Cholecalciferol (vitamin D3) is used both as a dietary supplement and a rodenticide. It appears to be toxic at a much lower dose when consumed in a bait form than when ingested as a technical grade agent. Most rodenticide baits contain 0.075% cholecalciferol. Incidence of vitamin D3 toxicosis in animals is relatively less than that of anticoagulant and bromethalin toxicosis. Relay toxicosis from vitamin D3 has not been documented. One international unit (1 IU) of vitamin D3 in nutritional supplement is equivalent to 0.025 mcg of cholecalciferol.
Cholecalciferol toxicosis is characterized by hyperphosphatemia and hypercalcemia, leading to renal failure, cardiac abnormalities, hypertension, CNS depression, anorexia, vomiting, diarrhea, and lethargy. The increased calcium and phosphorus can lead to calcification of soft tissue, notably the highly vascular areas of kidneys and lungs, as well as within the walls of the great blood vessels.
Clinical signs generally develop within 18–36 hr of ingestion; initial signs can include depression, anorexia, polyuria, and polydipsia. The serum phosphorus more commonly rises first, at ~12–24 hr after ingestion, with serum calcium levels rising within another 12–24 hr. Nausea, vomiting, hematemesis, and depression are common as the clinical signs progress. It is important to obtain a baseline biochemistry profile as early as possible after the exposure, so that each animal can be monitored based on individual values.
Ingestion of vitamin D3 at >0.1 mg/kg may require decontamination (induction of emesis and administration of activated charcoal) and monitoring of serum calcium, phosphorus, and renal values. Emesis can be induced within 2 hr of exposure with 3% hydrogen peroxide or apomorphine in dogs and xylazine in cats. Activated charcoal at 1–2 g/kg is an appropriate initial dose for decontamination, and a second half dose after ~6–8 hr may be helpful. In addition, use of cholestyramine, a bile acid sequestrant, may be useful to decrease the body burden of vitamin D3 that undergoes enterohepatic recirculation with bile acids. However, the efficacy of cholestyramine to reduce vitamin D3 levels in dogs has not been determined. The recommended dosage is 0.3–0.5 g/kg, dissolved in liquid and administered orally every 6–8 hr for 3–5 days, depending on the initial dose of cholecalciferol ingested. Premature initiation of calciuresis (see below) may disrupt normal calcium-phosphorus metabolism, triggering osteoclasts to move additional calcium into the blood stream, artificially increasing serum calcium and phosphorus levels and mimicking vitamin D3 toxicosis.
Once the biochemical values begin to increase, there are two approaches to management. The first is to promote calciuresis by administering normal (0.9%) saline at 2–3 times normal rates. Furosemide at 2.5–4.5 mg/kg, PO, every 6–8 hr promotes calcium excretion but can also increase fluid loss (so hydration status should be monitored). Prednisolone at 1–3 mg/kg, PO, bid-tid, can reduce bone resorption as well as decrease calcium absorption from the intestine. Treatment with a phosphate binder (aluminum hydroxide 30–90 mg/kg, PO, in divided doses) to decrease phosphorus absorption and feeding a diet low in calcium should also be considered.
The preferred treatment for persistent significant hypercalcemia is pamidronate, an injectable bisphosphonate that inhibits osteoclastic bone resorption. It is administered at 1.3–2 mg/kg via slow IV infusion in saline over 2 hr. After administration, as the calcium and phosphorus levels start to decrease, supportive therapies (furosemide, prednisolone) should be tapered. A repeat dose may be required if significant hypercalcemia redevelops.
In the past, use of salmon calcitonin (administered at 4–6 IU/kg, SC, every 2–3 hr) has been suggested to decrease calcium and phosphorus levels, but this treatment is no longer used commonly. The two major disadvantages are that some animals may become refractory to calcitonin, and that once this therapy is instituted the use of pamidronate is not helpful.
Calcium and phosphorus levels should be monitored and treated until they return to baseline. Treatment may have to be continued for days or weeks because of the lipophilic nature of vitamin D3. Renal function should be monitored, and other clinical signs treated as needed.