ETIDRONATE DISODIUM

Chemistry - An analog of pyrophosphate, etidronate disodium (also known as EHDP, Na2EHDP, or sodium etidronate) is a biphosphonate agent that occurs as a white powder and is freely soluble in water. Unlike pyrophosphate, etidronate is resistant to enzymatic degradation in the gut.

Storage, Stability, Compatibility

Store tablets in tight containers at room temperature. After dilution, the injectable product is stable for 48 hours at room temperature.

Pharmacology - ETIDRONATE DISODIUM

Etidronate's primary site of action is bone. It reduces normal and abnormal boneresorption. This effect can reduce hypercalcemia associated with malignant neoplasms. Etidronatecan also increase serum phosphate concentrations, presumably by increasing the renal tubularreabsorption of phosphate. Some early studies in lab animals suggest that etidronate may inhibit theformation of bone metastases with some tumor types.
Uses, Indications - The primary use in small animals at this time for etidronate is in the treatmentof severe hypercalcemia associated with neoplastic disease. Etidronate is also indicated in humansfor the treatment of Paget's disease and heterotopic ossification (e.g., after total hip replacement). Itis being evaluated for the treatment of osteoporosis in humans as well.

Pharmacokinetics - ETIDRONATE DISODIUM

Oral absorption is poor and dose dependent. As little as 1% of a dose(smaller doses) may be absorbed; with higher doses, 6-10% may be absorbed. After oral dosing, the drug is rapidly cleared from blood and 50% of the drug absorbed goes into bone. At usualdoses, it appears that etidronate does not cross the placenta. Duration of effect may be very prolonged. In humans, effects have persisted for up to one year after discontinuation in patient's with
Paget's disease. Effects for hypercalcemia may last for 11 days. Absorbed etidronate is excretedunchanged by the kidneys. Approximately 50% of the absorbed dose is excreted within 24 hours, the remainder is chemisorbed to bone and then slowly eliminated.

Contraindications, Precautions, Reproductive Safety

Etidronate is considered contraindicatedfor the treatment of hypercalcemia in patients with renal function impairment (serum creatinines > 5mg/dl). Risk vs. benefit should be carefully considered in patients with bone fractures (delayshealing), enterocolitis (higher risk of diarrhea), cardiac failure (especially with parenteral etidronateas patients may not tolerate the extra fluid load) or in patients with renal function impairment(serum creatinines 2.5 - 5 mg/dl).
Etidronate's safety during pregnancy has not been established. Rabbits given oral doses 5 timesthose recommended in humans, demonstrated no overt problems with offspring. Rats given verylarge doses IV, showed skeletal malformations. It is unknown if the drug enters milk.

Adverse Effects, Warnings

Adverse effects are not well described in small animals. In humans, diarrhea and nausea (with higher oral doses), and bone pain/tenderness are most the likely adverseeffects reported.
Do not confuse etidronate with etretinate or etomidate.

Overdosage, Acute Toxicity

Very little information is available at this time. Overdoses may result in hypocalcemia (ECG changes may occur), bleeding problems (secondary to rapid chelation ofcalcium) and proximal renal tubule damage.
Use standard gut emptying protocols after oral ingestion when warranted. IV calcium administration (e.g., calcium gluconate) may be used to reverse hypocalcemia. Intensive monitoring issuggested.

Drug Interactions

Absorption of oral etidronate may be inhibited by antacids (containingcalcium, magnesium or aluminum), milk or other foods high in calcium content, ormineral supplements or medications containing iron, magnesium, calcium or aluminum.
Separate etidronate doses from these substances by at least two hours.
Laboratory Considerations - Etidronate may interfere with bone uptake of technetium Tc 99mmedronate or technetium Tc 99m oxidronate