b'2018 AAEP CONVENTION PREVIEWAuburn Laboratories Inc.,Booth 1236Auburn Laboratories Inc. continues its innovations in nutrition with APF Pro, which the company has developed to address the specific needs of the top-level equine athlete. Building on the unique stress protection of the original APF, APF Pro contains Aralia to sup-port gastric health and Rhaponticumto promote muscle development. APF Pro has been formulated to target the negative metabolic impact of stress and to help protect the equine athlete from the adverse effects of stress encountered during training, traveling, competing, and being housed in unfamiliar surround-ings. Auburn Laboratories Inc. credits the uniquely beneficial herbal ingredients in APF Pro (Eleutherococcus senticosus, Rhodiola rosea, Schizandra chinensis, Ara-lia mandschurica, Rhaponticum cartham-COURTESY AAEPoides) for its multifaceted nutritional sup-port, which the company says provides improved recovery from athletic training, More than 6,000 veterinarians, students, and other industry professionals will have the opportunitypromotes gastric health, may enhance to listen to 100+ hours of horse health presentations. immunomodulation, and helps manage EQUISUL- SDTexposure to this product. If an allergic reaction occurs (e.g., skin rash,is only slightly lower than plasma concentrations. Concentrations ofaThe correlation between in vitro susceptibility data and clinicaltrimethoprim are usually higher in the lungs, kidney, and liver than in theeffectiveness is unknown.blood. Sulfadiazine and trimethoprim are both eliminated primarily bybThe lowest MIC to encompass 50% and 90% of the most susceptiblePRECAUTIONS isolates, respectively.c One isolate of S. equi subsp. zooepidemicus was not tested.(Sulfadiazine/Trimethoprim)Prescribing antibacterial drugs in the absence of a proven or stronglyconcentrations of both sulfadiazine and trimethoprim are several-foldhigher than blood concentrations.1 Sulfadiazine and trimethoprim are Oral Suspension animals and may increase the risk of development of drug-resistant20% and 35% bound to plasma protein, respectively. Administration ofEFFECTIVENESSanimal pathogens. sulfadiazine and trimethoprim with food has no apparent effect on the absorption of sulfadiazine but the absorption of trimethoprim is decreased.effectiveness of EQUISUL-SDT administered at 24 mg/kg body weight, For use in horses only.The administration of antimicrobials, including sulfadiazine and trimetho- orally, twice daily for 10 days for the treatment of lower respiratory tract prim, to horses under conditions of stress may be associated with acuteBased on a study in fed horses, trimethoprim concentrations followinginfections in horses caused by Streptococcus equi subsp. zooepidemicus. NADA 141-360 diarrhea that can be fatal. If acute diarrhea or persistent changes in fecalrepeat oral administration of 24 mg/kg EQUISUL-SDT to 6 horsesIn this study, a total of 182 horses were treated with EQUISUL-SDT, and consistency are observed, additional doses of EQUISUL-SDT should notreached peak concentration in 0.5 to 12.0 hours. The median plasma88 horses were treated with saline. One hundred seventy-three horses CAUTION be administered and appropriate therapy should be initiated. elimination half-life was 3 hours, with a range of 2.31 to 4.96 hours. Peak(112 EQUISUL-SDT and 61 saline) were included in the statistical analysis. Federal law (USA) restricts this drug to use by or on the order of asulfadiazine concentrations were reached within 1.0 to 12.0 hours inTherapeutic success was characterized by absence of fever and no licensed veterinarian. The safe use of EQUISUL-SDT has not been evaluated in breeding, preg- the same study. The median plasma elimination half-life for sulfadiazine nant, or lactating horses. Potentiated sulfonamides should only be used inwas approximately 7.80 hours, with a range of 6.78 to 10.39 hours. Onlyimprovement or resolution of clinical signs of lower respiratory tract infection DESCRIPTION minor accumulation of both drugs was observed following repeat oralby Day 17. The observed success rates are 58.9% (66/112) and 14.8% EQUISUL-SDT is a broad-spectrum antimicrobial from the potentiatedto the fetus. Use of potentiated sulfonamides during pregnancy has beenadministration of EQUISUL-SDT and both drugs reached steady state(9/61) for the EQUISUL-SDT and saline-treated groups, respectively. sulfonamide class of chemotherapeutic agents. These two drugsassociated with an increased risk of congenital abnormalities that mayby day 3. Sulfadiazine and trimethoprim key steady state parameters block different sequential steps in the biosynthesis of nucleic acids.associated with administration in 6 fed horses over a period of 7 daysTable 4 summarizes the statistical analysis results on the overall success rate. Sulfadiazine inhibits bacterial synthesis of dihydrofolic acid by competingplacenta, are excreted in milk, and may cause hyperbilirubinemia-inducedare found in Table 2.with para-aminobenzoic acid. Trimethoprim blocks the productionneurotoxicity in nursing neonates. Table 4. Overall Clinical Effectiveness Resultsof tetrahydrofolic acid from dihydrofolic acid by reversibly inhibitingTable 2. Median (Range) of sulfadiazine and trimethoprim dihydrofolate reductase. The effect of the dual action is to reduce theDecreased hematopoetic activity and blood dyscrasias have been asso- pharmacokinetics parameters following repeat dosing of 24 mg/kgEquisul-SDT Saline P-value*minimum inhibitory concentration of each agent (synergism) and tociated with the use of elevated doses and/or prolonged administrationbid EQUISUL-SDT for 7 days to six horses in fed conditionconvert a bacteriostatic action to a bactericidal action. Sulfadiazine is theof potentiated sulfonamides. EQUISUL-SDT should be discontinued ifLeast Square Means 61% 13.1% 0.0123non-proprietary name for 4-amino-N-2-pyrimidinylbenzenesulfonamide.prolonged clotting times, or decreased platelet, white blood cell or redDrug Sulfadiazine Trimethoprim * P-value and estimated success rates are based on back-transformed Trimethoprim is the non-proprietary name for 5-[(3,4,5trimethoxyphenyl) blood cell counts are observed. mean estimates from the statistical analysis.methyl]-2,4-pyrimidinediamine. Tmax (hr) 4.758.50 Sulfonamides should be used with caution in horses with impaired hepatic(1.0012.00) (0.5012.00)Figure 1. Structure of sulfadiazine function. Although rare, sulfonamide use has been associated withCmax (g/mL) 17.630.78ANIMAL SAFETYfulminant hepatic necrosis in humans. (10.1031.15) (0.601.14) In a target animal safety study, EQUISUL-SDT was administered orally to 32 healthy adult horses at 0 (0X), 24 (1X), 72 (3X), or 120 (5X) mg/kg Neurologic abnormalities have been reported in several species followingAUC 012 (last dose)159.35 5.47 twice daily for 30 days. Loose stool was the most common abnormal administration of potentiated sulfonamides. In horses, potentiated(hr*g/mL) (73.90282.54) (3.3110.91) observation. Observations of loose stool (pellets with liquid or unformed/sulfonamides have been associated with gait alterations and behaviorcowpile stool) occurred more often in horses treated with EQUISUL-SDT changes that resolved after discontinuation of the drug. T 1/2 (hr) 7.80 3.00 with the incidence of loose stool increasing in a dose related manner. All Figure 2. Structure of trimethoprim (6.7810.39) (2.314.96) incidents of loose stool were self-limiting and resolved without treatment. The safe use of EQUISUL-SDT has not been evaluated in horses less than 1 year of age. MICROBIOLOGYEQUISUL-SDT is the combination of the sulfonamide sulfadiazine andhigher mean serum creatinine concentrations, and those in the 3X and ADVERSE REACTIONS trimethoprim. These two drugs block sequential steps in nucleic acids biosynthesis. Sulfadiazine inhibits bacterial synthesis of dihydrofolicalbumin concentrations. Statistically higher mean neutrophil counts and Each mL of EQUISUL-SDT contains 400 mg combined active ingredientsbreeds, ranging from 1 to 25 years of age, which had been treated withacid by competing with para-aminobenzoic acid. Trimethoprim blocksmean serum gamma glutamyl transferase (GGT) activity were seen in either EQUISUL-SDT (n = 182) or with a saline control (n = 88) arethe production of tetrahydrofolic acid from dihydrofolic acid by reversiblythe 1X and 5X groups. Individual animal creatinine, GGT, and albumin (333 mg sulfadiazine and 67 mg trimethoprim) in an aqueous suspension. summarized in Table 1. At least one episode of loose stool of varyinginhibiting dihydrofolate reductase. The two drugs act synergistically,concentrations remained within the reference range. Individual animal severity was observed in 69 of 182 (38%) of the EQUISUL-SDT-treatedreducing the minimum inhibitory concentration of each, while enhancing3/mcL INDICATION horses, and 29 of 88 (33%) saline control horses. Of those animalsthe bacteriostatic action of each separately to a bactericidal actionelevations in absolute neutrophil counts ranged up to 7.09 x 103 /mcL). (reference range: 1.96-5.31 x 10EQUISUL-SDT is indicated for the treatment of lower respiratory tractexperiencing loose stool, 2 of 182 (1.1%) of the EQUISUL-SDT-treatedwhen combined.infections in horses caused by susceptible strains of Streptococcus equihorses and 0 of 88 (0%) placebo-treated horses were removed from theBased upon blood concentrations obtained during the study, it was noted subsp. zooepidemicus. that the sulfadiazine and trimethoprim plasma concentrations did not EQUISUL-SDT administered as a combined sulfadiazine-trimethoprim Both cases of diarrhea in this study were self-limiting and resolved withoutdose of 24 mg/kg body weight twice daily for 7 days provided concen- increase in proportion to dose. For sulfadiazine, a 3X and 5X dose DOSAGE AND ADMINISTRATION treatment within 510 days after discontinuation of EQUISUL-SDT. trations of sulfadiazine and trimethoprim with T>MIC90 (%T) values ofresulted in an average exposure of 2.0X and 2.6X the concentrations Shake well before use. Table 1. Number of Horses with Adverse Reactions During the100% and 98% respectively. The minimum inhibitory concentration (MIC)observed following a 1X dose. For trimethoprim, the corresponding values values for EQUISUL-SDT against indicated pathogens isolated from lowerwere 2.5X and 3.5X as compared to the 1X dose. Furthermore, marked Field Study with EQUISUL-SDT respiratory tract infections in horses enrolled in a 20102011 effective- intersubject variability, particularly with sulfadiazine, resulted in substantial Administer EQUISUL-SDT orally at the dosage of 24 mg combined activeoverlap of individual subject blood levels across the three dosing groups.ingredients per kilogram body weight (10.9 mg/lb) twice daily for 10 days. EQUISUL-SDT can be administered by volume at 2.7 mL per 45.4 kgAdverse Equisul-SDT Saline control accordance with the Clinical and Laboratory Standards Institute (CLSI)STORAGE CONDITIONS(2.7 mL/100 lb) body weight. Reactions (n=182) (n=88) Approved Standard M31-A3 using a broth microdilution system and 3%Store at 5986 F (1530 C). Brief periods up to 104 F (40 C) Loose stool 69 (38%) 29 (33%) lysed horse blood. are permitted. Protect from freezing.CONTRAINDICATIONS (including diarrhea)EQUISUL-SDT is contraindicated in horses with a known allergy toTable 3. Trimethoprim/sulfadiazine minimum inhibitory concentrationHOW SUPPLIEDsulfadiazine, sulfonamide class antimicrobials, or trimethoprim. Colic 3 (1.6%) 2 (2.2%) (MIC) valuesa of isolates recovered from horses with lower respiratoryEQUISUL-SDT is available in the following package sizes:infection caused by Streptococcus equi subsp. zooepidemicus WARNING Diarrhea 2 (1.1%) 0 (0%) treated with EQUISUL-SDT in the U.S. (20102011) 135 mL280 mLDo not use in horses intended for human consumption. To report suspected adverse events, for technical assistance or to560 mLobtain a copy of the MSDS, contact Aurora Pharmaceutical LLC atTreatment Outcome Success Failure 900 mLHUMAN WARNINGS 888-215-1256 or www.aurorapharmaceutical.com. For additionalNumber of Isolates 65c 46Not for use in humans. For use in animals only. Keep this and allinformation about adverse drug experience reporting for animal[footnote]drugs out of the reach of children. Consult a physician in the casedrugs, contact FDA at 1-888-FDA-VETS or online at http://www.fda. Time of Sample Collection Pre-Treatment Pre-Treatmentof accidental human exposure. gov/AnimalVeterinary/SafetyHealth. MIC 50b (g/mL) 0.25/4.75 0.25/4.75 1Kahn CM, Line S, eds.The Merck Veterinary Manual.Antimicrobial drugs, including sulfonamides, can cause mild toCLINICAL PHARMACOLOGY MIC 90b (g/mL) 0.25/4.75 0.25/4.75 10th Ed. Merck & Co. 2010.severe allergic reactions in some individuals. Avoid direct contactFollowing oral administration, EQUISUL-SDT is rapidly absorbed and of the product with the skin, eyes, mouth, and clothing. Persons withwidely distributed throughout body tissues. Sulfadiazine levels are usuallyMIC Range (g/mL) 0.12/2.40.12/2.4 a known sensitivity to sulfonamides or trimethoprim should avoidhighest in the kidney, while the tissue concentration in other tissuesto 0.5/9.5 to 0.5/9.538November 2018The Horse | TheHorse.com'