b'O SPHOS(clodronate injection)Bisphosphonate. For use in horses only.Brief Summary (For Full Prescribing Information, see package insert)CAUTION: Federal (USA) law restricts this drug to use by or onthe order of a licensed veterinarian.DESCRIPTION: Clodronate disodium is a non-amino, chloro- containing bisphosphonate. Chemically, clodronate disodium is (dichloromethylene) diphosphonic acid disodium salt and ismanufactured from the tetrahydrate form.INDICATION: For the control of clinical signs associated with navicular syndrome in horses.CONTRAINDICATIONS: Horses with hypersensitivity to clodronatedisodium should not receive OSPHOS. Do not use in horses with impaired renal function or with a history of renal disease.WARNINGS: Do not use in horses intended for human consumption.HUMAN WARNINGS: Not for human use. Keep this and all drugs out of the reach of children. Consult a physician in case of accidental human exposure.PRECAUTIONS: OSPHOS has been associated with renal toxicity.Concurrent administration of other potentially nephrotoxic drugs should be approached with caution and renal function should be monitored. Use of bisphosphonates in patients with conditions or diseases affecting renal function is not recommended. Horses should be well-hydrated prior to and after the administration of OSPHOS due to the potential for adverse renal events. Water intake and urine output should be monitored for 3-5 days post-treatment and any changes from baseline should elicit further evaluation. As a class, bisphosphonates may be associated with gastrointestinal and renal toxicity. Sensitivity to drug associated adverse reactions varies with the individual patient. Renal and gastrointestinal adverse reactions may be associated with plasma concentrations of the drug. Bisphosphonates are excreted by the kidney; therefore, conditions causing renalimpairment may increase plasma bisphosphonate concentrations resulting in an increased risk for adverse reactions. Concurrent administration of other potentially nephrotoxic drugs should be ap- proached with caution and renal function should be monitored. Use of bisphosphonates in patients with conditions or diseases affecting renal function is not recommended. Administration of bisphosphonates hasbeen associated with abdominal pain (colic), discomfort, and agitation Ein horses. Clinical signs usually occur shortly after drug administration and may be associated with alterations in intestinal motility. In horses Ntreated with OSPHOS these clinical signs usually began within 2 hours of treatment. Horses should be monitored for at least 2 hours following administration of OSPHOS.I Bisphosphonates affect plasma concentrations of some minerals and Lelectrolytes such as calcium, magnesium and potassium, immediately post-treatment, with effects lasting up to several hours. Caution Pshould be used when administering bisphosphonates to horses with conditions affecting mineral or electrolyte homeostasis (e.g. hyperka-I lemic periodic paralysis, hypocalcemia, etc.).The safe use of OSPHOS has not been evaluated in horses less Cthan 4 years of age. The effect of bisphosphonates on the skeleton of growing horses has not been studied; however, bisphosphonates ISinhibit osteoclast activity which impacts bone turnover and may affect bone growth.Bisphosphonates should not be used in pregnant or lactating mares,Dor mares intended for breeding. The safe use of OSPHOS has not been evaluated in breeding horses or pregnant or lactating mares. Bisphosphonates are incorporated into the bone matrix, from where Ethey are gradually released over periods of months to years. The INextent of bisphosphonate incorporation into adult bone, and hence, the amount available for release back into the systemic circulation, is directly related to the total dose and duration of bisphosphonate Uuse. Bisphosphonates have been shown to cause fetal developmental F Qabnormalities in laboratory animals. The uptake of bisphosphonates OR EVE into fetal bone may be greater than into maternal bone creating a ERY possible risk for skeletal or other abnormalities in the fetus. Many drugs, including bisphosphonates, may be excreted in milk and may be absorbed by nursing animals.Increased bone fragility has been observed in animals treated with bisphosphonates at high doses or for long periods of time. Bisphosphonates inhibit bone resorption and decrease bone turnover which may lead to an inability to repair micro damage within the bone. In humans, atypical femur fractures have been reported in patients on long term bisphosphonate therapy; however, a causal relationship has not been established.ADVERSE REACTIONS: The most common adverse reactions reported in the field study were clinical signs of discomfort or nervousness, colic and/or pawing. Other signs reported were lip licking, yawning, head shaking, injection site swelling, and hives/pruritus.The intramuscularPOST-APPROVAL EXPERIENCE (December 2018): The following adverse events are based on post-approval adverse drug experience reporting. Not all adverse events are reported to FDA/CVM. It is not bisphosphonate injection always possible to reliably estimate the adverse event frequency or establish a causal relationship to product exposure using these data.The following adverse events are listed in decreasing order of reporting frequency: renal failure, polyuria, polydipsia, abdominal pain, for control of clinical signsanorexia, lethargy, hypercalcemia, behavioral disorder, discomfort, hyperkalemia, hyperactivity, recumbency, hyperthermia, injection site reactions, muscle tremor, urticaria, hyperglycemia, and fracture. In associated with Navicular Syndromesome cases, death has been reported as an outcome of the adverse Learn more onlineevents listed above.INFORMATION FOR HORSE OWNERS: Owners should be advised to:in horses 4 years of age and olderNOT administer NSAIDs.www.dechra-us.com Ensure horses have access to adequate water before andwww.osphos.comafter administration of OSPHOS. Observe their horse for at least 2 hours post-treatment forsigns of colic, agitation, and/or abnormal behavior.As with all drugs, side effects may occur. The most common adverse reactions reported in the field study were clinical If a horse appears uncomfortable, nervous, or experiences signs of discomfort or nervousness, colic and/or pawing. Other signs reported were: lip licking, yawning, head shaking, cramping post-treatment, hand walk the horse for 15 minutes. injection site swelling, and hives/pruritus. Osphos should not be used in pregnant or lactating mares, or mares If signs do not resolve contact the veterinarian. Monitor water intake and urine output for 3-5 days post-treatment.intended for breeding. Use of Osphos in patients with conditions affecting renal function or mineral or electrolyte Contact their veterinarian if the horse displays abnormalhomeostasis is not recommended. Refer to the prescribing information for complete details or visit www.osphos.com.clinical signs such as changes in drinking and urination,appetite, and attitude.CAUTION: Federal law restricts this drug to use by or on the order of licensed veterinarian.Manufactured for: Dechra Veterinary Products7015 College Blvd., Suite 525, Overland Park, KS 66211 * Freedom of Information Summary, Original New Animal Drug Application, approved by FDA under NADA # 141-427, for OSPHOS. April 28, 2014.866-933-2472Dechra Veterinary Products US and the Dechra D logo are registered trademarks of Dechra Pharmaceuticals PLC. 2019 Dechra Ltd.2019 Dechra Ltd. OSPHOS is a registered trademark of Dechra Ltd. All rights reserved. Approved by FDA under NADA # 141-427'