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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. When given orally, penicillins may cause GI effects (anorexia, vomiting, diarrhea). Because the penicillins may also alter gut ﬂora, antibiotic-associated diarrhea can occur and allow the proliferation of resistant bacteria in the colon (superinfections). 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. Some penicillins (ticarcillin, carbenicillin, azlocillin, mezlocillin, pipera cillin and nafcillin) have been implicated in causing bleeding problems in humans. These drugs are infrequently used systemi-cally in veterinary species and veterinary ramiﬁcations of this 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 nei-ther have there been any documented teratogenic problems associ-ated with these drugs. In humans, the FDA categorizes this drug as catego ry 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. ) However, use only when the potential ben-eﬁts outweigh the risks. Penicillins are excreted in maternal milk in low concentrations; use pote ntially could cause diarrhea, candidiasis, or allergic re-sponse in the nursing offspring. Overdosage/Acute Toxicity Acute oral penicillin overdoses are unlikely to cause signiﬁcant problems other than GI distress, but other effects are possible (see Adverse effects). In humans, very high dosages of parenteral peni-cillins, especially in patients with renal disease, have induced CNS effec ts. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving penicillins and may be of signiﬁcance in veterinary patients: T ! AMINOGLYCOSIDES : In vitro studies have demonstrated that peni-cillins can have synergistic or additive activity against certain bacteria when used with aminoglycosides or cephalosporins. T ! BACTERIOSTATIC ANTIBIOTICS (e. g., chloramphenicol, erythromycin, tetracyclines ): Use with penicillins is generally not recommended, particularly in acute infections where the organism is proliferat-ing rapidly as penicillins tend to perform better on actively grow-ing bacteria. T ! PROBENECID : Competitively blocks the tubular secretion of most penicillins, thereby increasing serum levels and serum half-lives. Laboratory Considerations T ! Penicillins may cause false-positive urine glucose determinations when using cupric-sulfate solution (Benedict's Solution, Clinit-est®). T ests utilizing glucose oxidase (Tes-Tape®, Clinistix®) ar e not affected by penicillin. T ! In humans, clavulanic acid and high dosages of piperacillin have caused a false-positive direct Combs' test. T ! As penicillins and other beta-lactams can inactivate aminogly-cosides in vitro (and in vi vo in patients in renal failure), serum concentrations of aminoglycosides may be falsely decreased if the patient is also receiving beta-lactam antibiotics and the serum is stored prior to analysis. It is recommended that if the assay is delayed, samples be frozen and, if possible, drawn at times when the beta-lactam antibiotic is at a trough. Monitoring T ! Because penicillins usually have minimal toxicity associated with their use, monitoring for efﬁcacy is usually all that is required unless toxic signs develop. T ! Serum levels and therapeutic drug monitoring are not routinely done with these agents. Client Information T ! Owners should be instructed to give oral penicillins on an empty stomach, unless using amoxicillin or GI effects (anorexia, vomit-ing) occur. T ! Compliance with the therapeutic regimen should be stressed. T ! Reconstituted oral suspensions should be kept refrigerated and discarded after 14 days, unless labeled otherwise. PENICILLIN G (pen-i-sill-in jee) PENICILLIN ANTIBIOTIC Prescriber Highlights TT Prototypical penicillin agent used for susceptible gram-positive aerobes & anaerobes; best used parenterally TT Contraindications: Known hypersensitivity (unless no other options) TT Adverse Effects: Hypersensitivity possible. Very high dos-es may cause CNS effects. TT Benzathine penicillin only effective against extremely sensitive agents TT Certain species may be sensitive to procaine penicillin G Uses/Indications Natural penicillins remain the drugs of choice for a variety of bac-teria, including group A beta-hemolytic streptococci, many gram-positiv e anaerobes, spirochetes, gram-negative aerobic cocci, and some gram-negative aerobic bacilli. Generally, if a bacteria remains susceptible to a natural penicillin, either penicillin G or V is pre-ferred for treating that infection as long as adequate penetration of the dr ug to the site of the infection occurs and the patient is not hypersensitive to penicillins. 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 b eta-lactam antibiotics have been shown to bind to several en-zymes (carboxypeptidases, transpeptidases, endopeptidases) within the bact erial cytoplasmic membrane that are involved with cell wall	pppbs.pdf
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 dr ugs have that are not explained by the inﬂuence of beta-lacta-mases. Like other beta-lactam antibiotics, penicillins are generally co nsidered more effective against actively growing bacteria. The natural penicillins (G and K) have similar spectrums of ac-tivity, but penicillin G is slightly more active in v itro on a weight basis against many organisms. This class of penicillin has in vitro activity against most spirochetes and gram-positive and gram-neg-ative aerobic cocci, but not penicillinase producing strains. They hav e activity against some aerobic and anaerobic gram-positive bacilli such as Bacillus anthracis, Clostridium spp. (not C. difﬁcile), Fusobacterium, and Actinomyces. The natural penicillins are cus-tomarily inactive against most gram-negative aerobic and anaero-bic bacilli, and all Rickettsia, mycobacteria, fungi, Mycoplasma, and vir uses. Pharmacokinetics Penicillin G potassium is poorly absorbed orally because of rapid acid-catalyzed hydrolysis. When administered on an empty (fasted) stomach, oral bioavailability is only about 15-30%. If given with food, absorption rate and extent will be decreased. Penicillin G potassium and sodium salts are rapidly absorbed af-ter IM injections and yield high peak levels usually within 20 min-utes of administration. In horses, equivalent doses given either IV or IM demonstrated that IM dosing will provide serum levels above 0. 5 micrograms/m L for about twice as long as IV administration [app rox. 3-4 hours (IV) vs. 6-7 hours (IM)]. Procaine penicillin G is slowly hydrolyzed to penicillin G after IM inje ction. Peak levels are much lower than with parenterally ad-ministered aqueous penicillin G sodium or potassium, but serum lev els are more prolonged. Benzathine penicillin G is also very slowly absorbed after IM injec tions after being hydrolyzed to the parent compound. Serum levels can be very prolonged, but levels attained generally only ex-ceed MIC's for the most susceptible streptococci, and the use of be nzathine penicillin G should be limited to these infections when other penicillin therapy is impractical. After absorption, penicillin G is widely distributed throughout the b ody with the exception of the CSF, joints and milk. In lactating dairy cattle, the milk to plasma ratio is about 0. 2. CSF levels are gen-erally only 10% or less of those found in the serum when meninges are not inﬂamed. Levels in the CSF may be greater in patients with inﬂamed meninges or if probenecid is given concurrently. Binding to plasma proteins is approximately 50% in most species. Penicillin G is principally excreted unchanged into the urine throug h renal mechanisms via both glomerular ﬁltration and tu-bular secretion. Elimination half-lives are very rapid and are usually one hour o r less in most species (if normal renal function exists). 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). Do not administer systemic antibiotics orally in patients with sep ticemia, shock, or other grave illnesses as absorption of the medi-cation from the GI tract may be signiﬁcantly delayed or diminished; pare nteral (preferably IV) routes should be used for these cases. High doses of penicillin G sodium or potassium, particularly in small animals with a preexisting electrolyte abnormality, renal dis-ease, or congestive heart failure may cause electrolyte imbalances. Other injectable penicillins, such as ticarcillin, carbenicillin, and ampicillin, have signiﬁcant quantities of sodium per gram and may cause electrolyte imbalances when used in large dosages in suscep-tible patients. Certain species (snakes, birds, turtles, Guinea pigs, and chinchil-las) are reportedly sensitive to procaine penicillin G. 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 ag ents and can manifest as rashes, fever, eosinophilia, neu-tropenia, agranulocytosis, thrombocytopenia, leukopenia, anemias, ly mphadenopathy, or full-blown anaphylaxis. In humans, it is esti-mated that up to 15% of patients hypersensitive to cephalosporins wil l also be hypersensitive to penicillins. The incidence of cross-reactivity in veterinary patients is unknown. When given orally, penicillins may cause GI effects (anorexia, vo miting, diarrhea). Because the penicillins may also alter gut ﬂora, antibiotic-associated diarrhea can occur and allow the proliferation of resistant bacteria in the colon (superinfections). 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. 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 out-weigh the risks. In humans, the FDA categorizes this drug as category B fo r 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 tri-mesters. ) In a separate system evaluating the safety of drugs in ca-nine and feline 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. ) Penicillins are excreted in maternal milk in low concentrations; use c ould potentially cause diarrhea, candidiasis, or allergic re-sponses in nursing offspring. Overdosage/Acute Toxicity Acute oral penicillin overdoses are unlikely to cause signiﬁcant problems other than GI distress, but other effects are possible (see Adverse Effects). In humans, very high dosages of parenteral penicillins, especially those 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 penicillin G and may be of signiﬁcance in veterinary patients: !TAMINOGLYCOSIDES : In vitro studies have demonstrated that peni-cillins can have synergistic or additive activity against certain bacteria when used with aminoglycosides or cephalosporins. !TBACTERIOSTATIC ANTIBIOTICS (e. g., chloramphenicol, erythromycin, tetracyclines ): Use with penicillins is generally not recommended, particularly in acute infections where the organism is proliferat-	pppbs.pdf
ing rapidly as penicillins tend to perform better on actively grow-ing bacteria. !TMETHOTREXATE : Penicillins may decrease renal elimination of MTX !TPROBENECID : Competitively blocks the tubular secretion of most penicillins, thereby increasing serum levels and serum half-lives. Laboratory Considerations !TAs penicillins and other beta-lactams can inactivate aminogly-cosides in vitro (and in vivo in patients in renal failure), serum concentrations of aminoglycosides may be falsely decreased if the patient is also receiving beta-lactam antibiotics and the serum is stored prior to analysis. It is recommended that if the assay is delayed, samples be frozen and, if possible, drawn at times when the beta-lactam antibiotic is at a trough. !TPenicillin G can cause falsely elevated serum uric acid values if the copper-chelate method is used; phosphotungstate and uricase methods are not affected !TPenicillins may cause false-positive urine glucose determinations when using cupric-sulfate solution (Benedict's Solution, Clinit-est®). T ests utilizing glucose oxidase (Tes-Tape®, Clinistix ®) are not affected by penicillin. Doses !TDOGS: For susceptible infections: a) Penicillin G potassium: For bacteremia, systemic infections: 20,000-40,000 Units/kg IV q4- 6h for as long as necessary. For orthopedic infections: 20,000-40,000 Units/kg IV q6h for as long as necessary. Pr ophylaxis for orthopedic surgery: 40,000 Units/kg IV one hour prior to surgery, and if surgery lasts longer than 90 minu tes a second dose is given. For soft tissue infections: 40,000-60,000 Units/kg PO q8h for as long as necessary. Penicillin G procaine: 20,000- 40,000 Units/kg IM, SC q12-24h for as long as necessary. Penicillin G benzathine: 40,000 IU/kg IM q5 days. (Greene, Hartmannn et al. 2006) b) Penicillin G potassium/sodium: 20,000 U nits/kg IV, IM, or SC q6h Pe nicillin G procaine: 22,000 Units/kg IM, SC q12h. Doses may be increased to 80,000 IU/kg per day; Actinomyces in-fections may require 100,000-200,000 IU/kg IM daily. (Ford and A ronson 1985) c) Penicillin G potassium/sodium: 20,000 U nits/kg IV, IM, q4h or 40,000 IU/kg PO on an empty stomach q6h Penicillin G procaine: 20,000 Units/kg IM, SC q12-24h. Pe nicillin G benzathine: 40,000 IU/kg q5 days IM (Kirk 1989) d) For leptospiremia: 25,000-40,000 U/kg IV or IM q12-24h fo r 14 days. For the renal carrier state of leptospirosis: Doxy-cycline 5-10 mg/kg PO twice daily of doxycycline for an ad-ditional 14 days after penicillin G therapy (Ross and Rentko 2000) e) For adjunctive therapy of septicemia: Penicillin G sodium/ potassi um: 25,000 IU/kg IV q6h. T oo rapid IV infusions may cause neurologic signs; hypersensitivity may also occur. (Goodwin and Schaer 1989) !TCATS: For susceptible infections: a) Penicillin G potassium: For soft tissue, systemic infections: 40,000 IU/kg PO q6-8h fo r as long as necessary. Penicillin G procaine: For soft tissue infections: 20,000 Units/kg IM, SC q12h for as long as necessary. Fo r orthopedic infections: 20,000-40,000 Units/kg IM q8h for as long as necessary. For resistant organisms (Actinomyces): 50,000-100,000 Units/kg IM, SC q12h for as long as necessary. Pe nicillin G benzathine: 50,000 IU/kg IM q5 days. (Greene, Hartmannn et al. 2006) b) Penicillin G potassium/sodium: 20,000-40,000 Units/kg IV, IM, q6h Pe nicillin G procaine: 22,000 Units/kg IM, SC q12h. Doses may be increased to 80,000 IU/kg per day; Actinomyces in-fections may require 100,000-200,000 IU/kg IM daily (Ford and A ronson 1985) c) Penicillin G potassium/sodium: 20,000 U nits/kg IV, IM, q4h or 40,000 IU/kg PO on an empty stomach q6h Penicillin G procaine: 20,000 Units/kg IM, SC q12-24h. Pe nicillin G benzathine: 40,000 IU/kg q5 days IM (Kirk 1989) d) Penicillin G sodium or potassium: 22,000-55,000 IU/kg IV or IM q6-8h (Aronson and Aucoin 1989) !TFERRETS: For susceptible infections: a) Procaine Pen G: 20,000-40,000 IU/kg IM once a day to twice daily; So dium or potassium Pen G: 20,000 IU/kg SC, IM or IV q4h or 40,000 IU/kg PO three times daily (Williams 2000) !TRABBITS, RODENTS, SMALL MAMMALS: a) Rabbits: Penicillin G Procaine 20,000-84,000 IU/kg SC, IM q24h f or 5-7 days for venereal spirochetosis (Ivey and Mor-risey 2000) b) Hedgehogs: 40,000 IU/kg IM once daily (Smith 2000) !TCATTLE (and other ruminants unless speciﬁed): For susceptible infections: a) Penicillin G procaine: 44,000- 66,000 Units/kg IM, SC once daily Pe nicillin G benzathine: 44,000-66,000 Units/kg IM, or SC q2days (Upson 1988) b) For bovine respiratory disease complex: Procaine penicillin G 66,000 IU/kg IM or SC once daily. Recommend 20-day slaughter withdrawal at this dosage. (Hjerpe 1986) c) Procaine penicillin G: 40,000 IU/kg IM once daily Pr ocaine penicillin G/benzathine penicillin G combination: 40,000 IU/kg IM once (Howard 1986) d) Procaine penicillin G: 10,000-20,000 IU/kg IM q12-24h. Benzathine penicillin G: 10,000- 20,000 IU/kg, IM, SC q48h (Jenkins 1986) !THORSES: For susceptible infections: a) For gram-positive aerobes: Penicillin G potassium or sodi-um: 10,000-20,000 Units/kg IV or IM q6h. For serious gram-positive infections (e. g., te tanus, botulism, C. difﬁcile enterocolitis in foals): Penicillin G sodium or potas-sium 22,000-44,000 Units/kg IV q6h	pppbs.pdf
Susceptible bacterial infections: Penicillin G procaine: 22,000-44,000 Units/kg IM q12h (Whittem 1999) b) Treatment of carriers with S. equi inf ections of the gutteral pouches: Administration of both systemic and topical peni-cillin G appears to improve treatment success rate. Before to pical therapy, remove all visible inﬂammatory material re-moved from gutteral pouch. T o make a gelatin/penicillin G mix of 50 m L for gutteral pouch instillation: 1) Weigh out 2 grams gelatin (Sigma G-6650 or household) and add 40 m L o f sterile water. 2) Heat or microwave to dissolve. Cool to 45-50°C, 3) Add 10 m L sterile water to a 10 million unit sodium peni-cillin G for injection vial and mix with the cooled gelatin to t otal volume of 50 m L. 4) Dispense into syringes and leave overnight in the refrigerator. Inst illation is easiest through a catheter inserted up the nose and endoscopically guided into the pouch opening with the last inch bent at an angle to aid entry under the pouch ﬂap. Elevate horse's head for 20 minutes after infusion. (Verheyen, Newton et al. 2000) c) For treatment of botulism: Penicillin G sodium or potassium 22,000- 44,000 IU/kg IV four times daily (do not use oral penicillin therapy) (Johnston and Whitlock 1987) d) For strangles: Early in infection when only fever and depres-sion are present: procaine penicillin G 22,000 IU/kg IM or SC q12h, or aqueous salts (sodium or potassium) penicillin G 22,000 IU/kg IM, IV or SC q6h. If lymphadenopathy noted in otherwise healthy and alert horse do not treat. If lymph-adenopathy present and horse is depressed, febrile, anorexic and espe cially if dyspneic, treat as above. (Foreman 1999) e) For fo als: Penicillin G Na or K: 20,000-50,000 U/kg IV q6-8h; Procaine penicillin G 22,000-50,000 U/kg IM q12h (Brumbaugh 1999) f) For foals: Penicillin G sodium or potassium: 20,000-50,000 U/kg IV q6h Penicillin G Procaine: 20,000-50,000 U/kg IM q6h (Furr 1999) !TSWINE: For susceptible infections: a) Procaine penicillin G: 40,000 IU/kg IM once daily. Procaine penicillin G/benzathine penicillin G combination: 40,000 IU/kg IM onc e (Howard 1986) b) Procaine penicillin G: 6,600 IU/kg IM once daily for not more than 4 days Pr ocaine penicillin G/benzathine penicillin G combination: 11,000-22,000 IU/kg IM once (Wood 1986) !TBIRDS: For susceptible infections: a) In turkeys: Procaine penicillin G/benzathine penicillin G co mbination: 100 mg/kg IM of each drug once a day or every 2 days. Use cautiously in small birds as it may cause procaine toxicity. (Clubb 1986) Monitoring !TBecause penicillins usually have minimal toxicity associated with 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. Client Information !TOwners should be instructed to give oral penicillins to animals with an empty stomach, unless using amoxicillin or if GI effects (anorexia, vomiting) occur. !TCompliance with the therapeutic regimen should be stressed. Chemistry/Synonyms Penicillin G is considered natural penicillin and is obtained from cultures Penicillium chrysogenum and is available in several different salt forms. Penicillin G potassium (also known as benzylpenicillin potassium, aqueous or crystalline penicillin) occurs as colorless or white crystals, or white crystalline powder. It is very soluble in water and sparingly soluble in alcohol. Potency of penicillin G potassium is usually expressed in terms of Units. One mg of penicillin G po-tassium is equivalent to 1440-1680 USP Units (1355-1595 USP Units for the powder for injection). After reconstitution, penicillin G potassium powder for injection has a p H of 6-8. 5, and contains 1. 7 m Eq of potassium per 1 million Units. Penicillin G sodium (also known as benzylpenicillin sodium, aque ous or crystalline penicillin) occurs as colorless or white crys-tals, or white to slightly yellow, crystalline powder. Approximately 25 mg are soluble in 1 m L of water. Potency of penicillin G so-dium is usually expressed in terms of Units. One mg of penicillin G so dium is equivalent to 1500-1750 USP Units (1420-1667 USP Units for the powder for injection). After reconstitution, penicillin G sodium powder for injection has a p H of 6-7. 5, and contains 2 m Eq of sodium per 1 million Units. Penicillin G procaine (also known as APPG, Aqueous Procaine Pe nicillin G, Benzylpenicillin Procaine, Procaine Penicillin G, Procaine Benzylpenicillin) is the procaine monohydrate salt of penicillin G. In vivo it is hydrolyzed to penicillin G and acts as a depot, or repository form, of penicillin G. It occurs as white crystals or very ﬁne, white crystalline powder. Approximately 4-4. 5 mg are soluble in 1 m L of water and 3. 3 mg are soluble in 1 m L of alcohol. Potency of penicillin G procaine is usually expressed in terms of Units. One mg of penicillin G procaine is equivalent to 900-1050 USP Units. The commercially available suspension for injection is buffered with sodium citrate and has a p H of 5-7. 5. It is preserved with methylparaben and propylparaben. Penicillin G Benzathine (also known as Benzathine Benzyl-penicillin, Benzathine Penicillin G, Benzylpenicillin Benzathine, Dibe nzylethylenediamine Benzylpenicillin) is the benzathine tet-rahydrate salt of penicillin G. It is hydrolyzed in vivo to penicillin G and acts as a long-acting form of penicillin G. It occurs as an odorless, white, crystalline powder. Solubilities are 0. 2-0. 3 mg/m L of water and 15 mg/m L of alcohol. One mg of penicillin G benza-thine is equivalent to 1090-1 272 USP Units. The commercially available suspension for injection is buffered with sodium citrate and has a p H of 5-7. 5. It is preserved with methylparaben and propylparaben. Penicillin G may also be known as: benzylpenicllin, crystalline pe nicillin G, penicillin, Bicillin C-R®, Masti-Clear®, Permapen®, and Pﬁzerpen®. Storage/Stability/Compatibility Penicillin G sodium and potassium should be protected from mois-ture to prevent hydrolysis of the compounds. Penicillin G potas-sium tablets and powder for oral solution should be stored at room te mperature in tight containers; avoid exposure to excessive heat. After reconstituting, the oral powder for solution should be stored from 2-8°C (refrigerated) and discarded after 14 days.	pppbs.pdf
Penicillin G sodium and potassium powder for injection can be stored at room temperature (15-30°C). After reconstituting, the injectable solution is stable for 7 days when kept refrigerated (2-8°C) and for 24 hours at room temperature. Penicillin G procaine should be stored at 2-8°C; avoid freezing. Benzathine pe nicillin G should be stored at 2-8°C. All commonly used IV ﬂuids (some Dextran products are physi-cally incompatible ) and the following drugs are reportedly physically compatible with penicillin G potassium: ascorbic acid injection, calcium chloride/gluconate, cephapirin sodium, chlorampheni-col sodium succinate, cimetidine HCl, clindamycin phosphate, colistimethat e sodium, corticotropin, dimenhydrinate, diphen-hydramine HCl, ephedrine sulfate, erythromycin gluceptate/lac-tobionate, hydrocortisone sodium succinate, kanamycin sulfate, lidocaine HC l, methicillin sodium, methylprednisolone sodium succinate, metronidazole with sodium bicarbonate, nitrofurantoin sodium, polymyxin B sulfate, potassium chloride, prednisolone so-dium phosphate, procaine HCl, prochlorperazine edisylate, sodium iodide, s ulﬁsoxazole diolamine, and verapamil HCl. The following drugs/solutions are either physically incompatible or data conﬂicts regarding compatibility with penicillin G potassi-um injection: amikacin sulfate, aminophylline, cephalothin sodium, chlorp romazine HCl, dopamine HCl, heparin sodium, hydroxyzine HCl, lincomycin HCl, metoclopramide HCl, oxytetracycline HCl, pentobarbital sodium, prochlorperazine mesylate, promazine HCl, promethazine HCl, sodium bicarbonate, tetracycline HCl, and vi-tamin B-complex with C. The following drugs/solutions are reportedly physically compat-ible with penicillin G sodium injection: Dextran 40 10%, dextrose 5% (some degradation may occur if stored for 24 hours), sodium chloride 0. 9% (some degradation may occur if stored for 24 hours), calcium chloride/gluconate, chloramphenicol sodium succinate, cimetidine HCl, clindamycin phosphate, colistimethate sodium, diphenhydramine HCl, erythromycin lactobionate, gentamicin sul-fate, hydrocortisone sodium succinate, kanamycin sulfate, methicil-lin sodium, nitrofurantoin sodium, polymyxin B sulfate, predniso-lone sodium phosphate, procaine HCl, verapamil HCl, and vitamin B-complex w ith C. The following drugs/solutions are either physical ly incompatible or data conﬂicts regarding compatibility with penicillin G sodium injection: amphotericin B, bleomycin sulfate, cephalothin sodium, chlorpromazine HCl, heparin sodium, hydroxyzine HCl, lincomy-cin HCl, methylprednisolone sodium succinate, oxytetracycline HCl, potassi um chloride, prochlorperazine mesylate, promethazine HCl and tetracycline HCl. 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 VETERINARY-LABELED PRODUCTS: Note : Withdrawal times are for labeled dosages only. Penicillin G Procaine Injection 300,000 Units/m L in 100 m L and 250 m L vials: Variety of trade names available. Depending on product, approved for use in: cattle, sheep, horses, and swine. Not intended for use in horses used for food. Do not exceed 7 days of treatment in non-lactating dairy cattle, beef cattle, swine or sheep; 5 days in lactat-ing dairy cattle. Treatment should not exceed 4 consecutive days. Withdrawal times vary depending on the product are for the labeled dosage o f 6,600 U/kg once daily (rarely used clinically today). Actual withdrawal times may be longer. Milk withdrawal times (at labeled doses) = 48 hours. Slaughter withdrawal: Calves (non-ruminating) = 7 days; cattle = 4-10 days; sheep = 8-9 days; swine = 6-7 days; refer to label f or more information. Penicillin G Procaine Mastitis Syringes 100,000 units/m L in 10 m L units: Go-D ry® (G. C. Hanford) (OTC) Milk withdrawal (at labeled doses) = 72 hours. Slaughter withdrawal (at labeled doses) = 14 days. For use in dry cows only. Masti-Clear® (G. C. Hanford) Milk with-drawal (at labeled doses) = 60 hours. Slaughter withdrawal (at la-beled doses) = 3 days. Administer no more than 3 consecutive doses or withdra wal times must lengthen. There are also mastitis syringes in combination with novobiocin (Al-badry Plus®) or dihydrostreptomycin (Quartermaster®) Penicillin G Benzathine 150,000 U/m L with Penicillin G Procaine Injec-tion 150,000 Units/m L for Injection in 100 m L and 250 m L vials: Vari-ety of trade names available. Approved (most products) in horses and beef cattle. Not approved for horses intended for food use. Slaughter withdrawal: cattle = 30 days (at labeled doses). Actual species approv-als and withdrawal times may vary with the product; refer to the label of the pr oduct you are using. HUMAN-LABELED PRODUCTS: Penicillin G (Aqueous) Sodium Powder for Injection: 5,000,000 units & 20,000,000 units in vials; Pﬁzerpen® (Pﬁzer); generic (Sandoz); (Rx) Penicillin G (Aqueous) Potassium Injection (Premixed, frozen): 1,000,000 units, 2,000,000 units & 3,000,000 units in 50 m L Galaxy containers; generic (Baxter); (Rx) Penicillin G (Procaine Injection: 600,000 Units/vial in 1 m L Tubex & 1,200,000 U nits/vial in 2 m L Tubex; generic; (Monarch); (Rx) Penicillin G Benzathine IM Injection: 600,000 units/dose in 1 m L Tubex ; 1,200,000 units/dose in 2 m L Tubex and 2 m L Isoject; 2,400,000 units/dose in 4 m L pre-ﬁllled syringes; Bicillin L-A® (Monarch); Per-mapen® (Roerig); (Rx) Penicillin G Benzathine/Penicillin G Procaine IM Injection: 600,000 units/dose (300,000 units each penicillin G benzathine and penicillin G procaine) in 1 m L Tubex; 1,200,000 units/dose (600,000 units each penicillin G benzathine and penicillin G procaine) in 2 m L Tubex; 2,400,000 units/dose (1,200,000 units each penicillin G benzathine and penicillin G procaine) in 4 m L syringes; 1,200,000 units/dose (900,000 units penicillin G benzathine and 300,000 units penicillin G procaine) in 2 m L Tubex; Bicillin C-R® and Bicillin C-R 900/300® (Monarch); (Rx) PENICILLIN V POTASSIUM (pen-i-sill-in Vee) Phenoxymethylpenicillin ORAL PENICILLIN ANTIBIOTIC Prescriber Highlights TT Oral natural penicillin TT Contraindications: Known hypersensitivity (unless no other options) TT Adverse Effects: GI effects or hypersensitivity possible TT Best to give on an empty stomach Uses/Indications Penicillins have been used for a wide range of infections in various species. See the dosage section for more information.	pppbs.pdf
Pharmacology/Actions The natural penicillins (G and K) have similar spectrums of activ-ity, but penicillin G is slightly more active in v itro on a per weight basis against many organisms. This class of penicillin has in vitro activity against most spirochetes and gram-positive and gram-neg-ative aerobic cocci, but not penicillinase producing strains. They hav e activity against some aerobic and anaerobic gram-positive bacilli such as Bacillus anthracis, Clostridium spp. (not C. difﬁcile), Fusobacterium, and Actinomyces. The natural penicillins are cus-tomarily inactive against most gram-negative aerobic and anaero-bic bacilli, and all Rickettsia, mycobacteria, fungi, Mycoplasma, and vir uses. Although penicillin V may be slightly less active than peni-cillin G against organisms susceptible to the natural penicillins, its sup erior absorptive characteristics after oral administration make it a better choice against mild to moderately severe infections when oral administration is desired in monogastric animals. Penicillins are usually bactericidal against susceptible bacteria and a ct by inhibiting mucopeptide synthesis in the cell wall result-ing in a defective barrier and an osmotically unstable spheroplast. The exact mechanism for this effect has not been deﬁnitively deter-mined, but beta-lactam antibiotics have been shown to bind to sev-eral enzymes (carboxypeptidases, transpeptidases, endopeptidases) within the bacterial cytoplasmic membrane that are involved with cell wall synthesis. The different afﬁnities that various beta-lactam antibiotics have for these enzymes (also known as penicillin-binding proteins; 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 co nsidered more effective against actively growing bacteria. Pharmacokinetics The pharmacokinetics of penicillin V are very similar to penicillin G with the exception of oral bioavailability and the percent of the drug that is bound to plasma proteins. Penicillin V is signiﬁcantly more resistant to acid-catalyzed inactivation in the gut and bio-availability after oral administration in humans is approximately 60-73%. In veterinary species, bioavailability in calves is only 30%, but studies performed in horses and dogs demonstrated that thera-peutic serum levels can be achieved after oral administration. In do gs, food will decrease the rate and extent of absorption. Distribution of penicillin V follows that of penicillin G but, at least in humans, the drug is bound to a larger extent to plasma proteins (approximately 80% with penicillin V vs. 50% with penicillin G). Like penicillin G, penicillin V is excreted rapidly in the urine via the kidney. Elimination half-lives are generally less than 1 hour in animals with normal renal function; an elimination half-life of 3. 65 hours has been reported after oral dosing in horses (Schwark et al. 1983). 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). Do not administer systemic antibiotics orally in patients with sep ticemia, shock, or other grave illnesses as absorption of the medi-cation from the GI tract may be signiﬁcantly delayed or diminished. Par enteral (preferably IV) routes should be used for these cases. 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 ag ents and can manifest as rashes, fever, eosinophilia, neu-tropenia, agranulocytosis, thrombocytopenia, leukopenia, anemias, ly mphadenopathy, or full-blown anaphylaxis. In humans, it is esti-mated that up to 15% of patients hypersensitive to cephalosporins wil l also be hypersensitive to penicillins. The incidence of cross-reactivity in veterinary patients is unknown. When given orally, penicillins may cause GI effects (anorexia, vo miting, diarrhea). Because the penicillins may also alter gut ﬂora, antibiotic-associated diarrhea can occur and allow the proliferation of resistant bacteria in the colon (superinfections). 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. 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 out-weigh the risks. Certain species (snakes, birds, turtles, Guinea pigs, and c hinchillas) are reported to be sensitive to penicillins. High doses of penicillin G sodium or potassium, particularly in small animals with a preexisting electrolyte abnormality, renal disease, or congestive heart failure may cause electrolyte imbalances. Other injectable penicillins, such as ticarcillin, carbenicillin, and ampicil-lin, have signiﬁcant quantities of sodium per gram and may cause ele ctrolyte imbalances when used in large dosages in susceptible patients. In humans, the FDA categorizes this drug as category B fo r 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 ). Penicillins are excreted in maternal milk in low concentrations; use c ould potentially cause diarrhea, candidiasis, or allergic re-sponse in nursing offspring. Overdosage/Acute Toxicity Acute oral penicillin overdoses are unlikely to cause signiﬁcant problems other than GI distress, but other effects are possible (see Adverse effects). In humans, very high dosages of parenteral peni-cillins, especially in patients with renal disease, have induced CNS eff ects. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving penicillin V potassium and may be of signiﬁcance in veterinary patients: !TAMINOGLYCOSIDES : In vitro studies have demonstrated that peni-cillins can have synergistic or additive activity against certain bacteria when used with aminoglycosides or cephalosporins. !TBACTERIOSTATIC ANTIBIOTICS (e. g., chloramphenicol, erythromycin, tetracyclines ): Use with penicillins is generally not recommended, particularly in acute infections where the organism is proliferat-ing rapidly as penicillins tend to perform better on actively grow-ing bacteria.	pppbs.pdf
T ! METHOTREXATE : Penicillins may decrease renal elimination of MTX T ! PROBENECID : Competitively blocks the tubular secretion of most penicillins, thereby increasing serum levels and serum half-lives. Laboratory Considerations T ! As penicillins and other beta-lactams can inactivate aminogly-cosides in vitro (and in vivo in patients in renal failure), serum concentrations of aminoglycosides may be falsely decreased if the patient is also receiving beta-lactam antibiotics and the serum is stored prior to analysis. It is recommended that if the assay is delayed, samples be frozen and, if possible, drawn at times when the beta-lactam antibiotic is at a trough. T ! Penicillin V can cause falsely elevated serum uric acid values if the copper-chelate method is used; phosphotungstate and uricase methods are not affected T ! Penicillins may cause false-positive urine glucose determinations when using cupric-sulfate solution (Benedict's Solution, Clinit-est®). T ests utilizing glucose oxidase (Tes-Tape®, Clinistix®) ar e not affected by penicillin. Doses T ! DOGS: For susceptible infections: a) 5. 5-11 mg/kg PO q6-8h (Aronson and Aucoin 1989) b) For soft tissue infections: 10 mg/kg PO q8h for 7 days. (Gree ne, Hartmannn et al. 2006) T ! CATS: For susceptible infections: a) 5. 5-11 mg/kg PO q6-8h (Aronson and Aucoin 1989) b) For soft tissue infections: 10 mg/kg PO q8h for 7 days. (Gree ne, Hartmannn et al. 2006) T ! HORSES: For susceptible infections: a) 110,000 U/kg (68. 75 mg/kg) PO q8h (may yield supra-opti-mal levels against uncomplicated infections by sensitive or-ganisms) (Schwark et al. 1983) b) 110,000 U/kg PO q6-12h (Brumbaugh 1987) Monitoring T ! Because penicillins usually have minimal toxicity associated with 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. Client Information T ! Unless otherwise instructed by the veterinarian, this drug should be given on an empty stomach, at least 1 hour before feeding or 2 hours after feeding T ! Keep oral suspension in the refrigerator and discard any unused suspension after 14 days Chemistry/Synonyms A natural-penicillin, penicillin V is produced from Penicillium chrysogenum and is usually commercially available as the potassium salt. Penicillin V potassium occurs as an odorless, white, crystalline powder that is very soluble in water and slightly soluble in alcohol. Potency of penicillin V potassium is usually expressed in terms of weight (in mg) of penicillin V, but penicillin V units may also be used. One mg of penicillin V potassium is equivalent to 1380-1610 USP Units of penicillin V. Manufacturers however generally state that 125 mg of penicillin V potassium is approximately equivalent to 200,000 USP units of penicillin V. Penicillin V may also be known as: phenoxymethylpenicillin, fenoxime tilpenicilina, penicillin, phenoxymethyl, phenomycil-line, phenoxymethyl penicillin, phenoxymethylpenicillinum, and Veetids ®. Storage/Stability Penicillin V potassium tablets and powder for oral solution should be stored in tight containers at room temperature (15-30°C). After reconstitution, the oral solution should be stored at 2-8°C (refrig-erated) and any unused portion discarded after 14 days. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Penicillin V Potassium Tablets: 250 mg & 500 mg; Veetids® (Geneva); generic; (Rx) Penicillin V Potassium Powder for Oral Solution: 25 mg/m L and 50 mg/m L in 100 m L and 200 m L; Veetids ® (Geneva); generic; (Rx) PENTAZOCINE LACTATE PENTAZOCINE HCL (pen-taz-oh-seen) Talwin® PARTIAL OPIATE AGONIST Prescriber Highlights TT Partial opiate agonist analgesic used in a variety of spe-cies; usage is decreasing TT Contraindications: Known hypersensitivity TT Caution: Head trauma, increased CSF pressure or other CNS dysfunction, hypothyroidism, severe renal insufﬁcien-cy, adrenocortical insufﬁciency (Addison's), & geriatric or severely debilitated patients TT Not a replacement for surgery or medical treatment for horses with colic TT Adverse Effects: HORSES: Transient ataxia, CNS excite-ment, increased pulse, & respiratory rate. DOGS: Saliva-tion most prevalent; ataxia, ﬁne tremors, seizures, em-esis, & swelling at injection site possible TT CATS: Use is controversial; may cause dysphoric reactions TT C-IV controlled substance Uses/Indications Pentazocine is labeled for the symptomatic relief of pain of colic in horses and for the amelioration of pain accompanying postopera-tive recovery from fractures, trauma, and spinal disorders in dogs. It has also be en used as an analgesic in cats (see Adverse Effects below) and swine. Pharmacology/Actions While considered a partial opiate agonist, pentazocine exhibits many of the same characteristics as the true opiate agonists. It is reported to have an analgesic potency of approximately one-half that of morphine and ﬁve times that of meperidine. It is a very weak antagonist at the mu opioid receptor when compared to naloxone.	pppbs.pdf
It will not antagonize the respiratory depression caused by drugs like morphine, but may induce symptoms of withdrawal in human patients physically dependent on narcotic agents. Besides its analgesic properties, pentazocine can cause respira-tory depression, decreased GI motility, sedation, and it possesses antit ussive effects. Pentazocine tends to have less sedative qualities in animals than other opiates and is usually not used as a pre-oper-ative medication. In dogs, pentazocine can cause a transient decrease in blood pr essure; in humans, increases in cardiac output, heart rate, and blood pressure can be seen. Pharmacokinetics Pentazocine is well absorbed following oral, IM, or SC administra-tion. Because of a high ﬁrst-pass effect, only about 20% of an oral dose will enter the systemic circulation in patients with normal he-patic function. After absorption, the drug is distributed widely into tissues. In the e quine, it has been shown to be 80% bound to plasma proteins. Pentazocine will cross the placenta and neonatal serum levels have been measured at 60-65% of maternal levels at delivery. It is not clearly known if or how much pentazocine crosses into milk. The drug is primarily metabolized in the liver with resultant ex-cretion by the kidneys of the metabolites. In the horse, approximate-ly 30% of a given dose is excreted as the glucuronide. Pentazocine and its metabolites have been detected in equine urine for up to 5 days following an injection. Apparently, less than 15% of the drug is excreted by the kidneys in an unchanged form. Plasma half-lives have been reported for various species: Humans = 2 -3 hrs; Ponies = 97 min. ; Dogs = 22 min. ; Cats = 84 min. ; Swine = 49 min. Volumes of distribution range from a high of 5. 09 L/kg in ponies to 2. 78 L/kg in cats. In horses, the onset of action has been reported to be 2-3 minutes following IV dosing with a peak effect at 5-10 minutes. Contraindications/Precautions/Warnings The drug is contraindicated in patients having known hypersensi-tivity to it. All opiates should be used with caution in patients with hy pothyroidism, severe renal insufﬁciency, adrenocortical insufﬁ-ciency (Addison's), and geriatric or severely debilitated patients. Like other opiates, pentazocine must be used with extreme cau-tion in patients with head trauma, increased CSF pressure or other CNS d ysfunction (e. g., coma). Pentazocine should not be used in place of appropriate therapy (medical &/or surgical) for equine colic, but only as adjunctive treatment for pain. Adverse Effects In dogs, the most predominant adverse reaction following paren-teral administration is salivation. Other potential side effects at usual doses include ﬁne tremors, emesis, and swelling at the injec-tion site. At very high doses (6 mg/kg) dogs have been noted to de velop ataxia, ﬁne tremors, convulsions, and swelling at the injec-tion site. Horses may develop transient ataxia and clinical signs of CNS ex citement. Pulse and respiratory rates may be mildly elevated. The use of pentazocine in cats is controversial. Some clinicians claim that the dr ug causes dysphoric reactions that preclude its use in this species, while others disagree and state that drug may be safely used. Reproductive/Nursing Safety Because reproductive studies have not been done in dogs, the manufacturer does not recommend its use in pregnant bitches or bitches intended for breeding. Studies performed in laboratory ani-mals have not demonstrated any indications of teratogenicity. In humans, the FDA categorizes this drug as category C fo r use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) Safety for use during lactation has not been established. Overdosage/Acute Toxicity There is little information regarding acute overdose situations with pentazocine. For oral ingestions, the gut should be emptied if indi-cated and safe to do so. Clinical signs should be managed by sup-portive treatment (O 2, p ressor agents, IV ﬂuids, mechanical ven-tilation) and respiratory depression can be treated with naloxone. Re peated doses of naloxone may be necessary. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving pentazocine and may be of signiﬁcance in veterinary patients: !TCNS DEPRESSANTS, OTHER (e. g., anesthetic agents, antihistamines, phenothiazines, barbiturates, tranquilizers, alcohol, etc. ): May cause increased CNS or respiratory depression; dosage may need to be decreased !TFLUOXETINE (and OTHER SSRI'S ): May be at increased risk for sero-tonin syndrome Laboratory Considerations !TPentazocine may cause decreases for urinary 17-hydroxycorticos-teroid determinations Doses !TDOGS: For analgesia: a) Initially 1. 65 mg/kg; up to 3. 3 mg/kg IM. Duration of effect ge nerally lasts 3 hours. If dose is repeated, use different injec-tion site. (Package Insert; Tal win®-V—Winthrop) b) 1-6 mg/kg IM or SC q1-3h (Hendrix and Hansen 2000) c) 1-4 mg/kg IM, IV q2-4h (Otero 2006a) !TCATS: Note : Pentazocine can cause dysphoria in cats; alternative analge-sics are recommended. !TFERRETS: a) 5-10 mg/kg SC or IM q4h (Williams 2000) !TRABBITS, RODENTS, SMALL MAMMALS: a) Rabbits: Post-operative analgesia: 5-20 mg/kg SC, IV, or IM q4h (Iv ey and Morrisey 2000) !THORSES: Studies have demonstrated that pentazocine is not as an effective an-algesic as either butorphanol or ﬂunixin in horses. Many clinicians no long er recommend its use. ( Note : ARCI UCGFS Class 3 Drug) For analgesia: a) 0. 33 mg/kg slowly in jugular vein. In cases of severe pain, a se cond dose (0. 33 mg/kg) be given IM 15 minutes later (Package Insert; Talwin®-V—Winthrop) b) 0. 4-0. 9 mg/kg IV. Duration of analgesia may last only 10-30 minu tes following an IV dose. (Thurmon and Benson 1987) c) For standing chemical restraint for castrations: Administer ac epromazine at 0. 088 mg/kg (or 40 mg/450 kg) IV after about 10 minutes when patient is obviously tranquilized, give pentazocine at 0. 5 mg/kg (225 mg/450kg) IV and then administer local anesthetic to each cord and the incision sites on ventral surface of the scrotum. (Abrahamsen 2007b)	pppbs.pdf
T ! SWINE: For analgesia: a) 2 mg/kg IM q4h as needed (Jenkins 1987) Monitoring T ! Analgesic efﬁcacy T ! Respiratory rate/depth T ! Appetite/bowel function T ! CNS effects Client Information T ! Clients should report any signiﬁcant changes in behavior, appe-tite, bowel, or urinary function in their animals. Chemistry/Synonyms A synthetic partial opiate agonist, pentazocine is commercially available as two separate salts. The hydrochloride salt, which is found in oral dosage forms, occurs as a white, crystalline powder. It is soluble in water and freely soluble in alcohol. The commercial injection is prepared from pentazocine base with the assistance of lactic acid. This allows the drug to be soluble in water. The p H of this product is adjusted to a range of 4-5. Pentazocine is a weak base with an approximate p K a of 9. 0. Pentazocine may also be known as: NIH-7958, NSC-107430, pentazo cinum, Win-20228, Talacen®, and Talwin®. Storage/Stability/Compatibility The tablet preparations should be stored at room temperature and in tight, light-resistant containers. The injectable product should be kept at room temperature; avoid freezing. The following agents have been reported to be physically com-patible when mixed with pentazocine lactate: atropine sulfate, benzquinamide HCl, butorphanol tartrate, chlorpromazine HCl, dimenhydrinate, diphenhydramine HCl, droperidol, fentanyl cit-rate, hydromorphone, hydroxyzine HCl, meperidine HCl, metoclo-pramide, morphine sulfate, perphenazine, prochlorperazine edi-sylate, promazine HCl, promethazine HCl, and scopolamine HBr. The fol lowing agents have been reported to be physically incompat-ible when mixed with pentazocine lactate: aminophylline, amobar-bital sodium, ﬂunixin meglumine, glycopyrrolate, pentobarbital sodium, p henobarbital sodium, secobarbital sodium, and sodium bicarbonate. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 3 substance. See the appendix for more information. HUMAN-LABELED PRODUCTS: Pentazocine Lactate Injection: 30 mg/m L in 10 m L vials, Uni-Amps & amps; 1 m L and 2 m L ﬁll in 2 m L Carpuject; Talwin® (Abbott Hospi-tal Products); (Rx, C-IV) Pentazocine HCl and Naloxone HCl Tablets (Scored): 50 mg (as hy-drochloride) & 0. 5 mg naloxone; Talwin NX® (Sanoﬁ Winthrop); generic; (Royce); (Rx, C-IV) Pentazocine HCl and Aspirin Tablets: 12. 5 mg/325 mg aspirin; Tal-win ® Compound (Sanoﬁ Winthrop); (Rx, C-IV) Pentazocine HCl and Acetaminophen Tablets: 25 mg/650 mg acet-aminophen; Talacen ® (Sanoﬁ Winthrop); generic; (Rx, C-IV) PENTOBARBITAL SODIUM (pen-toe-bar-bi-tal) Nembutal® BARBITURATE Note : Pentobarbital and combinations with pentobarbital (e. g., pheny-toin) for euthanasia have a separate monograph listed under Euthanasia Agents Prescriber Highlights TT Barbiturate used therapeutically as a sedative/anes-thetic, & treating intractable seizures; also used for euthanasia TT Contraindications: Known hypersensitivity, severe liver disease, nephritis, or severe respiratory depression (large doses). Caution: Hypovolemia, anemia, borderline hypoa-drenal function, or cardiac or respiratory disease. Use with caution in cats (sensitive to respiratory depression). TT Adverse Effects: respiratory depression (if using for anes-thesia have ventilatory support available), hypothermia, or excitement post-anesthesia (dogs) TT When giving IV, administer SLOWLY (unless for euthana-sia); very irritating if given SC or perivascularly; do not give IA TT Numerous drug interactions Uses/Indications Once pentobarbital was the principal agent used for general anes-thesia in small animals, but this has been largely supplanted by the use of inhalant anesthetic agents. It is still commonly used as an anesthetic in laboratory situations, for rodents and occasionally as a sedative agent in dogs and cats. Pentobarbital can be used for treating intractable seizures sec-ondary to convulsant agents (e. g., strychnine) or secondary to CNS toxins ( e. g., tetanus). It should not be used to treat seizures caused by lidocaine intoxication. For refractory status epilepticus not con-trolled with diazepam and phenobarbital, pentobarbital can be used, bu t propofol is preferred by some as it causes less cardiovas-cular depression and recoveries can be smoother. Pentobarbital has been used as a sedative and anesthetic agent in horses, cattle, swine, sheep, and goats. Often the drug is given after a preanesthetic agent in order to reduce pentobarbital dosages and resultant side effects. Pentobarbital is a major active ingredient in several euthana-sia solutions. This indication is discussed in the monograph for Euthanasia A gents. Pharmacology/Actions While barbiturates are generally considered CNS depressants, they can invoke all levels of CNS mood alteration from paradoxical ex-citement to deep coma and death. While the exact mechanisms for the CNS eff ects caused by barbiturates are unknown, they have been shown to inhibit the release of acetylcholine, norepinephrine, and glutamate. The barbiturates also have effects on GABA and pento-barbital has been shown to be GABA-mimetic. At high anesthetic doses, barb iturates have been demonstrated to inhibit the uptake of calcium at nerve endings. The degree of depression produced is dependent on the dosage, route of administration, pharmacokinetics of the drug, and species treated. Additionally, effects may be altered by patient age, physi-	pppbs.pdf
cal condition, or concurrent use of other drugs. The barbiturates depress the sensory cortex, lessen motor activity, and produce seda-tion at low dosages. In humans, it has been shown that barbiturates re duce the rapid-eye movement (REM) stage of sleep. Barbiturates have no true intrinsic analgesic activity. In most species, barbiturates cause a dose-dependent respira-tory depression, but, in some species, they can cause slight respira-tory stimulation. At sedative/hypnotic doses, respiratory depression is similar to that during normal physiologic sleep. As doses increase, the medullary respiratory center is progressively depressed with re-sultant decreases in rate, depth, and volume. Respiratory arrest may oc cur at doses four times lower than those will cause cardiac arrest. These drugs must be used very cautiously in cats; they are particu-larly sensitive to the respiratory depressant effects of barbiturates. Besides the cardiac arresting effects of the barbiturates at eutha-natizing dosages, the barbiturates have other cardiovascular effects. In the dog, pentobarbital has been demonstrated to cause tachy-cardia, decreased myocardial contractility and stroke volume, and de creased mean arterial pressure and total peripheral resistance. The barbiturates cause reduced tone and motility of the intes-tinal musculature, probably secondary to its central depressant ac-tion. The thiobarbiturates (thiamylal, thiopental) may, after initial de pression, cause an increase in both tone and motility of the in-testinal musculature; however, these effects do not appear to have muc h clinical signiﬁcance. Administration of barbiturates reduces the sensitivity of the motor end-plate to acetylcholine, thereby slightly relaxing skeletal muscle. Because the musculature is not completely relaxed, other skeletal muscle relaxants may be neces-sary for surgical procedures. There is no direct effect on the kidney by the barbiturates, but sev ere renal impairment may occur secondary to hypotensive effects in overdose situations. Liver function is not directly affected when used acutely, but hepatic microsomal enzyme induction is well documented with extended barbiturate (especially phenobarbital) administration. Although barbiturates reduce oxygen consumption of all tissues, no change in metabolic rate is measurable when given at sedative dosages. Basal metabolic rates may be reduced with re-sultant decreases in body temperature when barbiturates are given at anesthet ic doses. Pharmacokinetics Pentobarbital is absorbed quite rapidly from the gut after oral or rectal administration with peak plasma concentrations occurring between 30-60 minutes after oral dosing in humans. The onset of action usually occurs within 15-60 minutes after oral dosing and within 1 minute after IV administration. Pentobarbital, like all barbiturates, distributes rapidly to all body tiss ues with highest concentrations found in the liver and brain. It is 35-45% bound to plasma proteins in humans. Although less lipophilic than the ultra-short acting barbiturates (e. g., thiopental), pentobarbital is highly lipid soluble and patient fat content may alter the distributive qualities of the drug. All barbiturates cross the placenta and enter milk (at concentrations far below those of plasma). Pentobarbital is metabolized in the liver principally by oxida-tion. Excretion of the drug is not appreciably enhanced by increased urine ﬂow or alkalinizing the urine. Ruminants (especially sheep and goats) metabolize pentobarbital at a very rapid rate. The elimi-nation half-life in the goat has been reported to be approximately 0. 9 hrs. Conversely, the half-life in dogs is approximately 8 hours; in man, it r anges from 15-50 hours. Contraindications/Precautions/Warnings Use cautiously in patients who are hypovolemic, anemic, have bor-derline hypoadrenal function, or cardiac or respiratory disease. Large doses are contraindicated in patients with nephritis or severe respiratory dysfunction. Barbiturates are contraindicated in pa-tients with severe liver disease or who have demonstrated previous hy persensitivity reactions to them. When administering IV, give SLOWLY. Use for cesarean section is not recommended because of fetal respiratory depression. Cats tend to particularly sensitive to the respiratory depressant effects of barbiturates; use with caution in this species. Female cats appear to be more susceptible to the effects of pentobarbital than male cats. Adverse Effects Because of the respiratory depressant effects of pentobarbital, re-spiratory activity must be closely monitored and respiratory as-sistance must be readily available when using anesthetic dosages. Pe ntobarbital may cause excitement in dogs during recovery from anesthetic doses. Hypothermia may develop in animals receiving pentobarbital if exposed to temperatures below 27°C (80. 6°F). The barbiturates can be very irritating when administered SC or perivascularly; avoid these types of injections. Do not administer intra-arterially. 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 be neﬁts 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 class: D (Contraindicated. These drugs have been shown to cause congenital malformations or embryotoxicity. ) Exercise caution when administering to the nursing mother, since small amounts are excreted in maternal milk. Drowsiness in nursing offspring has been reported. Overdosage/Acute Toxicity In dogs, the reported oral LD 50 is 85 mg/kg and IV LD 50 is 40-60 mg/kg. Fatalities from ingestion of meat from animals euthanized by pentobarbital have been reported in dogs. Treatment of pentobar-bital overdose consists of removal of ingested product from the gut if ap propriate and offering respiratory and cardiovascular support. Forced alkaline diuresis is of little beneﬁt for this drug. Peritoneal or hemodialysis may be of beneﬁt in severe intoxications. Drug Interactions Most clinically signiﬁcant interactions have been documented in humans with phenobarbital; however, these interactions may also be of signiﬁcance in animals receiving pentobarbital, especially with chronic therapy. !TACETAMINOPHEN : Increased risk for hepatotoxicity, particularly when large or chronic doses of barbiturates are given. !TLIDOCAINE : Fatalities have been reported when dogs suffering from lidocaine-induced seizures were treated with pentobarbital. Until this interaction is further clariﬁed, it is suggested that lidocaine-induced seizures in dogs be treated initially with diazepam. !TPHENYTOIN : Barbiturates may affect the metabolism of phenytoin, and phenytoin may alter barbiturate levels; monitoring of blood levels may be indicated. !TRIFAMPIN : May induce enzymes that increase the metabolism of barbiturates.	pppbs.pdf
The following drugs may increase the effect of pentobarbital: !!ANTIHISTAMINES !!CHLORAMPHENICOL !!OPIATES !!PHENOTHIAZINES !!VALPROIC ACID Pentobarbital (particularly after chronic therapy) may decrease the effect of the following drugs/drug classes by lowering their serum concentrations: !!ANTICOAGULANTS, ORAL (WARFARIN ) !!BETA-BLOCKERS !!CHLORAMPHENICOL !!CLONAZEPAM !!CORTICOSTEROIDS !!CYCLOSPORINE !!DOXORUBICIN !TDOXYCYCL INE (may persist for weeks after barbiturate discontinued) !!ESTROGENS !!GRISEOFULV IN !!METHADONE !!METRONIDAZOLE !!QUINIDINE !!PAROXETINE !!PHENOTHIAZINES !!PROGESTINS !!THEOPHYLLINE !!TRICYCLIC ANTIDEPRESSANTS !!VERAPAMIL Laboratory Considerations !TBarbiturates may cause increased retention of bromosulfophthalein (BSP; sulfobromophthalein) and give falsely elevated results. It is recommended that barbiturates not be administered within the 24 hours before BSP retention tests. Doses Note : In order to avoid possible confusion, doses used for eutha-nasia are listed separately under the monograph for euthanasia solu tions. !TDOGS: As a sedative: a) 2-4 mg/kg IV (Kirk 1986) b) 2-4 mg/kg PO q6h (Davis 1985a) Fo r anesthesia: a) 30 mg/kg IV to effect (Kirk 1986) b) 10-30 mg/kg IV to effect (Morgan 1988) c) 24-33 mg/kg IV (Booth 1988a) Fo r chemical restraint for ventilatory support: a) 4 mg/kg initially IV; then 2-4 mg/kg/hr thereafter [Given co ncomitantly with oxymorphone: 0. 2 mg/kg (up to 4. 5 mg) IV; then 0. 1 mg/kg every 2 hours thereafter] (Pascoe 1986) For post-myelographic seizures: a) 2-4 mg/kg IV (to effect) (Walter, Feeney, and Johnston 1986) Fo r status epilepticus: a) Give to effect and not as a speciﬁc dose. Dose range is 3-15 mg/kg IV. (Platt and Mc Donnell 2000) b) 3-15 mg/kg IV SLOWLY to effect. Goal is heavy sedation, not s urgical planes of anesthesia. May need to repeat in 4-8 hours. (Raffe 1986) !TCATS: As a sedative: a) 2-4 mg/kg IV (Kirk 1986) b) 2-4 mg/kg PO q6h (Davis 1985a) Fo r status epilepticus: a) 5-15 mg/kg IV to effect (Morgan 1988) b) 3-15 mg/kg IV SLOWLY to effect. Goal is heavy sedation, not s urgical planes of anesthesia. May need to repeat in 4-8 hours. (Raffe 1986) For anesthesia: a) 25 mg/kg IV, an additional 10 mg/kg IV may be given if ini-tial dose is inadequate (Booth 1988a) !TSMALL MAMMALS/RODENTS: For chemical restraint: Mice: 30-80 mg/kg IP Rats: 40-60 mg/kg IP Hamsters/Gerbils: 70-80 mg/kg IP Guinea pig: 15-40 mg/kg IP; 30 mg/kg IV Rabbits: 20-60 mg/kg IV (Burke 1999) !TCATTLE: a) 30 mg/kg IV to effect, repeat as needed for chlorinated hy-drocarbon toxicity (Smith 1986) b) As an anesthetic in calves (over one month of age): 15-30 mg/kg IV (T hurmon and Benson 1986) c) As a sedative: 1-2 grams IV in an adult cow (given until animal b ecomes unsteady and rear limb weakness occurs). 3 grams will usually induce recumbency. (Thurmon and Ben-son 1986) !THORSES: Note : Pentobarbital is generally not considered an ideal agent for use in the adult horse due to possible development of excitement and injury when the animal is “knocked down. ” ( Note : ARCI UCGFS Class 2 Drug) a) 3-15 mg/kg IV (Robinson 1987) b) 15-18 mg/kg IV for light anesthesia (Schultz 1986) !TSWINE: a) 30 mg/kg IV to effect (Howard 1986) b) As an anesthetic: 15-30 mg/kg IV (Thurmon and Benson 1986) !TSHEEP: As an anesthetic: a) 20-30 mg/kg IV (Thurmon and Benson 1986) b) Adult Sheep: 11-54 mg/kg IV (average dose 24 mg/kg IV). Anesthesia required for longer than 15-30 minutes will re-quire additional doses. Lambs: 15-26 mg/kg IV (will induce anesthesia for 15 min-utes). Additional 5. 5 mg/kg IV will give another 30 minutes of effect. (Booth 1988a) !TGOATS: As an anesthetic: a) 20-30 mg/kg IV (Thurmon and Benson 1986) b) 25 mg/kg IV slowly, duration of satisfactory anesthesia will last onl y 20 minutes or so. (Booth 1988a) Monitoring !TLevels of consciousness and/or seizure control !TRespiratory and cardiac signs !TBody temperature !TIf using chronically, routine blood counts and liver function tests should be performed.	pppbs.pdf
TClient Information T ! his drug is best used in an inpatient setting or with close profes-sional supervision. T ! If dosage forms are dispensed to clients, they must be in instruct-ed to keep them away from children; dispense in child-resistant packaging. Chemistry/Synonyms Pentobarbital sodium occurs as odorless, slightly bitter tasting, white, crystalline powder or granules. It is very soluble in water and freely soluble in alcohol. The p K a of the drug has been reported to range from 7. 85-8. 03 and the p H of the injection is from 9-10. 5. Alcohol or propylene glycol may be added to enhance the stability of the injectable product. Pentobarbital may also be known as: aethaminalum, mebubar-bital, mebumal, pentobarbitalum, or pentobarbitone. Storage/Stability/Compatibility The injectable product should be stored at room temperature; the suppositories should be kept refrigerated. The aqueous solution is not very stable and should not be used if it contains a precipitate. Because precipitates may occur, pentobarbital sodium should not be added to acidic solutions. The following solutions and drugs have been reported to be physical ly compatible with pentobarbital sodium: dextrose IV so-lutions, Ringer's injection, lactated Ringer's injection, Saline IV solutio ns, dextrose-saline combinations, dextrose-Ringer's com-binations, dextrose-Ringer's lactate combinations, amikacin sul-fate, aminophylline, atropine sulfate (for at least 15 minutes, not 24 hours), calci um chloride, cephapirin sodium, chloramphenicol sodium succinate, hyaluronidase, hydromorphone HCl, lidocaine HCl, neostigmine methylsulfate, scopolamine HBr, sodium bicar-bonate, sodium iodide, thiopental sodium, and verapamil HCl. The following drugs have been reported to be physically incompat-ible with pentobarbital sodium: benzquinamide HCl, butorphanol tartrate, chlorpromazine HCl, cimetidine HCl, chlorpheniramine maleate, codeine phosphate, diphenhydramine HCl, droperidol, fentanyl citrate, glycopyrrolate, hydrocortisone sodium succinate, hydroxyzine HCl, insulin (regular), meperidine HCl, nalbuphine HCl, norepinephrine bitartrate, oxytetracycline HCl, penicillin G potassium, pentazocine lactate, phenytoin sodium, prochlorpera-zine edisylate, promazine HCl, promethazine HCl, and streptomy-cin sulfate. Compatibility is dependent upon factors such as p H, conce ntration, temperature, and diluent used; consult specialized references for more speciﬁc information. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 2 substance. See the appendix for more information. HUMAN-LABELED PRODUCTS: Pentobarbital Sodium Injection: 50 mg/m L in 2 m L Tubex; generic; (Wyeth-Ayerst); (Rx, C-II) Pentobarbital is a Class-II controlled substance and detailed records must be maintained w ith regard to its use and disbursement. PENTOSAN POLYSULFATE SODIUM (pen-toe-san) PPS, Cartrophen-Vet®, Elmiron® ANTIINFLAMMATORY, OSTEOARTHRITIS DISEASE-MODIFIER Prescriber Highlights TT May be useful in treating osteoarthritis in dogs, cats & horses; may be used as adjunctive treatment of feline interstitial cystitis (feline idiopathic lower urinary tract disease—FLUTD) TT Efﬁcacy for FLUTD not well-documented TT Adverse effects uncommon, but can cause bleeding, GI effects TT Use with caution prior to surgery or with other drugs af-fecting coagulation TT In the USA, only human oral product available; may be expensive Uses/Indications Pentosan may be useful in treating osteoarthritis in dogs, cats, and horses. It has been used as an adjunctive treatment of feline intersti-tial cystitis (feline idiopathic lower urinary tract disease—FLUTD). Studies using p entosan for FLUTD have demonstrated that it is not effective for short-term, acute lower urinary tract disease, but some patients may beneﬁt when it is used for chronic, persistent signs associated with FLUTD. Pharmacology/Actions Pentosan has a mild analgesic effect when used for interstitial cys-titis. The mechanism for its action in treating interstitial cystitis is not known, but it is postulated that it may adhere to bladder wall mucosal membranes and act as a “buffer” to prevent irritating com-pounds in urine from reaching bladder cells. Pentosan has disease-modifying effects on osteoarthritic joints similar to p olysulfated glycosoaminoglycans. It apparently modu-lates cytokine action, preserves preoteoglycan content and stimu-lates hyaluronic acid synthesis. Pentosan has antiinﬂammatory, hypolipid emic, anticoagulant (considerably weaker than heparin— 1/15th), and ﬁbrinolytic properties. These effects potentially could increase synovial blood ﬂow and reduce joint inﬂammation. Pharmacokinetics In rats, 10-20% of the calcium derivative (pentosan polysulfate calcium) is absorbed after oral dosing. In humans, only about 3% of an oral dose of pentosan polysulfate sodium is absorbed. It dis-tributes primarily to the uroepithelium of the genitourinary tract with smalle r concentrations found in the liver, spleen, lung skin, bone marrow, and periosteum. About two-thirds of absorbed drug is desulfated in the liver and spleen within one hour; about 3. 5% of the absorbed drug is excreted into the urine. Contraindications/Precautions/Warnings Pentosan is contraindicated in patients hypersensitive to it. Use this drug with caution in animals also receiving other medications that can affect coagulation, or having surgery in the near future.	pppbs.pdf
Adverse Effects Pentosan is usually well tolerated. Adverse effects of pentosan in vet-erinary species appear to be mild and transitory in nature. In dogs, vo miting, anorexia, lethargy, or mild depression are possible. When used orally in cats, pentosan seems to be tolerated well, but oral dosing twice daily can be stressful for both cat and owner. Because pentosan has some anticoagulant effects, bleeding is possible in any species and may be more likely in animals receiving other drugs that affect coagulation (e. g., aspirin), or undergoing stressful exer-cise. In horses, pentosan causes dose-dependent increases in partial thro mboplastin time (PTT) up to 24 hours post-dose. In a small percentage of humans (<2%) taking the medication, transient in-creases in liver enzymes have been reported. Reproductive/Nursing Safety In humans, pentosan is designated by the FDA as a category B drug (Animal studies have not 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 during the ﬁrst trimester of pregnancy, and there is no evidence of risk in later trimesters. ) Pentosan is likely safe to use during nursing. Overdosage/Acute Toxicity Information regarding overdoses is not readily available. Potentially, overdoses could cause bleeding, thrombocytopenia, GI distress, and liver function abnormalities. At the present time, treatment recom-mendations are basically supportive in nature. If an oral overdose oc curs, consider protocols for drug removal from the gut. Drug Interactions No speciﬁc drug interactions were located; use this drug cautiously with other drugs that can affect coagulation (e. g., NSAIDs, aspirin, hep-arin, etc. ). Laboratory Considerations No laboratory interactions or considerations were noted Doses !TDOGS: As a chondroprotective for osteoarthritis (OA): a) High loading dose: 20 mg/kg PO twice weekly for 5 weeks (for tr eatment of OA signs of pain, lameness and stiffness); Me-dium Loading dose: 10 mg/kg PO once weekly for 12 weeks (fo r management of OA after joint surgery); Maintenance dose: 10 mg/kg once weekly for 4 weeks as needed. Always give on an empty stomach. (Label information; Cartrophen-Vet® Capsules—Arthropharm) b) 3 mg/kg IM or SC on four occasions with an interval of 5-7 day s between injections (Label information; Pentosan 100® Injection —Nature Vet) !TCATS: For treatment of persistent or recurrent FLUTD: a) 2-16 mg/kg PO q12h (Bartges 2002b) b) 8 mg/kg PO q12h (Lane 2002a) !THORSES: For treating osteoarthritis: a) Intramuscular administration: 3 mg/kg IM on four occasions with an interval of 7 days between injections. Int ra-articular injection: Prepare site as for surgery. Avoid iodine based skin preps; use a neutral soapless skin cleanser. A 20 g non-cutting needle is preferred. Introduce into joint space with steady, even pressure. Allow approximately 1 m L of synovial ﬂuid to escape. Attach syringe with pentosan into the syringe and withdraw more synovial ﬂuid to enter syringe, if p ossible. Inject mixture back into joint; draw back once or twice to mix pentosan and joint ﬂuid within the joint. Firmly bandage and conﬁne for 3-4 hours, then remove bandage. Rest horse for 2 weeks and follow with another 2 weeks of graded walking exercise before returning to work. (Label in-formation; Pe ntosan Equine® Injection—Nature Vet) Monitoring !TWhen used for veterinary indications clinical efﬁcacy is the pri-mary monitoring parameter. !TWhen administered into joints, animals should be assessed for intra-articular bleeding. Client Information !TIn cats, pentosan (human product) is usually dosed at 1/2 cap-sule (50 mg) twice daily. One half the contents of a commercially av ailable capsule may be emptied into an empty gelatin capsule and administered. !TGive oral medication on an empty stomach Chemistry/Synonyms A heparin-like compound, pentosan polysulfate sodium is a mix-ture of linear polymers of beta-1->4-linked xylose that are usually sulfat ed at the 2-and 3-positions. Average molecular weight is be-tween 4000 and 6000. It is not derived from animal sources, but fro m Beechwood hemicellulose. Pentosan may also be known as: pentosan polysulphate sodium; PZ-68; so dium pentosan polysulphate; sodium xylanpolysulphate; SP-54, Cartrophen-Vet®, Fibrase®, Fibrezym®, Fibrocid®, Fibrocide®, Hemoclar®, Lelong Contusions®, Elmiron®, Pentosan®, Polyanion®, Tavan®-SP 54, and Thrombocid®. Storage/Stability Unless otherwise labeled, store oral pentosan products at controlled room temperature (15-30°C; 59-86°F) and injectable pentosan products under refrigeration and protected from light. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: No products currently available in USA. In several other countries, Cart rophen-Vet® is available as oral 100 mg capsules (pentosan polysulfate calcium) labeled for use in dogs. Injectable pentosan polysulfate sodium 100mg/m L (Pentosan 100® Injection, and Cartrophen-Vet® Injection) labeled for use in dogs and pentosan polysulfate sodium 250 mg/m L (Pentosan Equine® Injec-tion) for horses are available in several countries. HUMAN-LABELED PRODUCTS: Pentosan Polysulfate Sodium Capsules: 100 mg; Elmiron® (Baker Norton); (Rx)	pppbs.pdf
PENTOXIFYLLINE (pen-tox-ih-ﬁ-leen) PTX, Trental® HEMORRHEOLOGIC, IMMUNOMODULATORY AGENT Prescriber Highlights TT Compound that increases erythrocyte ﬂexibility & may decrease negative effects of endotoxemia TT Contraindications: Retinal or cerebral hemorrhage, in-tolerant or hypersensitive to it or other xanthines (i. e., theophylline) TT Caution: Severe hepatic or renal impairment, or at risk for hemorrhage TT Adverse Effects: GI tract (vomiting/inappetence) most common. Potentially: Dizziness, other GI, CNS, or cardio-vascular effects Uses/Indications In horses, pentoxifylline has been used as adjunctive therapy for cu-taneous, vasculitis, endotoxemia and for the treatment of navicular disease. Pentoxifylline has been used in dogs to treat immune-mediated dermat ologic conditions, enhance healing, and reduce inﬂamma-tion caused by ulcerative dermatosis in Shelties and Collies and for othe r conditions where improved microcirculation may be of beneﬁt. It is being investigated for adjunctive therapy for dilated cardiomyopathy in Doberman pinschers. Pentoxifylline has been tried in conjunction with prednisolone to decr ease vasculitis associated with FIP in cats. Pentoxifylline's major indications for humans include symptom-atic treatment of peripheral vascular disease (e. g., intermittent clau-dication, sickle cell disease, Raynaud's, etc. ) and cerebrovascular dis-eases where blood ﬂow may be impaired in the microvasculature. Pharmacology/Actions The mechanisms for pentoxifylline's actions are not fully under-stood. The drug increases erythrocyte ﬂexibility probably by inhib-iting erythrocyte phosphodiesterase and decreases blood viscosity by red ucing plasma ﬁbrinogen and increasing ﬁbrinolytic activity. Pentoxifylline is postulated to reduce negative endotoxic effects of cyt okine mediators via its phosphodiesterase inhibition. Pharmacokinetics In horses, after PO administration of crushed, sustained-release tablets, pentoxifylline is rapidly absorbed with a wide interpatient variation of bioavailability that averages around 68%. Bioavailability may decrease with continued administration over several days. The authors concluded that 10 mg/kg q12h PO yields serum lev-els equivalent to those observed after administration of therapeutic doses to humans and ho rses. In dogs, pentoxifylline reportedly has a bioavailability of ap-proximately 50% with peak levels occurring about 1-3 hours after dosing. S erum half-life is approximately 6-7 hours for the parent compound, 36 hours for active metabolite 1, and 8 hours for active metabolite 5. In humans, pentoxifylline absorption from the gastrointestinal trac t is rapid and almost complete, but a signiﬁcant ﬁrst-pass ef-fect occurs. Food affects the rate, but not the extent, of absorption. While the dist ributive characteristics have not been fully described, it is known that the drug enters maternal milk. Pentoxifylline is me-tabolized both in the liver and erythrocytes; all identiﬁed metabo-lites appear to be active. Contraindications/Precautions/Warnings Pentoxifylline should be considered contraindicated in patients who have been intolerant to the drug or xanthines (e. g., theophyl-line, caffeine, theobromine) in the past and those with cerebral hemorr hage or retinal hemorrhage. It should be used cautiously in patients with severe hepatic or renal impairment and those at risk for hemorrhage. Adverse Effects Most commonly reported adverse effects involve the GI tract (vom-iting/inappetence) or CNS (excitement, nervousness). Erythema multifo rme may occur rarely, secondary to pentoxifylline therapy in dogs. In horses, IV administration may be associated with transient leukocy tosis, muscle fasiculations, sweating on shoulders and ﬂanks, and mild increases in heart rate. Oral dosing at 10 mg/kg or less appears to be well tolerated. There are reports of dizziness and headache occurring in a small perc entage of humans receiving the drug. Other adverse effects, pri-marily GI, CNS, and cardiovascular related, have been reported in people, but are considered to occur rarely. Veterinary experience is limited with pentoxifylline and animal adverse effects may differ. Reproductive/Nursing Safety 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. ) Pentoxifylline may be teratogenic at high dosages. Pentoxifylline and its metabolites are excreted in maternal milk. Because o f the potential for tumorigenicity (seen in rats), use cau-tiously in nursing patients. Overdosage/Acute Toxicity Humans overdosed with pentoxifylline have demonstrated signs of ﬂushing, seizures, hypotension, unconsciousness, agitation, fever, somnolence, GI distress and ECG changes. One patient who ingest-ed 80 mg/kg recovered completely. Overdoses should be treated us-ing the usual methods of appropriate gut emptying and supportive therapies. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving pentoxifylline and may be of signiﬁcance in veterinary patients: T ! ANTIHYPERTENSIVE DRUGS : With pentoxifylline may increase hy-potensive effect T ! NSAIDS : Use of non-steroidal antiinﬂammatory agents with pen-toxifylline in horses is controversial. Some sources state that when used for endotoxemia in horses, pentoxifylline's beneﬁcial effects are negated by NSAIDs, but one study showed superior efﬁcacy when ﬂunixin and pentoxifylline were used together, compared with either used alone. T ! PLATELET-AGGREGATION INHIBITORS (e. g., aspirin, clopidogrel ): In-creased risk for bleeding T ! THEOPHYLLINE : Serum levels may be increased when used concur-rently with pentoxifylline T ! WARFARIN : When pentoxifylline is used with warfarin or other an-ticoagulants, increased risk of bleeding may result; use together with enhanced monitoring and caution	pppbs.pdf
Doses T ! DOGS: a) For dermatologic conditions (e. g., dermatomyositis, ear margin seb orrhea/necrosis, ulcerative dermatitis of collies/ shelties, contact dermatitis, atopy and any disease with un-derlying vasculitis): 10 mg/kg PO q8h, if the disease does not respo nd, 15 mg/kg PO q8h may be effective (Merchant 2000) b) 10 mg/kg PO 2-3 times daily (Marsella 1999) c) For dermatologic disorders including dermatomyositis, vas-culitis, erythema multiforme, cutaneous and renal vasculitis of Gr eyhounds (Alabama rot), and allergic contact dermati-tis: 10-30 mg/kg PO q 12 hours (Campbell 1999) d) For familial canine dermatomyositis: 25 mg/kg PO q12h ap-pears to be an effective beginning dose (Rees and Boothe 20003) e) For atopic dermatitis: 10-15 mg/kg PO q8-12h. A 6-8 week course o f therapy may be required to assess efﬁcacy. (White 2003d) f) For vasculitis, dermatomyositis: 10 mg/kg PO q8h (Boord 2007) g) For vasculitis: 15 mg/kg PO q8h (Hillier 2006d) T ! CATS: T o reduce vasculitis in cats with FIP: a) 100 mg per cat PO twice daily (with prednisolone at 2-4 mg/ kg/day PO; taper every two weeks). T ! HORSES: (Note : ARCI UCGFS Class 4 Drug) a) 10 mg/kg q12h PO yields serum levels equivalent to those observ ed after administration of therapeutic doses to hu-mans and horses. OK to crush the sustained-release tablets and mix with molasses. If efﬁcacy wanes with time, consider increasing the dose to 15 mg/kg PO twice daily or 10 mg/kg PO three times a day. In the experience of the authors, 10 mg/kg PO twice daily for 30 days results in clinical response in horses with cutaneous vasculitis. (Liska, Akucewich et al. 2006) T o reduce cytokine effects in endotoxemia: a) 7. 5 mg/kg PO q12h, efﬁcacy may be improved if used with ﬂunixin (Smith 2003b) b) 8 mg/kg PO q8h (Bar ton 2003) For adj unctive treatment of equine pastern dermatitis: a) If clinical signs do not resolve after 14 days of topical and other immuno modulating therapy, add pentoxifylline at 4-8 mg/kg PO q12h (Yu 2003) For adjunctive treatment of navicular disease: a) 6 grams per day PO for 6 weeks (Livesay 1996) T o increase oxygenation of placenta in placentitis: a) 7. 5 mg/kg PO q12h (Tr oedsson 2003) T o increase the circulation to the podotrochlea: a) 4. 5-7 mg/kg PO three times daily (Turner 1999) Monitoring T ! Efﬁcacy T ! Adverse effects Client Information T ! Give with food to reduce the GI effects of pentoxifylline T ! Clients should understand that veterinary experience with this medication is limited and that the risk versus beneﬁt proﬁle is not well-deﬁned Chemistry/Synonyms A synthetic xanthine derivative structurally related to caffeine and theophylline, pentoxifylline occurs as a white, odorless, bitter-tast-ing, crystalline powder. At room temperature, approximately 77 mg are soluble in o ne m L of water and 63 mg in one m L of alcohol. Pentoxifylline may also be known as: BL-191, oxpentifylline, or pento xifyllinum and Trental®. Storage/Stability The commercially available tablets should be stored in well-closed containers, protected from light at 15-30°C. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 4 substance. See the appendix for more information. HUMAN-LABELED PRODUCTS: Pentoxifylline Controlled/Extended Release Tablets: 400 mg; Trental® (Hoechst Marion Roussel); generic; (Purepac); (Rx) PERGOLIDE MESYLATE (per-go-lide) Permax® DO PAMINE AGONIST Prescriber Highlights TT Dopamine agonist that can help control signs associated with equine Cushing's disease TT Apparently, very well tolerated in horses TT May be signiﬁcant expense involved, since treatment is life-long TT Commercial availability an issue; may need to obtain via compounding pharmacies Uses/Indications The primary use for pergolide in veterinary medicine is in treat-ment of horses for pituitary pars intermedia dysfunction (PPID), commonl y called equine Cushing's disease. Pharmacology/Actions Pergolide is a potent agonist at dopamine receptors D1 and D2 and is 10-1000 times more potent than bromocriptine. It is thought that pituitary pars intermedia dysfunction (PPID) in horses is a do-paminergic degenerative disease and pergolide (or dopamine) can reduc e expression of proopiomelanocortin (POMC) peptides from the pars intermedia. These peptides are implicated in causing the signs associated with PPID. Pharmacokinetics No information on pergolide pharmacokinetics in horses was lo-cated. In humans, the drug is orally absorbed (estimated 60% bio-available) and is 90% bound to plasma proteins. At least 10 differ-ent metabolites have been identiﬁed, some of which are active. The principle rou te of elimination is via the kidneys. Contraindications/Precautions Pergolide is contraindicated in patients hypersensitive to it or other ergot derivatives.	pppbs.pdf
TAdverse Effects Pergolide appears to be very well tolerated in horses. Adverse effects reported in humans include: nervous system complaints (dyski-nesia, hallucinations, somnolence and insomnia), gastrointestinal co mplaints (nausea, vomiting, diarrhea, constipation), transient hypotension, and rhinitis. Reproductive/Nursing Safety Safety of pergolide in pregnant horses has not been established. In humans, pergolide is designated by the FDA as a category B drug (Animal studies have not 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 during the ﬁrst trimester of pregnancy, and there is no evidence of risk in later trimesters. ) It is not known if pergolide enters maternal milk; however, like other ergot-derivative dopamine agonists, it may interfere with actation. Overdosage/Acute Toxicity There is limited information available on pergolide overdoses. Potential effects include GI disturbances, CNS effects, seizures, and hypotension. There were 15 exposures to pergolide mesylate re ported to the ASPCA Animal Poison Control Center (APCC; www. apcc. aspca. org) during 2005-2006. All of these 15 reported cases were dogs with 6 showing clinical signs. Common ﬁndings in dogs recorded in decreasing frequency included vomiting, lethargy, depression, hyperactivity, and hypertension. Treatment is supportive. Phenothiazines may decrease CNS stim ulation effects. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving pergolide and may be of signiﬁcance in veterinary patients: !TDOPAMINE ANTAGONISTS (i. e., phenothiazines ): May decrease the ef-fects of pergolide !TMETOCLOPRAMIDE : May decrease the effects of pergolide Laboratory Considerations No speciﬁc laboratory interactions or considerations were noted for this drug. Doses !THORSES: For treatment of Equine “Cushing's-like” Disease [pituitary pars intermedia dysfunction (PPID)]: a) Initial dose is usually 0. 5 mg per day. Reassess at 4-8 weeks by means of dexamethasone suppression test and blood glu-cose (if hyperglycemia was present prior to treatment). If not nor mal, increase dose in 0. 25 mg increments and reassess as above. Most horses respond clinically in 6 weeks and usually at 0. 75-1. 25 mg per day. Treatment must be continued for life. (Dybdal 1997) Monitoring !TDexamethasone suppression test (baseline and at 4-8 weeks post pergolide therapy initiation, repeat in 4-8 weeks if dosage is ad-justed) !TBlood glucose (baseline, and if abnormal and repeat as per dex-amethasone suppression test) !TClinical signs (hair coat, weight, PU/PD, etc. ) !TPeriodic CBC and clinical chemistry panel Client Information !TClients should understand that pergolide does not cure the dis-ease and it may take several weeks to months to see efﬁcacy. !Treatment is required for the life of the horse and the drug can be expensive. !TProper nutrition and weight control can be very important to the successful treatment of this disease. Chemistry/Synonyms An ergot derivative, dopamine receptor agonist, pergolide occurs as white to off-white powder that is slightly soluble in water, de-hydrated alcohol, or chloroform. It is very slightly soluble in ac-etone; practically insoluble in ether and sparingly soluble in methyl alcohol. P ergolide mesylate may also be known as: LY-127809, pergolide mesilate, pergolidi mesilas, Celance®, Nopar®, Parkotil®, Parlide®, or Pharken®. Storage/Stability Store pergolide tablets in tight containers at room temperature (25°C; 77°F); excursions permitted to 15-30°C (59-86°F). Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: None Due to an increased potential for heart valve damage associated with pergolide use in humans, all dosage forms were withdrawn from the US market in the Spring of 2007. Pergolide may be available from compounding pharmacies for veterinary use.	pppbs.pdf
PHENOBARBITAL SODIUM PHENOBARBITAL (fee-noe-bar-bi-tal) BARBITURATE Prescriber Highlights TT Barbiturate used primarily as an antiseizure medication; also used as a sedative agent TT Contraindications: Known hypersensitivity, severe liver disease, nephritis, or severe respiratory depression (large doses) TT Caution: Hypovolemia, anemia, borderline hypoadrenal function, or cardiac or respiratory disease; use with cau-tion in cats (sensitive to respiratory depression) TT Adverse Effects: DOGS: Anxiety/agitation or lethargy (when initiating treatment); profound depression, (even at low doses) is possible. Sedation, ataxia, polydipsia, polyuria, polyphagia can be seen at moderate to high serum levels. Increase in liver enzymes possible, but overt hepatotoxicity relatively uncommon. Rare: Anemia, thrombocytopenia or neutropenia. TT Adverse Effects: CATS: Ataxia, lethargy, polyphagia/ weight gain & polydipsia/polyuria. Rare: Immune-mediat-ed reactions & bone marrow hypoplasia TT When administering IV, give SLOWLY; do not give SC or perivascularly (very irritating) TT Drug Interactions; drug-lab interactions TT C-IV controlled substance Uses/Indications Although some believe that bromide salts are now the treatment of ﬁrst choice for treating epilepsy in dogs (especially young dogs and those with liver disease), many still choose phenobarbital for dogs because of its favorable pharmacokinetic proﬁle, relative safety, ef-ﬁcacy, low cost, and ability to treat epilepsy at sub-hypnotic doses. Phenobarb ital is still widely considered the drug of ﬁrst choice for treating epilepsy in cats. It is also occasionally used as an oral seda-tive agent in both species. Because it has a slightly longer onset of actio n, it is used principally in the treatment of status epilepticus in dogs, cats, and horses to prevent the recurrence of seizures after they have been halted with either a benzodiazepine or short-acting barbiturate. Phenobarbital may also useful in controlling excessive feline vocalization while riding in automobiles. In cattle, the microsomal enzyme stimulating properties of phe-nobarbital has been suggested for its use in speeding the detoxiﬁca-tion of organochlorine (chlorinated hydrocarbon) insecticide poi-soning. Additionally, phenobarbital has been used in the treatment and pre vention of neonatal hyperbilirubinemia in human infants. It is unknown if hyperbilirubinemia is effectively treated in veteri-nary patients with phenobarbital. Pharmacology/Actions While barbiturates are generally considered CNS depressants, they can invoke all levels of CNS mood alteration from paradoxical ex-citement to deep coma and death. While the exact mechanisms for the CNS eff ects caused by barbiturates are unknown, they have been shown to inhibit the release of acetylcholine, norepinephrine, and glutamate. The barbiturates also have effects on GABA and pento-barbital has been shown to be GABA-mimetic. At high anesthetic doses, barb iturates have been demonstrated to inhibit the uptake of calcium at nerve endings. The degree of depression produced is dependent on the dosage, route of administration, pharmacokinetics of the drug, and species treated. Additionally, effects may be altered by patient age, physi-cal condition, or concurrent use of other drugs. The barbiturates depr ess the sensory cortex, lessen motor activity, and produce seda-tion at low dosages. In humans, it has been shown that barbiturates reduc e the rapid-eye movement (REM) stage of sleep. Barbiturates have no true intrinsic analgesic activity. In most species, barbiturates cause a dose-dependent respira-tory depression, but, in some species, they can cause slight respira-tory stimulation. At sedative/hypnotic doses, respiratory depression is similar to that during normal physiologic sleep. As doses increase, the medullary respiratory center is progressively depressed with re-sultant decreases in rate, depth, and volume. Respiratory arrest may occur at doses four times lower than those will cause cardiac arrest. These drugs must be used very cautiously in cats; they are particu-larly sensitive to the respiratory depressant effects of barbiturates. The barbiturates cause reduced tone and motility of the intes-tinal musculature, probably secondary to its central depressant ac-tion. Administration of barbiturates reduces the sensitivity of the motor e ndplate to acetylcholine, thereby slightly relaxing skeletal muscle. Because the musculature is not completely relaxed, other skeletal muscle relaxants may be necessary for surgical procedures. There is no direct effect on the kidney by the barbiturates, but sever e renal impairment may occur secondary to hypotensive effects in overdose situations. Liver function is not directly affected when used acutely, but hepatic microsomal enzyme induction is well documented with extended barbiturate (especially phenobarbital) administration. Although barbiturates reduce oxygen consumption of all tissues, no change in metabolic rate is measurable when given at sedative dosages. Basal metabolic rates may be reduced with re-sultant decreases in body temperature when barbiturates are given at anesthetic doses. Pharmacokinetics The pharmacokinetics of phenobarbital have been thoroughly studied in humans and in a more limited fashion in dogs, cats, and horses. Phenobarbital is slowly absorbed from the GI tract. Bioavailabilities range from 70-90% in humans, approximately 90% in dogs, and absorption is practically complete in adult horses. Peak levels occur in 4-8 hours after oral dosing in dogs, and in 8-12 hours in humans. Phenobarbital is widely distributed throughout the body, but because o f its lower lipid solubility, it does not distribute as rapidly as most other barbiturates into the CNS. The amount of phenobar-bital bound to plasma proteins has been reported to be 40-50%. The re ported apparent volumes of distribution are approximately: Horse ≈ 0. 8 L/kg; Foals ≈ 0. 86 L/kg; Dogs ≈ 0. 75 L/kg. The drug is metabolized in the liver primarily by hydroxylat-ed oxidation to p-hydroxyphenobarbital; sulfate and glucuronide conjug ates are also formed. The elimination half-lives reported in humans range from 2-6 days; in dogs from 12-125 hours with an average of approximately 2 days. Because of its ability to induce the hepatic enzymes used to metabolize itself (and other drugs), elimi-nation half-lives may decrease with time along with concomitant re-ductions in serum levels. Some dogs may have half lives of less than 24 hours and may require 3 times daily dosing for maximal control. An elimination half-life of 34-43 hours has been reported in cats. Elimination half-lives in horses are considerably shorter with values reported of approximately 13 hours in foals and 18 hours in adult horses. Phenobarbital will induce hepatic microsomal enzymes	pppbs.pdf
and it can be expected that elimination half-lives will decrease with time. Approximately 25% of a dose is excreted unchanged by the kidney. Alkalinizing the urine and/or substantially increasing urine ﬂow will increase excretion rates. Anuric or oliguric patients may accumulate unmetabolized drug; dosage adjustments may need to be made. Changes in diet, body weight, and body composition may alter the p harmacokinetics of phenobarbital in dogs and necessitate dos-age adjustment. Contraindications/Precautions/Warnings Use cautiously in patients that are hypovolemic, anemic, have bor-derline hypoadrenal function, or cardiac or respiratory disease. Large doses are contraindicated in patients with nephritis or severe respiratory dysfunction. Barbiturates are contraindicated in pa-tients with severe liver disease or who have demonstrated previous hy persensitivity reactions to them. When administering IV, give slowly (not more than 60 mg/min-ute); too rapid IV administration may cause respiratory depression. Co mmercially available injectable preparations (excluding the ster-ile powder) must not be administered subcutaneously or perivascu-larly as signiﬁcant tissue irritation and possible necrosis may result. Ap plications of moist heat and local inﬁltration of 0. 5% procaine HCl solution have been recommended to treat these reactions. Adverse Effects Dogs may exhibit increased clinical signs of anxiety/agitation or lethargy when initiating therapy. These effects are generally transi-tory in nature. Occasionally dogs will exhibit profound depression at lo wer dosage ranges (and plasma levels). Polydipsia, polyuria, and polyphagia are also quite commonly displayed at moderate to high serum levels and may falsely infer a diagnosis of Cushing's dis-ease; these signs are usually controlled by limiting intake of both fo od and water. Sedation and/or ataxia often become signiﬁcant concerns as serum levels reach the higher ends of the therapeutic range. Rarely, anemia, thrombocytopenia or neutropenia may oc-cur which are reversible if detected early. Increases in liver enzymes are well described for phenobarbital in dogs and are not necessarily indicative of liver dysfunction, but if serum ALT or ALP are greater than 4-5 times the upper limit of normal, or if any elevation of AST and GGT are noted, it should raise concern. Phenobarbital should generally be discontinued if any increases in serum bilirubin, total serum bile acids or hypoalbumenemia are seen. Frank hepatic fail-ure is uncommon and is usually associated with higher serum levels (>30- 40 mcg/m L). Phenobarbital may rarely cause superﬁcial necrolytic dermatitis (SND) in dogs associated with changes in hepatocytes (severe pa-renchymal collapse with glycogen-laden hepatocytes and moderate ﬁbr osis sharply demarcated by nodules of normal hepatic paren-chyma) distinct from that seen with phenobarbital hepatotoxicity. Cats may develop ataxia, persistent sedation and lethargy, pol yphagia/weight gain, and polydipsia/polyuria. Rarely, immune-mediated reactions and bone marrow hypoplasia (thrombocytope-nia, neutropenia) may be seen. Cats, unlike dogs, apparently do not ha ve the issues of increased liver enzymes. Very high dosages (10-40 mg/kg/day) have caused coagulopathies in cats. Although there is much less information regarding its use in hor ses (and foals in particular), it would generally be expected that adverse effects would mirror those seen in other species. Reproductive/Nursing Safety Phenobarbital has been associated with rare congenital defects and bleeding problems in newborns, but may be safer than other anticonvulsants. In humans, the FDA categorizes this drug as cat-egory D for use during pregnancy (There is evidence of human fetal r isk, but the potential beneﬁts from the use of the drug in pregnant wome n 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 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. ) Exercise caution when administering to a nursing mother since small amounts are excreted in maternal milk. Drowsiness in nurs-ing offspring has been reported. Overdosage/Acute Toxicity There were 346 exposures to phenobarbital reported to the ASPCA Animal Poison Control Center (APCC; www. apcc. aspca. org) dur-ing 2005-2006. In these cases 304 were dogs with 54 showing clinical signs and the remaining 42 reported cases were cats with 10 showing clinical signs. Common ﬁndings in dogs recorded in decreasing frequency included ataxia, sedation, lethargy, coma and recumbency. Common ﬁndings in cats recorded in decreasing fre-quency included vomiting, ataxia, mydriasis, sedation, blindness and ce ntral nervous system depression. Treatment of a phenobarbital overdose consists of removal of ingest ed product from the gut, if appropriate, and giving respirato-ry and cardiovascular support. Activated charcoal has been demon-strated to be of considerable beneﬁt in enhancing the clearance of phe nobarbital, even when the drug was administered parenterally. Charcoal acts as a “sink” for the drug to diffuse from the vasculature back into the gut. Forced alkaline diuresis can also be of substantial beneﬁt in augmenting the elimination of phenobarbital in patients with normal renal function. Peritoneal dialysis or hemodialysis may be helpful in severe intoxications or in anuric patients. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving phenobarbital and may be of signiﬁcance in veterinary patients: !TACETAMINOPHEN : Increased risk for hepatotoxicity, particularly when large or chronic doses of barbiturates are given !TMONAMINE OXIDASE (MAO) INHIBITORS (e. g., amitraz, possibly selegi-line): May prolong phenobarbital effects !TPHENYTOIN : Barbiturates may affect the metabolism of phenytoin, and phenytoin may alter barbiturate levels; monitoring of blood levels may be indicated !TRIFAMPIN : May induce enzymes that increase the metabolism of barbiturates The f ollowing drugs may increase the effects of phenobarbital: !!ANTIHISTAMINES !!CHLORAMPHENICOL !!OPIATES ! !PHENOTHIAZINES !!VALPROIC ACID Phenobarbital (particularly after chronic therapy) may decrease the effect of the following drugs/drug classes by lowering their serum concentrations: !!ANTICOAGULANTS, ORAL (WARFARIN ) !!BETA-BLOCKERS !!CHLORAMPHENICOL !!CLONAZEPAM ! !CORTICOSTEROIDS ! !CYCLOSPORINE !!DOXORUBICIN !TDOXYCYCL INE (may persist for weeks after barbiturate discontinued)	pppbs.pdf
!!ESTROGENS !!GRISEOFULV IN ! !METHADONE !!METRONIDAZOLE !!QUINIDINE !!PAROXETINE ! !PHENOTHIAZINES !!PROGESTINS !!THEOPHYLLINE !!TRICYCLIC ANTIDEPRESSANTS !!VERAPAMIL Laboratory Considerations !TBarbiturates may cause increased retention of bromosulfophthalein (BSP; sulfobromophthalein) and give falsely elevated results. It is recommended that barbiturates not be administered within the 24 hours before BSP retention tests; or, if they must, (e. g., for seizure control) the results be interpreted accordingly. !TPhenobarbital can alter thyroid testing. Decreased total and free T4, normal T3, and either normal or increased TSH have been reported. It has been suggested to wait at least 4 weeks after dis-continuing phenobarbital to perform thyroid testing. !TIn some dogs, phenobarbital may cause a false positive low dose dexamethasone suppression test, by increasing the clearance of dexamethasone. Phenobarbital apparently has no effect either on ACTH stimulation tests or on the hormonal equilibrium of the adrenal axis. Doses !TDOGS: For treatment of idiopathic epilepsy: a) Initial oral dose: 2. 5 mg/kg PO twice daily; to reach steady state levels faster may give an IV loading dose of 20 mg/kg. Adjust dosage based upon therapeutic levels, efﬁcacy, and ad-verse effects. (Podell 2000) b) Perform CBC, Biochem proﬁle and urology study. Initial dose: 2 (1-2. 5) mg/kg q12h. Increase the dosage 50-100% in puppies due to their increased metabolic rate; adjust dos-ages based upon serum levels. (Quesnel 2000) c) Initially, 2-4 mg/kg PO divided into 2-3 doses per day. If ineff ective, may increase in a stepwise fashion to a maximum of 18-20 mg/kg/day (divided 2-3 times a day). Sudden dis-continuation of the drug may result in seizures. (Le Couteur 1999) d) Loading dose of 16-20 mg/kg once IV; maintenance dose of 2- 5 mg/kg PO q12h. (Knipe 2006a) e) Begin at 3. 5 mg/kg PO twice daily. Monitor at 2 to 4 weeks and 3 months later to detect induction. If response is insuf-ﬁcient, increase dose sufﬁciently to increase trough level by 3 t o 5 mcg/m L increments, rechecking at 2 to 4 weeks after each dose increase. Monitor at 3 to 12 month intervals once steady-state is achieved. As concentrations approach 30 mcg/m L, begin monitoring hepatic function test (bile acids, albumin, BUN, chol). As concentrations approach 35 mcg/ m L, consider adding an additional drug. Avoid any other drug metabolized by the liver. Consider hepatoprotectant drugs if liver dysfunction is of concern. (Axlund 2004b) For treatment of status epilepticus: a) If seizures persist after diazepam therapy (2 or more seizures re cur; or gross motor activity persists) give phenobarbital bo-lus of 2-5 mg/kg (can be repeated at 20 minute intervals, up to two times). Add phenobarb to diazepam infusion at a rate of 2-10 mg/hour. If seizures are sustained or high frequency se izures recur, consider pentobarbital coma. (Quesnel 2000) For sedation: a) 2. 2-6. 6 mg/kg PO twice daily (Walton 1986) b) Treatment of irritable bowel syndrome: 2. 2 mg/kg PO twice daily (M organ 1988) c) For adjunctive treatment of compulsive behaviors: 2-20 mg/ kg q12- 24h (Line 2000) !TCATS: Treatment of idiopathic epilepsy: a) Perform CBC, Biochem proﬁle and urology study. Initial dose: 2 (1-2. 5) mg/kg q12h. Increase the dosage 50-100% possibly in kittens due to their increased metabolic rate; ad-just dosages based upon serum levels. (Quesnel 2000) b) For status epilepticus: If seizures persist after diazepam thera-py (2 or more seizures recur; or gross motor activity persists) gi ve phenobarbital bolus of 2-5 mg/kg (can be repeated at 20 minute intervals, up to two times). Add phenobarb to di-azepam infusion at a rate of 2-10 mg/hour. If seizures are sustaine d or high frequency seizures recur, consider pento-barbital coma. For oral maintenance therapy: 1-2 mg/kg PO every 12 hours; adj ust dosages based upon serum levels (Shell 2000) c) Loading dose of 16-20 mg/kg once IV; maintenance dose of 1- 5 mg/kg PO q12h. (Knipe 2006a) d) Starting dose is 1-2 mg/kg (usually 3. 25-15 mg/cat) PO q12h. M easure trough serum levels 2-3 weeks after initiating therapy and after each dosage change. In the cat, therapeutic levels are likely 50-100 mcmol/L (lower than those in dogs). If seizure control is good, but levels are subtherapeutic, dose does not need to be increased. Measure phenobarbital lev-els, CBC and serum chemistries every 6 months. (Cochrane 2007) Sedation; for controlling excessive feline vocalization for situ-ational distress (e. g., riding in automobiles): a) 2-3 mg/kg PO as needed (Overall 2000) !TFERRETS: a) 1-2 mg/kg PO 2-3 times daily (Williams 2000) b) Loading dose of 16-20 mg/kg once IV; maintenance dose of 1- 2 mg/kg PO q8-12h. (Knipe 2006a) !TCATTLE: For enzyme induction in organochlorine toxicity: a) 5 grams PO for 3-4 weeks, off 3-4 weeks, then repeat for 3-4 more weeks (Smith 1986) !THORSES: (Note : ARCI UCGFS Class 2 Drug) a) Loading dose of 12 mg/kg IV over 20 minutes, then 6. 65 mg/ kg IV ov er 20 minutes every 12 hours (Duran et al. 1987) b) Adult horses: Loading dose of 16-20 mg/kg once IV; main-tenance dose of 1-5 mg/kg PO twice daily. Fo als: Loading dose of 16-20 mg/kg once IV; maintenance dose of 100-500 mg (total dose) PO twice daily. (Knipe 2006a) c) Foals for seizures: 20 mg/kg diluted with normal saline to a vol ume of 30-35 m L infused over 25-30 minutes IV, then 9 mg/kg diluted and infused as above q8h. Recommend moni-toring serum levels if possible. (Spehar et al. 1984) Monitoring !TAnticonvulsant (or sedative) efﬁcacy !TAdverse effects (CNS related, PU/PD, weight gain) !TSerum phenobarbital levels if lack of efﬁcacy or adverse reactions	pppbs.pdf
noted. Some recommend that all dogs have their phenobarbital level monitored once a year and cats monitored every 6 months. Although there is some disagreement among clinicians, thera-peutic serum levels in dogs (15-45 mcg/m L; 65-194 mcmol/L) are thought to be similar to those in humans. Therapeutic levels in cats may be closer to 12-30 mcg/m L (50-129 mcmol/L). Ani-mals on bromides and phenobarbital may require lower serum levels for seizure control. If phenobarbital was not “loaded”, wait at least 5-6 half-lives (approximately 12-14 days in dogs and 9-10 days in cats) before measuring serum concentrations; time of sampling does not appear to be signiﬁcant T ! If used chronically, routine CBC's, liver enzymes (especially ALT and AST), and bilirubin at least every 6 months. Client Information T ! For successful epilepsy treatment compliance with prescribed therapy must be stressed. Encourage client to give doses at the same time each day. T ! Keep medications out of reach of children and stored in child-resistant packaging. T ! Veterinarian should be contacted if animal develops signiﬁcant adverse reactions (including clinical signs of anemia and/or liver disease) or seizure control is unacceptable. Chemistry/Synonyms Phenobarbital, a barbiturate, occurs as white, glistening, odorless, small crystals or a white, crystalline powder with a melting point of 174°-178°C and a p K a of 7. 41. One gram is soluble in approxi-mately 1000 m L of water; 10 m L of alcohol. Compared to other barbitur ates it has a low-lipid solubility. Phenobarbital sodium occurs as bitter-tasting, white, odorless, ﬂaky cry stals or crystalline granules or powder. It is very soluble in water, soluble in alcohol, and freely soluble in propylene glycol. The injectable product has a p H of 8. 5-10. 5. SI units (mcmol/L) are multiplied by 0. 232 to convert pheno-barbital levels to conventional units (mcg/m L). Phenobarbital may also be known as fenobarbital, phenemalum, phenobar bitalum, phenobarbitone, phenylethylbarbituric acid, or phenylethylmalonylurea, Luminal Sodium® and Solfoton®. Storage/Stability/Compatibility Phenobarbital tablets should be stored in tight, light-resistant con-tainers at room temperature (15-30°C); protect from moisture. Phenobarb ital elixir should be stored in tight containers at 20-20°C. Phenobarbital sodium injection should be stored at room tem-perature (15-30°C). Aqueous solutions of phenobarbital are not very stable. Prop ylene glycol is often used in injectable products to help stabi-lize the solution. Solutions of phenobarbital sodium should not be added to acidic solutions nor used if they contain a precipitate or are grossly discolored. The following solutions and drugs have been reported to be physical ly compatible with phenobarbital sodium: Dextrose IV solutions, Ringer's injection, lactated Ringer's injection, Saline IV solutions, dextrose-saline combinations, dextrose-Ringer's combi-nations, dextrose-Ringer's lactate combinations, amikacin sulfate, aminophy lline, atropine sulfate (stable for at least 15 minutes, but not 24 hours), calcium chloride and gluconate, cephapirin sodium, dimenhydrinate, polymyxin B sulfate, sodium bicarbonate, thio-pental sodium, and verapamil HCl. The following drugs have been reported to be physically incom-patible with phenobarbital sodium: benzquinamide HCl, cephalot-hin sodium, chlorpromazine HCl, codeine phosphate, ephedrine sulfate, fentanyl citrate, glycopyrrolate, hydralazine HCl, hydrocor-tisone sodium succinate, hydroxyzine HCl, insulin (regular), me-peridine HCl, morphine sulfate, nalbuphine HCl, norepinephrine bitartr ate, oxytetracycline HCl, pentazocine lactate, procaine HCl, prochlorperazine edisylate, promazine HCl, promethazine HCl, and streptomycin sulfate. 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 VETERINARY-LABELED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 2 substance. See the appendix for more information. HUMAN-LABELED PRODUCTS: Phenobarbital Tablets: 15 mg, 16 mg (tablets and capsules), 30 mg, 60 mg, 90 mg, & 100 mg; Solfoton® (ECR Pharm); generic; (Rx, C-IV) Phenobarbital Elixir: 15 mg/5m L in pt and UD 5 m L, 10 m L and 20 m L; 20 mg/5m L in pt, g al, UD 5 m L and 7. 5 m L; generic; (Rx, C-IV) Phenobarbital Sodium Injection: 30 mg/m L, 60 mg/m L, 65 mg/m L, & 130 mg/m L in 1 m L Tubex, Carpujects and vials; Luminal Sodium® (Hospira); generic; (Rx; C-IV) PHENOXYBENZAMINE HCL (fen-ox-ee-ben-za-meen) Dibenzyline® ALPHA-ADRENERGIC BLOCKER Prescriber Highlights TT Alpha-adrenergic blocker used in small animals: detru-sor areﬂexia, pheochromocytoma (hypertension); horses: laminitis or diarrhea TT Contraindications: When hypotension would be deleteri-ous; possibly glaucoma or diabetes mellitus, horses with clinical signs of colic. Caution: CHF or other heart dis-ease, renal damage, or cerebral/coronary arteriosclerosis TT Adverse Effects: Hypotension, hypertension (rebound), miosis, increased intraocular pressure, tachycardia, inhi-bition of ejaculation, nasal congestion, weakness/dizzi-ness, & GI effects (e. g., nausea, vomiting). Constipation may occur in horses. TT May need to be obtained from compounding pharmacy TT Drug Interactions Uses/Indications Phenoxybenzamine is used in small animals primarily for its effect in reducing internal urethral sphincter tone in dogs and cats when urethral sphincter hypertonus is present. It can also be used to treat the hypertension associated with pheochromocytoma prior to sur-gery or as adjunctive therapy in endotoxicosis. In horses, phenoxybenzamine has been used for preventing or treating laminitis in its early stages and to treat secretory diarrheas.	pppbs.pdf
Pharmacology/Actions Alpha-adrenergic response to circulating epinephrine or norepi-nephrine is noncompetitively blocked by phenoxybenzamine. The eff ect of phenoxybenzamine has been described as a “chemical sympathectomy. ” No effects on beta-adrenergic receptors or on the parasympathetic nervous system occur. Phenoxybenzamine causes cutaneous blood ﬂow to increase, bu t little effects are noted on skeletal or cerebral blood ﬂow. Phenoxybenzamine can also block pupillary dilation, lid retraction, and nictitating membrane contraction. Both standing and supine blood pressures are decreased in humans. Pharmacokinetics No information was located on the pharmacokinetics of this agent in veterinary species. In humans, phenoxybenzamine is variably absorbed from the GI, with a bioavailability of 20-30%. Onset of action of the drug is slow (several hours) and increases over several days after regular dosing. Effects persist for 3-4 days after discon-tinuation of the drug. Phenoxybenzamine is highly lipid soluble and may accumulate in b ody fat. It is unknown if it crosses the placenta or is excreted into milk. The serum half-life is approximately 24 hours in humans. It is metabolized (dealkylated) and excreted in both the urine and bile. Contraindications/Precautions/Warnings Phenoxybenzamine is contraindicated in horses with clinical signs of colic and in patients when hypotension would be undesirable (e. g., shock, unless ﬂuid replacement is adequate). One author (Labato 1988) lists glaucoma and diabetes mellitus as contraindica-tions for the use of phenoxybenzamine in dogs. Phenoxybenzamine should be used with caution in patients with CHF or other heart disease as drug-induced tachycardia can occur. It should be used cautiously in patients with renal damage or cerebral/coronary arteriosclerosis. Adverse Effects Adverse effects associated with alpha-adrenergic blockade include: hypotension, hypertension, miosis, increased intraocular pressure, tachycardia, sodium retention, inhibition of ejaculation, and nasal congestion. Additionally, it can cause weakness/dizziness and GI ef-fects (e. g., nausea, vomiting). Constipation may occur in horses. Reproductive/Nursing Safety Phenoxybenzamine has been shown to cause abnormalities in the closure of the patent ductus in guinea pigs. In humans, the FDA cat-egorizes this drug as category C fo r 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 st udies in humans. ) It is unknown if phenoxybenzamine is excreted into milk. Overdosage/Acute Toxicity Overdosage of phenoxybenzamine may yield signs of postural hy-potension (dizziness, syncope), tachycardia, vomiting, lethargy, or shoc k. Treatment should consist of emptying the gut if the ingestion was r ecent and there are no contraindications to those procedures. Hypotension can be treated with ﬂuid support. Epinephrine is con-traindicated (see Drug Interactions) and most vasopressor drugs are ineff ective in reversing the effects of alpha-blockade. Intravenous norepinephrine (levarterenol) may be beneﬁcial, however, if clini-cal signs are severe. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving phenoxybenzamine and may be of signiﬁcance in veterinary patients: !TEPINEPHRINE : If used with drugs that have both alpha-and be-ta-adrenergic effects increased hypotension, vasodilatation or tac hycardia may result !TPHENYLEPHRINE : Phenoxybenzamine will antagonize the effects of alpha-adrenergic sympathomimetic agents !TRESERPINE : Phenoxybenzamine can antagonize the hypothermic effects of reserpine Doses !TDOGS: T o treat functional urethral obstruction by decreasing sympa-thetic-mediated urethral tone: a) 0. 25 mg/kg PO q12-24h or 2. 5- 20 mg (total dose) PO q12-24h (Lane 2000) b) 0. 25 mg/kg PO q12h (L ulich 2004) c) 0. 25-0. 5 mg/kg PO once or twice daily (Coates 2004) d) 5-15 mg (total dose) PO q12h (Bartges 2003a) Tre atment of hy per tension associated w ith pheochromocy toma: a) 0. 2-1. 5 mg/kg PO twice daily for 10-14 days before surgery; start at low end of dosage range and increase until blood pressure reduced to desired range. Propranolol (0. 15-0. 5 mg/kg PO three times a day) may be added to help control arrhythmias and hypertension. Beta-blockers must be used with phenoxybenzamine or severe hypertension may result. (Wheeler 1986) b) Initial dose is 0. 25 mg/kg PO twice daily, followed by gradual increase every few days until dog shows improvement or signs of hypotension. Maximum dosage is around 1. 5-2 mg/ kg twice daily. (Reusch 2006) For adjunctive treatment of endotoxicosis with appropriate an-timicrobial agents, steroids (if indicated), and other supportive care: a) 0. 25 -0. 5 mg/kg PO q6h (Coppock and Mostrom 1986) !TCATS: T o treat functional urethral obstruction by decreasing sympa-thetic-mediated urethral tone: a) 2. 5-7. 5 mg/cat PO once to twice daily (Osborne, Kruger et al. 2000) b) 1. 25 -7. 5 mg (total dose) PO q12-24h (Lane 2000) c) 2. 5-10 mg (total dose) PO q24h (Bartges 2003a) For short-term treatment of hypertension: a) 0. 5 mg/kg q12h (Spar kes 2003b) b) 2. 5 mg (total dose) q12h increasing by 2. 5 mg up to a maxi-mum of 10 mg (total dose) q12h PO (Brovido 2002) c) 2. 5-7. 5 mg per cat q8-12h (Waddell 2005) !THORSES: (Note : ARCI UCGFS Class 3 Drug) a) T o decrease urethral sphincter tone in horses with blad-der paresis: 0. 7 mg/kg PO 4 times a day (in combination with bethanechol at 0. 25-0. 75 mg/kg PO 2-4 times a day) (Schott II and Carr 2003) b) For adjunctive treatment of laminitis (developmental phase): 1 mg/kg IV q12h for 2 doses (Brumbaugh, Lopez et al. 1999) c) For treatment of profuse, watery diarrhea: 200-600 mg q12h (Clar k 1988)	pppbs.pdf
Monitoring T ! Clinical efﬁcacy (adequate urination, etc. ) T ! Blood pressure, if necessary/possible Client Information T ! Contact veterinarian if animal has continuing problems with weakness, appears dizzy, collapses after standing, or has persis-tent vomiting. GI upset may be reduced if the drug is given with meals. Chemistry/Synonyms An alpha-adrenergic blocking agent, phenoxybenzamine HCl oc-curs as an odorless, white crystalline powder with a melting range of 136°- 141° and a p K a of 4. 4. Approximately 40 mg are soluble in 1 m L of water and 167 mg are soluble in 1 m L of alcohol. Phenoxybenzamine may also be known as: SKF-688A, Diben yline®, Dibenzyran®, or Fenoxene®. Storage/Stability Phenoxybenzamine capsules should be stored at room temperature in well-closed containers. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None; contact compounding pharmacies for dosage form availability. The ARCI (Racing Commissioners International) has designated this drug as a class 3 substanc e. See the appendix for more information. HUMAN-LABELED PRODUCTS: Phenoxybenzamine HCl Capsules: 10 mg; Dibenzyline® (Wellspring); (Rx) PHENYLBUTAZONE (fen-ill-byoo-ta-zone) Butazolidin®, “Bute” NON-STEROIDAL ANTIINFLAMMATORY AGENT Prescriber Highlights TT NSAID used primarily in horses; little reason to use in dogs today TT Contraindications: Known hypersensitivity, history or preexisting hematologic or bone marrow abnormalities, preexisting GI ulcers, food producing animals TT Caution: Foals or ponies, preexisting renal disease, CHF, other drug allergies TT Adverse Effects: HORSES: Oral & GI erosions & ulcers, hypoalbuminemia, diarrhea, anorexia, & renal effects. DOGS: GI ulceration, sodium & water retention, dimin-ished renal blood ﬂow, blood dyscrasias. TT Do not give IM or SC; IA injections may cause seizures TT Drug Interactions; lab interactions Uses/Indications One manufacturer lists the following as the indications for phe-nylbutazone: “For the relief of inﬂammatory conditions associ-ated with the musculoskeletal system in dogs and horses. ” (Package Insert; Butaz olidin®—Coopers). It has been used primarily for the treatment of lameness in horses and, occasionally, as an analgesic/ antiinﬂammatory, antipyretic in dogs, cattle, and swine. Pharmacology/Actions Phenylbutazone has analgesic, antiinﬂammatory, antipyretic, and mild uricosuric properties. The proposed mechanism of action is by the inhibition of cyclooxygenase, thereby reducing prostaglan-din synthesis. Other pharmacologic actions phenylbutazone may induce inc lude reduced renal blood ﬂow and decreased glomerular ﬁltration rate, decreased platelet aggregation, and gastric mucosal damage. Pharmacokinetics Following oral administration, phenylbutazone is absorbed from both the stomach and small intestine. The drug is distributed throughout the body with highest levels attained in the liver, heart, lungs, kidneys, and blood. Plasma protein binding in horses exceeds 99%. Both phenylbutazone and oxyphenbutazone cross the placen-ta and are excreted into milk. The serum half-life in the horse ranges from 3. 5-6 hours, and like aspirin is dose-dependent. Therapeutic efﬁcacy, however, may last for more than 24 hours, probably due to the irreversible bind-ing of phenylbutazone to cyclooxygenase. In horses and other spe-cies, phenylbutazone is nearly completely metabolized, primarily to oxp henbutazone (active) and gamma-hydroxyphenylbutazone. Oxyphenbutazone has been detected in horse urine up to 48 hours after a single dose. Phenylbutazone is more rapidly excreted into alkaline than acidic urine. Other serum half-lives reported for animals are: Cattle ≈ 40-55 hr s; Dogs ≈ 2. 5-6 hrs; Swine ≈ 2-6 hrs. ; Rabbits ≈ 3 hrs. Contraindications/Precautions/Warnings Phenylbutazone is contraindicated in patients with a history of or preexisting hematologic or bone marrow abnormalities, preexisting GI ulcers, and in food producing animals or lactating dairy cattle. Cautious use in both foals and ponies is recommended because of increased incidences of hypoproteinemia and GI ulceration. Foals with a heavy parasite burden or that are undernourished may be more susceptible to developing adverse effects. Phenylbutazone may cause decreased renal blood ﬂow and so-dium and water retention, and should be used cautiously in animals with pre existing renal disease or CHF. Because phenylbutazone may mask clinical signs of lameness in horses f or several days following therapy, unethical individuals may use it to disguise lameness for “soundness” exams. States may have different standards regarding the use of phenylbutazone in track animals. Complete elimination of phenylbutazone in horses may take 2 months and it can be detected in the urine for at least 7 days following administration. Phenylbutazone is contraindicated in pa-tients demonstrating previous hypersensitivity reactions to it, and should be use d very cautiously in patients with a history of allergies to other drugs. Do not administer injectable preparation IM or SC as it is very irritating (swelling, to necrosis and sloughing). Intracarotid injec-tions may cause CNS stimulation and seizures. Adverse Effects While phenylbutazone is apparently a safer drug to use in horses and dogs than in people, serious adverse reactions can still occur. T oxic effects that have been reported in horses include oral and GI erosions and ulcers, hypoalbuminemia, diarrhea, anorexia, and re-nal effects (azotemia, renal papillary necrosis). Unlike humans, it does not appear that phenylbutazone causes much sodium and wa-ter retention in horses at usual doses, but edema has been reported. In do gs, however, phenylbutazone may cause sodium and water re-tention, and diminished renal blood ﬂow. Phenylbutazone-induced blood dyscrasias and hepatotoxicity have also been reported in dogs.	pppbs.pdf
The primary concerns with phenylbutazone therapy in humans in-clude its bone marrow effects (agranulocytosis, aplastic anemia), re nal and cardiovascular effects (ﬂuid retention to acute renal fail-ure), and GI effects (dyspepsia to perforated ulcers). Other serious co ncerns with phenylbutazone include hypersensitivity reactions, neurologic, dermatologic, and hepatic toxicities. IM or SC injection can cause swelling, necrosis and sloughing. Int racarotid injections may cause CNS stimulation and seizures. Therapy should be halted at ﬁrst signs of any toxic reactions (e. g., anorexia, oral lesions, depression, reduced plasma proteins, increased serum creatinine or BUN, leukopenia, or anemias). The use of sucralfate or the H 2 blockers (cimetidine, ranitidine) have been suggested for use in treating the GI effects. Misoprostol, a prostaglandin E analog, may also be useful in reducing the gastro-intestinal effects of phenylbutazone. Reproductive/Nursing Safety Although phenylbutazone has shown no direct teratogenic effects, rodent studies have demonstrated reduced litter sizes, increased neonatal mortality, and increased stillbirth rates. Phenylbutazone should, therefore, be used in pregnancy only when the potential beneﬁts of therapy outweigh the risks associated with it. In a system evaluating the safety of drugs in canine and feline pr egnancy (Papich 1989), this drug is categorized as 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. ) The safety of phenylbutazone during nursing has not been de-termined; use with caution. Overdosage/Acute Toxicity Manifestations (human) of acute overdosage with phenylbutazone include a prompt respiratory or metabolic acidosis with compensa-tory hyperventilation, seizures, coma, and acute hypotensive crisis. In an acute overdose, clinical signs of renal failure (oliguric, with proteinuria and hematuria), liver injury (hepatomegaly and jaun-dice), bone marrow depression, and ulceration (and perforation) of the GI tract may develop. Other symptoms reported in humans include: nausea, vomiting, abdominal pain, diaphoresis, neurologic and psychiatric symptoms, edema, hypertension, respiratory de-pression, and cyanosis. There were 47 exposures to phenylbutazone reported to the ASPCA A nimal Poison Control Center (APCC; www. apcc. aspca. org) during 2005-2006. In these cases 45 were dogs with 7 showing clinical signs. The remaining 2 reported cases consisted of 1 equine and 1 cat neither of which showed clinical signs. Common ﬁndings in dogs recorded in decreasing frequency included tremors, vomit-ing, anorexia, death and diarrhea. Standard overdose procedures should be followed (empty gut fol lowing oral ingestion, etc. ). Supportive treatment should be in-stituted as necessary and intravenous diazepam used to help con-trol seizures. Monitor ﬂuid therapy carefully, as phenylbutazone may cause ﬂuid r etention. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving phenylbutazone and may be of signiﬁcance in veterinary patients: !TFUROSEMIDE : Phenylbutazone may antagonize the increased renal blood ﬂow effects caused by furosemide !THEPATOTOXIC DRUGS : Phenylbutazone administered concurrently with hepatotoxic drugs may increase the chances of hepatotoxic-ity developing !TNSAIDS : Concurrent use with other NSAIDs may increase the po-tential for adverse reactions, however, some clinicians routinely use p henylbutazone concomitantly with ﬂunixin in horses. One study did not show synergistic actions with ﬂunixin, but did however, when phenylbutazone and ketoprofen were “stacked”. !TPENICILLAMINE : May increase the risk of hematologic and/or renal adverse reactions !TPENICILLIN G : Phenylbutazone may increase plasma half-life of penicillin G !TSULFONAMIDES : Phenylbutazone could potentially displace sul-fonamides from plasma proteins; increasing the risk for adverse eff ects !TWARFARIN : Phenylbutazone could potentially displace warfarin from plasma proteins; increasing the risk for bleeding Laboratory Considerations !TPhenylbutazone and oxyphenbutazone may interfere with thyroid function tests by competing with thyroxine at protein binding sites or by inhibiting thyroid iodine uptake. Doses !TDOGS: Note : With the release of safer and approved NSAIDs, it is this author's (Plumb) opinion that there is little reason to use this agent today in dogs. a) 14 mg/kg PO three times daily initially (maximum of 800 mg/day regardless of weight), titrate dose to lowest effective dose (Package Insert; Butazolidin®—Coopers) b) For analgesia: 1-5 mg/kg PO q8h (Taylor 2003a) !TCATTLE: Note: The Food and Drug Administration (FDA) has issued an order prohibiting the extralabel use of phenylbutazone animal and human drugs in female dairy cattle 20 months of age or older. In addition, many believe that phenylbutazone use in any food animal should be banned. a) 4 mg/kg IV or orally q24h (Koritz 1986) b) 4-8 mg/kg PO or 2-5 mg/kg IV (Howard 1986) c) 10-20 mg/kg PO, then 2. 5-5 mg/kg q24h or 10 mg/kg every 48 hours PO ( Jenkins 1987) !THORSES: a) 4. 4-8. 8 mg/kg q24hrs PO or 3-6 mg/kg q12h IV (Do not ex ceed 8. 8 mg/kg/day (Jenkins 1987) b) 1-2 grams IV per 454 kg (1000 lb. ) horse. Injection should be made slowly and with care. Limit IV administration to no more than 5 successive days of therapy. Follow with oral forms if necessary; or 2-4 grams PO per 454kg (1000 lb. ) horse. Do not exceed 4 grams/day. Use high end of dosage range initially, then titrate to lowest effective dose. (Package Insert; Butazolidin®—Coopers) c) For adjunctive treatment of colic (to reduce endotoxic ef-fects): 2. 2 mg/kg twice daily (Moore 1999) d) For adjunctive treatment of laminitis: 4. 4 mg/kg IV or PO twic e daily (Brumbaugh, Lopez et al. 1999) !TSWINE: a) 4 mg/kg IV or orally q24h (Koritz 1986) b) 4-8 mg/kg PO or 2-5 mg/kg IV (Howard 1986)	pppbs.pdf
TMonitoring T ! Analgesic/antiinﬂammatory/antipyretic effect T ! Regular complete blood counts with chronic therapy (especially in dogs). The manufacturer recommends weekly CBC's early in therapy, and biweekly with chronic therapy T ! Urinalysis &/or renal function parameters (serum creatinine/ BUN) with chronic therapy T ! Plasma protein determinations, especially in ponies, foals, and debilitated animals. Client Information T ! Do not administer injectable preparation IM or SC. T ! Approved for use in dogs and horses not intended for food. T ! he Food and Drug Administration (FDA) has issued an order prohibiting the extralabel use of phenylbutazone animal and hu-man drugs in female dairy cattle 20 months of age or older. T ! While phenylbutazone is not approved for use in beef cattle, and its use is discouraged, it is used. A general guideline for meat withdrawal times are: one dose = 30 days, 2 doses = 35 days, and 3 doses = 40 days. Contact FARAD for more information. Chemistry/Synonyms A synthetic pyrazolone derivative related chemically to aminopy-rine, phenylbutazone occurs as a white to off-white, odorless crys-talline powder that has a p K a of 4. 5. I t is very slightly soluble in water and 1 gram will dissolve in 28 m L of alcohol. It is tasteless at ﬁrst, but has a slightly bitter after-taste. Phenylbutazone may also be known as: butadiene, fenilbutazo-na, bute, or phenylbutazonum, and Phenylbute®. Storage/Stability Oral products should be stored in tight, child-resistant containers if possible. The injectable product should be stored in a cool place (46-56° F) or kept refrigerated. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Note : The Food and Drug Administration (FDA) has issued an order prohibiting the extralabel use of phenylbutazone animal and human drugs in female dairy cattle 20 months of age or older. Phenylbutazone Tablets: 100 mg, & 200 mg; Many trade name and gener ic products available. Approved for use in dogs. (Rx) Phenylbutazone Tablets: 1 gram; Many trade name and generic prod-ucts available. Approved for use in horses. Not to be used in animals used for f ood. (Rx) Phenylbutazone Oral Powder: 1 gram in 10 grams of powder to be mixed int o feed. Phenylbute® Powder (Phoenix), (Rx). Labeled for use in horses. Phenylbutazone Paste Oral Syringes: containing 6 grams or 12 grams/ syringe: Many trade name and generic products available. Approved for use in horses not intended for food purposes. (Rx) Phenylbutazone Injection: 200 mg/m L in 100 m L vials: Many trade name and ge neric products available. Approved for use in horses. Not to be used in horses intended for food. (Rx) HUMAN APPROVED PRODUCTS: None PHENYLEPHRINE HCL (SYSTEMIC) (fen-ill-ef-rin) Neo-Synephrine® ALPHA-ADRENERGIC AGONIST Prescriber Highlights TT Alpha-adrenergic used parenterally to treat hypotension without overt cardiostimulation TT Contraindications: Severe hypertension, ventricular tachy-cardia, or hypersensitive to it. Extreme Caution: Geriatric patients, patients with hyper th yroidism, bradycardia, par-tial heart block, or other heart disease TT Not a replacement for adequate volume therapy in pa-tients with shock TT Adverse Effects: Reﬂex bradycardia, CNS effects (excite-ment, restlessness, headache), & rarely, arrhythmias TT Blood pressure must be monitored TT Extravasation injuries with phenylephrine can be very serious Uses/Indications Phenylephrine has been used to treat hypotension and shock (after adequate volume replacement), but many clinicians prefer to use an agent that also has cardiostimulatory properties. Phenylephrine is recommended for use to treat hypotension secondary to drug overdoses or idiosyncratic hypotensive reactions to drugs such as phenothiazines, adrenergic blocking agents, and ganglionic block-ers. Its use to treat hypotension resulting from barbiturate or other CNS dep ressant agents is controversial. Phenylephrine has been used to increase blood pressure to terminate attacks of paroxysmal supraventricular tachycardia, particularly when the patient is also hypotensive. Phenylephrine has been used to both treat hypoten-sion and prolong the effects of spinal anesthesia. Ophthalmic uses of phenylephrine include use for some diag-nostic eye examinations, reducing posterior synechiae formation, and relie ving pain associated with complicated uveitis. It has been applied intranasally in an attempt to reduce nasal congestion. Pharmacology/Actions Phenylephrine has predominantly post-synaptic alpha-adrenergic effects at therapeutic doses. At usual doses, it has negligible beta effects, but these can occur at high doses. Phenylephrine's primary effects, when given intravenously, include peripheral vasoconstriction with resultant increases in diastolic and systolic blood pressures, small decreases in cardiac output, and an increase in circulation time. A reﬂex bradycardia (blocked by atropine) can occur. Most vascular beds are constricted (renal splanchnic, pulmonary, cutaneous), but coronary blood ﬂow is increased. Its alpha effects can cause contraction of the pregnant uterus and constriction of uterine blood vessels. Pharmacokinetics After oral administration, phenylephrine is rapidly metabolized in the GI tract and cardiovascular effects are generally unattainable via this route of administration. Following IV administration, pressor effects begin almost immediately and will persist for up to 20 min-utes. The onset of pressor action after IM administration is usually within 10-15 min utes, and will last for approximately one hour.	pppbs.pdf
It is unknown if phenylephrine is excreted into milk. It is metabo-lized by the liver, and the effects of the drug are also terminated by uptak e into tissues. Contraindications/Precautions/Warnings Phenylephrine is contraindicated in patients with severe hyperten-sion, ventricular tachycardia or those who are hypersensitive to it. It should be used with extreme caution in geriatric patients, pa-tients with hyperthyroidism, bradycardia, and partial heart block or with other heart disease. Phenylephrine is not a replacement for adequate volume therapy in patients with shock. Adverse Effects At usual doses, a reﬂex bradycardia, CNS effects (excitement, rest-lessness, headache) and, rarely, arrhythmias are seen. Blood pres-sure must be monitored to prevent hypertension. Extravasation injuries with phenylephrine can be very serious (necr osis and sloughing of surrounding tissue). Patient's IV sites should be routinely monitored. Should extravasation occur, inﬁl-trate the site (ischemic areas) with a solution of 5-10 mg phen-tolamine (Regitine®) in 10-15 m L of normal saline. A syringe with a ﬁne needle should be used to inﬁltrate the site with many injections. 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 fe tus, 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 if these agents are excreted in maternal milk; ex ercise caution when administering to a nursing patient. Overdosage/Acute Toxicity Overdosage of phenylephrine can cause hypertension, seizures, vomiting, paresthesias, ventricular extrasystoles, and cerebral hem-orrhage. There were 36 exposures to phenylephrine reported to the ASPCA A nimal Poison Control Center (APCC; www. apcc. aspca. org) during 2005-2006. In these cases all 36 were dogs with 12 showing clinical signs. Common ﬁndings in dogs recorded in de-creasing frequency included vomiting, inappropriate urination, hy-pertension, cyanosis and hypersalivation. Hypertension, if severe, can be treated by the administration of phentolamine (an alpha blocking agent). Should cardiac ar-rhythmias require treatment, use a beta-blocking drug such as pr opranolol. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving phenylephrine (system-ically) and may be of signiﬁcance in veterinary patients: !TALPHA-ADRENERGIC BLOCKERS (phentolamine, phenothiazines, phe-noxybenzamine ): Higher dosages of phenylephrine may be re-quired to attain a pressor effect if these agents have been used prior to therapy !TANESTHETICS, GENERAL (halogenated ): Phenylephrine potentially may induce cardiac arrhythmias when used with halothane anesthesia !TATROPINE (and other anticholinergics ): Block the reﬂex bradycar-dia caused by phenylephrine !TBETA-ADRENERGIC BLOCKERS : The cardiostimulatory effects of phenylephrine can be blocked !TDIGOXIN : Use with phenylephrine may cause increased myocar-dium sensitization !TMONAMINE OXIDASE (MAO) INHIBITORS (e. g., amitraz, possibly selegi-line): Monoamine oxidase (MAO) inhibitors should not be used with phenylephrine because of a pronounced pressor effect !TOXYTOCIN : When used concurrently with oxytocic agents, pressor effects may be enhanced !TSYMP ATHOMIMETIC AGENTS (epinephrine ): Tachycardia and serious arrhythmias are possible Doses !TDOGS: a) As a constant rate infusion: 1-3 mcg/kg/minute in either 0. 9% sodi um chloride or D 5W (Dhupa and Shaffron 1995) b) As a constant rate infusion: 0. 5-3 mcg/kg/minute. (Ko 2007) c) As a vasopressor in catastrophic stages of hypovolemic shock: 1- 3 mcg/kg/min (Rudloff 2002) !TCATS: a) As a constant rate infusion: 1-3 mcg/kg/minute in either 0. 9% sodi um chloride or D 5W (Dhupa and Shaffron 1995) b) As a constant rate infusion: 0. 5-3 mcg/kg/minute. (Ko 2007) c) As a vasopressor in catastrophic stages of hypovolemic shock: 1-3 mcg/kg/min (Rudloff 2002) !THORSES: (Note : ARCI UCGFS Class 3 Drug) a) 5 mg IV (Enos and Keiser 1985) Monitoring !TCardiac rate/rhythm !TBlood pressure, and blood gases if possible Client Information !TParenteral phenylephrine should only be used by professionals in a setting where adequate monitoring is possible Chemistry/Synonyms An alpha-adrenergic sympathomimetic amine, phenylephrine HCl occurs as bitter-tasting, odorless, white to nearly white crystals with a melting point of 145-146°C. It is freely soluble in water and alco-hol. The p H of the commercially available injection is 3-6. 5. Phenylephrine may also be known as: fenilefrina, phenylephri-num, or m-synephrine, AH-che w D®, Little Colds Decongestant for Infants & Children®, Lusonal®, Nasop®, Neo-Synephrine®, Sudogest PE®, and Sudafed PE®. Storage/Stability/Compatibility The injectable product should be stored protected from light. Do not use solutions if they are brown or contain a precipitate. Oxidation of the drug can occur without a color change. T o protect against oxidation, the air in commercially available ampules for injection is replaced with nitrogen and a sulﬁte added. Phenylephrine is reported to be physically compatible with all commonly used IV solutions and the following drugs: chloram-phenicol sodium succinate, dobutamine HCl, lidocaine HCl, potas-sium chloride, and sodium bicarbonate. While stated to be physi-cally incompatible with alkalis, it is stable with sodium bicarbonate solutions. Phenylephrine is reported to be incompatible with ferric salts, oxidizing agents, and metals.	pppbs.pdf
Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: There are oral combination products marketed as “cough” syrups for veterinary use that contain phenylephrine, pyrilamine (antihis-tamine), guaifenesin, sodium citrate, and sometimes ammonium chlorid e. The ARCI (Racing Commissioners International) has designated this drug as a class 3 substanc e. See the appendix for more information. HUMAN-LABELED PRODUCTS: Phenylephrine HCl Tablets: 10 mg (regular, chewable & orally disin-tegrating); AH-chew D ® (WE Pharm); Sudafed PE® (Pﬁzer); Sudogest PE® (Major); Nasop® (Hawthorn); (OTC or Rx) Phenylephrine HCl Oral Suspension/Liquid/Drops: 2. 5 mg/m L, 7. 5 mg/5 m L & 2 mg (as phenylephrine HCl)/m L; in 15 m L, 20 m L, 30 m L or 118 m L; AH-chew D® (WE Pharm); Little Colds Decongestant for Infants & Children® (Vetco); Lusonal® (Wra Ser); (OTC or Rx) Phenylephrine HCl Strips: 10 mg; Sudafed ® PE Quick-dissolve (Pﬁzer Consumer Healthcare); (OTC) Phenylephrine HCl Injection: 1% (10 mg/m L) in 1 m L and 5 m L vials and 1 m L Uni-Nest amps; Neo-Synephrine® (Sanoﬁ Winthrop); generic; (Rx) Phenylephrine is also available in ophthalmic and intranasal dosage forms and in combination with antihistamines, analgesics, deconges-tants, etc., for oral administration in humans. PHENYLPROPANOLAMINE HCL (fen-ill-proe-pa-nole-a-meen) PPA SYMPATHOMIMETIC Prescriber Highlights TT Sympathomimetic used primarily for urethral sphincter hypotonus TT Caution: Glaucoma, prostatic hypertrophy, hyperthyroid-ism, diabetes mellitus, cardiovascular disorders, or hypertension TT Adverse Effects: Restlessness, irritability, hypertension, & anorexia Uses/Indications Phenylpropanolamine is used chieﬂy for the treatment of urethral sphincter hypotonus and resulting incontinence in dogs and cats. It has also been used in an attempt to treat nasal congestion in small animals. Pharmacology/Actions While the exact mechanisms of phenylpropanolamine's actions are undetermined, it is believed that it indirectly stimulates both alpha-and beta-adrenergic receptors by causing the release of norepi-nephrine. Prolonged use or excessive dosing frequency can deplete norepine phrine from its storage sites, and tachyphylaxis (decreased response) may ensue. Tachyphylaxis has not been documented in dogs or cats when used for urethral sphincter hypotonus, however. Pharmacologic effects of phenylpropanolamine include in-creased vasoconstriction, heart rate, coronary blood ﬂow, blood pressur e, mild CNS stimulation, and decreased nasal congestion and appetite. Phenylpropanolamine can also increase urethral sphincter tone and produce closure of the bladder neck; its prin-ciple veterinary indications are because of these effects. Pharmacokinetics No information was located on the pharmacokinetics of this agent in veterinary species. In humans, phenylpropanolamine is readily absorbed after oral administration and has an onset of action (nasal decongestion) of about 15-30 minutes with duration of effect last-ing approximately 3 hours (regular capsules or tablets). Phenylpropanolamine is reportedly distributed into various tis-sues and ﬂuids, including the CNS. It is unknown if it crosses the placenta or enters milk. The drug is partially metabolized to an ac-tive metabolite, but 80-90% is excreted unchanged in the urine within 24 hour s of dosing. The serum half-life is approximately 3-4 hours. Contraindications/Precautions/Warnings Phenylpropanolamine should be used with caution in patients with glaucoma, prostatic hypertrophy, hyperthyroidism, diabetes melli-tus, cardiovascular disorders, or hypertension. Adverse Effects Most likely side effects include restlessness, irritability, urine reten-tion, tachycardia, and hypertension. Anorexia may be a problem in some animals. R are reports of “stroke” have occurred in dogs given therapeutic dosages of phenylpropanolamine. Reproductive/Nursing Safety Phenylpropanolamine may cause decreased ovum implantation; uncontrolled clinical experience, however, has not demonstrated any untoward effects during pregnancy. Overdosage/Acute Toxicity Clinical signs of overdosage may consist of an exacerbation of the adverse effects listed above or, if a very large over-dose, severe car-diovascular (hypertension to rebound hypotension, bradycardias to tachy cardias, and cardiovascular collapse) or CNS effects (stimula-tion to coma) can be seen. There were 255 exposures to phenylpropanolamine reported to the ASPCA Animal Poison Control Center (APCC; www. apcc. aspca. org) during 2005-2006. In these cases 250 were dogs with 59 showing c linical signs. The remaining 5 cases were cats that showed no clinical signs. Common ﬁndings in dogs recorded in decreasing frequency included hypertension, piloerection, vomiting, bradycar-dia and mydriasis. A dog ingesting 48 mg/kg of PPA has been reported (Crandell and Ware 2005). Ventricular tachycardia and regions of myocardial necrosis were noted. All abnormalities resolved within 6 months. If the overdose was recent, empty the stomach using the usual precau tions and administer charcoal and a cathartic. Treat clinical signs supportively as they occur. Do not use propranolol to treat hypertension in bradycardic patients and do not use atropine to treat bradycardia. Hypertension may be managed with a phenothi-azine (e. g., acepromazine—very low dose such as 0. 02 mg/kg IV or IM). If phenothiazines do not normalize blood pressure, consider using a CRI of nitroprusside. Contact an animal poison control center for further guidance.	pppbs.pdf
Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving phenylpropanolamine and may be of signiﬁcance in veterinary patients: T ! HALOTHANE : An increased risk of arrhythmias developing can oc-cur if phenylpropanolamine is administered to patients who have rece ived cyclopropane or a halogenated hydrocarbon anesthetic agent. Propranolol may be administered should these occur. T ! MONAMINE OXIDASE (MAO) INHIBITORS (e. g., amitraz, possibly sele-giline ): Phenylpropanolamine should not be given within two weeks of a patient receiving monoamine oxidase inhibitors T ! NSAIDS : An increased chance of hypertension if given concomi-tantly with NSAIDs, including aspirin T ! RESERPINE : An increased chance of hypertension if given concomitantly T ! SYMP ATHOMIMETIC AGENTS, OTHER : Phenylpropanolamine should not be administered with other sympathomimetic agents (e. g., ephedrine) as increased toxicity may result T ! TRICYCLIC ANTIDEPRESSANTS (clomipramine, amitriptyline, etc. ): An increased chance of hypertension if given concomitantly Doses T ! DOGS: For urethral sphincter hypotonus: a) 12. 5-50 mg PO q8h (Labato 1988), (Polzin and Osborne 1985), (Bartg es 2003a) b) Using the time-release 75 mg capsules: Dogs weighing less than 40 lbs: 1/2 capsule PO daily. Dogs 40-100 lbs: 1 capsule PO daily. Dogs weighing >100 lbs: 1. 5 capsules PO per day. (Label information; Cystolamine® —VPL) c) 1-1. 5 mg/kg PO two to three times a day controls 74-92% of do gs with primary sphincter mechanism incontinence. Over half of dogs not responding to regular PPA will respond to sustained-release PPA. Incontinence control becomes less over time in some dogs. (Chew 2007) d) 5-50 mg per dog PO q8h or 1. 5 mg/kg PO q8h-12h (Ver-nau 2006) For re trograde ejaculation: a) 3-4 mg/kg PO twice daily may be tried. (Fontbonne 2007) T ! CATS: For urethral sphincter hypotonus: a) 12. 5 mg PO q8h (Labato 1988), (Polzin and Osborne 1985) b) 1. 5 mg/kg PO q8h (Bartg es 2003a) c) 1. 1-2. 2 mg/kg PO two to three times daily (Lane 2003) Monitoring T ! Clinical effectiveness T ! Adverse effects (see above) T ! Blood pressure Client Information T ! In order for this drug to be effective, it must be administered as directed by the veterinarian; missed doses will negate its effect. It may take several days for the full beneﬁt of the drug to take place. T ! Contact veterinarian if the animal demonstrates ongoing changes in behavior (restlessness, irritability) or if incontinence persists or increases. Chemistry/Synonyms A sympathomimetic amine, phenylpropanolamine HCl occurs as a white crystalline powder with a slightly aromatic odor, a melting range between 191°-194°C, and a p K a of 9. 4. One gram is soluble in approximately 1. 1 m L of water or 7 m L of alcohol. Phenylpropanolamine may also be known as: (+/-)-norephed-rine, dl-norephedrine or PPA, Cysto lamine®, Proin®, Propalin®, Uricon®, and Uriﬂex-PT®. Storage/Stability/Compatibility Store phenylpropanolamine products at room temperature in light-resistant, tight containers. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Phenylpropanolamine Chewable Tablets: 25 mg, 50 mg, & 75 mg; Proin® (PRN Pharmacal), Propalin® (Vetoquinol), Uriﬂex-PT® (But-ler), Uricon® (Neogen); (Rx). Labeled for use in dogs. Pheny lpropanolamine Timed-Release Capsules: 75 mg; Cysto lamine® (VPL); (Rx). Labeled for use in dogs. Phenylpropanolamine oral solution: 25 mg/m L in 60 m L bottles; Proin® D rops (PRN Pharmacal) (Rx); 50 mg/m L in 30 m L and 100 m L bottles; (Rx). Labeled for use in dogs. The ARCI (Racing Commissioners International) has designated this drug as a class 3 substanc e. See the appendix for more information. In the USA, phenylpropanolamine is classiﬁed as a list 1 chemical (drugs that can be used as precursors to manufacture methamphet-amine) and in some states it may be a controlled substance or have other rest rictions placed upon its sale. Be alert to persons desiring to purchase this medication. HUMAN-LABELED PRODUCTS: Note : Because of potential adverse effects in humans, phenylpropa-nolamine has been removed from the US market for human use. PHENYTOIN SODIUM (fen-i-toe-in) Dilantin® ANTICONVULSANT, ANTIDYSRHYTHMIC Prescriber Highlights TT Rarely used (in USA) for seizures in small animals; sus-tained release formulations may be useful (not available in USA) TT Potentially useful as a treatment for ventricular dysrhyth-mias in horses or digoxin-induced arrhythmias in dogs or horses; may be useful in cats with m yok emia and neuro-myotonia TT Contraindications: Hypersensitivity; IV use contraindi-cated for 2nd or 3rd degree heart block, sinoatrial block, Adams-Stokes syndrome, or sinus bradycardia. TT Adverse Effects: DOGS: Anorexia & vomiting, ataxia, se-dation, gingival hyperplasia, hepatotoxicity. CATS: Ataxia, sedation, anorexia, der mal atroph y syndrome, thrombo-cytopenia TT Potentially teratogenic; many drug interactions possible	pppbs.pdf
Uses/Indications Because of its undesirable pharmacokinetic proﬁles in dogs and cats, the use of phenytoin as an anticonvulsant for long-term treat-ment of epilepsy has diminished over the years and few use it today fo r this purpose. It remains, however, of interest due to its efﬁcacy in humans, and the potential for sustained-release products to be marketed for dogs. Until then prerequisites for successful therapy in dogs include: a motivated client who will be compliant with multiple daily dosing and willing to assume the ﬁnancial burden of high dose phenytoin therapy and therapeutic drug monitoring expenses. Although not commonly used, phenytoin has been employed as an o ral or IV antiarrhythmic agent in both dogs and cats. It has been described as the drug of choice for digitalis-induced ventricu-lar arrhythmias in dogs. A cat with myokemia and neuromyotonia was t reated with phenytoin in a recent case report (Galano, Olby et al. 2005). Phenytoin has been studied as a treatment for ventricular dys-rhythmias in horses and preliminary reports demonstrate efﬁcacy (W ijnberg and Ververs 2004). It has been suggested that phenytoin be used as adjunctive treat-ment of hypoglycemia secondary to hyperinsulinism, but appar-ently, little clinical beneﬁt has resulted from this therapy. Pharmacology/Actions The anticonvulsant actions of phenytoin are thought to be caused by the promotion of sodium efﬂux from neurons, thereby inhibit-ing the spread of seizure activity in the motor cortex. It is believed that e xcessive stimulation or environmental changes can alter the sodium gradient, which may lower the threshold for seizure spread. Hydantoins tend to stabilize this threshold and limit seizure propa-gation from epileptogenic foci. The cardiac electrophysiologic effects of phenytoin are similar (not id entical) to that of lidocaine (Group 1B). It depresses phase O slightly and can shorten the action potential. Its principle cardiac use is in the treatment of digitalis-induced ventricular arrhythmias. Phenytoin can inhibit insulin and vasopressin (ADH) secretion. Pharmacokinetics After oral administration, phenytoin is nearly completely absorbed in humans, but in dogs, bioavailabilities may only be about 40%. Phenytoin is well distributed throughout the body and about 78% bound to plasma proteins in dogs (vs. 95% in humans). Protein binding may be reduced in uremic patients. Small amounts of phenytoin may be excreted into the milk and it readily crosses the placenta. The drug is metabolized in the liver with much of the drug con-jugated to a glucuronide form and then excreted by the kidneys. Phen ytoin will induce hepatic microsomal enzymes, which may enhance the metabolism of itself and other drugs. The serum half-life (elimination) differences between various species are striking. Phenytoin has reported half-lives of 2-8 hours in dogs, 8 hours in horses, 15-24 hours in humans, and 42-108 hours in cats. Because of the pronounced induction of hepatic enzymes in dogs, phenytoin metabolism is increased with shorter half-lives within 7-9 days after starting treatment. Puppies possess smaller volumes of distribution and shorter elimination half-lives (1. 6 hours) than adult dogs. Contraindications/Precautions/Warnings Some data suggest that additive hepatotoxicity may result if phe-nytoin is used with either primidone or phenobarbital. Weigh the pot ential risks versus the beneﬁts before adding phenytoin to either of these drugs in dogs. Phenytoin is contraindicated in patients known to be hypersen-sitive to it or other hydantoins. Intravenous use of the drug is con-traindicated in patients with 2nd or 3rd degree heart block, sinoa-trial block, Adams-Stokes syndrome, or sinus bradycardia. Adverse Effects Adverse effects in dogs associated with high serum levels include anorexia and vomiting, ataxia, and sedation. Liver function tests should be monitored in patients on chronic therapy as hepatotox-icity (elevated serum ALT, decreased serum albumin, hepatocellu-lar hypertrophy and necrosis, hepatic lipidosis, and extramedullary hemat opoiesis) have been reported. Gingival hyperplasia has been reported in dogs receiving chronic therapy. Oral absorption may be enhanced and GI upset decreased if given with food. Cats exhibit ataxia, sedation, and anorexia secondary to accu-mulation of phenytoin and high serum levels. Cats have also been re ported to develop thrombocytopenia and a dermal atrophy syn-drome secondary to phenytoin. High plasma concentrations of phenytoin in horses can cause ex citement and recumbency. 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 be neﬁts 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 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. ) Phenytoin is excreted in maternal milk. Because of the potential fo r serious adverse reactions in nursing offspring, consider whether to accept the risks, discontinue nursing or to discontinue the drug. Overdosage/Acute Toxicity Clinical signs of overdosage may include sedation, anorexia, and ataxia at lower levels, and coma, hypotension, and respiratory depression at higher levels. Treatment of overdoses in dogs is de-pendent on the severity of the clinical signs demonstrated, since do gs rapidly clear the drug. Severe intoxications should be handled supportively. Drug Interactions !TCHLORAMPHENICOL : A case report of chloramphenicol increasing the serum half-life of phenytoin from 3 to 15 hours in a dog has been reported. Note : The following interactions are from the human literature: because of the signiﬁcant differences in pharmacokinetics in dogs and cats, their veterinary signiﬁcance will be variable. This list includes only agents used in small animal medicine, many more agents have been implicated in the human literature: !TLITHIUM : The toxicity of lithium may be enhanced. !TMEPERIDINE : Phenytoin may decrease the analgesic properties me-peridine, but enhance its toxic effects. !TPHENOBARBITAL/PRIMIDONE : The pharmacologic effects of primi-done may be altered. Some data suggest that additive hepatotox-icity may result if phenytoin is used with either primidone or phe nobarbital. Weigh the potential risks versus the beneﬁts be-fore adding phenytoin to either of these drugs in dogs. The f ollowing agents may increase the effects of phenytoin : !!ALLOPURINOL !!CHLORAMPHENICOL !!CHLORPHENIRAMINE	pppbs.pdf
T!!CIMETIDINE !!DIAZEPAM !!ETHANOL !!ISONIAZID !!PHENYLBUTAZONE !!SALICYLATES !!SULFONAMIDES !!TRIMETHOPRIM !!VALPROIC ACID The following agents may decrease the pharmacologic activity of phenytoin : !!ANTACIDS !!ANTINEOPLASTICS !!BARBITURATES ! !CALCIUM (DIETAR Y AND GLUCONATE) !!DIAZOXIDE !!ENTERAL FEEDINGS !!FOLIC ACID !!NITROFURANTOIN !!PYRIDOXINE !!THEOPHYLLINE Phenytoin may decrease the pharmacologic activity of the following agents : !!CORTICOSTEROIDS !!DISOPYRAMIDE !!DOPAMINE ! !DOXYCYCLINE !!ESTROGENS !!FUROSEMIDE !!QUINIDINE Doses !TDOGS: For treatment of seizures: a) 15-40 mg/kg PO three times daily (Morgan 1988) b) 20-35 mg/kg three times daily (Bunch 1986) c) Initially, 8. 8-17. 6 mg/kg PO in divided doses, then gradually increase or decrease dose to maintain control. May take sev-eral days for seizure control to be attained. (Package insert; Dilant in® Veterinary—Parke-Davis) (Plumb's Note ): Because of the extremely fast half-life of phe-nytoin in dogs, it is unlikely that this dosage regimen (“c”) wil l attain serum levels of 10-20 micrograms/m L which are thought to be necessary for adequate seizure control. For treatment of ventricular arrhythmias: a) Up to 10 mg/kg IV in increments of 2-4 mg/kg or 20-35 mg/kg PO thre e times daily (Moses 1988) b) 10 mg/kg slowly IV; 30-50 mg/kg PO q8h (Ware 2003) Fo r treatment (or prophylaxis) of digitalis intoxication: a) 50 mg/kg PO q8h; long-term use may cause increases in ser um alkaline phosphatase and increased hepatic cell size. (Kittleson 2006c) For treatment of hypoglycemia secondary to tumor: a) 6 mg/kg PO two to three times daily (Morgan 1988) !TCATS: Note : Because cats can easily accumulate this drug and develop clinical signs of toxicity, the use of phenytoin is very controver-sial in this species. Diligent monitoring is required. a) For treatment of ventricular arrhythmias: 2-3 mg/kg PO q24h (W ilcke 1985) b) For treatment of seizures: 2-3 mg/kg daily PO; 20 mg/kg per week (Bunch 1986) !THORSES: (Note : ARCI UCGFS Class 4 Drug) a) For seizures: 2. 83-16. 43 mg/kg PO q8h to obtain serum lev-els from 5-10 micrograms/m L. Suggest monitoring serum lev els to adjust dosage. (Kowalczyk and Beech 1983) b) For digoxin induced arrhythmias: 10-22 mg/kg PO q12h. Ad verse effects are muscle fasciculations and sedation. (Mogg 1999) c) For treatment of ventricular dysrhythmias: For persistent ve ntricular extra systoles or ventricular tachycardia where conventional treatment has failed: 20 mg/kg PO q12h ini-tially for the ﬁrst 3-4 doses, followed by a maintenance dose of 10-15 mg/kg PO q12h. Suggest monitoring plasma con-centrations. (Wijnberg and Ververs 2004) Monitoring !TLevel of seizure control; sedation/ataxia !TBody weight (anorexia) !TLiver enzymes (if chronic therapy) and serum albumin !TSerum drug levels if signs of toxicity or lack of seizure control Client Information !TNotify veterinarian if patient becomes anorexic, lethargic, ataxic, or seizures are not adequately controlled. !The importance of regular dosing is imperative for successful therapy. Chemistry/Synonyms A hydantoin-derivative, phenytoin sodium occurs as a white, hy-groscopic powder which is freely soluble in water and warm pro-pylene glycol, and soluble in alcohol. Because phenytoin sodium slowly undergoes partial hydrolysis in aq ueous solutions to phenytoin (base) with the resultant solu-tion becoming turbid, the commercial injection contains 40% pro-pylene glycol and 10% alcohol. The p H of the injectable solution is app roximately 12. Phenytoin sodium is used in the commercially available cap-sules (both extended and prompt) and the injectable preparations. Phen ytoin (base) is used in the oral tablets and suspensions. Each 100 mg of phenytoin sodium contains 92 mg of the base. Phenytoin may also be known as: diphenylhydantoin, DPH, fen-itoina, phenantoinum, or phenytoinum, Dilant in®, and Phenytek®. Storage/Stability/Compatibility Store capsules at room temperature (below 86°F) and protect from light and moisture. Store phenytoin sodium injection at room temperature and protect from freezing. If injection is frozen or re-frigerated, a precipitate may form which should resolubolize when warme d. A slight yellowish color will not affect either potency or efﬁcacy, but do not use precipitated solutions. Injectable solutions at less than a p H of 11. 5 will precipitate. No problems with adsorp-tion to plastic have been detected thus far. Phenytoin sodium injection is generally physically incompatible with most IV solutions (upon standing) and drugs. It has been suc-cessfully mixed with sodium bicarbonate and verapamil HCl.	pppbs.pdf
Because an infusion of phenytoin sodium is sometimes desir-able, several studies have been performed to determine whether such a procedure can be safely done. The general conclusions and recommendations of these studies are: 1) use either normal saline or lactated Ringer's; 2) a concentration of 1 mg/m L phenytoin be used; 3) start infusion immediately and complete in a relatively short time; 4) use a 0. 22 µm in-line IV ﬁlter; 5) watch the admix-ture carefully. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 4 substance. See the appendix for more information. HUMAN-LABELED PRODUCTS: Phenytoin Sodium Extended-Release Capsules: 30 mg, 100 mg, 200 mg and 300 mg; Dilantin Kapseals® (Parke-Davis); Phenytek® (Bertek); generic, (Rx) Phenytoin Oral Suspension: 25 mg/m L in 240 m L; Dilantin-125® (P arke-Davis); generic (Alpharma); (Rx) Phenytoin Sodium, Prompt Capsules: 100 mg (92 mg phenytoin); gener ic; (Rx) Phenytoin Tablets: 50 mg (chewable); Dilantin® I nfa-Tabs (Parke-Davis); (Rx) Phenytoin Sodium Injection: 50 mg/m L (46 mg/m L phenytoin) in 2 m L and 5 m L amps, 2 m L Dosettes & vials; generic (Elkins-Sinn); (Rx) PHEROMONES (fer-i-mones) Feliway®, D. A. P. ® PHEROMONE BEHA VIOR MODIFIER Prescriber Highlights TT Commercially available pheromones may be useful in CATS for urine marking or spraying, vertical scratching, avoidance of social contact, loss of appetite, stressful situations, or inter-cat aggression; DOGS: Behaviors as-sociated with fear or stress or for calming in new envi-ronments or situations; HORSES: Alleviating stressful situations TT May need adjunctive therapy (behavior modiﬁcation, drug therapy) for negative behaviors TT Dog/Cat products are administered via the environment; Equine product administered intranasally TT Appears to be safe Uses/Indications In cats, FFP may be useful in treating urine marking or spraying, vertical scratching, avoidance of social contact, loss of appetite, stressful situations, or inter-cat aggression. Behavioral modiﬁcation and/or concomitant drug therapy may be required. In dogs, DAP may be useful in treating behaviors associated with fear or stress (e. g., separation anxiety, destruction, excessive bark-ing, house soiling, licking, phobias) or calming animals in new en-vironments or situations. In horses, EAP may be useful in alleviating stressful situations (e. g., t ransport, shoeing, clipping, new environments, training). Pharmacology/Actions Appeasing pheromones produced during nursing are thought to ex-ist with all mammals. They are detected by the Jacobson's organ or vome ro-nasal organ (VNO). The VNO is more sensitive in young animals, but is believed to continue to function in older animals as well. It is not well understood what neurotransmitters or neu-rochemical processes are involved for pheromones to exhibit their effe cts. In most animals, pheromones have a general calming effect. In cats, the F3 facial pheromone is thought to inhibit urine marking, encourage feeding, and enhance exploratory behaviors in unfamiliar situations. The F4 pheromone is a so-called allomarking pheromone that calms and familiarizes the cat with its surroundings. Pharmacokinetics No information located. Contraindications/Precautions/Reproductive Safety No information located. Adverse Effects No signiﬁcant adverse effects were located for these products and are unlikely to occur. Overdosage/Acute Toxicity No speciﬁc animal toxicity data was located. Although the ingredi-ents in these products are not thought toxic, the manufacturer rec-ommends that humans accidentally exposed resulting in an adverse react ion should report to a physician or poison control center. Drug Interactions None were located. Effects may be reduced or negated by concur-rent use of drugs that cause CNS stimulation. Laboratory Considerations No information was located. Doses T ! CATS: a) Diffusers: Diffuser vial lasts approximately 4 weeks and cov-ers 500-650 sq. ft. Plug diffuser into electric outlet in the room most often used by the animal. Do not cover diffuser or place behind or under furniture. When plugged in, do not touch diffuser with wet hands or metal objects. Do not touch diffuser with uncovered hands during, or immediately after use. May require up to 72 hours to saturate area, so effects may not be immediate. (Label Information; Feliway® Diffus-er—VPL) b) Spray: Do not spray directly on cats. Pump spray approxi-mately 4 inches from site, 8 inches from the ﬂoor. One spray per ap plication site. Clean urine marks with clear water only. Urine marks and prominent objects (furniture, window or doorframes) should be sprayed 1-2 times daily for 30 days. If cat is observed rubbing its own facial pheromones onto a spot, treatment is no longer necessary at that location. Maintenance sprays every 2-3 days may be required. Inter-cat aggression problems may require behavior modiﬁcation and concomitant drug therapy. (Label Information; Feliway® Spray —VPL) T ! DOGS: a) Diffusers: Diffuser vial lasts approximately 4 weeks and cov-ers 500-650 sq. ft. Plug diffuser into electric outlet in the room most often used by the animal. Do not cover diffuser or place behind or under furniture. When plugged in, do not touch diffuser with wet hands or metal objects. Do not touch diffuser with uncovered hands during, or immediately after	pppbs.pdf
use. May require up to 72 hours to saturate area, so effects may not be immediate. (Label Information; Feliway® Diffus-er—VPL) b) Spray: Do not spray directly on dogs. May spray in car, kennels, crates, carriers, or on neck bandanas. Spray ap-proximately 20 minutes prior to travel, etc. When entering unfamiliar places/r ooms, spray twice day in the area. (Label Information; D. A. P. ® Spray —VPL) T ! HORSES: a) Administer 2 sprays into each nostril 1/2 hour before antici-pated stress or event. After administration, keep horse in a non-stressful environment for 1/2 hour to achieve best re-sults. (Label Information; Modipher EQ ® Spray —VPL) Monitoring T ! Clinical efﬁcacy Chemistry Mammalian pheromones are fatty acids. Dog appeasing pheromone (DAP) is a synthetic derivative of bitch intermammary pheromone. Feline pheromone is a synthetic analog of feline cheek gland secre-tions (feline facial pheromone; FFP). The commercially available prod uct available in the USA is an analog of the F3 fraction of the pheromone. Equine appeasing pheromone (EAP) is derived from maternal pheromones found in the “wax area” close to the mam-mae of nursing mares. Storage/Stability/Compatibility Unless otherwise labeled, store at room temperature and do not mix with other ingredients or substances. Keep products out of reach of children. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Feline Facial Pheromone (FFP-F3 fraction) Diffuser (electric diffuser plus a 2% FFP vial) 48 m L vial; Feliway® Diffuser (Farnam); Comfort Zone® Feline (Farnam); (OTC) Feline Facial Pheromone (FFP-F3 fraction) Spray 10% 75 m L bot-tle; Feliway® Spr ay (VPL); Comfort Zone® Spray for Cats (Farnam); (OTC) Dog Appeasing Pheromone (DAP) Diffuser (electric diffuser plus a 2% DAP vial) 48 m L vial; D. A. P. ® Diffuser (VPL); (OTC) Dog Appeasing Pheromone 2% (DAP) Spray 60 m L bottle; D. A. P. ® Sp ray (VPL); Comfort Zone® Spray for Dogs (Farnam); (OTC) Dog Appeasing Pheromone (DAP) 48 m L with or without plug in adapte r; Comfort Zone® Canine (Farnam); (OTC) Dog Appeasing Pheromone Collar; D. A. P. ® Collar (VPL), (OTC) Equine Appeasing Pheromone (EAP) 0. 1% Spray 7. 5 m L bottle, Mo-dipher EQ® Mist with E. A. P. (VPL); (OTC) A product (not currently available in the USA) called Feli Fr iend® contains a synthetic F4 fraction of FFP. HUMAN-LABELED PRODUCTS: None PHOSPHATE, PARENTERAL POTASSIUM PHOSPHATE SODIUM PHOSPHATE ELECTROLYTE Prescriber Highlights TT For treatment or prevention of hypophosphatemia TT Contraindications: Hyperphosphatemia, hypocalcemia, oliguric renal failure, or if tissue necrosis is present; Potassium phosphate contraindicated if hyperkalemia present; sodium phosphate if hypernatremia present TT Caution: Cardiac (esp. if receiving digoxin) or renal disease TT Adverse Effects: Hyperphosphatemia, resulting in hy-pocalcemia, hypotension, renal failure or soft tissue min-eralization; hyperkalemia or hypernatremia are possible TT Dilute before giving IV Uses/Indications Phosphate is useful in large volume parenteral ﬂuids to correct or prevent hypophosphatemia when adequate oral phosphorous in-take is not possible. Hypophosphatemia may cause hemolytic ane-mia, thrombocytopenia, neuromuscular and CNS disorders, bone and joint pain, and decompensation in patients with cirrhotic liver disease. There is some controversy whether “a low phos” indicates that treatment is necessary. Pharmacology/Actions Phosphate is involved in several functions in the body, including calcium metabolism, acid-base buffering, B-vitamin utilization, bone deposition, and several enzyme systems. Pharmacokinetics Intravenously administered phosphate is eliminated via the kid-neys. It is glomerularly ﬁltered, but up to 80% is reabsorbed by the tubules. Contraindications/Precautions/Warnings Both potassium and sodium phosphate are contraindicated in pa-tients with hyperphosphatemia,hypocalcemia,oliguric renal failure, or if t issue necrosis is present. Potassium phosphate is contraindi-cated in patients with hyperkalemia. It should be used with caution in patients with cardiac or renal disease. Particular caution should be used in using this drug in patients receiving digitalis therapy. Sodium phosphate is also contraindicated in patients with hype rnatremia. Adverse Effects Overuse of parenteral phosphate can result in hyperphosphatemia, resulting in hypocalcemia (refer to the Overdose section for more information). Phosphate therapy can also result in hypotension, renal failure or soft tissue mineralization. Either hyperkalemia or hypernatremia may result in susceptible patients. 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. )	pppbs.pdf
It is not known whether this drug is excreted in maternal milk. It is unlikely to be of concern. Overdosage/Acute Toxicity Patients developing hyperphosphatemia secondary to intrave-nous therapy with potassium phosphate should have the infusion sto pped and be given appropriate parenteral calcium therapy to re-store serum calcium levels. Serum potassium should be monitored and tr eated if required. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving phosphates and may be of signiﬁcance in veterinary patients: !TALUMINUM and CALCIUM SALTS (oral) and SEVELAMER : May reduce phosphorus levels !TANGIOTENSIN CONVERTING ENZYME INHIBITORS (ACE Inhibitors ): May cause potassium retention. When used with potassium products such as potassium phosphate, hyperkalemia can result. !TDIGOXIN : Potassium salts (potassium phosphate) must be used very cautiously in patients on digitalis therapy and should not be used in digitalized patients with heart block !TPOTASSIUM SPARING DIURETICS (e. g., spironolactone ): May cause po-tassium retention. When used with potassium products such as potassi um phosphate, hyperkalemia can result. Doses Both sodium and potassium phosphate injections must be diluted before intravenous administration. !TDOGS & CAT S: For hypophosphatemia: a) For signiﬁcant hypophosphatemia (<1. 5 mg/dl) in patients unable to receive oral supplementation: 0. 06-0. 18 m M/kg IV given over 6 hours (0. 01-0. 03 m M/kg/hr). Recheck se-rum phosphorous before continuing. Usually may stop ther-apy when serum phosphorous level reaches 2 mg/dl. (Hardy and A dams 1989) b) Cats: For severe hypophosphatemia in diabetic ketoacidosis: Using potassium phosphate give 0. 01-0. 03 m M/kg/hr for 6 hours IV. Recheck serum phosphorous before continuing. In order to provide enough potassium without inducing hyper-phosphatemia, supply 50-75% of patient's potassium using potassi um chloride and the remainder as potassium phos-phate. (Peterson and Randolph 1989) c) Correct underlying cause if possible. If serum phosphorus co ncentration is >1. 5 mg/dl and unlikely to decrease further, no treatment is usually necessary. If <1. 5 mg/dl, clinical signs or hemolysis present, treat. Also, consider treating during the ﬁrst 24 hours of therapy for DKA. Goal of therapy is to main-tain serum phosphorus >2 mg/dl without causing hyper-phosphatemia. Oral phosphate supplementation is preferred; eithe r a buffered phosphate laxative (e. g., Phospho-Soda), balanced commercial diet or milk. Severe hypophosphatemia is treated with intravenous therapy: Using either potassium phosphate (3 m Mol phosphate/m L and 4. 4 m Eq potassium/ m L) or sodium phosphate (if potassium supplementation is contraindicated; 3 m Mol phosphate/m L and 4 m Eq sodium/ m L) give 0. 01-0. 03 m Mol/kg/hr preferably by CRI. Avoid hyperphosphatemia. Monitor serum phosphorus every 6-8 hours and adjust dose. (Nelson and Elliott 2003b) d) In treating diabetic ketoacidosis, 1/3 of the IV potassium should b e administered as potassium phosphate, particularly in small dogs and cats who are most susceptible to hemolysis caused by hypophosphatemia. Use caution as over supple-mentation of phosphorus can result in metastatic calciﬁca-tion and hypocalcemia. (Greco 2007b) e) Cats with DKA and a serum phosphorus of < 2 mg/d L: CRI of potassium phosphate at 0. 03-0. 06 m Mol/kg/hr; severe cases of hypophosphatemia (< 1 mg/d L) may require doses as high as 0. 12-0. 2 m Mol/kg/hr. Recheck phosphorus after 6-12 hours. Alternatively may provide half the potassium requirements as KCl and half as K Phos. (Waddell 2007b) Monitoring !TSerum inorganic phosphate (phosphorous) !TOther electrolytes, including calcium Chemistry Potassium phosphate injection is a combination of 224 mg monobasic potassium phosphate and 236 mg dibasic potassium phosphate. The p H of the injection is 6. 5 and has an osmolarity of 7357 m Osm/L. Sodium phosphate injection is a combination of 276 mg mono basic sodium phosphate and 142 mg dibasic sodium phos-phate. The p H of the injection is 5. 7 and has an osmolarity of about 7000 m Osm/L. Because commercial preparations are a combination of monoba-sic and dibasic forms, prescribe and dispense in terms of m Moles of phosphate. Storage/Stability/Compatibility Unless otherwise instructed by the manufacturer, store potassium or sodium phosphate injection at room temperature; protect from freezing. Phosphates may be physically incompatible with metals such as calcium and magnesium. Potassium phosphate injection is reportedly physically compat-ible with the following intravenous solutions and drugs: amino ac-ids 4%/dextrose 25%, D 10LRS, D 10R inger's, Dextrose 2. 5%-10% injection, sodium chloride 0. 45%-0. 9%, magnesium sulfate, me-toclopramide HCl, and verapamil HCl. Potassium phosphate injection is reportedly physically incom-patible with the following solutions or drugs: D 2. 5 in half nor-mal Ringer's or LRS, D 5 in R inger's, D 10/sodium chloride 0. 9%, Ringer's injection, LRS, and dobutamine HCl. Compatibility is de-pendent upon factors such as p H, concentration, temperature and dilue nt used; consult specialized references or a hospital pharmacist for more speciﬁc information. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None There are no parenteral phosphate-only products approved for veter-inary medicine. There are several proprietary phosphate-containing pr oducts available that may also include calcium, magnesium, potas-sium, and/or dextrose; refer to the individual product's labeling for spe ciﬁc dosage information. Trade names for these products include: Magnadex®—Osborn, Norcalciphos®—SKB, Cal-Dextro® Special, and #2, (Fort Dodge), and CMPK®, and Cal-Phos® #2 (T ech Ameri-ca). They are legend (Rx) drugs. HUMAN-LABELED PRODUCTS: Potassium Phosphate Injection; each m L provides 3 m M of phos-phate (99. 1 mg/dl of phosphorous) and 4. 4 m Eq of potassium per m L in 5, 10, 15, 30, and 50 m L vials; generic; (Rx) Sodium Phosphate Injection; each m L provides 3 m M of phosphate (93 mg/d l of phosphorous) and 4 m Eq of sodium per m L in 10, 15, 30, and 50 m L vials; generic; (Rx)	pppbs.pdf
PHYSOSTIGMINE SALICYLATE (fye-zoh-stig-meen sah-lis-ah-layt) Antilirium® CHOLINESTERASE INHIBITOR Prescriber Highlights TT Cholinesterase inhibitor that may be used for the adjunc-tive treatment of ivermectin toxicity in dogs, as a pro-vocative agent for the diagnosis of narcolepsy in dogs & horses, or as a treatment f or anticholinergic toxicity TT Crosses into the CNS, so it is effective for treating central anticholinergic toxicity, but also increases the risks for central physostigmine toxic effects (e. g., seizures) TT Must be administered with direct patient supervision; toxic effects from this drug can be serious Uses/Indications Physostigmine has been used for the adjunctive treatment of iver-mectin toxicity in dogs, as a provocative agent for the diagnosis of narcolepsy in dogs and horses, and as a treatment for anticholin-ergic toxicity. Because of the potential for serious adverse effects, use of p hysostigmine as an antidote is generally reserved for very serious toxicity affecting the CNS. Otherwise, safer alternatives such as neostigmine or pyridostigmine are preferred. While physostigmine has been used to antagonize the CNS de-pressant effects of benzodiazepines in humans, it should not be used fo r this purpose because of the potential toxicity and non-speciﬁc action of physostigmine. Pharmacology/Actions Physostigmine reversibly inhibits the destruction of acetylcholine by acetylcholinesterase, thereby increasing acetylcholine at receptor sites. Because physostigmine is a tertiary amine, unlike the quater-nary amine cholinesterase inhibitors neostigmine and pyridostig-mine, it crosses the blood-brain barrier and inhibits acetylcholinest-erase both centrally and peripherally. Pharmacologic effects include miosis, bro nchial constriction, hypersalivation, muscle weakness, and sweating (in species with sweat glands). At higher dosages, cho-linergic crisis can occur; seizures, bradycardia, tachycardia, asystole, nausea, vomit ing, diarrhea, depolarizing neuromuscular block, pulmonary edema, and respiratory paralysis are possible. Pharmacokinetics Physostigmine is rapidly absorbed from the GI tract (no oral dos-age form available), subcutaneous tissue or mucous membranes. After parenteral administration, physostigmine readily crosses the blood-brain barrier into the CNS. Peak effects occur within 5 min-utes after IV administration; about 25 minutes after IM dosing. The majority of administered drug is rapidly destroyed via hydrolysis by cholinesterases. Very small amounts can be eliminated unchanged into the urine. Duration of pharmacologic effects can be from 30 minutes to 5 hours; average duration is 30-60 minutes. Contraindications/Precautions/Warnings Contraindications for humans and, presumably, animal patients in-clude: prior hypersensitivity reactions to physostigmine or sulﬁtes, bronc hoconstrictive disease (asthma), gangrene, diabetes mellitus, cardiovascular disease, mechanical obstruction of the GI or uri-nary tract, any vagotonic state, or the concurrent use of choline es-ters ( e. g., bethanechol, methacholine) or neuromuscular blocking agents ( e. g., succinylcholine)—see Drug Interactions. When physostigmine is used in the absence of anticholinergic toxicity or to treat tricyclic or tetracyclic antidepressant overdoses, there is an increased risk for cholinergic crisis. Rapid IV administration increases the potential for bradycardia, hype rsalivation, or seizures. In humans, it should be given intrave-nously at a slow, controlled rate not exceeding 1 mg/minute (adults) and 0. 5 mg/min (children). B ecause of the risks for toxicity, atropine should be readily avail-able (see Overdosage). Physostigmine injection contains benzyl alcohol which may be toxic in neo natal animals. Adverse Effects Adverse effects are a result of the drug's pharmacologic actions and, except for hypersensitivity reactions, are dose related depending upon concurrent anticholinergic effects secondary to anticholin-ergics on board. Pharmacologic effects include miosis, bronchial constr iction, hypersalivation, muscle weakness, and sweating (in species with sweat glands). At higher dosages, cholinergic crisis can occur; seizures, bradycardia, tachycardia, asystole, nausea, vomit-ing, diarrhea, depolarizing neuromuscular block, pulmonary ede-ma, and respiratory paralysis are possible. Reproductive/Nursing Safety Little information is available, but it would be expected that phys-ostigmine would cross the placenta. T eratogenic effects (behavioral, bioche mical and metabolic) have reportedly been observed in mice studies. Weigh the potential risks of using physostigmine during pregnancy versus its potential beneﬁts. In humans, the FDA catego-rizes alendronate as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no ad-equate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) I t is not known if physostigmine enters milk, but it would un-likely pose much risk to nursing offspring. Overdosage/Acute Toxicity Overdoses or acute toxicity can be life-threatening (see Adverse Reactions), however, because of the short duration of effect, sup-portive care may be all that is required. Treatment of serious acute toxicity includes mechanical ventilation, repeated bronchial aspi-ration, and administration of IV atropine. Refer to the Atropine monogr aph for dosages for cholinergic toxicity. Readministration of atropine may be required. Pralidoxime (2-PAM) may be useful in reversing the ganglionic and skeletal muscle effects of physostig-mine. Refer to the Pralidoxime monograph for more information. An animal p oison control center may be helpful in assisting with case management. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving physostigmine and may be of signiﬁcance in veterinary patients: T ! CHOLINE ESTERS (bethanechol, carbachol, methacholine ) or ORGANO-PHOSPHATES : Physostigmine may cause additive adverse effects T ! SUCCINYLCHOLINE : Physostigmine (high doses) may cause muscle fasiculations or depolarization block (very high doses), which may be additive to the effects of succinylcholine-like neuromus-cular blockers Laboratory Considerations None were noted	pppbs.pdf
TDoses T ! DOGS: a) T o temporarily reverse the CNS effects of ivermectin toxico-sis in support of the diagnosis: 1 mg (total dose) IV (Mealey 2006) b) T o temporarily reverse the CNS effects of ivermectin toxico-sis in support of the diagnosis: 1 mg (total dose)/12 hours IV. May r everse ivermectin-induced coma for 30-90 minutes. In comatose patients, it does not appear to induce seizures, but seizure-like activity can be observed in patients with only minor ataxia and confusion. (Estrada 2002) c) Provocative test for narcolepsy/cataplexy if feeding test (10 pieces of highly tasty food that the dog loves to eat in a row 12-24 inches apart; affected dogs will usually take 2 minutes or longer to eat the food and will have several attacks) is not successful: Physostigmine at 0. 025 mg/kg IV, wait 9-15 min-utes and observe response to stimulus (food test or similar). If clinical signs do not appear, may try a higher dose of 0. 05 mg/kg as above. Subsequent testing can be done at doses of 0. 075 mg/kg and 1 mg/kg as above. Increased severity of signs that may p ersist for 15-45 minutes in response to stimulus is indicative of cataplexy/narcolepsy. (Shell 2003b) T ! HORSES: (Note : RCI Class 3 drug) a) Provocative test in diagnosing cataplexy or narcolepsy: 0. 05-0. 1 mg/kg slow IV will precipitate a cataplectic attack within 3- 10 minutes after administration in affected horses. Untoward effects may include colic or cholinergic stimula-tion. (Andrews and Matthews 2004). b) Provocative test in diagnosing cataplexy or narcolepsy: 0. 06-0. 08 mg/kg IV. Lack of positive response does not rule out diagnosis of narcolepsy. Diarrhea can occur and caution is advised as horse can cause colic. (Mayhew 2005b) T ! CATTLE: a) For reversal of tall larkspur (Delphinium barbeya) poisoning: 0. 04-0. 08 mg/kg IV rapidly; serial injections may be neces-sary. (Pﬁster, Panter et al. 1994) Monitoring T ! Direct patient supervision required for monitoring adverse effects T ! Heart rate, blood pressure; monitor heart rhythm if heart rate is abnormal Client Information T ! his medication must be administered in a setting where direct veterinary supervision is available Chemistry/Synonyms Physostigmine salicylate is made from an extract of Physostigma venenosum (Calabar Bean) seeds. It occurs as white, shining, odor-less, crystals or crystalline powder. Upon exposure to heat, light, air, or exp osure to traces of metals for a long period, it develops a red tint. One gram is soluble in 75 m L of water and 16 m L of alcohol. The injection has a p H of 3. 5-5. Physostigmine salicylate may also be known as eserine salicylate, physost igmine monosalicylate and Anticholium®. Storage/Stability/Compatibility The injection (ampules) should be stored below 40°C and preferably between 15-30°C. Protect from light and freezing. Physostigmine is labeled for human use to be administered IV undiluted. It may be given via a Y-site or stopcock port on IV set, but it should not be added to IV solutions. IM dosing (although not approved) is not uncommon in humans. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 3 substance. See the appendix for more information. HUMAN-LABELED PRODUCTS: Physostigmine Salicylate Injection: 1mg/m L in 2 m L ampules, also contains benzyl alcohol 2% and 0. 1% sodium metabisulﬁte; Antilirium® (Forest), generic; (Rx) PHYTONADIONE VITAMIN K 1 (fye-toe-na-dye-ohne) Vitamin K1, Mephyton® ANTIDOTE, FAT SOLUBLE VITAMIN Prescriber Highlights TT Used for the treatment of anticoagulant rodenticide toxic-ity, dicumarol toxicity associated with sweet clover inges-tion in ruminants, sulfaquinoxaline toxicity, & in bleeding disorders associated with faulty for mation of vitamin K-dependent coagulation factor s TT Contraindications: Hypersensitivity; does not correct hy-poprothrombinemia due to hepatocellular damage. TT Adverse Effects: Anaphylactoid reactions after IV admin-istration, IM use may result in acute bleeding from the site of injection during the early stages of treatment. SC injections or oral dosages may be slowly or poor ly ab-sorbed in hypovolemic animals. TT May require 6-12 hours for effect TT Small gauge needles are recommended for use when injecting SC or IM Uses/Indications The principal uses of exogenously administered phytonadione is in the treatment of anticoagulant rodenticide toxicity. It is also used for treating dicumarol toxicity associated with sweet clover inges-tion in ruminants, sulfaquinoxaline toxicity, and in bleeding dis-orders associated with faulty formation of vitamin K-dependent coagulatio n factors. Pharmacology/Actions Vitamin K 1 is necessary for the synthesis of blood coagulation fac-tors II, VII, IX, and X in the liver. It is believed that Vitamin K 1 is involv ed in the carboxylation of the inactive precursors of these fac-tors to form active compounds. Pharmacokinetics Phytonadione is absorbed from the GI tract in monogastric animals via the intestinal lymphatics, but only in the presence of bile salts. Oral absorption of phytonadione may be signiﬁcantly enhanced by administration with fatty foods. The relative bioavailability of the drug is increased 4-5 times in dogs given canned dog food with the dose. After oral administration, increases in clotting factors may not occur until 6-12 hours later. In humans, oral administration may be more rapidly absorbed than with SC administr ation. Phytonadione may concentrate in the liver for a short period of time, but is not appreciably stored in the liver or other tissues.	pppbs.pdf
Only small amounts are distributed across the placenta in pregnant animals. Exogenously administered phytonadione enters milk. The elimination of Vitamin K 1 is not well understood. Contraindications/Precautions/Warnings Many veterinary clinicians state that the intravenous use of phy-tonadione is contraindicated because of increased risk of anaphy-laxis development, and while intravenous phytonadione is used in h uman medicine and several intravenous dosage regimens are outlined below in the Dosage section, the FDA-CVM has warned to avoid administering the drug IV. However, in human medicine, intravenous phytonadione is recommended (with caution) for se-vere bleeding associated with very high INR. Phytonadione is con-traindicated in patients hypersensitive to it or any component of its fo rmulation. Vitamin K does not correct hypoprothrombinemia due to hepa-tocellular damage. Adverse Effects Anaphylactoid reactions have been reported following IV admin-istration of Vitamin K1; use with extreme caution (See Contra-indications above). Intramuscular administration may result in acu te bleeding from the site of injection during the early stages of treatment. Small gauge needles are recommended for use when in-jecting SC or IM. Subcutaneous injections or oral dosages may be slow ly or poorly absorbed in animals that are hypovolemic. Because 6-12 hours may be required for new clotting factors to be synthesized after phytonadione administration, emergency needs for clotting factors must be provided by giving blood products. Reproductive/Nursing Safety Phytonadione crosses the placenta only in small amounts, but its safety has not been documented in pregnant animals. 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 ther e are no adequate studies in humans; or there are no animal re-production studies and no adequate studies in humans. ) Vitamin K is excreted in maternal milk, but is unlikely to have neg ative effects in nursing offspring. Overdosage/Acute Toxicity Phytonadione is relatively non-toxic, and it would be unlikely that toxic clinical signs would result after a single overdosage. However, refer to 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 phytonadione and may be of signiﬁcance in veterinary patients: !TANTIBIOTICS, ORAL : Although chronic antibiotic therapy should have no signiﬁcant effect on the absorption of phytonadione, these drugs may decrease the numbers of vitamin K producing bacteria in the gut !TMINERAL OIL : Concomitant administration of oral mineral oil may reduce the absorption of oral vitamin K. !TWARFARIN : As would be expected, phytonadione antagonizes the anticoagulant effects of coumarin (and indanedione agents. There are many drugs that may prolong or enhance the effects of anticoagulants and antagonize some of the therapeutic effects of phytonadione, including: phenylbutazone, aspirin, chloramphenicol, sulfonamides diazoxide, allopurinol, cimetidine, metronidazole, ana-bolic steroids, erythromycin, ketoconazole, propranolol, and thyroid drugs. Doses !TDOGS & CAT S: For adjunctive therapy of acute liver failure: a) 1-5 mg/kg PO or SC q24h (Rosanski 2002) Fo r anticoagulant rodenticide toxicity: a) For known warfarin, fumarin, pindone, or valone ingestions: 1 mg/kg PO once daily for 4-6 days. Fo r known bromadiolone or brodifacoum ingestions: 2. 5 mg/kg PO once daily usually for 2-3 weeks (bromadiolone duration unknown). For known diphacinone or chlorphacinone ingestions: 2. 5-5 mg/kg PO for 3-4 weeks. Note : Usual dosages and duration—use oral route (with one teaspoon of canned dog food) if animal not vomiting, other-wise SC route preferred over IV. Therapy must be continued fo r as long as rodenticide is inhibiting vitamin K 1 epoxide recycling. (Felice and Murphy 1995) b) For acute cases: Handle animal gently. Avoid IM injections; gi ve fresh, whole blood transfusion 10-20 m L/kg IV (ﬁrst half rapidly, then at 20 drops/minute). Give oxygen if hypox-ic; if dyspneic consider radiographs and thoracentesis for in-trathoracic hemorrhage. Then give phytonadione as below. For subacute cases: Give phytonadione at 2-3 mg/kg SC q12h f or large dogs and 5 mg/kg SC q12h for small dogs and cats. Repeat until coagulation times are normal. Follow with oral phytonadione at 2. 5-3 mg/kg PO divided three times daily for 4-6 days if short acting coumarin (e. g., warfarin) or up to 30 days for long-acting agents. (Grauer and Hjelle 1988) !TRABBITS, RODENTS, SMALL MAMMALS: a) Mice, Rats, Gerbils, Hamsters, Guinea pigs: 1-10 mg/kg IM (Adamcak and O tten 2000) !TCATTLE: For anticoagulant rodenticide toxicity: a) Initially 0. 5-2. 5 mg/kg IV in D 5W at a rate of 10 mg/minute. Subsequent doses may be given IM or SC. Second generation agents may require 3-4 weeks of treatment. (Bailey 1986b) b) 0. 5-2. 5 mg/kg IM, if IV use is necessary (avoid if possible), dilu te in saline or D 5W/saline and give very slowly (not to exceed 5 mg/minute). (Upson 1988) c) For acute hypoprothrombinemia with hemorrhage: 0. 5-2. 5 mg/kg IV, not to exceed 10 mg/minute in mature animals and 5 mg/minute in newborn and very young animals. For non-acute hypoprothrombinemia: 0. 5-2. 5 mg/kg IM or SC (Labe l directions; Veda-K 1®—Vedco) For sweet clover (dicumarol) toxicity: a) Give blood if necessary, then phytonadione 1 mg/kg IV or IM; r epeat 2-3 times daily for 2 days. (Osweiler and Ruhr 1986) !THORSES: For warfarin (or related compounds) toxicity: a) 500 mg SC q4-6h until one-stage prothrombin time (OSPT) re turns to normal control values. Whole blood or fresh plas-ma may also be necessary early in the course of treatment. (By ars 1987) b) 0. 5-2. 5 mg/kg IM, if IV use is necessary (avoid if possible), dilu te in saline or D 5W/saline and give very slowly (not to exceed 5 mg/minute). (Upson 1988)	pppbs.pdf
T ! SWINE: For warfarin (or related compounds) toxicity: a) 0. 5-2. 5 mg/kg IM, if IV use is necessary (avoid if possible), dilute in saline or D 5W/saline and give very slowly (not to exceed 5 mg/minute). (Upson 1988) T ! SHEEP & GOATS: For warfarin (or related compounds) toxicity: a) 0. 5-2. 5 mg/kg IM, if IV use is necessary (avoid if possible), dilute in saline or D 5W/saline and give very slowly (not to exceed 5 mg/minute). (Upson 1988) T ! BIRDS: For hemorrhagic disorders: a) 0. 25-0. 5 m L/kg IM of the 10 mg/m L injectable product. Commonl y used before surgery where hemorrhage is antici-pated. (Mc Donald 1989) b) 0. 2-2. 5 mg/kg IM as needed; usually only 1-2 injections are requir ed. May also be used prophylactically when amprolium and sulfas are administered. (Clubb 1986) Monitoring T ! Clinical efﬁcacy (lack of hemorrhage) T ! One-stage prothrombin time (OSPT); INR Client Information T ! Because it may take several weeks to eliminate some of the anti-coagulant rodenticides from the body, clients must be counseled on the imp ortance of continuing to administer the drug (phy-tonadione) for as long as instructed or renewed bleeding may occur. T ! Unless otherwise instructed, oral phytonadione should be ad-ministered with food, preferably foods high in fat content. T ! During therapy, animals should be kept quiet whether at home or hospitalized. Chemistry/Synonyms A naphthoquinone derivative identical to naturally occurring vi-tamin K 1, phytonadione occurs as a clear, yellow to amber, viscous liquid. I t is insoluble in water, slightly soluble in alcohol and soluble in lipids. Phytonadione may also be known as: methylphytylnaphthochi-nonum, phylloquinone, phytomenadionum, phytomenadione, vitamin K1, Am T ech®, Glakay®, Aqua-Mephyton®, K1®, K-Caps®, K-Chews ®, K-Ject®, KP®, Kanakion®, Kanavit®, Kavit ®, Kaytwo ®, Kaywan®, Kenadion®, Konakion®, Konakion Novum®, Mephyton®, Pertix-Solo®, Veda-K1, Vikatron®, Vita-Jec®, or Vitamon K®. Storage/Stability/Compatibility Phytonadione should be protected from light at all times, as it is quite sensitive to light. If used as an intravenous infusion, the con-tainer should be wrapped with an opaque material. Tablets and capsules should be sto red in well-closed, light-resistant containers. Because most veterinary clinicians state that phytonadione is contr aindicated for intravenous use; consult specialized references or a hospital pharmacist for more speciﬁc information on compat-ibility of phytonadione with other agents. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Phytonadione Oral Capsules: 25 mg; K-Caps® (Butler), Veda-K1® Capsules (Vedco), Veta-K 1® (Bimeda), Vitamin K 1 (Phoenix Phar-maceutical, RXV); (Rx) Labeled for use in dogs and cats. Phytonadione Oral Capsules: 50 mg; Vitamin K 1 Do uble Strength® (Phoenix); (Rx) Labeled for use in dogs. Phytonadione Oral Tablets, Chewable: 25 mg, 50 mg; Vitamin K 1 Chew able® (V. E. T. ), Vitamin K1 Chewablet® (Pala-T ech), K-Chews® (Butler); (Rx). Products may be labeled for use in dogs and cats. Phytonadione Aqueous Colloidal Solution for Injection: 10 mg/m L in 30 m L and 100 m L vials; Am Tech® Vitamin K 1 (IVX), K-Ject® (Butler), Veda-K 1® Injection (Vedco), Vita-Jec® (RXV), Vitamin K 1 (Vet T ek, Bimeda, Neogen, Phoenix Pharmaceutical), (Rx) Labeled for use dogs, cats, cattle, calves, horses, swine, sheep, and goats. No withdrawal times listed. HUMAN-LABELED PRODUCTS: Phytonadione Tablets: 5 mg; Mephyton® (Merck); (Rx) Phytonadione Injection, Emulsion: 2 mg/m L (aqueous colloidal solu-tion) & 10 mg/m L in 0. 5 m L & 1 m L amps; generic (Hospira); (Rx) PIMOBENDAN (pi-moe-ben-den) Vetmedin® INODILATOR Prescriber Highlights TT Oral drug that may be useful in treatment of congestive heart failure in dogs TT Limited clinical experience, particularly in North America; many ongoing studies being performed TT May increase risks for arrhythmias Uses/Indications Pimobendan is used to treat dogs with congestive heart failure sec-ondary to dilated cardiomyopathy or chronic mitral valve insufﬁ-ciency (CMVI). Pharmacology/Actions Pimobendan is a so-called inodilator; it has both inotropic and va-sodilator effects. Pimobendan usually decreases heart rate (negative chronot rope) in animals with CHF. Its inotropic effects occur via inhibition of phosphodiesterase III (PDE-III) and by increasing in-tracellular calcium sensitivity in the cardiac contractility apparatus. Cardiac contractility is enhanced without an increase in myocardial oxygen consumption, as pimobendan does not increase intracel-lular calcium levels. Its vasodilator effects are via vascular PDE-III inhibition and b oth arterial and venous dilation occur. Pharmacokinetics In dogs, following a single oral administration of 0. 25 mg/kg pi-mobendan peak levels of the parent compound and the active me-tabolite were observed 1-4 hours post-dose (mean: 2 and 3 hours, respec tively). Food decreased the bioavailability of an aqueous so-lution of pimobendan, but the effect of food on the absorption of pimobendan from chewable tablets is unknown. The steady-state volume of distribution of pimobendan is 2. 6 L/kg. Protein binding of pimobendan and the active metabolite in dog plasma is >90%. Pimobendan is oxidatively demethylated to a pharmacologically ac-tive metabolite which is then conjugated with sulfate or glucuronic acid and e xcreted mainly via feces. Clearance of pimobendan is approximately 90 m L/min/kg, and the terminal elimination half-lives of pimobendan and the active metabolite are approximately 0. 5 hours and 2 hours, respectively. Plasma levels of pimobendan and the ac tive metabolite were below quantiﬁable levels by 4 and 8 hours respectively after oral administration.	pppbs.pdf
In humans with heart failure, pimobendan is rapidly absorbed with peak levels occurring in less than one hour after dosing. The volume of distribution was about 3. 2 L/kg; clearance about 25 m L/ min/kg. T erminal half-life is slightly less than 3 hours. Contraindications/Precautions/Warnings Pimobendan is contraindicated in animals hypersensitive to it, with hypertrophic cardiomyopathy, aortic stenosis, or any other condi-tion where an augmentation of cardiac output is inappropriate for funct ional or anatomic reasons. It should be used with caution in patients with uncontrolled cardiac arrhythmias. The label states the drug has not been evaluated in dogs younger than 6 months of age, dogs with congenital heart defects, diabetes mellitus or other serious metabolic diseases, dogs used for breed-ing, or pregnant or lactating bitches. Adverse Effects Because clinical experience with this drug is still limited, the adverse effect proﬁle is still being developed. In a US ﬁeld trial (56 day), the adverse effect incidence (at least one occurrence reported per dog) was: poor appetite (38%), lethargy (33%), diarrhea (30%), dyspnea (29%), azotemia (14%), weakness and ataxia (13%), pleural effu-sion (10%), syncope (9%), cough (7%), sudden death (6%), ascites (6%), and hear t murmur (3%). In a study comparing cardiac adverse effects of pimobendan with benazepril (Chetboul, Lefebvre et al. 2007), dogs with mitral valve regurgitation had increases in systolic function but also devel-oped worsening mitral valve disease and speciﬁc mitral valve lesions (acu te hemorrhages, endocardial papilloform hyperplasia on the dorsal surfaces of the leaﬂets, and inﬁltration of chordae tendinae by glycosaminoglycans) not seen in the benazepril group. The authors recommend that patients with mitral valve disease that are treated chronically with pimobendan be regularly and cautiously examined for any worsening mitral valvular lesions and regurgitation. There is some evidence that pimobendan may increase the devel-opment of arrhythmias. Atrial ﬁbrillation or increased ventricular ec topic beats have been reported in dogs on pimobendan, but be-cause cardiomyopathy can cause arrhythmias, a causative effect has not b een fully established. A trial of pimobendan in humans with heart failure demonstrated an increased mortality rate while on the drug, but this result has not been duplicated in canine studies. Reproductive/Nursing Safety The label states the drug has not been evaluated in dogs used for breeding, or pregnant or lactating bitches. When pimobendan was given in high dosages (300 mg/kg) to pregnant laboratory animals, increased resorptions occurred. Rabbits given 100 mg/kg showed no adverse fetal effects. No information on the safety of pimobendan during nursing was locat ed. Overdosage/Acute Toxicity No speciﬁc information was located. In case of an animal overdose, contact an animal poison control center. Drug Interactions In ﬁeld trials, the drug is labeled as being used safely with furo-semide, digoxin, enalapril, atenolol, nitroglycerin, hydralazine, diltiaz em, antiparasitic products (including heartworm preventa-tive), antibiotics, famotidine, theophylline, levothyroxin, diphenhy-dramine, hydrocodone, metoclopramide and butorphanol. The U. K. label states that “pimobendan-induced increase in con-tractility of the heart are attenuated in the presence of the calcium antago nist verapamil and the beta-antagonist propranolol. ” It is as-sumed that other drugs in these categories (e. g., diltiazem, atenolol) may also ha ve effect. Milrinone, a human drug that also inhibits phosphodiesterase, has b een used with a variety of other drugs (e. g., cardiac glycosides, lidocaine, hydralazine, prazosin, quinidine, nitroglycerin, furosemi-de, warfarin, spironolactone, heparin, potassium) without apparent pr oblems, but because pimobendan also increases calcium sensitiv-ity, comparing the two drugs may not be fully informative. Laboratory Considerations No laboratory interactions or special considerations were located. Doses !TDOGS: a) For management of the signs of mild, moderate or severe co ngestive heart failure due to A V valve insufﬁciency or di-lated cardiomyopathy: 0. 5 mg/kg total daily dose. Divide daily dose into two portions that are not necessarily equal (using whole and half tablets) and administer approximately 12 hours apart. (Label directions; Vetmedin®—B-I) b) For treatment of congestive heart failure secondary to myx-omatous mitral valve disease (MMVD): 0. 4-0. 6 mg/kg PO div ided twice daily (Lombard 2004) c) For treatment of heart failure secondary to dilated cardio-myopathy or chronic mitral valve insufﬁciency: 0. 25 mg/kg PO twic e daily (O'Grady, Minors et al. 2004) d) 0. 2-0. 6 mg/kg PO divided q12h (U. K. Label directions; Ve tmedin®—BI; 2003) Monitoring !TCardiovascular parameters used to monitor heart function, in-cluding ECG (rate/rhythm), blood pressure, echo studies, clinical signs, etc. Client Information !TGive medication approximately one hour before feeding. !TClients should understand that there is limited clinical experi-ence with this drug, that there may be risks (arrhythmias) associ-ated with its use, and that pimobendan is a treatment, and not a cure for heart failure. !TCompliance with the veterinarian's instructions is essential. !TKeep out of reach of children. Chemistry/Synonyms A benzimidazole-derivative phosphodiesterase inhibitor, pimoben-dan occurs as a white or slightly yellowish, hygroscopic powder. It is p ractically insoluble in water and slightly soluble in acetone or methyl alcohol. Pimobendans's chemical name is: 4,5-Dihydro-6-[2-(p-methyoxyphenyl)-5-benzimidazolyl]-5-methyl-3(2H) pyridazinone. It has a molecular weight of 334. 4. Pimobendan may also be known as: UDCG-115, Acar di®, and Vetmedin®. Storage/Stability Unless otherwise labeled, pimobendan chewable tablets or capsules should be stored at room temperature below 25°C (77°F) in a dry place.	pppbs.pdf
Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Pimobendan Chewable Tablets: 1. 25 mg, 2. 5 mg and 5 mg: Vetme-din® (B-I); (Rx). Approved for use in dogs. HUMAN-LABELED PRODUCTS: None PIPERACILLIN SODIUM (pype-er-ah-sill-in) Pipracil® EXTENDED SPECTRUM PENICILLIN Prescriber Highlights TT Extended-action penicillin, with good gram-negative spec-trum, including many strains of Pseudomonas TT Limited experience in veterinary medicine, but appears quite safe TT Also available with a beta-lactamase inhibitor (tazobac-tam); see the next monograph Uses/Indications Although veterinary experience is limited with piperacillin or pip-eracillin/tazobactam, these drugs have expanded coverage against many bacteria and may be suitable for empiric use until culture and susceptibility data are available, or for surgical prophylaxis when gram-negative or mixed aerobic/anaerobic infections are concerns. Pharmacology/Actions Piperacillin is a bactericidal, extended action acylaminopenicillin that inhibits septum formation and cell wall synthesis in susceptible bacteria. It has a wide spectrum of activity against many aerobic and anaerobic gram-positive (including many enterococci) and gram-negative bacteria. It has a similar spectrum 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 aminopenicillins, it is susceptible to inactivation by beta-lactamases. The addition of a beta-lactamase inhibitor (tazobactam) in the product Zosyn® (see next monograph), increases piperacillin's spectrum of activity against many beta lactamase producing strains of bacteria. Pharmacokinetics Limited information is available for veterinary species. In mares, piperacillin has an elimination half-life of about 7 hours. IM bio-availability is 86% and protein binding about 19%. In humans, piperacillin is not appreciably absorbed from the gut so it must be administered parenterally. After IM administra-tion peak levels occur in about 30 minutes. The drug exhibits low prote in binding and has a volume of distribution of 0. 1L/kg. It is widely distributed into many tissues and ﬂuids including lung, gall-bladder, intestinal mucosa, uterus, bile, and interstitial ﬂuid. With inﬂamed mening es, piperacillin levels in the CSF are approximately 30% those in serum. If meninges are normal, CSF concentrations are only about 6% of serum levels. Piperacillin crosses the placenta and is distributed into milk in low concentrations. Piperacillin is metabolized somewhat in the liver to a desethyl metabolite that has only minimal antibacterial activity. Piperacillin is primarily (68%) eliminated unchanged in the urine via active tubular secretion and glomerular ﬁltration; it is also excreted in the bile. Elimination half-life in humans is approximately one hour. Contraindications/Precautions/Warnings Piperacillin should not be used in patients with documented hyper-sensitive reactions to a beta-lactam. Because of sodium content, high dosages of piperacillin may adve rsely affect patients with cardiac failure or hypernatremic conditions. Dosage adjustment may be required in patients with signiﬁcant-ly decreased renal function (Cr Cl <40 m L/min). Adverse Effects Piperacillin is generally well tolerated. Hypersensitivity reac-tions are possible. Local effects (thrombophlebitis, etc. ) associated with intr avenous injection or pain after IM injection may occur. Alterations in gut ﬂora may lead to antibiotic-associated diarrhea. In humans, piperacillin has caused coagulation abnormalities on oc casion, particularly in patients with renal failure. Very high doses may cause neurotoxicity (seizures); again, these are more likely in patients with diminished renal function. Superinfections with Clostridium difﬁcile have been reported rarely. Reproductive/Nursing Safety Piperacillin is thought relatively safe to use during pregnancy. No teratogenic effects have been attributed to it in either humans or laboratory animals. In humans, the FDA categorizes piperacillin 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. ) Piperacillin is distributed in milk in low concentrations; it is likely saf e to use during nursing. Overdosage/Acute Toxicity Single overdoses are unlikely to pose much risk although very large overdoses may cause vomiting, diarrhea, or neurotoxicity. Dogs re-ceiving up to 800 mg/kg/day of piperacillin/tazobactam for 6 months demo nstrated no serious toxic effects. Doses at 400 mg/kg/day or greater caused some transient effects to the liver (glycogen granules in the cytoplasm and increases in smooth endoplasmic reticulum in hepatocytes) that were mostly reversed after one month. Treatment for overdoses, if required, is supportive. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving piperacillin and may be of signiﬁcance in veterinary patients: T ! AMINOGLYCOSIDES (amikacin, gentamicin, tobramycin ): In vitro stud-ies have demonstrated that penicillins can have synergistic or additiv e activity against certain bacteria when used with amino-glycosides. Beta-lactam antibiotics, however, can inactivate amin-oglycosides in vitr o 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. T ! ANTICOAGULANTS : Because piperacillin may rarely affect platelets, increased monitoring of coagulation parameters is suggested for patients on heparin or warfarin T ! METHOTREXATE : Piperacillin may increase MTX serum levels T ! PROBENECID : Can reduce the renal tubular secretion of piperacil-lin thereby maintaining higher systemic levels for longer periods; this pote ntial “beneﬁcial” interaction requires further investiga-tion before dosing recommendations can be made for veterinary patients ! !VECURONIUM : Piperacillin may prolong neuromuscular blockade	pppbs.pdf
Laboratory Considerations T ! Urine glucose determinations when using cupric sulfate solution (Benedict's Solution, Clinitest®): Piperacillin may cause false-positive results; tests utilizing glucose oxidase (Tes-Tape®, Clinis-tix®) are not affected by piperacillin T ! Aminoglycoside serum quantitative analysis : As penicillins and oth-er beta-lactams can inactivate aminoglycosides in vitr o (and in vivo in patients in renal failure or when penicillins are used in massive dosages), serum concentrations of aminoglycosides may be falsely decreased if the patient 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 froze n and, if possible, drawn at times when the beta-lactam an-tibiotic is at a trough. T ! Direct antiglobulin (Coombs' ) tests : False-positive results may occur T ! Urine protein : May produce false-positive urine protein results with the sulfosalicylic acid and boiling test, nitric acid test, or the acetic acid test. Strips using bromophenol blue reagent (e. g., Multi-Stix®) do not appear to be affected by high levels of peni-cillins in the urine. Doses T ! DOGS/CAT S: a) For bacteremia with or without endocarditis: 30 mg/kg IV q6h for 7- 14 days. (Calvert and Wall 2006) b) For respiratory infections: 25-50 mg/kg IV q8h. (Greene and Reiner o 2006) c) Dogs: For systemic treatment of otitis media or prolifera-tive otitis externa complicated by gram-negative (especially Pseudo monas) bacteria: 20 mg/kg SC three times daily. (Bloom 2006d) T ! BIRDS: a) For Bordetella avium infec tions: 150 mg/kg IM q8-12h; minimum treatment period is two weeks. (Flammer 2006) b) For susceptible infections: 100 mg/kg IM two to three times daily. (A ntinoff 2004) T ! HORSES: a) For susceptible infections: 15-50 mg/kg IV or IM q6-12h. (Bert one and Horspool 2004) T ! REPTILES: a) For susceptible infections: 100 mg/kg route not speciﬁed q48h. (Antino ff 2004) b) Snakes: 100 mg/kg IM q24h (Mader 2004) Monitoring T ! Efﬁcacy for the infection treated (WBC, clinical signs, etc. ) Client Information T ! Limited experience in veterinary medicine T ! Best suited for inpatient use Chemistry/Synonyms Piperacillin sodium occurs as a white or almost white, hygroscopic powder. It is freely soluble in water or alcohol. A 40% solution has a p H of 5-7. Pipera cillin sodium for injection contains 42. 5 mg (1. 85 m Eq) sodium per gram. Piperacillin may also be known as: piperacillinum, BL-P 1908, Cl 867, CL 227 193, T 12220, TA 058, Pipracil®, and Pipril®. Storage/Stability/Compatibility Piperacillin powder for injection vials should be stored at controlled room temperature (20-25°C). Conventional vials should be reconstituted with 5 m L of di-luent per gram of piperacillin. Suitable diluents include 0. 9% so-dium chloride, sterile water for injection, D 5W, and ba cteriostatic saline or water for injection. Once reconstituted, further dilute for intravenous infusion with 50-150 m L of 0. 9% sodium chloride, LRS (must be given within 2 hours) or D 5W. IV infusion of diluted products should be over at least 30 minutes. IV infusion from the contents of the reconstituted vials should be administered over at least 3-5 minutes to reduce the chance for vein irritation. Once reconstituted, vials should be used within 4 hours of initial puncture. The manufacturer recommends not freezing reconstitut-ed vials. IV bags (50-150 m L) containing further diluted product are stable for up to 24 hours at room temperature and one week if refrigerated. As no preservatives are used, sterility is not assured in stored reconstituted products. For IM use, 5 m L of 0. 5% or 1% lidocaine injection (without epinephr ine) may be added to a 2 gram vial and used immediately. Do not mix with aminoglycosides. Intravenous admixture solu-tions containing potassium, clindamycin, or hydrocortisone sodi-um succinate are reported compatible with piperacillin. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Piperacillin Sodium Injection (powder for reconstitution): 2, 3, & 4 g (as base) vials, 40 g bulk vials; generic (American Pharmaceutical Partners); (Rx) PIPERACILLIN SODIUM + TAZOBACTAM (pype-er-ah-sill-in; tay-zoh-bak-tam) Zosyn® EXTENDED SPECTRUM PENICILLIN + BETA-LACTAMASE INHIBITOR Prescriber Highlights TT Extended action parenteral penicillin with a beta lacta-mase inhibitor; has increased spectrum of activity when compared with piperacillin alone, but is more expensive TT Limited experience or research in veterinary medicine, but appears quite safe Uses/Indications Although veterinary experience is limited with piperacillin or pip-eracillin/tazobactam, these drugs have expanded coverage against many bac teria and may be suitable for empiric use until culture and susceptibility data are available, or for surgical prophylaxis when gram-negative or mixed aerobic/anaerobic infections are concerns. Pharmacology/Actions For information on piperacillin, refer to the preceding monograph. Tazobactam irreversibly binds to beta-lactamases thereby “protect-ing” the beta-lactam ring of piperacillin from hydrolysis. When	pppbs.pdf
tazobactam is combined with piperacillin, it extends piperacillin's spectrum of activity to those bacteria that produce beta-lactamases of Richmond-Sykes types II-V that would otherwise render it inef-fective. It has slightly more activity than either clavulanate or sul-bactam against some Type I beta-lactamases. Tazobactam has minimal antibacterial activity when used alone, bu t in combination with piperacillin, synergistic effects may result. It is more potent than sulbactam and, unlike clavulanic acid, does not induce chromosomal beta-lactamases at serum concentrations achieved. Pharmacokinetics For information on the pharmacokinetics of piperacillin, refer to the previous monograph; tazobactam's pharmacokinetics generally mirrors that of piperacillin. In dogs, piperacillin reduced the renal clearance of tazobactam, presumably due to competition for tubu-lar secretion. Contraindications/Precautions/Warnings Piperacillin/tazobactam should not be used in patients with docu-mented hypersensitive reactions to a beta-lactam or beta-lactamase inhibit or. Because of sodium content, high dosages of piperacillin/tazobac-tam may adversely affect patients with cardiac failure or hyperna-tremic conditions. Dosage adjustment may be required in patients with signiﬁcant-ly decreased renal function (Cr Cl <40 m L/min). Adverse Effects Piperacillin/tazobactam is generally well tolerated. Hypersensitivity reactions are possible. Local effects (thrombophlebitis, etc. ) associ-ated with intravenous injection may occur. Alterations in gut ﬂora may lea d to antibiotic-associated diarrhea. In humans, piperacillin has caused coagulation abnormalities on occasion, particularly in patients with renal failure. Very high doses may cause neurotoxicity (seizures); again, this is more likely in patients with diminished renal function. Superinfections with Clostridium difﬁcile have been rarely reported. Reproductive/Nursing Safety Piperacillin/tazobactam is thought relatively safe to use during pregnancy. No teratogenic effects have been attributed to either drug in either humans or laboratory animals. In humans, the FDA categorizes piperacillin/tazobactam as category B for use during pregnancy (Animal studies have not yet demonstrated risk to the fe-tus, 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. ) Piperacillin is distributed in milk in low concentrations. It is not know n if tazobactam enters milk. This drug combination is likely safe to use during nursing. Overdosage/Acute Toxicity Single overdoses are unlikely to pose much risk although very large overdoses may cause vomiting, diarrhea, or neurotoxicity. Dogs receiving up to 800 mg/kg/day of piperacillin/tazobactam for 6 months demonstrated no serious toxic effects. Doses at 400 mg/ kg/day or greater caused some transient effects to the liver (glyco-gen granules in the cytoplasm and increases in smooth endoplas-mic reticulum in hepatocytes) that were mostly reversed after one month. T reatment for overdoses, if required, is supportive. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving piperacillin/tazobactam and may be of signiﬁcance in veterinary patients: !TAMINOGLYCOSIDES (amikacin, gentamicin, tobramycin ): In vitro stud-ies have demonstrated that penicillins can have synergistic or addit ive activity against certain bacteria when used with amino-glycosides. Beta-lactam antibiotics however, can inactivate amin-oglycosides in v itro 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. !TANTICOAGULANTS : Because piperacillin may rarely affect platelets, increased monitoring of coagulation parameters is suggested for patients on heparin or warfarin. !TMETHOTREXATE : Piperacillin may increase MTX serum levels !TPROBENECID : Can reduce the renal tubular secretion of both pip-eracillin and tazobactam, thereby maintaining higher systemic lev els for a longer period of time; this potential “beneﬁcial” inter-action requires further investigation before dosing recommenda-tions can be made for veterinary patients. !TVECURONIUM : Piperacillin may prolong neuromuscular blockade Laboratory Considerations !TUrine glucose determinations when using cupric sulfate solution (Benedict's Solution, Clinitest®): Piperacillin may cause false-positive results. T ests utilizing glucose oxidase (Tes-Tape®, Clin-istix®) are not affected by piperacillin. !TAminoglycoside serum quantitative analysis : As penicillins and oth-er beta-lactams can inactivate aminoglycosides in v itro (and in vivo in patients in renal failure or when penicillins are used in massive dosages), serum concentrations of aminoglycosides may be falsely decreased if the patient 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 fro zen and, if possible, drawn at times when the beta-lactam an-tibiotic is at a trough. !TDirect antiglobulin (Coombs' ) tests : False-positive results may occur !TUrine protein : Piperacillin may produce false-positive urine pro-tein results with the sulfosalicylic acid and boiling test, nitric acid test, or the acetic 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 !TDOGS/CAT S: a) For single-agent therapy of intra-abdominal sepsis: 50 mg/ kg IV or IM q4-6h for 5-7 days; dose extrapolated from human dosage with limited studies in dogs or cats. (Greene 2006) b) For bacterial sepsis in dogs: 3. 375 g (total dose per dog) IV q6h o r 4. 5 g (total dose per dog) IV q8h for 7 days. (Greene, Hartmannn et al. 2006) !TBIRDS: a) For susceptible infections: Reconstitute to 200 mg/m L and administ er at 100 mg/kg IM q8-12h; for severe polymicro-bic bacteremia give 100 mg/kg IV q6h; for preoperative or-thopedic or coelomic surgery: 100 mg/kg IM q12h. (Nemetz and Le nnox 2006)	pppbs.pdf
Monitoring T ! Efﬁcacy for the infection treated (CBC, clinical signs, etc. ) Client Information T ! Limited experience in veterinary medicine T ! Best suited for inpatient use Chemistry/Synonyms Piperacillin sodium/tazobactam sodium occurs as a white or almost white, cryodessicated powder. Tazobactam is structurally related to sulbactam and a penicillanic acid sulfone derivative. The commer-cially available piperacillin/tazobactam injection contains 2. 79 m Eq of sodi um and 0. 25 mg of EDTA per gram of piperacillin. Tazobactam may also be known as: CL 298741, or YTR 830H. Pipera cillin may also be known as piperacillinum, BL-P 1908, Cl 867, CL 227193, T 12220, and TA 058. International trade names for piperacillin/tazobactam include: Tazobac®, Tazocin®, Zosyn® and others. PIPERAZINE (pi-per-a-zeen) Pipa-Tabs® ANTIPARASITIC (ASCARIDS) Prescriber Highlights TT Anthelmintic for ascarids in a variety of species TT Contraindications: Chronic liver, kidney disease, & gastro-intestinal hypomotility. TT Caution: Seizure disorders, horses with heavy infestations of P. equorum TT Adverse Effects: Unlikely, but diarrhea, emesis, or ataxia possible Storage/Stability/Compatibility Piperacillin/tazobactam injection vials and ADD-Vantage vials should be stored at controlled room temperature (20-25°C). Conventional vials should be reconstituted with 5 m L of diluent per g ram of piperacillin. Suitable diluents include 0. 9% sodium chloride, sterile water for injection, and bacteriostatic saline or wa-ter for injection. Once reconstituted, further dilute for intravenous infusion with 50-150 m L of 0. 9% sodium chloride, LRS (reformu-lated product only—see below) or D 5W. IV infusio n should be over at least 30 minutes. Once reconstituted, vials should be used immediately. It is rec-ommended to discard after 24 hours if kept at room temperature or 48 hour s if stored in the refrigerator. The manufacturer rec-ommends not freezing reconstituted vials. IV bags (50-150 m L) containing fur ther diluted product are stable for up to 24 hours at room temperature and one week if refrigerated. As no preservatives are used, sterility is not assured in stored reconstituted products. Zosyn® (piperacillin/tazobactam) injection underwent a formu-lation change in 2006. Sodium citrate (buffer) and EDTA (metal chelato r) were added that made it compatible with lactated Ringer's injection and via simultaneous Y-site administration at speciﬁc concentrations of gentamicin and amikacin (but not tobramycin). This reformulated product has a yellow background behind the Zosyn® name on the label. Refer to the package insert for speciﬁc information on diluent and concentration compatibility. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Piperacillin Sodium & Tazobactam Injection (lyophilized powder for injection); Zosyn® (Wyeth); (Rx): 2. 25 g (piperacillin 2 g/tazobactam 0. 25 g) in vials and ADD-Van-tage ® vials; contains 4. 69 m Eq sodium 3. 375 g (piperacillin 3 g/tazobactam 0. 375 g) in vials and ADD-Van-tage ® vials; contains 7. 04 m Eq sodium 4. 5 g (piperacillin 4 g/tazobactam 0. 5 g) in vials and ADD-Vantage® v ials; contains 9. 36 m Eq sodium 40. 5 g bulk vials (piperacillin 36 g/ tazobactam 4. 5 g); in bulk vials; contains 84. 5 m Eq so dium Also available in 3. 375 g/50 m L and 4. 5 g/100 m L premixed, frozen Galaxy® co ntainers. Uses/Indications Piperazine is used for the treatment of ascarids in dogs, cats, horses, swine and poultry. Piperazine is considered safe to use in animals with concurrent gastroenteritis and during pregnancy. Pharmacology/Actions Piperazine is thought to exert “curare-like” effects on susceptible nematodes, thereby paralyzing or narcotizing the worm and allow-ing it to be passed out with the feces. The neuromuscular block-ing effect is believed to be caused by blocking acetylcholine at the myone ural junction. In ascarids, succinic acid production is also inhibited. Pharmacokinetics Piperazine and its salts are reportedly readily absorbed from the proximal sections of the GI tract and the drug is metabolized and excreted by the kidneys. Absorptive, distribution, and elimination kinetics on individual species were not located. Contraindications/Precautions/Warnings Piperazine should be considered contraindicated in patients with chronic liver or kidney disease, and those with gastrointestinal hy-pomotility. There is some evidence in humans that high-dose pip-erazine may provoke seizures in patients with a history of seizures, or with re nal disease. If used in horses with heavy infestations of P. equorum, rupture or blockage of intestines is possible due to the rapid death and de-tachment of the worm. Adverse Effects Adverse effects are uncommon at recommended doses, but diar-rhea, emesis, and ataxia may be noted in dogs or cats. Horses and foals g enerally tolerate the drug quite well, even at high dosage rates, but a transient softening of the feces may be seen. Other ad-verse effects have been seen at toxic dosages; refer to the Overdosage sectio n below for more information. Reproductive/Nursing Safety In a system evaluating the safety of drugs in canine and feline preg-nancy (Papich 1989), this drug is categorized as class: A (Pro bably 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 labora-tory animals or women. ) No information was located on use during nursing, but it prob-ably is safe to use.	pppbs.pdf
Overdosage/Acute Toxicity Acute massive overdosage can lead to paralysis and death, but the drug is generally considered to have a wide margin of safety. The oral LD 50 of piperazine adipate in mice is 11. 4 g/kg. In cats, adverse effects occur within 24 hours after a toxic dose is ing ested. Emesis, weakness, dyspnea, muscular fasciculations of ears, whiskers, tail and eyes, rear limb ataxia, hypersalivation, de-pression, dehydration, head-pressing, positional nystagmus and slow ed pupillary responses have all been described after toxic in-gestions. Many of these effects may also be seen in dogs after toxic pipe razine ingestions. Treatment is symptomatic and supportive. If ingestion was re-cent, use of activated charcoal and a cathartic has been suggested. Int ravenous ﬂuid therapy and keeping the animal in a quiet, dark place is recommended. Recovery generally takes place within 3-4 days. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving piperazine and may be of signiﬁcance in veterinary patients: !TCHLORPROMAZINE : Although data conﬂicts, piperazine and chlo-rpromazine may precipitate seizures if used concomitantly !TLAXATIVES : The use of purgatives (laxatives) with piperazine is not recommended as the drug may be eliminated before its full ef-ﬁcacy is established !TPYRANTEL/MORANTEL : Piperazine and pyrantel/morantel have antagonistic modes of action and should generally not be used together Laboratory Considerations !TPiperazine can have an effect on uric acid blood levels, but refer-ences conﬂict with regard to the effect. Both falsely high and low val ues have been reported; interpret results cautiously. Doses CAUTION: Piperazine is available in several salts that contain varying amounts of piperazine base (see Chemistry below). Many of the doses listed below do not specify what salt (if any) is used in the dosage calculations. If the dose is in question, refer to the actual product information for the product you are using. !TDOGS: For treatment of ascarids ( Note : Because larval stages in the host's tissues may not be affected by the drug, many clinicians recom-mend retreating about 2-3 weeks after the ﬁrst dose): a) 45-65 mg of base/kg PO; for pups less than 2. 5 kg: 150 mg maximum. (Cornelius and Roberson 1986) b) 110 mg/kg PO (Chiapella 1988) c) 100 mg/kg PO; repeat in 3 weeks (Morgan 1988) d) 20-30 mg/kg PO once (Davis 1985) e) 110 mg/kg PO; repeat in 21 days (Kirk 1989) f) 45-65 mg/kg (as base) PO (Roberson 1988b) !TCATS: For treatment of ascarids ( Note : Because larval stages in the host's tissues may not be affected by the drug, many clinicians recom-mend retreating about 2-3 weeks after the ﬁrst dose): a) 45-65 mg of base/kg PO; 150 mg maximum (Cornelius and Ro berson 1986) b) 110 mg/kg PO (Chiapella 1988) c) 100 mg/kg PO; repeat in 3 weeks (Morgan 1988) d) 20-30 mg/kg PO once (Davis 1985) e) 110 mg/kg PO; repeat in 21 days (Kirk 1989) f) 45-65 mg/kg (as base) PO (Roberson 1988b) !TRABBITS, RODENTS, SMALL MAMMALS: a) Mice, rats, hamsters, gerbils, and rabbits: For pinworms: Pip-erazine citrate in drinking water at 3 grams/liter for 2 weeks. (Bur ke 1999) b) Rabbits: For Pinworms: Piperazine citrate 100 mg/kg PO q24h f or 2 days. Piperazine adipate: Adults: 200-500 mg/kg PO q24h for 2 days. Y oung rabbits: 750 mg/kg, PO once daily for 2 days. Wash the perianal area. (Ivey and Morrisey 2000) c) Mice, Rats, Gerbils, Hamsters, Guinea pigs, Chinchillas: For pinw orms/tapeworms using piperazine citrate: 2-5 mg/m L drinking water for 7 days, off 7 days and repeat (Adamcak and Otten 2000) !THORSES: There are combination products available for use in horses (see Dosage Forms/Preparations section) that contain piperazine with increased efﬁcacy against nematodes and other helminths. Refer to the individual products' package insert for more infor-mation. a) 110 mg/kg (base) PO; repeat in 3-4 weeks. Retreating at 10-week intervals for P. equorum infections in young animals is re commended. (Roberson 1988b) b) 200 mg/kg, PO. Maximum of 80 grams in adults, 60 grams in year lings, and 30 grams in foals. (Brander, Pugh, and Bywater 1982) !TCATTLE, SHEEP & GOATS: Because of high resistance of many nematode species to pipera-zine, it is rarely used alone in these species. !TSWINE: For Ascaris suum and Oesophagostomum: a) 0. 2-0. 4% in the feed, or 0. 1-0. 2% in the drinking water. All medicat ed water or feed must be consumed within 12 hours, so fasting or withholding water overnight may be beneﬁcial to ensure adequate dosing; retreat in 2 months. Safe in young animals, and during pregnancy. Drug withdrawal times not determined for swine. (Paul 1986) b) 110 mg/kg (as base). Citrate salt usually used in feed as a one-day treatment, and hexahydrate in drinking water. Dose must be consumed in 8-12 hours. Withholding water or feed the previous night may be beneﬁcial. (Roberson 1988b) !TBIRDS: a) For ascarids in poultry (not effective in psittacines): 100-500 mg/kg PO onc e; repeat in 10-14 days (Clubb 1986) b) For nematodes: Piperazine citrate: 45-100 mg/kg single dose or 6-10 grams/gallon for 1-4 days. In raptors: 100 mg/kg. In parakeets and canaries: 0. 5 mg/gram (Stunkard 1984) c) For Ascaridia galli in poultry: 32 mg/kg (as base) (approxi-mately 0. 3 grams for each adult) given in each of 2 successive fe edings or for 2 days in drinking water. Citrate or adipate salts are usually used in feed and the hexahydrate in drinking water. (Roberson 1988b) Monitoring !TClinical and/or laboratory efﬁcacy !TAdverse effects Client Information !TClients should be instructed to administer only the amount prescribed and to relate any serious adverse effects to the veterinarian.	pppbs.pdf
TChemistry/Synonyms Piperazine occurs as a white, crystalline powder that may have a slight odor. It is soluble in water and alcohol. Piperazine is available commercially in a variety of salts, including citrate, adipate, phos-phate, hexahydrate, and dihydrochloride. Each salt contains a vari-able amount of piperazine (base): adipate (37%), chloride (48%), citrate (35%), dihydrochloride (50-53%), hexahydrate (44%), phosphate (42%), and sulfate (46%). Piperazine may also be known as diethylendiamin, dispermin, hexahydr opropyrazin, piperazinum, and Pipa-Tabs®. Storage/Stability Unless otherwise speciﬁed by the manufacturer, piperazine prod-ucts should be stored at room temperature (15-30°C). Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Piperazine Dihydrochloride tablets equivalent to 50 mg or 250 mg base. Pipa-Tabs® (Vet-A-Mix); (Rx). Approved for use in dogs and cats. Additional OTC products and combination products may be avail-able for a variety of species. Products and/or trade names include: Al-falfa Pellet Horse Wormer, Tasty Paste® Dog & P uppy Wormer, Wonder Wormer™ for Horses, D-Worm™ Liquid Wormer for Cats and Dogs, Wazine®-17, Wazine®-34, Hartz® Advanced Care™ Liquid Wormer, Hartz® Advanced Care™ Once-a-Month® Wormer for Kittens and Cats, Hartz® Advanced Care™ Once-a-Month® Wormer for Dogs, Ser-geant's® Vetscription® Worm-A way® for Cats, Sergeant's® Vetscription® Sure Shot® Liquid Wormer for Cats & Kittens, Piperazine-17 Medicat-ed, Worm Eze™ Canine Anthelmintic, Worm Eze™ Feline Anthelmintic Paste, W orm Eze™ Canine & Feline Anthelmintic Liquid. HUMAN-LABELED PRODUCTS: None PIRLIMYCIN HCL (per-li-mye-sin) Pirsue® INTRAMAMMARY LINCOSAMIDE ANTIBIOTIC Prescriber Highlights TT Lincosamide antibiotic for intramammary use in dairy cattle TT Milk withdrawal (at labeled doses) = 36 hours after last treatment; Meat withdrawal (at labeled doses) = 9 days Uses/Indications Pirlimycin mastitis tubes are indicated for the treatment of clinical and subclinical mastitis caused by susceptible organisms in lactat-ing dairy cattle. Pharmacology/Actions Like other lincosamides, pirlimycin acts by binding to the 50S ri-bosomal subunit of susceptible bacterial RNA, thus interfering with bac terial protein synthesis. It is primarily active against gram-positive bacteria, including a variety of species of staphylococcus (S. aureus, S. epidermidis, S. chromogenes, S. hyicus, S. xylosus), strep tococcus (S. agalactiae, S. dysgalactiae, S. uberis, S. bovis) and Enterococcus faecalis. Organisms with a MIC of ≤2 mcg/m L ar e considered suscep-tible, and organisms with a MIC value of 4 mcg/m L are considered resistant. If using a 2 microgram disk for Kirby-Bauer plate testing, a zone diameter of ≤12mm indicates resistance and a diameter of *13mm indicates susceptibility. Pharmacokinetics Little information is available; the manufacturer states that the drug penetrates the udder well and is absorbed systemically from the ud-der and then secreted into the milk of all four quarters. Tissue levels in treat ed quarters of pirlimycin are approximately 2-3 times those found in the extracellular ﬂuid. Contraindications/Precautions/Warnings No information was noted. Adverse Effects No adverse affects, including udder irritation have been reported thus far. Milk from untreated quarters must be disposed of during with-drawal time as residues may be detected from untreated quarters. Reproductive/Nursing Safety No information was noted. Overdosage/Acute Toxicity No data was located. Drug Interactions Because erythromycin and clindamycin have shown antagonism in vitro, this could also occur with pirlimycin. Laboratory Considerations T ! he established tolerance of pirlimycin in milk is 0. 4 ppm. Doses T ! CATTLE: a) Lactating Dairy Cattle: Infuse one syringe into each affected quarte r; repeat one time in 24 hours. See label directions for more speciﬁc information on administrative techniques. (Package Insert; Pirsue®—Upjohn) Monitoring T ! Efﬁcacy T ! Withdrawal periods Client Information T ! Be sure clients understand dosage recommendations and with-drawal periods. T ! Milk from untreated quarters must be disposed of during with-drawal time as residues may be detected from untreated quar-ters. Chemistry/Synonyms Pirlimycin HCl is a lincosamide antibiotic. It has a molecular weight of 465. 4. Pirlimycin HCl may also be known as U-57930E and Pirsue®. Storage/Stability Store syringes at or below 25°C (77°F); protect from freezing.	pppbs.pdf
Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Pirlimycin HCl Sterile Solution 50 mg (equiv. to free base) in a 10 m L disposable teat syringe; Pirsue® Aqueous Gel (Pﬁzer); (Rx). Approved for use in lactating dairy cattle. Milk withdrawal (at labeled doses) = 36 hours after last treatment; Meat withdrawal (at labeled doses) = 9 days HUMAN-LABELED PRODUCTS: None PIROXICAM (peer-ox-i-kam) Feldene® NON-STEROIDAL ANTIINFLAMMATORY, ANTI-TUMOR Prescriber Highlights TT NSAID with antiinﬂammatory & antitumor (indirect) activity TT Contraindications: Hypersensitivity or severely allergic to aspirin or other NSAIDs. Extreme Caution: Active, or a history of GI ulcer disease or bleeding disorders. Caution: Severely compromised cardiac function TT Use in cats is controversial; use with extreme caution TT Adverse Effects: GI ulceration & bleeding, renal papillary necrosis, & peritonitis TT Probably safer NSAIDs available for pain/inﬂammation for dogs & cats Uses/Indications In dogs, piroxicam may be beneﬁcial in reducing the pain and in-ﬂammation associated with degenerative joint disease, but there are safer alt ernatives available. Its primary use is in dogs as adjunctive treatment of bladder transitional cell carcinoma. It may also be of beneﬁt in squamous cell carcinomas, mammary adenocarcinoma, and transmissible venereal tumor (TVT). There is some use of it in cats for its anti-tumor effects, but it must be used with extreme caution in this species. Pharmacology/Actions Like other non-steroidal antiinﬂammatory agents, piroxicam has antiinﬂammatory, analgesic, and antipyretic activity. The drug's an-tiinﬂammatory activity is thought to be primarily due to its inhibi-tion of prostaglandin synthesis, but additional mechanisms (e. g., super oxide formation inhibition) may be important. As with other NSAIDs, piroxicam can affect renal function, cause GI mucosal damage, and inhibit platelet aggregation. Piroxicam's antitumor effects are believed to be due to its action on the imm une system and not because of direct effects on tumor cells. Pharmacokinetics After oral administration, piroxicam is well absorbed from the gut. While the presence of food will decrease the rate of absorption, it will not decrease the amount absorbed. It is not believed that ant-acids signiﬁcantly affect absorption. After single oral doses in cats, piroxicam is well absorbed with an oral bioavailability of about 80%. Peak levels occur in approxi-mately 3 hours. Elimination half-life after intravenous dosing is about 12 hours. Pir oxicam is highly bound to plasma proteins. In humans, syn-ovial levels are about 40% of those found in plasma. Maternal milk conce ntrations are only about 1% of plasma levels. In humans, piroxicam has a very long plasma half-life (about 50 hours). The drug is principally excreted as metabolites in the urine after hepatic biotransformation. Contraindications/Precautions/Warnings Piroxicam is contraindicated in patients hypersensitive to it or who are severely allergic to aspirin or other NSAIDs. It should be used only when its potential beneﬁts outweigh the risks in patients with active or history of GI ulcer disease or bleeding disorders. Because peripheral edema has been noted in some human patients, it should be used with caution in patients with severely compromised cardiac function. Piroxicam has not been evaluated for use in cats. It must be used with extr eme caution, if at all, in this species. Adverse Effects Like other NSAIDs used in dogs, piroxicam has the potential for causing signiﬁcant GI ulceration and bleeding. The therapeutic window for the drug is very narrow in dogs, as doses as low as 1 mg/ kg given daily have caused signiﬁcant GI ulceration, renal papillary necrosis, and peritonitis. Other adverse effects reported in humans and potentially possible in dogs include: CNS effects (headache, dizziness, etc. ), otic effects (tinnitus), elevations in hepatic function tests, pruritus and rash, and peripheral edema. Renal papillary ne-crosis has been seen in dogs at post-mortem but, apparently, clini-cal effects have not been noted with these occurrences. Reproductive/Nursing Safety Animal studies have not demonstrated any teratogenic effects as-sociated with piroxicam. The drug is excreted into milk in very low conce ntrations (about 1% found in maternal plasma). 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 ar e no adequate studies in humans; or there are no animal repro-duction studies and no adequate studies in humans. ) If using in the third tr imester or near delivery in humans, the FDA categorizes all NSAIDs 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. ) Most NSAIDs are excreted in maternal milk; use with caution in nursing patie nts. Overdosage/Acute Toxicity There is limited information available, but dogs may be more sensi-tive to the drugs ulcerative effects than are humans. There were 87 exposures to piroxicam reported to the ASPCA Animal Po ison Control Center (APCC; www. apcc. aspca. org) dur-ing 2005-2006. In these cases 76 were dogs with 8 showing clini-cal signs and 11 were cats with 3 showing clinical signs. Common ﬁndings in d ogs recorded in decreasing frequency included vom-iting, abdominal pain, diarrhea, lethargy and abnormal colored feces. Common ﬁndings in cats recorded in decreasing frequency included vomiting. As with any NSAID, overdosage can lead to gastrointestinal and renal e ffects. Decontamination with emetics and/or activated char-coal is appropriate. For doses where GI effects are expected, the use of gast rointestinal protectants is warranted. If renal effects are also expected, ﬂuid diuresis is should be considered. Patients ingesting	pppbs.pdf
signiﬁcant overdoses should be monitored carefully and treated supportively. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving piroxicam and may be of signiﬁcance in veterinary patients: !TAMINOGLYCOSIDES (gentamicin, amikacin, etc. ): Increased risk for nephrotoxicity !TANTICOAGULANTS (heparin, LMWH, warfarin ): Increased risk for bleeding possible !TASPIRIN : When aspirin is used concurrently with piroxicam, plasma levels of piroxicam could decrease and an increased like-lihood of GI adverse effects (blood loss) could occur. Concomi-tant administration of aspirin with piroxicam cannot be recom-mended. !TBISPHOSPHONATES (alendronate, etc. ): May increase risk for GI ulceration !TCISPLATIN : Piroxicam may potentiate the renal toxicity of cisplatin when used in combination !TCORTICOSTEROIDS : Concomitant administration with NSAIDs may signiﬁcantly increase the risks for GI adverse effects !TFUROSEMIDE : Piroxicam may reduce the saluretic and diuretic ef-fects of furosemide !THIGHLY PROTEIN BOUND D RUGS (e. g., phenytoin, valproic acid, oral anti-coagulants, other antiinﬂammatory agents, salicylates, sulfonamides, and the sulfonylurea antidiabetic agents ): Because piroxicam is highly bound to plasma proteins (99%), it potentially could dis-place other highly bound drugs; increased serum levels and dura-tion of actions may occur. Although these interactions are usually of little concern clinically, use together with caution. !TMETHOTREXATE : Serious toxicity has occurred when NSAIDs have been used concomitantly with methotrexate; use together with extreme caution Laboratory Considerations !TPiroxicam may cause falsely elevated blood glucose values when using the glucose oxidase and peroxidase method using ABTS as a chromogen. Doses !TDOGS: As an adjunctive therapy of transitional cell carcinomas, squamous cell carcinomas, and palliative therapy for other neo-plastic diseases: a) 0. 3 mg/kg PO once a day (Frimberger and London 2003) b) 0. 3 mg/kg PO once a day. Give with food. Consider add-ing misoprostol at 3 mcg/kg, PO q8h for dogs who tolerate NSAIDs p oorly. Discontinue if severe irritation or ulceration occurs. Treat ulcers and if signs abate, may resume piroxicam with misoprostol. (Frimberger 2000) c) For adjuvant therapy for splenic hemangiosarcoma (stage II): E toposide 50 mg/m2 PO once daily for 3 weeks, alternat-ing 3 week cycles with cyclophosphamide at 12. 5-25 mg/m2 PO o nce daily. Piroxicam is given at 0. 3 mg/kg PO every day. Continue until disease recurrence and progression is noted. (Lana, U'ren et al. 2007) d) For transitional cell carcinoma after laser ablation of the pr imary tumor: Mitoxantrone at IV 5 mg/m2 every 3 weeks for 4 treatments. Piroxicam was given at a dosage of 0. 3 mg/ kg PO once daily for the remaining life of the dog. (Upton, Tanger et al. 2006) As an antiinﬂammatory/analgesic: a) 0. 3 mg/kg PO every other day (q48h) (Boothe 1992), (Han-sen 2003b) !TCATS: As an adjunctive therapy of transitional cell carcinomas, but may be of limited utility in squamous cell carcinoma: a) 0. 3 mg/kg PO q24-72h. Gastric protectants (misoprostol, H2 blockers sucralfate, omeprazole) may be useful to pre-vent/teat GU ulceration. Use with caution in patients with pr e-existing renal disease and avoid use with other neph-rotoxic drugs. Fluid supplementation may be warranted. (Smith 2003a) !TRABBITS, RODENTS, SMALL MAMMALS: Rabbits: For fracture associated limb swelling: a) 0. 1-0. 2 mg/kg PO q8h for 3 weeks (Ivey and Morrisey 2000) Monitoring !TAdverse Effects (particularly GI bleeding) !TLiver function and renal function tests should be monitored oc-casionally with chronic use Client Information !THave clients monitor for GI ulceration/bleeding (anorexia, tarry stools, etc. ). !TDo not exceed dosage recommendations without veterinarian's approval. It has been suggested to give the drug with food to re-duce GI upset potential. Chemistry/Synonyms An oxicam derivative non-steroidal antiinﬂammatory agent, piroxi-cam occurs as a white, crystalline solid. It is sparingly soluble in wate r. Piroxicam is structurally not related to other non-steroidal antiinﬂammatory agents. Piroxicam may also be known as: CP-16171, piroxicamum or PIR O; many trade names are available. Storage/Stability Capsules should be stored at temperatures less than 30°C in tight, light-resistant containers. When stored as recommended, capsules have an expiration date of 36 months after manufacture. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 4 substance. See the appendix for more information. HUMAN-LABELED PRODUCTS: Piroxicam Capsules: 10 mg & 20 mg; Feldene® (Pﬁzer); generic; (Rx) Plasma-Lyte—see the section on intravenous ﬂuids in the Appendix	pppbs.pdf
POLYSULFATED GLYCO SAMINOGLYCAN ( PSGAG) (pol-ee-sulf-ayte-ed glye-kose-a-meen-ohe-glye-kan) Adequan®, Chondroprotec® PROTEOLYTIC ENZYME INHIBITOR; CHONDROPROTECTANT Prescriber Highlights TT Proteolytic enzyme inhibitor used IM or intra-articularly for non-infectious &/or traumatic joint dysfunction & as-sociated lameness of the carpal joints in horses & non-infectious degenerative &/or traumatic arthritis in dogs TT Contraindications: Intra-articular injection if patient hy-persensitive to PSGAG. Should not be used in place of other treatments when infection suspected or present, or when surger y or joint immobilization required TT Adverse Effects: IM use: Unlikely. Intra-articular: Post-injection inﬂammation possible. Dogs: Dose-related inhi-bition of coagulation/hemostasis possible. Uses/Indications PSGAG administered either IM or IA is indicated for the treatment of non-infectious and/or traumatic joint dysfunction and associ-ated lameness of the carpal joints in horses. Some studies have in-dicated that PSGAG is much less effective in joints where there has been a cute trauma but no degradative enzymes present. It is also approved for the control of signs associated with non-infectious degenerative and/or traumatic arthritis in dogs. Pharmacology/Actions In joint tissue, PSGAG inhibits proteolytic enzymes that can de-grade proteoglycans (including naturally occurring glycosamino-glycans), thereby preventing or reducing decreased connective tissue ﬂexibility, resistance to compression, and resiliency. By acting as a precursor, PSGAG increases the synthesis of proteoglycans, reduces inﬂammation by reducing concentrations of prostaglandin E 2 (re-leased in response to joint injury) and increases hyaluronate con-centrations in the joint, thereby restoring synovial ﬂuid viscosity. Pharmacokinetics PSGAG is deposited in all layers of articular cartilage and prefer-entially taken up by osteoarthritic cartilage. When administered IM, articular levels will with time exceed those found in the serum. After IM injection, peak joint levels are reached in 48 hours and persist up to 96 hours. Contraindications/Precautions/Warnings PSGAG is contraindicated for intra-articular administration in pa-tients hypersensitive to it. While the manufacturer states there are no cont raindications for IM use of the drug, the drug should not be used in place of other therapies in cases where infection is present or suspected, or in place of surgery or joint immobilization where indicated. Some clinicians feel that PSGAG should not be used within one week o f arthrotomy in dogs, because it may cause increased bleed-ing. This effect apparently has not been conﬁrmed in the literature, howev er. Adverse Effects Adverse effects are unlikely when using the IM route. Intra-articular administration may cause a post-injection inﬂammation (joint pain, effusion, swelling, and associated lameness) secondary to sensitivity reactions, traumatic injection technique, overdosage, or the number or frequency of the injections. Treatment consisting of antiinﬂammatory drugs, cold hydrotherapy, and rest is recom-mended. Although rare, joint sepsis secondary to intraarticular in-jection is possible; strict aseptic technique should be employed to minimize this occur rence. In dogs, a dose-related inhibition of coagulation/hemostasis has been d escribed. Reproductive/Nursing Safety Reproductive studies have apparently not been performed; use with caution during pregnancy or in breeding animals (the manufac-turer does not recommend use in breeding animals). In humans, the FDA categorizes glycosaminoglycans as category B for use during pregnancy (Animal studies have not yet demon-strated 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 glycosaminoglycans are excreted in ma-ternal milk, but is unlikely to be of signiﬁcant concern. Overdosage/Acute Toxicity Doses ﬁve times those recommended (2. 5 grams) given IM to horses twice weekly for 6 weeks revealed no untoward effects. Approximately 2% of horses receiving overdoses (up to 1250 mg) IA showed transient clinical signs associated with joint inﬂammation. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving PSGAG and may be of signiﬁcance in veterinary patients: While speciﬁc drug interactions have not been detailed to date, using this pr oduct in conjunction with either steroids or non-ste-roidal antiinﬂammatory agents could mask the signs and clinical signs associate d with septic joints. There is some concern that since PSGAG is a heparin analog that it should not be used in conjunction with other NSAIDs or other anticoagulants. Clinical signiﬁcance remains unclear, but use together with caution. Doses T ! HORSES: a) For IM administration: 500 mg IM (of IM product) every 4 days f or 28 days. Thoroughly cleanse injection site before in-jecting. Do not mix with other drugs or chemicals. (Pac kage Insert; Adequan® I. M. ) For intra-articular administration: 250 mg (of IA product) IA once a week for 5 weeks. Joint area should be shaved, and cleansed as if a surgical procedure, prior to injecting. Do not mix with other drugs or chemicals. (Package Insert; Ad-equan® I. A. ) b) For IM injection: 500 mg IM every 3-4 days for a minimum of 4 and preferably, 7 treatments. For int ra-articular injection: As above; author recommends adding 125 mg of amikacin for injection into the IA injection to reduce potential for infection. (Nixon 1992)	pppbs.pdf
TT ! DOGS: For the treatment of non-infectious degenerative and/or trau-matic arthritis: a) 4. 4 mg/kg IM twice weekly for up to 4 weeks. (Label informa-tion; Adequan® Canine—Luitpold) b) 1. 1-4. 8 mg/kg IM every 4 days for six doses and then as neede d (Kelly 1995) c) Osteoarthritis: 5 mg/kg IM twice a week (Mc Laughlin 2000) d) Osteoarthritis: 5 mg/kg IM once weekly (Hardie and Grauer 2007) T ! CATS: As a chondroprotective drug: a) 1. 1-4. 8 mg/kg IM every 4 days for six doses and then as neede d (Kelly 1995) b) 2 mg/kg IM every 3-5 days for 4 treatments; only anecdotal exper ience in cats. (Kerwin 2007) T ! RABBITS, RODENTS, SMALL MAMMALS: a) Rabbits: For arthritis: 2. 2 mg/kg SC or IM every 3 days for 21-28 days, then once ever y 2 weeks (Ivey and Morrisey 2000) Monitoring T ! Efﬁcacy T ! Joint inﬂammation/infection if administered IA. Client Information T ! he IA product must be administered by veterinary profession-als; the IM product could, with proper instruction, be adminis-tered by the owner. Chemistry/Synonyms Polysulfated glycosaminoglycan (PSGAG) is chemically similar to natural mucopolysaccharides found in cartilaginous tissues. PSGAG is reportedly an analog of heparin. Polysulfated glycosaminoglycan is also known as PSGAG, Adequan® and Chondr oprotec®. Storage/Stability/Compatibility Commercial products should be stored in a cool place 8-15°C (46-59°F). The manufacturer recommends discarding any unused portion from the vial or ampule and, also does not recommend mixing with any other drug or chemical. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Polysulfated Glycosaminoglycan for Intra-Articular Injection: 250 mg/m L in 1 m L single use vials, boxes of 6; Adequan® I. A. (Luitpold); (Rx). Approved for use in horses, (not in those intended for food). Polysulfated Glycosaminoglycan for Intra-Muscular Injection: 100 mg/m L in 5 m L glass ampules or 5 m L vials, boxes of 4; Adequan® I. M. (Luitpold); (Rx). Approved for use in horses, (not in those in-tended for food). Polysulfated Glycosaminoglycan for IM Injection: 100 mg/m L; Ad-equan® Canine (Luitpold); (Rx). Approved for use in dogs. Polysulfated Glycosaminoglycan T opical Solution: sterile solution of 1000 mg in 10 m L vials. Approved for use on horses. No reported side effects. Chondroprotec® (Neogen) (Rx) HUMAN-LABELED PRODUCTS: None PONAZURIL (poe-naz-yoor-ill) Marquis® ANTIPROTOZOAL Prescriber Highlights TT Equine approved triazine for treating EPM TT Adverse Effect proﬁle not well established; in ﬁeld trials: rashes, hives, blisters, or GI signs noted TT Treatment is relatively expensive Uses/Indications Ponazuril is indicated for the treatment of equine protozoal myelo-encephalitis (EPM) caused by Sarcocystis neurona. Ponazuril could potentially be useful in treating Neospora cani-num and T oxoplasma infections in dogs or cats. Pharmacology/Actions The triazine class of antiprotozoals are believed to target the “plas-tid” body, an organelle found in the members of the Apicomplexa phyl um, including Sarcocystis neurona. In vitro levels required to kill Sarcocystis neurona range from 0. 1-1 mcg/m L. Pharmacokinetics After daily (5 mg/kg) oral administration to horses, ponazuril reaches its peak serum levels in about 18 days and peak CSF levels in about 15 days. Peak CSF levels are about 1/20th (0. 21 mcg/m L) those found in the serum. Elimination half-life from serum aver-ages about 4. 5 days. Contraindications/Precautions/Warnings None were noted. Before treating, other conditions that can cause ataxia should be ruled out. Adverse Effects Limited experience at time of writing. Field trials showed some ani-mals developing blisters on nose and mouth or a rash/hives. Single animals deve loped diarrhea, mild colic or seizures. Successful treatment may not negate all the clinical signs associ-ated with EPM. Keratoconjunctivitis sicca (KCS) has been reported in some dogs, especially those breeds with a predilection towards develop-ing KCS or when the drug was given in overdose quantities. Reproductive/Nursing Safety Safety during pregnancy or in lactating mares has not been evaluated. Overdosage/Acute Toxicity Daily doses of up to 30 mg/kg (6X) primarily caused loose feces. Moderate edema of the uterine epithelium was noted on histopa-thology for female horses receiving the 6X dose. Drug Interactions/Laboratory Considerations None noted	pppbs.pdf
Doses T ! DOGS, CAT S: a) For Neosporosis or T oxoplasmosis: 7. 5-15 mg/kg PO once daily fo r 28 days. Dose extrapolated between doses for horses and mice. (Greene, Hartmannn et al. 2006) b) For coccidiosis: Anecdotally, 15-30 mg/kg PO once or re-peated after 7-10 days. (Hurley 2007) T ! HORSES: For EPM: a) 5 mg/kg, PO once daily for 28 days. See the package insert for sp eciﬁc dosing instructions. (Package insert; Marquis®— Bayer) Monitoring T ! Clinical efﬁcacy Client Information T ! For this drug to be effective it must be given as prescribed. T ! Contact veterinarian if rashes, hives, blisters, or GI signs develop. T ! Clients should be forewarned of the considerable expense associ-ated with this drug and that clinical improvement may be mar-ginal or not occur at all in some horses treated. Chemistry/Synonyms Related to other antiprotozoals such as toltrazuril, ponazuril is a triazine antiprotozoal (anticoccidial) agent. The commercially available oral paste is white to off-white in color and odorless; p H is 5. 7-6. Ponazuril may also be known as: ICI-128436, Marquis®, and Ponalrestat®. Storage/Stability Store the paste at room temperature (15-30°C). Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Ponazuril Oral Paste (15% w/w): 127-gram tubes; each gram of paste contains 150 mg of ponazuril; each syringe is enough to treat a 1200 lb. horse for 7 days. Marquis® (Bayer); (Rx). Not for use in horses intended for food. HUMAN-LABELED PRODUCTS: None Potassium Bromide-see Bromides Potassium Iodide-see Iodide, Potassium POTASSIUM CHLORIDE POTASSIUM GLUCONATE (po-tass-ee-um) Cal-Dextro® K, Tumil-K® ELECTROLYTE Prescriber Highlights TT Used for treatment or prevention of hypokalemia TT Contraindications: Hyperkalemia, renal failure or severe renal impairment, severe hemolytic reactions, untreated Addison's disease, acute dehydration, GI motility impair-ment (solid oral dosage forms) TT Caution: Patients on digoxin TT Adverse Effects: Hyperkalemia. Oral therapy: GI distress; IV therapy may be irritating to veins TT Intravenous potassium salts must be diluted before ad-ministering & drug must be given slowly TT Acid/base, hydration status important TT Drug Interactions Uses/Indications Potassium supplementation is used to prevent or treat potassium deﬁcits. When feasible and appropriate, because it is generally safer, oral or nutritional therapy is generally preferred over parenteral potassium administration. Pharmacology/Actions Potassium is the principal intracellular cation in the body. It is es-sential in maintaining cellular tonicity; nerve impulse transmission; smooth, ske letal and cardiac muscle contraction; and maintenance of normal renal function. Potassium is also used in carbohydrate utilization and protein synthesis. Pharmacokinetics Potassium is primarily (80-90%) excreted via the kidneys with the majority of the remainder excreted in the feces. Very small amounts may be excreted in perspiration (animals with sweat glands). Contraindications/Precautions/Warnings Potassium salts are contraindicated in patients with hyperkalemia, renal failure or severe renal impairment, severe hemolytic reac-tions, untreated Addison's disease, and acute dehydration. Solid oral d osage forms should not be used in patients where GI mo-tility is impaired. Use cautiously in digitalized patients (see Drug Inter actions). Because potassium is primarily an intracellular electrolyte, se-rum levels may not adequately reﬂect the total body stores of potas-sium. Acid-base balance may also mask the actual potassium pic-ture. Patients with systemic acidosis conditions may appear to have hype rkalemia when, in fact, they may be signiﬁcantly low in total body potassium. Conversely, alkalosis may cause a falsely low serum potassium value. Assess renal and cardiac function prior to thera-py and closely monitor serum potassium levels. Supplementation should gene rally occur over 3-5 days to allow equilibration to occur between extracellular and intracellular ﬂuids. Some clinicians feel that if acidosis is present or a concern, use potassium acetate, citrate or bicarbonate; if alkalosis is present, use potassium chloride.	pppbs.pdf
Adverse Effects The major problem associated with potassium supplementation is the development of hyperkalemia. Clinical signs associated with hyperkalemia can range from muscular weakness and/or GI dis-turbances to cardiac conduction disturbances. Clinical signs can be exa cerbated by concomitant hypocalcemia, hyponatremia, or aci-dosis. Intravenous potassium salts must be diluted before adminis-tering and given slowly (see Doses). Oral therapy can cause GI distress and IV therapy may be irritat-ing to veins. Reproductive/Nursing Safety Monitored potassium supplementation is unlikely to have negative effects during pregnancy or lactation. Overdosage/Acute Toxicity Fatal hyperkalemia may develop if potassium salts are administered too rapidly IV or if potassium renal excretory mechanisms are im-paired. Clinical signs associated with hyperkalemia are noted in the Ad verse Effects section above. Treatment of hyperkalemia is depen-dent upon the cause and/or severity of the condition and can con-sist of: discontinuation of the drug with ECG, acid/base and elec-trolyte monitoring, glucose/insulin infusions, sodium bicarbonate, calcium therapy, and polystyrene sulfonate resin. It is suggested to refer to other references appropriate for the species being treated for speciﬁc protocols for the treatment of hyperkalemia. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving potassium and may be of signiﬁcance in veterinary patients: !TACE INHIBITORS (e. g., enalapril ): Potassium retention may occur; increased risk for hyperkalemia !TDIGOXIN : In patients with severe or complete heart block who are receiving digitalis therapy, it is often recommended not to use potassium salts !TNSAIDS : Oral potassium given with non-steroidal antiinﬂam-matory agents may increase the risk of gastrointestinal adverse effects !TPOTASSIUM-SPARING DIURETICS (e. g., spironolactone ): Potassium re-tention may occur; increased risk for hyperkalemia Doses !TDOGS & CAT S: For hypokalemia: a) Intravenous replacement: If animal has normal renal func-tion, IV KCl not to exceed 0. 5 m Eq/kg/hr. Use IV replace-ment very cautiously in animals with impaired renal func-tion or in those receiving potassium-sparing diuretics. Subcutaneous replacement: If IV use is unfeasible or rapid co rrection is unnecessary, may add KCl to SC ﬂuids; do not exceed 30 m Eq of potassium per liter. Oral replacement: Potassium gluconate PO at a rate of 2. 2 m Eq per 100 calories of required energy intake or potassium gluconate elixir (20 m Eq/m L) for dogs at 5 m L q8-12h PO (Bell and Osborne 1986) b) Oral using Tumil-K ® (Virbac): 1/4 teaspoonful (2 m Eq) per 4. 5 kg body weight PO in food twice daily. Adjust dose as nec essary. (Package insert; Tumil-K®—Virbac). c) Intravenous replacement: potassium chloride IV at a rate not t o exceed 0. 5 m Eq/hour. Concentration of replacement ﬂuid should exceed 60 m Eq/L. Begin oral supplementation as soon as possible using potassium gluconate for dogs at a dose of 2-44 m Eq/day depending on body size; cats get 2-4 m Eq/da y. (Peres 2000) d) Potassium administration should be considered on the ba-sis of how much potassium to administer to the patient, not how much to add to a bag of ﬂuid. Dosages usually range from maintenance (0. 05-0. 1 m Eq/kg/hour) to 0. 5 m Eq/kg/ hour. (Hansen 2007c) !TRUMINANTS: For hypokalemia: a) In “downer” cows: 80 g sodium chloride and 20 g potassium chlo ride in 10 liters of water PO via stomach tube. Provide a bucket containing similar solution for cow to drink and another containing fresh water. (Caple 1986) b) 50 grams PO daily; 1 m Eq/kg/hr IV drip (Howard 1986) c) For severe hypokalemia (<2. 3 m Eq/L) with severe muscle weakness or recumbency: Isotonic potassium chloride (11. 5 grams of potassium chloride per 1 liter of sterile water) at a rate of 4 m L/kg/hour. Combined with large doses of oral potassium salts (i. e., 200 grams of KCl per day. (Smith 2006) Monitoring Level and frequency of monitoring associated with potassium ther-apy is dependent upon the cause and/or severity of hypokalemia, acid/base abnormalities, renal function, concomitant drugs admin-istered, or disease states and can include: !TSerum potassium !TOther electrolytes !TAcid/base status !TGlucose !TECG !TCBC !TUrinalyses Chemistry/Synonyms Potassium chloride occurs as either white, granular powder or as colorless, elongated, prismatic, or cubical crystals. It is odorless and has a saline taste. One gram is soluble in about 3 m L of water and is insoluble in alcohol. The p H of the injection ranges from 4-8. One gram of potassium chloride contains 13. 4 m Eq of potassium. A 2 m Eq/m L solution has an osmolarity of 4000 m Osm/L. Potassium chloride may also be known as KCl. Potassium gluconate occurs as white to yellowish white, crystal-line powder or granules. It is odorless, has a slightly bitter taste, and is freely soluble in water. One gram of potassium gluconate contains 4. 3 m Eq of potassium. Potassium Chloride may also be known as: KCl, cloreto de po-tassio, E508, kalii chloridum, or kalium chloratum. Potassium Gluconate may also be known as: E577, K-G Elix ir®, Kaon®, Kaylixir®, Potasoral®, Potassiject®, Potassium-Rougier®, Renakare®, Sopa-K®, Tumil-K®, and Ultra-K®. Storage/Stability/Compatibility Potassium gluconate oral products should be stored in tight, light resistant containers at room temperature (15-30°C), unless other-wise instructed by the manufacturer. Unless otherwise directed by the manufacturer, potassium chlo-ride products should be stored in tight, containers at room tem-perature (15-30°C); protect from freezing. Potassium chloride for injection is reportedly physically compat-ible with the following intravenous solutions and drugs (as an addi-tive): all commonly used intravenous replacement ﬂuids (not 10% fat e mulsion), aminophylline, amiodarone HCl, bretylium tosylate, calcium gluconate, carbenicillin disodium, cephalothin sodium,	pppbs.pdf
cephapirin sodium, chloramphenicol sodium succinate, cimetidine HCl, clindamycin phosphate, corticotropin (ACTH), cytarabine, dimenhydrinate, dopamine HCl, erythromycin gluceptate/lactobi-onate, heparin sodium, hydrocortisone sodium succinate, isoprot-erenol HCl, lidocaine HCl, metaraminol bitartrate, methicillin so-dium, methyldopate HCl, metoclopramide HCl, nafcillin sodium, norepine phrine bitartrate, oxacillin sodium, oxytetracycline HCl, penicillin G potassium, phenylephrine HCl, piperacillin sodium, sodium bicarbonate, tetracycline HCl, thiopental sodium, vanco-mycin HCl, verapamil HCl, and vitamin B-complex with C. Potassium chloride for injection compatibility information conﬂicts or is dependent on diluent or concentration factors with the follow-ing drugs or solutions: fat emulsion 10%, amikacin sulfate, dobu-tamine HCl, methylprednisolone sodium succinate (at Y-site), pen-icillin G sodium, and promethazine HCl (at Y-site). Compatibility is dep endent upon factors such as p H, concentration, temperature, and diluent used; consult specialized references or a hospital phar-macist for more speciﬁc information. Potassium chloride for injection is reportedly physically incom-patible with the following solutions or drugs: amphotericin B, diaz-epam (at Y-site), and phenytoin sodium (at Y-site). PRALIDOXIME CHLORIDE 2-PAM CHLORIDE (pra-li-dox-eem) Protopam Chloride® ANTIDOTE; CHOLINESTERASE REACTIV ATOR Prescriber Highlights TT Cholinesterase reactivator used for adjunctive treatment of organophosphate poisoning TT Contraindications: Hypersensitivity; generally not recom-mended for carbamate poisoning TT Caution: Renal impairment, patients receiving anticho-linesterase agents for the treatment of myasthenia gravis TT Adverse Effects: Rapid IV injection may cause tachycar-dia, muscle rigidity, transient neuromuscular blockade, or laryngospasm TT Most-effective if given within 24 hours of exposure Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: There are several products for parenteral use that contain potassium; refer to the tables in the appendix or individual proprietary veteri-nary products (e. g., Cal-Dext ro® K—Fort Dodge) for additional in-formation. Potassium Chloride IV Solution: 2 m Eq (149 mg) in 10 m L vials; Potassij ect® (Butler); generic; (Rx) Oral Products: Potassium Gluconate Tablets: 2 m Eq (468 mg). Labeled for use in cats and dogs; T umil-K® (Virbac), Renakare® (Neogen); (Rx) Potassium Gluconate Oral Powder: Each 0. 65 gram 4 oz (1/4 tea-spoonful) contains 2 m Eq of potassium in 4 oz. Containers; Rena-kar e® (Neogen); Tumil-K® ( Virbac) (Rx). Labeled for use in dogs and cats. Potassium Gluconate Gel: Each 2. 34 gm (1/2 teaspoonful) contains 2 m Eq of potassium in 5 oz tubes; Tumil-K® Gel (Virbac), Renakare® (Neogen) (Rx). Labeled for use in dogs and cats. HUMAN-LABELED PRODUCTS: Not a complete list. Parenteral Products: Potassium Chloride for Injection Concentrate (Must be diluted before administering ): 2 m Eq/m L in 250 m L and 500 m L; 10 m Eq in 5 m L, 10 m L, 50 m L and 100 m L vials & 5 m L additive syringes; 20 m Eq in 10 m L and 20 m L vials, 10 m L additive syringes and amps; 30 m Eq in 15 m L, 20 m L, 30 m L and 100 m L vials and 20 m L additive syringes; 40 m Eq in 20 m L, 30 m L, 50 m L and 100 m L vials, 20 m L amps and additive syringes; 60 m Eq and 90 m Eq in 30 m L vials; generic; (Rx) Potassium acetate for injection and potassium phosphate for in-jection (see Phosphate monograph) are also available. There are a multitud e of human-labeled potassium salts for oral use available in several dosage forms; refer to human drug references for more infor-mation on these products. Tablets, controlled/sustained release tab-lets and capsules, effervescent tablets, liquids, and powder in varying strengths a vailable; (OTC and Rx) Potassium Citrate—see Citrate Salts Uses/Indications Pralidoxime is used in the treatment of organophosphate poison-ing, often in conjunction with atropine and supportive therapy. Pharmacology/Actions Pralidoxime reactivates cholinesterase that has been inactivated by phosphorylation secondary to certain organophosphates. Via nu-cleophilic attack, the drug removes and binds the offending phos-phoryl group attached to the enzyme, which is then excreted. Pharmacokinetics Pralidoxime is only marginally absorbed after oral dosing; oral dos-age forms are no longer available in the United States. It is distribut-ed primarily throughout the extracellular water. Because of its qua-ternary ammonium structure, it is not believed to enter the CNS in signiﬁcant quant ities, but recent studies and clinical responses have led some to question this belief. Pralidoxime is thought to be metabolized by the liver and ex-creted as both metabolite(s) and unchanged drug in the urine. Contraindications/Precautions/Warnings Pralidoxime is contraindicated in patients hypersensitive to it. Pralidoxime is generally not recommended for use in instances of carbamate poisoning because inhibition is rapidly reversible, but there is some controversy regarding this issue. Pralidoxime should be used with caution in patients receiving anticholineste rase agents for the treatment of myasthenia gravis as it may precipitate a myasthenic crisis. It should also be used cautious-ly and at a reduced dosage rate in patients with renal impairment. Adverse Effects At usual doses, pralidoxime generally is safe and free of signiﬁcant adverse effects. Rapid IV injection may cause tachycardia, muscle rigidity, transient neuromuscular blockade, and laryngospasm. Pralidoxime must generally be given within 24 hours of expo-sure to be effective, but some beneﬁts may occur, particularly in large expos ures, if given within 36-48 hours.	pppbs.pdf
TReproductive/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 this drug is excreted in maternal milk; exer cise caution. Overdosage/Acute Toxicity The acute LD 50 of pralidoxime in dogs is 190 mg/kg and, at high dosages, causes signs associated with its own anticholinesterase ac-tivity. Clinical signs of toxicity in dogs may be exhibited as muscle weakness, ataxia, v omiting, hyperventilation, seizures, respiratory arrest, and death. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving pralidoxime and may be of signiﬁcance in veterinary patients: T ! BARBITURATES : Anticholinesterases can potentiate the action of barbiturates; use with caution. T ! CIMETIDINE, SUCCINYLCHOLINE, THEOPHYLLINE, RESERPINE, and RE-SPIRATORY DEPRESSANT DRUGS (e. g., narcotics, phenothiazines ): Use should be avoided in patients with organophosphate toxicity. Doses Note : Often used in conjunction with atropine; refer to that mono-graph and/or the references below for more information. T ! DOGS & CAT S: For organophosphate poisoning: a) Pralidoxime works best when combined with atropine. Prali-doxime at 20 mg/kg, 2-3 times a day. Initial dose may be give n either IM or slow IV. Subsequent doses may be given IM or SC. (Refer to reference for more speciﬁc guidelines re-garding adjunctive therapy) (Fikes 1990) b) 10-15 mg/kg IM or SC q8-12h; 36 hour minimum (Firth 2000) c) Give atropine ﬁrst at 0. 1 mg/kg IV, followed by an additional 0. 3 mg/kg IM. Then pralidoxime at 50 mg/kg diluted in 10% glucose and administered via slow IV. If a severe poisoning and muscle weakness has not been relieved, may give another dose in one hour. For small dogs or cats, pralidoxime may be administered IM or IP. Reduce dose in presence of renal failure. Recovery should occur gradually over 48 hours. (El Bahri 2002) d) Dogs: 50 mg/kg; Cats 20 mg/kg. Give IV slowly or with ﬂu-ids over a 30-minute period. Repeat in one hour if clinical signs pe rsist and then q8h for 24-48 hours. Author recom-mends using pralidoxime in animals that are severely de-pressed, weak, and anorectic one or more days after exposure if not pr eviously treated with pralidoxime. In animals that have clinical signs intensiﬁed (e. g., respiratory depression), reduce dose and give as repeated one-hour infusions every 4-8 hours in combination with atropine (0. 04-0. 4 mg/kg) once or as needed (Mount 1989) e) Cats: 20 mg/kg IM or IV within ﬁrst 24 hours of exposure. May r epeat q6-8h and combine with atropine or give sepa-rately. Do not use in carbamate toxicity. (Reid and Oehme 1989) T ! CATTLE: Note : When used in food animals, FARAD recommends a 28 day meat and a 6 day milk withdrawal time. (Haskell, Payne et al. 2005) For organophosphate poisoning: a) 25-50 mg/kg as a 20% solution IV over 6 minutes; or as a maximum of 100 mg/kg/da y as an IV drip (Smith 1986) T ! HORSES: For organophosphate poisoning: a) 20 mg/kg (may require up to 35 mg/kg) IV and repeat q4-6h (Oehme 1987c) T ! BIRDS: For organophosphate poisoning: a) 10-20 mg/kg q8-12h (route not speciﬁed) with atropine (0. 2-0. 5 mg/kg IM q3-4h). (Jones 2007a) Monitoring T ! Pralidoxime therapy is monitored via the clinical signs associated with organophosphate poisoning. For more information, refer to one of the references outlined in the dosage section. Client Information T ! his agent should only be used with close professional supervision. Chemistry/Synonyms A quaternary ammonium oxime cholinesterase reactivator, prali-doxime chloride occurs as a white to pale yellow, crystalline powder with a p K a o f 7. 8-8. It is freely soluble in water. The commercially available injection has a p H of 3. 5-4. 5 after reconstitution. Pralidoxime Chloride may also be known as: 2-Formyl-1-meth-ylpyridinium chloride oxime, 2-PAM, 2-PAM chloride, 2-PAMCl, 2-pyridine ald oxime methochloride and Protopam®. Storage/Stability Unless otherwise instructed by the manufacturer, pralidoxime chloride powder for injection should be stored at room tempera-ture. After reconstituting with sterile water for injection, the solu-tion should be used within a few hours. Do not use sterile water with prese rvatives added. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Pralidoxime Chloride Powder for Injection: 1 g in 20 m L single-use vials; Protopam® Chloride (Wyeth-Ayerst); (Rx) PRAZIQUANTEL (pra-zi-kwon-tel) Droncit® ANTICESTODAL ANTIPARASITIC Prescriber Highlights TT Anticestodal anthelmintic also may be useful for some other parasites TT Contraindications: Puppies less than 4 weeks old or kit-tens less than 6 weeks old; hypersensitivity to the drug TT Adverse Effects: Uncommon after oral use; pain at injec-tion site, anorexia, salivation, vomiting, lethargy, weak-ness, or diarrhea possible after using injectable	pppbs.pdf
Uses/Indications Praziquantel is indicated for (approved labeling) for the treatment of Dipylidium caninum, Taenia pisiformis, and Echinococcus granu-losis in dogs, and D ipylidium caninum and Taenia taeniaeformis in cats. Fasting is not required nor recommended before dosing. A single dose is usually effective, but measures should be taken to pre-vent reinfection, particularly against D. caninum. Praziquantel can also be used for treating Alaria spp. in dogs and cats and Spirometra mansonoides infections in cats. Praziquantel has been used in birds and other animals, but it is us ually not economically feasible to use in large animals. In hu-mans, praziquantel is used for schistosomiasis, other trematodes (lung, liver, intestinal ﬂukes) and tapeworms. It is not routinely ef-fective in treating F. hepatica infections in humans. Combination products can give a wide spectrum of internal parasit e control in a variety of species. Pharmacology/Actions Praziquantel's exact mechanism of action against cestodes has not been determined, but it may be the result of interacting with phos-pholipids in the integument causing ion ﬂuxes of sodium, potas-sium and calcium. At low concentrations in v itro, the drug appears to impair the function of their suckers and stimulates the worm's motility. At higher concentrations in vitro, praziquantel increases the contraction (irreversibly at very high concentrations) of the worm's strobilla (chain of proglottids). In addition, praziquantel causes irreversible focal vacuolization with subsequent cestodal disintegration at speciﬁc sites of the cestodal integument. In schistosomes and trematodes, praziquantel directly kills the parasit e, possibly by increasing calcium ion ﬂux into the worm. Focal vacuolization of the integument follows and the parasite is phagocytized. Pharmacokinetics Praziquantel is rapidly and nearly completely absorbed after oral administration, but there is a signiﬁcant ﬁrst-pass effect. Peak se-rum levels are achieved between 30-120 minutes in dogs. Praziquantel is distributed throughout the body. It crosses the intest inal wall and across the blood-brain barrier into the CNS. Praziquantel is metabolized in the liver to metabolites of un-known activity. It is excreted primarily in the urine; elimination half-life is ap proximately 3 hours in the dog. Contraindications/Precautions/Warnings The manufacturer recommends not using praziquantel in puppies less than 4 weeks old or in kittens less than 6 weeks old. However, a combination product containing praziquantel and febantel from the same manufacturer is approved for use in puppies and kittens of all ages. No other contraindications are listed for this compound from the manufacturer. In humans, praziquantel is contraindicated in patients hypersensitive to the drug. Adverse Effects When used orally, praziquantel can cause anorexia, vomiting, leth-argy, or diarrhea in dogs, but the incidence of these effects is less than 5%. In cats, adverse effects were quite rare (<2%) in ﬁeld trials using oral praziquantel, with salivation and diarrhea being reported. A greater incidence of adverse effects has been reported after us-ing the injectable product. In dogs, pain at the injection site, vomit-ing, drowsiness, and/or a staggering gait were reported from ﬁeld tr ials with the drug. Some cats (9. 4%) showed clinical signs of diar-rhea, weakness, vomiting, salivation, sleepiness, transient anorexia, and/or pain at the inje ction site. Reproductive/Nursing Safety Praziquantel is considered safe to use in pregnant dogs or cats. In humans, the FDA categorizes this drug as category B for use dur-ing pregnancy (Animal studies have not yet demonstrated risk to the fe tus, 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 trimes-ter 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: 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. ) Praziquantel appears in maternal milk at a concentration of ap-proximately 25% of that in maternal serum, but is unlikely to pose harm t o nursing offspring. Overdosage/Acute Toxicity Praziquantel has a wide margin of safety. In rats and mice, the oral LD50 is at least 2 g/kg. An oral LD 50 could not be determined in dogs, as at doses greater than 200 mg/kg, the drug induced vom-iting. Parenteral doses of 50-100 mg/kg in cats caused transient ataxia and depression; injected doses at 200 mg/kg were lethal in cats. There were 51 exposures to praziquantel reported to the ASPCA Animal Poison Control Center (APCC; www. apcc. aspca. org) dur-ing 2001-2006. In these cases 24 were dogs and 27 were cats. No clinical sig ns were reported. Drug Interactions Reportedly in humans, synergistic activity occurs with praziquantel and oxamniquine in the treatment of schistosomiasis. The clinical implications of this synergism in veterinary patients is not clear. Doses !TDOGS: a) For susceptible cestodes: IM or SC using the 56. 8 mg/m L inje ctable product: Body weight: Dose ≤5 lbs: 17 mg (0. 3 m L) 6-10 lbs: 28. 4 mg (0. 5 m L) 11-25 lbs: 56. 8 mg (1 m L) 25 lbs: 0. 2 m L/5 lb body weight; maximum 3 m L Oral: Using the 34 mg canine tablet: Body weight: Dose ≤5 lbs: 17 mg (1/2 tab) 6- 10 lbs: 34 mg (1 tab) 11-15 lbs: 51 mg (1. 5 tabs) 16-30 lbs: 68 mg (2 tabs) 31-45 lbs: 102 mg (3 tabs) 46-60 lbs: 136 mg (4 tabs) 60 lbs: 170 mg (5 tabs maximum); (Package insert; Droncit® Injectable and Tablets—Bayer) b) For Echinococcus granulosis: 10 mg/kg (Sherding 1989) c) For Diphyllobothrium sp p: 7. 5 mg/kg PO once (Kirkpatrick, Knochenhauer, and Jacobsen 1987) d) For Spirometra mansonoides o r Diphyllobothrium erinacei: 7. 5 mg/kg, PO once daily for 2 days (Roberson 1988a) e) For treatment of Paragonimiasis (Paragonimus kellicotti): 23- 25 mg/kg PO q8h for 3 days (Reinemeyer 1995), (Hawk-ins 2000)	pppbs.pdf
Tf) For treatment of liver ﬂukes (Platynosum or Opisthorchiidae families): 20 -40 mg/kg PO once daily for 3-10 days (Ta-boada 1999) g) For Alaria spp. : 20 mg/kg PO (Ballweber 2004) h) For giardia using Dr ontal Plus®: Use label dose once daily PO for 3 days. (Lappin 2006b) !TCATS: a) For susceptible cestodes: IM or SC using the 56. 8 mg/m L inje ctable product: Body weight: Dose <5 lbs: 11. 4 mg (0. 2 m L) 5- 10 lbs: 22. 7 mg (0. 4 m L) *10 lbs: 34. 1 mg (0. 6 m L maximum) Oral: Using the 23 mg feline tab Body weight: Dose <4 lbs:11. 5 mg (1/2 tab) 5- 11 lbs: 23 mg (1 tab) >11 lbs: 34. 5 mg (1. 5 tabs) (Package insert; Droncit® Injectable and Tablets—Bayer) b) For treatment of Paragonimiasis (Paragonimus kellicotti): 23- 25 mg/kg PO q8h for 3 days (Reinemeyer 1995); (Hawk-ins 2000) c) For treatment of Giardia infections: Give two small dog tab-lets of Drontal Plus® (febantel 113. 4 mg; pyrantel 22. 7 mg; p raziquantel 22. 7 mg) once daily PO for 5 days. (Scorza, Radecki et al. 2004) d) For Alaria spp. : 20 mg/kg PO (Ballweber 2004) e) For Spirometra mansonoides: 30-35 mg/kg PO. (Bowman 2006b) !TRABBITS, RODENTS, SMALL MAMMALS: a) Chinchillas: 6-10 mg/kg PO (Hayes 2000) b) For tapeworms in mice, rats, hamsters and gerbils: 30 mg/kg, PO o nce (note the high dosage required) (Burke 1999) c) Mice, Rats, Gerbils, Hamsters, Guinea pigs, Chinchillas: For tape worms: 6-10 mg/kg PO (Adamcak and Otten 2000) !TSHEEP & GOATS: a) For all species of Moniezia, Stilesia, or Avitellina: 10-15 mg/ kg (Ro berson 1988a) !THORSES: For labeled parasites using the oral gel combination of moxidec-tin/praziquantel: a) Dial in the weight of the animal on the syringe. Adminis-ter gel by inserting the syringe applicator into the animal's mouth through the interdental space and depositing the gel in the back of the mouth near the base of the tongue. Once the syringe is removed, the animal's head should be raised to insure proper swallowing of the gel. Horses weighing more than 1250 lb require additional gel from a second syringe. (Label Directions; Quest® Plus—Fort Dodge) !TLLAMAS: For susceptible parasites: a) 5 mg/kg, PO (Fowler 1989) !TBIRDS: For susceptible parasites (tapeworms): a) 1/4 of one 23 mg tablet/kg PO; repeat in 10-14 days. Add to feed or give by gavage. Injectable form is toxic to ﬁnches. (Clubb 1986) b) For common tapeworms in chickens: 10 mg/kg (Roberson 1988a) c) For cestodes and some trematodes: Direct dose: 5-10 mg/ kg PO or IM as a single dose-or-12 mg of crushed tablets baked into a 9”x9”x2” cake. Finches should have their regular food withheld and be pre-exposed to a non-medicated cake. (Marshall 1993) !TREPTILES: For cestodes and some trematodes in most species: a) 7. 5 mg/kg PO once; repeat in 2 weeks PO (Gauvin 1993) For removal of common tapeworms in snakes: a) 3. 5 -7 mg/kg (Roberson 1988a) Monitoring !TClinical efﬁcacy Client Information !TFasting is neither required nor recommended before dosing. A single dose is usually effective, but measures should be taken to prevent reinfection, particularly against D. caninum. !Tablets may be crushed or mixed with food. !TBecause tapeworms are often digested, worm fragments may not be seen in the feces after using. Chemistry/Synonyms A prazinoisoquinoline derivative anthelmintic, praziquantel occurs as a white to practically white, hygroscopic, bitter tasting, crystal-line powder, either odorless or having a faint odor. It is very slightly solub le in water and freely soluble in alcohol. Praziquantel may also be known as: EMBAY-8440, praziquan-telum, Biltricide®, Bio-C est®, Cercon®, Cesol®, Cestox®, Cisticid®, Combo Care®, Cysticide®, Droncit®, Drontal®, Ehliten®, Equimax®, Extiser Q®, Mycotricide®, Opticide®, Quest® Plus, Praquantel®, Prasikon®, Prazite®, Prozitel ®, Sincerck®, Teniken®, Virbantel®, Waycital®, or Zifartel® and Zimecterin Gold Paste®. Storage/Stability/Compatibility Unless otherwise instructed by the manufacturer, praziquantel tablets should be stored in tight containers at room temperature. Protect from light. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Praziquantel Tablets: 23 mg (feline); 34 mg (canine); Droncit® Tablets (Bayer); generic; (Rx; OTC). Approved for use in cats and dogs. Praziquantel Injection: 56. 8 mg/m L in 10 m L and 50 m L vials; Droncit ® Injection (Bayer); generic; (Rx). Approved for use in cats and dogs. Combination Products: Tablets: 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. Chewable Tablets: Praziquantel 30 mg/pyrantel pamoate 30 mg; & Pr aziquantel 114 mg/pyrantel pamoate 114 mg chewable tablets; Virbantel Flavored Chewables® (Virbac); (OTC). Approved for use in dogs. Tablets: Praziquantel/pyrantel pamoate plus febantel; Dr ontal® Plus Tablets (Bayer); (Rx); small, medium and large dog sizes. Approved for dogs and puppies 3 weeks of age or older and weighing 2 lb. or greater. Oral Gel: containing 20 mg/m L moxidectin and 125 mg/m L of prazi-quantel in 11. 6 g syringes (sufﬁcient to treat one 1150 lb horse); Quest® P lus (Fort Dodge); Combo Care® Equine Oral Gel (Farnam); (OTC). Approved for use in horse or ponies not intended for food purposes.	pppbs.pdf
Oral Paste: containing 1. 87% ivermectin and 14. 03% of praziquan-tel in oral syringes (sufﬁcient to treat one 1320 lb horse); Equimax® (Pﬁze r); (OTC). Approved for use in horse or ponies not intended for food purposes. Oral Paste: containing 1. 55% ivermectin and 7. 75% of praziquan-tel in oral syringes (sufﬁcient to treat one 1250 lb horse); Zimecte rin Gold Paste® (Merial); (OTC). Approved for use in horse or ponies not intended for food purposes. HUMAN-LABELED PRODUCTS: Praziquantel Tablets (Film-coated): 600 mg; Biltricide® (Bayer); (Rx) PRAZOSIN HCL (pra-zoe-sin) Minipress® ALPHA-1 ADRENERGIC BLOCKER Prescriber Highlights TT Alpha 1-blocker that may be useful for adjunctive treat-ment of CHF, systemic hypertension, or pulmonary hyper-tension in dogs TT Also used to reduce sympathetic tone to treat functional urethral obstruction in dogs & cats TT Caution: Chronic renal failure or preexisting hypotensive conditions TT Adverse Effects: Potentially hypotension, CNS effects (lethargy, dizziness, etc. ), & GI effects Uses/Indications Prazosin is less well studied in dogs than hydralazine, and its capsule dosage form makes it less convenient for dosing. Prazosin, however, appears to have fewer problems with causing tachycardia, and its venous dilation effects may be an advantage over hydralazine when preload reduction is desired. It could be considered for therapy for the adjunctive treatment of CHF, particularly when secondary to mitral or aortic valve insufﬁciency when hydralazine is ineffective or not tolerated. Prazosin may also be used for the treatment of systemic hypertension or pulmonary hypertension in dogs. Pharmacology/Actions Prazosin's effects are a result of its selective, competitive inhibition of alpha 1-adrenergic receptors. It reduces blood pressure and pe-ripheral vascular resistance and, unlike hydralazine, has dilatory ef-fects on both the arterial and venous side. Prazosin signiﬁcantly reduces systemic arterial and venous blood pressur es, and right atrial pressure; cardiac output is increased in patients with CHF. Moderate reductions in blood pressure, pulmo-nary vascular resistance, and systemic vascular resistance are seen in these patie nts. Heart rates can be moderately decreased or un-changed. Unlike hydralazine, prazosin does not seem to increase renin r elease so diuretic therapy is not mandatory with this agent (but is usually beneﬁcial in CHF). Pharmacokinetics The pharmacokinetic parameters for this agent were not located for veterinary species. In humans, prazosin is variably absorbed after oral administration. Peak levels occur in 2-3 hours. Prazosin is widely distributed throughout the body and is ap-proximately 97% bound to plasma proteins. Prazosin is minimally distribu ted into milk. It is unknown if it crosses the placenta. Prazosin is metabolized in the liver and some metabolites have acti vity. Metabolites and some unchanged drug (5-10%) are pri-marily eliminated in feces via the bile. Contraindications/Precautions/Warnings Prazosin should be used with caution in patients with chronic renal failure or preexisting hypotensive conditions. Adverse Effects Syncope secondary to orthostatic hypotension has been reported in people after the ﬁrst dose of the drug. This effect may persist if the dosage is too high for the patient. CNS effects (lethargy, dizzi-ness, etc. ) may occur, but are usually transient in nature. GI effects (nausea, vomit ing, diarrhea, constipation, etc. ) have been reported. Tachyphylaxis (drug tolerance) has been reported in humans, but dosage adjustment, temporarily withdrawing the drug, &/or add-ing an aldosterone antagonist (e. g., spironolactone) usually corrects this. 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. ) Prazosin is excreted in small amounts in maternal milk and un-likely to pose much risk to nursing offspring. Overdosage/Acute Toxicity There were 7 exposures to prazosin 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 1 reported cat case that showed clinical signs. Clinical signs in that dog in decreasing frequency included hyperactivity. Tachycardia was seen in the cat. Evacuate gastric contents and administer activated charcoal us-ing standard precautionary measures if the ingestion was recent and if cardio vascular status has been stabilized. Treat shock using volume expanders and pressor agents if necessary. Monitor and support renal function. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving prazosin and may be of signiﬁcance in veterinary patients: T ! BETA-BLOCKING A GENTS (e. g., propranolol ): May enhance the pos-tural hypotensive effects seen after the ﬁrst dose of prazosin T ! CLONIDINE : May decrease prazosin antihypertensive effects T ! SILDENAFIL (and other PDE INHIBITORS ): May increase risk for hypotension T ! VERAPAMIL or NIFEDIPINE : May cause synergistic hypotensive ef-fects when used concomitantly with prazosin Doses T ! DOGS: a) For adjunctive treatment of heart failure: 1 mg PO three times daily for dogs weighing less than 15 kg; 2 mg three times daily PO for dogs weighing more than 15 kg (Kittleson 1985b), (Atkins 2007a) b) For hypertension: 1-4 mg (total dose) PO q12-24 hours (Brow n and Henik 2000) c) For hypertension in a large dog: 1 mg (total dose) PO q8-12h (Ware 2003) d) T o decrease urethral resistance: 1 mg per 15 kg of body weight PO q8h (Lane 2000)	pppbs.pdf
e) For functional urethral obstruction: 1 mg/15 kg of body weight PO q8 -24h (Lulich 2004) f) T o decrease urethral resistance: 1 mg per 15 kg of body weight PO q12-24h (Bar tges 2006a), (Vernau 2006) !TCATS: T o decrease urethral resistance: a) 0. 5 mg (total dose) PO q8h or 0. 03 mg/kg IV (Lane 2000) b) 0. 03 mg/kg IV (Osborne, Kruger et al. 2000) c) For functional urethral obstruction: 0. 25-0. 5 mg/cat (total dose) PO q12 -24h (Lulich 2004), (Coates 2004), (Vernau 2006) Monitoring !TBaseline thoracic radiographs !TMucous membrane color; CRT !TIf possible, arterial blood pressure and venous PO 2 Client Information !TCompliance with directions is necessary to maximize the beneﬁts from this drug. If possible, give medication with food. !TNotify veterinarian if patient's condition deteriorates or if the animal becomes lethargic or depressed. Chemistry/Synonyms A quinazoline-derivative postsynaptic alpha 1-adrenergic blocker, prazosin HCl occurs as a white to tan powder. It is slightly soluble in water and very slightly soluble in alcohol. Prazosin may also be known as: CP-12299-1, furazosin hy-drochloride, prazosini hydrochloridum; many trade names are available. Storage/Stability Prazosin capsules should be stored in well-closed containers at room temperature. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 3 substance. See the appendix for more information. HUMAN-LABELED PRODUCTS: Prazosin Capsules: 1 mg, 2 mg & 5 mg (as base); Minipress® (Pﬁzer); PREDNISOLONE PREDNISOLONE SODIUM SUCCINATE PREDNISOLONE ACETATE PREDNISONE (pred-niss-oh-lone); (pred-ni-zone) For more information refer to the monograph: Glucocorticoids, General Information or to the manufacturer's product informa-tion for veterinary labeled products. Note : Although separate entities, prednisone and prednisolone are of-ten considered bioequivalent; most species rapidly convert prednisone to prednisolo ne in the liver. Horses, cats and patients in frank hepatic failure do not appear to either absorb or convert prednisone to predni-solone efﬁciently. Use either prednisolone or an alternative glucocorti-coid in these patients when possible. Prescriber Highlights T!Classic glucocorticoids used for many conditions in many species. Antiinﬂammatory activity is 4X more potent than hydrocortisone; has some mineralocorticoid activity T!Contraindications (relative): Systemic fungal infections T!Caution: Active bacterial infections, corneal ulcer, Cushin-goid syndrome, diabetes, osteoporosis, chronic psychotic reactions, predisposition to thrombophlebitis, hyperten-sion, CHF, renal insufﬁciency T!Goal of therapy is to use as much as is required & as little as possible for as short an amount of time as possible T!Prednisone poorly absorbed after oral use in horses; pred-nisone may not be readily converted to prednisolone in cats. Prednisolone is preferred in these two species. T!Primary adverse effects are “Cushingoid” in nature with sustained use T!Many potential drug & lab interactions generic (Rx) Uses/Indications Glucocorticoids have been used in an attempt to treat practically every malady that afﬂicts man or animal, but there are three broad uses and dosage ranges for use of these agents. 1) Replacement of glucocorticoid activity in patients with adrenal insufﬁciency, 2) as an antiinﬂammatory agent, and 3) as an immunosuppressive. Among some of the uses for glucocorticoids include treatment of: endocrine conditions (e. g., adrenal insufﬁciency), rheumatic dis-eases (e. g., rheumatoid arthritis), collagen diseases (e. g., systemic lupus), alle rgic states, respiratory diseases (e. g., asthma), dermato-logic diseases (e. g., pemphigus, allergic dermatoses), hematologic disorde rs (e. g., thrombocytopenias, autoimmune hemolytic ane-mias), neoplasias, nervous system disorders (increased CSF pres-sure), GI diseases (e. g., ulcerative colitis exacerbations), and renal diseases (e. g., nephrotic syndrome). Some glucocorticoids are used topically in the eye and skin for various conditions or are injected intra-articularly or intra-lesionally. The above listing is certainly not complete.	pppbs.pdf
In general, in using glucocorticoids, the following principles should be followed: 1. Glucocorticoids can mask disease! Try not to use them until you ha ve a diagnosis. 2. Make a speciﬁc diagnosis! 3. Determine course from outset. 4. Determine endpoint before you starting treating. 5. Use the least potent form for the minimal time. 6. Know where glucocorticoids inappropriate. (Behrend 2007) Pharmacology/Actions Glucocorticoids have effects on virtually every cell type and system in mammals. An overview of the effects of these agents follows: Cardiovascular System : Glucocorticoids can reduce capillary per-meability and enhance vasoconstriction. A relatively clinically in-signiﬁcant positive inotropic effect can occur after glucocorticoid administ ration. Increased blood pressure can result from both the drugs' vasoconstrictive properties and increased blood volume that may be produced. Cells : Glucocorticoids inhibit ﬁbroblast proliferation, macrophage response to migration inhibiting factor, sensitization of lympho-cytes, and the cellular response to mediators of inﬂammation. Gluc ocorticoids stabilize lysosomal membranes. CNS/A utonomic Nervous System : Glucocorticoids can lower seizure threshold, alter mood and behavior, diminish the response to pyro-gens,stimulate appetite,and maintain alpha rhythm. Glucocorticoids are ne cessary for normal adrenergic receptor sensitivity. Endocrine System : When animals are not stressed, glucocorticoids will suppress the release of ACTH from the anterior pituitary, thereby reducing or preventing the release of endogenous corticos-teroids. Stress factors (e. g., renal disease, liver disease, diabetes) may some times nullify the suppressing aspects of exogenously admin-istered steroids. Release of thyroid-stimulating hormone (TSH), fol licle-stimulating hormone (FSH), prolactin and luteinizing hor-mone (LH) may all be reduced when glucocorticoids are adminis-tered at pharmacological doses. Conversion of thyroxine (T 4) t o triiodothyronine (T 3) may be reduced in glucocorticoids and plas-ma levels of parathyroid hormone increased. Glucocorticoids may inhibit osteoblast function. Vasopressin (ADH) activity is reduced at the renal tubules and diuresis may occur. Glucocorticoids inhibit insulin binding to insulin-receptors and the post-receptor effects of insulin. Hematopoietic System : Glucocorticoids can increase the numbers of circulating platelets, neutrophils, and red blood cells, but platelet aggregation is inhibited. Decreased amounts of lymphocytes (pe-ripheral), monocytes, and eosinophils are seen as glucocorticoids can se quester these cells into the lungs and spleen and prompt de-creased release from the bone marrow. Removal of old red blood ce lls is diminished. Glucocorticoids can cause involution of lym-phoid tissue. GI Tract a n d Hepatic System : Glucocorticoids increase the secre-tion of gastric acid, pepsin, and trypsin. They alter the structure of mucin and decrease mucosal cell proliferation. Iron salts and calcium absorption are decreased while fat absorption increases. Hepatic changes can include increased fat and glycogen depos-its within hepatocytes, increased serum levels of alanine amin-otransferase (ALT), and gamma-glutamyl transpeptidase (GGT). Si gniﬁcant increases can be seen in serum alkaline phosphatase levels. Glucocorticoids can cause minor increases in BSP (bromo-sulfophthalein) retention time. Immune System (also see Cells and Hematopoietic System): Glucocorticoids can decrease circulating levels of T-lymphocytes; inhibit lymphokines; inhibit neutrophil, macrophage, and mono-cyte migration; reduce production of interferon; inhibit phagocyto-sis and chemotaxis; antigen processing; and diminish intracellular killing. Speciﬁc acquired immunity is affected less than nonspeciﬁc immune responses. Glucocorticoids can also antagonize the com-plement cascade and mask the clinical signs of infection. Mast cells are decreased in number and histamine synthesis is suppressed. Many of these effects only occur at high or very high doses and there are species differences in response. Metabolic effects : Glucocorticoids stimulate gluconeogenesis. Lipogenesis is enhanced in certain areas of the body (e. g., abdomen) and adipose tissue can be redistributed away from the extremities to the trunk. Fatty acids are mobilized from tissues and their oxi-dation is increased. Plasma levels of triglycerides, cholesterol, and gl ycerol are increased. Protein is mobilized from most areas of the body (not the liver). Musculoskeletal : Glucocorticoids may cause muscular weakness (also caused if there is a lack of glucocorticoids), atrophy, and os-teoporosis. Bone growth can be inhibited via growth hormone and somat omedin inhibition, increased calcium excretion and inhibi-tion of vitamin D activation. Resorption of bone can be enhanced. Fibr ocartilage growth is also inhibited. Ophthalmic : Prolonged corticosteroid use (both systemic or topically to the eye) can cause increased intraocular pressure and glaucoma, cataracts, and exophthalmos. Reproductive Tract, Pregnancy, & Lactation : Glucocorticoids are prob-ably necessary for normal fetal development. They may be required fo r adequate surfactant production, myelin, retinal, pancreas, and mammary development. Excessive dosages early in pregnancy may lead to teratogenic effects. In horses and ruminants, exogenous ste-roid administration may induce parturition when administered in th e latter stages of pregnancy. Glucocorticoids unbound to plasma proteins will enter milk. High dosages or prolonged administration to mothers may potentially inhibit the growth of nursing newborns. Renal, Fluid, & Electrolytes : Glucocorticoids can increase potassium and calcium excretion; sodium and chloride reabsorption and ex-tracellular ﬂuid volume. Hypokalemia and/or hypocalcemia occur ra rely. Diuresis may occur following glucocorticoid administration. Skin: Thinning of dermal tissue and skin atrophy can be seen with glucocorticoid therapy. Hair follicles can become distended and alopecia may occur. Pharmacokinetics Plasma half-life is not meaningful from a therapy standpoint when evaluating systemic corticosteroids. Prednisolone and prednisone are intermediate acting corticosteroids with a biologic “half-life” of 12-36 hours. Contraindications/Precautions/Warnings Systemic use of glucocorticoids is generally considered contrain-dicated in systemic fungal infections (unless used for replacement ther apy in Addison's), when administered IM in patients with idio-pathic thrombocytopenia, and those hypersensitive to a particular co mpound. Sustained-released injectable glucocorticoids are con-sidered contraindicated for chronic corticosteroid therapy of sys-temic diseases. Animals that have received glucocorticoids systemically, other than w ith “burst” therapy, should be tapered off the drugs. Patients who have received the drugs chronically should be tapered off slowly as endogenous ACTH and corticosteroid function may re-turn slowly. Should the animal undergo a “stressor” (e. g., surgery, tr auma, illness, etc. ) during the tapering process or until normal adrenal and pituitary function resume, additional glucocorticoids should be administered.	pppbs.pdf
Adverse Effects Adverse effects are generally associated with long-term administra-tion of these drugs, especially if given at high dosages or not on an alt ernate day regimen. Effects generally are manifested as clini-cal signs of hyperadrenocorticism. When administered to young, gr owing animals, glucocorticoids can retard growth. Many of the potential effects, adverse and otherwise, are outlined above in the Pharmacology section. In dogs, polydipsia (PD), polyphagia (PP), and polyuria (PU) may all be seen with short-term “burst” therapy as well as with alternate-day maintenance therapy on days when giving the drug. Adverse effects in dogs can include: dull, dry haircoat, weight gain, panting, vomiting, diarrhea, elevated liver enzymes, pancreatitis, GI ulceration, lipidemias, activation or worsening of diabetes mellitus, muscle wasting, and behavioral changes (depression, lethargy, vi-ciousness). Discontinuation of the drug may be necessary; chang-ing to an alternate steroid may also alleviate the problem. With the ex ception of PU/PD/PP, adverse effects associated with antiinﬂam-matory therapy are relatively uncommon. Adverse effects associated with immunosuppressive doses are more common and potentially more severe. Cats generally require higher dosages than dogs for clinical effect, bu t tend to develop fewer adverse effects. Occasionally, polydipsia, polyuria, polyphagia with weight gain, diarrhea, or depression can be seen. Long-term, high dose therapy can lead to “Cushingoid” ef-fects, however. Reproductive/Nursing Safety Corticosteroid therapy may induce parturition in large animal spe-cies during the latter stages of pregnancy. In humans, the FDA cat-egorizes this drug as category C fo r 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. ) In a separate system evaluating the safety of drugs in canine and feline pregnancy (Papich 1989), this drug is categorized as 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. ) Use with caution in nursing dams. Glucocorticoids unbound to plasma p roteins will enter milk. High dosages or prolonged admin-istration to mothers may potentially inhibit growth, interfere with end ogenous corticosteroid production or cause other unwanted ef-fects in nursing offspring. In humans, however, several studies sug-gest that amounts excreted in breast milk are negligible when pred-nisone or prednisolone doses in the mother are less than or equal to 20 mg/da y or methylprednisolone doses are less than or equal to 8 mg/day. Larger doses for short periods may not harm the infant. Overdosage/Acute Toxicity Glucocorticoids when given short-term are unlikely to cause harm-ful effects, even in massive dosages. One incidence of a dog develop-ing acute CNS effects after accidental ingestion of glucocorticoids has b een reported. Should clinical signs occur, use supportive treat-ment if required. Chronic usage of glucocorticoids can lead to serious adverse ef-fects. Refer to Adverse Effects above for more information. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving oral prednisolone/pred-nisone and may be of signiﬁcance in veterinary patients: !TAMPHOTERICIN B : When administered concomitantly with gluco-corticoids may cause hypokalemia !TANTICHOLINESTERASE AGENTS (e. g., pyridostigmine, neostigmine, etc. ): In patients with myasthenia gravis, concomitant glucocor-ticoid with these agents may lead to profound muscle weakness. If possible, discontinue anticholinesterase medication at least 24 hours prior to corticosteroid administration. !TASPIRIN (salicylates ): Glucocorticoids may reduce salicylate blood levels !TCYCLOPHOSPHAMIDE : Glucocorticoids may also inhibit the hepatic metabolism of cyclophosphamide; dosage adjustments may be required. !TCYCLOSPORINE : Concomitant administration of may increase the blood levels of each, by mutually inhibiting the hepatic metabo-lism of each other; clinical signiﬁcance of this interaction is not clear !TDIGOXIN : Secondary to hypokalemia, increased risk for arrhythmias !TDIURETICS, POTASSIUM-DEPLETING (furosemide, thiazides ): When administered concomitantly with glucocorticoids may cause hypokalemia !TEPHEDRINE : May increase metabolism of glucocorticoids !TESTROGENS : The effects of hydrocortisone, and possibly other glu-cocorticoids, may be potentiated by concomitant administration with est rogens !TINSULIN : Requirements may increase in patients receiving gluco-corticoids !TKETOCONAZOLE : May decrease metabolism of glucocorticoids !TMITOTANE : May alter the metabolism of steroids; higher than usu-al doses of steroids may be necessary to treat mitotane-induced adr enal insufﬁciency !TNSAIDS : Administration of other ulcerogenic drugs with gluco-corticoids may increase risk !TPHENOBARBITAL : May increase the metabolism of glucocorticoids !TPHENYTOIN : May increase the metabolism of glucocorticoids !TRIFAMPIN : May increase the metabolism of glucocorticoids !TVACCINES : Patients receiving corticosteroids at immunosuppres-sive dosages should generally not receive live attenuated-virus va ccines as virus replication may be augmented; a diminished immune response may occur after vaccine, toxoid, or bacterin administration in patients receiving glucocorticoids Laboratory Considerations !TGlucocorticoids may increase serum cholesterol and urine glucose levels. !TGlucocorticoids may decrease serum potassium. !TGlucocorticoids can suppress the release of thyroid stimulat-ing hormone (TSH) and reduce T3 & T4 values. Thyroid gland atrophy has been reported after chronic glucocorticoid admin-istration. Uptake of I 131 by the thyroid may be decreased by glucocorticoids. !TReactions to skin tests may be suppressed by glucocorticoids. !TFalse-negative results of the nitroblue tetrazolium test for systemic bacterial infection s may be induced by glucocorticoids. Doses !TDOGS: For adjunctive treatment of neoplasms: For more information on using prednisone or prednisolone as part of chemotherapy protocols, refer to the protocols found in the appendix or other dosages/protocols found in numer-	pppbs.pdf
ous references, including: Withrow and Mac Ewen's Small Animal Clinical Oncology, 4th Ed. (Withrow and Vail 2007); Canine and Feline Geriatric Oncology (Villalobos 2007); Small Animal Inter-nal Medicine, 3rd Edition (Ne lson and Couto 2003); Textbook of Veterinary Internal Medicine: Diseases of the Dog and Cat 6th Edi-tion (Ettinger and Feldman 2005); and The 5-Minute Veterinary Consult Canine & Feline, 3rd Ed. (Tilley and Smith 2004). a) Brain tumors (palliative therapy): Prednisone 0. 5-1 mg/kg PO o nce a day to every other day. (Fenner 1988); Prednisone 0. 5-1 mg/kg PO twice daily for several days, then decrease dosag e over the next week or month, dependent on patient's needs (Le Couteur and Turrel 1986) b) For adjunctive therapy in canine lymphomas: COAP (cyclophosphamide, vincristine, cytosine arabinoside, prednisone) protocol: Prednisone: 50 mg/m2 PO every day fo r one week, then 25 mg/m2 every other day. COP (no cytosine arabinoside) protocol: Prednisone 25 mg/ m2 PO every other day. CHOP (d oxorubicin instead of cytosine arabinoside): Pred-nisone 25 mg/m2 PO every other day (Couto 1986) c) For adjunctive therapy for multiple myeloma: Prednisone 0. 5 mg/kg PO once daily. Used with melphalan: 0. 1 mg/kg PO o nce daily for 10 days, then 0. 05 mg/kg PO once daily or with cyclophosphamide: 1 mg/kg PO once daily (if resistance develops to melphalan). (Jenkins 1985) d) For macroglobulinemia: Prednisone 0. 5 mg/kg PO once daily. Used with chlorambucil: 0. 2 mg/kg PO once daily for 10 days, then 0. 1 mg/kg PO once daily or with cyclophos-phamide: 1 mg/kg PO once daily (if resistance develops to chlo rambucil) (Jenkins 1985) For adjunctive treatment of respiratory disorders: a) Chronic bronchitis: Prednisone 0. 5-1 mg/kg PO once a day to e very other day (Bauer 1988) b) Allergic bronchitis: Prednisolone sodium succinate: 2-4 mg/ kg IV or IM (do not give via rapid IV infusion). In chroni-cally symptomatic patient: prednisone 0. 5-1. 5 mg/kg/day PO (Baue r 1988) c) For adjunctive therapy of collapsing trachea: Initially, prednisolone 0. 25-0. 5 mg/kg PO twice daily for 7- 10 days (Prueter 1988b) Prednisone: 0. 5 mg/kg, PO once or twice a day. Discontinue if no improvement in one week. Corticosteroids must be used caut iously in this condition and rarely make a difference in the long-term outcome of therapy. (Fingland 1989) d) For allergic (eosinophilic) bronchitis or pneumonitis: Pred-nisone 1-2 mg/kg/day divided two to three times a day. Ev-ery 7-10 days decrease total steroid dose by 1/4-1/2 as long as sig ns are controlled. After 3-4 weeks, every other day or every third day therapy may be attempted. (Noone 1986) e) For adjunctive therapy of parasitic pulmonary hypersensitiv-ities: T o suppress inﬂammation prior to parasite elimination: Pr ednisolone 1-2 mg/kg PO divided into 2-3 doses (Noone 1986) For adjunctive therapy in liver disorders: Note : Because pred-nisone requires conversion to the active compound predniso-lone by the liver, some clinicians believe that only prednisolone should be use d in patients with liver disease. a) For cholangitis: Prednisolone 1-2 mg/kg PO once daily for at least 1 month. Then give every other day for another 2-3 months and consider discontinuing and monitoring for re-lapse. (Cornelius and Bjorling 1988) b) For chronic lymphocytic-plasmacytic or autoimmune hepa-titis: 2. 2 mg/kg, PO once daily for several weeks and then tape red to 1. 1 mg/kg every other day. If dogs cannot tolerate or fail prednisone may add azathioprine. (Twedt 1999) c) Copper-induced hepatopathy: Prednisolone 0. 5-1 mg/kg PO di vided twice daily (used during acute stages). Used with chelation therapy and dietary copper restriction. (Cornelius and Bjorling 1988) For adjunctive therapy of disorders of the gastrointestinal tract: a) For eosinophilic colitis: Prednisolone 1-2 mg/kg PO for 7- 10 days. Gradually decrease dose over following 3-4 weeks to a minimal dosage that will control clinical signs. Some cases will require additional alternate-day therapy for an additional 3-4 weeks. (De Novo 1988) b) For eosinophilic enteritis: Prednisolone 1-3 mg/kg PO once daily ; gradually taper to every other day dosing for mainte-nance. May use injectable forms if dog is vomiting or mal-absorption is severe. Therapy may be necessary for weeks to months. Do not use until intestinal biopsy sites are healed (usually 7-10 days). (Chiapella 1988); Prednisone 0. 5 mg/kg, PO once daily initially; reduce gradu-ally to alternate day therapy (Hall and Twedt 1989); Pr ednisolone: 0. 5-1 mg/kg twice daily for 5-7 days, then decrease to 0. 5 mg/kg/day for 5-7 days. Taper dose to al-ternate-day therapy as condition dictates. Additional therapy fo r 3-4 weeks is often necessary. Relapses can occur. (De-Novo 1986) c) For eosinophilic colitis when dietary and parasitic infesta-tions have been eliminated or when other appropriate ther-apy has been unsuccessful: Prednisolone 0. 5-1 mg/kg two times a day; taper dose gradually over a 3-4 week period to the lowest effective dose. (Chiapella 1986) d) For plasmacytic/lymphocytic enteritis: Prednisolone 2. 2 mg/ kg PO divided twice daily for 5-10 days, then 1. 1 mg/kg/day for 5-10 days. Then taper by reducing steroid dosage by 1/2 every 10-14 days until alternate-day dosage is attained or symptoms recur. (Chiapella 1988) e) For adjunctive therapy of chronic superﬁcial gastritis (if pre-dominance of lymphocyte and plasma cell inﬁltration seen on biopsy): Prednisone 0. 5-1 mg/kg PO divided twice daily initially and reduced over a 3 month period to lowest, alter-nate-day effective dosage (Hall and Twedt 1989) f) Ulcerative colitis: May cause some patients' condition to wo rsen. Use only after an unsuccessful trial of sulfasalazine. Use with caution. Prednisolone 1-2 mg/kg/day PO for 5-7 days; then 0. 5 mg/kg/day for an additional 5-7 days; then 0. 25-0. 5 mg/kg PO every other day for 10-14 days. Con-tinue sulfasalazine during steroid therapy. If signiﬁcant im-provement is not seen within the ﬁrst 7 days of therapy, ste-roids are tapered and discontinued more rapidly. (De Novo 1988) g) For food allergy or intolerance: Prednisone 0. 5 mg/kg PO onc e daily; taper dose weekly if clinical response dictates. Discontinue when clinical remission ensues. (Chiapella 1988) h) For adjunctive therapy of endotoxemia secondary to GDV: Pr ednisolone sodium succinate: 11 mg/kg IV (Bellah 1988); Prednisolone sodium succinate 10 mg/kg (Orton 1986) i) For eosinophilic gastritis: Prednisone 0. 5 mg/kg once daily fo r 1-2 weeks; gradually taper to 0. 12 mg/kg, PO every other day (Twedt and Magne 1986)	pppbs.pdf
j) For adjunctive therapy of intestinal lymphangiectasia: pred-nisolone 2-3 mg/kg/day. Once remission is attained, may ta-per to a maintenance dosage. Not all cases respond. (Sherd-ing 1986) k) For adjunctive therapy of refractory wheat-sensitive enterop-athy in Irish Setters: Prednisolone 0. 5 mg/kg every 12 hours fo r one month. Then begin a reducing dosage schedule. (Batt 1986) l) For dogs who respond poorly to conventional therapy (en-zyme replacement, dietary modiﬁcation, vitamin supple-mentation, and antibiotics) for exocrine pancreatic insufﬁ-ciency: Predniso(lo)ne 1-2 mg/kg every 12 hours for 7-14 day s. May reduce over 4-6 weeks as patient tolerates. (Wil-liams 1989) For adrenal diseases: a) For adjunctive treatment of hypoadrenal crisis: Prednisolone sodi um succinate: 4-20 mg/kg IV over 2-4 minutes, prefer-ably after ACTH response test is completed. IV normal saline is us ually sufﬁcient therapy during the ﬁrst hour until ACTH response test is completed. Prednisolone sodium succinate may be repeated in 2-6 hours or dexamethasone may be added to IV infusion at 0. 05-0. 2 mg/kg q12h. Prednisolone sodium succinate possesses some mineralocorticoid activity, while dexamethasone does not. (Feldman 1989) b) For glucocorticoid supplementation in chronic or subacute adr enal insufﬁciency: Predniso(lo)ne 0. 2-0. 4 mg/kg PO per day (Feldman, Schrader, and Twedt 1988) c) For glucocorticoid supplementation if azotemia or other symp toms of glucocorticoid deﬁciency result: Predniso(lo) ne 0. 1-0. 3 mg/kg PO per day (Schrader 1986) d) For glucocorticoid “coverage” before and after adrenal tu-mor removal: Prednisolone sodium succinate 1-2 mg/kg IV e ither at 1 hour prior to surgery or at the time of anes-thesia induction. May also add to IV ﬂuids and administer IV d uring the procedure. Repeat dosage at end of procedure; may give IM or IV. Glucocorticoid supplementation must be maintained using an oral product (initially predniso(lo) ne 0. 5 mg/kg twice daily, cortisone acetate 2. 5 mg/kg twice daily, or dexamethasone 0. 1 mg/kg once daily). Slowly taper to maintenance levels (predniso(lo)ne 0. 2 mg/kg once a day, or cortisone acetate 0. 5 mg/kg two times a day) over 7-10 days. Should complications develop during the taper, reiniti-ate doses at 5 times the maintenance dose. Most dogs can sto p exogenous steroid therapy in about 2 months (based on an ACTH stimulation test). (Peterson 1986) e) For glucocorticoid “coverage” in animals who have iatrogenic sec ondary adrenocortical insufﬁciency and/or HPA suppres-sion: Animals exhibiting mild to moderate signs of glucocorti-coid deﬁciency: Predniso(lo)ne 0. 2 mg/kg PO every other day For animals with HPA suppression undergoing a “stress” fac-tor: Prednisolone sodium succinate 1-2 mg/kg just before and aft er stressful events (e. g., major surgery). Continue with lower dosages until at least 3rd post-operative day. Access to a water-soluble form of glucocorticoid should be available should animal “collapse. ” (Kemppainen 1986) f) For symptoms of glucocorticoid deﬁciency (anorexia, diar-rhea, listlessness) or in well-controlled patients receiving mi-totane (Lysodren®) therapy for hyperadrenocorticism under-going a “stress”: Prednisone 2. 2 mg/kg PO for 2 days, then 1 mg/kg f or 2 days, then 0. 5 mg/kg for 3 days, then 0. 5 mg/kg every other day for one week, then stop. Reintroduce therapy or readjust dosage should symptoms recur. (Feldman 1989) For adjunctive or alternative medical management of hy perinsulinism: a) Prednisone 0. 5 mg/kg PO divided twice daily initially; in-crease dose as required, to maintain euglycemia (Kay, Kruth, and Tw edt 1988) b) Prednisolone 1 mg/kg divided twice-daily PO, then decrease to a minimally effective dosage (Lothrop 1989) Fo r adjunctive therapy of toxicoses: a) For cholecalciferol toxicity: Prednisone 1-2 mg/kg PO two to thr ee times daily (Grauer and Hjelle 1988a) b) For adjunctive therapy of endotoxicosis secondary to gar-bage or carrion ingestion: Prednisolone sodium succinate 5- 7 mg/kg IV every 4 hours (Coppock and Mostrom 1986) For adjunctive therapy of reproductive disorders: a) In bitches prone to relapse after initial therapy of eclamp-sia (puerperal tetany): Prednisone 0. 25 mg/kg PO once daily dur ing lactation and slowly withdrawn (Barton and Wolf 1988); Prednisolone 0. 5 mg/kg twice daily (Russo and Lees 1986) Fo r adjunctive therapy of heartworm disease (considered by some clinicians to be contraindicated during treatment for rou-tine post-adulticide therapy as pulmonary thromboses may be pr omoted): a) Prednisolone 1-2 mg/kg PO divided two times a day. Reduce dosag e over next 7-14 days. (Knight 1988) b) Dogs with severe cough, hemoptysis, or extensive parenchy-mal involvement: Prior to adulticide therapy, prednisolone 1- 2 mg/kg PO divided twice daily and tapered over a 10-14 day period (Noone 1986) c) For pneumonitis associated with occult heartworm disease: Pr ednisone 1-2 mg/kg daily for 3-5 days. After steroids are stopped, give adulticide therapy immediately. (Calvert and Rawlings 1986) For CNS disorders: a) For granulomatous meningoencephalitis: Prednisone: 1-2 mg/kg PO daily for the life of the patient. (Fenner 1988); prednisone 2-3 mg/kg PO divided twice daily for 2 weeks, then slowly reduce dosage over several weeks; long-term therapy is recommended. (Schunk 1988a) b) For reticulosis: Prednisone: 1-2 mg/kg/day PO until symp-toms begin to subside, then begin taper. Continue low-dose onc e a day or every other day therapy indeﬁnitely. (Fenner 1988); Prednisone 2-3 mg/kg PO divided twice daily for 2 weeks, then slowly reduce dosage over several weeks; long-term therapy is recommended. (Schunk 1988a) Predniso(lo)ne: 2 mg/kg PO for 1 week, then 1 mg/kg/day for 1 w eek, then 0. 5 mg/kg/day for 1 week, then 0. 5 mg/kg every other day for 1 week, then 0. 25 mg/kg every other day for 1 week, then 0. 25 mg/kg every 3rd day (Riis 1986) c) For adjunctive therapy of hydrocephalus: For long-term manage ment, prednisone 0. 5 mg/kg, PO every other day may be tried. (Fenner 1988) Prednisone 0. 25-0. 5 mg/kg PO two times a day; continue if impr ovement is noted within one week and decrease dosage at weekly intervals to 0. 1 mg/kg PO every other day eventu-ally. Maintain dose for at least one month. (Shores 1989) d) For adjunctive medical therapy of intervetebral disk disease (IVD): Ce rvical IVD: Prednisolone 0. 5 mg/kg PO twice daily for 3 days, then 0. 5 mg/kg once daily for 3-5 days;	pppbs.pdf
Thoracolumbar IVD: Prednisolone 0. 5-1 mg/kg SC or PO twice daily for 2-3 days, then taper dosage over next 3-5 days (Schunk 1988a) e) For adjunctive therapy of spondylopathy: Ce rvical: For dogs with slowly progressive course and still ambulatory, use prednisone: 1-2 mg/kg PO divided twice daily initially. Gradually reduce dose every 2 weeks until reach 0. 5 mg/kg PO every other day. Lumbosacral: Prednisone: 1 mg/kg PO divided twice daily initially. Gradually reduce dose to 0. 5 mg/kg, PO every other day (Sc hunk 1988a) f) For adjunctive therapy of White Dog Shaker Syndrome: Pr ednisone 0. 25 mg/kg PO twice daily for 10 days, then once a day for 10 days, then every other day for 10 days (Fenner 1988) g) For adjunctive therapy of generalized tremor syndrome: Pr edniso(lo)ne 3 m/kg each AM for 5 days, then decreased to alternate mornings for 5 days, then begin a phased with-drawal of drug. May require long-term low-dose alternate day the rapy. (Farrow 1986) h) For nonbacterial suppurative meningitis: After cultures are co nﬁrmed negative, prednisone 2 mg/kg for 10 days, then ta-per slowly over 1 month (Fenner 1986b) i) For adjunctive therapy of dogs diagnosed with canine wob-bler syndrome with signs of mild to moderate paraparesis, te traparesis, or ataxia: Prednisolone 1-2 mg/kg twice daily initially, decrease gradually over a 5 day period to 0. 5-1 mg/ kg on alternate days (Trotter 1986) For hematologic disorders: a) For autoimmune hemolytic anemia: Prednisolone 1-4 mg/ kg PO daily divided two times a day. Add immunosuppres-sive agent (e. g., cyclophosphamide, azathioprine) if PCV does not stab ilize within 48-72 hours. May take several months to wean off drugs. (Maggio-Price 1988) b) For adjunctive therapy of pure red blood cell aplasia (PRCA): Pr ednisolone 2 mg/kg divided two times a day. If no in-creases in reticulocyte count in 2-weeks, increase to 4 mg/kg, two times a day. If reticulocyte counts remain low after 4-6 weeks add cyclophosphamide (30-50 mg/m2 on 4 consecu-tive days each week). Continue prednisolone. Discontinue cyc lophosphamide if neutropenia or thrombocytopenia oc-curs. If reticulocyte count increases, cyclophosphamide may be discontinued and prednisolone slowly tapered to alternate day therapy. (Weiss 1986) c) For immune-mediated thrombocytopenia: Prednisolone 1- 3 mg/kg PO divided two to three times a day. Do not give IM injections. If platelet-count increases, prednisolone dose may be tapered by 50% every 1-2 weeks. Reduction in dose should be done slowly over several months. (Johnessee and Hurvitz 1983) For dermatologic or other immune-mediated disorders: a) For adjunctive therapy of urticaria and angioedema: Pred-nisone 2 mg/kg PO or IM twice daily (Giger and Werner 1988) b) For canine atopy: Predniso(lo)ne 0. 5 mg/kg PO twice daily initial ly for 5-10 days, then taper to the minimum effective alternate-day dosage (Giger and Werner 1988) c) For adjunctive ﬂea allergy dermatitis: Prednisolone 1 mg/kg PO o nce a day for 1 week, the every other day at a minimally effective dose (Giger and Werner 1988) d) As an immunosuppressant for auto-immune skin diseases: Pr edniso(lo)ne 2. 2 mg/kg twice daily until remission; then taper to lowest effective every other day dosage (Giger and Werner 1988) e) For type II (cytotoxic) hypersensitivity: Predniso(lo)ne 2 mg/kg tw o times a day. Once in remission, dosage may be reduced to a maintenance level. Other immunosuppressants may be required (Wilcke 1986) f) For adjunctive therapy of urticaria, shock, and/or respiratory arr est secondary to contrast media hypersensitivity: Predni-solone sodium succinate 10 mg/kg IV (Walter, Feeney, and Johnst on 1986) g) For adjunctive therapy of surface pyodermas: Predniso(lo)ne 1 mg/kg/day f or 5-7 days (Ihrke 1986) h) For eosinophilic ulcer: Prednisolone 2-4. 4 mg/kg PO once a da y; for chronic cases use prednisolone 0. 5-1 mg/kg PO every other day (De Novo 1988) Miscellaneous Indications: a) For boxer cardiomyopathy: In patients not responding to an-tiarrhythmic agents: Prednisolone 1 mg/kg twice daily for 10 day s (Ware and Bonagura 1986) b) As an appetite stimulant: Prednisolone 0. 25-0. 5 mg/kg PO ev ery day, every other day, or intermittently as needed. (Macy and Ralston 1989) c) For adjunctive therapy of posterior uveitis: Prednisolone 2. 2 mg/kg o nce daily; gradually reduce dose as inﬂammation is controlled (Swanson 1989) d) For chronic, proliferative, pyogranulomatous laryngitis: Pr ednisolone 1 mg/kg twice daily PO; decrease dosage week-ly (Prueter 1988a) e) For adjunctive or alternate therapy for hypercalcemia: Pred-nisolone 1-1. 5 mg/kg PO q12h. Has a delayed onset of ac-tion and a 4-8 day duration of response. (Kruger, Osborne, and Polzin 1986) f) A s an antiinﬂammatory in the adjunctive treatment of oti-tis interna: Prednisone 0. 25 mg/kg/day for ﬁrst 5-7 days of tr eatment (Neer 1988) g) For adjunctive therapy of myasthenia gravis: Prednisone 0. 5 mg/kg/day PO. Increase in 0. 5 mg/kg/day increments every 2-4 days until total dose of 2 mg/kg/day is attained. After remission is achieved, gradually shift to every other day ther-apy. Should patient worsen during period when prednisone dose is increased, reduce dose and increase the intervals be-tween dosage increases. May take several weeks to see a posi-tive response. After signs are controlled, reduce dosage every 4 w eeks until maintenance dose is determined. Cytotoxic drugs may be indicated should symptoms not be controlled or if dosage cannot be reduced. (Le Couteur 1988) !TCATS: Note : Use prednisolone in place of prednisone in this species whenever possible. Cats may not absorb or convert prednisone as we ll as dogs. As an immunosuppressive agent: a) Predniso(lo)ne: Initially 2-4 mg/kg daily in divided doses. Tap er to alternate day, low-dose therapy as rapidly as patient allows. (Gorman and Werner 1989) For adjunctive treatment of respiratory disorders: a) Allergic bronchitis: Prednisolone sodium succinate: 1-3 mg/kg IV or IM (do not give via rapid IV infusion) (Bauer 1988)	pppbs.pdf
Tb) For adjunctive therapy of feline asthma: Predniso(lo)ne: 1-2 mg/kg/da y (P apich 1986); c) For adjunctive emergency therapy: Prednisolone sodium suc-cinate 50-100 mg IV. For non-emergency cases: Prednisone 5 mg PO three times daily initially, then rapidly decrease to alternate day use (or discontinue) (Noone 1986) For adjunctive therapy of disorders of the gastrointestinal tract: a) For plasmacytic/lymphocytic enteritis: Prednisolone 2. 2 mg/ kg PO divided twice daily for 5-10 days, then 1. 1 mg/kg/day for 5-10 days, then taper by reducing steroid dosage by 1/2 every 10-14 days until alternate-day dosage is attained or symptoms recur (Chiapella 1988) b) For small intestinal inﬂammatory bowel disease: Prednisone 1- 2 mg/kg/day divided into 2 doses. Mild to moderate cases generally will respond to the lower dosage. If severe, use the higher dose and treat for 2-4 weeks or until symptoms re-solve. In severe cases characterized by anorexia, weight loss, and c hronic diarrhea, use an initial dose of 4 mg/kg/day for 2 weeks. If response is good, decrease dose by 1/2 after 2 weeks and again by 1/2 at 4 weeks. Eventually, alternate day thera-py can be attained and should be maintained for 3 months. So me cats may have drugs discontinued in 3 months or long-term alternate day (or every 3rd day dosing) may be required. (T ams 1986) For adjunctive therapy of feline plasma cell gingivitis-pharyngitis: a) Prednisolone 1-2 mg/kg PO once daily (De Novo, Potter, and Woolfson 1988) Fo r adjunctive therapy of feline heartworm disease: a) For crisis due to embolization; Prednisolone 4. 4 mg/kg three times daily with careful IV ﬂuid therapy (Dillon 1986) Fo r dermatologic conditions: a) For adjunctive treatment of ﬂea allergy: Predniso(lo)ne 1-2 mg/kg PO q12h for 5 days, then gradually taper to alter-nate-day therapy (usually 1-2 mg/kg every other evening) (Kw ochka 1986) b) For idiopathic feline miliary dermatoses: Predniso(lo)ne 1- 2 mg/kg PO q12h for 5-7 days, then reduce gradually to alternate-day therapy at 1-2 mg/kg. Rarely is effective for long-term use. (Kwochka 1986) c) For linear granulomas: Prednisolone 0. 5 mg/kg twice daily initial ly, with taper (Thoday 1986) d) For eosinophilic ulcer: Prednisolone 2-4. 4 mg/kg PO once a da y; for chronic cases use prednisolone 0. 5-1 mg/kg PO every other day (De Novo, Potter, and Woolfson 1988) As adjunctive therapy for feline neoplasias (lymphosarcoma, acu te lymphoid leukemia, mast cell neoplasms): a) 20-50 mg/m2 q24-48h PO, SC or IV (Couto 1989). See also the pr otocols noted in the canine dosage section. !TCATTLE: For adjunctive therapy of cerebral edema secondary to polioen-cephalomalacia: a) Prednisolone 1-4 mg/kg intravenously (Dill 1986) Fo r adjunctive therapy of aseptic laminitis: a) Prednisolone (assuming sodium succinate salt) 100-200 mg IM or IV; continue therapy for 2-3 days (Berg 1986) Fo r glucocorticoid activity: a) Prednisolone sodium succinate: 0. 2-1 mg/kg IV or IM (Ho ward 1986) !TRABBITS, RODENTS, SMALL MAMMALS: a) Rabbits: Rarely indicated. Use with caution; concurrent gas-troprotectant is recommended. For spinal trauma: 0. 25-0. 5 mg/kg PO q12h for 3 days, then once daily for 3 days, then once every other day for 3 doses. As an antiinﬂammatory: 0. 5-2 mg/kg PO (Ivey and Mor-risey 2000) b) Mice, Rats, Gerbils, Hamsters, Guinea pigs, Chinchillas: 0. 5-2. 2 mg/kg IM or SC (Adamcak and Otten 2000) !TFERRETS: As an antiinﬂammatory or for insulinoma (postsurgical or non-surgical cases): a) 0. 5-2 mg/kg PO or IM (frequency not speciﬁed) (Williams 2000) !THORSES: (Note : ARCI UCGFS Class 4 Drug) Note : Prednisone does not appear to be absorbed very well after oral dosing; use prednisolone or another oral steroid. For adjunctive therapy of COPD: a) Prednisolone: Initially, 600-800 mg IM or PO in a 450 kg hor se. May be possible to decrease dose and go to alternate day dosing. Doses as low as 200 mg every other day may be effective. (Beech 1987a) For glucocorticoid effects: a) Prednisolone sodium succinate: 0. 25-1 mg/kg IV, Pr edniso(lo)ne tablets 0. 25-1 mg/kg PO; Prednisolone ac-etate: 0. 25-1 mg/kg IM or 10-25 mg subconjunctivally (Ro binson 1987) !TLLAMAS: For steroid-responsive pruritic dermatoses secondary to allergic origins: a) Prednisone: 0. 5-1 mg/kg PO initially, gradually reduce dos-age to lowest effective dose given every other day (Rosychuk 1989) !TSWINE: For glucocorticoid activity: a) Prednisolone sodium succinate: 0. 2-1 mg/kg IV or IM (Ho ward 1986) !TBIRDS: As an antiinﬂammatory: a) Prednisolone: 0. 2 mg/30 gram body weight, or dissolve one 5 mg tablet in 2. 5 m L of water and administer 2 drops orally. Give twice daily. Decrease dosage schedule if using long-term. (Clubb 1986) For treatment of shock: a) Prednisolone sodium succinate (10 mg/m L): 0. 1-0. 2 m L/100 gr ams body weight. Repeat every 15 minutes to effect. In large birds, dosage may be decreased by 1/2. (Clubb 1986) !TREPTILES: For shock in most species using prednisolone sodium succinate: a) 5-10 mg/kg IV as needed (Gauvin 1993) Monitoring Monitoring of glucocorticoid therapy is dependent on its reason for use, dosage, agent used (amount of mineralocorticoid activity), dosage schedule (daily versus alternate day therapy), duration of therapy, and the animal's age and condition. The following list may not be appropriate or complete for all animals; use clinical assess-ment and judgment should adverse effects be noted: !TWeight, appetite, signs of edema !TSerum and/or urine electrolytes !Total plasma proteins, albumin	pppbs.pdf
T ! Blood glucose T ! Growth and development in young animals T ! ACTH stimulation test if necessary Client Information T ! Clients should carefully follow the dosage instructions and not discontinue the drug abruptly without consulting with veterinar-ian beforehand. T ! Clients should be briefed on the potential adverse effects that can be seen with these drugs and instructed to contact the veterinar-ian should these effects become severe or progress. Chemistry/Synonyms Prednisolone and prednisone are synthetic glucocorticoids. Prednisolone and prednisolone acetate occur as odorless, white to practically white, crystalline powders. Prednisolone is very slightly soluble in water and slightly soluble in alcohol. The acetate ester is practically insoluble in water and slightly soluble in alcohol. The sodium succinate ester is highly water-soluble. Prednisone occurs as an odorless, white to practically white, crystalline powder. Prednisone is very slightly soluble in water and slightly soluble in alcohol. Prednisolone is also known as deltahydrocortisone or meta-cortandralone. Prednisone may also be known as: delta(1)-cortisone, 1,2-dehydrocortisone, deltacortisone, deltadehydrocortisone, meta-cortandracin, NSC-10023, prednisonum; many trade names are available. Storage/Stability/Compatibility Prednisolone and prednisone tablets should be stored in well-closed containers. All prednisone and prednisolone products should be stored at temperatures less than 40°, and preferably be-tween 15-30°C; avoid freezing liquid products. Do not autoclave. Oral liquid preparations of prednisone should be stored in tight containers. Do not refrigerate prednisolone syrup. Prednisolone sodium succinate should be stored at room tem-perature and protected from light (store in carton). After reconsti-tution, the product is recommended for immediate use and not to be stor ed for later use. Little data appears to be available regarding the compatibility of pr ednisolone sodium succinate injection (Solu-Delta Cortef®— Upjohn) with other products. A related compound, prednisolone sodium phosphate is reportedly physically compatible with the fol-lowing drugs/solutions: ascorbic acid injection, cephalothin so-dium, cytarabine, erythromycin lactobionate, ﬂuorouracil, hepa-rin sodium, methicillin sodium, penicillin G potassium/sodium, tetr acycline HCl, and vitamin B-Complex with C. It is reportedly physically incompatible with: calcium gluconate/gluceptate, dimen-hydrinate, metaraminol bitartrate, methotrexate sodium, prochlo-rperazine edisylate, polymyxin B sulfate, promazine HCl, and pro-methazine. Compatibility is dependent upon factors such as p H, conce ntration, temperature, and diluent used; consult specialized references or a hospital pharmacist for more speciﬁc information. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: A zero tolerance of residues in milk for these compounds have been established for dairy cattle. All these agents require a prescription (Rx). Known approved-veterinary products for systemic use are in-dicated below. The ARCI (Racing Commissioners International) has designated this drug as a class 4 substanc e. See the appendix for more information. Prednisolone Tablets: 5 mg, 20 mg: Prednis-T ab® (Vedco, Phoenix Pharmaceutical, Vet-A-Mix); generic; (Rx). Approved for use in dogs. Prednisolone, T etracycline, Novobiocin Tablets: each tablet contains 60 mg te tracycline, 60 mg novobiocin, 1. 5 mg prednisolone. Delta Albaplex®; each tablet contains 180 mg tetracycline, 180 mg novo-biocin, and 4. 5 mg prednisolone Delta A lbaplex® 3X (Pﬁzer); (Rx). Approved for use in dogs. Prednisolone & Trimeprazine Tartrate Tablets: each tablet contains trimep razine 5 mg and prednisolone 2 mg. Temaril-P® (Pﬁzer Ani-mal Health); (Rx). Approved for use in dogs. HUMAN-LABELED PRODUCTS: Prednisolone Tablets: 5 mg generic; (Rx) Prednisolone Sodium Phosphate Orally Disintegrating Tablets: 10 mg, 15 mg & 30 mg (as base); Orapred ODT® (Alliant Pharmaceuti-cals); (Rx) Prednisolone Syrup/Oral Liquid or Solution: 1 mg/m L, 3 mg/m L; in 120 m L, 237 m L. 240 m L and 480 m L; Prelone® (Aero); Pediapred® (UCB Pharma); Orapred® (Bio Marin); generic; (Rx) Prednisone Tablets: 1 mg, 2. 5 mg, 5 mg, 10 mg, 20 mg & 50 mg; Meti-cor ten® (Schering); Orasone® (Solvay); Panasol-S® (Seatrace); Delta-sone® (Upjohn); Prednic en-M® (Central); Sterapred® and Sterapred DS® (Merz); generic; (Rx) Prednisone Oral Solution/Syrup: 1 mg/m L in 120 m L, 240 m L, 500 m L and UD 5 m L; 5 mg/m L in 30 m L; Prednisone and Prednisone Intensol® Concentrate (Roxane); Liquid Pred® (Muro); (Rx) Ophthalmic solutions/suspensions are available. PRIMAQUINE PHOSPHATE (prim-ah-kwin) ANTIPROTOZOAL Prescriber Highlights TT Antiprotozoal agent considered the drug of choice for treating Babesia felis in cats; does not apparently “cure” the infection; repeated courses of therapy may be necessary TT May also be useful in treating Hepatazoon canis in dogs or Plasmodium spp. in birds TT Most common adverse effect in cats is nausea; giving with food may help TT Very narrow therapeutic index (safety margin); must be careful in determining dosages TT Monitoring CBC mandatory Uses/Indications Primaquine is considered the drug of choice for treating Babesia felis in cats. Primaquine does not apparently “cure” the infection; repeated courses of therapy may be necessary. It may be useful in treating Hepatazoon canis in dogs or Plasmodium spp. in birds. In humans, primaquine is used for treatment and prophylaxis for ma-laria and treating Pneumocystis pneumonia.	pppbs.pdf
TPharmacology/Actions Primaquine's antiprotozoal mechanism of action is not well under-stood, but it may be related to it binding and altering protozoal DNA. Pharmacokinetics No pharmacokinetic information was located for small animals. In humans, primaquine rapidly absorbed with high (96%) systemic bioavailability. It is extensively distributed and rapidly metabolized in the liver to carboxyprimaquine. It is not known if this metabo-lite has any antiprotozoal activity. Elimination half-life is around 6 hours f or primaquine; 24 hours for carboxyprimaquine. Contraindications/Precautions/Warnings Primaquine is contraindicated in patients with known hypersen-sitivity to it. In humans, it is contraindicated in patients receiving other bone marrow suppressant medications or patients susceptible to granulocytopenia (e. g., lupus, rheumatoid arthritis). The CDC states the drug is contraindicated in individuals with G-6-PD de-ﬁciency, and during pregnancy or lactation (unless nursing infant de termined not to be G-6-PD deﬁcient). Adverse Effects Vomiting is the most common adverse effect in cats associated with primaquine; dosing with food may help alleviate this problem. Other concerns include myelosuppression, methemoglobinemia and hemolysis. Safety margin is particularly narrow with this drug in cats (see Overdoses). Reproductive/Nursing Safety The CDC recommends using chloroquine or meﬂoquine for hu-mans during pregnancy and to defer using primaquine until after de livery primarily because primaquine can cause hemolytic anemia in G-6-PD deﬁcient fetuses. It is also contraindicated during lacta-tion in nursing infants unless they are determined not to be G-6-PD deﬁcient. While signiﬁcance for veterinary patients is not clear, pr imaquine should be avoided during pregnancy and lactation. Overdosage/Acute Toxicity In cats, it has been reported that dosages greater than 1 mg/kg can be lethal. Overdoses should initially be handled aggressively using standardized protocols for removal of drug from the gut and to pre-vent absorption. Because of the potential seriousness of overdoses, it is recommended to contact an animal poison control center for guidance. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving primaquine and may be of signiﬁcance in veterinary patients: !TQUINACRINE : May potentiate the toxicity of one another; use of primaquine within 3 months of quinacrine is not recommended !TBONE MARROW DEPRESSANT DRUGS (e. g., amphotericin B, azathioprine, chloramphenicol, many antineoplastic drugs ) or HEMOLYTIC DRUGS (e. g., acetohydroxamic acid, sulfonylureas, quinidine, sulfonamides ): Use with primaquine may cause increased risk for toxicity Laboratory Considerations No speciﬁc concerns noted Doses !TCATS: Note: Dosing for humans for primaquine is usually described in terms of primaquine base, but dosages for cats may not direct-ly specify whether primaquine is being dosed as the phosphate or as the base. Because primaquine has an extremely narrow therapeutic index in cats, this is problematic as a 26. 3 mg pri-maquine phosphate tablet contains only 15 mg of primaquine base. Additionally, commercially available tablets are usually too concentrated to be accurately dosed in domestic cats; a special-ized compounding pharmacy should be employed to prepare a suitable dosage form. Be clear as to the amount of primaquine base or phosphate wanted per dose. a) For Babesia felis: 0. 5 mg (as base)/kg PO once daily for 1-3 da ys. (Greene, Hartmannn et al. 2006) b) For Babesia felis: 1 mg (total dose per cat) primaquine phos-p hate PO every 36 hours for 4 treatments, then 1 mg (total dose) per cat every 7 days for 4 treatments. The drug does not sterilize the infection. (Lobetti 2005) c) For Babesia felis: Primaquine phosphate 1 mg/kg IM one t ime. (Birkenheuer 2005) Note : IM dosage form must be compounded. Monitoring !TCBC; weekly while treating !TImproved clinical signs (increased appetite and body weight, im-provement in anemia) Client Information !This drug has a very low safety margin when used in cats; exact adherence with the prescribed dosage is very important; do not double-up the next dose if a dose was previously missed !TGive dose with food to reduce chance for GI problems (vomiting) Chemistry/Synonyms Primaquine phosphate is an 8-amino-quinoline compound that occurs as an orange-red, odorless, bitter-tasting, crystalline powder. It is soluble (1 gram in 15 m L) in water and practically insoluble in alcohol. 1 mg of primaquine phosphate contains 0. 57 mg of pri-maquine base. Primaquine may also be known as primachina, primachinum, pr imaquina or SN 13272. Storage/Stability Primaquine phosphate tablets should be stored in a tight, light re-sistant container below 40°C, preferably between 15-30°C. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Primaquine Phosphate Tablets: 26. 3 mg (equivalent to 15 mg pri-maquine base); generic; (Rx)	pppbs.pdf
PRIMIDONE (pri-mi-done) Mysoline®, Neurosyn® ANTICONVULSANT Prescriber Highlights TT Phenobarbital precursor that may be useful for treating seizures in dogs; most recommend using phenobarbital instead TT Contraindications: Severe liver disease or patients with demonstrated previous hypersensitivity. Large Doses Con-traindicated: Nephritis or severe respiratory dysfunction TT Extreme Caution: Cats TT Caution: Hypovolemic, anemic, have borderline hypoadre-nal function, or cardiac or respiratory disease TT Adverse Effects: DOGS: anxiety & agitation when initiat-ing therapy, increases in liver enzymes, hepatic lipidosis, hepatocellular hypertroph y/necrosis, extramedullary hematopoiesis, depression, polydipsia, polyuria, & polyphagia, anorexia, tachycardia, dermatitis, episodic hyperventilation, urolith formation; rarely megaloblastic anemia TT Possibly more hepatotoxic than phenobarbital to dogs TT Most of the anticonvulsant activity comes from the phe-nobarbital metabolite of primidone TT Drug Interactions, lab interactions Uses/Indications Primidone is indicated for seizure control (idiopathic epilepsy, epi-leptiform convulsions) in the dog. Because it is rapidly converted into phe nobarbital in this species (see Pharmacokinetics below), and has a greater incidence of hepatotoxicity and behavioral ef-fects, most neurologists do not recommend its use. However, some clinicians fe el that some animals not responding to phenobarbital do beneﬁt from primidone therapy, perhaps as a result that PEMA has been demonstrated to potentiate the anticonvulsant activity of phenobarbital in animals. When compared with phenobarbital, increased incidence of hepatotoxicity associated with primidone is considered the major limitation to long-term therapy with this agent. Primidone is considered more toxic in rabbits and cats than in humans or dogs. Pharmacology/Actions Primidone and its active metabolites, phenylethamalonamide (PEMA) and phenobarbital have similar anticonvulsant actions. While the exact mechanism for this activity is unknown, these agents raise seizure thresholds or alter seizure patterns. Pharmacokinetics Primidone is slowly absorbed after oral administration in the dog, with peak levels occurring 2-4 hours after dosing. The bioavail-ability of primidone in humans has been reported as 60-80%. Primidone is rapidly converted to PEMA and phenobarbital in the dog. Serum half-lives of primidone, PEMA, and phenobarbital have been reported to be 1. 85 hrs, 7. 1 hrs, and 41 hours, respectively (Y eary 1980). In the dog, a 250 mg dose of primidone is approxi-mately equivalent to 60 mg of phenobarbital (Platt 2005). Primidone, like phenobarbital (possibly due to the phenobarbi-tal?), can induce hepatic microsomal enzymes that can increase the rate of metabolism of itself and other drugs. For more information on the pharmacokinetics of phenobarbi-tal, refer to its monograph. Contraindications/Precautions/Warnings Many clinicians and the veterinary manufacturers of primidone feel that primidone is contraindicated in cats, other clinicians dis-pute this, but it is recommended that primidone be used in cats only w ith extreme caution. Use cautiously in patients who are hy-povolemic, anemic, have borderline hypoadrenal function, or car-diac or respiratory disease. Large doses are contraindicated in pa-tients with nephritis or severe respiratory dysfunction. Primidone is cont raindicated in patients with severe liver disease or have had hypersensitivity reactions. When converting dogs from primidone to phenobarbital, it has been suggested do this slowly (1/4 of the dose each month) (Platt 2005). Adverse Effects Adverse effects in dogs are similar for both primidone and phe-nobarbital. Dogs may exhibit increased clinical signs of anxiety and agitatio n when initiating therapy. These effects may be transi-tory in nature and often will resolve with small dosage increases. Occasionall y, dogs will exhibit profound depression at lower dosage ranges (and plasma levels). Polydipsia, polyuria, and polyphagia are quite commonly displayed at moderate to high serum levels; these are best controlled by limiting intake of both food and water. Sedation and/or ataxia often become signiﬁcant concerns as serum levels reach the higher ends of the therapeutic range. Increases in liver enzymes (ALT, ALP, glutamate dehydrogenase) and decr eased serum albumin with chronic therapy are common (up to 70% of dogs treated), and more prevalent than with pheno-barbital. Hepatic lipidosis, hepatocellular hypertrophy and necro-sis, and extramedullary hematopoiesis can be seen after 6 months of ther apy. Serious hepatic injury probably occurs in approximately 6-14% of dogs treated. In dogs, anorexia, tachycardia, dermatitis, episodic hyperven-tilation, urolith formation and, rarely, megaloblastic anemia have also been r eported with primidone therapy. Reproductive/Nursing Safety The effects of primidone in pregnancy are unknown. In pregnant humans, procarbazine is designated by the FDA as a category D drug (There is evidence of human fetal risk, but the potential ben-eﬁts from the use of the drug in pregnant women may be acceptable despite its p otential risks. ) In a separate system evaluating the safety of drugs in canine and feline pregnancy (Papich 1989), this drug is categorized as 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. ) Primidone appears in maternal milk in substantial quantities. It is s uggested that if somnolence occurs in nursing newborns to consider discontinue nursing. Overdosage/Acute Toxicity Because primidone is rapidly metabolized to phenobarbital in dogs, similar clinical signs (sedation to coma, anorexia, vomiting, nystagmus) are seen and corresponding procedures should be used for the treatment of acute primidone overdose. This includes the removal of ingested product from the gut if appropriate, and offer-ing respiratory and cardiovascular support. Activated charcoal has been demonstrated to be of considerable beneﬁt in enhancing the	pppbs.pdf
clearance of phenobarbital, even when the drug was administered parenterally. Charcoal acts as a “sink” for the drug to diffuse from the vasculature back into the gut. Forced alkaline diuresis can be of considerable beneﬁt in augmenting the elimination of phenobarbi-tal in patients with normal renal function. Peritoneal or hemodialy-sis may also be helpful in severe intoxications or in anuric patients. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving primidone or pheno-barbital (primidone's active metabolite) and may be of signiﬁcance in ve terinary patients: !TACETAMINOPHEN : Increased risk for hepatotoxicity, particularly when large or chronic doses of barbiturates are given !TCARBONIC ANHYDRASE INHIBITORS (e. g., acetazolamide ): Oral ad-ministration may decrease the GI absorption of primidone. !TMONAMINE OXIDASE (MAO) INHIBITORS (e. g., amitraz, possibly selegi-line): May prolong phenobarbital effects !TPHENYTOIN : Barbiturates may affect the metabolism of phenytoin, and phenytoin may alter barbiturate levels; monitoring of blood levels may be indicated !TRIFAMPIN : May induce enzymes that increase the metabolism of barbiturates The following drugs may increase the effects of phenobarbital: !!ANTIHISTAMINES !!CHLORAMPHENICOL !TOPIATES !TPHENOTHIAZINES !!VALPROIC ACID Phenobarbital (particularly after chronic therapy) may decrease the effect of the following drugs/drug classes by lowering their serum concentrations: !!ANTICOAGULANTS, ORAL (WARFARIN ) !!BETA-BLOCKERS !!CHLORAMPHENICOL !!CLONAZEPAM !!CORTICOSTEROIDS !!CYCLOSPORINE !!DOXORUBICIN !TDOXYCYCL INE (may persist for weeks after barbiturate discontinued) !!ESTROGENS !!GRISEOFULV IN !!METHADONE !!METRONIDAZOLE !!QUINIDINE !!PAROXETINE !!PHENOTHIAZINES !!PROGESTINS !!THEOPHYLLINE !TTRICYCLIC ANTIDEPRESSANTS !!VERAPAMIL Laboratory Considerations !TBarbiturates may cause increased retention of bromosulfophthalein (BSP; sulfobromophthalein) and give falsely elevated results. It is recommended that barbiturates not be administered within the 24 hours before BSP retention tests; or if they must, (e. g., for sei-zure control) the results be interpreted accordingly. !TPhenobarbital can alter thyroid testing. Decreased total and free T4, normal T3, and either normal or increased TSH have been reported. It has been suggested to wait at least 4 weeks after dis-continuing phenobarbital to perform thyroid testing. !TIn some dogs, phenobarbital may cause a false positive low dose dexamethasone suppression test, by increasing the clearance of dexamethasone. Phenobarbital apparently has no effect either on ACTH stimulation tests or on the hormonal equilibrium of the adrenal axis. Doses !TDOGS: a) Initially, 10-30 mg/kg per day divided into 2-3 doses (Le C outeur 1999) b) 10 mg/kg PO q8h; not recommended as ﬁrst choice (Taylor 2003b) !TCATS: a) 11-22 mg/kg three times daily (Davis 1985b) b) 20 mg/kg, PO q12h (Neff-Davis 1985) Monitoring !TAnticonvulsant efﬁcacy !TAdverse effects (CNS related, PU/PD, weight gain) !TSerum phenobarbital levels if lack of efﬁcacy or adverse reactions noted. Although there is some disagreement, therapeutic serum lev els in dogs are thought to mirror those in people at 15-40 micrograms/m L. See the phenobarbital monograph for more in-formation. !TIf used chronically, routine CBCs and liver enzymes at least every 6 months Client Information !TCompliance with therapy must be stressed to clients for success-ful epilepsy treatment. Encourage giving daily doses at same time eac h day. !TVeterinarian should be contacted if animal develops signiﬁcant adverse reactions (including clinical signs of anemia and/or liver disease) or if seizure control is unacceptable. Chemistry/Synonyms An analog of phenobarbital, primidone occurs as a white, odor-less, slightly bitter-tasting, crystalline powder with a melting point of 279°-284°C. One gram is soluble in approximately 2000 m L of water or 200 m L of alcohol. Primidone may also be known as: hexamidinum, prima-clone, primidonum, Cy ral®, Epidona®, Liskantin®, Mylepsinum®, Mysoline®, Neurosyn®, Prysoline®, Resimatil®, or Sertan®. Storage/Stability Tablets should be stored in well-closed containers preferably at room temperature. The oral suspension should be stored in tight, light-resistant containers preferably at room temperature; avoid freezing. Commercially available suspension and tablets generally have expiration dates of 5 years after manufacture. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Primidone Tablets: 50 mg and 250 mg; Neurosyn® (Boehringer In-gelheim); generic; (Rx). Approved for use in dogs. The ARCI (Racing Commissioners International) has designated this drug as a c lass 3 substance. See the appendix for more information.	pppbs.pdf
HUMAN-LABELED PRODUCTS: Primidone Tablets: 50 mg & 250 mg; Mysoline® (Xcell Pharm); ge-neric; (Rx) PROBENECID (proh-ben-eh-sid) Benemid®, Benuryl® URICOSURIC; RENAL TUBULAR SECRETION INHIBITOR Prescriber Highlights TT Uricosuric & renal tubular secretion inhibitor that may be useful for treating gout (particularly in reptiles) TT Probenecid is associated with many drug interactions as it inhibits the renal tubular secretion of numerous drugs, including several beta-lactam antibiotics; some interac-tions may be beneﬁcial, others may increase potential for toxicity TT Little experience using this drug in mammals other than humans Uses/Indications Although there has been very limited clinical use or research on probenecid in veterinary medicine, it can be useful in treating gout (hyperuricemia), particularly in reptiles. Probenecid's effect in inhibiting renal tubular secretion of certain beta-lac tam antibiotics and other weak organic acids is of interest for increasing serum concentrations, or reducing doses and dosing frequency of these drugs. This may allow greater efﬁcacy (but also toxic effects) and reduce the cost or dosing frequency of expensive human drugs. Probenecid has a signiﬁcantly long elimination half-life in dogs (about 18 hours), which may make it particularly useful in this species; however, at present there is little research supporting this use of probenecid in veterinary patients. Pharmacology/Actions Probenecid reduces serum uric acid concentrations by enhancing uric acid excretion into the urine by competitively inhibiting urate reabsorption at the proximal renal tubules. Probenecid competitively inhibits tubular secretion of weak or-ganic acids including the penicillins, some cephalosporins (not cef-triaxone, ceftazidime, or cefoperazone), sulbactam and tazobactam (not clavulanic a cid), oseltamivir, etc. Pharmacokinetics There is limited information available for veterinary species. In dogs, information on oral bioavailability was not located, but after intravenous administration the distribution half-life was 2. 3 hours and apparent volume of distribution at steady state was 0. 46 L/kg. Probenecid exhibits biphasic concentration dependent plasma pro-tein binding characteristics in the dog and appears to bind less to plasma prot eins than in humans. Plasma clearance was 0. 343 m L/ min/kg and elimination half-life was 17. 7 hours, which is consider-ably longer than in humans (6. 5 hrs) or sheep (1. 55 hrs) (Kakizaki, Y okoy ama et al. 2005). After administration to mares, probenecid had an oral bioavail-ability of approximately 90%. The drug is highly bound (99. 9%) to eq uine plasma proteins. Elimination half-life is approximately 90-120 minutes. In humans, absorption after oral administration is rapid and complet e. The drug is converted in the liver to glucuronidated, car-boxylated, and hydroxylated compounds that have uricosuric and renal t ubular secretion inhibition activity. Elimination half-life is dosage dependent and large dosages (above 500 mg) have longer half-lives. Contraindications/Precautions/Warnings Probenecid should not be used in patients with, or susceptible to, uric acid renal or bladder calculus formation or urate neph-ropathy (e. g., cancer c hemotherapy with rapidly cytolytic agents). Probenecid requires sufﬁcient renal function to be effective; efﬁcacy decreases with increasing renal function impairment. The drug has no efﬁcacy in human patients with a creatine clearance of less than 30 m L/min. Probenecid is not usually recommended for treating gout in birds as it can exa cerbate the condition. Adverse Effects An accurate adverse effect proﬁle for probenecid has not been de-termined for animal patients. In humans, probenecid occasionally causes headac he, gastrointestinal effects (inappetance, nausea, mild vomiting), or rashes. When used for gout, it can initially cause an increased rate of gouty attacks unless prophylaxis with colchicine is used concurrently. Rarely, hypersensitivity, bone marrow suppres-sion, hepatotoxicity, or nephrotic syndrome have been reported in humans. Reproductive/Nursing Safety Probenecid apparently crosses the placenta, but adverse effects to fetuses have not been reported. In humans, the FDA categorizes probenecid 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 demonstrat-ed a risk to the fetus in the ﬁrst trimester of pregnancy, and there is no evidenc e of risk in later trimesters. ) It is unknown if probenecid enters milk, but it is unlikely to pose much risk t o nursing offspring. Overdosage/Acute Toxicity Limited information is available. One massive (>45 g) overdose in a human patient caused CNS stimulation, seizures, protracted vom-iting and respiratory failure. Consider contacting an animal poison control center for guid-ance with large overdoses. Generally, probenecid overdoses should initially be handled using standardized protocols for removal of drug from the gut and preventing absorption. Treat supportively, but use caution co-administrating drugs that may compete with probenecid for tubular secretion. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving probenecid and may be of signiﬁcance in veterinary patients: T ! ACYCLOVIR : Increased acyclovir serum concentrations; probenecid can decrease renal excretion T ! ANTINEOPLASTICS (rapidly cytolytic ): Increased chance of uric acid nephropathy T ! ASPIRIN (and other salicylates ): Salicylates antagonize the uricosu-ric effects of probenecid T ! BENZODIAZEPINES (lorazepam, oxazepam ): Probenecid may prolong action or reduce time for onset of action	pppbs.pdf
T ! BETA-LACTAM ANTIBIOTICS (including penicillins and some cepha-losporins ): Probenecid may increase serum concentrations by re-ducing renal excretion T ! BETA-LACTAMASE INHIBITORS (including sulbactam and tazobactam, but not clavulanic acid ): Probenecid may increase serum concen-trations by reducing renal excretion T ! CHLORPROPAMIDE (and potentially other sulfonylureas ): Probenecid decreases elimination; hypoglycemia is possible T ! CIPROFLOXACIN : Probenecid reduces renal tubular secretion by about 50% T ! DAPSONE : Possible accumulation of dapsone or its active metabolites T ! FUROSEMIDE : Increased serum furosemide levels T ! HEPARIN : Probenecid may increase and prolong heparin's effects T ! METHOTREXATE : Probenecid may increase levels; increased risks for toxicity T ! NSAIDS (including carprofen, ketoprofen & potentially others ): Probenecid may increase plasma levels and increase risks for toxicity T ! NITROFURANTOIN : Reduced urine levels; increased chance for sys-temic toxicity T ! OSELTAMIVIR : Probenecid may increase serum concentrations by reducing renal excretion T ! RIFAMPIN : Probenecid may reduce hepatic uptake of rifampin and serum levels can be increased; use together is not recommended as effect is inconsistent and can lead to toxicity T ! SULFONAMIDES : Probenecid decreases renal elimination of sulfon-amides, but as free serum concentrations of sulfonamides are not increased this interaction is not therapeutically beneﬁcial and may increase risks for sulfonamide toxicity T ! THIOPENTAL : Anesthesia may be extended or dose required for an-esthesia decreased Laboratory Considerations The following laboratory alterations have been reported in humans with probenecid and may be of signiﬁcance in veterinary patients: T ! Urine glucose determinations : When using cupric sulfate solution (Benedict's Solution, Clinitest®): Probenecid may cause false-positive results. T ests utilizing glucose oxidase (Tes-Tape®, Clin-istix®) are not affected. T ! Theophylline levels : Serum theophylline levels may be falsely el-evated (Schack and Waxtler technique) T ! 17-ketosteroid concentrations in urine : May be decreased T ! Phosphorus : Probenecid may increase phosphorus reabsorption in hypoparathyroid patients T ! Aminohippuric acid (PAH) or Phenolsulphonphthalein (PSP) clearance studies : Probenecid decreases renal clearance T ! Renal function studies using iodohippurate sodium I 123 or I 131, or technetium TC 99 : Decreased kidney uptake T ! Homovanillic acid (HVA) or 5-Hydroxyindoleacetic acid (5-HIAA ): Probenecid inhibits transport from CSF into blood Doses T ! REPTILES: For gout: a) 250 mg PO q12h; can be increased as needed. Suggested dos-age based upon human data as dose is not established for rept iles. (Johnson-Delaney 2005d) b) 40 mg/kg PO q12h (Coke 2004) c) 250 mg PO twice daily; may increase as needed. (de la Na-varre 2003a) Monitoring T ! Depending on purpose for use: serum and urine uric acid, if con-comitant urine alkalinization is used, consider monitoring acid-base balance Client Information T ! In small animals, there is little scientiﬁc data supporting using probenecid for increasing blood levels of drugs that compete with probenecid for renal excretion; probenecid's adverse effects are not well known in these patients Chemistry/Synonyms Probenecid is a sulfonamide derivative that occurs as a white, to practically white, practically odorless, ﬁne, crystalline powder. It is practically insoluble in water and soluble in alcohol. Probenecid may also be known as: probenecidas, probenecidum, Benemid ® and Benuryl ®. Storage/Stability Probenecid tablets should be stored at room temperature in well-closed containers. Expiration dates are generally 3-5 years after manufacture. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Probenecid Tablets: 0. 5 g (500 mg); generic; (Rx) Also available as ﬁxed-dose tablets containing probenecid 500 mg and colchicine 0. 5 mg, but this dosage form is unlikely to be useful in veterinary patients. PROCAINAMIDE HCL (proe-kane-a-mide) Pronestyl® ANTIARRHYTHMIC Prescriber Highlights TT Antiarrhythmic used primarily for treatment of ventricular premature complexes (VPC's), ventricular tachycardia; efﬁcacy is questionable in dogs TT Contraindications: Myasthenia gravis; hypersensitive to drug, procaine or other chemically related drugs; torsade de pointes; or 2nd or 3rd degree heart block (unless arti-ﬁcially paced) TT Extreme Caution: Cardiac glycoside intoxication, systemic lupus; Caution: Signiﬁcant hepatic, renal disease or CHF TT Adverse Effects: DOGS: Blood level related: GI effects, weakness, hypotension, negative inotropism, widened QRS complex & QT intervals, AV block, multiform ven-tricular tachycardias. Possible: fevers & leukopenias TT Profound hypotension can occur if injected too rapidly IV TT Consider dosage reduction in patients with renal failure, CHF, or critically ill TT Drug Interactions	pppbs.pdf
Uses/Indications Procainamide potentially may be useful for the treatment of ven-tricular premature complexes (VPC's), ventricular tachycardia, or supraventricular tachycardia associated with Wolff-Parkinson-White (WPW) syndrome with wide QRS complexes. Higher doses may be beneﬁcial in the treatment of supraventricular tachycardias, although procainamide cannot be considered a ﬁrst-line agent for this dysrhythmia. Pharmacology/Actions A class 1A antiarrhythmic agent, procainamide exhibits cardiac ac-tion similar to that of quinidine. It is considered both a supraven-tricular and ventricular antidysrhythmic. Procainamide prolongs the r efractory times in both the atria and ventricles, decreases myo-cardial excitability, and depresses automaticity and conduction ve-locity. It has anticholinergic properties that may contribute to its eff ects. Procainamide's effects on heart rate are unpredictable, but it usually causes only slight increases or no change. It may exhibit negative inotropic actions on the heart, although cardiac outputs are generally not affected. On ECG, QRS widening, and prolonged PR and QT intervals can b e seen. The QRS complex and T wave may occasionally show some slight decreases in voltage. Pharmacokinetics After IM or IV administration, the onset of action is practically immediate. After oral administration in humans, approximately 75-95% of a dose is absorbed in the intestine, but some patients absorb less than 50% of a dose. Food, delayed gastric emptying, or decreased stomach p H may delay oral absorption. In dogs, it has been reported that the oral bioavailability is approximately 85% and the absorption half-life is 0. 5 hours; however, there is an appar-ent large degree of variability in both bioavailability and half-life of absor ption. Distribution of procainamide is highest into the CSF, liver, splee n, kidneys, lungs, heart and muscles. The volume of distribu-tion in dogs is approximately 1. 4-3 L/kg. It is only approximately 20% p rotein bound in humans and 15% in dogs. Procainamide can cross the placenta and is excreted into milk. The elimination half-life in dogs has been reported to be vari-able; most studies report values between 2-3 hours. In humans, pr ocainamide is metabolized to N-acetyl-procainamide (NAPA), an active metabolite. It appears, however, that dogs do not form ap-preciable amounts of NAPA from procainamide as they are unable to appreciably acetylate aromatic and hydrazine amino groups. In the dog, approximately 90% (50-70% unchanged) of an intrave-nous dose is excreted in the urine as procainamide and metabolites within 24 hour s after dosing. Contraindications/Precautions/Warnings Procainamide may be contraindicated in patients with myasthenia gravis (see Drug Interactions). Procainamide is contraindicated in patients hypersensitive to it, procaine or other chemically related drugs. In humans, procainamide is contraindicated in patients with systemic lupus erythematosus (SLE), but it is unknown if it ad-versely affects dogs with this condition. Procainamide should not be used in patients with torsade de pointes, or with 2nd or 3rd de-gree heart block (unless artiﬁcially paced). Procainamide should be used with extreme caution, if at all, in patie nts with cardiac glycoside intoxication. It should be used with caution in patients with signiﬁcant hepatic or renal disease or with congestive heart failure. It has been recommended to not use procainamide in Doberman pinsche rs and boxers with dilated cardiomyopathy or dogs with sub-aortic stenosis; the drug may be proarrhythmic in certain patients susceptible to tachyarrhythmic-induced sudden death. (Kittleson 2006c) Adverse Effects Adverse effects are generally dosage (blood level) related in the dog. Gastrointestinal effects may include anorexia, vomiting, or diar-rhea. Effects related to the cardiovascular system can include weak-ness, hypotension, negative inotropism, widened QRS complex and QT intervals, A V block, multiform ventricular tachycardias. Fevers and leukopenias are a possibility. Profound hypotension can occur if injected too rapidly IV. In humans an SLE syndrome can occur, but its incidence has not been established in the dog. Dosages should usually be reduced in patients with renal failure, co ngestive heart failure, or those who are critically ill. 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 fe tus, 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 thes e drugs are safe if they are not administered when the animal is near term. ) Both procainamide and NAPA are excreted in maternal milk and absor bed in nursing offspring. It should be used with caution in nursing patients; consider using milk replacer if the drug is to be continued. Overdosage/Acute Toxicity Clinical signs of overdosage can include hypotension, lethargy, con-fusion, nausea, vomiting, and oliguria. Cardiac signs may include wid ening of the QRS complex, junctional tachycardia, ventricular ﬁbrillation, or intraventricular conduction delays. If an oral ingestion, emptying of the gut and charcoal adminis-tration may be beneﬁcial to remove any unabsorbed drug. IV ﬂuids, plus dopamine, phenylephrine, or norepinephrine could be consid-ered to treat hypotensive effects. A 1/6 molar intravenous infusion of sodium lactate may be used in an attempt to reduce the cardio-toxic effects of procainamide. Forced diuresis using ﬂuids and di-uretics along with reduction of urinary p H can enhance the renal ex cretion of the drug. T emporary cardiac pacing may be necessary should severe A V block occur. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving procainamide and may be of signiﬁcance in veterinary patients: Use with caution with other antidysrhythmic agents, as additive cardiot oxic or other toxic effects may result. !TAMIODARONE : May increase procainamide levels, procainamide dose may need to be reduced !TANTICHOLINESTERASE AGENTS (e. g., pyridostigmine, neostigmine): Procainamide may antagonize effects in patients with myasthe-nia gravis !TCIMETIDINE : May increase procainamide levels !THYPOTENSIVE DRUGS : Procainamide may enhance effect !TLIDOCAINE : T oxic effects may be additive, and cardiac effects unpredictable	pppbs.pdf
!TNEUROMUSCULAR BLOCKING AGENTS : Procainamide may potentiate or prolong the neuromuscular blocking activity !TQUINIDINE : T oxic effects may be additive, and cardiac effects un-predictable !TPHENYTOIN : T oxic effects may be additive, and cardiac effects un-predictable !TPROPRANOLOL : T oxic effects may be additive, and cardiac effects unpredictable !TRANITIDINE : May increase procainamide levels !TTRIMETHOPRIM : May increase procainamide levels Doses !TDOGS: a) For ventricular tachyarrhythmias: When used IV: intermit-tent boluses of 2-4 mg/kg IV slowly (over two minutes) up to a total dose of 12-20 mg/kg until arrhythmia controlled and then a CRI may be started at 10-40 mcg/kg/minute. PO use at: 20-30 mg/kg PO q6-8h (could be too low—previous recommendations of 8-20 mg/kg PO q6-8h are almost cer-tainly too low). (Kittleson 2006c) b) For acute management of SVT's: After drugs have been used to slow A V nodal conduction (i. e., diltiazem), procainamide at 6-8 mg/kg IV over 3 minutes or 6-20 mg/kg IM may ter-minate atrial tachyarrhythmias. For chronic management: 10-20 mg/kg PO q6-8h; higher dosag es of up to 40 mg/kg q6h have been necessary to treat junctional SVT's in some dogs (Wright 2000) c) For ventricular tachycardia: For acute treatment of VT: 10- 15 mg/kg IV bolus over 1-2 minutes; if continued par-enteral administration required may use a constant rate IV infusion at 25-50 mcg/kg/minute. For chronic treatment: 10-20 mg/kg PO q6h (Moise 2000) d) For ventricular tachycardia: 6. 6-8. 8 mg/kg slowly IV over 5 minu tes, then give as a CRI at 40-100 mcg/kg/minute. (Fine 2006) e) For chronic treatment of ventricular arrhythmias: 20-23 mg/kg PO q8h (Me urs 2002) f) Using sustained-release tablets: 20 mg/kg PO q8h; For intra-venous therapy: 6-8 mg/kg IV bolus, 20-40 mcg/kg/min CRI (Ho gan 2004) !TCATS: For chronic management of SVT's: a) 3-8 mg/kg PO q6-8h. (Wright 2000) b) 1-2 mg/kg slowly IV; 10-20 mcg/kg/minute constant rate IV infusion. Oral dose: 7. 5-20 mg/kg q (6 to) 8h (Ware 2000) !THORSES: (Note : ARCI UCGFS Class 4 Drug) a) For atrial ﬁbrillation (not as effective as quinidine); also has be en used for ventricular tachycardia: IV at 1 mg/kg/min, not too exceed 20 mg/kg (20 minutes) total dose. Alternatively administer 25-35 mg/kg PO q8h. (Kimberly and Mc Gurrin 2006) b) For V-Tach: 1 mg/kg/minute IV up to a total dose of 20 mg/ kg; o r 25-35 mg/kg PO q8h (Mogg 1999) Monitoring !TECG; continuously with IV dosing !TBlood pressure, during IV administration !TClinical signs of toxicity (see Adverse Effects/Overdosage) !T Serum levels Because of the variability in pharmacokinetics reported in the dog, it is recommended to monitor therapy using serum drug levels. Be cause dogs apparently do not form the active metabolite NAPA in appreciable quantities, the therapeutic range for procainamide is controversial. Therapeutic ranges from 3-8 mcg/m L to 8-20 mcg/ m L have been suggested. This author would suggest using the lower range as a guideline to initiate therapy, but not to hesitate increas-ing doses to attain the higher values if efﬁcacy is not achieved and to xicity is not a problem. Digitalis-induced ventricular arrhythmias may require substantially higher blood levels for control. Trough levels are usually speciﬁed when monitoring oral therapy. Because NAPA is routinely monitored with procainamide in human medi-cine, it may be necessary to request to the laboratory that NAPA val ues need not be automatically run for canine patients. In horses, therapeutic levels have been suggested as 4-10 mcg/ m L f or procainamide and 10-30 mcg/dl as procainamide and NAPA together. (Kimberly and Mc Gurrin 2006) Client Information !TOral products should be administered at evenly spaced inter-vals throughout the day/night. Unless otherwise directed, give the medication at least 1 hour before feeding to animal with an empty stomach. !TNotify veterinarian if animal's condition deteriorates or clinical signs of toxicity (e. g., vomiting, diarrhea, weakness, etc. ) occur. Chemistry/Synonyms Structurally related to procaine, procainamide is used as an anti-arrhythmic agent. Procainamide HCl differs from procaine by the substitution of an amide group for the ester group found on pro-caine. It occurs as an odorless, white to tan, hygroscopic, crystalline po wder with a p K a of 9. 23 and a melting range from 165°-169°C. It is very soluble in water and soluble in alcohol. The p H of the injectable product ranges from 4-6. Procainamide may also be known as: novocainamidum. pro-cainamidi chloridum, procainamidi hydrochloridum, Biocor yl®, Procan®, Procanbid®, or Pronestyl®. Storage/Stability/Compatibility The solution may be used if the color is no darker than a light am-ber. Refrigeration may retard the development of oxidation, but the solu tion may be stored at room temperature. The injectable product is reportedly physically compat-ible with sodium chloride 0. 9% injection, and water for injection. Procainamide is also physically compatible with dobutamine HCl, lidocaine HCl, and verapamil HCl. 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 VETERINARY-LABELED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 4 substance. See the appendix for more information.	pppbs.pdf
HUMAN-LABELED PRODUCTS: Procainamide HCl Injection: 500 mg/m L in 2 m L vials; generic; (Rx) Procainamide HCl Capsules: 250 mg, 375 mg & 500 mg; generic; (Rx) Procainamide HCl Tablets: 375 mg & 500 mg; Pronesty l® (Apoth-econ); (Rx) Procainamide HCl Extended-Release Tablets: 250 mg, 500 mg, 750 mg & 1000 mg (Note : These products are not recommended for ini-tial therapy and have not been extensively used in veterinary medi-cine. ); Procanbid® (Monarch); generic; (Rx) PROCARBAZINE HCL (proe-kar-ba-zeen) Matulane® ANTINEOPLA STIC Prescriber Highlights TT Atypical alkylating agent that is used in MOPP lymphoma protocols for dogs/cats & for GME in dogs; enters CNS TT Contraindications: Hypersensitivity to drug, inadequate bone marrow reserve TT Caution: Hepatic/renal impairment, use with other CNS depressant drugs TT Adverse Effects: GI, myelosuppression, central & periph-eral nervous system, hepatic TT Teratogen TT Drug interactions TT May need to be reformulated in an oil-based solution to dose appropriately; commercial preparation is very expensive Uses/Indications In veterinary medicine, procarbazine is used as part of MOPP pro-tocols (mechlorethamine, vincristine, procarbazine, prednisone) to treat l ymphomas in dogs and cats. It may be of beneﬁt in treating granulomatous meningoencephalitis (GME) in dogs. Pharmacology/Actions Procarbazine's precise mode of action is not well understood, but it is considered by most to be an alkylating agent, as it appears to inhibit protein, RNA, and DNA synthesis. Procarbazine is auto-oxidized into hydrogen peroxide, which may also directly damage DNA. Pharmacokinetics No data speciﬁc for dogs or cats was located. In humans, procarba-zine is well absorbed after oral administration and rapidly equili-brates between the CSF and plasma. Peak levels in plasma occur in about one hour; in the CSF, about 30-90 minutes after dosing. Procarbazine is almost entirely metabolized in the liver and kidney. Metabolic products are cytotoxic and excreted in the urine. Contraindications/Precautions/Warnings Procarbazine is contraindicated in patients known to be hypersen-sitive to it or with inadequate bone marrow reserve as determined by bone mar row aspirate. Because procarbazine can cause CNS depression, use with ex-treme caution with other CNS depressant drugs. Use with caution in patients with impaired renal or hepatic function. Adverse Effects When dosed as recommended for dogs and cats, procarbazine is relatively well tolerated. In dogs, procarbazine toxicity appears to mirror that seen in humans. Gastrointestinal effects (nausea, vom-iting, hepatotoxicity) and myelosuppression (thrombocytopenia, leukop enia) can be seen. Thrombocytopenia nadirs usually occur at about 4 weeks. Because it is often used in combination with other chemotherapy agents (MOPP), myelosuppression and GI effects (hemorrhagic gastritis) may be enhanced. CNS effects may be noted and include sedation or agitation. Peripheral neuropathy can occur and includes loss of tendon reﬂexes, paresthesias and myalgia. In humans, it is recommended to discontinue therapy if any of the follo wing occur: CNS signs, leukopenia (WBC <4000 mm3), thrombocytopenia (platelets <100,000 mm3), hypersensitivity, stomatitis (at sign of ﬁrst ulceration), diarrhea, and hemorrhage or bleeding. Resume therapy at a lower dosage only when effects clear. Reproductive/Nursing Safety Procarbazine is potential teratogen. In pregnant humans, procarba-zine is designated by the FDA as a category D drug (The re 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. ) It is unknown if procarbazine enters milk. It is recommended to use milk replac er if the dam requires procarbazine. Overdosage/Acute Toxicity The LD50 for laboratory animals range from 150 mg/kg (rabbits) to 1. 3 g/kg (mice). Treat overdoses aggressively to remove drug from the gut if overdose was within an hour or two. Anticipated ad-verse effects would be extensions of the drug's adverse effect proﬁle (GI, bone marrow suppression, CNS effects). Monitor and support as necessary. 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 procarbazine and may be of signiﬁcance in veterinary patients: ! !ALCOHOL : May cause severe nausea and vomiting T ! CNS DEPRESSANT DRUGS (e. g., barbiturates, opiates, antihistamines, phenothiazines, etc. ): Because procarbazine can cause CNS de-pression, use with extreme caution with other CNS depressant drugs. C oma and death have been reported when procarbazine has been used with opiates. T ! FOODS WITH HIGH TYRAMINE CONTENT (aged cheese, yogurt ): Pro-carbazine exhibits some monoamine oxidase inhibitory (MAOI) acti vity; serious hypertension may result T ! SYMP ATHOMIMETICS (phenylpropanolamine, etc. ): Procarbazine ex-hibits some monoamine oxidase inhibitory (MAOI) activity; se-rious hypertension may result T ! TRICYCLIC ANTIDEPRESSANTS (e. g., clomipramine, amitriptyline, etc. ): Procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity. Do not use concurrently with tricyclic antide-pressant drugs. Laboratory Considerations None were noted	pppbs.pdf
Doses T ! DOGS: For lymphoma rescue: a) For MOPP lymphoma rescue: Mechlorethamine: 3 mg/m2 IV days 1 and 7; Vincristine: 0. 7 mg/m2 IV days 1 and 7; Pro-carbazine: 50 mg/m2 PO daily days 1-14; Prednisone: 30 mg/m2 PO daily day 1-14. No treatment given days 15-28 and then protocol is repeated at 4 weeks. Protocol may be severely myelosuppressive. (Meleo 2003) b) Using the DOPP protocol (particularly when mechlore-thamine is not available): Substitu te Dactinomycin: 0. 5 mg/m2 IV days 0 and 7; Vincristine: 0. 7 mg/m2 IV days 0 and 7; Procar bazine: 50 mg/m2 (for dogs >0. 8 mg/m2 give dose to the nearest 50 mg; >0. 4 mg, but <0. 8 mg/m2 give to the nearest 50 mg, but give every other day; dogs <0. 4 mg/m2 reformulate into 10 mg capsules and give to the nearest 20 mg) PO daily days 0-13; Prednisone: 30-40 mg/m2 PO daily days 0-13. No tr eatment given days 15-28 and then protocol is repeat-ed at 4 weeks. Protocol may be severely myelosuppressive. Evaluat e CBC on days 7 and 28. If neutrophil count is <2,000 cells/mc L, delay treatment for 3 days and recheck; monitor for cumulative thrombocytopenia. (Rassnick 2006) For treatment of granulomatous meningoencephalitis (GME): a) 25-50 mg/m2 PO once daily, initially with prednisone treat-ment. After the ﬁrst month of therapy, we attempt to reduce procar bazine dose to every other day. Monitor CBC weekly for ﬁrst month, and then monthly thereafter. Wear gloves when handling. T o prepare a 10 mg/m L oil-based solution: Five 50 mg capsules, oil-based ﬂavor (chicken, liver, ﬁsh) drops, 0. 25 teaspoonful of silica gel (to keep in suspension), and gradually add sesame oil to a total of 25 m L. Assigned expiration date of 30 days. (Cuddon and Coates 2002) T ! CATS: For MOPP lymphoma rescue: a) Mechlorethamine: 3 mg/m2 IV days 1 and 7; Vincristine: 0. 5 mg/m2 IV day s 1 and 7; Procarbazine: 50 mg/m2 PO daily days 1-14; Prednisone: 30 mg/m2 PO daily day 1-14. No treatment given days 15-28 and then protocol is repeated at 4 weeks. Cats may require 5 week cycle due to myelosuppres-sion. (Meleo 2003) b) Mechlorethamine: 3 mg/m2 IV days 0 and 7; Vincristine: 0. 025 mg/kg IV days 0 and 7; Procarbazine: 10 mg (total dose) PO daily da ys 0-14; Prednisone: 5 mg (total dose) PO twice daily continuously. May also be considered for inducing ﬁrst remission in cats. Anorexia may be reduced if procarbazine is given every other day or given with metoclopramide. (Frim-berger 2002) Monitoring T ! Baseline: CBC, hepatic and renal function, urinalysis T ! Repeat CBC at least once weekly for the ﬁrst month of treatment and then monthly T ! In humans, it is recommended to repeat urinalysis, transaminas-es/alkaline phosphatase, and BUN at least weekly Client Information T ! Avoid skin contact with the medication. Wear gloves or wash hands thoroughly after dosing. Avoid contact with patient's sa-liva or urine. T ! Contact veterinarian immediately if any signs associated with toxicity occur. These could include vomiting, lack of appetite, diarrhea, bleeding, depression or agitation, bleeding, sores in mouth, lameness, etc. Chemistry/Synonyms A derivative of hydrazine, procarbazine HCl occurs as a white to pale yellow crystalline powder having a slight odor. It is soluble, but unstable in water or aqueous solutions. Procarbazine may also be known as: Ibenzemethyzin, NSC-77213, Ro-4-6467/1, MIH, N-Methylhydrazine, Matulane®, N atulan®, and Natulanar®. Storage/Stability/Compatibility Procarbazine capsules should be stored in airtight containers, pro-tected from light at temperatures less than 40°C (preferably between 15-30°C, (59 -86°F). An expiration date of 4 years is assigned after the date of manufacture. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Procarbazine HCl Capsules: 50 mg; Matulane® (Sigma Tau); (Rx) PROCHLORPERAZINE (proe-klor-per-a-zeen) Compazine®, Compro® PHENOTHIAZINE ANTIEMETIC Prescriber Highlights TT Phenothiazine used alone as an antiemetic; formerly in combination with an anticholinergic for other GI effects (e. g., diarrhea) TT Relative Contraindications: Hypovolemia or shock & in patients with tetanus or strychnine intoxication TT Caution: Hepatic dysfunction, cardiac disease, general debilitation, or very young animals TT Adverse Effects: Sedation or hypotension Uses/Indications Prochlorperazine as a single agent is used in dogs and cats as an an-tiemetic. The only approved products for animals are combination prod ucts containing prochlorperazine, isopropamide, with or with-out neomycin (Darbazine®, Neo-Darbazine®—SKB Labs) which are no lo nger marketed in the USA. The approved indications for these products include: vomiting, non-speciﬁc gastroenteritis, drug induced diarrhea, infectious diarrhea, spastic colitis, and motion sickness in dogs and cats (injectable product only). Pharmacology/Actions The basic pharmacology of prochlorperazine is similar to that of the other phenothiazines (refer to the acepromazine monograph for more information). Prochlorperazine has weak anticholinergic effects, strong extrapyramidal effects, and moderate sedative effects. It has a strong antiemetic effect which is its primary reason for use in both human and veterinary medicine.	pppbs.pdf
Pharmacokinetics Little information is available regarding the pharmacokinetics of prochlorperazine in animals, although it probably follows the gen-eral patterns of other phenothiazine agents in absorption, distribu-tion, and elimination. Contraindications/Precautions/Warnings Animals may require lower dosages of general anesthetics following phenothiazines. Cautious use and smaller doses of phenothiazines should be given to animals with hepatic dysfunction, cardiac dis-ease, or general debilitation. Because of their hypotensive effects, phe nothiazines are relatively contraindicated in patients with hy-povolemia or shock. It should not be used for tetanus or strychnine into xication due to effects on the extrapyramidal system. Use cau-tiously in very young or debilitated animals. Adverse Effects Alone, prochlorperazine is most likely to cause sedation or hypotension. 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 fe tus, 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 thes e drugs are safe if they are not administered when the animal is near term. ) A related compound, chlorpromazine has been detected in ma-ternal milk. Although few cases are documented, a milk to plasma rat io of 0. 5-0. 7 or less is reported. Prochlorperazine is unlikely to pose signiﬁcant risk to nursing animals. Overdosage/Acute Toxicity Refer to the information listed in the acepromazine monograph. Acute extrapyramidal clinical signs (torticollis, tremor, salivation) have been successfully treated with injectable diphenhydramine in humans. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving prochlorperazine or other phenothiazines and may be of signiﬁcance in veterinary patients: !TANTACIDS : May cause reduced GI absorption of oral phenothiazines !TANTIDIARRHEAL MIXTURES (e. g., Kaolin/pectin, bismuth subsali-cylate mixtures ): May cause reduced GI absorption of oral phenothiazines !TCNS DEPRESSANT AGENTS (barbiturates, narcotics, anesthetics, etc. ): May cause additive CNS depression if used with phenothiazines !TDOPAMINE : Phenothiazines may decrease pressor effects !TEPINEPHRINE : Phenothiazines block alpha-adrenergic receptors and concomitant epinephrine can lead to unopposed beta-activ-ity causing vasodilation and increased cardiac rate !TMETOCLOPRAMIDE : Phenothiazines may potentiate the extrapyra-midal effects of metoclopramide !TOPIATES : May enhance the hypotensive effects of the phenothiaz-ines; dosages of prochlorperazine may need to be reduced when used with an opiate !TORGANOPHOSPHATE AGENTS : Phenothiazines should not be given within one month of worming with these agents as their effects may be potentiated !TPARAQUAT : T oxicity of the herbicide paraquat may be increased by prochlorperazine !TPHENYTOIN : Metabolism may be decreased if given concurrently with phenothiazines !TPHYSOSTIGMINE : T oxicity may be enhanced by prochlorperazine !TPROCAINE : Activity may be enhanced by phenothiazines !TPROPRANOLOL : Increased blood levels of both drugs may result if administered with phenothiazines !TWARFARIN : Prochlorperazine may decrease anticoagulant effect Doses !TDOGS: As an antiemetic: a) 0. 5 mg/kg IM or SC q8h; ensure adequate hydration (Washa-bau and Elie 1995), (Simpson 2003c), (Marks 2006) b) 0. 1 mg/kg IM q6-8h; use with extreme caution in dehydrat-ed or hypotensive animals. (Silverstein 2003) c) 0. 1-0. 5 mg/kg IM or SC q6-8h (Otto 2005) !TCATS: As an antiemetic: a) 0. 5 mg/kg SC or IM three times a day; ensure adequate hy-dration (Simpson 2003c) b) 0. 5 mg/kg IM or SC q8h (Washabau and Elie 1995), (Marks 2006) c) 0. 1-0. 5 mg/kg IM or SC q6-8h (Otto 2005) Monitoring !TCardiac rate/rhythm/blood pressure if indicated and possible to measure !TAnti-emetic/anti-spasmodic efﬁcacy; hydration and electrolyte status !TBody temperature (especially if ambient temperature is very hot or cold) Client Information !TObserve animal for at least one hour following dosing. Dry mouth may be relieved by applying small amounts of water to animal's tongue for 10-15 minutes. !TMay discolor the urine to a pink or red-brown color; this is not abnormal. !TProtracted vomiting and diarrhea can be serious; contact veteri-narian if clinical signs are not alleviated. Contact veterinarian if animal e xhibits abnormal behavior, becomes rigid or displays other abnormal body movements. Chemistry/Synonyms Prochlorperazine, a piperazine phenothiazine derivative, is avail-able commercially as the base in rectal formulations, the edisylate salt in injectable and oral solutions, and as the maleate salt in oral tablets and capsules. Each 8 mg of the maleate salt and 7. 5 mg of the edisylate salt are approximately equivalent to 5 mg of prochlo-rperazine base. The base occurs as a clear, to pale yellow, viscous liquid that is ve ry slightly soluble in water and freely soluble in alcohol. The edi-sylate salt occurs as white to very light yellow, odorless, crystalline po wder. 500 mg are soluble in 1 m L of water and 750 m L of alco-hol. The maleate salt occurs as a white or pale yellow, practically od orless, crystalline powder. It is practically insoluble in water or alcohol.	pppbs.pdf
The commercial injection is a solution of the edisylate salt in sterile water. It has a p H of 4. 2-6. 2. Prochlorperazine may also be known as: chlormeprazine, proc hlorpemazine, Compazine®, Compro®, Prochlor®, Prorazin®, Stemetil®, or Tementil®. Storage/Stability/Compatibility Store in tight, light resistant containers at room temperature. Avoid temperatures above 40°C and below freezing. A slight yellowing of the oral or injectable solution has no effects on potency or efﬁcacy, but do not use if a precipitate forms or the solution is substantially discolored. The following products have been reported to be physically compatible when mixed with prochlorperazine edisylate injection: all usual IV ﬂuids, ascorbic acid injection, atropine sulfate, bu-torphanol tartrate, chlorpromazine HCl, dexamethasone sodium phosphate, droperidol, fentanyl citrate, glycopyrrolate, hydroxyzine HCl, lidocaine HCl, meperidine HCl, metoclopramide, morphine sulfate, nafcillin sodium, nalbuphine HCl, pentazocine lactate, per-phenazine, promazine HCl, promethazine, scopolamine HBr, so-dium bicarbonate, and vitamin B complex with C. The following drugs have been reported to be physically incom-patible when mixed with prochlorperazine edisylate: aminophylline, amphotericin B, ampicillin sodium, calcium gluceptate, chloram-phenicol sodium succinate, chlorothiazide sodium, dimenhydri-nate, hydrocortisone sodium succinate, methohexital sodium, pen-icillin G sodium, phenobarbital sodium, pentobarbital sodium, and thiopental sodium. Do not mix with other drugs/diluents having parabens as preservatives. 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 VETERINARY-LABELED PRODUCTS: None; Darbazine® is no longer available. The ARCI (Racing Commissioners International) has designated this drug as a class 2 substanc e. See the appendix for more information. HUMAN-LABELED PRODUCTS: Prochlorperazine edisylate for Injection: 5 mg/m L in 2 m L and 10 m L vials; Compazine® (Glaxo Smith Kline); generic; (Rx) Prochlorperazine syrup: 1 mg/m L (as edisylate) in 120 m L; Com-pazine ® (Glaxo-Smith Kline); (Rx) Prochlorperazine Tablets: 5 mg & 10 mg (as maleate); 10 mg & 15 mg (as maleate) s ustained release capsules; Compazine® (Smith Kline Bee-cham); generic; (Rx) Prochlorperazine (base) Suppositories: 2. 5 mg, 5 mg, and 25 mg; Compazine® (Glax o Smith Kline); Compro® (Paddock); generic; (Rx) PROMETHAZINE HCL (proe-meth-a-zeen) Phenergan® PHENOTHIAZINE Prescriber Highlights TT Phenothiazine used as an antihistamine & antiemetic in small animals TT Relatively little experience with this drug in veterinary medicine; not frequently recommended for use TT Adverse Effects: sedation or anticholinergic effects Uses/Indications Promethazine may be useful in dogs and cats as an antiemetic. Because of its antihistamine actions, it has been tried for treating pruritus in atopic dogs, but its efﬁcacy has been poor. Pharmacology/Actions The basic pharmacology of promethazine is similar to that of the other phenothiazines (refer to the acepromazine monograph for more information). It exhibits antiemetic, antihistaminic, anticho-linergic, sedative, and local anesthetic actions. Pharmacokinetics Little information is available regarding the pharmacokinetics of promethazine in animals, although it probably follows the general patterns of other phenothiazine agents in absorption, distribution, and elimination. In humans, the drug is well absorbed following oral or rectal administrat ion, and via IM injection. Sedative effects occur within minutes of IV administration and persist for several hours. The drug is metabolized in the liver and these metabolites are eliminat-ed primarily in the urine. Elimination half-life in humans is about 10 hours. Contraindications/Precautions/Warnings Animals may require lower dosages of general anesthetics following phenothiazines. Cautious use and smaller doses of phenothiazines should be given to animals with hepatic dysfunction, cardiac dis-ease, or general debilitation. Because of their hypotensive effects, phenothiazines ar e relatively contraindicated in patients with hy-povolemia or shock. Do not use in patients with tetanus or strych-nine intoxication due to effects on the extrapyramidal system. Use cautiously in v ery young or debilitated animals. In humans, promethazine has a “black box warning” to not use the medicatio n in children less than 2 years old; fatal respiratory depression has occurred in that patient group. Adverse Effects Little experience has been reported with this drug in animals, but prochlorperazine would most likely cause sedation or anticholin-ergic effects (dry mouth, etc. ). 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. )	pppbs.pdf
It is not known whether promethazine is distributed into milk; a related compound, chlorpromazine has been detected in maternal milk. Although few cases are documented, a milk to plasma ratio of 0. 5-0. 7 or less is reported. Promethazine is unlikely to pose signiﬁ-cant risk to nursing animals. Overdosage/Acute Toxicity Refer to the information listed in the acepromazine monograph. Acute extrapyramidal clinical signs (torticollis, tremor, salivation) have been successfully treated with injectable diphenhydramine in humans. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving promethazine or other phenothiazines and may be of signiﬁcance in veterinary patients: !TANTACIDS : May cause reduced GI absorption of oral phenothiazines !TANTIDIARRHEAL MIXTURES (e. g., Kaolin/pectin, bismuth subsali-cylate mixtures ): May cause reduced GI absorption of oral phenothiazines !TATROPINE & OTHER ANTICHOLINERGICS : May have additive effects when used with promethazine !TCNS DEPRESSANT AGENTS (barbiturates, narcotics, anesthetics, etc. ): May cause additive CNS depression if used with phenothiazines !TEPINEPHRINE : Phenothiazines block alpha-adrenergic receptors and concomitant epinephrine can lead to unopposed beta-activ-ity causing vasodilation and increased cardiac rate !TMETOCLOPRAMIDE : Phenothiazines may potentiate the extrapyra-midal effects of metoclopramide !TMONOAMINE OXIDASE INHIBITORS : May potentiate extrapyramidal effects !TOPIATES : May enhance the hypotensive effects of the phenothiaz-ines; dosages of prochlorperazine may need to be reduced when used w ith an opiate !TORGANOPHOSPHATE AGENTS : Phenothiazines should not be given within one month of worming with these agents as their effects may be potentiated Laboratory Considerations !TPromethazine can cause false positive results for salicylates in urine !TPromethazine can cause false positive or false negative results for chorionic gonadotropin in urine Doses !TDOGS/CAT S: As an antiemetic: a) 2 mg/kg PO or IM once daily (Dowling 2003a) As an ant ihistamine: a) 0. 2-0. 4 mg/kg PO three to four times a day. (Morgan 2003) b) 0. 2-0. 4 mg/kg PO, IV, IM three to four times a day. (Bernard 1997) Monitoring !TEfﬁcacy Client Information !TDry mouth may be relieved by applying small amounts of water to animal's tongue for 10-15 minutes !TMay cause sedation or behavior changes; contact veterinarian if these are a concern !TProtracted vomiting or diarrhea can be serious; contact veteri-narian if clinical signs are not alleviated !TContact veterinarian if animal exhibits abnormal movements or becomes rigid Chemistry/Synonyms Promethazine HCl occurs as a white to faint yellow, practically odorless, crystalline powder. It slowly oxidizes and acquires a blue color on prolonged exposure to air. Promethazine HCl is freely soluble in water, in hot dehydrated alcohol, and in chloroform, but practically insoluble in acetone, ether, or ethyl acetate. The p H of a 5% solution in water is between 4-5. Promethazine may also be known as: Lilly 01516, PM 284, RP 3277, p rometazina or Phenergan®. There are many other trade names available. Storage/Stability/Compatibility Store tablets at room temperature (20-25°C) in tight, light resis-tant containers. The syrup should be stored from 15-25°C and pr otected from light. The injection should be stored at room temperature 20-25°C and p rotected from light. Keep in covered carton until time of use. Do not use if a precipitate forms or the solution is discolored. Promethazine can be adsorbed to plastic IV bags and tubing. Promethazine suppositories should be stored in the refrigerator (2- 8°C) The following products have been reported to be physically com-patible when promethazine injection is mixed with them: all usual IV ﬂuids, amikacin, ascorbic acid, buprenorphine, butorphanol, ci-metidine, diphenhydramine, fentanyl, ﬂuconazole, glycopyrrolate, hy dromorphone, hydroxyzine, meperidine, metoclopramide, mi-dazolam, ondansetron, pancuronium, pentazocine, procainamide, and ranit idine. Solutions of promethazine hydrochloride are incompatible with alkaline substances, which can precipitate promethazine base. The following drugs have been reported to be physically incom-patible when mixed with promethazine HCl: aminophylline, bar-biturates, benzylpenicillin salts, carbenicillin sodium, chloram-phenicol sodium succinate, chlorothiazide sodium, cefoperazone, dimenh ydrinate, doxorubicin (in a liposomal formulation), furo-semide, heparin sodium, hydrocortisone sodium succinate, mor-phine sulfate, and nalbuphine HCl. Compatibility is dependent upo n 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 VETERINARY-LABELED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 3 substance. See the appendix for more information. HUMAN-LABELED PRODUCTS: Promethazine HCl for Injection: 25 mg/m L in 1 m L amps & 50 mg/ m L (For IM use only) in 1 m L amps; Phenergan (Wyeth); generic; (Rx) Promethazine HCl syrup: 1. 25 mg/m L in 473 m L; generic; (Rx) Promethazine HCl Tablets: 12. 5 mg, 25 mg & 50 mg; Phe nergan® (Wyeth); generic; (Rx) Promethazine HCl Suppositories: 12. 5 mg, 25 mg, and 50 mg; Phe n-ergan® (Wyeth), Phe nadoz® (Paddock), generic; (Rx)	pppbs.pdf
PROPANTHELINE BROMIDE (proe-pan-the-leen) Pro-Banthine® QUATERNARY ANTIMUSCARINIC Prescriber Highlights TT Quaternary antimuscarinic agent used for its antispas-modic/antisecretory for treatment of diarrhea, hyper-reﬂexic detrusor or urge incontinence & anticholinergic responsive bradycardias. In horses, IV to reduce colonic peristalsis & relax rectum to allow easier examination & surger y. TT Contraindications: Hypersensitivity to anticholinergics, tachycardias secondary to thyrotoxicosis or cardiac insuf-ﬁciency, myocardial ischemia, unstable cardiac status during acute hemorrhage, GI obstructive disease, para-lytic ileus, severe ulcerative colitis, obstructive uropathy, or myasthenia gravis (unless used to re verse adverse muscarinic effects secondary to therapy). TT Extreme Caution: Known or suspected GI infections, au-tonomic neuropathy. Caution: hepatic or renal disease, hyperth yroidism, hypertension, CHF, tachyarrhythmias, prostatic hypertrophy, esophageal reﬂux, & geriatric or pediatric patients. TT Adverse Effects: Similar to atropine (dry mouth, dry eyes, urinary hesitancy, tachycardia, constipation, etc. ), but less effects on eye or CNS. Cats may exhibit vomiting & hy-persalivation. High doses may cause ileus. Uses/Indications In small animal medicine propantheline bromide has been used for its antispasmodic/antisecretory effects in the treatment of diarrhea. It is also employed in the treatment of hyperreﬂexic detrusor or urge incontinence and as oral treatment in anticholinergic respon-sive bradycardias. In horses, propantheline has been used intrave-nously to reduce colonic peristalsis and for relaxing the rectum to allow easier r ectal examination and surgery. Pharmacology/Actions An antimuscarinic with similar actions as atropine, propantheline is a quaternary ammonium compound and does not cross appre-ciably into the CNS. It should not exhibit the same extent of CNS adve rse effects that atropine possesses. For further information, re-fer to the atropine monograph. Pharmacokinetics Quaternary anticholinergic agents are not completely absorbed after oral administration because they are completely ionized. In humans, peak levels occur about 2 hours after oral administra-tion. Food apparently decreases the amount of drug absorbed. Propanthe line is reportedly variably absorbed in dogs; dosages should be adjusted for each patient. The distribution of propantheline has not been extensively studied, b ut like other quaternary antimuscarinics, propantheline is poorly lipid soluble and does not extensively penetrate into the CNS or eye. Propantheline is believed to be prevalently metabolized in the GI and/or li ver; less than 5% of an oral dose is excreted unchanged in the urine. Contraindications/Precautions/Warnings Use of propantheline should be considered contraindicated if the patient has a history of hypersensitivity to anticholinergic drugs, tachycardias secondary to thyrotoxicosis or cardiac insufﬁciency, myocardial ischemia, unstable cardiac status during acute hem-orrhage, GI obstructive disease, paralytic ileus, severe ulcerative colitis, o bstructive uropathy, or myasthenia gravis (unless used to reverse adverse muscarinic effects secondary to therapy). Antimuscarinic agents should be used with extreme caution in patients w ith known or suspected GI infections. Propantheline or other antimuscarinic agents can decrease GI motility and prolong retention of the causative agent(s) or toxin(s) resulting in pro-longed clinical signs. Antimuscarinic agents must also be used with extre me caution in patients with autonomic neuropathy. Antimuscarinic agents should be used with caution in patients with hepat ic disease, renal disease, hyperthyroidism, hypertension, CHF, tachyarrhythmias, prostatic hypertrophy, esophageal reﬂux, and in geriatric or pediatric patients. Adverse Effects With the exception of fewer effects on the eye and the CNS, propan-theline can be expected to have a similar adverse reaction proﬁle as atro pine (dry mouth, dry eyes, urinary hesitancy, tachycardia, constipation, etc. ). Vomiting and hypersalivation have also been reported in cats. High doses may lead to the development of ile-us with resultant bacterial overgrowth in susceptible animals. For more info rmation, refer to the atropine monograph. 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. ) Although anticholinergics (especially atropine) may be excreted in milk and can cause toxicity and reduce milk production, it is unknown if propantheline enters maternal milk. Use with caution in nursing patients. Overdosage/Acute Toxicity Because of its quaternary structure, it would be expected that mini-mal CNS effects would occur after an overdose of propantheline when c ompared to atropine. See the information listed in the at-ropine monograph for more information on the clinical signs that may be see n following an overdose. If a recent oral ingestion, emptying gut contents and admin-istration of activated charcoal and saline cathartics may be war-ranted. Treat clinical signs supportively and symptomatically. Do not use phe nothiazines as they may contribute to anticholinergic effects. Fluid therapy and standard treatments for shock may be instituted. The use of physostigmine is controversial and should probably be rese rved for cases where the patient exhibits either extreme agi-tation and is at risk for injuring themselves or others, or where su-praventricular tachycardias and sinus tachycardias are severe or life threatening. The usual dose for physostigmine (human) is 2 mg IV slowly (for average sized adult); if no response may repeat every 20 minutes until reversal of toxic antimuscarinic effects or cholinergic effects takes place. The human pediatric dose is 0. 02 mg/kg slow IV (repeat q10 minutes as above) and may be a reasonable choice for treatment of small animals. Physostigmine adverse effects (bron-choconstriction, bradycardia, seizures) may be treated with small doses of IV at ropine.	pppbs.pdf
Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving propantheline and may be of signiﬁcance in veterinary patients: !TANTIHISTAMINES : May enhance the activity of propantheline !TBENZODIAZEPINES : May enhance the activity of propantheline !TCIMETIDINE : Propantheline may decrease the absorption of cimetidine !TCORTICOSTEROIDS (long-term use): May increase intraocular pressure !TMEPERIDINE : May enhance the activity of propantheline !TNITRATES : May potentiate the adverse effects of propantheline !TNITROFURANTOIN : Propantheline may enhance actions !TPHENOTHIAZINES : May enhance the activity of propantheline !TSYMP ATHOMIMETICS : Propantheline may enhance actions !TRANITIDINE : Propantheline delays the absorption, but increases the peak serum level of ranitidine; the relative bioavailability of ranit idine may be increased by 23% when propantheline is ad-ministered concomitantly with ranitidine !TTHIAZIDE DIURETICS : Propantheline may enhance actions Doses !TDOGS: For detrusor hyperreﬂexia, urge incontinence: a) 0. 2 mg/kg PO q6-8h; increase dose if necessary to the low-est dose that will control clinical signs (Polzin and Osborne 1985) b) 7. 5-30 mg (total dose) PO once a day to q8h (Bartges 2003a) c) 7. 5-15 mg (total dose) PO q12h; occasionally dosages of 30 mg q8h are required (Lane 2000) Fo r sinus bradycardia, incomplete A V block, etc. : a) 0. 25-0. 5 mg/kg PO q8-12h (Hogan 2004) b) 7. 5-30 mg PO q8-12h; usually well tolerated, but improve-ment is usually partial and often temporary. (Rishniw and Tho mas 2000) For colitis, irritable bowel syndrome, etc. a) 0. 25 mg/kg PO three times a day; do not use longer than 48- 72 hours (48 hours for acute colitis) (De Novo 1988) b) 0. 5 mg/kg two to three times daily (Chiapella 1986) As an antiemetic/antidiarrheal: a) 0. 25 mg/kg PO q8h (D e Novo 1986) !TCATS: For detrusor hyperreﬂexia, urge incontinence: a) 0. 25-0. 5 mg/kg PO q12-24h. Empirical dosage. Further studies required to substantiate beneﬁcial effect. (Osborne, Lulich et al. 2003b) b) 5-7. 5 mg (total dose) PO once a day to once every 3 days (Lane 2000) c) 5-7. 5 mg (total dose) PO q8h; 7. 5 mg PO q72h (Bartges 2003a) Fo r sinus bradycardia, incomplete A V block, etc. : a) Although generally ineffective, a trial may be attempted us-ing: 0. 8-1. 6 mg/kg three times daily (Harpster 1986) b) 7. 5 mg PO q8-12h; usually well tolerated, but improvement is us ually partial and often temporary (Rishniw and Thomas 2000) For chronic colitis: a) 0. 5 mg/kg two to three times daily (Chiapella 1986) As an antiemetic/antidiarrheal: a) 0. 25 mg/kg PO q8h (D e Novo 1986) !THORSES: T o reduce rectal contractions: a) During oocyte collection: 0. 04 mg/kg IV (Carnevale and Cou tinho da Silva 2003) b) 30 mg IV to inhibit peristalsis for 2 hours during rectal sur-gery (Merkt et al. 1979) Note : There is no commercially available injectable product available in the U. S. A. Should a preparation be made from oral tablets, it should be freshly prepared and ﬁltered through a 0. 22 micron-ﬁlter before administering. Use with caution. Monitoring Dependent on reason for use: !TClinical efﬁcacy !THeart rate and rhythm if indicated !TAdverse effects Client Information !TDry mouth may be relieved by applying small amounts of water to animal's tongue for 10-15 minutes. !TProtracted vomiting and diarrhea can be serious; contact veteri-narian if symptoms are not alleviated. Chemistry/Synonyms A quaternary ammonium antimuscarinic agent, propantheline bro-mide occurs as bitter-tasting, odorless, white or practically white cry stals, with a melting range of 156-162° (with decomposition). It is very soluble in both water and alcohol. Propantheline bromide may also be known as: bromuro de pr opantelina, propanthelini bromidum, Banthine®, Bropantil®, Corrigast®, Ercorax Roll-on®, Ercoril®, Ercotina®, Pantheline®, Probamide®, Propantel®, or Propanthel®. Storage/Stability Propantheline bromide tablets should be stored at room tempera-ture in tight containers. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Propantheline Bromide Tablets: 7. 5 mg & 15 mg; Pro-Banthine® (Schiapparelli Searle); generic; (Rx)	pppbs.pdf
PROPIONIBACTERIUM ACNES INJECTION (proe-pee-ohe-bak-ter-ee-um ak-nees) Immunoregulin®, Eqstim® IMMUNOSTIMULANT Prescriber Highlights TT Immunostimulant for Staph pyoderma, Fe LV, feline her-pes, equine respiratory infections TT Contraindications: Hypersensitivity to compound, canine lymphoma, or leukemias with CNS involvement. Caution: Cardiac dysfunction TT Adverse Effects: Lethargy, hyperthermia, chills, & anorex-ia. Anaphylactic reactions are possible TT Extravasation may cause local tissue inﬂammation Uses/Indications The manufacturer's label notes the product (Immunoregulin®) “... indicated in the dog as adjunct to antibiotic therapy in the treatment of chronic recurring canine pyoderma to decrease the severity and extent of lesions and increase the percentage of dogs free of lesions after the appropriate therapeutic period. ” The equine product (Eq Stim®) is labeled as an immunostimulant for adjunc-tive therapy of primary or secondary viral or bacterial respiratory trac t infections Additionally, it has been used as an immunostimulant for the adjunct ive treatment of feline rhinotracheitis and feline leukemia virus-induced disease. In dogs, it may be of use in the adjunctive treatment of oral melanoma and mastocytoma. Unfortunately, controlled studies documenting efﬁcacy were not located for these potential indications. Pharmacology/Actions A non-speciﬁc immunostimulant, Propionibacterium acnes in-jection may induce macrophage activation, lymphokine produc-tion, increase natural killer cell activity, and enhance cell-mediated immunity. Pharmacokinetics No information was noted. Contraindications/Precautions/Warnings Propionibacterium acnes injection is contraindicated in patients hypersensitive to it. It should also be considered contraindicated in canine lymphoma or leukemias with CNS involvement. Use with caution in patients with cardiac dysfunction. Adverse Effects Occasionally within hours after injection, lethargy, increased body temperature, chills, and anorexia may be noted. Anaphylactic reac-tions have also been reported. Extravasation may cause local tissue inﬂammation. L ong-term toxicity studies have demonstrated vom-iting, anorexia, malaise, fever, acidosis, increased water consump-tion, and hepatitis. Reproductive/Nursing Safety Safe use during pregnancy has not been established. Overdosage/Acute Toxicity No overdosage information was noted; the manufacturer states that the antidote is epinephrine, presumably for the treatment of ana-phylactic reactions. Drug Interactions The manufacturer states that the immunostimulant effects may be compromised if given concomitantly with glucocorticoids or other immune suppressing drugs ; manufacturer recommends discontinu-ing steroids at least 7 days prior to initiating therapy. Doses T ! DOGS: For labeled indications (as adjunct to antibiotic therapy in the treatment of chronic recurring canine pyoderma): a) Shake well. Give via intravenous route at the following dos-ages: For animals weighing up to 15 lbs = 0. 25-0. 5 m L; 15-45 lbs = 0. 25-1 m L; 45-75 lbs = 1-1. 5 m L; >75 lbs = 1. 5-2 m L. During the ﬁrst two weeks, give 4 times at 3-4 day inte rvals, then once weekly until symptoms abate or sta-bilize. Maintenance doses once per month are recommended. (Packag e Insert; Immunoregulin®) b) For adjunctive therapy of chronic recurrent canine pyoder-ma: 0. 03-0. 07 m L/kg twice weekly for 10 weeks (combined with antibiot ic therapy) (Barta 1992) T ! CATS: For adjunctive therapy of feline retrovirus infections: a) 0. 5 m L IV twice weekly for 2 weeks, then one injection week-ly for 20 weeks or until cat is seronegative. (Mc Caw 1994) b) 0. 25-0. 5 m L IV twice weekly then every other week for 16 weeks (Le vy 2004) c) As an antiviral immunostimulant in cats to increase he-matopoiesis in Fe LV-positive cats: 5 lb cats: 0. 25 m L IV, IP twice w eekly for 2 weeks, then once weekly until remission and once monthly after that to maintain clinical improve-ment. For 10 lb cats: 0. 5 m L IV, IP twice weekly for 2 weeks, then onc e weekly for 3 weeks and once monthly for 2 months for a total of nine injections after that to maintain clinical improvement. Some protocols suggest follow-up with injec-tions once weekly for 20 weeks or longer as needed. Others suggest follow-up with once weekly until clinical remission, and then once per month. (Greene, Hartmannn et al. 2006) T ! HORSES: As an immunostimulant for adjunctive therapy of primary or secondary viral or bacterial respiratory tract infections: a) Using Eq Stim®: 1 m L per 114kg (250 lb) body weight IV q48-72h (Flamino 2003) b) Using Eq S tim®: 1 m L per 114kg (250 lb) body weight IV. Rep eat dosage on day 3 (or day 4), at day 7, and weekly as needed (Label information; Eqstim®—Neogen) Monitoring T ! Efﬁcacy T ! Adverse effects (see above) Chemistry/Synonyms Propionibacterium acnes injection is an immunostimulant agent, containing nonviable Propionibacterium acnes suspended in 12. 5% ethanol in saline. Propionibacterium acnes may also be known as: Coryne bacterium parvum; NSC-220537, Arthrokehlan A®, Coparvax®, Corymunun®, Eqstim®, Imunoparvum®, and Immunoregulin®.	pppbs.pdf
Storage/Stability Store refrigerated; do not freeze. Shake well before using. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Propionibacterium acnes (non-viable) IV: 0. 4 mg/m L in 5 m L and 50 m L vials; Immunoregulin® (Neogen); (OTC-biologic; manufacturer states that use is restricted to use by, or under the supervision of a veterinarian). Labeled for use in dogs. Eqstim® (Neogen). For use in horses and restricted to use by or under to the supervision of a veterinarian. HUMAN-LABELED PRODUCTS: None PROPOFOL (proe-po-fole) Rapinovet®, Propo Flo®, Diprivan® INJECTABLE ANESTHETIC Prescriber Highlights TT Short-acting injectable hypnotic agent TT Contraindications: Hypersensitivity to it or any compo-nent of the product TT Caution: Severe stress or having undergone trauma, hy-poproteinemia, hyperlipidemia, seizures, or anaphylaxis history TT Adverse Effects: Transient respiratory depression is com-mon but usually clinically tolerable. Apnea possible, especially if given too rapidly. May cause histamine release; anaph ylactoid reactions possible. Hypotension, seizure-lik e clinical signs (paddling, opisthotonus, myoclo-nic twitching) during induction. Repeated doses in Cats: Increased Heinz body production, slowed recoveries, an-orexia, lethargy, malaise, & diarrhea TT Little, if any, analgesia is provided TT Consider dose reduction if using other CNS depressant TT Sufﬁcient monitoring & patient-support capabilities are mandatory TT Cats with preexisting liver disease may be susceptible to longer recovery times Uses/Indications In appropriate patients, propofol may be useful as an induction agent (especially before endotracheal intubation or an inhalant an-esthetic), and as an anesthetic for outpatient diagnostic or minor proc edures (e. g., laceration repair, radiologic procedures, minor dentistry, minor biopsies, endoscopy, etc. ). Propofol is used as a treatment for refractory status epilepticus, as it te nds to cause less cardiovascular depression and recoveries can be smoother than with pentobarbital. Propofol may be of particular usefulness for use in Greyhounds and in patients with preexisting cardiac dysrhythmias. At low dosages, propofol is being investigated as an appetite stimulant in dogs. Propofol may be safely used in animals with liver or renal disease and mild to mode rate cardiac disease. In dogs, propofol's labeled indications are: 1) for induction of anesthesia; 2) for maintenance of anesthesia for up to 20 minutes; 3) for induction of general anesthesia where maintenance is pro-vided by inhalant anesthetics. Pharmacology/Actions Propofol is a short acting hypnotic unrelated to other general anes-thetic agents. Its mechanism of action is not well understood. In dogs, propofol produces rapid yet smooth and excitement-free anesthesia induction (in 30-60 seconds) when given slowly IV. Sub-anesthetic dosages will produce sedation, restraint and an unawareness of surroundings. Anesthetic dosages produce uncon-sciousness and good muscle relaxation. Propofol's cardiovascular effects include arterial hypotension, brad ycardia, (especially in combination with opiate premedicants) and negative inotropism. It causes signiﬁcant respiratory depres-sion, particularly with rapid administration or very high dosages. Prop ofol also decreases intraocular pressure, increases appetite and has antiemetic properties. It does not appear to precipitate malig-nant hyperthermia and has little or no analgesic properties. Pharmacokinetics After IV administration, propofol rapidly crosses the blood brain barrier and has an onset of action usually within one minute. Duration of action after a single bolus lasts about 2-5 minutes. It is highly bound to plasma proteins (95-99%), crosses the placenta, is highly lipophilic, and reportedly enters maternal milk. Propofol's short duration of action is principally due to its rapid redistr ibution from the CNS to other tissues. It is rapidly biotrans-formed in the liver via glucuronide conjugation to inactive metab-olites, which are then excreted primarily by the kidneys. Because cats do not glucuronidate as well as dogs or humans, this may help explain their problems with consecutive day administration (see Adverse Effects below). There is limited data available on propofol's pharmacokinetic paramete rs in dogs. The steady state volume of distribution is >3L/ kg, elimination half-life about 1. 4 hours, and clearance about 50 m L/kg/min. Contraindications/Precautions/Warnings Propofol is contraindicated in patients hypersensitive to it or any component of the product. It should not be used in patients where general anesthesia or sedation is contraindicated. Propofol should only be used in facilities where sufﬁcient monitoring and patient-support capabilities are available. Because patients that are in shock, under severe stress, or have undergo ne trauma may be overly sensitive to the cardiovascular and respiratory depressant effects of propofol, it should be used with caution in these patients. Adequate perfusion should be main-tained before and during propofol anesthesia; dosage adjustments may be nec essary. Because propofol is so highly bound to plasma proteins, patients with hy poproteinemia may be susceptible to untoward effects; gen-eral anesthetic agents may be a safer choice in these patients. The beneﬁts of propofol should be weighed against its risks in patients w ith a history of hyperlipidemia, seizures or anaphylactic reactions. Cats with preexisting liver disease may be susceptible to longer recovery times. Adverse Effects Transient respiratory depression is common but is usually clinically tolerable. However, there is a relatively high incidence of apnea with resultant cyanosis if propofol is given too rapidly; it should be given slowly (25% of the calculated dose every 30 seconds until desired effect). Treat with assisted ventilation until spontaneous ventilation resumes.	pppbs.pdf
Propofol has been documented to cause histamine release in some patients and anaphylactoid reactions (rare) have been noted in humans. Propofol has direct myocardial depressant properties and resultant arterial hypotension has been reported. Occasionally, dogs may exhibit seizure-like clinical signs (pad-dling, opisthotonus, myoclonic twitching) during induction, that, if p ersist, may be treated with intravenous diazepam. Propofol may have both anticonvulsant and seizure-causing properties. It should be used with caution in patients with a history of, or active seizure disorders, but some clinicians believe however, that propofol is ac-tually more appropriate to use in seizure patients or in high seizure-risk p rocedures (e. g., myelography) than is thiopental. While propofol is not inexpensive, it should ideally be used in a sing le-use fashion, as it is a good growth medium (contains no preservative) for bacteria. When used in combination with other CNS depressant premed-icants (e. g., ac epromazine, narcotics, diazepam, etc. ), a decrease in dosage of about 25% (from the single agent dose) should be consid-ered. In very thin animals, consider dosage reduction as well. When used repeatedly (once daily) in cats, increased Heinz body pr oduction, slowed recoveries, anorexia, lethargy, malaise, and di-arrhea have been noted. Heinz body formation is due to oxidative injur y to RBCs and has been documented in cats with other pheno-lic compounds as well. Consecutive use in dogs appears to be safe. Pain upon injection has been reported in humans, but does not ap pear to be a clinically signiﬁcant problem for dogs or cats. Extravasation of injection is not irritating nor does it cause tissue sloughing. Propofol does not provide good analgesia, so appropriate anal-gesic agents should be used before and after painful procedures. Reproductive/Nursing Safety Propofol crosses the placenta and its safe use during pregnancy has not been established. High dosages (6X) in laboratory animals caused increased maternal death and decreased offspring surviv-al rates after birth. In humans, the FDA categorizes this drug as cate gory 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 humans, propofol is not recommended for use in nursing mother s because propofol is excreted in maternal milk and the effects of oral absorption of small amounts of propofol are not known. Use with caution in nursing veterinary patients. Overdosage/Acute Toxicity Overdosages are likely to cause signiﬁcant respiratory depression and, potentially, cardiovascular depression. Treatment should con-sist of propofol discontinuation, artiﬁcial ventilation with oxygen, and if necessary, symptomatic and supportive treatment for car-diovascular depression (e. g., intravenous ﬂuids, pressors, anticho-linergics, etc. ). Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving propofol and may be of signiﬁcance in veterinary patients: !TANESTHETICS, INHALATION (halothane, isoﬂurane ): Propofol serum concentrations may be increased !TANESTHETICS, LOCAL : Propofol dosage requirements for sedation or hypnosis reduced !TANTICHOLINERGICS : Propofol-induced bradycardia may be exac-erbated in animals, particularly when opiate premedicants are used !TCLONIDINE : When used as a premed, may reduce propofol dosage requirements !TCNS DEPRESSANTS : Increased sedative, anesthetic, and cardiorespi-ratory depression possible !TDRUGS T HAT INHIBIT THE HEPATIC P-450 ENZYME SYSTEM (e. g., chloram-phenicol, cimetidine, ketoconazole, etc. ): May potentially increase the recovery times associated with propofol; clinical signiﬁcance is unclear, but it may be of signiﬁcance in cats !TFENTANYL : In pediatric (human) patients increased risk for bradycardia !TMEDETOMIDINE : When propofol is used after medetomidine, hy-poxemia may occur; dosage adjustments may be required along with a dequate monitoring !TMIDAZOLAM : May have synergistic effects with propofol, midazo-lam plasma concentrations may be increased up to 20% !TOPIATES : May increase the serum concentrations of both the opi-ate and propofol if used together Doses !TDOGS & CAT S: Note : The Rapinovet® (Schering-Plough) package insert has very detailed dosing recommendations for both induction and main-tenance of general anesthesia with propofol, including dosage adjustments when acepromazine, xylazine, butorphanol, oxy-morphone or medetomidine premedication is used. As an anesthe tic: a) As a single injection (25% of the calculated dose every 30 sec onds until desired effect): For healthy, unpremedicated animal: 6 mg/kg IV; Fo r healthy, premedicated animal: After tranquilizer (e. g., acepromazine) = 4 mg/kg IV; after sedative (e. g., xylazine, opioids) = 3 mg/kg IV. As a constant infusion: Fo r sedation only: 0. 1 mg/kg/minute; For minor surgery: 0. 6 mg/kg/min, or 1 m L (10 mg) per minute per 12-25 kg of body weight (Robinson, Sanderson et al. 1993) b) Dogs: For induction without premedication: 5-6 mg/kg IV; With acepromazine (0. 05 mg/kg IM, IV, or SC), propofol gi ven at 3-4 mg/kg IV; With acepromazine and oxymorphone (0. 09 mg/kg IM, IV or SC), propofol given at 2. 3 mg/kg IV. Xylazine or medeto-midine premeds may reduce propofol dose further. Cats: Premed with acepromazine (0. 05-1 mg/kg IM) with or without an analgesic such as butorphanol (0. 2-0. 4 mg/ kg IM) and induce with propofol at 4-6 mg/kg IV. Doses of propofol at 8-13 mg/kg IV will allow intubation without topical anesthesia, lower propofol dose if topical anesthesia is used. (Mathews 1999) c) 6 mg/kg IV; in healthy animals 25% of the calculated dose is a dministered every 30 seconds until intubation is possi-ble. After induction, duration of anesthesia is only 2. 5-9. 4 minu tes. Maintenance anesthesia obtained using either in-halational agents or a continuous infusion of propofol at ap-proximately 0. 4 mg/kg/minute. If anesthesia appears inad-equate, a small bolus of 1 mg/kg followed by an increase in the infusio n rate by 25%. If infusion is too deep, discontinue infusion until suitable anesthesia level is achieved. An infu-	pppbs.pdf
sion dose of 0. 1 mg/kg/min appears to be suitable dose for sedation in the dog. (Ilkiw 1992) d) As an induction agent for halothane or isoﬂurane anesthesia: 6. 6 mg/kg IV given over 60 seconds to unpremedicated dogs. Best ac hieved by early intubation and administration of the inhalant following propofol induction. (Bufalari, Miller et al. 1998) For refractory status epilepticus: a) Using IV bolus or constant rate IV infusion: 0. 1-0. 6 mg/kg/ minute. Use only in settings where deﬁnitive airway control and hemodynamic support can occur. (Platt and Mc Donnell 2000) b) If seizures persist after diazepam and phenobarbital therapy: 3-6 mg/kg IV followed by an infusion of 8-12 mg/kg/hour. Must closely monitor for hypoventilation and may require mechanical ventilatory support. (Munana 2004b) c) If seizures persist after diazepam and phenobarbital therapy in dog s: Propofol IV bolus at 1-3. 5 mg/kg up to 6 mg/kg followed by a CRI using a syringe pump of 0. 1-0. 25 mg/kg/ minute (up to 0. 6 mg/kg/minute) for 6-12 hours and then gradually decreased; maximum duration of propofol CRI is approximately 48 hours. If used in cats, carefully monitor PVC and CBC (Heinz body anemia, hemolytic anemia) and propofol dose should be kept as low, and duration of treat-ment as short, as possible. (Knipe 2006b) T ! RABBITS, RODENTS, SMALL MAMMALS: a) Rabbits: 5-14 mg/kg slow IV (20 mg/kg/minute) to effect; not rec ommended as the sole agent for maintenance (Ivey and Morrisey 2000) b) Mice: 26 mg/kg IV. Rats: 10 mg/kg IV (Adamcak and Otten 2000) T ! REPTILES: a) Iguanas: 3 mg/kg IV via either intraosseous catheter or into the coc cygeal or ventral abdominal vein. Wait 3-5 minutes before giving additional increments. May also be used in tor-toises. (Heard 1999) b) 5-15 mg/kg IV or IO; in snakes intracardiac route is usually used (Innis 2003) Monitoring T ! Level of anesthesia/CNS effects T ! Respiratory depression T ! Cardiovascular status (cardiac rate/rhythm; blood pressure) Chemistry/Synonyms Propofol is an alkylphenol derivative (2,6-diisopropylphenol). The commercially available injection is an emulsion containing 100 mg/ m L of soybean oil, 22. 5 mg/m L of glycerol, and 12 mg/m L of egg lecithin. The emulsion has a p H of 7-8. 5. Propofol may also be known as disoprofol. Propofol may also be known as: disoprofol, ICI-35868, propo-folum, Ansiven®, Bioprofol ®, C ryotol ®, Diprofol ®, Diprivan®, Disoprivan®, Fresofol®, Ivofol ®, Klimofol®, Oleo-Lax®, Pofol ®, Profolen ®, Pronest®, Propoabbott®, Propocam®, Propo Flo®, Propovan®, Provive ®, Rapino vet®, Recofol®, or Recofol®. Storage/Stability/Compatibility Store propofol injection below 22°C (72°F), but not below 4°C (40°F. ); do not refrigerate or freeze. Protect from light. Shake well before using. Do not use if the emulsion has separated. The manufacturer recommends discarding any unused portion at the end of the anesthetic procedure or after 6 hours, whichever occurs sooner. Propofol is physically compatible with the commonly used IV solutions (e. g., LRS, D 5W) when injected into a running IV line. Drugs that are reported to be compatible with Y-site administration include (partial listing): ampicillin, butorphanol, calcium glucon-ate, cefazolin, cefoxitin, clindamycin, dexamethasone sodium phos-phate, dexmetomidine, diphenhydramine, dobutamine, dopamine, epinephr ine, fentanyl, furosemide, heparin sodium, insulin, ket-amine, lorazepam, magnesium sulfate, mannitol, naloxone, pento-barbital, phenobarbital, potassium chloride, propranolol, sodium bicarbo nate, succinylcholine, thiopental, and vecuronium. It is incompatible with atracurium and vecuronium. Refer to specialized references or a hospital pharmacist for more information. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Propofol Injectable: 10 mg/m L in 5 m L and 20 m L (single use) vials; Rapinovet® (Schering Plough); Propo Flo® (Abbott); (Rx). Approved for use in dogs and cats. The ARCI (Racing Commissioners International) has designated this drug as a class 2 substanc e. See the appendix for more information. HUMAN-LABELED PRODUCTS: Propofol Injection, Emulsion: 10 mg/m L in 20 m L amps & vials, 50 m L and 100 m L infusion vials and 50 m L preﬁlled single-use syring-es; Diprivan® (Astra Zeneca); Propofol (Baxter); (Rx) PROPRANOLOL HCL (proe-pran-oh-lole) Inderal® BETA-ADRENERGIC BLOCKER Prescriber Highlights TT Non speciﬁc beta blocker primarily used in veterinary medicine as an antiarrhythmic agent TT Contraindications: Heart failure, hypersensitivity to this class of agents, greater than 1st degree heart block, or sinus bradycardia; generally contraindicated in patients with CHF unless secondary to a tachyarrhythmia respon-sive to beta-blockers or with bronchospastic lung disease TT Caution: Signiﬁcant renal or hepatic insufﬁciency, sinus node dysfunction, labile diabetic patients, digitalized or digitalis intoxicated patients TT Adverse Effects: Bradycardia, lethargy, & depression, im-paired AV conduction, CHF or worsening of heart failure, hypotension, syncope, diar rhea, hypoglycemia, & bron-choconstriction TT May mask (treat) clinical signs of thyrotoxicosis TT If discontinuing drug, consider gradual withdrawal TT Drug Interactions Uses/Indications While propranolol is used for hypertension, migraine headache pro-phylaxis, and angina in human patients, it is used primarily in veter-inary medicine for its antiarrhythmic effects. Dysrhythmias treated with pr opranolol include: atrial premature complexes, ventricular premature complexes, supraventricular premature complexes and tachyarrhythmias, ventricular or atrial tachyarrhythmias secondary to digitalis, atrial tachycardia secondary to Wolff-Parkinson-White	pppbs.pdf
(WPW) with normal QRS complexes, and atrial ﬁbrillation (gener-ally in combination with digoxin). Propranolol reportedly improves cardia c performance in animals with hypertrophic cardiomyopathy. It has been used to treat systemic hypertension and clinical signs as-sociated with thyrotoxicosis and pheochromocytoma. Pharmacology/Actions Propranolol blocks both beta 1-and beta 2-adrenergic recep-tors in the myocardium, bronchi, and vascular smooth muscle. Pr opranolol does not have any intrinsic sympathomimetic activity (ISA). Additionally, propranolol possesses membrane-stabilizing effects (quinidine-like) affecting the cardiac action potential and direct myocardial depressant effects. Cardiovascular effects second-ary to propranolol include: decreased sinus heart rate, depressed A V co nduction, diminished cardiac output at rest and during exercise, decreased myocardial oxygen demand, decreased hepatic and renal blood ﬂow, reduced blood pressure, and inhibition of isoprotere-nol-induced tachycardia. Electrophysiologic effects on the heart incl ude decreased automaticity, increased or no effect on effective refractory period, and no effect on conduction velocity. Additional pharmacologic effects of propranolol, include in-creased airway resistance (especially in patients with bronchoc-onstrictive disease), prevention of migraine headaches, increased ut erine activity (more so in the non-pregnant uterus), decreased platelet aggregability, inhibited glycogenolysis in cardiac and skel-etal muscle, and increased numbers of circulating eosinophils. Pharmacokinetics Propranolol is well absorbed after oral administration, but a rapid ﬁrst-pass effect through the liver reduces systemic bioavailability to approximately 2-27% in dogs, thereby explaining the signiﬁcant difference between oral and intravenous dosages. These values re-portedly increase with chronic dosing. Hyperthyroid cats may have increase d bioavailability of propranolol when compared with nor-mal cats. Propranolol is highly lipid soluble and readily crosses the blood-br ain barrier. The apparent volume of distribution has been report-ed to 3. 3-11 L/kg in the dog. Propranolol crosses the placenta and ent ers milk (at very low levels). In humans, propranolol is approxi-mately 90% bound to plasma proteins. Propranolol metabolization occurs principally by the liver. An ac tive metabolite, 4-hydroxypropranolol, has been identiﬁed after oral administration in humans. Less than 1% of a dose is excreted unchanged into the urine. The half-life in dogs has been reported to range from 0. 77-2 hours, and in horses, less than 2 hours. It has been reported that hyperthyroid cats have a decreased clearance of propranolol when compared with normal cats. Contraindications/Precautions/Warnings Propranolol is contraindicated in patients with overt heart fail-ure, hypersensitivity to this class of agents, greater than 1st degree heart block, or sinus bradycardia. Non-speciﬁc beta-blockers are generally contraindicated in patients with CHF unless secondary to a tachyarrhythmia responsive to beta-blocker therapy. They are also relatively contraindicated in patients with bronchospastic lung disease. Propranolol should be used cautiously in patients with signiﬁ-cant renal or hepatic insufﬁciency, or with sinus node dysfunction. Propranolol can mask the clinical signs associated with hypogly-cemia. It can also cause hypoglycemia or hyperglycemia and, there-fore, should be used cautiously in labile diabetic patients. Propranolol can mask the clinical signs associated with thyro-toxicosis, but it has been used clinically to treat the clinical signs associat ed with this condition. Use propranolol cautiously with digitalis or in digitalis intoxi-cated patients; severe bradycardias may result. Adverse Effects It is reported that adverse effects most commonly occur in geriat-ric animals or those that have acute decompensating heart disease. Clinical ly relevant adverse effects include: bradycardia, lethargy and depression, impaired A V conduction, CHF or worsening of heart failure, hypotension, hypoglycemia, and bronchoconstriction. Syncope and diarrhea have also been reported in canine patients. Exacerbations of clinical signs have been reported following abr upt cessation of beta-blockers in humans. It is recommended to withdraw therapy gradually in patients who have been receiving the drug chronically. 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 fe tus, 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: 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. ) Propranolol is excreted in maternal milk. Use with caution in nur sing patients. Overdosage/Acute Toxicity The most predominant clinical signs expected would be hypoten-sion and bradycardia. Other possible effects could include: CNS (de pressed consciousness to seizures), bronchospasm, hypogly-cemia, hyperkalemia, respiratory depression, pulmonary edema, other ar rhythmias (especially A V block), or asystole. There were 94 exposures to propranolol HCl reported to the ASPCA A nimal Poison Control Center (APCC; www. apcc. aspca. org) during 2005-2006. In these cases 86 were dogs with 4 show-ing clinical signs and 8 cats with 2 showing clinical signs. Common ﬁndings in dogs recorded in decreasing frequency included brady-cardia, hypotension, collapse and depression. Common ﬁndings in cats re corded in decreasing frequency included bradycardia. If overdose is secondary to a recent oral ingestion, emptying the gut and charcoal administration may be considered but use caution since coma and seizures may develop rapidly. Monitor patient's ECG, blood glucose, potassium and, if possible, blood pressure; treatment of the cardiovascular and CNS effects are symptomatic. Use ﬂuids and pressor agents to treat hypotension. Bradycardia may be treated with atropine. If atropine fails, isoproterenol given cautiously has been recommended. Use of a transvenous pacemaker may be neces-sary. Cardiac failure can be treated with digoxin, diuretics, oxygen and, if necessary, IV aminophylline. Glucagon (5-10 mg IV; hu-man dose) may increase heart rate and blood pressure and reduce the car diodepressant effects of propranolol. Seizures generally will respond to IV diazepam. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving propranolol and may be of signiﬁcance in veterinary patients: !TANTACIDS : May reduce oral propranolol absorption; separate dos-es by at least one hour !TANESTHETICS, GENERAL : Additive myocardial depression may oc-cur with the concurrent use of propranolol and myocardial de-pressant anesthetic agents	pppbs.pdf
T T!TANTICHOLINERGICS : May negate cardiac effects of beta-blockers !TCALCIUM CHANNEL BLOCKERS : Concurrent use of beta-blockers with calcium channel blockers (or other negative inotropes) should be done with caution, particularly in patients with preex-isting cardiomyopathy or CHF !TCIMETIDINE : May decrease the metabolism of propranolol and in-crease blood levels !TDIURETICS : May increase risk for hypotension !TEPINEPHRINE : Unopposed alpha effects of epinephrine may lead to rapid increases in blood pressure and decrease in heart rate !TFLUOXETINE : May decrease propranolol metabolism; complete heart block reported in one human !TINSULIN and other ANTIDIABETIC DRUGS : Propranolol may prolong the hypoglycemic effects of insulin therapy !TLIDOCAINE : Clearance may be impaired by propranolol !TMETHIMAZOLE, PROPYLTHIOURACIL : Propranolol doses may need to be decreased when initiating therapy !TPHENOTHIAZINES : May increase risk for hypotension !TRESERPINE : May have additive effects with propranolol !TSUCCINYLCHOLINE, TUBOCURARINE : Effects may be enhanced with propranolol therapy !TSYMP ATHOMIMETICS (metaproterenol, terbutaline, beta effects of epinephrine, phenylpropanolamine, etc. ): May have their actions blocked by propranolol !TTHEOPHYLLINE : Effects of theophylline (bronchodilation) may be blocked by propranolol !TTHYROID HORMONES : May decrease the effects of beta blocking agents Doses !TDOGS: a) For susceptible cardiac arrhythmias: 0. 02 mg/kg IV slowly (up t o a maximum of 1 mg/kg). Oral dose: 0. 1-0. 2 mg/kg initially PO q8h, up to a maximum of 1. 5 mg/kg q8h (Ware 2000) b) As a beta-blocker for adjunctive therapy in heart failure: 0. 1-0. 2 mg/kg PO q8h (start low and titrate) (Fox 2003a) c) For loud-noise phobias: 5-40 mg/dog q8h (Crowell-Davis 1999) !TCATS: a) For susceptible cardiac arrhythmias: 0. 02 mg/kg IV slowly (up t o a maximum of 1 mg/kg). Oral dose: 2. 5 mg (up to 10 mg) total dose per cat q 8-12h (Ware 2000) b) For susceptible cardiac arrhythmias: 0. 02 mg/kg IV over one minu te; can repeat up to a maximum of four times as needed based upon response (Cote 2004) c) As a beta-blocker for adjunctive therapy in heart failure: 2. 5-10 mg (total dose) PO q8h (start low and titrate) (Fox 2003a) d) For adjunctive therapy of hypertension: 2. 5-5 mg (total dose) PO q8 -12h (Sparkes 2003b) e) For adjunctive therapy (to control neuromuscular and car-diovascular effects) in feline hyperthyroidism: 2 mg/kg (6. 25 mg pe r cat) once daily (Behrend 1999) f) For loud-noise phobias: 0. 25 mg/kg as needed (Crowell-Da-vis 1999) !TFERRETS: For hypertrophic cardiomyopathy: 0. 5-2 mg/kg PO or SC once a day to twice a day (Williams 2000) !THORSES: (Note : ARCI UCGFS Class 3 Drug) a) For V-Tach: 0. 05-0. 16 mg/kg IV. Note : negative inotropic and chronotropic effects may be undesirable. (Mogg 1999) b) For V-Tach: 0. 03-0. 15 mg/kg IV or 0. 3-0. 7 mg/kg PO q8h. Co nsidered not as effective as lidocaine; decreases ventricu-lar rate even if it does not restore sinus rhythm. T oxic effects incl ude bradycardia, A V block, proarrhythmic, negative ino-trope and hypotension. Use with caution in animals with air-way disease (bronchoconstriction). (Kimberly and Mc Gur-rin 2006) c) Oral: Days 1 and 2: 175 mg three times a day; Days 3 and 4: 275 mg three times a day; Days 5 and 6: 350 mg three times daily. Intravenous: Days 1 and 2: 25 mg two times a day; Days 3 and 4: 50 mg two times a day; Days 5 and 6: 75 mg twice daily (Hilwig 1987) Monitoring !TECG !Toxicity (see Adverse Effects/Overdosage) !TBlood pressure if administering IV Client Information !To be effective, the animal must receive all doses as prescribed. !TNotify veterinarian if animal becomes lethargic or becomes exer-cise intolerant, begins wheezing, develops shortness of breath or cough, or presents a change in behavior or attitude. Chemistry/Synonyms A non-speciﬁc beta-adrenergic blocking agent, propranolol HCl occurs as a bitter tasting, odorless, white to almost white powder with a p K a of 9. 45 and a melting point of about 161°C. One gram of propranolol is soluble in about 20 m L of water or alcohol. At a p H from 4-5, solutions of propranolol will ﬂuoresce. The commercially available injectable solutions are adjusted with citric acid to a p H 2. 8-3. 5. Propranolol may also be known as: AY-64043, ICI-45520, NSC-91523, p ropranololi hydrochloridum; many trade names are available. Storage/Stability/Compatibility All propranolol preparations should be stored at room temperature (15-30°C) and protected from light. Propranolol solutions will de-compose rapidly at alkaline p H. Propranolol injection is reported to be physically compatible with D 5W, 0. 9% sodium chloride, or lac-tated Ringer's injection. It is also physically compatible with dobu-tamine HCl, verapamil HCl, and benzquinamide HCl. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Propranolol HCl Tablets: 10 mg, 20 mg, 40 mg, 60 mg, 80 mg & 90 mg; Inderal® (Wyeth-Ayerst); generic; (Rx) Propranolol HCl Extended/Sustained-Release Capsules: 60 mg, 80 mg, 120 mg & 160 mg; Inderal® LA (Wyeth-Ayerst); Inno Pran® XL (Reliant); generic; (Rx) Propranolol for Injection: 1 mg/m L in 1 m L amps or vials; Inde ral® (Wyeth-Ayerst); generic; (Rx) Propranolol Oral Solution: 4 mg/m L & 8 mg/m L in 500 m L and UD5 m L pat ient cups, and 80 mg/m L concentrate in 30 m L; Propranolol Intensol® and Propranolol HCl® (Roxane); (Rx)	pppbs.pdf
In addition, ﬁxed dose combination products containing propra-nolol and hydrochlorothiazide are available to treat hypertension in humans. Prostaglandin F 2 alpha—see Dinoprost Tromethamine PROTAMINE SULFATE (proe-ta-meen) ANTIDOTE (HEPARIN) Prescriber Highlights TT Protein that complexes with heparin (treatment of over-doses); may also be useful for Bracken Fern poisoning TT Contraindications: Hypersensitivity to protamine TT Adverse Effects: If injected IV too rapidly: Acute hypoten-sion, bradycardia, pulmonary hypertension, & dyspnea; hypersensitivity possible TT Monitor for heparin “rebound effect” Uses/Indications Protamine is used in all species for the treatment of heparin over-dosage when signiﬁcant bleeding occurs. While protamine will neu-tralize the anti-thrombin effects of low molecular weight heparins (e. g., dalt eparin or enoxaparin), it does not completely inhibit their anti-Xa activity. Laboratory animal studies however, shows it does improve microvascular bleeding associated with LMWH overdoses. Protamine has been suggested for use for Bracken Fern toxicity in ruminants (see Doses). Pharmacology/Actions Protamine is strongly basic and heparin, strongly acidic; protamine complexes with heparin to form an inactive stable salt. Protamine has intrinsic anticoagulant activity, but its effects are weak and rare-ly cause problems. Pharmacokinetics After IV injection, protamine binds to heparin within 5 minutes. The exact metabolic fate of the heparin-protamine complex is not known, but there is evidence that the complex is partially metabo-lized and/or degraded by ﬁbrinolysin thus freeing heparin. Contraindications/Precautions/Warnings Protamine is contraindicated in patients who have demonstrated hypersensitivity or intolerance to the drug in the past. Adverse Effects If protamine sulfate is injected IV too rapidly, acute hypotension, bradycardia, pulmonary hypertension, and dyspnea can occur. These effects are usually absent or minimized when the drug is ad-ministered slowly (over 1-3 minutes). Hypersensitivity reactions have also be en reported. A heparin “rebound” effect has been reported where anticoagu-lation and bleeding occur several hours after heparin has apparent-ly been neutralized. This may be due to either a release of heparin from e xtravascular compartments or the release of heparin from the protamine-heparin complex. 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 this drug is excreted in maternal milk. Overdosage/Acute Toxicity Because protamine has inherent anticoagulant activity, overdoses of protamine may, theoretically, result in hemorrhage; however, in one human study, overdoses of 600-800 mg resulted only in mild, transient effects on coagulation. The LD 50 of protamine in mice is 100 mg/kg. Drug Interactions; Laboratory Considerations None were located. Doses T ! DOGS & CAT S (and presumably other species): For heparin overdosage: a) Give 1-1. 5 mg protamine sulfate to antagonize each mg (≈100 units) of heparin via slow IV injection. Reduce dose as time increases between heparin dose and start of treatment (after 30 minutes give only 0. 5 mg). (Bailey 1986a) b) Administer 1 mg protamine for each 100 Units of heparin to be inactivated. Decrease protamine dose by 1/2 for every 30 minutes that have lapsed since heparin was administered (Plumb's Note : This may be ineffective if heparin has been administered by deep SC injection). Give dose slowly IV, do not give at a rate faster than 50 mg over a 10-minute period. (Adams 1988b) T ! CATTLE: For Bracken Fern (Pteridium spp. ) poisoning: a) In combination with whole blood (2. 25-4. 5L), 1 injection of 10 m L of 1% protamine sulfate IV (Osweiler and Ruhr 1986) Monitoring T ! See the Heparin monograph Client Information T ! Should only be used in a setting where adequate monitoring fa-cilities are available. Chemistry/Synonyms Simple, low molecular weight, cationic proteins, protamines occur naturally in the sperm of ﬁsh. Commercially available protamine sulfate is produced from protamine obtained from the sperm or mature testes of salmon (or related species). It occurs as a ﬁne, white to off-white crystalline or amorphous powder that is spar-ingly soluble in water and very slightly soluble in alcohol. The injec-tion is available as either a prepared solution with a p H of 6-7 or a lyop hilized powder that has a p H of 6. 5-7. 5 after reconstituting. Protamine Sulfate may also be known as: protamine sulphate, protamini sulfas, sulfato de protamina, Prosulf®, or Prota ®. Storage/Stability/Compatibility The powder for injection should be stored at room temperature (15-30°C), and the injection (liquid) in the refrigerator (2-8°C); avoid freezing. The injection is stable at room temperature for at least 2 weeks, however. The powder for injection should be used im-mediately if reconstituted with Sterile Water for Injection and with-in 72 hours if reconstituted with Bacteriostatic Water for Injection.	pppbs.pdf
It is recommended to use either D 5W or normal saline for protamine sulfate infusions. Cimetidine and verapamil are reported to be physically compatible with protamine sulfate for injection. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Protamine Sulfate Injection: 10 mg/m L preservative-free in 5 m L and 25 m L vials; generic; (Rx) PSEUDOEPHEDRINE HCL (soo-doe-e-fed-rin) Equiphed®, Sudafed® SYMPATHOMIMETIC Prescriber Highlights TT Oral sympathomimetic used primarily for urethral sphinc-ter hypotonus when phenylpropanolamine unavailable TT Caution: Glaucoma, prostatic hypertrophy, hyperthyroid-ism, diabetes mellitus, cardiovascular disorders, or hypertension TT Adverse Effects: Restlessness, irritability, hypertension, & anorexia TT Restricted drug in USA; can be used as a precursor to manufacture methamphetamine Uses/Indications Pseudoephedrine is used primarily as a substitute for phenylpropa-nolamine for the treatment of urinary incontinence (dribbling) in dogs. It may also be used as an oral decongestant. Pharmacology/Actions While the exact mechanisms of pseudoephedrine's actions are un-determined, it is believed that it indirectly stimulates both alpha-and beta- (to a lesser degree) adrenergic receptors by causing the release of norepinephrine. Pharmacologic effects of pseudoephedrine include increased vasoco nstriction, heart rate, coronary blood ﬂow, blood pressure, mild CNS stimulation, and decreased nasal congestion and appe-tite. Pseudoephedrine can also increase urethral sphincter tone and prod uce closure of the bladder neck. Pharmacokinetics Pseudoephedrine is rapidly and nearly completely absorbed from the GI tract. Food may delay the absorption somewhat, but not the extent. In children, the apparent volume of distribution is about 2. 5 L/kg. Pseudoephedrine is only partially metabolized and the bulk is excreted unchanged in the urine. Urine p H can affect excretion rates. Alkaline urine (p H 8) can prolong half-life while acidic urine (p H 5) can decrease it. Contraindications/Precautions/Warnings Pseudoephedrine should be used with caution in patients with glaucoma, prostatic hypertrophy, hyperthyroidism, diabetes mel-litus, cardiovascular disorders or hypertension. Adverse Effects Adverse effects are dose related and adrenergic in nature with CNS excitement/restlessness/insomnia, and rapid heart rate the most likely to be seen at usual doses. Decreased appetite is possible. Increases in blood pressure and arrhythmias are possible in suscep-tible individuals, particularly at high doses. Because pseudoephedrine may be used to manufacture meth-amphetamine, be alert for clients wanting to purchase very large amounts of the drug. Reproductive/Nursing Safety Safe use has not been established during pregnancy; use with care. 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 humans, it is not recommended to use systemic pseudoephed-rine during breastfeeding as the drug enters maternal milk and in-fants may be very susceptible to the drug's effects. Use with caution in vete rinary patients. Overdosage/Acute Toxicity Overdoses of pseudoephedrine can cause hyperthermia, mydriasis, tachycardia, vomiting, disorientation, and seizures. In small ani-mals, adverse reactions may develop at doses of 5-6 mg/kg. Deaths have oc curred at doses of 10-12 mg/kg. There were 53 exposures to pseudoephedrine reported to the ASPCA Animal P oison Control Center (APCC; www. apcc. aspca. org) dur ing 2005-2006. In these cases all 53 were dogs with 6 showing clinical signs. Common ﬁndings in dogs recorded in de-creasing frequency included ataxia, vomiting, tremors, seizures and blindness. Large o verdoses should be treated with gastric evacuation (if not cont raindicated); otherwise, treat supportively and symptom-atically (e. g., propranolol for tachycardia, diazepam for seizures). Phenothiazines are preferred to treat hyperactivity, agitation, and tremors as diazepam may worsen dysphoria. It is recommended to contact an animal poison control center for further guidance in the case of a large pseudoephedrine overdose. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving pseudoephedrine and may be of signiﬁcance in veterinary patients: T ! MONAMINE OXIDASE (MAO) INHIBITORS (e. g., amitraz, possibly selegi-line): Pseudoephedrine should not be given within two weeks of a patient receiving monoamine oxidase inhibitors T ! RESERPINE : An increased chance of hypertension if given concomitantly T ! SYMP ATHOMIMETIC AGENTS, OTHER : Phenylpropanolamine should not be administered with other sympathomimetic agents (e. g., ephedrine ) as increased toxicity may result T ! TRICYCLIC ANTIDEPRESSANTS (clomipramine, amitriptyline, etc. ): An increased chance of hypertension if given concomitantly Doses T ! DOGS: a) For urinary incontinence, or as a decongestant: 0. 2-0. 4 mg/ kg (or p ractically, 15-60 mg total dose per dog) PO q8-12h (Tilley and Smith 2000) T ! HORSES: (Note : ARCI UCGFS Class 3 Drug) a) For use when an antihistamine/decongestant may be useful using the py rilamine/pseudoephedrine oral granules: 1/2 ounce (1 tablespoonful) per 1,000 lb body weight. May mix with feed and repeated at 12 our intervals if needed. Do not use at least 72 hours before sporting events. (Label informa-tion—veterinary products listed below)	pppbs.pdf
Monitoring T ! Efﬁcacy T ! Adverse effects (heart rate, CNS stimulation, appetite) Client Information T ! For this drug to be effective, it must be administered as directed by the veterinarian; missed doses will negate its effect. It may take several days for the full beneﬁt of the drug to take place. T ! Contact veterinarian if the animal demonstrates ongoing changes 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, pseudoe phedrina, Equi-Phar Equi-Hist 1200 Granules®, Drixoral®, Equiphed®, Histgranules®, Sudafed®, and Tri-Hist®. Storage/Stability PSYLLIUM HYDROPHILIC MUCILLOID (sill-i-yum hye-droe-ﬁll-ik myoo-sill-oid) Metamucil®, Equi-Psyllium® BULK FORMING GI LAXATIVE/ANTIDIARRHEAL Prescriber Highlights TT Bulk-forming agent used for treatment & prevention of sand colic in horses, as a laxative, & to increase stool consistency in patients with chronic, watery diarrhea TT Contraindications: Rabbits. Where prompt intestinal evacuation is required, & when fecal impaction or intesti-nal obstruction is present. TT Adverse Effects: Flatulence; if insufﬁcient liquid is given, increased possibility of esophageal or bowel obstruction 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. VETERINARY-LABELED PRODUCTS: 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 substanc e. See the appendix for more information. HUMAN-LABELED PRODUCTS: 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-or al 12 Hour Non-Drowsy Formula® (Schering-Plough Healthcare); (OTC, r estricted) 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, r estricted) 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 re mains 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 tr act. 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 muc osa 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 pat ient. 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.	pppbs.pdf
Overdosage/Acute Toxicity 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: T ! ASPIRIN (and other SALICYLATES ): Potential exists for psyllium to bind and reduce absorption if given at the same time; if possible, separate doses by 3 hours or more T ! DIGOXIN : Potential exists for psyllium to bind and reduce absorp-tion if given at the same time; if possible, separate doses by 3 hours or mor e T ! NITROFURANTOIN : 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 T ! DOGS: a) For a trial to treat chronic idiopathic large bowel diarrhea using Metamuc il®: 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 Co nnell and Hughey 1987) T ! CATS: 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) T ! HORSES: 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 be fore 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 T ! Stool consistency, frequency Client Information T ! Contact veterinarian if patient begins vomiting T ! Be sure animal has free access to water 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 Metamuc il®; 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 VETERINARY-LABELED PRODUCTS: Equine Enteric Colloid® (T echmix); Equi-Phar® Sweet Psyllium (V e-dco); (not for horses intended for food); Sandclear® (F arnam), An-ipsyll® Powder (AHC), Pure psyll® 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 o r 180; (Virbac) (OTC); Labeled for use in cats. Also contains barley malt extract powder, acacia and thiamine. HUMAN-LABELED PRODUCTS: 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 PAMOATE (pi-ran-tel) Strongid T®, Nemex® ANTIPARASITIC Prescriber Highlights TT Pyrimidine anthelmintic used primarily for ascarids in a variety of species TT Contraindications: Severely debilitated animals TT Adverse Effects: Unlikely, emesis possible in small 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: Strong ylus 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 sp p., 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 Oes ophagostomum spp. The drug has activity against the swine stomach worm (Hyostrongylus rubidus). Although not approved, pyrantel has been used in pet birds and llamas. Se e the Dosage section for more information.	pppbs.pdf
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 c holinesterase. 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 tart rate 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 f eces. 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 fe tus, 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 (P robably 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 Toxicity 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 !TDIETHYLCARBAMAZINE : Increased risk for adverse effects !TLEVAMISOLE : Because of similar mechanisms of action (and toxic-ity), do not use concurrently with pyrantel !TMORANTEL : Because of similar mechanisms of action (and toxic-ity), do not use concurrently with pyrantel !TORGANOPHOSPHATES : Increased risk for adverse effects !TPIPERAZINE : 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. !TDOGS: For susceptible parasites: a) For hookworms, or roundworms: 5 mg/kg PO after meals; re peat in 7-10 days (Willard 2003a) b) 15 mg/kg PO 30 minutes after a light meal. Re-treatment re commendations: 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 we ighing >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; table ts may be broken for accurate dosing. Not approved for cats but very safe and effective. (Blagburn 2005b) !TCATS: For susceptible parasites: a) Ascarids, Hookworms, Physaloptera: 5 mg/kg, PO; repeat in 2 we eks (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) !TRABBITS, RODENTS, SMALL MAMMALS: a) Rabbits: 15-10 mg/kg PO, repeat in 2-3 weeks (Ivey and Mo rrisey 2000) !THORSES: For susceptible parasites: a) 6. 6 mg (as base)/kg PO; 13. 2 mg (as base)/kg for cestodes (Ro binson 1987), (Roberson 1988b) b) 19 mg/kg, PO (Brander, Pugh, and Bywater 1982) c) Pyrantel tartrate: 12. 5 mg/kg, PO (Roberson 1988b) !TSWINE: For susceptible parasites: a) T o remove As caris 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 (Ro berson 1988b) c) For ascarids and nodular worms in potbellied pigs: 6. 6 mg/ kg PO (Br aun 1995) !TCATTLE, SHEEP & GOATS: For susceptible parasites: a) Pyrantel tartrate: 25 mg/kg, PO (Roberson 1988b)	pppbs.pdf
T ! LLAMAS: For susceptible parasites: a) 18 mg/kg, PO for one day (Cheney and Allen 1989), (Fowler 1989) T ! BIRDS: 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 (Mar shall 1993) Client Information T ! Shake suspensions well before administering. 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 VETERINARY-LABELED PRODUCTS: Note : Many products available; a partial listing of products follows: Pyrantel Pamoate Tablets: 22. 7 mg (of base), 113. 5 mg (of base); (OTC). A pproved 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 Strong id® 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: Strong id 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/pyrant el 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 d og 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-LABELED PRODUCTS: 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® (A pothecary); Reese's® Pinworm (Reese); (OTC) PYRIDOSTIGMINE BROMIDE (peer-i-oh-stig-meen) Mestinon® ANTICHOLINESTERASE AGENT Prescriber Highlights TT Anticholinesterase used for treatment of myasthenia gravis TT Contraindications: hypersensitivity to this class of com-pounds or bromides, patients with mechanical or physi-cal obstructions of the urinary or GI tract TT Caution: bronchospastic disease, epilepsy, hyperthyroid-ism, bradycardia or other arrhythmias, vagotonia, or GI ulcer diseases TT Adverse Effects: Usually dose related cholinergic effects GI (nausea, vomiting, diarrhea), salivation, sweating, re-spiratory (increased bronchial secretions, bronchospasm, pulmonary edema, respirator y 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 hydrol yzed 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 (quater nary 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.	pppbs.pdf
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 c holinesterases. 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 arr hythmias, 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 fe tus, 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 nur sing patients. Overdosage/Acute Toxicity 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 eff ects (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. Re fer 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: !TATROPINE : 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 !TCORTICOSTEROIDS : May decrease the anticholinesterase activity of pyridostigmine. After stopping corticosteroid therapy, drugs like pyridostigmine may cause increased anticholinesterase activity !TDEXPANTHENOL : Theoretically, dexpanthenol may have additive ef-fects when used with pyridostigmine !TDRUGS WITH NEUROMUSCULAR BLOCKING ABILITY (e. g., aminoglyco-side antibiotics ): May necessitate increased dosages of pyridostig-mine in treating or diagnosing myasthenic patients !TMAGNESIUM : Anticholinesterase therapy may be antagonized by administration of parenteral magnesium therapy, as it can have a direct depressant effect on skeletal muscle !TMUSCLE RELAXANTS : Pyridostigmine may prolong the Phase I block of depolarizing muscle relaxants (e. g., succinylcholine, decamethonium ) and edrophonium antagonizes the actions of non-depolarizing neuromuscular blocking agents (e. g., pancuro-nium, tubocurarine, gallamine, vecuronium, atracurium, etc. ) Doses !TDOGS: 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 pare nteral 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 co ntinue 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 pr ednisone (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 pr ednisone (2 mg/kg PO twice daily). Not uncommon for dogs to fully recover without treatment (spontaneous remis-sion). (Le Couteur 2005) !TCATS: For myasthenia gravis (MG): a) For acquired MG: Cats are sensitive to anticholinesterase age nts. 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 !TAnimals should be routinely monitored for clinical signs of cho-linergic toxicity (see Overdosage section above) and efﬁcacy of the the r apy Client Information !TClients should be instructed to report to the veterinarian clinical 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 smel ling, 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 br omidum, 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 table ts should be kept in tight containers. The extended-release tablets may become mottled with time, bu t this does not affect their potency.	pppbs.pdf
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-c omplex 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 VETERINARY-LABELED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 3 substance. See the appendix for more information. HUMAN-LABELED PRODUCTS: 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 (VITAMIN B-6) (peer-ih-dox-een) NUTRITIONAL B VITAMIN, ANTIDOTE Prescriber Highlights TT Pyridoxine may be beneﬁcial in the treatment of isoni-azid or crimidine toxicity, or delaying cutaneous toxicity of Doxil® (liposomal doxorubicin) TT Overdoses may cause peripheral neuropathy 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 ®). Pyr idoxine 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 depe ndency 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 h umans 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 pyrid oxine dependency syndrome in neonates. Pyridoxine administration at low dosages should be safe dur-ing nursing. Pyridoxine requirements of the dam may be increased during nur sing. Overdosage/Acute Toxicity 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. S igns 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: T ! CHLOR AMPHENICOL : May cause increased pyridoxine requirements T ! ESTROGENS : May cause increased pyridoxine requirements T ! HYDRALAZINE : May cause increased pyridoxine requirements T ! IMMUNOSUPPRESSANTS (e. g., azathioprine, chlorambucil, cyclo-phosphamide, corticosteroids ): May cause increased pyridoxine requirements T ! ISONIAZID : May cause increased pyridoxine requirements T ! PENICILLAMINE : May cause increased pyridoxine requirements T ! LEVODOPA : Pyridoxine may reduce levodopa efﬁcacy (no interac-tion when levodopa is used with carbidopa) T ! PHENOBARBITAL : High dose pyridoxine may decrease phenobarbi-tal serum levels T ! PHENYTOIN : High dose pyridoxine may decrease phenytoin serum concentration	pppbs.pdf
Laboratory Considerations The following laboratory alterations have been reported in humans with pyridoxine and may be of signiﬁcance in veterinary patients: T ! Urobilinogen in the spot test using Ehrlich's reagent : Pyridoxine may cause false-positive results T ! AST: Excessive dosages of pyridoxine may elevate AST Doses T ! DOGS/CAT S: 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) Do gs: T o delay the development of cutaneous toxicity (PPES; palmer-plantar-d yerythrodysesthesia) associated with doxo-rubicin containing pegylated liposomes (Doxil®): 50 mg PO three times daily during chemotherapy protocol period. (Vail, Chun et al. 1998) Monitoring T ! Other than evaluating efﬁcacy for its intended use, no signiﬁcant monitoring is required Client Information T ! Do not give more than prescribed by the veterinarian T ! Contact veterinarian if animal develops any abnormal signs such 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 fr eely 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), pref erably 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 VETERINARY-LABELED PRODUCTS: 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-LABELED PRODUCTS: 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). PYRILAMINE MALEATE (pye-ril-a-meen) Histall®, Equiphed® ANTIHISTAMINE Prescriber Highlights TT Injectable antihistamine TT Contraindications: None noted TT Adverse Effects: HORSES: CNS stimulation (nervousness, insomnia, convulsions, tremors, ataxia), palpitation, GI disturbances, CNS depression (sedation), muscular weak-ness, anorexia, lassitude & incoordination TT Drug Interactions 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 rece ptor 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.	pppbs.pdf
Overdosage/Acute Toxicity 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, ephedr ine, or amphetamines) to treat CNS depression. Most toxi-cologists however, recommend avoiding the use of CNS stimulants in the tr eatment 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: T ! ANTICOAGULANTS (heparin, warfarin ): Antihistamines may partially counteract the anticoagulation effects of heparin or warfarin T ! CNS DEPRESSANT DRUGS : Increased sedation can occur if pyril-amine is combined with other CNS depressant drugs T ! EPINEPHRINE : Pyrilamine may enhance the effects of epinephrine Laboratory Considerations T ! Antihistamines can decrease the wheal and ﬂare response to anti-gen skin testing. In humans, it is suggested that antihistamines be discontinued at least 4 days before testing. Doses T ! DOGS: a) 12. 5-25 mg PO four times a day; 25-125 mg IM (Swinyard 1975) T ! CATTLE: 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) T ! HORSES: (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 bod y 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) T ! SHEEP, SWINE: a) 0. 25-0. 5 gram IM (Swinyard 1975) Monitoring T ! Clinical efﬁcacy T ! Adverse effects 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, mepyr amini 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 VETERINARY-LABELED PRODUCTS: 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 Gr anules: 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 substanc e. See the appendix for more information. HUMAN-LABELED PRODUCTS: None PYRIMETHAMINE (pye-ri-meth-a-meen) Daraprim® ANTIPROTOZOAL Note : Also see the Pyrimethamine/Sulfadiazine, and Sulfadiazine/ Trimethoprim monographs Prescriber Highlights TT Folic acid inhibitor used primarily (in combination) for toxoplasmosis, H. americanum, neosporosis, & equine protozoal encephalomyelitis TT Contraindications: Hypersensitive to pyrimethamine TT Caution: Hematologic disorders; cats TT Adverse Effects: SMALL ANIMALS: Anorexia, malaise, vomiting, depression, & bone marrow depression (ane-mia, thrombocytopenia, leukopenia). Cats may be more likely to develop adverse reactions. HORSES: Leuk ope-nias, thrombocytopenia, & anemias; Baker's yeast or foli-nic acid may treat/prevent. TT Potentially teratogenic; avoid use in pregnancy TT Dosage form (25 mg tab only) may be inconvenient; un-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.	pppbs.pdf
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 l ungs, 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 ur ine. 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 be cause 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 re commend 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 table t dosage size makes successful dosing a challenge. In horses, pyrimethamine has caused leukopenias, thrombocy-topenia and anemias when used in combination with sulfonamides. Bak er'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 b een 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 re placer. Overdosage/Acute Toxicity 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 emp tying 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: !Tp-AMINOBENZOIC ACID (PABA ): PABA is reportedly antagonistic towards the activity of pyrimethamine; clinical signiﬁcance is unclear !TSULFONAMIDES : Pyrimethamine is synergistic with sulfonamides in activity against toxoplasmosis (and malaria) !TTRIMETHOPRIM : Use with pyrimethamine/sulfa is not recom-mended in humans as adverse effects may be additive, however, this co mbination has been used clinically in horses Doses !TDOGS: 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 fo r 1-2 weeks (Murtaugh 1988) b) For T oxoplasmosis: 0. 25-0. 5 mg/kg once daily for 28 days; Fo r 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 tr imethoprim/sulfa (15-30 mg/kg PO twice daily. (Blagburn 2005a) !TCATS: See warnings above. For toxoplasmosis: a) 0. 5-1 mg/kg PO once daily for 2 days, then 0. 25 mg/kg PO onc e 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)	pppbs.pdf
T ! HORSES: 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) T ! BIRDS: 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 T ! See adverse effects; CBC with platelet count T ! Clinical efﬁcacy Client Information T ! Clients should he instructed to monitor for clinical signs of ab-normal bleeding, lassitude, etc. that may signal development of hematolo g ic disorders. T ! Accurate dosing of the tablets in cats may be very difﬁcult as only 25 mg tablets are commercially available. Preferably, cus-tom prepared capsules containing the accurate dosage should be prepar ed. 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 solub le in alcohol. Pyrimethamine may also be known as: BW-50-63, pirimet-amina, pyrimethaminum, RP-4753, Darapr im®, 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 dr ug. 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 t emperature and discard after 7 days. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Pyrimethamine Tablets: 25 mg; Daraprim® (Glaxo Smith Kline); (Rx) PYRIMETHAMINE + SULFADIAZINE (pye-ri-meth-a-meen + sul-fa-dye-a-zeen) Re Balance® ANTIPROTOZOAL Note : Also see the Pyrimethamine, and Sulfadiazine/Trimethoprim monographs Prescriber Highlights TT Tetrahydrofolic acid inhibitor suspension labeled for the treatment of horses with equine protozoal myeloenceph-alitis (EPM) caused by Sarcocystis neurona TT May cause bone marrow suppression, GI effects, & “treatment crisis” (patient's signs worsen after beginning therapy) TT Daily treatment may be required for 3-9 months 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., trimetho prim, pyrimethamine) are used together, synergistic ef-fects can occur. When comparing pyrimethamine and trimethop-rim, pyrimethamine is more active against protozoal dihydrofolate reduc tase 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% o f 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 mar row 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),	pppbs.pdf
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 dr ug 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 t o 5 weeks. It is thought this may be the result of an inﬂamma-tory reaction secondary to dying parasites in the central nervous syst em. 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 t o 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 st udies 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 be en established; consider using milk replacer. Overdosage/Acute Toxicity 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 labe led 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 signiﬁcanc e in veterinary patients: !TANTACIDS : May decrease the bioavailability of sulfonamides if ad-ministered concurrently !THIGHLY PROTEIN-BOUND DRUGS (e. g., methotrexate, phenylbutazone, thiazide diuretics, salicylates, probenecid, phenytoin, warfarin ): Sul-fonamides may displace other highly bound drugs !Tp-AMINOBENZOIC ACID (PABA ): PABA is reportedly antagonistic towards the activity of pyrimethamine; clinical signiﬁcance is unclear !TTRIMETHOPRIM : Use with pyrimethamine/sulfa is not recom-mended in humans as adverse effects may be additive, however, this co mbination 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 patie nts: !TUrine glucose : Sulfonamides may give false-positive results when using the Benedict's method Doses !THORSES: For treatment of EPM: a) 20 mg/kg sulfadiazine with 1 mg/kg pyrimethamine; equiva-lent to 4 m L of Re B alance® 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 plung er. Treatment duration is based upon clinical response, but usually ranges from 90-270 days. (Label information; Re Balance®—Phoenix) Monitoring !TCBC (including platelets): baseline and at least monthly during therapy !TGI adverse effects !TClinical Efﬁcacy: Improvement in neuro signs, CSF Western Blot test negative Client Information !TShake well before using and store at room temperature; see dos-age information for instructions on proper administration !THorse may develop worsening signs after beginning treatment, probably due to local inﬂammation from dying parasites !TWatch for signs that may indicate toxicity including depression, 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 slightl y 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 VETERINARY-LABELED PRODUCTS: 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 B alance® Antiprotozoal Oral Suspension (Phoenix); (Rx) Approved for use in horses; not for use in horses intended for human consumption.	pppbs.pdf
HUMAN-LABELED PRODUCTS: A related compound for humans is: Sulfadoxine & Pyrimethamine Tablets: 500 mg sulfadoxine & 25 mg pyrimethamine; Fansidar® (Roche); (Rx) QUINACRINE HCL (qwin-a-krin) ANTIPROTOZOAL Prescriber Highlights TT Antiprotozoal that may be useful for treatment of Giardia, Leishmania, & coccidia. May improve clinical signs asso-ciated with giardial infection, but not eliminate infection TT Contraindications: Potentially, if hepatic dysfunction or pregnancy TT Adverse Effects: Yellowing of skin & urine color, (not of clinical importance); GI (anorexia, nausea, vomiting, diar-rhea), abnormal behaviors (“ﬂy biting”, agitation), pru-ritus, & fever. Potentially: Hypersensitivity, hepatopathy, aplastic anemia, corneal edema, & retinopath y. TT Availability an issue TT Potential teratogen TT Give with meals; have liquid available 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 intrapleur al 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 suppr ess 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 live r, 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). Quina crine 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, co rneal 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 d uring pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) Overdosage/Acute Toxicity 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 ar rhythmias. 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: T ! ALCOHOL : Quinacrine may cause a “disulﬁram-reaction” if used with alcohol. T ! HEPATOTOXIC DRUGS : Quinacrine concentrates in the liver and should be used with caution with hepatotoxic drugs (clinical sig-niﬁcance unknown). T ! PRIMAQUINE : Quinacrine increases the toxicity of primaquine (generally not used in veterinary medicine), and the two should not be used simultaneously. Laboratory Considerations T ! When urine is acidic, quinacrine can cause it to turn a deep yel-low color. By causing an interfering ﬂuorescence, quinacrine can cause falsely elevated values of plasma and urine cortisol values.	pppbs.pdf
Doses T ! DOGS: 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) T ! CATS: a) Giardia: 9 mg/kg PO once daily for 6 days; Coccidiosis: 10 mg/kg PO onc e 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) T ! REPTILES: a) For hemoprotozoal infections: 19-100 mg/kg PO q48h (ev-ery other day) for 2-3 weeks (de la Navarre 2003b) Monitoring T ! Efﬁcacy (fecal exams, reduction in diarrhea) T ! Adverse effects Client Information T ! Quinacrine should preferably be given after meals with plenty of liquids available. T ! Make sure clients understand the importance of compliance with 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 spar ingly 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 VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: None There currently are no quinacrine products being marketed in the USA. It may be available from compounding pharmacies. QUINIDINE GLUCONATE QUINIDINE POLYGALACTURONATE QUINIDINE SULFA TE (qwin-i-deen) Quinidex® ANTIARRHYTHMIC Prescriber Highlights TT Antiarrhythmic agent used in small animals & horses TT Contraindications: Hypersensitivity, myasthenia gravis; complete AV block with an AV junctional or idioven-tricular pacemaker; intraventricular conduction defects; digitalis intoxication with associated arrhythmias or A V conduction disorder s; aberrant ectopic impulses; or ab-normal rhythms secondary to escape mechanisms TT Extreme Caution: Any form of AV block or if any clinical signs of digoxin toxicity are exhibited TT Caution: Uncorrected hypokalemia, hypoxia, & disorders or acid-base balance; hepatic or renal insufﬁciency TT Adverse Effects: 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 TT Consider monitoring blood levels TT Administer at evenly spaced intervals throughout the day/night TT GI upset may be decreased if administered with food TT Do not allow animal to chew or crush sustained-release oral dosage forms TT Many drug Interactions Uses/Indications Quinidine is used in small animal or equine medicine for the treat-ment of ventricular arrhythmias (VPCs, ventricular tachycardia), refr actory 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 conduc tion times. Quinidine also possesses anticholinergic activity which decreases vagal tone and may facilitate A V conduction.	pppbs.pdf
Pharmacokinetics After oral administration, quinidine salts are nearly completely ab-sorbed from the GI, however, the actual amount that reaches the syst emic 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 br ain. 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 ur ine 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 gr avis; complete A V block with an A V junctional or idioventricu-lar pacemaker; intraventricular conduction defects (especially with pr onounced 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. Sig ns of toxicity include swelling of the nasal mucosa, ataxia, di-arrhea, colic, hypotension and, rarely, laminitis, paraphimosis and the d evelopment of urticarial wheals. Urticaria or upper respira-tory tract obstruction may be treated by discontinuing the drug and administ ering 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 fe tus, 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 te rm. ) 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 Toxicity 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, pl us 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 eff ects 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: !TAMIODARONE : May increase quinidine levels (signiﬁcantly) !TANTACIDS : May delay oral absorption; separate dosages !TANTIARRHYTHMIC AGENTS : Use with caution with other antidys-rhythmic agents, as additive cardiotoxic or other toxic effects may res ult !TANTICHOLINESTERASES (e. g., pyridostigmine, neostigmine ): Quini-dine may antagonize the effects of anticholinesterases in patients with m yasthenia gravis !TCIMETIDINE : Cimetidine may increase the levels of quinidine by inhibiting hepatic microsomal enzymes !TCLARITHROMYCIN : Increased risk for torsade de pointes !TDIGOXIN : 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. !TDILTIAZEM : Possible decreased clearance; increased elimination half-life of quinidine !THYPOTENSIVE AGENTS : Quinidine may potentiate the effects of other drugs having hypotensive effects !TKETOCONAZOLE : May reduce the metabolism of quinidine !TNEUROMUSCULAR BLOCKING AGENTS : Quinidine may increase the neuromuscular blocking effects of drugs like succinylcholine, tubocurarine, or atracurium !TPHENOBARBITAL, PHENYTOIN : May induce hepatic enzymes that metabolize quinidine thus reducing quinidine serum half-life by 50% !TPHENOTHIAZINES : Additive cardiac depressant effects may be seen !TRESERPINE : Additive cardiac depressant effects may be seen !TRIFAMPIN : May induce hepatic enzymes that metabolize quinidine thus reducing quinidine serum half-life by 50%	pppbs.pdf
!TURINARY ACIDIFIERS (e. g., methionine, ammonium chloride ): Drugs that acidify the urine (may increase the excretion of quinidine and decrease serum level !TURINARY ALKALINIZERS (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 !TVERAPAMIL : Possible decreased clearance; increased elimination half-life of quinidine; increased risk for hypotension !TWARFARIN : Coumarin anticoagulants with quinidine may increase the likelihood of bleeding problems Doses !TDOGS: a) For VPC's or ventricular tachycardia: Quinidine gluconate: 6. 6-22 mg/kg IM q2-4h or q8-12h PO (de layed 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 t oxicity 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) !TCATS: a) 6-16 mg/kg IM or PO q8h (Ware 2000) !THORSES: (Note : ARCI UCGFS Class 4 Drug) a) For atrial ﬁb without signs of heart failure: Keep horse quiet dur ing dosing stage. Monitor ECG either continuously or be-fore each dose. Horses with recent onset (<7 days) or whom de velop 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). Fo r 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 ne cessitate 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 ad verse 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 b pm, 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 fo r 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 oc cur, 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 monit oring levels. (Risberg 2005) Monitoring !TECG, continuous if possible !TBlood pressure, during IV administration !TClinical signs of toxicity (see Adverse Reactions/Overdosage) !TSerum levels. Therapeutic serum levels are believed to range from 2-7 micrograms/m L. Levels >10 mcg/m L are considered toxic. Client Information !TOral products should be administered at evenly spaced intervals throughout the day/night. GI upset may be decreased if admin-istered with food. !TDo not allow animal to chew or crush sustained-release oral dos-age forms. !TNotify veterinarian if animal's condition deteriorates or signs of 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, whit e 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 whit e, amorphous powder. It is sparingly soluble in water and freely soluble in hot 40% alcohol. Quinidine sulfate occurs as very bitter tasting, odorless, ﬁne, nee dle-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 a vailable. Quinidine Polygalacturonate may also be known as: Cardio quin®, Cardioquin®, Cardioquine®, Galactoquin®, Naticardina®, or Neochinidin Ritmocor®.	pppbs.pdf
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 injec tion. 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 VETERINARY-LABELED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 4 substance. See the appendix for more information. HUMAN-LABELED PRODUCTS: 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 v ials; generic (Lilly); (Rx) RAMIPRIL (ram-ih-prill) Altace®, Vasotop® ANGIOTENSIN CONVERTING ENZYME (ACE) INHIBITOR Prescriber Highlights TT ACE inhibitor used primarily as a vasodilator in the treat-ment of heart failure or hypertension; may be of beneﬁt in the treatment of chronic renal failure or protein losing nephropathies TT Not as much information or experience available as some other ACE inhibitors (e. g., enalapril) in dogs or cats TT Contraindications: Hypersensitivity to ACE inhibitors TT Caution: Pregnancy, patients with hyponatremia, coronary or cerebrovascular insufﬁciency, preexisting hematologic abnormalities, or a collagen vascular disease (e. g., SLE) TT Adverse Effects: Appears well tolerated in both dogs & cats. GI effects (anorexia, vomiting, diarrhea) possible; potentially: weakness, hypotension, & 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 dog s 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. Lik e 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 muc h higher afﬁnity for ramiprilat than for angiotensin-I. Because angiotensin-II concentrations are decreased, aldosterone secretion is reduced and plasma renin activity is increased. The cardiovascular effects of ramiprilat in patients with CHF include decreased total peripheral resistance, 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% o f 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 potent ial 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	pppbs.pdf