-life (approx. 1 hour) in rab-bits. (Ivey and Morrisey 2000) b) Chinchillas, Gerbils, Guinea Pigs, Hamsters, Mice, Rats: 15-30 mg/kg PO q12h; or 30 mg/kg IM q12h (Adamcak and Otten 2000) c) Chinchillas: 30 mg/kg PO, SC or IM q12h (Hayes 2000) catt Le:T! For susceptible infections:a) 44 mg/kg once daily IM or IV using 48% suspension (Upson 1988) b) 25 mg/kg, IV or IM q24h (Burrows 1980) c) Calves: 48 mg/kg IV or IM q24h (Baggot 1983) Ho RSe S: T! For susceptible infections:a) For respiratory tract infections: 15-30 mg/kg PO q12h. Give 30 minutes prior to feeding hay (grain is OK) (Foreman 1999)	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
850 Su LFa Diazine/t Rimet Ho PRim; Su LF amet Hoxazo Le/t Rimet Ho PRim b) Foals: 15 mg/kg IV q12h; 30 mg/kg PO q12h (Brumbaugh 1999) c) 22 mg/kg IV q24h or 30 mg/kg, PO q24h (Upson 1988) d) 30 mg/kg PO once daily or 21. 3 mg/kg IV once daily (Pack-age inserts; Tribrissen®—Coopers) e) Foals: 15 mg/kg PO or IV twice daily (Furr 1999) f) For EPM: Sulfadiazine 20 mg/kg (either alone or as a poten-tiated sulfa) PO once or twice a day with Pyrimethamine (1 mg/kg PO once a day) for 90-120 days (or longer). Monitor: CBC's (Moore 1999) SWine:T! For susceptible infections: a) 48 mg/kg, IM q24h (Baggot 1983) bi RDS:T! For susceptible infections:a) Using TMP/SMX oral suspension (240 mg/5 m L): 2 m L/kg PO twice daily. Good for many gram-positive and negative enteric and respiratory infections, particularly in hand-fed babies. May cause emesis in Macaws. (Mc Donald 1989) b) For respiratory and enteric infections in psittacines using the 24% injectable suspension: 0. 22 m L/kg IM once to twice daily. For coccidiosis in toucans and mynahs using TMP/SMX oral suspension (240 mg/5 m L): 2. 2 m L/kg once daily for 5 days. May be added to feed. For respiratory and enteric infections in hand-fed baby psitt-acines using TMP/SMX oral suspension (240 mg/5 m L): 0. 22 m L/30 grams twice daily to three times daily for 5-7 days. (Clubb 1986) c) Using oral suspension: 50-100 mg/kg (of combined prod-uct) PO q12h (Hoeffer 1995) d) Ratites: For T oxoplasma gondii: 30-50 mg/kg IM twice daily (Jenson 1998) Re Pti Le S:T! For susceptible infections:a) For most species: 30 mg/kg IM (upper part of body) once daily for 2 treatments, then every other day for 5-12 treat-ments. May be useful for enteric infections. (Gauvin 1993) b) For all species: 30 mg/kg IM, first two doses 24 hours apart and then every other day (Jacobson 1999) c) 15-25 mg/kg/day IM for 7-14 days (Lewbart 2001) monitoring Clinical efficacy T! Adverse effects; with chronic therapy, periodic complete blood T! counts should be considered Thyroid function tests should be considered (baseline and on-T! going) particularly in dogs receiving long-term treatment client information If using oral suspension, shake well before using; does not need T! to be refrigerated Animals must be allowed free access to water and must not be-T! come dehydrated while on therapy If dogs eyes are dry or become irritated contact veterinarian T! chemistry/Synonyms Trimethoprim occurs as odorless, bitter-tasting, white to cream-colored crystals or crystalline powder. It is very slightly soluble in water and slightly soluble in alcohol. Sulfadiazine occurs as an odorless or nearly odorless, white to slightly yellow powder. It is practically insoluble in water and spar-ingly soluble in alcohol. Sulfamethoxazole occurs as a practically odorless, white to off-white, crystalline powder. Approximately 0. 29 mg are soluble in 1 m L of water and 20 mg are soluble in 1 m L of alcohol. In combination, these products may be known as: Co-trimoxazole, SMX-TMP, TMP-SMX, trimethoprim-sulfamethox-azole, sulfamethoxazole-trimethoprim, sulfadiazine-trimethoprim, trimethoprim-sulfadiazine, TMP-SDZ, SDZ-TMP, Co-trimazine or by their various trade names. Storage/Stability Unless otherwise instructed by the manufacturer, trimethoprim/sulfadiazine and co-trimoxazole products should be stored at room temperature (15-30°C) in tight containers. Dosage Forms/Regulatory Status/Withdrawal t imes Vete Rina R y-Labe Le D PRo Duct S: Trimethoprim (TMP)/Sulfadiazine (SDZ) Oral Paste: Each gram con-tains 67 mg trimethoprim and 333 mg sulfadiazine. Available in 37. 5 gram (total weight) syringes; Tribrissen® 400 Oral Paste (Schering-Plough); (Rx). Approved for use in horses not intended for food. Trimethoprim/Sulfadiazine Sterile Injection: 48% in 100 m L vials: Di-Biotic® 48% (Phoenix Pharmaceutical), Tribrissen® 48% Injection (Schering-Plough); (Rx) Approved for use in horses not intended for food. Trimethoprim/Sulfadiazine Powder: 67 mg trimethoprim and 333 mg sulfadiazine per gram: Tucoprim® Powder (Pharmacia & Upjohn) in 200 g & 400 g bottles and 2000 g pails, Uniprim® Powder (Macleod) in 37. 5 g and 1,125 g packets, 200 g jar, and 12 kg box; (Rx). Approved for use in horses not intended for food. In Canada, trimethoprim and sulfadoxine are available for use in cat-tle and swine (Trivetrin®—Wellcome; Borgal®—Hoechst). Slaughter withdrawal = 10 days; milk withdrawal = 96 hours. Human-Labe Le D PRo Duct S: Trimethoprim (alone) Tablets: 100 mg and 200 mg; Proloprim® (Glaxo Wellcome); Trimpex® (Roche); generic; (Rx) Trimethoprim 80 mg and Sulfamethoxazole 400 mg Tablets; Trimethoprim 160 mg and Sulfamethoxazole 800 mg Tablets: Bactrim®, Bactrim-DS® (Roche); Septra®, Septra® DS, (Glaxo Well-come); generic; (Rx) Trimethoprim 8 mg/m L and Sulfamethoxazole 40 mg/m L oral sus-pension in 20 m L, 100 m L, 150 m L, 200 m L, 473 m L, and 480 m L; Septra® (Glaxo Wellcome); Cotrim® Pediatric (Lemmon), Sulfatrim®, (various); generic; (Rx) Trimethoprim 16 mg/5 m L (3. 2 mg/m L) and Sulfamethoxazole 80 mg/5 m L (16 mg/m L) for injection in 5 m L Carpuject; 80 mg/5 m L (16 mg/m L) trimethoprim and 400 mg/5 m L (80 mg/m L) sulfame-thoxazole in 10 m L, 20 m L, 30 m L multi-dose vials and 5 m L vials; Bactrim® IV (Roche); Septra® IV (Monarch); generic; (Rx)	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
Su LFa Dimet Hoxine 851 Sulfadi Met Hoxine (sul-fa-dye-meth-ox-een) Albon® Sulfonamide antimicrobial Prescriber Highlights Sulfonamide antimicrobial agent T T Contraindications: Hypersensitivity to sulfas, thiazides, or T T sulfonylurea agents; severe renal or hepatic impairment Caution: Diminished renal or hepatic function, or urinary T T obstruction. Adverse Effects: Can precipitate in the urine (esp. with T T high dosages for prolonged periods, acidic urine or highly concentrated urine). DOGS: Keratoconjunctivitis sicca, bone marrow depression, hypersensitivity reactions (rash-es, dermatitis), focal retinitis, fever, vomiting & nonseptic polyarthritis possible Potentially teratogenic; weigh risk vs. benefit T T uses/indications Sulfadimethoxine injection and tablets are approved for use in dogs and cats for respiratory, genitourinary, enteric and soft tissue infec-tions caused by susceptible organisms. Sulfadimethoxine is used in the treatment of coccidiosis in dogs although not approved for this indication. In horses, sulfadimethoxine injection is approved for the treat-ment of respiratory infections caused by Streptococcus equi. In cattle, the drug is approved for treating shipping fever com-plex, calf diphtheria, bacterial pneumonia and foot rot caused by susceptible organisms. In poultry, sulfadimethoxine is added to drinking water to treat coccidiosis, fowl cholera, and infectious coryza. Pharmacology/actions Sulfonamides are usually bacteriostatic agents when used alone. They are thought to prevent bacterial replication by competing with para-aminobenzoic acid (PABA) in the biosynthesis of tetra-hydrofolic acid in the pathway to form folic acid. Only microorgan-isms that synthesize their own folic acid are affected by sulfas. Microorganisms that are usually affected by sulfonamides in-clude some gram-positive bacteria, including some strains of strep-tococci, staphylococcus, Bacillus anthracis, Clostridium tetani, C. perfringens, and many strains of Nocardia. Sulfas also have in vitro activity against some gram-negative species, including some strains of Shigella, Salmonella, E. coli, Klebsiella, Enterobacter, Pasturella, and Proteus. Sulfas have activity against some rickettsia and proto-zoa (T oxoplasma, Coccidia). Unfortunately, resistance to sulfas is a progressing phenomenon and many strains of bacteria that were once susceptible to this class of antibacterial are now resistant. The sulfas are less efficacious in pus, necrotic tissue, or in areas with extensive cellular debris. Pharmacokinetics In dogs, cats, swine, and sheep, sulfadimethoxine is reportedly read-ily absorbed and well distributed. Relative volumes of distribution range from 0. 17 L/kg in sheep to 0. 35 L/kg in cattle and horses. The drug is highly protein bound. In most species, sulfadimethoxine is acetylated in the liver to acetylsulfadimethoxine and excreted unchanged in the liver. In dogs, the drug is not appreciably hepatically metabolized and renal excretion is the basis for the majority of elimination of the drug. Sulfadimethoxine's long elimination half-lives are a result of its appreciable reabsorption in the renal tubules. Serum half-lives reported in various species are: swine 14 hours; sheep 15 hours; horses 11. 3 hours. contraindications/Precautions/Warnings Sulfonamides are contraindicated in patients hypersensitive to them, thiazides, or sulfonylurea agents. They are also considered contraindicated in patients with severe renal or hepatic impairment and should be used with caution in patients with diminished renal or hepatic function, or urinary obstruction. Oral sulfonamides can depress the normal cellulytic function of the ruminoreticulum, but this effect is generally temporary and the animal adapts. adverse effects Sulfonamides (or their metabolites) can precipitate in the urine, particularly when given at high dosages for prolonged periods. Acidic urine or highly concentrated urine may also contribute to increased risk of crystalluria, hematuria, and renal tubule obstruc-tion. Different sulfonamides have different solubilities at various p H's. Alkalinization of the urine using sodium bicarbonate may prevent crystalluria, but it also decreases the amount available for tubular reabsorption. Crystalluria can usually be avoided with most of the commercially available sulfonamides by maintaining an ad-equate urine flow. Normal urine p H in herbivores is usually 8 or more, so crystalluria is not frequently a problem. Sulfonamides can also cause various hypersensitivity reactions or diarrhea by altering the normal gut flora. T oo rapid intravenous injection of the sulfas can cause muscle weakness, blindness, ataxia, and collapse. In dogs, keratoconjunctivitis sicca, bone marrow depression, hypersensitivity reactions (rashes, dermatitis), focal retinitis, fever, vomiting and nonseptic polyarthritis have been reported with sul-fonamides. Oral sulfonamides can depress the normal cellulytic function of the ruminoreticulum, but this effect is generally temporary and the animal adapts. Because solutions of sulfonamides are usually alkaline, they can cause tissue irritation and necrosis if injected intramuscularly or subcutaneously. Reproductive/nursing Safety Sulfas cross the placenta and may reach fetal levels of 50% or greater of those found in maternal serum; teratogenicity has been reported in some laboratory animals when given at very high doses. They should be used in pregnant animals only when the benefits clearly outweigh the risks of therapy. Sulfonamides are distributed into milk.	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
852 Su LFa Dimet Hoxine overdosage/acute t oxicity Acute toxicity secondary to overdoses apparently occurs only rarely in veterinary species. In addition to the adverse effects listed above, CNS stimulation and myelin degeneration have been noted after very high dosages. Drug interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving sulfonamides and may be of significance in veterinary patients: antaci DST! : May decrease the oral bioavailability of sulfonamides if administered concurrently Laboratory considerations Sulfonamides may give false-positive results for T! urine glucose de-terminations when using the Benedict's method. Doses Do GS:T! For susceptible infections:a) 25 mg/kg PO, IV, or IM once daily (Davis 1985), (Kirk 1989) b) 100 mg/kg PO, IV or IM once daily (Upson 1988) c) 55 mg/kg PO, or IV, or SC initially, then 27. 5 mg/kg once daily thereafter (Package insert; Albon®—Roche) For coccidiosis:a) 55 mg/kg PO initially on the first day of therapy, then 27. 5 mg/kg PO once daily for 9 days (Matz 1995) b) 50 mg/kg once daily for 10-14 days will eliminate oocyst ex-cretion in most dogs and cats. (Marks 2007c) c) During the infant period (2-6 weeks): 50 mg/kg PO on the first day followed by a daily dose of 25 mg/kg PO until symp-toms regress (Macintire 2004) cat S:T! For susceptible infections:a) 25 mg/kg PO, IV, or IM once daily (Davis 1985), (Kirk 1989) b) 100 mg/kg PO, IV or IM once daily (Upson 1988) c) 55 mg/kg PO, or IV, or SC initially, then 27. 5 mg/kg once daily thereafter (Package insert; Albon®—Roche) For coccidiosis: a) 50 mg/kg once daily for the first day, then 25 mg/kg once daily for 14-20 days. Sulfas are coccidiostatic. It is important that supportive care, including fluids and good nutrition be maintained during therapy. (Cornelius and Roberson 1986) b) 50 mg/kg once daily for 10-14 days will eliminate oocyst ex-cretion in most dogs and cats. (Marks 2007c) Fe RRet S:T! For susceptible infections: a) 25 mg/kg PO, SC or IM once daily (Williams 2000) b) For coccidiosis: 25 mg/kg PO once daily for 14 days. (John-son 2006c) Rabbit S, Ro Dent S, Sma LL mamma LS:T! a) Rabbits: 10-15 mg/kg PO q12h (Ivey and Morrisey 2000) b) Rabbits: For coccidiosis: 25 mg/kg PO once daily (Burke 1999) c) Hedgehogs: 2-20 mg/kg/day IM, SC or PO (Smith 2000) d) Mice, Rats, Gerbils, Hamsters, Guinea pigs, Chinchillas: As a coccidiostat: 50 mg/kg PO once, then 25 mg/kg PO once daily for 10-20 days or 75 mg/kg PO for 7-14 days (Adam-cak and Otten 2000)catt Le:T! For susceptible infections:a) 110 mg/kg PO or IV once daily (Upson 1988) b) 55 mg/kg IV initially, then 27. 5 mg/kg IV once daily (Baggot 1983) c) 110 mg/kg, PO q24h (Burrows 1980) d) 55 mg/kg PO or IV initially, then 27. 5 mg/kg q24h (Jenkins 1986) e) 55 mg/kg IV or PO initially, then 27. 5 mg/kg q24h IV or PO for up to 5 days. If using sustained release boluses: 137. 5 mg/kg PO every 4 days (Package insert; Albon®—Roche) Ho RSe S:T! For susceptible infections:a) 55 mg/kg, PO or IV q12h (Upson 1988) b) 55 mg/kg IV or PO initially, then 27. 5 mg/kg q24h IV (Pack-age insert; Albon®—Roche) Re Pti Le S:T! For susceptible infections: a) For coccidia: 90 mg/kg PO on day one and then 45 mg/kg PO on 5 successive days; may also be given IM or IV. Maintain adequate hydration. (Lewbart 2001) chemistry/Synonyms A long-acting sulfonamide, sulfadimethoxine occurs as an odorless or almost odorless, creamy white powder. It is very slightly soluble in water and slightly soluble in alcohol. Sulfadimethoxine may also be known as: solfadimetossina, solfadimetossipirimidina, sulphadimethoxine, Albon®, Amtech®, Chemiosalfa®, Deltin®, Di-Methox®, Risulpir®, Ritarsulfa®, SDM®, Sulfadren®, Sulfastop®, or Sulfasol®, and Sulfathox®. Storage/Stability Unless otherwise instructed by the manufacturer, store sulfadime-thoxine products at room temperature and protect from light. If crystals form due to exposure to cold temperatures, either warm the vial or store at room temperature for several days to resolubolize the drug; efficacy is not impaired by this process. Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: Sulfadimethoxine Injection: 400 mg/m L (40%) in 100 m L vials; Albon® Injection 40% (Pfizer Animal Health); Amtech® Sulfadime-thoxine Injection 40% (IV use only in cattle) (Phoenix Scientific), Di-Methox® Injection 40% (Agri Labs), generic; (Agripharm, Aspen, Butler, Durvet, Vedco), SDM® Injection (Phoenix Pharmaceutical); (Rx) Approved for use in dogs, cats, horses, swine and cattle. Not to be used in horses intended for food or calves to be processed for veal. Slaughter withdrawal (at labeled doses) = 5 days (cattle); milk with-drawal (at labeled doses) = 60 hours. Sulfadimethoxine Oral Tablets: 125 mg, 250 mg, and 500 mg; Albon® Tablets (Pfizer Animal Health); (Rx). Approved for use in dogs and cats. Sulfadimethoxine Oral Suspension: 50 mg/m L in 2 oz. and 16 oz. Bottles; Albon® (Pfizer); (Rx). Approved for use in dogs and cats. Sulfadimethoxine Oral Boluses: 5 g, and 15 g; Albon® (Pfizer); (OTC). Approved for use in cattle. Not to be used in calves to be processed for veal. No withdrawal period has been established for this in pre-ruminating calves. Slaughter withdrawal (at labeled doses) = 7 days (cattle); milk withdrawal (at labeled doses) = 60 hours. Sulfadimethoxine Oral Boluses Sustained-Release: 12. 5 g; Albon® SR (Pfizer); (Rx) Approved for use in non-lactating cattle. Slaughter	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
Su LFa Dimet Hoxine/o Rmeto PRim 853 withdrawal (at labeled doses) = 21 days (cattle), a withdrawal period has not been established for pre-ruminating calves. Not for use in calves intended to be processed for veal. Sulfadimethoxine Soluble Powder: 94. 6 g/packet (for addition to drinking water); Albon® (Pfizer), Di-Methox® Soluble Powder (Agri-Labs), generic; (Agri Pharm, Aspen, Durvet, Phoenix Scientific, Ve-dco), Sulfasol® (Med-Pharmex); (OTC) Approved for use in dairy calves, dairy heifers, beef cattle, broiler and replacement chickens only, and meat-producing turkeys. Slaughter withdrawal (at labeled doses) = 7 days (cattle); 5 days (poultry—do not use in chickens over 16 weeks old or in turkeys over 24 weeks old). Sulfadimethoxine 12. 5% Concentrated Solution (for addition to drinking water): Albon® (Pfizer), Amtech® generic; (Phoenix Scien-tific), Di-Methox® 12. 5% Oral Solution (Agri Labs), SDM® Solution (Phoenix Pharmaceutical), generic; (Agri Pharm, Aspen, Butler, Du-rvet, Vedco), Sulforal® (Med-Pharmex); (OTC). Approved for use in chickens, turkeys and cattle. Slaughter withdrawal (at labeled doses) = 7 days (for dairy calves, dairy heifers and beef cattle only. With-drawal for pre-ruminating calves has not been established) Not to be used in calves to be processed for veal; 5 days (poultry—do not use in chickens over 16 weeks old or in turkeys over 24 weeks old). Human-Labe Le D PRo Duct S: None Sulfadi Met Hoxine/ or Metopri M (or-me-toe-prim) Primor® Potentiated Sulfonamide antimicrobial Prescriber Highlights Potentiated sulfa similar to trimethoprim/sulfa. The fol-T T lowing apply to TMP/Sulfa & may correlate to this agent as well: Contraindications: Hypersensitive to sulfas, thiazides, or T T sulfonylurea agents; severe renal or hepatic impairment Caution: Diminished renal or hepatic function, or urinary T T obstruction or urolithiasis Adverse Effects: T T DOGS: Keratoconjunctivitis sicca, hyper-sensitivity (type 1 or type 3) acute neutrophilic hepatitis with icterus, vomiting, anorexia, diarrhea, fever, hemolytic anemia, urticaria, polyarthritis, facial swelling, polydipsia, crystalluria, hematuria, polyuria, cholestasis, hypothy-roidism, anemias, agranulocytosis, idiosyncratic hepatic necrosis in dogs. CATS: Anorexia, crystalluria, hematuria, leukopenias & anemias Potentially teratogenic, weigh risk vs. benefit T T uses/indications Sulfadimethoxine/ormetoprim is approved for the treatment of skin and soft tissue infections in dogs caused by susceptible strains of Staphylococcus aureus and E. coli. Pharmacology/actions Sulfadimethoxine/ormetoprim shares mechanisms of action and probably the bacterial spectrum of activity with trimethoprim/sulfa. Alone, sulfonamides are bacteriostatic agents, but in combination with either ormetoprim or trimethoprim, the potentiated sulfas are bactericidal. Potentiated sulfas sequentially inhibit enzymes in the folic acid pathway, thereby inhibiting bacterial thymidine synthe-sis. The sulfonamide blocks the conversion of para-aminobenzoic acid (PABA) to dihydrofolic acid (DFA) and ormetoprim blocks the conversion of DFA to tetrahydrofolic acid by inhibiting dihydrofo-late reductase. The potentiated sulfas have a fairly broad spectrum of activ-ity. Gram-positive bacteria that are generally susceptible include most streptococci, many strains of staphylococcus, and Nocardia. Many gram-negative organisms of the family Enterobacteriaceae are susceptible to the potentiated sulfas, but not Pseudomonas aeruginosa. Some protozoa (Pneumocystis carinii, Coccidia and T oxoplasma) are also inhibited by the combination. Potentiated sulfas reportedly have little activity against most anaerobes, but opinions on this vary. Resistance will develop more slowly to the combination of drugs, than to either one alone. In gram-negative organisms, resistance is usually plasmid-mediated. Pharmacokinetics The pharmacokinetics of sulfadimethoxine are outlined in the pre-vious monograph. Pharmacokinetic data for ormetoprim is not available at the time of this writing, but the manufacturer states that therapeutic levels are maintained over 24 hours at recommended doses. contraindications/Precautions/Warnings The manufacturer states that ormetoprim/sulfadimethoxine should not be used in dogs showing marked liver parenchymal damage, blood dyscrasias, or in those with a history of sulfonamide sensitivity. This combination should be used with caution in patients with pre-existing hepatic or thyroid disease. adverse effects This combination would be expected to exhibit an adverse reac-tion profile in dogs similar to that seen with trimethoprim/sulfa, including: keratoconjunctivitis sicca (which may be irreversible), acute neutrophilic hepatitis with icterus, vomiting, anorexia, diar-rhea, fever, hemolytic anemia, urticaria, polyarthritis, facial swell-ing, polydipsia, polyuria, and cholestasis. Acute hypersensitivity reactions manifesting as Type I, (anaphylaxis) or Type III reaction (serum sickness) can also be seen. Hypersensitivity reactions ap-pear to be more common in large breed dogs; Doberman Pinschers may possibly be more susceptible to this effect than other breeds. Other hematologic effects (anemias, agranulocytosis) are possible, but fairly rare. Long-term (8 weeks) therapy at recommended doses with orme-toprim/sulfadimethoxine (27. 5 mg/kg once daily) resulted in el-evated serum cholesterol, thyroid and liver weights, mild follicular thyroid hyperplasia, and enlarged basophilic cells in the pituitary. The manufacturer states that the principal treatment-related effect of extended or excessive usage is hypothyroidism. Reproductive/nursing Safety Safety of ormetoprim/sulfadimethoxine has not been established in pregnant animals. Reports of teratogenicity (cleft palate) have been reported in some lab animals with trimethoprim/sulfa. overdosage/acute t oxicity In experimental studies in dogs, doses greater than 80 mg/kg re-sulted in slight tremors and increased motor activity in some dogs. Higher doses may result in depression, anorexia, or seizures. It is suggested that very high oral overdoses be handled by emp-tying the gut using standard precautions and protocols and by treating clinical signs supportively and symptomatically.	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
854 Su LFa Sa Lazine Drug interactions; Laboratory considerations None have been noted for this combination, but it would be expect-ed that the potential interactions outlined for the trimethoprim/sulfa monograph would also apply to this combination; refer to that monograph for more information. Doses Do GS:T! For susceptible infections:a) Initially 55 mg/kg (combined drug) PO on the first day of therapy, then 27. 5 mg/kg PO once daily for at least 2 days after remission of clinical signs. Not approved for treatment longer than 21 days. (Package insert; Primor®—Pfizer) monitoring Clinical efficacy T! Adverse effects T! client information Animals must be allowed free access to water and must not be-T! come dehydrated while on therapy. chemistry/Synonyms A diaminopyrimidine structurally related to trimethoprim, orme-toprim occurs as a white, almost tasteless powder. The chemistry of sulfadimethoxine is described in the previous monograph. Sulfadimethoxine may also be known as: solfadimetossina, sol-fadimetossipirimidina, sulphadimethoxine, Chemiosalfa®, Deltin®, Risulpir®, Ritarsulfa®, Sulfadren®, Sulfastop®, or Sulfathox®. Ormetoprim may also be known as NSC-95072, ormetoprima, ormétoprime, ormetoprimum, or Ro-5-9754. Storage/Stability Unless otherwise instructed by the manufacturer, store tablets in tight, light resistant containers at room temperature. Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: Sulfadimethoxine/Ormetoprim Tablets (scored) 120's: 100 mg Sulfadimethoxine, 20 mg Ormetoprim240's: 200 mg Sulfadimethoxine, 40 mg Ormetoprim600's: 500 mg Sulfadimethoxine, 100 mg Ormetoprim1200's: 1000 mg Sulfadimethoxine, 200 mg Ormetoprim; Primor® (Pfizer); (Rx) Approved for use in dogs. Sulfadimethoxine/Ormetoprim medicated premix: 113. 5 g sulfadi-methoxine and 68. 1 g ormetoprim per pound in 50 lb bags. Approved for use in chickens [broilers, replacements (breeders and layers)], tur-keys, ducks, & Chukar partridges. Slaughter withdrawal (at labeled doses) = 5 days. Do not feed to chickens over 16 weeks or age, turkeys or ducks producing eggs for food. Rofenaid® 40 (Alpharma), Romet® 30 (Alpharma)—Approved for use in salmonids (trout and salmon) and catfish. Slaughter or release as stocker fish = 42 days. (OTC) Human-Labe Le D PRo Duct S: None Sulfa Salazine (sul-fa-sal-a-zeen) Azulfidine® Sulfonamide/Salicylate antibacterial/ immuno Su PPre SSive Prescriber Highlights Sulfa-analog that has GI antibacterial & antiinflamma-T T tory activity used for inflammatory bowel disease; has also been used for vasculitis Contraindications: Hypersensitivity to it, sulfas or salicy-T T lates; intestinal or urinary obstructions Caution: Liver, renal or hematologic diseases; cats T T Adverse Effects: T T DOGS: Keratoconjunctivitis sicca, anorex-ia, vomiting, cholestatic jaundice, hemolytic anemia, leu-kopenia, vomiting, decreased sperm counts & an allergic dermatitis. CATS: Anorexia, vomiting, anemias uses/indications Sulfasalazine is used for the treatment of inflammatory bowel dis-ease in dogs and cats. It has also been suggested for adjunctive use in treating vasculitis in dogs. Pharmacology/actions While the exact mechanism of action for its therapeutic effects in treating colitis in small animals has not been determined, it is believed that after sulfasalazine is cleaved into sulfapyridine and 5-aminosalicylic acid (5-ASA, mesalamine) by bacteria in the gut the antibacterial (sulfapyridine) and/or antiinflammatory (mesala-mine) activity alters the clinical signs/course of the disease. Levels of both drugs in the colon are higher then by giving them orally as separate agents. Pharmacokinetics Only about 10-33% of an orally administered dose of sulfasalazine is absorbed. Apparently, some of this absorbed drug is then excret-ed unchanged in the bile. Unabsorbed and biliary excreted drug is cleaved into 5-ASA and sulfapyridine in the colon by bacterial flora. The sulfapyridine component is rapidly absorbed, but only a small percentage of the 5-ASA is absorbed. Absorbed sulfapyridine and 5-ASA are hepatically metabolized and then renally excreted. contraindications/Precautions/Warnings Sulfasalazine is contraindicated in animals hypersensitive to it, sul-fonamides or salicylates. It is also contraindicated in patients with intestinal or urinary obstructions. It should be used with caution in animals with preexisting liver, renal or hematologic diseases. Because cats can be sensitive to salicylates (see the aspirin mono-graph), use caution when using this drug in this species. adverse effects Although adverse effects do occur in dogs, with keratoconjunctivi-tis sicca (KCS) reported most frequently, they are considered to oc-cur relatively uncommonly. Other potential adverse effects include anorexia, vomiting, cholestatic jaundice, hemolytic anemia, leuko-penia, vomiting, decreased sperm counts and an allergic dermatitis. Should decreased tear production be noted early, either reducing the dose or discontinuing the drug may prevent progression of KCS or increase tear production.	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
Su LFa Sa Lazine 855 Cats can occasionally develop anorexia and vomiting which may be alleviated by use of the enteric-coated tablets. Anemias second-ary to sulfasalazine are also potentially possible in cats. Reproductive/nursing Safety Although sulfasalazine has not been proven harmful to use during pregnancy and incidences of neonatal kernicterus in infants born to women taking sulfasalazine are low, it should only be used when clearly indicated. In laboratory animal studies (rats, rabbits), doses of six times normal (human) caused impairment of fertility in male animals; this effect is thought to be caused by the sulfapyridine component and was reversible upon discontinuation of the drug. In humans, the FDA categorizes this drug as category B for use during pregnancy (Animal studies have not yet demonstrated risk to the fetus, but there are no adequate studies in pregnant women; or animal studies have shown an adverse effect, but adequate studies in pregnant women have not demonstrated a risk to the fetus in the first trimester of pregnancy, and there is no evidence of risk in later trimes-ters. ) In a separate system evaluating the safety of drugs in canine and feline pregnancy (Papich 1989), this drug is categorized as in class: B (Safe for use if used cautiously. Studies in laboratory animals may have uncovered some risk, but these drugs appear to be safe in dogs and cats or these drugs are safe if they are not administered when the animal is near term. ) Sulfonamides are excreted in milk. In human newborns, they compete with bilirubin for binding sites on plasma proteins and may cause kernicterus. Use with caution in nursing patients. overdosage/acute t oxicity Little specific information is available regarding overdoses with this agent, but because massive overdoses could cause significant salicy-late and/or sulfonamide toxicity, standard protocols (empty stom-ach, cathartics, etc. ) should be considered. Urine alkalinization and forced diuresis may also be beneficial in selected cases. Drug interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving sulfasalazine and may be of significance in veterinary patients: c HLo RPRo P ami De T! : Hypoglycemic effects could be potentiated Di Goxin T! : Sulfasalazine may reduce absorption Fe RRou S Su LFate T! or other iron salts : May decrease the blood levels of sulfasalazine if administered concurrently; clinical significance is unknown Fo Lic aci DT! : Oral absorption may be inhibited Wa RF a Rin T! : Potentially sulfasalazine could potentiate warfarin Doses Do GS:T! For inflammatory large bowel disease:a) 20-30 mg/kg q8-12h PO. (Hall 2004) b) 10-15 mg/kg PO q8-12h for 2 weeks tapered to the lowest effective dose (Moore 2004) c) 20-48. 4 mg/kg (maximum total dose of one gram in refrac-tory patients) PO q8h. May consider an initial dose of 12. 5 mg/kg, q8h. Continue initial dose for a minimum of 4 weeks before modifying dosage. After signs of disease resolve, re-duce dosage by 25% at 2 week intervals and eventually dis-continue while maintaining dietary management. (Jergens and Willard 2000) d) For chronic colitis: If hypoallergenic diet does not control signs, sulfasalazine 20-50 mg/kg (up to a maximum of 1 gram) three times daily. Initial dosage usually 20-30 mg/ kg three times daily. Dose may be reduced at 2-4 week in-tervals if stool remains normal using the following protocol: Initially same dose given twice daily, then 50% of initial dose twice daily, then 50% of that dose once daily, then discon-tinue. Some dogs may require chronic therapy. (Leib 2000) e) Usual initial dose is 20-40 mg/kg q8h for 3 weeks, followed by 20-40 mg/kg PO q12h for 3 weeks, then 10-20 mg/kg q12h for 3 weeks. (Marks 2007b) f) 10-25 mg/kg PO three times a day for 4-6 weeks. With resolution of clinical signs, reduce dose by 25 percent at 2 week intervals and eventually discontinue while maintaining dietary management. (Washabau 2005) For adjunctive treatment of vasculitis:a) 20-40 mg/kg PO q8h (Hillier 2006d), (Griffin 2006) b) 25 mg/kg PO three times a day. (Bloom 2006b) cat S:T! For inflammatory large bowel disease:a) 10-20 mg/kg PO once daily. Use cautiously in cats because of their sensitivity to salicylates (Jergens and Willard 2000) b) 10-20 mg/kg PO q24 hours (once daily) tapered to the low-est effective dose (Moore 2004), (Marks 2007b) c) 10-20 mg/kg PO q8-12h (maximum of 10 days) (Dimski 1995) d) 10-20 mg/kg PO q8-24h; up to a maximum of 10 days treatment (Krecic 2002) Fe RRet S:T! a) 10-20 mg/kg PO 2-3 times a day (Williams 2000) b) 25 mg (total dose) PO twice daily (Weiss 2002b) monitoring Efficacy T! Adverse effects, particularly KCS; Schirmer tear tests should be T! performed prior to therapy (and on rechecks), especially in mid-dle-aged to older dogs Occasional CBC, liver function tests are warranted with chronic T! therapy client information Clients should monitor for clinical signs of KCS (dry cornea, T! blepharospasm, bilateral mucopurulent discharge) and report them to the veterinarian immediately. chemistry/Synonyms Sulfasalazine is basically a molecule of sulfapyridine linked by a diazo bond to the diazonium salt of salicylic acid. It occurs as an odorless, bright yellow to brownish-yellow fine powder. Less than 0. 1 mg is soluble in 1 m L of water and about 0. 34 mg is soluble in 1 m L of alcohol. Sulfasalazine may also be known as: salazosulfapyridine, sali-cylazosulfapyridine, sulfasalazinum, sulphasalazine, Azulfidine®, Aculfin®, Azulfin®, Colo-Pleon®, Pleon RA®, Pyralin®, SAS®, Salazine®, Salazopirina®, Salazoprin®, Salazopyrin®, Salazopyrina®, Salazopyrine®, Salisulf Gastroprotetto®, Salopyrine®, Saridine®, Sazo®, Sulazine®, or Ulco ®. Storage/Stability Sulfasalazine tablets (either plain or enteric-coated) should be stored at temperatures less than 40°C and preferably at room temperature (15-30°C, 59-86°F) in well-closed containers. The oral suspension should be stored at room temperature (15-30°C, 59-86°F); avoid freezing.	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
856 tau Rine Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: None Human-Labe Le D PRo Duct S: Sulfasalazine Tablets: 500 mg; Azulfidine® (Pfizer); (Rx); generic; (Rx) Sulfasalazine Delayed-Release Tablets: 500 mg (enteric coated); Azul-fidine® EN-tabs® (Pfizer); (Rx) Syrup of Ipecac-see Ipecac Syrup taurine (tor-een) amino acid nutritional Prescriber Highlights Amino acid used primarily for the treatment of taurine T T deficiency cardiomyopathies in cats & dogs May also be useful for many other conditions (T T e. g., sei-zures), but little supporting data available Very low toxic potential T T Laboratory considerations T T uses/indications Taurine has proven beneficial in preventing retinal degeneration and the prevention and treatment of taurine-deficiency dilated cardiomyopathy in cats. Although modern commercial feline diets have added taurine, some cats still develop taurine-deficiency as-sociated dilated cardiomyopathy. It may also be of benefit in tau-rine (±carnitine) deficient cardiomyopathy in American Cocker Spaniels and certain other breeds such as, Golden Retrievers, Labrador Retrievers, Newfoundlands, Dalmations, Portuguese Water Dogs, and English Bulldogs. Preliminary studies have shown evidence that it may be useful as adjunctive treatment for cardiac disease in animals even if taurine deficiency is not present. Because of its low toxicity, some have suggested it be tried for a multitude of conditions in humans and animals; unfortunately, little scientific evidence exists for these uses. Pharmacology/actions While classically considered a “non-essential” nutrient, taurine has been found to play several “essential” roles in various mammalian species. Taurine is important for bile acid conjugation, especially in cats and dogs. In vivo, taurine is synthesized from methionine. Cysteinesulfinic acid decarboxylase (CSAD) and vitamin B 6 are in-volved with this synthesis. Deficiencies of either will depress taurine synthesis. Cats are particularly susceptible to taurine deficiency as they have low CSAD activity and use taurine almost exclusively for bile acid conjugation. Additionally taurine is important in the modulation of calcium flux, thereby reducing platelet aggregation, stabilizing neuronal membranes, and affecting cardiac function. Taurine's effects on cardiac function include positive inotropic activity without affect-ing resting potential and modulating ionic currents across the cell membrane. Taurine is important for normal development of the CNS and it has a GABA-like effect that may make it useful for treat-ing some seizure disorders. Pharmacokinetics No specific information was located. Excess taurine is rapidly ex-creted in the kidneys, but if a deficiency exists, urinary excretion is reduced via reabsorption. contraindications/Precautions/Warnings While taurine is safe, it should not be used as a substitute for ad-equate diagnosis. adverse effects Taurine appears to be very well tolerated. Minor GI distress poten-tially could occur after oral dosing. overdosage/acute t oxicity No specific information was located, but toxic potential appears to be very low. Drug interactions None are reported. Laboratory considerations Because plasma levels may reflect the acute changes associated T! with dosing, whole blood levels are preferred to measure actual status of taurine in the body. Because intracellular levels of tau-rine are much higher than in plasma, hemolysis or collection of the buffy coat will negate the results. Doses Do GS:T! a) For taurine-deficiency related cardiomyopathy: In American Cocker Spaniels: Give 500 mg taurine PO q12h (with 1 gram of carnitine PO q12h) (Kittleson 2000) b) Complementary therapy for seizures: 400 mg/40 lbs of body weight PO twice daily. “May” help decrease seizure activity (Neer 2000) cat S:T! a) For taurine-deficiency related cardiomyopathy: 250 mg (per cat) PO q12-24h. Because taurine is safe and inexpensive, recommend using for any case of myocardial failure. (Fox 2000) b) Complementary therapy for seizures: 500 mg Per cat PO twice daily. “May” help decrease seizure activity (Neer 2000) monitoring Clinical efficacy T! Taurine levels (if possible and affordable; whole blood levels pref-T! erable to plasma/serum levels) chemistry/Synonyms Taurine, an amino acid also known as 2-aminosulphonic acid, has a molecular wt. of 125. Solubility in 100 m L of water at 20°C is 8. 8 grams. Storage/Stability Unless otherwise labeled, store taurine tablets or capsules at room temperature. Protect from light and moisture. Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: The following products are labeled for use in animals: Taurine Tablets: 250 mg: Formula V® Taurine Tablets (Pet Ag); La-beled for use in cats. Taurine Liquid: 375 mg/4 m L (one pump); Dyna-Taurine® (Harl-men); Labeled for use in dogs and cats.	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
te Poxa Lin 857 Human-Labe Le D PRo Duct S: There are several oral dosage form products available for taurine. T echnically considered a “nutrient” they are all OTC and may need to be obtained from health food stores. Most dosage forms available range from 125 mg to 500 mg. tepoxalin (te-pox-a-lin) Zubrin® non Steroidal antiinflammatory agent Prescriber Highlights NSAID dual inhibitor of COX & LOX indicated for the T T treatment of pain & inflammation associated with os-teoarthritis in dogs Adverse effect profile still being determined, but may T T cause more vomiting & diarrhea than some other ap-proved NSAIDs Rapidly disintegrating tablet dosage form may be useful T T in difficult to pill dogs uses/indications T epoxalin is indicated for the treatment of pain and inflammation associated with osteoarthritis in dogs. Because of the drug's inhibi-tory effects on leukotrienes, there is interest in seeing if it would be beneficial in the adjunctive treatment of allergic conditions in dogs. Pharmacology/actions T epoxalin is a dual inhibitor of both cyclooxygenase (COX) and 5-lipoxygenase (LOX). It inhibits both COX-1 and COX-2 enzymes, but it is not clear if it is COX-2 preferential in the dog (it is not COX-2 preferential in sheep uterine cells) or if its LOX inhibition reduces the adverse effects associated with COX-1 inhibition. By inhibiting COX-2 enzymes, tepoxalin reduces the production of prostaglandins associated with pain, hyperpyrexia and inflamma-tion. Its inhibition of LOX potentially reduces the production of leukotrienes, including leukotriene B4. As leukotriene B4 may con-tribute to increased GI tract inflammation by increasing cytokine production, neutrophil longevity and release of proteinases, inhibi-tion may reduce the GI effects routinely seen in dogs with COX-1 inhibitors. Leukotrienes may also contribute to inflammatory re-sponses seen in osteoarthritic conditions and their inhibition could reduce clinical signs seen with the condition. Pharmacokinetics After oral administration to dogs, tepoxalin is readily absorbed and peak levels occur between 2-3 hours post-dose. The presence of food in the gut increases bioavailability. T epoxalin is rapidly me-tabolized to several metabolites, including one that it active (tep-oxalin pyrazole acid). T epoxalin and tepoxalin pyrazole acid are highly bound to plasma proteins (98-99%). Elimination half-lives for tepoxalin and tepoxalin pyrazole acid are about 2 hours and 13 hours, respectively. Metabolites are eliminated in the feces; only 1% of the drug is eliminated in the urine. contraindications/Precautions/Warnings T epoxalin is contraindicated in dogs demonstrating prior hyper-sensitivity reactions to tepoxalin. It should be used with caution in patients with impaired hepatic, cardiovascular or renal function, or at risk for developing nephrotoxic affects associated with NSAIDs (i. e., dehydrated or on concomitant diuretic therapy). Patients with active gastrointestinal ulcers should probably not receive this drug. Dogs weighing less than 3 kg cannot be accurately dosed with avail-able dosage forms. Safety in dogs less than 6 months old has not been established. adverse effects Adverse effects most likely seen in dogs include diarrhea, vomiting, anorexia/inappetence, enteritis, and lethargy. In one study where dogs received labeled doses for 4 weeks, 22% of dogs developed di-arrhea and 20% vomited. It is unknown if giving the drug with food will decrease vomiting incidence. Other adverse effects reported (incidences <1%) include incoordination, incontinence, increased appetite, eating grass, flatulence, hair loss, and trembling. The manufacturer warns to discontinue the drug if signs such as inappetence, vomiting, fecal abnormalities, anemia, icterus, or lethargy are observed. Safety studies in dogs less than 6 months of age have not been completed. Reproductive/nursing Safety Safety of this drug has not been determined in pregnant, breeding, or lactating dogs; use with caution and with informed consent of client. overdosage/acute t oxicity Information on acute overdosage of tepoxalin was not located. Dogs receiving 300 mg/kg/day for 6 months showed decreases in total protein, albumin and calcium concentrations. At necropsy, all dogs showed gastric lesions. An acute overdose may cause signifi-cant GI distress and ulceration with GI bleeding. It is suggested to treat supportively and monitor CBC, hydration, renal function, and for evidence of GI bleeding. Contact an animal poison control cen-ter for more information. Drug interactions A study in normal dogs showed no significant changes in renal function when enalapril was used with tepoxalin. The following drug interactions have either been reported or are theoretical in humans or animals receiving tepoxalin and may be of significance in veterinary patients: a SPi Rin T! : May increase the risk of gastrointestinal toxicity (e. g., ul-ceration, bleeding, vomiting, diarrhea) co Rtico Ste Roi DST! : As concomitant corticosteroid therapy may in-crease the occurrence of gastric ulceration, avoid the use of these drugs when also using tepoxalin Di Goxin T! : NSAIDS may increase serum levels FLuconazo Le T! : Administration has increased plasma levels of cele-coxib in humans, it is unknown if fluconazole affects tepoxalin levels in dogs Fu Ro Semi De T! : NSAIDs may reduce saluretic and diuretic effects met Hot Rexate T! : Serious toxicity has occurred when NSAIDs have been used concomitantly with methotrexate; use together with extreme caution ne PHRotoxic DRu GST! (e. g., furosemide, aminoglycosides, amphotericin b, etc. ): May enhance the risk of nephrotoxicity n Sai DS, ot He R T! : May increase the risk of gastrointestinal toxicity (e. g., ulceration, bleeding, vomiting, diarrhea) Wa RF a Rin T! : The manufacturer cautions to closely monitor pa-tients also receiving drugs that are highly bound to plasma pro-teins (e. g., warfarin), as tepoxalin and its active metabolite are 98-99% protein bound in the dog	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
858 te Rbina Fine Hc L Laboratory considerations No specific laboratory interactions or considerations noted Doses Do GS:T! For pain and inflammation associated with osteoarthritis: a) On first day of treatment give 20 mg/kg PO (or 10 mg/kg PO); subsequently give 10 mg/kg PO once daily. Duration of treatment should be based on clinical response and patient tolerance to therapy. (Package insert; Zubrin®—Schering-Plough) monitoring Clinical efficacy T! Baseline and periodic CBC, chemistry panel (including bilirubin T! and serum creatinine) Signs associated with adverse effects (GI effects, appetite, vomit-T! ing, diarrhea, etc. ) client information When dosing, the person administering the tablet should place T! it in dog's mouth and hold mouth closed for approximately 4 seconds to assure tablet disintegration Absorption may be enhanced (and vomiting reduced?) if given T! with food Owners should be instructed to discontinue the drug and contact T! their veterinarian if diarrhea is severe or persists, or signs such as inappetence, vomiting, fecal abnormalities, anemia, icterus or lethargy are observed Dogs should have access to water; dehydration should be avoided T! The manufacturer provides a client information sheet and states T! to “Always provide client information sheet... ” chemistry/Synonyms A non-steroidal antiinflammatory agent (NSAID), tepoxalin occurs as a white, tasteless, crystalline material that is insoluble in water and soluble in alcohol and most organic solvents. The commer-cially available tablets contain a micronized form of the drug in a highly porous matrix that rapidly disintegrates in the mouth. Drug particles are released into the saliva and swallowed by the dog where it is absorbed in the intestines. T epoxalin may also be known as ORF-20485, RWJ-20485 and Zubrin®. Storage/Stability Tablets should be kept in their foil blister packs until used and stored at temperatures between 2-30°C (36-86°F). Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: T epoxalin Oral (rapidly-disintegrating) Tablets: 30 mg, 50 mg, 100 mg, 200 mg in foil blisters containing 10 tablets in boxes of 10 foil blisters; Zubrin® (Schering-Plough); (Rx). Approved for use in dogs. Human-Labe Le D PRo Duct S: Noneterbinafine Hcl (Sy Ste Mic) (ter-bin-ah-fin) Lamisil® antifungal Prescriber Highlights Oral & topical antifungal; used primarily for dermato-T T phytic infections, but may be useful for other fungi (e. g., aspergillus), especially in birds Comparatively (with azole antifungals) few drug T T interactions Appears to be very well tolerated, but limited experience; T T vomiting most likely adverse effect Caution if liver or renal disease T T Treatment is relatively expensive, but generics are now T T available uses/indications T erbinafine may be useful for treating dermatophytic and other fungal infections in dogs and cats. T erbinafine may also be useful for treating birds for systemic mycotic (e. g., aspergillosis) infections. Pharmacology/actions T erbinafine is an inhibitor of the synthesis of ergosterol, a compo-nent of fungal cell membranes. By blocking the enzyme squalene monooxygenase (squalene 2,3-epoxidase), terbinafine inhibits the conversion of squalene to sterols (especially ergosterol) and causes accumulation of squalene. Both these effects are thought to con-tribute to its antifungal action. T erbinafine's mechanism for inhib-iting ergosterol is different from the azole antifungals. Unlike the azole agents, terbinafine's actions are not mediated via the cytochrome P-450 enzyme system, and, therefore, do not have the concerns of drug interactions or altering testosterone or cortisol. T erbinafine primarily has clinical activity (fungicidal) against dermatophytic organisms (Microsporum spp., Trichophyton spp., etc. ). It may only be fungistatic against the yeasts (Candida spp. ). T erbinafine has activity against Aspergillus, Blastomyces, and Histoplasma but is usually not used clinically for infections caused by these organisms. Pharmacokinetics Little veterinary specific information is available. In cats dosed at 34-46 mg/kg PO once daily for 14 days terbinafine persisted in hair above MIC for several weeks. (Foust, Marsella et al. 2007) In humans, terbinafine given orally is greater than 70% ab-sorbed; after first pass, metabolism bioavailability is about 40%. Food may enhance absorption somewhat. T erbinafine is distributed to skin and into the sebum. Over 99% of drug in plasma is bound to plasma proteins. Drug in the circulation is metabolized in the liver and the effective elimination half-life is about 36 hours. The drug may persist in adipose tissue and skin for very long periods. contraindications/Precautions/Warnings T erbinafine is contraindicated in patients hypersensitive to it. The manufacturer does not recommend its use in patients with active or chronic liver disease or with significantly impaired renal function. If terbinafine is to be used in veterinary patents with markedly im-paired liver or renal function, do so with extreme caution; dosage adjustments should be considered.	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
te Rbuta Line Su LF ate 859 adverse effects Because of limited usage in veterinary patients the adverse effect profile is not well defined, but thus far, the drug appears to be well tolerated. GI effects (vomiting, inappetence, diarrhea) are possible. Very rarely in humans, liver failure, neutropenia or serious skin reactions (e. g., TEN, Stevens-Johnson syndrome) have occurred af-ter terbinafine use. Reproductive/nursing Safety High dose studies in pregnant rabbits and rats have not demon-strated overt fetotoxicity or teratogenicity, but definitive safety in pregnancy has not been determined. Use with caution (manufac-turer recommends NOT using in pregnant women). In humans, the FDA categorizes this drug as category B for use during pregnancy (Animal studies have not yet demonstrated risk to the fetus, but there are no adequate studies in pregnant women; or animal studies have shown an adverse effect, but adequate studies in pregnant women have not demonstrated a risk to the fetus in the first trimester of pregnancy, and there is no evidence of risk in later trimesters. ) The drug enters maternal milk at levels 7 times that found in plas-ma; the manufacturer recommends that mothers not nurse while taking this drug. Use with caution in nursing veterinary patients. overdosage/acute t oxicity Limited information; humans have taken doses of up to 5 grams without serious effects. Drug interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving terbinafine and may be of significance in veterinary patients: cyc Lo SPo Rine T! : T erbinafine may increase the elimination of cyclosporine Ri Fam Pin T! : May increase terbinafine clearance As it shares the same metabolic pathway (CYP2D6), terbinafine could affect the metabolism of: beta-b Locke RST! mao in Hibito RS T! (amitraz, selegiline ) SSRi'S T! (fluoxetine, etc. ) t Ricyc Lic anti De PRe SSant ST! Laboratory considerations No apparent issues Doses Do GS & cat S:T! For dermatophytic infections:a) 30-40 mg/kg PO once daily (Moriello 2004) b) 30 mg/kg PO once daily. Treatment should continue until two successive brush cultures (separated by two weeks) are negative. First culture can be taken 3-4 weeks after starting therapy. (Foil 2003b) c) In cases where other drugs are not tolerated: 25 mg/kg PO q24h. (Rosenkrantz 2006a) For adjunctive treatment (with topical therapy) of nasal Asper-gillus infections if the cribriform pate is penetrated:a) 5-10 mg/kg PO q12h for 3-6 months (Kuehn 2007) For pythiosis where advanced disease precludes complete surgi-cal excision:a) 10 mg/kg PO q24h with itraconazole (10 mg/kg PO twice daily) (Marks 2007a)For lagendiosis where disease precludes complete surgical excision: a) 5-10 mg/kg PO q24h with itraconazole (10 mg/kg PO q24h) with repeated aggressive surgical resection was effective in one dog with multifocal cutaneous lesions, but no systemic lesions. (Grooters 2007) bi RDS:T! For avian mycotic infections:a) 10-15 mg/kg PO q12-24h (Dalhausen, Lindstrom et al. 2000) b) 10-15 mg/kg PO q12-24h (suspend a 250 mg tablet in 25 m L water); Nebulization: 1 mg/m L (500 mg terbinafine plus 1 m L Mucomyst® plus 500 m L of distilled water). T erbinafine can be used in combination with itraconazole. (Flammer 2003a) monitoring Clinical efficacy T! Baseline liver enzymes and then as needed (especially if treating T! long-term) client information Costs of treating can be considerable T! Give with food, particularly if vomiting is a problem T! chemistry/Synonyms A synthetic allylamine antifungal, terbinafine HCl occurs as a white to off-white, fine, crystalline powder. It is slightly soluble in water and soluble in ethanol. T erbinafine HCl may also be known as: Alamil®, Daskil®, Daskyl®, Desenex Max®, Finex®, Lamisil®, Maditez®, Micosil®, or Terekol ®. Storage/Stability T erbinafine tablets should be stored at room temperature, in tight containers; protect from light. Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: None Human-Labe Le D PRo Duct S: T erbinafine HCl Tablets: 250 mg; Lamisil® (Novartis), generic; (Rx) A topical cream and spray (1%) are also available (Rx). terbutaline Sulfate (ter-byoo-ta-leen) Brethine® beta-adrenergic agoni St Prescriber Highlights Beta agonist used as a bronchodilator & sometimes to T T treat bradyarrhythmias Contraindications: Hypersensitivity to terbutaline T T Caution: Diabetes, hyperthyroidism, hypertension, seizure T T disorders, or cardiac disease (especially with concurrent arrhythmias) Adverse Effects: Increased heart rate, tremors, CNS ex-T T citement (nervousness) & dizziness; after parenteral in-jection in horses, sweating & CNS excitation are possible	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
860 te Rbuta Line Su LF ate uses/indications T erbutaline is used as a bronchodilating agent in the adjunctive treatment of cardiopulmonary diseases (including tracheobronchi-tis, collapsing trachea, pulmonary edema, and allergic bronchitis) in small animals. It may be of some benefit in treating bradyar-rhythmias in dogs and cats. T erbutaline has been used occasionally in horses for its broncho-dilating effects, but adverse effects, short duration of activity after IV administration and poor oral absorption have limited its use. It has been shown to be useful as a diagnostic agent to diagnose anhidrosis in horses after intradermal injection. Oral and intravenous terbutaline has been used successfully in humans for the inhibition of premature labor clinical signs. Pharmacology/actions T erbutaline stimulates beta-adrenergic receptors found princi-pally in bronchial, vascular, and uterine smooth muscles (beta 2); bronchial and vascular smooth muscle relaxation occurs with re-sultant reduced airway resistance. At usual doses it has little effect on cardiac (beta 1) receptors and usually does not cause direct car-diostimulatory effects. Occasionally, a tachycardia develops which may be a result of either direct beta stimulation or a reflex response secondary to peripheral vasodilation. T erbutaline has virtually no alpha-adrenergic activity. Pharmacokinetics The pharmacokinetics of this agent have apparently not been thoroughly studied in domestic animals. In humans, only about 33-50% of an oral dose is absorbed; peak bronchial effects occur within 2-3 hours and activity persists up to 8 hours. T erbutaline is well-absorbed following SC administration with an onset of action occurring within 15 minutes, peak effects at 30-60 minutes, and duration of activity up to 4 hours. In horses, terbutaline is very poorly absorbed after oral adminis-tration with a bioavailability <1%. When given IV, mean residence time is about 30 minutes in horses and the drug probably needs to be given as a constant rate infusion if used therapeutically. T erbutaline is distributed into milk at levels approximately 1% of the oral dose given to the mother. T erbutaline is principally ex-creted unchanged in the urine (60%), but is also metabolized in the liver to an inactive sulfate conjugate. contraindications/Precautions/Warnings T erbutaline is contraindicated in patients hypersensitive to it. One veterinary school formulary (Schultz 1986) states that terbutaline is contraindicated in dogs and cats with heart disease, especially with CHF or cardiomyopathy. It should be used with caution in patients with diabetes, hyperthyroidism, hypertension, seizure disorders, or cardiac disease (especially with concurrent arrhythmias). adverse effects Most adverse effects are dose-related and those that would be ex-pected with sympathomimetic agents, including increased heart rate, tremors, CNS excitement (nervousness) and dizziness. These effects are generally transient, mild and do not require discontinu-ation of therapy. After parenteral injection in horses, sweating and CNS excitation have been reported. Transient hypokalemia has been reported in humans receiving beta-adrenergic agents. If an animal is susceptible to developing hy-pokalemia, it is suggested that additional serum potassium moni-toring be done early in therapy. Reproductive/nursing Safety In humans, the FDA categorizes this drug as category B for use dur-ing pregnancy (Animal studies have not yet demonstrated risk to the fetus, but there are no adequate studies in pregnant women; or animal studies have shown an adverse effect, but adequate studies in pregnant women have not demonstrated a risk to the fetus in the first trimester of pregnancy, and there is no evidence of risk in later trimesters. ) T erbutaline is excreted in milk. In humans, nursing is not rec-ommended with systemic terbutaline therapy. overdosage/acute t oxicity Clinical signs of significant overdose after systemic administration may include arrhythmias (bradycardia, tachycardia, heart block, extrasystoles), hypertension, fever, vomiting, mydriasis, and CNS stimulation. If a recent oral ingestion, it should be handled like oth-er overdoses (empty gut, give activated charcoal and a cathartic) if the animal does not have significant cardiac or CNS effects. If cardi-ac arrhythmias require treatment, a beta-blocking agent (e. g., pro-pranolol) can be used, but may precipitate bronchoconstriction. Drug interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving terbutaline and may be of significance in veterinary patients: ane St Hetic S, in Ha Lation T! (e. g., halothane, isoflurane, methoxyflu-rane): Use with inhalation anesthetics may predispose the patient to ventricular arrhythmias, particularly in patients with preexist-ing cardiac disease—use cautiously beta-a DRene RGic b Lockin G a Gent ST! (e. g., propranolol ): May antago-nize the actions of terbutaline Di Goxin T! : Use with digitalis glycosides may increase the risk of car-diac arrhythmias monoamine oxi Da Se in Hibito RST! : May potentiate the vascular ef-fects of terbutaline Sym P at Homimetic S, ot He R T! : Use of terbutaline with other sym-pathomimetic amines may increase the risk of developing ad-verse cardiovascular effects t Ricyc Lic anti De PRe SSant ST! : May potentiate the vascular effects of terbutaline Doses Do GS:T! a) For a trial to treat intrathoracic tracheal collapse, expira-tory cough or dyspnea and marked exercise intolerance: 1. 25-5 mg (total dose) PO two to three times daily (Johnson 2004c) b) As a bronchodilator in chronic bronchitis: Small dogs: 0. 625-1. 25 mg (total dose) PO q12h; medium-sized dogs: 1. 25-2. 5 mg (total dose) PO q12h; large dogs: 2. 5-5 mg PO q12h (Johnson 2000) c) For bradyarrhythmias: 0. 2 mg/kg PO q8-12h; improvement usually partial and often temporary (Rishniw and Thomas 2000) d) For treatment of premature labor: 0. 03 mg/kg PO q8h or by continuous IV infusion to effect (Davidson 2004c) e) For tracheal collapse: Small dogs: 0. 625-1. 25 mg (total dose) PO q12h; medium-sized dogs: 1. 25-2. 5 mg (total dose) PO q12h; large dogs: 2. 5-5 mg PO q12h; 0. 01 mg/kg IV, IM or SC (Ettinger and Kantrowitz 2005)	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
te Sto Ste Rone 861 cat S:T! a) For acute exacerbations of feline asthma treated at home: 0. 01 mg/kg SC or IM; Beneficial response (decrease of re-spiratory rate or effort by 50%) occurs in 15-30 minutes. A heart rate that approaches 240 BPM indicates that the drug has been absorbed. (Padrid 2000) b) For feline asthma: 0. 312-0. 625 mg (total dose) per cat PO two to three times daily; may adjust dose up to 1. 25 mg in larger cats if needed (Noone 1999) c) For bradyarrhythmias: 0. 625 mg PO q8-12h; improvement usually partial and often temporary (Rishniw and Thomas 2000) d) For acute bronchoconstriction (initial crisis): 0. 01 mg/kg IV, SC, IM (Cohn 2007) Ho RSe S: T! (note : ARCI UCGFS Class 3 Drug) a) 0. 0033 mg/kg IV (Robinson 1987) monitoring Clinical symptom improvement; auscultation T! Cardiac rate, rhythm (if indicated)T! Serum potassium, early in therapy if animal susceptible to hy-T! pokalemia client information Contact veterinarian if animal's condition deteriorates or if it be-T! comes acutely ill chemistry/Synonyms A synthetic sympathomimetic amine, terbutaline sulfate occurs as a slightly bitter-tasting, white to gray-white, crystalline powder that may have a faint odor of acetic acid. One gram is soluble in 1. 5 m L of water or 250 m L of alcohol. The commercially available injection has its p H adjusted to 3-5 with hydrochloric acid. T erbutaline Sulfate may also be known as: KWD-2019, terbuta-line sulphate, terbutalini sulfas; many trade names are available. Storage/Stability/compatibility T erbutaline tablets should be stored in tight containers at room temperature (15-30°C). Tablets have an expiration date of 3 years beyond the date of manufacture. T erbutaline injection should be stored at room temperature (15-30°C) and protected from light. The injection has an expiration date of 2 years after the date of manufacture. T erbutaline injection is stable over a p H range of 1-7. Discolored solutions should not be used. It is physically compatible with D 5W and aminophylline. Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: None The ARCI (Racing Commissioners International) has designated this drug as a class 3 substance. See the appendix for more information. Human-Labe Le D PRo Duct S: T erbutaline Sulfate Tablets: 2. 5 mg & 5 mg; Brethine® (aai Pharma); generic; (Global) (Rx) T erbutaline Injection: 1 mg/m L in 1 m L vials & 2 m L amps with 1 m L fill; Brethine® (aai Pharma); generic; (Rx)te Sto Sterone cypionate te Sto Sterone enant Hatete Sto Sterone propionate (tess-toss-ter-ohn) androgenic hormone Prescriber Highlights Principle endogenous androgen used primarily for the T T treatment of testosterone-responsive urinary inconti-nence in neutered male dogs/cats; in bovine medicine to produce an estrus-detector animal Contraindications: Known hypersensitivity to the drug; T T prostate carcinoma. Caution: Renal, cardiac, or hepatic dysfunction Adverse Effects: Uncommon, but perianal adenomas, T T perineal hernias, prostatic disorders, & behavior changes possible Testosterone products are controlled substances (C-III)T T uses/indications The use of injectable esters of testosterone in veterinary medicine is limited primarily to its use in dogs (and perhaps cats) for the treat-ment of testosterone-responsive urinary incontinence in neutered males. T estosterone has been used to treat a rare form of dermatitis (exhibited by bilateral alopecia) in neutered male dogs. These drugs are also used in bovine medicine to produce an estrus-detector (teaser) animal in cull cows, heifers, and steers. The effectiveness of testosterone to increase libido, treat hypogo-nadism, aspermia, and infertility in domestic animals has been dis-appointing. Pharmacology/actions The principle endogenous androgenic steroid, testosterone is re-sponsible for many secondary sex characteristic of the male as well as the maturation and growth of the male reproductive organs and increasing libido. T estosterone has anabolic activity with resultant increased pro-tein anabolism and decreased protein catabolism. T estosterone causes nitrogen, sodium, potassium and phosphorus retention and decreases the urinary excretion of calcium. Nitrogen balance is im-proved only when an adequate intake of both calories and protein occurs. By stimulating erythropoietic stimulating factor, testosterone can stimulate the production of red blood cells. Large doses of ex-ogenous testosterone can inhibit spermatogenesis through a nega-tive feedback mechanism inhibiting luteinizing hormone (LH). T estosterone may help maintain the normal urethral muscle tone and integrity of the urethral mucosa in male dogs. It may also be necessary to prevent some types of dermatoses. Pharmacokinetics Orally administered testosterone is rapidly metabolized by the GI mucosa and the liver (first-pass effect); very little reaches the sys-temic circulation. The esterified compounds, testosterone enanthate and cypionate are less polar than testosterone and more slowly ab-sorbed from lipid tissue after IM injection. The duration of action of these compounds may persist for 2-4 weeks after IM injection. T estosterone propionate reportedly has a much shorter duration of	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
862 te Sto Ste Rone action than the enanthate or cypionate esters. Because absorption is dependent upon several factors (volume injected, perfusion, etc. ), duration of action may be variable. T estosterone is highly bound to a specific testosterone-estradiol globulin (98% in humans). The quantity of this globulin determines the amount of drug that is in the free or bound form. The free form concentration determines the plasma half-life of the hormone. T estosterone is metabolized in the liver and is, with its metabo-lites, excreted in the urine (≈90%) and the feces (≈6%). The plasma half-life of testosterone has been reported to be between 10-100 minutes in humans. The plasma half-life of testosterone cypionate has been reported to be 8 days. contraindications/Precautions/Warnings T estosterone therapy is contraindicated in patients with known hy-persensitivity to the drug or prostate carcinoma. It should be used with caution in patients with renal, cardiac or hepatic dysfunction. adverse effects Adverse effects are reportedly uncommon when injectable testos-terone products are used in male dogs to treat hormone-responsive incontinence. Perianal adenomas, perineal hernias, prostatic disor-ders, and behavior changes (aggression) are all possible, however. Behavioral changes have been reported in cats. Polycythemia has been reported in humans receiving high dosages of testosterone. High dosages or chronic usage may result in oligospermia or infer-tility in intact males. Reproductive/nursing Safety In humans, the FDA categorizes this drug as category X for use during pregnancy (Studies in animals or humans demonstrate fetal abnormalities or adverse reaction; reports indicate evidence of fetal risk. The risk of use in pregnant women clearly outweighs any pos-sible benefit. ) In a separate system evaluating the safety of drugs in canine and feline pregnancy (Papich 1989), this drug is categorized as in class: D (Contraindicated. These drugs have been shown to cause congenital malformations or embryotoxicity. ) It is not known whether androgens are excreted in milk; con-sider using milk replacer if using testosterone in nursing patients. overdosage/acute t oxicity No specific information was located; refer to the Adverse Effects section for further information. Drug interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving testosterone and may be of significance in veterinary patients: co Rtico Ste Roi DST! : Androgens may enhance the edema that can be associated with ACTH or adrenal steroid therapy in Su Lin; o Ra L anti Diabetic a Gent S T! : T estosterone may decrease se-rum glucose levels PRo PRano Lo LT! : T estosterone cypionate may increase propranolol clearance Wa RF a Rin T! : T estosterone may increase anticoagulant effects Laboratory considerations Concentrations of protein bound iodine (PBI) can be decreased T! in patients receiving testosterone therapy, but the clinical signifi-cance of this is probably not important. Androgen agents can de-crease amounts of thyroxine-binding globulin and decrease total t4 concentrations and increase resin uptake of T 3 and T 4. Free thyroid hormones are unaltered and clinically, there is no evi-dence of dysfunction. Both T! creatinine and creatine excretion can be decreased by testos-terone T estosterone can increase the urinary excretion of T! 17-ketosteroids Androgenic/anabolic steroids may alter T! blood glucose levels Androgenic/anabolic steroids may suppress T! clotting factors ii, V, Vii, and x Doses Do GS:T! For testosterone-responsive urinary incontinence (may be used with phenylpropanolamine) in males:a) T estosterone propionate: approximately 2 mg/kg IM or SC 3 times per week. T estosterone cypionate: 200 mg IM once per month (La Bato 1988), (Polzin and Osborne 1985) b) T estosterone propionate: 2. 2 mg/kg IM q2-3 days. T estoster-one cypionate: 2. 2 mg/kg IM once per month (Moreau and Lappin 1989), (Chew, Di Bartola, and Fenner 1986) c) T estosterone cypionate: 2. 2 mg/kg IM q4-8 weeks (Lane 2002b) d) T estosterone propionate: 2. 2 mg/kg IM or SC every 2-3 days. T estosterone cypionate: 2. 2 mg/kg every 30 days or 200 mg IM every 30 days. (Bartges 2006a) For estrus control: a) T estosterone enanthate or cypionate 0. 5 mg/kg IM once every 5 days or methyltestosterone tablets 25 mg PO twice a week; this dose is for Greyhound-sized dogs. (Purswell 1999) T o reduce mammary gland enlargement seen in pseudopregnancy: a) T estosterone enanthate or cypionate 0. 5-1 mg/kg IM once (Purswell 1999) cat S:T! For infertility or reduced libido: Using either testosterone cypi-onate or propionate: a) 0. 1-1 mg every other day or every third day for 3-5 injec-tions IM or SC. Not indicated for testis descent. (Verstegen 2000) For testosterone-responsive urinary incontinence (may be used with phenylpropanolamine) in males: a) T estosterone propionate 5-10 mg IM as needed (Barsanti and Finco 1986), (Osborne, Kruger et al. 2000), (Bartges 2006a) catt Le:T! T o produce an estrus-detector (teaser) animal (cull cows, heifers, steers):a) T estosterone propionate 200 mg IM on day 1 and on days 4-9. On day 10, give 1 gram IM and attach a chinball marker and put with the breeding herd. T o maintain the teaser give 1 gram booster every 10-14 days. Alternatively, initially give testosterone enanthate 0. 5 gram IM and 1. 5 gram SC (divided in two separate locations). Af-ter 4 days attach chinball marker and put in with breeding herd. T o maintain, give 0. 5-0. 75 gram SC every 10-14 days. (Wolfe 1986) monitoring Efficacy T! Adverse effects T!	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
tet Racyc Line Hc L 863 chemistry/Synonyms The esterified compounds, testosterone cypionate, enanthate, and propionate are available commercially as injectable products. T estosterone cypionate occurs as an odorless to having a faint odor, creamy white or white, crystalline powder. It is insoluble in water, soluble in vegetable oils, and freely soluble in alcohol. T estosterone cypionate has a melting range of 98°-104°C. It may also be known as testosterone cyclopentylpropionate. T estosterone enanthate occurs as an odorless to having a faint odor, creamy white or white, crystalline powder. It is soluble in veg-etable oils, insoluble in water and melts between 34-39°C. T estosterone propionate occurs as odorless, creamy white to white, crystals or crystalline powder. It is insoluble in water, freely soluble in alcohol and soluble in vegetable oils. T estosterone propi-onate melts between 118-123°C. T estosterone Cypionate may also be known as: testosterone cyclopentylpropionate, testosterone cypionate, Deposteron®, Depotrone®, Depo-Testosterone®, Duratest®, Scheinpharm Testone-Cyp®, T-Cypionate®, Testex®, Testiormina®, Testred®, Virilon®, or dep Andro®. T estosterone Propionate may also be known as: NSC-9166, testosteroni propionas, Malogen in Oil®, Sostenon®, Sustanon®, Testanon 25®, Testex®, Testoviron®, Testoviron Depot®, Testovis®, Tesurene®, or Virormone®. Storage/Stability/compatibility The commercially available injectable preparations of testosterone cypionate, enanthate and propionate should be stored at room tem-perature; avoid freezing or exposing to temperatures greater than 40°C. If exposed to low temperature a precipitate may form, but should redissolve with shaking and rewarming. If a wet needle or syringe is used to draw up the parenteral solutions, cloudy solutions may result, but will not affect the drug's potency. Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: No known testosterone products (with the exception of combinations with estradiol as growth promotant implants) approved for use in veterinary species were located. T estosterone propionate (200 mg) is available in combination with estradiol benzoate (20 mg) as a growth promotant. Trade names include Component E-H® (Vet Life); (OTC) and Synovex-H® (Fort Dodge); (OTC). For use in heifers weighing 400 or more pounds. T estosterone propionate (200 mg) with estradiol benzoate (28 mg); Synovex-Plus® (Fort Dodge); (OTC); for steers. The ARCI (Racing Commissioners International) has designated this drug as a class 4 substance. See the appendix for more information. Human-Labe Le D PRo Duct S: T estosterone Cypionate (in oil) Injection: 100 mg/m L, and 200 mg/m L in 1 m L and 10 m L vials; Depo-Testosterone® (Pharmacia); ge-neric (Watson); (Rx, C-III) T estosterone Enanthate (in oil) Injection: 200 mg/m L in 5 m L multi-dose vials and 1 m L syringes; Delatestyl® (Savient); (Rx, C-III) T estosterone Propionate Injection (in oil): 100 mg/m L in 10 m L vials; available generically; (Rx, C-III) T estosterone Pellets: 75 mg (0. 2 mg stearic acid, 2 mg polyvinylpyr-rolidone) in 1 pellet/vials; Testopel ® (Bartor Pharmacal); (Rx, C-III) T estosterone Transdermal System: Release Rates: 5 and 2. 5 mg/24 hour, total testosterone contents: 24. 3 mg and 12. 2 mg (respectively): Androderm® (Watson Pharma); (Rx, C-III) T estosterone Gel: 1% testosterone in 2. 5 g or 5 g packets of gel to de-liver 25 mg or 50 mg testosterone and metered-dose pumps to deliver 75 g or 60 metered 1. 25 g doses; Andro Gel® 1% (Unimed Pharm. ); Testim® (Auxilium Pharm); (Rx, C-III) T estosterone, Buccal System: 30 mg testosterone in blister packs; Stri-ant® (Columbia); (Rx, C-III) tetracycline Hcl (tet-ra-sye-kleen) Aquadrops®, Panmycin® tetracycline antibiotic Prescriber Highlights Prototype tetracycline antibiotic; many bacteria are now T T resistant, but still may be very useful to treat mycoplas-ma, rickettsia, spirochetes, & Chlamydia Dosing frequency may be an issue for small animals T T Contraindications: Hypersensitivity T T Extreme Caution: Pregnancy T T Caution: Liver or renal insufficiency T T Adverse Effects: GI distress, staining of developing teeth T T & bones, superinfections, photosensitivity; long-term use may cause uroliths. CATS: Do not tolerate very well. HORSES: If stressed may break with diarrheas (oral use). RUMINANTS: High oral doses can cause ruminal microflora depression & ruminoreticular stasis; rapid IV of undiluted propylene glycol-based products can cause intravascular hemolysis & cardiodepressant effects; IM: local reactions, yellow staining & necrosis may be seen at the injection site uses/indications While tetracycline still is used as an antimicrobial, most small ani-mal clinicians prefer doxycycline and large animal clinicians prefer oxytetracycline when a tetracycline is indicated to treat susceptible infections. The most common use of tetracycline HCl today is in combination with niacinamide for the treatment of certain im-mune-mediated skin conditions in dogs, such as pemphigus. Pharmacology/actions T etracyclines generally act as bacteriostatic antibiotics and inhibit protein synthesis by reversibly binding to 30S ribosomal subunits of susceptible organisms, thereby preventing binding to those ri-bosomes of aminoacyl transfer-RNA. T etracyclines are believed to reversibly bind to 50S ribosomes and additionally alter cytoplasmic membrane permeability in susceptible organisms. In high concen-trations, tetracyclines can inhibit protein synthesis by mammalian cells. As a class, the tetracyclines have activity against most mycoplas-ma, spirochetes (including the Lyme disease organism), Chlamydia, and Rickettsia. Against gram-positive bacteria, the tetracyclines have activity against some strains of staphylococcus and streptococci, but resistance of these organisms is increasing. Gram-positive bac-teria that are usually covered by tetracyclines include Actinomyces spp., Bacillus anthracis, Clostridium perfringens and tetani, Listeria monocytogenes, and Nocardia. Among gram-negative bacteria that tetracyclines usually have in vitro and in vivo activity include	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
864 tet Racyc Line Hc L Bordetella spp., Brucella, Bartonella, Haemophilus spp., Pasturella multocida, Shigella, and Y ersinia pestis. Many or most strains of E. coli, Klebsiella, Bacteroides, Enterobacter, Proteus and Pseudomonas aeruginosa are resistant to the tetracyclines. While most strains of Pseudomonas aeruginosa show in vitro resistance to tetracyclines, those compounds attaining high urine levels (e. g., tetracycline, oxytetracycline) have been associated with clinical cures in dogs with UTI secondary to this organism. Oxytetracycline and tetracycline share nearly identical spec-trums of activity and patterns of cross-resistance and a tetracycline susceptibility disk is usually used for in vitro testing for oxytetracy-cline susceptibility. T etracyclines have antiinflammatory and immunomodulating effects. They can suppress antibody production and chemotaxis of neutrophils; inhibit lipases, collagenases, prostaglandin synthesis, and activation of complement component 3. Pharmacokinetics Both oxytetracycline and tetracycline are readily absorbed after oral administration to fasting animals. Bioavailabilities are ap-proximately 60-80%. The presence of food or dairy products can significantly reduce the amount of tetracycline absorbed, with re-ductions of 50% or more possible. After IM administration, tetra-cycline is erratically and poorly absorbed with serum levels usually lower than those attainable with oral therapy. T etracyclines as a class, are widely distributed to heart, kidney, lungs, muscle, pleural fluid, bronchial secretions, sputum, bile, sa-liva, urine, synovial fluid, ascitic fluid, and aqueous and vitreous humor. Only small quantities of tetracycline and oxytetracycline are distributed to the CSF, and therapeutic levels may not be achiev-able. While all tetracyclines distribute to the prostate and eye, doxy-cycline or minocycline penetrate better into these and most other tissues. T etracyclines cross the placenta, enter fetal circulation and are distributed into milk. The volume of distribution of tetracycline is approximately 1. 2-1. 3 L/kg in small animals. The amount of plasma protein binding is about 20-67% for tetracycline. In cattle, the volume of distribution for oxytetracycline is between 1 and 2. 5 L/kg. Milk to plasma ratios for oxytetracycline and tetracycline are 0. 75 and 1. 2-1. 9, respectively. Both oxytetracycline and tetracycline are eliminated unchanged primarily via glomerular filtration. Patients with impaired renal function can have prolonged elimination half-lives and accumu-late the drug with repeated dosing. These drugs apparently are not metabolized, but are excreted into the GI tract via both biliary and nonbiliary routes and may become inactive after chelation with fe-cal materials. The elimination half-life of tetracycline is approxi-mately 5-6 hours in dogs and cats. contraindications/Precautions/Warnings T etracycline is contraindicated in patients hypersensitive to it or other tetracyclines. Because tetracyclines can retard fetal skeletal de-velopment and discolor deciduous teeth, they should only be used in the last half of pregnancy when the benefits outweigh the fetal risks. Oxytetracycline and tetracycline are considered more likely to cause these abnormalities than either doxycycline or minocycline. In patients with renal insufficiency or hepatic impairment, tet-racycline must be used cautiously; lower than normal dosages are recommended with enhanced monitoring of renal and hepatic function. Avoid concurrent administration of other nephrotoxic or hepatotoxic drugs if tetracyclines are administered to these pa-tients. Monitoring of serum levels should be considered if long-term therapy is required. adverse effects Oxytetracycline and tetracycline given to young animals can cause discoloration of bones and teeth to a yellow, brown, or gray color. High dosages or chronic administration may delay bone growth and healing. T etracyclines in high levels can exert an antianabolic effect that can cause an increase in BUN and/or hepatotoxicity, particularly in patients with preexisting renal dysfunction. As renal function deteriorates secondary to drug accumulation, this effect may be exacerbated. In ruminants, high oral doses can cause ruminal microflora de-pression and ruminoreticular stasis. Rapid intravenous injection of undiluted propylene glycol-based products can cause intravascular hemolysis with resultant hemoglobinuria. Propylene glycol based products have also caused cardiodepressant effects when admin-istered to calves. When administered IM, local reactions, yellow staining, and necrosis may be seen at the injection site. In small animals, tetracyclines can cause nausea, vomiting, an-orexia, and diarrhea. Cats do not tolerate oral tetracycline or oxytet-racycline very well, and may present with clinical signs of colic, fever, hair loss, and depression. There are reports that long-term tetracycline use may cause urolith formation in dogs. Horses that are stressed by surgery, anesthesia, trauma, etc., may break with severe diarrheas after receiving tetracyclines (especially with oral administration). T etracycline therapy (especially long-term) may result in over-growth of non-susceptible bacteria or fungi (superinfections). T etracyclines have also been associated with photosensitivity re-actions and, rarely, hepatotoxicity or blood dyscrasias. Reproductive/nursing Safety In humans, the FDA categorizes this drug as category D for use dur-ing pregnancy (There is evidence of human fetal risk, but the potential benefits from the use of the drug in pregnant women may be acceptable despite its potential risks. ) In a separate system evaluating the safety of drugs in canine and feline pregnancy (Papich 1989), this drug is categorized as in class: D (Contraindicated. These drugs have been shown to cause congenital malformations or embryotoxicity. ) T etracyclines are excreted in milk, but because much of the drug will be bound to calcium in milk, it is unlikely to be of significant risk to nursing animals. overdosage/acute t oxicity T etracyclines are generally well tolerated after acute overdoses. Dogs given more than 400 mg/kg/day orally or 100 mg/kg/day IM of oxytetracycline did not demonstrate any toxicity. Oral overdoses would most likely be associated with GI disturbances (vomiting, anorexia, and/or diarrhea). Should the patient develop severe em-esis or diarrhea, fluids and electrolytes should be monitored and replaced if necessary. Chronic overdoses may lead to drug accumu-lation and nephrotoxicity. High oral doses given to ruminants, can cause ruminal micro-flora depression and ruminoreticular stasis. Rapid intravenous injection of undiluted propylene glycol-based products can cause intravascular hemolysis with resultant hemoglobinuria. Rapid intravenous injection of tetracyclines has induced tran-sient collapse and cardiac arrhythmias in several species, presum-ably due to chelation with intravascular calcium ions. Overdose quantities of drug could exacerbate this effect if given too rapidly IV. If the drug must be given rapidly IV (less than 5 minutes), some clinicians recommend pre-treating the animal with intravenous calcium gluconate.	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
tet Racyc Line Hc L 865 Drug interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving tetracyclines and may be of significance in veterinary patients: ato Vaquone T! : T etracyclines have caused decreased atovaquone levels beta-Lactam o R amino GL yco Si De antibiotic S T! : Bacteriostatic drugs, like the tetracyclines, may interfere with bactericidal activ-ity of the penicillins, cephalosporins, and aminoglycosides; there is some controversy regarding the actual clinical significance of this interaction, however. Di Goxin T! : T etracyclines have increased the bioavailability of digox-in in a small percentage of human patients and caused digoxin toxicity. These effects may persist for months after discontinua-tion of the tetra cycline. Di Va Lent o R t Ri Va Lent cation S T! (oral antacids, saline cathartics or other Gi products containing aluminum, calcium, iron, magne sium, zinc, or bismuth cations ): When orally administered, tetracyclines can chelate divalent or trivalent cations that can decrease the ab-sorption of the tetracycline or the other drug if it contains these cations; it is recommended that all oral tetracyclines be given at least 1-2 hours before or after the cation-containing products. met Hoxy FLu Rane T! : Fatal nephrotoxicity has occurred in humans when used with tetracycline; concomitant use with oxytetracy-cline not recommended Wa RF a Rin T! : T etracyclines may depress plasma prothrombin ac-tivity and patients on anticoagulant therapy may need dosage adjustment Laboratory considerations T etracyclines (not minocycline) may cause falsely elevated values T! of urine catecholamines when using fluorometric methods of de-termination. T etracyclines reportedly can cause false-positive T! urine glucose re-sults if using the cupric sulfate method of determination (Bene-dict's reagent, Clinitest®), but this may be the result of ascorbic acid that is found in some parenteral formulations of tetracy-clines. T etracyclines have also reportedly caused false-negative results in determining urine glucose when using the glucose oxi-dase method (Clinistix®, Tes-Tape®). Doses Do GS:T! For discoid lupus erythematosus:a) For dogs weighing 10 kg or more: 500 mg of niacinamide and 500 mg of tetracycline PO q8h. For dogs weighing from 5-10 kg: 250 mg of each PO q8h. For dogs weighing <5 kg: 100 mg of each PO q8h. Improvement is usually noted with-in 6 weeks. (White 2000) b) Dogs weighing more than 10 kg: 500 mg of niacinamide and 500 mg of tetracycline PO q8h. For dogs weighing less than 10 kg: 250 mg of each PO q8h. May use in combination with corticosteroids and Vitamin E. If adverse effects become a problem, reduce dose of niacinamide first. May also try this regimen for pemphigus foliaceous or pemphigus erythema-tous. (Campbell 1999) c) For various immune-mediated diseases (discoid lupus ery-thematosus, pemphigus erythematosus, pemphigus folia-ceous, vasculitis, sterile pyelogranuloma, dermatomyositis and lupoid onychodystrophy: For dogs less than 10 kg: 250 mg each of niacinamide and tetracycline PO three times dai-ly. For dogs larger than 10 kg: 500 mg each of niacinamide and tetracycline PO three times daily. May substitute doxycy-cline for tetracycline at 5 mg/kg PO once a day. (Tapp 2002) For susceptible infections:a) For UTI: 16 mg/kg PO q8h for 7-14 days; For Rickettsiosis, Borreliosis: 22 mg/kg PO q8h for 14 days; For systemic bacteremia, brucellosis: 22-50 mg/kg PO q8h for 28 days. (Greene, Hartmannn et al. 2006) b) For Rocky Mountain Spotted Fever: 22 mg/kg q8h for 14-21 days (Sellon and Breitschwerdt 1995) c) 20 mg/kg PO q8-12h; (may give with food if GI upset oc-curs; avoid or reduce dose in animals with renal or severe liver failure; avoid in young, pregnant or breeding animals) (Vaden and Papich 1995) d) 22-33 mg/kg PO q8h (Aronson and Aucoin 1989) e) For Lyme disease: 22 mg/kg PO q8h for 14 days (Breitschw-erdt 2000) f) For small intestinal bacterial overgrowth: 5-10 mg/kg PO q8h for 28 days; has been effective for uncomplicated cases (Ludlow and Davenport 2000) g) For rickettsial diseases: Ehrlichiosis: 22 mg/kg, PO three times daily for at least 14 days Salmon poisoning: 22 mg/kg, PO three times daily for 10-14 days or 7 mg/kg IV three times daily Rocky Mountain Spotted Fever: 22 mg/kg, PO three times daily for 10-14 days (Lissman 1988) For facial tear staining: a) 5-10 mg/kg/day or 50 mg per dog per day. Results are vari-able. (Kern 1986) For pleurodesis: a) Using capsules or aqueous solution; mix 20 mg/kg in 4 m L per kg of saline and infuse into pleural space (Morgan 1988) cat S:T! For susceptible infections:a) For soft tissue infections: 20 mg/kg PO q8h for 21 days; For Hemotropic mycoplasmosis: 10-25 mg/kg PO q8-12h for 21 days;For bacteremia, systemic infections: 7 mg/kg IV, IM q12h as long as necessary. (Greene, Hartmannn et al. 2006) b) For rickettsial diseases: 16 mg/kg, PO three times daily for 21 days (Morgan 1988) c) 20 mg/kg PO q8-12h; (may give with food if GI upset oc-curs; avoid or reduce dose in animals with renal or severe liver failure; avoid in young, pregnant or breeding animals) (Vaden and Papich 1995) d) 22-33 mg/kg PO q8h (Aronson and Aucoin 1989) Fe RRet S:T! For susceptible infections: a) 25 mg/kg PO 2-3 times daily (Williams 2000) Rabbit S, Ro Dent S, Sma LL mamma LS: T! a) Rabbits: 50-100 mg/kg PO q8-12h (Ivey and Morrisey 2000) b) Chinchillas: 50 mg/kg PO q8-12h (Hayes 2000) c) Chinchillas, Guinea Pigs, Rats: 20 mg/kg, PO q12h. Mice: 20 mg/kg, PO q12h or 50-60 mg/liter of drinking water Ham-sters: 30 mg/kg, PO q6h or 400 mg/liter, drinking water. Ger-bils: 20 mg/kg, PO or IM q24h (Adamcak and Otten 2000)	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
866 tet Racyc Line Hc L catt Le T! : For susceptible infections in calves: a) 11 mg/kg orally (Howard 1986) b) 11 mg/kg, PO twice daily for up to 5 days (Label directions; Polyotic ®—American Cyanamid) SHee P:T! For susceptible infections: a) 11 mg/kg, PO twice daily for up to 5 days (Label directions; Polyotic ®—American Cyanamid) Ho RSe S:T! For susceptible infections: a) 5-7. 5 mg/kg IV q12h (Brumbaugh 1987) SWine:T! For susceptible infections: a) 22 mg/kg, PO for 3 to 5 days in drinking water (Label direc-tions; Polyotic ®—American Cyanamid) bi RDS:T! For susceptible infections:a) For treatment of psittacosis in conjunction with LA-200® (see oxytetracycline doses) and/or medicated pellets and/or Keet Life: Using 25 mg/m L oral suspension, mix 2 teaspoons-ful to 1 cup of soft food. For mild respiratory disease (especially flock treatment): Mix 1 teaspoonful of 10 g/6. 4 oz. soluble powder per gallon of drinking water. Used as an adjunct for psittacosis with other tetracycline forms. Will not reach therapeutic levels by itself. Prepare fresh solution twice daily, as potency is rapidly lost. (Mc Donald 1989) b) Mix 1 teaspoonful of 10 g/6. 4 oz. soluble powder per gal-lon of drinking water and administer for 5-10 days. Prepare fresh solution 2-3 times daily, as potency is rapidly lost. For converting regimen to pelleted feeds administer oral suspension by gavage at 200-250 mg/kg once or twice daily until feeds are accepted. Is not an adequate therapy for long-term treatment of chlamydiosis (psittacosis) (Clubb 1986) monitoring Adverse effects T! Clinical efficacy T! Long-term use or in susceptible patients: periodic renal, hepatic, T! hematologic evaluations client information Avoid giving this drug orally within 1-2 hours of feeding, giving T! milk or other dairy products If gastrointestinal upset occurs, giving with a small amount of T! food may help, but this may also reduce the amount of drug ab-sorbed chemistry/Synonyms An antibiotic obtained from Streptomyces aureofaciens or derived semisynthetically from oxytetracycline, tetracycline HCl occurs as a moderately hygroscopic, yellow, crystalline powder. About 100 mg/m L is soluble in water and 10 mg/m L soluble in alcohol. T etracycline base has a solubility of about 0. 4 mg per m L of water and 20 mg per m L of alcohol. Commercially available tetracycline HCl for IM injection also contains magnesium chloride, procaine HCl and ascorbic acid. T etracycline may also be known as: tetracyclini hydrochloridum; many trade names are available. Storage/Stability/compatibility Unless otherwise instructed by the manufacturer, tetracycline oral tablets and capsules should be stored in tight, light resistant con-tainers at room temperature (15-30°C). The oral suspension and powder for injection should be stored at room temperature; avoid freezing the oral suspension. After reconstituting the IM product, it may be stored at room temperature but should be used within 24 hours. After reconstitut-ing the intravenous product with sterile water to a concentration of 50 mg/m L, the preparation is stable for 12 hours at room tempera-ture. If further diluted in an appropriate IV fluid, use immediately. T etracycline HCl for intravenous injection is reportedly physi-cally compatible with the following IV fluids and drugs: 0. 9% so-dium chloride, D 5W, D 5W in normal saline, Ringer's injection, lactated Ringer's injection, 10% invert sugar, dextrose-Ringer's and lactated Ringer's combinations, ascorbic acid, cimetidine HCl, colistimethate sodium, corticotropin, ephedrine sulfate, isoprotere-nol HCl, kanamycin sulfate, lidocaine HCl, metaraminol bitartrate, norepinephrine bitartrate, oxytetracycline HCl, oxytocin, potassi-um chloride, prednisolone sodium phosphate, procaine HCl, pro-mazine HCl, and vitamin B complex with C. Drugs that are reportedly physically incompatible with tetracy-cline, data conflicts, or compatibility is concentration/time depen-dent, include: amikacin sulfate, aminophylline, ampicillin sodium, amobarbital sodium, amphotericin B, calcium chloride/gluconate, carbenicillin disodium, cephalothin sodium, cephapirin sodium, chloramphenicol sodium succinate, dimenhydrinate, erythromycin gluceptate/lactobionate, heparin sodium, hydrocortisone sodium succinate, meperidine HCl, morphine sulfate, methicillin sodium, methohexital sodium, methyldopate HCl, oxacillin sodium, peni-cillin G potassium/sodium, phenobarbital sodium, sodium bicar-bonate, thiopental sodium, and warfarin sodium. Compatibility is dependent upon factors such as p H, concentration, temperature, and diluent used; consult specialized references or a hospital phar-macist for more specific information. Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: There are a variety of T etracycline HCl Soluble Powder (as a water additive) products that are available in various concentrations and sizes. Usual concentrations are either 25 grams/lb or 324 grams/lb and these products may be available in several sizes; may be approved for use in swine, cattle, or poultry. Withdrawal time may vary de-pending on age of animal and product. An oral combination product containing tetracycline, novobiocin and prednisone (Delta Albaplex®) is also available; see the novobiocin monograph for more information. Human-Labe Le D PRo Duct S: T etracycline HCl Capsules: 250 mg, and 500 mg; Sumycin®-250 & -500 (Par); generic; (Rx) T etracycline HCl Oral Suspension: 25 mg/m L in 473 m L; Sumycin® Syrup (Par); (Rx) Theophylline—see Aminophylline	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
t Hiaben Dazo Le 867 t Hiabendazole (thye-a-ben-da-zole) anthelmintic; antifungal Prescriber Highlights Benzimidazole anthelmintic; has antifungal (dermato-T T phytes) activity Contraindications: None noted T T Adverse Effects: T T DOGS: Vomiting, diarrhea, hair loss, & lethargy. Dachshunds may be particularly sensitive to thiabendazole. Toxic epidermal necrolysis (TEN) is rarely seen. Parasitic-resistance is an issue T T Many veterinary products no longer available T T uses/indications Thiabendazole has been used for the removal of the following para-sites in dogs: ascarids (Toxocara canis, T. leonina), Strongyloides ster-coralis, and Filaroides. It has been used systemically as an anti-fun-gal agent in the treatment of nasal aspergillosis and penicillinosis. T opical and otic use of thiabendazole for the treatment of various fungi is also commonly employed. Thiabendazole is indicated (labeled) for the removal of the following parasites in cattle: Haemonchus spp., Ostertagia spp., Trichostrongylus spp., Nematodirus spp., Cooperia spp. and Oesophagostomum radiatum. Thiabendazole is indicated (labeled) for the removal of the fol-lowing parasites in sheep and goats: Haemonchus spp., Ostertagia spp., Trichostrongylus spp., Nematodirus spp., Cooperia spp., Chabertia spp., Bunostomum spp. and Oesophagostomum spp. Thiabendazole is indicated (labeled) for the removal of the following parasites in horses: Strongylus spp., craterstomum spp., Oesphagodontus spp., Posteriostomum spp., Cyathostomum spp., Cylicocylus spp., Cylicostephanus spp., Oxyuris spp., and Parasacaris spp. Thiabendazole is indicated (labeled) for the removal or preven-tion of the following parasites in swine: large roundworms (Ascaris suum) (prevention), and in baby pigs infested with Strongyloides ransomi. Although not approved, thiabendazole has been used in pet birds and llamas. See the Dosage section for more information. In many geographic areas, significant thiabendazole resistance problems have developed and, for many parasites, other anthelm-intics would be a better choice for treatment. When used topically, thiabendazole has antidermatophytic properties. Pharmacokinetics Thiabendazole is relatively well absorbed (for a benzimidazole) and is distributed throughout body tissues. Peak levels occur in ap-proximately 2-7 hours after dosing. Absorbed drug is rapidly me-tabolized in the liver by hydroxylation, glucuronidation and sulfate formation. Within 48 hours of dosing, 90% of the drug is excreted in the urine (as metabolites) and 5% in the feces. Less than 1% of the drug is excreted in the urine unchanged. Five days after a dose, the drug is virtually eliminated from the body. adverse effects At recommended doses, thiabendazole is usually well tolerated in approved species. In dogs, vomiting, diarrhea, hair loss, and leth-argy are possible side effects, notably with high dose or long-term therapy. Dachshunds have been reported to be particularly sensi-tive to thiabendazole. T oxic epidermal necrolysis (TEN) has been reported in dogs receiving thiabendazole, but the incidence appears to be very rare. Reproductive/nursing Safety Thiabendazole has not been demonstrated to be a teratogen and is considered generally safe to use during pregnancy. However, in high doses it has been implicated in causing toxemia in ewes. In humans, the FDA categorizes this drug as category C for use dur-ing pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) In a separate system evaluating the safety of drugs in canine and feline pregnancy (Papich 1989), this drug is categorized as in class: B (Safe for use if used cautiously. Studies in laboratory animals may have un-covered some risk, but these drugs appear to be safe in dogs and cats or these drugs are safe if they are not administered when the animal is near term. ) It is not known whether this drug is excreted in milk, but it is unlikely to be of clinical concern in nursing patients. overdosage/t oxicity Thiabendazole has a safety margin of at least 20 times the recom-mended dose in horses. Doses of 800-1000 mg/kg are necessary to cause anorexia and depression in sheep. The minimum lethal dose is 700 mg/kg in cattle and 1200 mg/kg in sheep. It is unlikely that a modest overdose would cause significant problems. If a massive overdose occurs, treat supportively and symp-tomatically. See the Adverse effects section for more information. Drug interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving thiabendazole and may be of significance in veterinary patients: t Heo PHy LLine T! : Thiabendazole may compete with xanthines for metabolizing sites in the liver, thereby increasing xanthine blood levels Doses note : There are no veterinary commercial products for systemic use currently being marketed in the USA. Do GS:T! As an antiparasitic agent:a) For treatment of Strongyloides stercoralis: 50-60 mg/kg PO (T odd, Paul, and Di Pietro 1985) b) For treatment of Filaroides (now called Oslerus) infections: 35 mg/kg PO twice daily for 5 days, then 70 mg/kg PO twice daily for 21 days. Prednisone can also be given at 0. 55 mg/kg, PO twice daily every other day (Ettinger, Kantrowitz et al. 2000) As an antifungal agent:a) For treatment of nasal aspergillosis/penicillinosis infec-tions: 30-70 mg/kg divided q12h PO in food for 20-45 days (Roudebush 1985) b) For the treatment of aspergillosis: 20 mg/kg PO, once a day or divided twice daily; (with or without ketoconazole: 20 mg/kg PO, once a day or divided twice daily). Maintenance therapy: 10-20 mg/kg PO once a day (Greene, O'Neal, and Barsanti 1984)	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
868 t Hiamine Hc L c) For penicillinosis: With appropriate adjunctive surgical cu-rettage and topical therapy, thiabendazole: 20 mg/kg/day PO for 4-6 weeks (Barsanti 1984) d) For aspergillosis: Administer 10 mg/kg as nasal flush. Dilute in 10-20 m L of water. Flush twice daily for 10 days. Orally: 20 mg/kg/day divided twice daily for 6 weeks (Mor-gan 1988) e) For treatment of nasal aspergillosis: 20 mg/kg divided q12h PO for 6-8 weeks. If anorexia or nausea develops, may with-draw drug and then gradually reintroduce to the full dosage. Administer with food to enhance absorption and reduce an-orexia. May be effective in 40-50% of dogs treated. (Sharp 1989) Rabbit S, Ro Dent S, Sma LL mamma LS:T! a) Rabbits: For pinworms: 50-100 mg/kg PO for 5 days or 50 mg/kg PO, repeat in 3 weeks (Ivey and Morrisey 2000) b) Mice, Rats, Gerbils, Hamsters, Guinea pigs: 100 mg/kg, PO for 5 days. Chinchillas: 50-100 mg/kg PO for 5 days (Adamcak and Ot-ten 2000) c) For pinworms in Mice, Rats, Hamsters, Gerbils and Rabbits: 50 mg/kg, PO once (Burke 1999) catt Le:T! For susceptible parasites:a) 66 mg/kg PO; 110 mg/kg PO for Cooperia and severe infec-tions of other susceptible nematodes. Retreat treatment in 2-3 weeks if indicated (Paul 1986), (Roberson 1988b) b) 50-100 mg/kg PO (Brander, Pugh, and Bywater 1982) Ho RSe S:T! For susceptible parasites:a) 44 mg/kg, PO (Robinson 1987) b) 44 mg/kg; 88 mg/kg for ascarids (Roberson 1988b) c) 50-100 mg/kg PO (Brander, Pugh, and Bywater 1982) SWine:T! For susceptible parasites:a) For baby pigs with Strongyloides ransomi: 62-83 mg/kg PO, retreat in 5-7 days if necessary. T o prevent Ascaris suum: Feed at 0. 05-0. 1% per ton of feed for 2 weeks, then 0. 005-0. 02% per ton for 8-14 weeks (Paul 1986) b) 75 mg/kg, PO (Roberson 1988b) c) 50 mg/kg, PO (Brander, Pugh, and Bywater 1982) SHee P & Goat S:T! For susceptible parasites:a) 44 mg/kg PO; 66 mg/kg PO for severe infections in goats (Paul 1986), (Roberson 1988b) b) 50-100 mg/kg PO (sheep) (Brander, Pugh, and Bywater 1982) LLama S:T! For susceptible parasites:a) 50-100 mg/kg PO for 1-3 days. Use higher dosage rate over several days when animal is severely parasitized. (Cheney and Allen 1989) b) 66 mg/kg PO (Fowler 1989) bi RDS:T! For susceptible parasites:a) For ascarids: 250-500 mg/kg PO once. Repeat in 10-14 days. For Syngamus trachea: 100 mg/kg, PO once a day for 7-10 days (Clubb 1986)b) For ascarids, Capillaria, gapeworms:Chickens, pheasants, turkeys, and pigeons: Mix 0. 5% in feed for 10 days or administer orally at 44 mg/kg as a single dose. Psittacines: 44 mg/kg PO; do not exceed this dose. Falcons: 100 mg/kg PO as a single dose (Stunkard 1984) c) For thorny headed worms in waterfowl and raptors: 250 mg/ lb (Stunkard 1984) client information Shake suspension well before using. T! Follow veterinarian's or label's directions carefully. T! chemistry/Synonyms The prototypic benzimidazole, thiabendazole occurs as an odorless or nearly odorless, tasteless, white to practically white powder. It has a melting range of 296°-303°C and a p K a of 4. 7. Thiabendazole is practically insoluble in water and slightly soluble in alcohol. Thiabendazole may also be known as: E233, MK-360, tia-bendazolum, tiabendazole, Benzol ®, Eprofil®, Foldan®, Folderm®, Mintezol®, Thiaben®, Thianax®, Tiabenzol®, Tiabiose®, Tiaplex®, Triasox®, or Tutiverm ®. Storage/Stability Thiabendazole tablets, boluses and oral suspension should be stored in tight containers. Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: None in the USA for systemic use. Thiabendazole is an active ingredi-ent in the topical/otic preparation Tresaderm®. Food residue tolerances: 0. 1 ppm in uncooked meat of cattle, pheas-ants, swine, sheep and goats; 0. 05 ppm in milk. Human-Labe Le D PRo Duct S: Thiabendazole Chewable Scored Tablets: 500 mg; Mintezol® (Merck); (Rx) Thiabendazole Oral Suspension: 100 mg/m L in 120 m L; Mintezol® (Merck); (Rx) Thiacetarsamide (no longer available)—See Melarsomine t Hia Mine Hcl vita Min b 1 (thye-a-min) nutritional; b vitamin Prescriber Highlights A “B” vitamin used for treatment or prevention of thia-T T mine deficiency. May be useful for adjunctive treatment of lead poisoning & ethylene glycol toxicity Contraindications: hypersensitivity to it T T Adverse Effects: hypersensitivity reactions (rarely); ten-T T derness, or muscle soreness after IM injection Drug Interactions; lab interactions T T	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
t Hiamine Hc L 869 uses/indications Thiamine is indicated in the treatment or prevention of thiamine deficiency states. Clinical signs of thiamine deficiency may be manifested as gastrointestinal (anorexia, salivation), neuromuscu-lar/CNS signs (ataxia, seizures, loss of reflexes), or cardiac effects (brady-or tachyarrhythmias). Deficiency states may be secondary to either a lack of thiamine in the diet or the presence of thiamine destroying compounds in the diet (e. g., bracken fern, raw fish, am-prolium, thiaminase-producing bacteria in ruminants). Thiamine has also been used in the adjunctive treatment of lead poisoning and ethylene glycol toxicity (to facilitate the conversion of glyoxylate to nontoxic metabolites). Pharmacology/actions Thiamine combines with adenosine triphosphate (ATP) to form a compound (thiamine diphosphate/thiamine pyrophosphate) that is employed for carbohydrate metabolism, but does not effect blood glucose concentrations. Absence of thiamine results in decreased transketolase activity in red blood cells and increased pyruvic acid blood concentrations. Without thiamine triphosphate, pyruvic acid is not converted into acetyl-Co A; diminished NADH results with anaerobic glycolysis producing lactic acid. Lactic acid production is further increased secondary to pyruvic acid conversion; lactic acidosis may occur. Pharmacokinetics Thiamine is absorbed from the GI tract and is metabolized by the liver. Elimination is renal, the majority of the drug is eliminated as metabolites. contraindications/Precautions/Warnings Thiamine injection is contraindicated in animals hypersensitive to it or to any component of it. adverse effects Hypersensitivity reactions have occurred after injecting this agent. Some tenderness or muscle soreness may result after IM injection. Reproductive/nursing Safety In humans, the FDA categorizes this drug as category A for use dur-ing pregnancy (Adequate studies in pregnant women have not dem-onstrated a risk to the fetus in the first trimester of pregnancy, and there is no evidence of risk in later trimesters. ) If used in doses greater than the RDA, the FDA categorizes this drug as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) It is not known whether this drug is excreted in milk, but it should not be of clinical concern. overdosage/acute t oxicity Very large doses of thiamine in laboratory animals have been asso-ciated with neuromuscular or ganglionic blockade, but the clinical significance is unknown. Hypotension and respiratory depression may also occur with massive doses. A lethal dose of 350 mg/kg has been reported. Generally, no treatment should be required with most overdoses. Drug interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving thiamine and may be of significance in veterinary patients: neu Romu Scu La R b Lockin G a Gent S:T! Thiamine may enhance the activity of neuromuscular blocking agents; clinical significance is unknown Laboratory considerations Thiamine may cause false-positive T! serum uric acid results when using the phosphotungstate method of determination or uro-bilinogen urine spot tests using Ehrlich's reagent The Schack and Wexler method of determining T! theophylline con-centrations may be interfered with by large doses of thiamine Doses Do GS:T! For thiamine deficiency: a) 5-50 mg IM, SC, or IV (depending on formulation) (Phil-lips 1988b) b) 1-2 mg IM (Greene and Braund 1989) c) 2 mg/kg, PO once daily (Davis 1985) d) 100-250 mg SC twice daily for several days until regression of symptoms with complete recovery (Hoskins 1988) For adjunctive treatment for ethylene glycol toxicity: a) 100 mg/day PO (Morgan 1988) cat S:T! For thiamine deficiency:a) 100-250 mg parenterally twice a day (experimentally, as little as 1 mg is effective) (Armstrong and Hand 1989) b) 1-2 mg IM (Greene and Braund 1989) c) 4 mg/kg, PO once daily (Davis 1985) d) 100-250 mg SC twice daily for several days until regression of symptoms with complete recovery (Hoskins 1988) e) 10-20 mg/kg IM or SC two to three times daily until signs abate, then 10 mg/kg PO once daily for 21 days (Morgan 1988) catt Le:T! For thiamine deficiency:a) For polioencephalomalacia: Initially, 10 mg/kg IV; then, 10 mg/kg IM twice daily for 2-3 days. If no improvement with-in 4 days, may be advisable to recommend slaughter. (Dill 1986) b) 10-20 mg/kg IM or SC 3 times daily; if giving IV dilute in isotonic saline or isotonic dextrose. (Walz 2006a) c) 10 mg/kg up to 4 times a day; first dose may be given via slow IV and subsequent doses IM. Less severely affected animals may respond to lower or less frequent dosing. Severely af-fected animals may benefit from corticosteroids (dexametha-sone 1-2 mg/kg) and mannitol (1 g/kg in a 20% solution IV through a filtered IV set). (Cebra 2005) For adjunctive therapy of lead poisoning: a) 2 mg/kg IM (at same time as Ca EDTA therapy); total daily dose 8 mg/kg (Brattan and Kowalczyk 1989) Ho RSe S:T! For thiamine deficiency:a) 0. 5-5 mg/kg IV, IM or PO (Robinson 1987) b) 100-1000 mg IM, SC, or IV (depending on formulation) (Phillips 1988b) For adjunctive treatment of perinatal asphyxia syndrome (hy-poxic ischemic encephalopathy): a) Foals: 1 gram in one liter of fluids IV once a day (Slovis 2003b) SWine:T! For thiamine deficiency: a) 5-100 mg IM, SC, or IV (depending on formulation) (Phil-lips 1988b)	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
870 t Hio Guanine SHee P & Goat S:T! For thiamine deficiency: a) For polioencephalomalacia: Initially, 10 mg/kg IV; then, 10 mg/kg IM twice daily for 2-3 days. If no improvement with-in 4 days, may be advisable to recommend slaughter. (Dill 1986) b) Sheep: 20-200 mg IM, SC, or IV (depending on formula-tion) (Phillips 1988b) monitoring Efficacy T! client information Epidemiologic investigation as to the cause of thiamine deficien-T! cy (diet, plants, raw fish, etc. ) should be performed with neces-sary changes made to prevent recurrence chemistry/Synonyms A water-soluble “B” vitamin, thiamine HCl occurs as bitter-tasting, white, small hygroscopic crystals, or crystalline powder that has a characteristic yeast-like odor. Thiamine HCl is freely soluble in wa-ter, slightly soluble in alcohol and has p K as of 4. 8 and 9. 0. The com-mercially available injection has a p H of 2. 5-4. 5. Thiamine HCl may also be known as: aneurine hydrochlo-ride, thiamin hydrochloride, thiamine chloride, thiamini hydro-chloridum, thiaminii chloridum, vitamin B-1; many trade names available. Storage/Stability/compatibility Thiamine HCl for injection should be protected from light and stored at temperatures less than 40°C and preferably between 15-30°C; avoid freezing. Thiamine HCl is unstable in alkaline or neutral solutions or with oxidizing or reducing agents. It is most stable at a p H of 2. Thiamine HCl is reportedly physically compatible with all com-monly used intravenous replacement fluids. Compatibility is de-pendent upon factors such as p H, concentration, temperature, and diluent used; consult specialized references or a hospital pharmacist for more specific information. Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: Thiamine HCl for Injection: 200 mg/m L in 100 m L and 250 m L vials; Amtech® Thiamine Hydrochloride Injection (Phoenix Scientific), Am-Vet® Thiamine Hydrochloride 200 Mg, (Neogen), generic, (Vet T ek, IVX, Vedco), Vita-Jec® Thiamine HCl (RXV); (Rx) Thiamine HCl for Injection: 500 mg/m L in 100 m L vials; Am-Vet® Thiamine Hydrochloride 500 mg (Neogen), generic, (Butler, IVX, Ve-dco); (Rx). Labeled for use in horses, dogs and cats. Thiamine HCl Dietary Supplement: 8,200 mg/lb. ; Horse Care Durvit B-1 Crumbles® (Durvet); (OTC), Labeled for use in horses. Thiamine HCl Supplement: 500 mg/oz in 1. 5 lb, 4 lb and 20 lb con-tainers; Thia-Dex® (Neogen), Vitamin B-1 Powder® (AHC); (OTC). Labeled for use in dogs & horses. There are several B-complex vitamin preparations available that may also have thiamine included. Human-Labe Le D PRo Duct S: Thiamine Tablets: 50 mg, 100 mg, and 250 mg; generic; (OTC) Thiamine Enteric Coated Tablets: 20 mg; Thiamilate® (Tyson); (OTC) Thiamine HCl Injection: 100 mg/m L in 1 m L, 2 m L multi-dose vials and 2 m L Tubex; generic; (Rx)t Hioguanine (thye-oh-gwah-neen) antineo Pla Stic Prescriber Highlights Oral purine analog antineoplastic that may be useful as T T adjunctive treatment for acute lymphocytic or granulo-cytic leukemia in dogs or cats Contraindications: Hypersensitivity to thioguanine T T Caution: Hepatic dysfunction, bone marrow depression, T T infection, renal function impairment (adjust dosage), or history of urate urinary stones Potentially mutagenic & teratogenic; use milk replacer if T T nursing Adverse Effects: GI effects, bone marrow suppression, T T hepatotoxicity, pancreatitis, GI (including oral) ulceration, & dermatologic reactions Cats may be more susceptible than dogs to adverse T T effects Low therapeutic index; monitoring mandatory T T uses/indications Thioguanine may be useful as adjunctive therapy for acute lympho-cytic or granulocytic leukemia in dogs or cats. Pharmacology/actions Intracellularly, thioguanine is converted to ribonucleotides that cause the synthesis and utilization of purine nucleotides to beblocked. The drug's cytotoxic effects are believed to occur when these substituted nucleotides are inserted into RNA and DNA. Thioguanine has limited immunosuppressive activity. Extensive cross-resistance usually occurs between thioguanine and mercaptopurine. Pharmacokinetics Thioguanine is administered orally, but absorption is variable. In humans, only about 30% of a dose is absorbed. Thioguanine is dis-tributed into the DNA and RNA of bone marrow, but several doses may be necessary for this to occur. It does not apparently enter the CNS, but does cross the placenta. It is unknown whether it enters maternal milk. Thioguanine is rapidly metabolized primarily in the liver to a methylate derivative that is less active (and toxic) than the parent compound. This and other metabolites are eliminated in the urine. contraindications/Precautions/Warnings Thioguanine is contraindicated in patients hypersensitive to it. The drug should be used cautiously (risk versus benefit) in patients with hepatic dysfunction, bone marrow depression, infection, re-nal function impairment (adjust dosage) or with a history of urate urinary stones. Thioguanine has a very low therapeutic index and should only be used by clinicians with experience in the use of cyto-toxic agents and able to monitor therapy appropriately. adverse effects At usual doses, GI effects (nausea, anorexia, vomiting, diarrhea) may occur in small animals. However, bone marrow suppression, hepatotoxicity, pancreatitis, GI (including oral) ulceration, and dermatologic reactions are potentially possible. Cats may be par-ticularly susceptible to the hematologic effects of thioguanine.	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
t Hio Guanine 871 Reproductive/nursing Safety Thioguanine is potentially mutagenic and teratogenic and not rec-ommended for use during pregnancy. In humans, the FDA catego-rizes this drug as category D for use during pregnancy (There is evidence of human fetal risk, but the potential benefits from the use of the drug in pregnant women may be acceptable despite its potential risks. ) Although it is unknown whether thioguanine enters milk, use of milk replacer is recommended for nursing bitches or queens. overdosage/acute t oxicity T oxicity may be acute (GI effects) or delayed (bone marrow depres-sion, hepatotoxicity, gastroenteritis). It is suggested to use standard protocols to empty the GI tract if ingestion was recent and treat supportively. Drug interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving thioguanine and may be of significance in veterinary patients: He Patotoxic DRu GST! (e. g., halothane, ketoconazole, valproic acid, phenobarbital, primidone, etc. ): Thioguanine should be used cau-tiously with other drugs that can cause hepatotoxicity immuno Su PPRe SSi Ve DRu GST! (e. g., azathioprine, cyclophosphamide, corticosteroids ): Use with other immunosuppressant drugs may increase the risk of infection mye Lo Su PPRe SSi Ve DRu GST! (e. g., chloramphenicol, flucytosine, ampho-tericin b, or colchicine ): Use extreme caution when used concur-rently with other drugs that are also myelosuppressive, including many of the other antineoplastics and other bone marrow de-pressant drugs; bone marrow depression may be additive Vaccine S, Li Ve T! : Live virus vaccines should be used with caution during therapy, if at all Laboratory considerations Thioguanine may increase serum T! uric acid levels in some patients Doses Do GS:T! a) For acute lymphocytic and granulocytic leukemia: 40 mg/m2 PO once daily (q24 hours) for 4-5 days, then every 3rd day thereafter (Jacobs, Lumsden et al. 1992) b) As part of protocols for treatment of acute myelogenous leukemias: Protocol 1: Cytarabine 100 mg/m2 SC daily for 2-6 days; Thioguanine 50 mg/m2 PO q24-48h. Protocol 2: Cytarabine 100 mg/m2 SC daily for 2-6 days; Thioguanine 50 mg/m2 PO q24-48h; Doxorubicin 10 mg/m2 IV once a week (Couto 2003) cat S:T! a) For acute lymphocytic and granulocytic leukemia: 25 mg/m2 PO once daily (q24 hours) for 1-5 days, then every 30 days thereafter as necessary (Jacobs, Lumsden et al. 1992) monitoring Hemograms (including platelets) should be monitored closely; T! initially every 1-2 weeks and every 1-2 months once on mainte-nance therapy. It is recommended by some clinicians that if the WBC count drops to between 5,000-7,000 cells/mm 3 the dose be reduced by 25%. If WBC count drops below 5,000 cells/mm3 treatment should be discontinued until leukopenia resolves Liver function tests; serum amylase, if indicated T! Efficacy T!client information Clients must be briefed on the possibilities of severe toxicity de-T! veloping from this drug, including drug-related neoplasms or mortality. Clients should contact veterinarian if the animal exhibits clinical T! signs of abnormal bleeding, bruising, anorexia, vomiting, jaun-dice, or infection. Although, no special precautions are necessary with handling in-T! tact tablets, it is recommended to wash hands after administering the drug. chemistry/Synonyms A purine analog antineoplastic agent, thioguanine occurs as a pale yellow, odorless or practically odorless, crystalline powder. It is in-soluble in water or alcohol. Thioguanine may also be known as: NSC-752, 6-thiogua-nine, TG, 6-TG, 2-Amino-6-mercaptopurine, WR-1141, Lanvis®, Tabloid®, or Tioguanina®. Storage/Stability Store tablets in tight containers at room temperature. Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: None Human-Labe Le D PRo Duct S: Thioguanine Tablets: 40 mg; Tabloid® (Glaxo Smith Kline); (Rx)	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
872 t Hio Penta L So Dium t Hiopental Sodiu M (thye-oh-pen-tal) Pentothal® ul tra-Short acting thiobarbiturate Prescriber Highlights Ultra-short acting thiobarbiturate used for anesthesia in-T T duction or anesthesia for very short procedures Contraindications: Absolute contraindications: absence T T of suitable veins for IV administration, history of hyper-sensitivity reactions to barbiturates, status asthmaticus. Relative contraindications: severe cardiovascular disease or preexisting ventricular arrhythmias, shock, increased intracranial pressure, myasthenia gravis, asthma, & con-ditions where hypnotic effects may be prolonged (e. g., severe hepatic disease, myxedema, severe anemia, ex-cessive premedication, etc. ). Greyhounds (& other sight hounds) metabolize thiobarbiturates much more slowly than other breeds; consider using methohexital instead. HORSES: preexisting leukopenia; thiopental alone may cause excessive ataxia & excitement Avoid: Extravasation, intra-carotid or intra-arterial injec-T T tions, & use of concentrations of less than 2% in sterile water. Too rapid IV administration can cause significant vascular dilatation & hypoglycemia Adverse Effects: T T DOGS: Ventricular bigeminy CATS: Apnea after injection, mild arterial hypotension. HORSES: Excite-ment & severe ataxia (if used alone); transient leukope-nias, hyperglycemia, apnea, moderate tachycardia, mild respiratory acidosis Severe CNS toxicity & tissue damage has occurred T T in horses receiving intra-carotid injections of thiobarbiturates C-III controlled substance T T uses/indications Because of its rapid action and short duration, in young, healthy animals, thiopental is excellent induction agent (rapid IV bolus) for general anesthesia with other anesthetics or as the sole anesthet-ic agent for very short procedures. In sick or debilitated animals, thiopental may be used in a more cautious manner (IV, slowly to effect). Pharmacology/actions Because of their high lipid solubility, thiobarbiturates rapidly enter the CNS and produce profound hypnosis and anesthesia. They are also known as ultrashort-acting barbiturates. See the monograph: Barbiturates, Pharmacology of, for additional information. Pharmacokinetics Following IV injection of therapeutic doses, hypnosis and anesthe-sia occur within one minute. The drug rapidly enters the CNS and then redistributes to muscle and adipose tissue in the body. The short duration of action (10-30 minutes) after intravenous dosing of thiopental is due less to rapid metabolism than to this redistribu-tion out of the CNS and into muscle and fat stores. Greyhounds and other sight hounds may exhibit longer recovery times than other breeds. This may be due to these breeds low body fat levels or differ-ences in the metabolic handling of the thiobarbiturates. Although anesthesia is short, recovery periods may require several hours. Thiopental is metabolized by the hepatic microsomal system and several metabolites have been isolated. The elimination half-life in dogs has been reported as being approximately 7 hours and in sheep, 3-4 hours. Very little of the drug is excreted unchanged in the urine (0. 3% in humans), so dosage adjustments are not neces-sary in patients with chronic renal failure. contraindications/Precautions/Warnings The following are considered absolute contraindications to the use of thiopental: absence of suitable veins for IV administration, his-tory of hypersensitivity reactions to the barbiturates, and status asthmaticus. Relative contraindications include: severe cardiovascu-lar disease or preexisting ventricular arrhythmias, shock, increased intracranial pressure, myasthenia gravis, asthma, and conditions where hypnotic effects may be prolonged (e. g., severe hepatic dis-ease, myxedema, severe anemia, excessive premedication, etc. ). These relative contraindications do not preclude the use of thio-pental, but dosage adjustments must be considered and the drug must be given slowly and cautiously. Because greyhounds (and other sight hounds) metabolize thio-barbiturates much more slowly than methohexital, many clini-cians recommend using methohexital instead. In horses, thiopental should not be used if the patient has preexisting leukopenia. Some clinicians feel that thiopental should not be used alone in the horse as it may cause excessive ataxia and excitement. Concentrations of less than 2% in sterile water should not be used as they may cause hemolysis. Extravasation and intra-arterial injections should be avoided because of the high alkalinity of the solution. Severe CNS toxicity and tissue damage has occurred in horses receiving intra-carotid injections of thiobarbiturates. adverse effects In dogs, thiopental has an approximate arrhythmogenic incidence of 40%. Ventricular bigeminy is the most common arrhythmia seen; it is usually transient and generally responds to additional oxygen. Administration of catecholamines may augment the ar-rhythmogenic effects of the thiobarbiturates, while lidocaine may inhibit it. Cardiac output may also be reduced, but is probably only clinically significant in patients experiencing heart failure. Dose-related apnea and hypotension may be noted. Cats are susceptible to developing apnea after injection and may develop a mild arterial hypotension. Horses can exhibit clinical signs of excitement and severe ataxia during the recovery period if the drug is used alone. Horses can develop transient leukopenias and hyperglycemia after administra-tion. A period of apnea and moderate tachycardia and a mild respi-ratory acidosis may also develop after dosing. T oo rapid IV administration can cause significant vascular dilatation and hypoglycemia. Repeated administration of thiopen-tal is not advised as recovery times can become significantly pro-longed. Parasympathetic side effects (e. g., salivation, bradycardia) may be managed with the use of anticholinergic agents (atropine, glycopyrrolate). Prolonged recoveries may occur when repeated dosages of thio-pental are administered. Thiopental's high p H (10-11) can cause significant tissue irri-tation and necrosis if administered perivascularly; administration through an IV catheter is advised. Reproductive/nursing Safety Thiopental readily crosses the placental barrier and should be used with caution during pregnancy. In humans, the FDA categorizes this drug as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
t Hio Penta L So Dium 873 no adequate studies in humans. ) In a separate system evaluating the safety of drugs in canine and feline pregnancy (Papich 1989), this drug is categorized as in class: C (These drugs may have potential risks. Studies in people or laboratory animals have uncovered risks, and these drugs should be used cautiously as a last resort when the benefit of therapy clearly outweighs the risks. ) Small amounts of thiopental may appear in milk following ad-ministration of large doses, but is unlikely to be of clinical signifi-cance in nursing animals. overdosage/acute t oxicity Treatment of thiobarbiturate overdosage consists of supporting respirations (O 2, mechanical ventilation) and giving cardiovascular support (do not use catecholamines, e. g., epinephrine, etc. ). Drug interactions A fatal interaction has been reported in a dog receiving the propri-etary product, Diathal® (no longer marketed; contained procaine penicillin G, dihydrostreptomycin sulfate, diphemanil methylsul-fate, and chlorpheniramine) and the related compound thiamylal. The following drug interactions have either been reported or are theoretical in humans or animals receiving thiopental and may be of significance in veterinary patients: c Loni Dine T! : IV clonidine prior to induction may reduce thiopen-tal dosage requirements by up to 37% cn S De PRe SSant S, ot He R T! : May enhance respiratory and CNS depressant effects Diazoxi De T! : Potential for hypotension e Pine PHRine, no Re Pine PHRine T! : The ventricular fibrillatory ef-fects of epinephrine and norepinephrine may be potentiated when used with thiobarbiturates and halothane metoc Lo PRami De T! : Given prior to induction may reduce thio-pental dosage requirements mi Dazo Lam T! : May potentiate hypnotic effects o Piate ST! : Given prior to induction may reduce thiopental dosage requirements PHenot Hiazine ST! : May potentiate thiopental effects; hypotension possible PRobeneci DT! : May displace thiopental from plasma proteins Su LFonami De ST! : Thiopental and sulfas may displace one another from plasma proteins Doses note : Atropine sulfate (or glycopyrrolate) is often administered prior to thiobarbiturate anesthesia to prevent parasympathetic side effects; however, some clinicians question whether routine-administration of anticholinergic agents is necessary. Thiobarbiturates are administered strictly to effect; doses are guidelines only. Do GS:T! a) 13. 2-26. 4 mg/kg IV depending on duration of anesthesia required (Package insert; Pentothal®—Ceva Laboratories) b) 15-17 mg/kg IV for brief (7-10 minutes) anesthesia; 18-22 mg/kg IV for moderate (10-15 minutes) duration; 22-29 mg/kg IV for longer (15-25 minutes) duration (Booth 1988a) c) 22 mg/kg IV; or 15. 4 mg/kg IV after tranquilization; or 11 mg/kg IV after narcotic premedication (Mandsager 1988) d) Usually dosed at 12-15 mg/kg, with one-third of the drug administered rapidly and any additional amount adminis-tered to effect. Repeated doses will accumulate resulting in prolonged recoveries; residual effect may last several hours. (Hellyer 2005a)cat S:T! a) 13. 2-26. 4 mg/kg IV depending on duration of anesthesia required (Package insert; Pentothal®—Ceva Laboratories) b) 22 mg/kg IV; or 15. 4 mg/kg IV after tranquilization; or 11 mg/kg IV after narcotic premedication (Mandsager 1988) c) Usually dosed at 12-15 mg/kg, with one-third of the drug administered rapidly and any additional amount adminis-tered to effect. Repeated doses will accumulate resulting in prolonged recoveries; residual effect may last several hours. (Hellyer 2005a) Rabbit S, Ro Dent S, Sma LL mamma LS:T! a) Rabbits: 15-30 mg/kg IV to effect (Ivey and Morrisey 2000) b) For chemical restraint: Mice: 50 mg/kg IP; Rats: 40 mg/kg IP; Hamsters/Gerbils: 30-40 mg/kg IP; Guinea pig: 15-30 mg/ kg IV; Rabbits: 15- 30 mg/kg IV (Burke 1999) catt Le:T! a) 8. 14-15. 4 mg/kg IV; For unweaned calves from which food has been withheld for 6-12 hours: no more than 6. 6 mg/kg IV for deep surgical anesthesia (Pentothal® package insert; Ceva Laboratories) b) For calves under 2 weeks of age: 15-22 mg/kg IV slowly until complete muscular relaxation takes place, duration of anes-thesia usually lasts 10-12 minutes (Booth 1988a) c) 5. 5 mg/kg IV after sedation and administration with guaife-nesin; or 8. 8-11 mg/kg IV after tranquilization (Mandsager 1988) Ho RSe S:T! (note : ARCI UCGFS Class 2 Drug) a) With preanesthetic tranquilization: 6-12 mg/kg IV (an aver-age of 8. 25 mg/kg is recommended); Without preanesthetic tranquilization: 8. 8-15. 4 mg/kg IV (an average horse: 9. 9-11 mg/kg IV) (Package insert; Pentothal®—Ceva Laboratories) b) One gram of thiopental per 90 kg body weight as a 10% solu-tion given evenly over 20 seconds 15 minutes after premedi-cation with either 0. 22 mg/kg IV xylazine or 0. 05 mg/kg IV acepromazine (Booth 1988a) c) 5. 5 mg/kg IV after sedation and administration with guaife-nesin; or 8. 8-11 mg/kg IV after tranquilization (Mandsager 1988) SWine:T! a) 5. 5-11 mg/kg IV (Package insert; Pentothal®—Ceva Labora-tories) b) For swine weighing 5-50 kg: 10-11 mg/kg IV (Booth 1988a) SHee P: T! 9. 9-15 mg/kg IV depending on depth of anesthesia required (Package insert; Pentothal®—Ceva Laboratories) Goat S:T! a) 20-22 mg/kg IV after atropine (0. 7 mg/kg) IM (Booth 1988a) monitoring Level of hypnosis/anesthesia T! Respiratory status; cardiac status (rate/rhythm/blood pressure)T! client information This drug should only be used by professionals familiar with its effects in a setting where adequate respiratory support can be performed.	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
874 t Hiote P a chemistry/Synonyms A thiobarbiturate, thiopental occurs as a bitter tasting, white to off-white, crystalline powder or a yellow-white hygroscopic powder. It is soluble in water (1 gram in 1. 5 m L) and alcohol. Thiopental has a p K a of 7. 6 and is a weak organic acid. Thiopental sodium may also be known as: thiopentone sodium, natrium isopentylaethylthiobarbituricum, penthiobarbital sodique, thiomebumalnatrium cum natrii carbonate, thiopentalum natri-cum, thiopentobarbitalum solubile, tiopentol sodico, Anesthal®, Bensulf®, Farmotal®, Hipnopento®, Inductal®, Intraval®, Nesdonal®, Pensodital®, Pentothal®, Sandothal®, Sodipental®, Thionembutal®, Thiopentax®, Tiobarbital®, or Trapanal®. Storage/Stability/compatibility When stored in the dry form, thiopental sodium is stable indefi-nitely. Thiopental should be diluted with only sterile water for injection, sodium chloride injection, or D 5W. Concentrations of less than 2% in sterile water should not be used as they may cause hemolysis. After reconstitution, solutions are stable for 3 days at room temperature and 7 days if refrigerated; however, as no pre-servative is present, it is recommended it be used within 24 hours after reconstitution. After 48 hours, the solution has been reported to attack the glass bottle in which it is stored. Thiopental may also adsorb to plastic IV tubing and bags. Do not administer any solu-tion that has a visible precipitate. Preparation of Solution for administration: Use only sterile water for injection, normal saline, or D 5W to dilute. A 5 gram vial di-luted with 100 m L will yield a 5% solution and diluted with 200 m L will yield a 2. 5% solution. Discard reconstituted solutions after 24 hours. The following agents have been reported to be physically compat-ible when mixed with thiopental: aminophylline, chloramphenicol sodium succinate, hyaluronidase, hydrocortisone sodium succinate, neostigmine methylsulfate, oxytocin, pentobarbital sodium, phe-nobarbital sodium, potassium chloride, scopolamine HBr, sodium iodide, and tubocurarine chloride (recommendations conflict with regard to tubocurarine; some clinicians recommend not mixing with thiopental). The following agents have been reported to be physically incom-patible when mixed with thiopental: Ringer's injection, Ringer's in-jection lactate, amikacin sulfate, atropine sulfate, benzquinamide, cephapirin sodium, chlorpromazine, codeine phosphate, dimen-hydrinate, diphenhydramine, ephedrine sulfate, glycopyrrolate, hydromorphone, insulin (regular), levorphanol bitartrate, mep-eridine, metaraminol, morphine sulfate, norepinephrine bitartrate, penicillin G potassium, prochlorperazine edisylate, promazine HCl, promethazine HCl, succinylcholine chloride, and tetracycline HCl. Compatibility is dependent upon factors such as p H, concentra-tion, temperature, and diluent used; consult specialized references or a hospital pharmacist for more specific information. Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: None presently being marketed in USA. The ARCI (Racing Commissioners International) has designated this drug as a class 2 substance. See the appendix for more information. Human-Labe Le D PRo Duct S: Thiopental Sodium Powder for Injection: 2% (20 mg/m L) in 1 g, 2. 5 g and 5 g kits; 400 mg Min-I-Mix vials with Min-I-Mix injector; Ready-to-Mix and Ready-to-Mix Life Shield syringes; 2. 5% (25 mg/m L) in 250 mg and 500 mg Min-I-Mix vials; 500 mg, 1 g, 2. 5 g, 5 g and 10 g kits, 250 mg and 500 mg Ready-to-Mix syringes and Ready-to-Mix Life Shield syringes; Pentothal® (Abbott); generic; (Rx, C-III)t Hiotepa (thye-oh-tep-ah) antineo Pla Stic Prescriber Highlights Antineoplastic used systemically for carcinomas, intrac-T T avitary for neoplastic effusions, & intravesical for transi-tional carcinomas; rarely used in small animal oncology Contraindications: Hypersensitivity to thiotepa; Caution: T T Hepatic dysfunction, bone marrow depression, infection, tumor cell infiltration of bone marrow, renal dysfunction, or history of urate urinary stones Adverse Effects: Leukopenia most likely adverse effect; T T other hematopoietic toxicity (thrombocytopenia, anemia, pancytopenia), GI toxicity possible. Intracavitary or intra-vesical instillation can also cause hematologic toxicity. Potentially teratogenic; use milk replacer if patient T T nursing Monitor diligently T T uses/indications Veterinary indications for thiotepa include: systemic use for adjunc-tive therapy against carcinomas, and intracavitary use for neoplastic effusions. In dogs with transitional cell bladder carcinoma, intra-vesical instillation of thiotepa had significantly less efficacy (mean survival time = 57 days) when compared to a systemic doxorubicin/cyclophosphamide protocol (mean survival time = 259 days). Pharmacology/actions Thiotepa is an alkylating agent, thereby interfering with DNA repli-cation and RNA transcription. It is cell cycle non-specific. Thiotepa has some immunosuppressive activity. When given via the intrac-avitary route, thiotepa is thought to control malignant effusions by a direct antineoplastic effect. Pharmacokinetics Thiotepa is poorly absorbed from the GI tract. Systemic absorp-tion is variable from the pleural cavity, bladder, and after IM in-jection. Some studies in humans have shown that absorption from bladder mucosa ranges from 10-100% of an administered dose. Distribution characteristics are not well described; it is unknown if the drug enters maternal milk. Thiotepa is extensively metabolized and then excreted in the urine. contraindications/Precautions/Warnings Thiotepa is contraindicated in patients hypersensitive to it. The drug should be used cautiously (weigh risk versus benefit) in pa-tients with hepatic dysfunction, bone marrow depression, infection, tumor cell infiltration of bone marrow, renal function impairment (adjust dosage) or with a history of urate urinary stones. Thiotepa has a very low therapeutic index and should only be used by cli-nicians with experience in the use of cytotoxic agents and able to monitor therapy appropriately. adverse effects When used systemically, leukopenia is the most likely adverse effect seen in small animals. Other hematopoietic toxicity (thrombocy-topenia, anemia, pancytopenia) may be noted. Intracavitary or in-travesical instillation of thiotepa may cause hematologic toxicity. GI toxicity (vomiting, diarrhea, stomatitis, intestinal ulceration) may	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
t Hy Rot Ro Pin 875 be noted and human patients have reported dizziness and headache as well. Reproductive/nursing Safety Thiotepa is potentially mutagenic and teratogenic and is not recom-mended for use during pregnancy. In humans, the FDA categorizes this drug as category D for use during pregnancy (There is evidence of human fetal risk, but the potential benefits from the use of the drug in pregnant women may be acceptable despite its potential risks. ) Although it is unknown whether thiotepa enters milk, use of milk replacer is recommended for nursing bitches or queens. overdosage/acute t oxicity There is no specific antidote for thiotepa overdose. Supportive ther-apy, including transfusions of appropriate blood products, may be beneficial for treatment of hematologic toxicity. Drug interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving thiotepa and may be of significance in veterinary patients: immuno Su PPRe SSi Ve DRu GST! (e. g., azathioprine, cyclophosphamide, corticosteroids ): Use with other immunosuppressant drugs may increase the risk of infection mye Lo Su PPRe SSi Ve DRu GST! (e. g., chloramphenicol, flucytosine, ampho-tericin b, or colchicine ): Use extreme caution when used concur-rently with other drugs that are also myelosuppressive, including many of the other antineoplastics and other bone marrow de-pressant drugs; bone marrow depression may be additive Vaccine S, Li Ve T! : Live virus vaccines should be used with caution during therapy, if at all Laboratory considerations Thiotepa may increase serum T! uric acid levels in some patients Doses Do GS:T! a) For intracavitary use neoplastic effusions or systemically for adjunctive therapy of carcinomas: 0. 2-0. 5 mg/m2 intracavi-tary; IV. (Jacobs, Lumsden et al. 1992) monitoring Efficacy T! CBC with platelets T! client information Clients must be briefed on the possibilities of severe toxicity de-T! veloping from this drug, including drug-related neoplasms or mortality Clients should contact veterinarian should the animal exhibit T! clinical signs of abnormal bleeding, bruising, anorexia, vomiting, jaundice, or infection chemistry/Synonyms An ethylene derivative alkylating agent antineoplastic, thiotepa oc-curs as fine, white crystalline flakes. The drug has a faint odor and is freely soluble in water or alcohol. Thiotepa may also be known as: NSC-6396, TESPA, thio-phosphamide, triethylenethiophosphoramide, TSPA, WR-45312, Ledertepa ®, Onco Tiotepa®, Tespamin®, or Thioplex®. Storage/Stability Store both the powder and the reconstituted solution refrigerat-ed (2-8°C) and protected from light. Do not use solution that is grossly opaque (slightly opaque is OK) or if a precipitate is present. If refrigerated, reconstituted solutions are stable for up to 5 days. Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: None Human-Labe Le D PRo Duct S: Thiotepa Lyophilized Powder for Injection: 15 mg & 30 mg in vials; Thioplex® (Amgen); generic, (Sicor); (Rx) t Hyrotropin t Hyrotropin alfa (rh t SH) (thye-roe-troe-pin) Thyroid Stimulating Hormone, TSH hormone Prescriber Highlights Hormone used for thyroid stimulating hormone (TSH) test T T for thyroid function Contraindications: Adrenocortical insufficiency, hyperthy-T T roidism, coronary thrombosis, hypersensitivity to bovine thyrotropin Adverse Effects: Hypersensitivity (especially with repeat-T T ed injections)Availability (of bovine source TSH) and expense (human T T product) may be issues uses/indications The labeled indications for the formerly available veterinary prod-uct Dermathycin® (Mallinckrodt) was for “the treatment of acan-thosis nigricans and for temporary supportive therapy in hypothy-roidism in dogs. ” In actuality however, TSH is used in veterinary medicine principally as a diagnostic agent in the TSH stimulation test to diagnose primary hypothyroidism. Pharmacology/actions Thyrotropin increases iodine uptake by the thyroid gland and in-creases the production and secretion of thyroid hormones. With prolonged use, hyperplasia of thyroid cells may occur. Pharmacokinetics No specific information was located; exogenously administered TSH apparently exerts maximal increases in circulating T 4 approxi-mately 4-8 hours after IM or IV administration. contraindications/Precautions/Warnings A previous veterinary manufacturer (Coopers), listed adrenocorti-cal insufficiency and hyperthyroidism as contraindications to TSH use for treatment purposes in dogs. In humans, TSH is contrain-dicated in patients with coronary thrombosis, untreated Addison's disease, or hypersensitive to bovine thyrotropin. adverse effects Because the product is derived from bovine sources, anaphylaxis may occur in patients sensitive to bovine proteins, particularly with repeated use.	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
876 tiamu Lin Reproductive/nursing Safety In humans, the FDA categorizes this drug as category C for use dur-ing pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) It is not known whether the drug is excreted in human milk, but is unlikely to be clinically significant when used for diagnostic purposes. overdosage/acute t oxicity Chronic administration at high dosages can produce clinical signs of hyperthyroidism. Massive overdoses can cause clinical signs re-sembling thyroid storm. Refer to the levothyroxine monograph for more information on treatment. Drug interactions; Laboratory considerations Refer to the information listed in the Levothyroxine monograph for more information. Doses Do GS:T! For TSH stimulation test: a) Draw pre-dose baseline sample. Administer 0. 1 IU/kg IV (maximum of 5 IU). Collect sample for T 4 6 hours after dose. (Peterson and Ferguson 1989) b) 5 IU IV or 0. 1 IU/kg IV. Measure serum T 4 at 0 hours (pre-sample) and 4 or 6 hours after dose (Morgan 1988) c) Using the bovine product: Measure pre-dose (basal) T4; then 0. 1 Units/kg (maximum of 5 Units) IV. Measure post-dose T4 at 6 hours. Using the human recombinant product: 50-100 mcg (0. 05-0. 1 mg) IV; Measure serum T 4 at 0 hours (pre-sam-ple) and 4 hours post. Product may be frozen for at least 8 weeks with no loss of potency. (Scott-Moncrieff 2006b) cat S:T! For TSH stimulation test:a) Draw pre-dose baseline sample. Administer 1 IU/kg IV or 2. 5 IU IM. Collect sample for T 4 6 hours after dose. (Peterson and Ferguson 1989) b) 2. 5 IU IV. Measure serum T 4 at 0 hours (pre-sample) and 4 or 6 hours after dose. (Morgan 1988) Ho RSe S:T! For TSH stimulation test: a) Draw pre-dose sample, then 5-10 IU of bovine TSH IV. Draw follow-up samples 4-8 hours after dosing. Normal thyroid gland should produce a 2-4 times increase in serum T3 and T 4 levels. (Chen and Li 1987) client information Usually, TSH will be administered by professional staff T! chemistry/Synonyms Commercially available thyrotropin (human; rh TSH) is now avail-able only as a lyophilized powder for reconstitution obtained via DNA recombinant technology. Originally obtained from bovine an-terior pituitary glands, thyrotropin is a highly purified preparation of thyroid-stimulating hormone (TSH). Thyrotropin is a glycopro-tein and has a molecular weight of approximately 28,000-30,000. Thyrotropin is measured in International Units (IU), with 7. 5 mi-crograms of thyrotropin approximately equivalent to 0. 037 units. Thyrotropin may also be known as: thyroid-stimulating hor-mone, thyrotrophic hormone, thyrotropin, TSH, Ambinon®, Thyreostimulin®, Thyrogen®, or Thytropar®. Storage/Stability Thyrotropin alfa (unreconstituted) should be stored between 2-8°C (36-46°F). If necessary, the reconstituted solution can be stored up to 24 hours between 2-8°C (36-46°F), while avoiding microbial contamination. However, it is reportedly stable if kept refrigerated (2-8°C) up to 4 weeks and up to 8 weeks if frozen (-20°C). After reconstitution visually inspect each vial for particulate matter or discoloration before use. Do not use any vial exhibiting particulate matter or discoloration. Do not use after the expiration date on the vial. Protect from light. Thyrotropin lyophilized powder for injection (Bovine) is report-edly stable in the dry state. However, the veterinary manufacturer recommended storing the powder below 59°F, and after reconsti-tuting, storing in the refrigerator and discarding any unused drug after 48 hours. It has been suggested however, that reconstituted TSH (bovine) is stable for at least 3 weeks when refrigerated. Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: None Human-Labe Le D PRo Duct S: Thyrotropin (Thyroid Stimulating Hormone) Powder for Injection, Lyophilized: 1. 1 mg thyrotropin alfa (less than or equal to 4 IU)/vial in kits of two 1. 1 mg single-use vials of thyrotropin alfa and two 10 m L vials of diluent; Thyrogen® (Genzyme); (Rx) Thyroxine Sodium—See Levothyroxine Sodium tia Mulin (tye-am-myoo-lin) Denagard® diter Pine antibiotic Prescriber Highlights Antibiotic used primarily in swine T T Contraindications: Access to feeds containing polyether T T ionophores (e. g., monensin, lasalocid, narasin, or salino-mycin); swine over 250 pounds Adverse Effects are unlikely T T Variable withdrawal times depending on dosage T T uses/indications Tiamulin is approved for use in swine to treat pneumonia caused by susceptible strains of Haemophilus pleuropneumoniae and swine dysentery caused by Treponema hyodysenteriae. As a feed additive, it is used to cause increased weight gain in swine. Pharmacology/actions Tiamulin is usually a bacteriostatic antibiotic, but can be bacteri-cidal in very high concentrations against susceptible organisms. The drug acts by binding to the 50S ribosomal subunit, thereby in-hibiting bacterial protein synthesis. Tiamulin has good activity against many gram-positive cocci, in-cluding most Staphylococci and Streptococci (not group D streps). It also has good activity against Mycoplasma and spirochetes. With the exception of Haemophilus spp. and some E. coli and Klebsiella strains, the drug's activity is quite poor against gram-negative or-ganisms.	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
tica Rci LLin Di So Dium 877 Pharmacokinetics Tiamulin is well absorbed orally by swine. Approximately 85% of a dose is absorbed and peak levels occur between 2-4 hours after a single oral dose. Tiamulin is apparently well distributed, with high-est levels found in the lungs. Tiamulin is extensively metabolized to over 20 metabolites, some having antibacterial activity. Approximately 30% of these metabolites are excreted in the urine with the remainder excreted in the feces. contraindications/Precautions/Warnings Tiamulin should not be administered to animals having access to feeds containing polyether ionophores (e. g., monensin, lasalocid, narasin, or salinomycin) as adverse reactions may occur. Not for use in swine over 250 pounds. Reproductive/nursing Safety T eratogenicity studies done in rodents demonstrated no terato-genic effects at doses up to 300 mg/kg. The manufacturer has con-cluded that the drug is not tumorigenic, carcinogenic, teratogenic, or mutagenic. adverse effects Adverse effects occurring with this drug at usual doses are consid-ered unlikely. Rarely, redness of the skin, primarily over the ham and underline, has been observed. It is recommended to discon-tinue the medication, provide clean drinking water, and hose down the area or move affected animals to clean pens. overdosage/acute t oxicity Oral overdoses in pigs may cause transient salivation, vomiting, and CNS depression (calming effect). Discontinue drug and treat symp-tomatically and supportively if necessary. Drug interactions Po Lyet He R iono PHo Re ST! (e. g., monensin, lasalocid, narasin, or salino-mycin ): Tiamulin should not be administered to animals having access to feeds containing polyether ionophores as adverse reac-tions may occur Linco Sami De S, mac Ro Li De S T! (e. g., clindamycin, lincomycin, erythromy-cin, tylosin ): Although not confirmed with this drug, concomitant use with other antibiotics that bind to the 50S ribosome could lead to decreased efficacy secondary to competition at the site of action Doses SWine:T! a) For swine dysentery: 7. 7 mg/kg PO daily in drinking water for 5 days. See package directions for dilution instructions. (Package insert; Denagard® Liquid Concentrate) b) For swine pneumonia: 23. 1 mg/kg PO daily in drinking wa-ter for 5 days. See package directions for dilution instruc-tions. (Package insert; Denagard® Liquid Concentrate) c) For use as a medicated premix: See the label for the product. monitoring Clinical efficacy T! client information Prepare fresh medicated water daily T! Avoid contact with skin or mucous membranes as irritation may T! occurchemistry/Synonyms A semisynthetic diterpene-class antibiotic derived from pleuromu-lin, tiamulin is available commercially for oral use as the hydrogen fumarate salt. It occurs as white to yellow, crystalline powder with a faint but characteristic odor. Approximately 60 mg of the drug are soluble in 1 m L of water. Tiamulin may also be known as: 81723-hfu, SQ-14055, SQ-22947 (tiamulin fumarate), and Denagard®. Storage/Stability Protect from moisture; store in a dry place. In unopened packets, the powder is stable up to 5 years. Fresh solutions should be pre-pared daily when using clinically. Dosage Forms/Regulatory Status Vete Rina R y a PPRo Ve D PRo Duct S: Tiamulin Medicated Premix: 10 g/1 lb in 35 lb bags. Approved for use in swine not weighing over 250 lbs. Slaughter withdrawal period at the 35 g/ton use is 2 days and at the 200 g/ton dose is 7 days. Dena-gard® 10 (Novartis); (OTC) Tiamulin Solution: 12. 3% tiamulin hydrogen fumarate in an aqueous base in 32 oz bottles. Approved for use in swine. Slaughter withdraw-al: treatment at 3. 5 mg/lb = 3 days, at 10. 5 mg/lb = 7 days. Denagard® Liquid Concentrate (Boehringer Ingelheim); Amtech® Tiamulin Liq-uid Concentrate (IVX); (OTC) Tiamulin Soluble Powder: 45% in 2. 28 oz packets (29. 1 g tiamulin per packet). Approved for use in swine. Slaughter withdrawal: treat-ment at 3. 5 mg/lb = 3 days, at 10. 5 mg/lb = 7 days. Denagard® Liquid Concentrate (Boehringer Ingelheim); Amtech® Tiamulin Soluble An-tibiotic (IVX); (OTC) Human a PPRo Ve D PRo Duct S: None ticarcillin di Sodiu M (tye-kar-sill-in) Ticar® Parenteral extended S Pectrum Penicillin Prescriber Highlights Parenteral, anti-pseudomonal penicillin T T Contraindications: Known hypersensitivity (unless no T T other options) Adverse Effects: Hypersensitivity possible; very high T T doses may cause CNS effects. Potentially could cause bleeding Treatment is relatively expensive T T uses/indications A ticarcillin disodium product was approved for intrauterine use in horses in the treatment of endometritis in horses caused by beta hemolytic streptococci, but is apparently no longer marketed. Ticarcillin disodium injection is used in veterinary species in the treatment of systemic Pseudomonas aeruginosa infections, often in combination with an appropriate aminoglycoside agent. When compared with carbenicillin, ticarcillin is about twice as potent (on a per weight basis) in the treatment against susceptible Pseudomonas. Synergy may occur against some Pseudomonas strains when used in combination with aminoglycosides, but in vitro inactivation of the aminoglycoside may also occur (see Drug Interactions) if the	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
878 tica Rci LLin Di So Dium drugs are physically mixed together or in patients with severe renal failure. Ticarcillin (alone and with clavulanate) has been used in a vari-ety of compounded preparations for otic use. Pharmacology/actions Penicillins are usually bactericidal against susceptible bacteria and act by inhibiting mucopeptide synthesis in the cell wall resulting in a defective barrier and an osmotically unstable spheroplast. The ex-act mechanism for this effect has not been definitively determined, but beta-lactam antibiotics have been shown to bind to several en-zymes (carboxypeptidases, transpeptidases, endopeptidases) within the bacterial cytoplasmic membrane that are involved with cell wall synthesis. The different affinities that various beta-lactam antibiot-ics have for these enzymes (also known as penicillin-binding pro-teins; PBPs) help explain the differences in spectrums of activity the drugs have that are not explained by the influence of beta-lacta-mases. Like other beta-lactam antibiotics, penicillins are generally considered more effective against actively growing bacteria. The extended-spectrum penicillins, sometimes called anti-pseudomonal penicillins, include both alpha-carboxypenicillins (carbenicillin and ticarcillin) and acylaminopenicillins (piperacillin, azlocillin, and mezlocillin). These agents have similar spectrums of activity as the aminopenicillins but with additional activity against several gram-negative organisms of the family Enterobacteriaceae, including many strains of Pseudomonas aeruginosa. Like the amin-openicillins, these agents are susceptible to inactivation by beta-lactamases. Pharmacokinetics Ticarcillin is not appreciably absorbed after oral administration and must be given parenterally to achieve therapeutic serum levels. When given IM to humans, the drug is readily absorbed with peak levels occurring about 30-60 minutes after dosing. The reported bioavailability in the horse after IM administration is about 65%. After parenteral injection, ticarcillin is distributed into pleural fluid, interstitial fluid, bile, sputum, and bone. Like other penicil-lins, CSF levels are low in patients with normal meninges (about 6% of serum levels), but increased (39% of serum levels) if menin-ges are inflamed. The volume of distribution is reportedly 0. 34 L/kg in dogs and 0. 22-0. 25 L/kg in the horse. The drug is 45-65% bound to serum proteins (human). Ticarcillin is thought to cross the placenta and found in small quantities in milk. In cattle, mas-titic milk levels of ticarcillin are approximately twice those found in normal milk, but are too low to treat most causal organisms. Ticarcillin is eliminated primarily by the kidneys, via both tu-bular secretion and glomerular filtration. Concurrent probenecid administration can slow elimination and increase blood levels. In humans, about 10-15% of the drug is metabolized by hydrolysis to inactive compounds. The half-life in dogs and cats is reportedly 45-80 minutes; about 54 minutes in the horse. Clearance is 4. 3 m L/ kg/min in the dog and 2. 8-3. 2 m L/kg/min in the horse. contraindications/Precautions/Warnings Penicillins are contraindicated in patients with a history of hyper-sensitivity to them. Because there may be cross-reactivity, use peni-cillins cautiously in patients who are documented hypersensitive to other beta-lactam antibiotics (e. g., cephalosporins, cefamycins, carbapenems). Ticarcillin has significant quantities of sodium per gram and may cause electrolyte imbalances when used in large dosages in susceptible patients. adverse effects Adverse effects with the penicillins are usually not serious and have a relatively low frequency of occurrence. Hypersensitivity reactions unrelated to dose can occur with these agents and can manifest as rashes, fever, eosinophilia, neu-tropenia, agranulocytosis, thrombocytopenia, leukopenia, anemias, lymphadenopathy, or full-blown anaphylaxis. In humans, it is esti-mated that up to 15% of patients hypersensitive to cephalosporins will also be hypersensitive to penicillins. The incidence of cross-reactivity in veterinary patients is unknown. Neurotoxicity (e. g., ataxia in dogs) has been associated with very high doses or very prolonged use. Although the penicillins are not considered hepatotoxic, elevated liver enzymes have been reported. Other effects reported in dogs include tachypnea, dyspnea, edema, and tachycardia. Ticarcillin has been implicated in causing bleeding problems in humans; veterinary ramifications of this potential effect are unclear. Reproductive/nursing Safety Penicillins have been shown to cross the placenta and safe use of them during pregnancy has not been firmly established, but neither have there been any documented teratogenic problems associated with these drugs; however, use only when the potential benefits outweigh the risks. In humans, the FDA categorizes this drug as category B for use during pregnancy (Animal studies have not yet demonstrated risk to the fetus, but there are no adequate studies in pregnant women; or animal studies have shown an adverse effect, but adequate studies in pregnant women have not demonstrated a risk to the fetus in the first trimester of pregnancy, and there is no evidence of risk in later trimesters. ) In a separate system evaluating the safety of drugs in canine and feline pregnancy (Papich 1989), this drug is categorized as in class: A (Probably safe. Although specific studies may not have proved he safety of all drugs in dogs and cats, there are no reports of adverse effects in laboratory animals or women. ) Although penicillins can be distributed into milk, it is unlikely that ticarcillin would be of clinical concern in nursing veterinary patients. overdosage/acute t oxicity In humans, very high dosages of parenteral penicillins, especially in patients with renal disease, have induced CNS effects. Drug interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving ticarcillin and may be of significance in veterinary patients: amino GL yco Si De S T! (e. g., amikacin, gentamicin, tobramycin ): In vitro studies have demonstrated that penicillins can have synergistic or additive activity against certain bacteria when used with amino-glycosides; however, beta-lactam antibiotics can inactivate amin-oglycosides in vitro and in vivo in patients in renal failure or when penicillins are used in massive dosages. Amikacin is considered the most resistant aminoglycoside to this inactivation. PRobeneci DT! : Can reduce the renal tubular secretion of ticarcillin, thereby maintaining higher systemic levels for a longer period of time Wa RF a Rin; He Pa Rin T! : As ticarcillin has been implicated in rarely causing bleeding, use with caution in patients receiving antico-agulant therapy	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
tica Rci LLin Di So Dium 879 Laboratory considerations aminoglycoside serum quantitative analysis T! : As penicillins and oth-er beta-lactams can inactivate aminoglycosides in vitro (and in vivo in pa tients in renal failure or when penicillins are used in massive dosages), serum concentrations of aminoglycosides may be falsely decreased if the pa tient is also receiving beta-lactam antibiotics and the serum is stored prior to analysis. It is recom-mended that if the aminoglycoside assay is delayed, samples be frozen and, if possible, drawn at times when the beta-lactam an-tibiotic is at a trough. Direct antiglobulin T! (coombs' ) tests : False-positive results may occur urine protein T! : May produce false-positive protein results with the sulfosalicylic acid and boiling test, nitric acid test, and the ace-tic acid test. Strips using bromophenol blue reagent (e. g., Multi-Stix®) do not appear to be affected by high levels of penicillins in the urine Doses Do GS:T! For susceptible infections:a) For susceptible (to ticarcillin) infections demonstrated to be resistant to other less expensive and more convenient anti-biotics. Ticarcillin: 15-25 mg/kg as an IV infusion over 15 minutes, followed by a constant rate IV infusion at 7. 5-15 mg/kg/hour (Trepanier 1999) b) For treatment of Pseudomonas aeruginosa infections in con-junction with an aminoglycoside: 50-75 mg/kg IV or IM q8h (Aucoin 2002b) c) For soft tissue, systemic infections: 15-25 mg/kg IV, IM, SC q6-8h as long as necessary; For septicemia: 40-50 mg/kg IV, IM q4-6h as long as necessary; For difficult, severe systemic infections: 100 mg/kg IV q6-8h as long as necessary. (Greene, Hartmannn et al. 2006) d) As an otic solution for adjunctive treatment of Pseudomonas otitis using ticarcillin: Dilute according to manufacturer's directions to a concentration of 2 mg/m L and apply 5-10 drops per ear every 12 hours. (Kwochka 2003a) cat S:T! For susceptible infections:a) For susceptible (to ticarcillin) infections demonstrated to be resistant to other less expensive and more convenient anti-biotics. Ticarcillin: 15-25 mg/kg as an IV infusion over 15 minutes, followed by a constant rate IV infusion at 7. 5-15 mg/kg/hour (Trepanier 1999) b) For treatment of Pseudomonas aeruginosa infections in con-junction with an aminoglycoside: 50-75 mg/kg IV or IM q8h (Aucoin 2002b) c) For Pseudomonas soft tissue, systemic infections: 15-24 mg/ kg IV, IM, SC q8h as long as necessary; For Pseudomonas systemic, bacteremia: 40-50 mg/kg IV q6h as long as necessary. (Greene, Hartmannn et al. 2006) Ho RSe S:T! For susceptible systemic infections: a) 22-44 mg/kg IV q6h. (Bertone 2003a) b) Foals: 40-60 mg/kg IV, IM q6-8h (Brumbaugh 1999) c) Foals: 50 mg/kg q6h IV or IM (Furr 1999)For treatment of endometritis secondary to susceptible bacteria: a) 6 grams intrauterine per day for 3 days during estrus. Re-constitute vial with 25 m L of Sterile Water for Injection, USP or Sodium Chloride Injection, USP. After dissolved, further dilute to a total volume of 100-500 m L with sterile water or sterile normal saline and aseptically instill into uterus. (Pack-age insert; Ticillin®—Beecham) bi RDS:T! For susceptible infections:a) 200 mg/kg IV or IM twice daily, three times daily or four times daily (Clubb 1986) b) 200 mg/kg IM or IV q8h (Hoeffer 1995) monitoring Because penicillins usually have minimal toxicity associated with T! their use, monitoring for efficacy is usually all that is required un-less toxic signs develop. Serum levels and therapeutic drug moni-toring are not routinely done with these agents. chemistry/Synonyms An alpha-carboxypenicillin, ticarcillin disodium occurs as a white to pale yellow, hygroscopic powder or lyophilized cake with p K as of 2. 55 and 3. 42. More than 600 mg is soluble in 1 m L of water. Potency of ticarcillin disodium is expressed in terms of ticarcillin and one gram of the disodium contains not less than 800 mg of ti-carcillin anhydrous. One gram of the commercially available injec-tion contains 5. 2-6. 5 m Eq of sodium and after reconstituting the injection has a p H of 6-8. Ticarcillin Disodium may also be known as: BRL-2288, ticarcil-linum natricum, Aerugipen®, Tarcil®, Ticar®, Ticarpen®, Ticillin®, or Triacilline®. Storage/Stability/compatibility Ticarcillin injectable powder for injection should be stored at tem-peratures of less than 30°C (room temperature or colder). If stored at room temperature after reconstitution, polymer con-jugates can form that may increase the likelihood of hypersensi-tivity reactions occurring, therefore, many clinicians recommend either refrigerating the solution or administering within 30 minutes of reconstitution. From a potency standpoint, the drug should be used generally within 24 hours if stored at room temperature and 72 hours if refrigerated, but the manufacturer has specific recom-mendations on stability depending on the concentration of the drug and the solution used; refer to the package insert. Frozen solutions are reportedly stable for at least 30 days when stored at-20°C. Ticarcillin disodium solutions are reportedly physically compati-ble with the following solutions and drugs: D 5W, Ringer's Injection, Lactated Ringer's Injection, sodium chloride 0. 9%, Sterile water for injection, acyclovir sodium, hydromorphone HCl, meperidine HCl, methylprednisolone sodium succinate, morphine sulfate, ranitidine HCl, perphenazine, and verapamil HCl. Ticarcillin disodium solutions are reportedly physically incom-patible with the aminoglycoside antibiotics; refer to the drug inter-action information in the Penicillins, General Information mono-graph for more information. Compatibility is dependent upon factors such as p H, concentration, temperature, and diluent used; consult specialized references or a hospital pharmacist for more specific information. Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: None Human-Labe Le D PRo Duct S: Ticarcillin Disodium Powder for Injection: (contains 5. 2 m Eq sodium/g) 3 g in vials; Ticar® (Glaxo Smith Kline); (Rx)	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
880 tica Rci LLin Di So Dium + c La Vu Lanate Pota SSium ticarcillin di Sodiu M + clavulanate pota SSiu M (tye-kar-sill-in; klav-yoo-lan-ate) Timentin® Parenteral extended SPectrum Penicillin + beta-l actama Se inhibitor Prescriber Highlights Parenteral, extended action penicillin with a beta lacta-T T mase inhibitor; has increased spectrum of activity when compared with ticarcillin alone, but is more expensive Used for serious systemic infections & as a compounded T T otic prep for Pseudomonas otitis Limited experience or research in veterinary medicine, T T but appears quite safe Patients with significantly impaired renal function or T T those receiving very high dosages may be more prone to develop platelet function abnormalities (bleeding) or CNS effects uses/indications Ticarcillin/clavulanate is used systemically to treat serious infections such as sepsis or nosocomial pneumonias in dogs, cats and horses. By adding clavulanate, enhanced spectrum of activity against beta-lactamase producing bacteria can be obtained. This drug combina-tion is sometimes used to treat Pseudomonas otitis in dogs. Pharmacology/actions See the Ticarcillin monograph for information on ticarcillin. By adding clavulanate, ticarcillin's efficacy can be extended against beta-lactamase-producing strains of otherwise resistant E. coli, Pasturella spp., Staphylococcus spp., Klebsiella, and Proteus. Clavulanic acid acts by competitively and irreversibly binding to beta-lactamases, including types II, III, IV, and V, and penicillinases produced by Staphylococcus. Type I beta-lactamases that are often associated with E. coli, Enterobacter, and Pseudomonas are not generally in-hibited by clavulanic acid. Clavulanic acid has only weak antibacterial activity when used alone and at present is only available in fixed-dose combinations with either amoxicillin (oral) or ticarcillin (parenteral). Unlike sulbactam or tazobactam, clavulanic acid (clavulanate) can induce chromosomal beta-lactamases. Synergy against Pseudomonas aeruginosa can occur when used with an aminoglycoside, but the drugs cannot be mixed together (see Drug Interactions). Pharmacokinetics Ticarcillin pharmacokinetics are presented in the monograph pre-ceding this one. There is no evidence to suggest that the addition of clavulanic acid alters ticarcillin pharmacokinetics. Clavulanic acid has an apparent volume of distribution of 0. 32 L/kg in dogs and is distributed (with ticarcillin) into the lungs, pleural fluid and peritoneal fluid. Low concentrations of both drugs are found in the saliva, sputum and CSF (uninflamed meninges). Higher concentrations in the CSF are expected when meninges are inflamed, but it is questionable whether therapeutic levels are attain able. Clavulanic acid is 13% bound to proteins in dog serum. Clavulanic acid is extensively metabolized in the dog (and rat) primarily to 1-amino-4-hydroxybutan-2-one. It is not known if this compound possesses any beta-lactamase inhibiting activity. Clavulanic acid is also excreted unchanged in the urine via glom-erular filtration. In dogs, 34-52% of a dose is excreted in the urine as unchanged drug and metabolites, 25-27% in the feces, and 16-33% into respired air. The elimination half-life for clavulanic acid in dogs is faster than is ticarcillin. contraindications/Precautions/Warnings Do not use this medication in patients with documented hypersen-sitivity reactions to penicillins or other beta-lactams. Dosage adjustments should be made in patients with signifi-cantly impaired renal function. adverse effects Although clinical experience with this medication in veterinary patients is limited, it appears to be well tolerated' potentially, hy-persensitivity reactions can occur. In humans, high dosages (par-ticularly in patients with renal insufficiency) have caused platelet dysfunction and bleeding, and CNS effects (headache, giddiness, hallucinations, seizures). Intramuscular administration can cause pain, but reconstituting with 1% lidocaine (see Storage/Stability/Compatibility) can alleviate this effect. Local irritation to veins after IV administration is possible and best avoided by using dilute con-centrations administered over not less than 30 minutes. Antibiotic-associated diarrhea or colitis may occur. Reproductive/nursing Safety Penicillins have been shown to cross the placenta and safe use dur-ing pregnancy has not been firmly established, but neither have there been any documented teratogenic problems associated with these drugs; however, use only when the potential benefits outweigh the risks. In humans, the FDA categorizes ticarcillin/clavulanate as category B for use during pregnancy (Animal studies have not yet demonstrated risk to the fetus, but there are no adequate studies in pregnant women; or animal studies have shown an adverse effect, but adequate studies in pregnant women have not demonstrated a risk to the fetus in the first trimester of pregnancy, and there is no evidence of risk in later trimesters. ) Although penicillins can be distributed into milk, it is unlikely that ticarcillin/clavulanate would be of significant clinical concern for nursing veterinary patients. overdosage/acute t oxicity A single inadvertent overdose is unlikely to cause significant mor-bidity. In humans, very high dosages of parenteral penicillins such as ticarcillin, especially in patients with renal disease, have induced CNS effects (hallucinations, headaches, seizures) and alterations in platelet function (bleeding). Drug interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving ticarcillin/clavulanate and may be of significance in veterinary patients: amino GL yco Si De S T! (e. g., amikacin, gentamicin, tobramycin ): In vitro studies have demonstrated that penicillins can have synergistic or additive activity against certain bacteria when used with amino-glycosides. However, beta-lactam antibiotics can inactivate amin-oglycosides in vitro and in vivo in patients in renal failure or when penicillins are used in massive dosages. Amikacin is considered the most resistant aminoglycoside to this inactivation. PRobeneci DT! : Can reduce the renal tubular secretion of ticarcillin, thereby maintaining higher systemic levels for a longer period of time; it does not affect the elimination of clavulanate	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
tica Rci LLin Di So Dium + c La Vu Lanate Pota SSium 881 Wa RF a Rin; He Pa Rin T! : As ticarcillin has been implicated in rarely causing bleeding, use with caution in patients receiving antico-agulant therapy Laboratory considerations aminoglycoside serum quantitative analysis T! : As penicillins and oth-er beta-lactams can inactivate aminoglycosides in vitro (and in vivo in pa tients in renal failure or when penicillins are used in massive dosages), serum concentrations of aminoglycosides may be falsely decreased if the pa tient is also receiving beta-lactam antibiotics and the serum is stored prior to analysis. It is recom-mended that if the aminoglycoside assay is delayed, samples be frozen and, if possible, drawn at times when the beta-lactam an-tibiotic is at a trough. Direct antiglobulin T! (coombs' ) tests : False-positive results may occur urine protein T! : May produce false-positive protein results with the sulfosalicylic acid and boiling test, nitric acid test, and the ace-tic acid test. Strips using bromophenol blue reagent (e. g., Multi-Stix®) do not appear to be affected by high levels of penicillins in the urine Doses note : Unless otherwise indicated, this drug combination is dosed on the basis of ticarcillin content. Do GS:T! a) For sepsis: 40-50 mg/kg q6-8h IV (Hardie 2000) b) 15-50 mg/kg q6-8h IV, IM or SC (Lappin 2003c) For Pseudomonas sepsis/bacteremia: 20-50 mg/kg IV q6-8h (Greene, Hartmannn et al. 2006) c) As an otic solution for adjunctive treatment of Pseudomonas otitis using the ticarcillin/clavulanic acid product—Timen-tin®): Dilute according to manufacturer's directions, then draw into 2 m L aliquots and freeze. Thaw and use each ali-quot as 0. 5 m L in each ear, twice daily. (White 2003c) cat S:T! a) For sepsis: 40-50 mg/kg q6-8h IV (Hardie 2000) b) For Pseudomonas sepsis/bacteremia: 40 mg/kg IV q6h (Greene, Hartmannn et al. 2006) c) 50 mg/kg IV or IM 4 times daily; may need more frequent dosing or constant rate infusion for resistant Pseudomonas infections (Trepanier 1999) d) 15-50 mg/kg q6-8h IV, IM or SC (Lappin 2003c) Ho RSe S:T! For susceptible infections: a) 50 mg/kg IV q6h (Bertone 2003a) b) Foals (neonatal septicemia): 40-60 mg/kg IV or IM q8h (Paradis 2003) c) Foals: 50 mg/kg IV or IM q6-8h (Brumbaugh 1999) monitoring Efficacy for the infection treated (WBC, clinical signs, etc. )T! Serum levels and therapeutic drug monitoring are not routinely T! performed with this drug client information Limited experience in veterinary medicine when used T! systemically Best suited for inpatient use T!chemistry/Synonyms An alpha-carboxypenicillin, ticarcillin disodium occurs as a white to pale yellow, hygroscopic powder or lyophilized cake with p K as of 2. 55 and 3. 42. More than 600 mg is soluble in 1 m L of water. Potency of ticarcillin disodium is expressed in terms of ticarcillin and one gram of the disodium contains not less than 800 mg of ticarcillin anhydrous. One gram of the commercially available in-jection contains 5. 2-6. 5 m Eq of sodium. A beta-lactamase inhibitor, clavulanate potassium occurs as an off-white, crystalline powder that has a p K a of 2. 7 (as the acid) and is very soluble in water and slightly soluble in alcohol at room tem-peratures. Although available commercially as the potassium salt, potency is expressed in terms of clavulanic acid. Ticarcillin Disodium may also be known as: BRL-2288, or ti-carcillinum natricum. Clavulanate potassium may also be known by the following synonyms: clavulanic acid, BRL-14151K, or kalii clavulanas. International trade names for ticarcillin/clavulanate in-clude Timentin® and Claventin®. Storage/Stability/compatibility Unused vials should be stored at room temperature (below 24°C, 75°F). A darkening of the sterile powder or solution indicates degrada-tion and loss of potency of clavulanate. For IM use, reconstitute vial with 2 m L of sterile water for injec-tion, sodium chloride for injection, or 1% lidocaine (without epi-nephrine) per gram of ticarcillin. Each m L of the resulting solution will contain approximately 385 mg/m L (1 gram per 2. 6 m L) ticar-cillin. For humans, IM injections are recommended to be made into a relatively large muscle and not to administer more than one gram (2. 6 m L) IM per injection site. For IV use, initially reconstitute 3. 1 gram vials with 13 m L of sodium chloride injection, dextrose 5% or LRS. Resulting solution will contain approximately 200 mg of ticarcillin per m L. If admin-istered IV at this concentration, give as slowly as possible. Ideally, dilute further to a concentration of 10-100 mg (ticarcillin)/m L with a suitable diluent (e. g., NS, LRS, D5W). Concentrations of 50 mg/m L or less will cause less vein irritation; the solution should be administered as slowly as possible (over at least 30 minutes). When vials are reconstituted (as above) to 200 mg/m L, the re-sulting solution is stable for 6 hours at room temperature and 72 hours when refrigerated. Stability for solutions diluted for IV infu-sion (10-100 mg/m L): Di Luent Room tem P Re FRi Ge Rate D FRozen NS 24 hrs 7 days 30 days D5W 24 hrs 3 days 7 days LRS 24 hrs 7 days 30 days All thawed solutions should be used within 8 hours and not refrozen. Ticarcillin/clavulanate should not be mixed with aminoglyco-sides (e. g., gentamicin, amikacin) and may not be compatible when infused at a Y-site with solutions containing amphotericin B cho-lesteryl sulfate complex, azithromycin, or vancomycin. Y-site com-patible drugs include (partial listing): propofol, dexmetomidine, cefepime, diltiazem, doxorubicin HCl liposomes, etoposide, famo-tidine, fluconazole, heparin sodium, hetastarch, regular insulin, meperidine, morphine sulfate, and ondansetron.	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
882 ti Letamine Hc L/zo Laze P am Hc L Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: None Human-Labe Le D PRo Duct S: Ticarcillin Disodium Powder for Injection (contains 4. 75 m Eq sodium/g) and Clavulanate Potassium (contains 0. 15 m Eq potassium/g): 3 g ticarcillin and 0. 1g clavulanic acid in 3. 1 g vials, piggyback bottles, ADD-Vantage vials and 31 g pharmacy bulk pack-ages; Timentin® (Glaxo Smith Kline); (Rx) Ticarcillin Powder for Injection (contains 18. 7 m Eq sodium/100 m L) and Clavulanate Potassium (contains 0. 5 m Eq potassium/100 m L): 3 g ticarcillin and 0. 1 g clavulanic acid/100 m L in 100 m L premixed, frozen Galaxy plastic containers; Timentin® (Glaxo Smith Kline); (Rx) tileta Mine Hcl/zolazepa M Hcl (tye-let-a-meen and zoe-laze-a-pam) Telazol® injectable ane Sthetic/tran Q uilizer Prescriber Highlights Injectable anesthetic/tranquilizer combination similar to T T ketamine/diazepam Contraindications: Pancreatic disease, rabbits, severe T T cardiac disease, use in cesarean section, or pulmonary disease Caution: Renal disease, large exotic cats (use avoided)T T Protect patient's eyes after using T T Dosages may need to be reduced in geriatric, debilitated, T T or animals with renal dysfunction. Adverse Effects: Respiratory depression, pain after IM in-T T jection, athetoid movements, tachycardia (esp. dogs), em-esis during emergence, excessive salivation & bronchial/tracheal secretions, transient apnea, vocalization, erratic &/or prolonged recovery, involuntary muscular twitching, hypertonia, cyanosis, cardiac arrest, pulmonary edema, muscle rigidity, & either hypertension or hypotension Monitor body temperature (may cause hypothermia) T T Class-III controlled substance T T uses/indications Telazol® is indicated for restraint or anesthesia combined with muscle relaxation in cats, and for restraint and minor procedures of short duration (≈30 minutes) which require mild to moderate analgesia in dogs. Although not officially approved, it has been used also in horses and many exotic and wild species. Pharmacology/actions In cats, tiletamine decreases cardiac rate and blood pressure after IM injections. Its effect on respiratory activity is controversial, and until these effects have been clarified, respiratory function should be closely monitored. The pharmacology of this drug combination is similar to that of ketamine and diazepam; for more information, refer to their monographs. Pharmacokinetics Little pharmacokinetic information is available for these agents. The onset of action may be variable and be very rapid; animals should be observed carefully after injection. In cats, the onset of action is reported to be within 1-7 minutes after IM injection. Duration of anesthesia is dependent on dosage, but is usually about 0. 33-1 hour at peak effect. This is reported to be approximately 3 times the duration of ketamine anesthesia. The duration of effect of the zolazepam component is longer than that of the tiletamine, so there is a greater degree of tranquilization than anesthesia during the recovery period. The recovery times vary in length from approximately 1-5. 5 hours. In dogs, the onset of action following IM injection averages 7. 5 minutes. The mean duration of surgical anesthesia is about 27 minutes, with recovery times averaging approximately 4 hours. The duration of the tiletamine effect is longer than that of zolazepam, so there is a shorter duration of tranquilization than there is anes-thesia. Less than 4% of the drugs are reported excreted unchanged in the urine in the dog. contraindications/Precautions/Warnings Telazol® is contraindicated in animals with pancreatic disease, or se-vere cardiac or pulmonary disease. Animals with renal disease may have prolonged duration of anesthetic action or recovery times. Because Telazol® may cause hypothermia, susceptible animals (small body surface area, low ambient temperatures) should be monitored carefully and supplemental heat applied if needed. Like ketamine, Telazol® does not abolish pinnal, palpebral, pedal, laryngeal, and pharyngeal reflexes and its use (alone) may not be adequate if sur-gery is to be performed on these areas. It has been reported that this drug is contraindicated in rabbits due to renal toxicity. Telazol® is generally avoided for use in large, exotic cats (con-traindicated in tigers) as it may cause seizures, permanent neuro-logic abnormalities, or death. Cats' eyes remain open after receiving Telazol®, and they should be protected from injury and an ophthalmic lubricant (e. g., Lacrilube®) should be applied to prevent excessive drying of the cornea. Cats reportedly do not tolerate endotracheal tubes well with this agent. Dosages may need to be reduced in geriatric, debilitated, or ani-mals with renal dysfunction. adverse effects Respiratory depression is a definite possibility, especially with higher dosages of this product. Apnea may occur; observe animal carefully. Pain after IM injection (especially in cats) has been noted which may be a result of the low p H of the solution. Athetoid move-ments (constant succession of slow, writhing, involuntary move-ments of flexion, extension, pronation, etc. ) may occur; do not give additional Telazol® in the attempt to diminish these actions. Large doses given SC or IM, versus small doses given IV, may result in longer, rougher recoveries. In dogs, tachycardia may be a common effect and last for 30 minutes. Insufficient anesthesia after recommended doses has been reported in dogs. Telazol® has been implicated in causing nephrosis in lagamorphs (rabbits/hares) and is usually not recommended for use in these species.	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
ti Letamine Hc L/zo Laze P am Hc L 883 Other adverse effects listed by the manufacturer include: em-esis during emergence, excessive salivation and bronchial/tracheal secretions (if atropine not administered beforehand), transient ap-nea, vocalization, erratic and/or prolonged recovery, involuntary muscular twitching, hypertonia, cyanosis, cardiac arrest, pulmonary edema, muscle rigidity, and either hypertension or hypotension. Reproductive/nursing Safety Telazol® crosses the placenta and may cause respiratory depres-sion in newborns; the manufacturer lists its use in cesarean section as being contraindicated. The teratogenic potential of the drug is unknown, and it is not recommended for use during any stage of pregnancy. overdosage/acute t oxicity The manufacturer claims a 2X margin of safety in dogs, and a 4. 5 times margin of safety in cats. A preliminary study in dogs (Hatch et al. 1988) suggests that doxapram at 5. 5 mg/kg will enhance respira-tions and arousal after Telazol®. In massive overdoses, it is suggested that mechanically assisted ventilation be performed if necessary and other clinical signs treated symptomatically and supportively. Drug interactions Little specific information is available presently on drug interac-tions with this product. ane St Hetic S, in Ha Lationa L T! : Dosage may need to be reduced when used concomitantly with Telazol® ba Rbitu Rate ST! : Dosage may need to be reduced when used con-comitantly with Telazol® c HLo Ram PHenico LT! : In dogs, chloramphenicol apparently has no effect on recovery times with Telazol®, but in cats, anesthesia is prolonged on average of 30 minutes by chloramphenicol. PHenot Hiazine ST! : Can cause increased respiratory and cardiac de-pression For potential additional interactions from the related compounds, ketamine and midazolam: Ketamine: neu Romu Scu La R b Locke RST! (e. g., succinylcholine and tubocurarine ): May cause enhanced or pro longed respiratory depression t Hy Roi D Ho Rmone S T! : When given concomitantly with ketamine, thyroid hormones have induced hypertension and tachycardia in humans; beta-blockers (e. g., propranolol ) may be of benefit in treating these effects Midazolam: ane St Hetic S, in Ha Lationa L T! : Midazolam may decrease the dosages required azo Le anti Fun Ga LST! (ketoconazole, itraconazole ), fluconazole ): May increase midazolam levels ca Lcium c Hanne L b Locke RS T! (diltiazem, verapamil ): May increase midazolam levels cimeti Dine T! : May increase midazolam levels cn S De PRe SSant S, ot He R T! : May increase the risk of respiratory de-pression mac Ro Li De ST! (erythromycin, clarithromycin ): May increase midazo-lam levels o Piate ST! : May increase the hypnotic ef fects of midazolam and hy-potension has been reported when used with meperidine. PHenoba Rbita LT! : May decrease peak levels and AUC of midazolam Ri Fam P in T! : May decrease peak levels and AUC of midazolam t Hio Penta LT! : Midazolam may decrease the dosages required Doses Do GS:T! a) For diagnostic purposes: 6. 6-9. 9 mg/kg IM For minor procedures of short duration: 9. 9-13. 2 mg/kg IM; If supplemental doses are necessary, give doses less than the initial dose and total dosage should not exceed 26. 4 mg/kg. Atropine 0. 04 mg/kg should be used concurrently to control hypersalivation. (Package Insert; Telazol®—Robins) b) Based upon the combination of drugs: 3-10 mg/kg IM or SC or 2-5 mg/kg IV (Mama 2002a) cat S:T! a) 9. 7-11. 9 mg/kg IM for procedures such as dentistry, abscess treatment, foreign body removal, etc. For procedures that re-quire mild to moderate levels of analgesia (lacerations, cas-tration, etc. ) use 10. 6-12. 5 mg/kg IM. For ovariohysterectomy and onychectomy use 14. 3-15. 8 mg/kg IM. If supplemental doses are necessary, give doses less than the initial dose and the total dosage should not exceed 72 mg/kg. Atropine 0. 04 mg/kg should be used concurrently to control hypersalivation. (Package Insert; Telazol®—Robins) b) Based upon the combination of drugs: 3-10 mg/kg IM or SC or 2-5 mg/kg IV (Mama 2002a) Ruminant S:T! As an induction agent for cattle, llamas/alpacas, goats, sheep:a) Xylazine at 0. 05-0. 1 mg/kg IV, IM, then Telazol® at 2-4 mg/ kg IV (IM). Caution: xylazine can cause severe hypoxemia and pulmonary edema in sheep. (Haskell 2005a) Rabbit S, Ro Dent S, Sma LL mamma LS:T! For chemical restraint:a) Gerbils: 20 mg/kg IP (in combination with xylazine 10 mg/kg) (Huerkamp 1995) b) Mice: 80-100 mg/kg IM. Rats: 20-60 mg/kg IM. Hamsters/Gerbils: 20-80 mg/kg IM. Guinea pig: 10-80 mg/kg IM. Rabbits: Not recommended (Burke 1999) c) Chinchillas: 20-40 mg/kg IM. Hamsters: 50-80 mg/kg IP for immobilization/anesthesia. Gerbils: 10-30 mg/kg IP. Mice: 80 mg/kg IP for immobilization Rats: 40 mg/kg IP for light anesthesia. Guinea pigs: 40-60 mg/kg IM for immobilization (Adamcak and Otten 2000) Fe RRet S:T! As a sedative/analgesic: a) 22 mg/kg IM combined with glycopyrrolate (0. 01 mg/kg IM). Rapid onset, but slow and rough recovery (3-4 hours) (Finkler 1999) b) Telazol® alone: 22 mg/kg IM; Telazol® (1. 5 mg/kg) plus xylazine (1. 5 mg/kg) IM; may re-verse xylazine with yohimbine (0. 05 mg/kg IM) Telazol® (1. 5 mg/kg) plus xylazine (1. 5 mg/kg) plus butorph-anol (0. 2 mg/kg) IM; may reverse xylazine with yohimbine (0. 05 mg/kg IM) (Williams 2000) Ho RSe S: T! (note : ARCI UCGFS Class 2 Drug) a) Xylazine 1. 1 mg/kg IV, 5 minutes prior to Telazol® at 1. 65-2. 2 mg/kg IV (Hubbell, Bednarski, and Muir 1989)	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf
884 ti Lmico Sin exotic SPecie S:T! a) An extensive list of suggested Telazol® dosages may be found in the article by E. Schobert entitled, “Telazol® Use in Wild and Exotic Animals” in the October 1987 issue of Veterinary Medicine. b) For carnivorous mammals (not tigers): 2-4 mg/m L usually provides adequate restraint. (Suedmeyer 2003) Re Pti Le S:T! a) Large Snakes: 3 mg/kg IM to facilitate handling and anesthe-sia. Administer 30-45 minutes prior to handling. Sedation may persist for up to 48 hours. May also be used in Crocodil-ians at 4-8 mg/kg. (Heard 1999) b) 3-10 mg/kg IM. Lizards and snakes can generally be treated with lower end of dosage range and chelonians may require high end. If sedation is inadequate, may give incrementally up to the maximum dose. Monitor closely for apnea and ven-tilate if required. (Innis 2003) c) Significant interspecies and interpatient differences in ef-fectiveness. At lower doses of 4-10 mg/kg sedation may be sufficient for some procedures (venipuncture, gastric la-vage, intubation for inhalation anesthesia). At higher doses (15-40 mg/kg), recovery may be greatly prolonged. Suggest starting out at 7-15 mg/kg the first few times this is used on reptiles in your practice (and to use on your own “in house” pets first!), and then use increasing dosages as needed. (Funk 2002) bi RDS:T! a) Ratites: 5 mg/kg IM or IV (Jenson 1998) monitoring Level of anesthesia/analgesia T! Respiratory function; cardiovascular status (rate, rhythm, BP if T! possible) Monitor eyes to prevent drying or injury T! Body temperature T! client information Should only be administered by individuals familiar with its use. chemistry/Synonyms Tiletamine is an injectable anesthetic agent chemically related to ketamine. Zolazepam is a diazepinone minor tranquilizer. The p H of the injectable product, after reconstitution, is 2. 2-2. 8. Tiletamine HCl may also be known as: CI-634, CL-399, CN-54521-2, or Telazol®. Zolazepam HCl may also be known as: CI-716. Storage/Stability After reconstitution, solutions may be stored for 4 days at room temperature and 14 days if refrigerated. Do not use solutions that contain a precipitate or are discolored. Dosage Forms/Regulatory Status Vete Rina R y-Labe Le D PRo Duct S: Tiletamine HCl (equivalent to 250 mg free base) and Zolazepam HCl (equivalent to 250 mg free base) as lyophilized powder/vial in 5 m L vials. When 5 m L of sterile diluent (sterile water) is added a concen-tration of 50 mg/m L of each drug (100 mg/m L combined) is pro-duced; Telazol® (Fort Dodge); (Rx, C-III). Approved for use in cats and dogs. Telazol® is a Class-III controlled substance. Human-Labe Le D PRo Duct S: Nonetil Mico Sin (til-mi-coe-sin) Micotil®, Pulmotil® macrolide antibiotic Prescriber Highlights Macrolide antibiotic used in cattle, sheep, & sometimes T T rabbits; used in swine as a medicated feed article Contraindications: Not to be used in automatically pow-T T ered syringes or to be given IVMay be fatal in swine (when injected) & non-human pri-T T mates; potentially in horses Adverse Effects: IM injections may cause a local tissue T T reaction resulting in trim loss; edema is possible at SC injection site Avoid contact with eyes T T In case of human injection, contact physician T T immediately uses/indications Tilmicosin is indicated for the treatment of bovine or ovine respi-ratory diseases (BRD) caused by Mannheimia ( Pasturella) haemo-lytica. Pharmacology/actions Like other macrolides, tilmicosin has activity primarily against gram-positive bacteria, although some gram-negative bacteria are affected and the drug reportedly has some activity against myco-plasma. Preliminary studies have shown that 95% of studied iso-lates of Pasturella haemolytica are sensitive. Pharmacokinetics Tilmicosin apparently concentrates in lung tissue. At 3 days post injection, the lung:serum ratio is about 60:1. MIC 95 concentrations (3. 12 micrograms/m L) for P. Haemolytica persist for a minimum of 3 days after a single injection. contraindications/Precautions/Warnings Not to be used in automatically powered syringes or to be given intravenously as fatalities may result. Tilmicosin has been shown to be fatal in swine (when injected), non-human primates and poten-tially, in horses. Avoid contact with eyes. Accidental self-injection can be fatal in humans. Do not use in automatically powered syringes. Emergency treatment includes applying ice to injection site and contacting a physician immediately. Emergency medical telephone numbers are 1-800-722-0987 or 1-317-276-2000. adverse effects If administered IM, a local tissue reaction may occur result-ing in trim loss. Edema may be noted at the site of subcutaneous injection. Reproductive/nursing Safety Safe use in pregnant animals or animals to be used for breeding purposes has not been demonstrated.	ctl5q-Veterinary_drug_hand_book_Plumbs.pdf