DIHYDROTACHYSTEROL, DHT

Chemistry - A vitamin D analog, dihydrotachysterol (DHT) occurs as odorless, colorless or whitecrystals, or crystalline white powder. It is practically insoluble in water, sparingly soluble invegetable oils, and soluble in alcohol. Dihydrotachysterol may also be known as DHT, dichysterol, or dihydrotachysterol2.

Storage, Stability, Compatibility

All DHT products should be stored at room temperature (15-30°C). Capsules or tablets should be stored in well-closed, light-resistant containers and the oral concentrate should be stored in tight, light-resistant containers.

Pharmacology - DIHYDROTACHYSTEROL, DHT

DHT is hydroxylated in the liver to 25-hydroxy-dihydrotachysterol which is the active form of the drug and is an analog of 1, 25-dihydroxyvitamin D. Vitamin D is considered a hormone and, in conjunction with parathormone (PTH) and calcitonin, regulates calcium home-ostasis in the body. Active analogues (or metabolites) of vitamin D enhance calcium absorption from the GI tract, promote reabsorption of calcium by the renal tubules, and increase the rate of accretion and resorption of minerals in bone.

Uses, Indications

DHT is used in small animals to treat hypocalcemia secondary to hypoparathyroidism or severe renal disease.

Pharmacokinetics - DIHYDROTACHYSTEROL, DHT

If fat absorption is normal, vitamin D analogs are readily absorbed from the GI tract (small intestine). Bile is required for adequate absorption and patients with steatorrhea, liver or biliary disease will have diminished absorption. DHT is hydroxylated in the liver to 25-hydroxydihydrotachysterol which is the active form of the drug. Unlike some other forms of vitamin D, DHT does not require parathormone activation in the kidneys.

Contraindications, Precautions, Reproductive Safety

DHT is contraindicated in patients withhypercalcemia, vitamin D toxicity, malabsorption syndrome, or abnormal sensitivity to the effects ofvitamin D. It should be used with extreme caution in patients with hyperphosphatemia (manyclinicians believe hyperphosphatemia or a combined calcium/phosphorous product of > 70 mg/dl isa contraindication to its use), or in patients with renal dysfunction (when receiving the drug for non-renal indications).

Adverse Effects, Warnings

Hypercalcemia, nephrocalcinosis and hyperphosphatemia are potential complications of DHT therapy. Symptoms of hypercalcemia include polydipsia, polyuria and anorexia. Monitoring of serum calcium levels is mandatory while using this drug

Overdosage, Acute Toxicity

Acute ingestions should be managed using established protocolsfor removal or prevention of the drug being absorbed from the GI. Orally administered mineral oilmay reduce absorption and enhance fecal elimination.
Hypercalcemia secondary to chronic dosing of the drug should be treated by first temporarily discontinuing DHT and exogenous calcium therapy. If the hypercalcemia is severe, furosemide, calcium-free IV fluids (e.g., normal saline), urine acidification, and corticosteroids may be employed. Because of the long duration of action of DHT (up to one week), hypercalcemia may persist. Restart DHT/calcium therapy at a reduced dosage with diligent monitoring when calcium serum levels return to the normal range.

Drug Interactions

Magnesium containing antacids may cause hypermagnesemia when usedwith vitamin D analogs.
Thiazide diuretics may cause hypercalcemia when given in conjunction with Vitamin D analogs.
Corticosteroids can nullify the effects of vitamin D analogs.
Phenytoin, barbiturates or primidone may induce hepatic enzyme systems and increase the metabolism of Vitamin D analogs thus decreasing their activity.
Patients on verapamil or digoxin are sensitive to the effects of hypercalcemia; intensified monitoring is required.
Mineral oil, sucralfate, cholestyramine, or colestipol may reduce the amount of drug absorbed.
Drug/Laboratory Interactions - Serum cholesterol levels may be falsely elevated by vitamin D analogs when using the Zlatkis-Zak reaction for determination.