Clodrophos x 15 ml.

PRODUCT AVAILABLE FOR EXPORT ONLY. CLODROPHOS® Injectable Disodium clodronate injection, 60 mg/mL THERAPEUTIC CLASSIFICATION: Bisphosphonate. DESCRIPTION: Disodium clodronate is a non-aminated, chlorine-containing bisphosphonate. Chemically, disodium clodronate is a disodium salt of (dichloromethylene)diphosphonic acid and is manufactured from the tetrahydrate form. ACTIVE INGREDIENTS: Each mL contains 60 mg of disodium clodronate (as disodium clodronate tetrahydrate) INDICATIONS: For the management of clinical signs associated with navicular syndrome in horses. DOSAGE AND ADMINISTRATION: Administer by intramuscular injection. Divide the total volume of the CLODROPHOS injection to be administered evenly among two (2) or three (3) separate injection sites. The recommended dose is 1.8 mg of disodium clodronate per kilogram of body weight (3 mL per 100 kg of body weight), up to a maximum dose of 900 mg (15 mL) per horse. Clinical improvement is most evident 2 months after treatment (see EFFICACY). If there is no response to initial therapy, the horse should be reevaluated. For horses that initially respond to a CLODROPHOS injection but do not maintain clinical improvement for 6 months, CLODROPHOS may be re-administered at 3- to 6-month intervals depending on the recurrence of clinical signs. For horses that respond to a CLODROPHOS injection and maintain clinical improvement for 6 months, the CLODROPHOS injection should be readministered after clinical signs reappear. CONTRAINDICATIONS: - Do not use injectable CLODROPHOS in horses with known hypersensitivity to disodium clodronate. - Do not use this product in horses with impaired renal function or a history of renal disease. PRECAUTIONS: - The effect of bisphosphonates on the skeletal system of growing horses has not been studied. The safe use of injectable CLODROPHOS in breeding horses or in pregnant or lactating mares has not been evaluated. - Ensure that horses are adequately hydrated when administering the product. - Concomitant administration of other potentially nephrotoxic drugs should be approached with caution, and renal function should be monitored. WARNINGS: - Keep out of reach of children. - Avoid contact with the skin or eyes. Accidental spills on the skin or in the eyes should be washed off with water. INFORMATION FOR HORSE OWNERS: Owners should be advised to observe their horse for at least 2 hours after treatment for signs of colic, agitation, and/or nervous system abnormalities. If a horse appears uncomfortable, nervous, or experiences cramps after treatment, the owner should be advised to lead the horse by hand for 15 minutes until the symptoms subside. Owners should be advised to contact their veterinarian if the horse shows any abnormal clinical signs. CLINICAL PHARMACOLOGY: Disodium clodronate is a nitrogen-free bisphosphonate that inhibits bone resorption by binding to hydroxyapatite crystals (inhibiting their formation and dissolution) and exerting direct cellular effects on osteoclasts (inhibiting osteoclast function). It has a high affinity for calcium phosphate in the solid phase and, therefore, accumulates in the bones. Once bound to the bone matrix, disodium clodronate enters osteoclasts undergoing resorption, alters their morphology, and reduces the number of active osteoclasts, regardless of the cause of osteoclast activity. Disodium clodronate increases bone mass by inhibiting bone resorption and slowing bone turnover. The structural formula of disodium clodronate is: In humans, 60 to 80% of intravenously administered disodium clodronate is excreted unchanged in the urine and 5% in the feces; The remainder of the dose is distributed to the bone. The bone residence time in horses could not be estimated. However, in numerous studies, the half-life of disodium clodronate in rodent bones (long bones and lumbar vertebrae) has been estimated to range from months to years. The pharmacokinetic profile of CLODROPHOS injectable following a single intramuscular administration in horses diagnosed with navicular syndrome at doses of 300 mg, 900 mg, and 1500 mg of disodium clodronate is characterized by rapid absorption of clodronic acid (0.5–0.7 h) and a more prolonged terminal elimination phase. The area under the plasma concentration-time curve (AUC) and the maximum concentration (Cmax) increased proportionally with the dose. A 900-mg dose administered intramuscularly has a plasma half-life of approximately 5.6 ± 2.6 hours, a Cmax of 7.5 ± 1.7 μg/mL, and a time to peak concentration (Tmax) of approximately 0.6 hours