Description: Dihydrotachysterol is an oral vitamin D analog. Many vitamin D analogs are commercially available, but the responsiveness of various conditions differs based on the pharmacologic properties of each vitamin D analog. Dihydrotachysterol is more expensive than ergocalciferol; however, it is preferred over ergocalciferol in patients with renal failure because of impaired synthesis of ergocalciferol to its most active form by the kidneys. Dihydrotachysterol is indicated in hypocalcemia associated with hypoparathyroidism and chronic or idiopathic tetany. Dihydrotachysterol was approved prior to 1982. Mechanism of Action: The activated form of dihydrotachysterol increases the intestinal absorption of calcium and promotes the mobilization of calcium from bone. Phosphaturia likely occurs secondary to increased calcium levels. In patients with chonic renal failure, dihydrotachysterol increases calcium absorption from the GI tract, decreases elevated parathyroid hormone and serum alkaline phosphatase levels, and reverses renal osteodystrophy and muscle weakness. This vitamin D analog has only weak antirachitic activity. Pharmacokinetics: Dihydrotachysterol is administered orally and is well absorbed if fat absorption is normal. Increased calcium concentrations occur several hours after administration. A maximal effect is usually observed in 2 weeks. The duration of action is approximately 2 weeks but can extend up to 9 weeks. Dihydrotachysterol is distributed and stored primarily in the liver. It is bound in plasma to alpha-globulins. Dihydrotachysterol is a reduction product of ergocalciferol. Activation occurs through conversion to 25-hydroxydihydrotachysterol in the liver. Unlike calcifediol, further conversion by the kidneys is not required. Elimination of vitamin D analogs and their metabolites occurs principally through the bile, with the remainder excreted renally.

Indications...Dosage For the treatment of hypocalcemia associated with hypoparathyroidism: Oral dosage: Adults and adolescents: Initially, 0.75�2.5 mg PO once daily for 4 days, then 0.2�1 mg PO once daily. Maximum maintenance dose is 1.5 mg/day. Children and infants: Initially, 1�5 mg PO once daily for 4 days, then 0.5�1.5 mg PO once daily. Neonates: 0.05�0.1 mg PO once daily. For the treatment of familial hypophosphatemia�: Oral dosage: Adults and children: Initially, 0.5�2 mg PO once daily. The usual maintenance dosage is 0.2�1.5 mg PO once daily. For the treatment of renal osteodystrophy�: Oral dosage: Adults: 0.1�0.6 mg PO once daily. Adolescents and children: 0.1-0.5 mg PO once daily. For the treatment of hypocalcemic tetany: Oral dosage: Adults: Initially, 0.75�2.5 mg PO once daily for 3 days. The usual maintenance dosage is 0.25 mg PO per week to 1 mg once daily, as needed. Children: Dosage not established. Patients with renal impairment: Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed. �non-FDA-approved indication

Oral Administration �All dosage forms: Dihydrotachysterol may be administered without regard to meals. �Oral solution: Administer using calibrated measuring device provided by the manufacturer to ensure dosage accuracy.

Contraindications Dihydrotachysterol should not be given to patients with hypercalcemia or hypervitaminosis D. Hypercalcemia can lead to soft tissue calcification and other toxicities. This should be considered when contemplating the use of vitamin D under these conditions. Dihydrotachysterol should be administered with caution to patients with cardiac disease, arteriosclerosis, or those receiving digoxin because hypercalcemia with cardiac arrhythmias can result. Vitamin D is classified as pregnancy category C. Problems in humans from normal daily intake of vitamin D have not been documented; however, hypercalcemia during pregnancy has been associated with suppression of parathyroid hormone in the neonate, resulting in mental retardation and congenital aortic stenosis. The risks to benefits of untreated hypoparathyroidism or hypophosphatemia in the mother should be considered before using vitamin D. This vitamin is distributed in small amounts into breast milk. The use of vitamin D during breast-feeding is controversial. Large doses of this vitamin should be avoided. Serum calcium concentrations in the infant should be monitored when using vitamin D in a nursing mother. Vitamin D should be used cautiously in those with hyperphosphatemia due to the risk of metastatic calcification, and it should be avoided in patients with renal osteodystrophy with hyperphosphatemia. Treatment with vitamin D may be initiated after stabilization of phosphorus levels. Use of excessive doses acutely or for a prolonged period can result in vitamin D-induced hypercalcemia manifest as nephrocalcinosis and other calcifications. These adverse reactions can be significant in patients with renal failure, even with usual dosages. Vitamin D analogs should be used with caution in patients with renal disease. Patients with sarcoidosis, and possibly other granulomatous diseases, may have increased sensitivity to the effects of vitamin D. Dihydrotachysterol should be used with caution in patients with hypoparathyroidism. Calcium or parathyroid hormone may need to be added to therapy

Interactions The use of other vitamin D analogs with dihydrotachysterol is not recommended because of the increased potential for additive effects and toxicity. In addition, due to dihydrotachysterol-induced increased serum phosphorus levels, concurrent administration of phosphorus salts may increase the toxicity of dihydrotachysterol. Magnesium-containing antacids and supplemental magnesium salts should be used cautiously in patients receiving dihydrotachysterol. Because vitamin D analogs can increase serum magnesium concentrations, the combined use of dihydrotachysterol and magnesium-containing antacids should be avoided, if possible, in patients with chronic renal failure. The concurrent use of vitamin D with calcium-containing antacids or othe calcium salts can cause hypercalcemia; in some patients, however, this combination may be beneficial. The chronic use of aluminum-containing antacids for hyperphosphatemia in conjunction with vitamin D can lead to increased aluminum concentrations and toxicity. This is of primary significance in patients with renal failure. Anticonvulsants, such as phenobarbital, phenytoin, and primidone, can decrease the activity of vitamin D by increasing its metabolism. In rare cases, this has caused anticonvulsant-induced rickets and osteomalacia. Vitamin D supplementation may be required in patients with inadequate dietary intake of vitamin D who are receiving chronic treatment with anticonvulsants. Dihydrotachysterol should be administered with caution to patients with cardiac disease or those receiving cardiac glycosides. Vitamin D may cause hypercalcemia which may affect the actions of the cardiac glycoside and/or lead to cardiac arrhythmias. Cholestyramine, colestipol, or mineral oil can decrease the intestinal absorption of dihydrotachysterol. If used concurrently, administration of the two agents should be staggered for the longest time interval possible. Orlistat decreases the body's absorption of dietary fat, which also affects the absorption of fat soluble vitamins. Concomitant use of thiazide diuretics and dihydrotachysterol in patients with hypoparathyroidism can result in hypercalcemia, which is likely due toincreased release of calcium from the bone. This condition may be transient or require discontinuation of the vitamin D analog.

Adverse Reactions Hypervitaminosis D, manifest as hypercalcemia, can occur. Early signs of hypercalcemia include fatigue, somnolence, headache, anorexia, xerostomia, metallic taste, nausea/vomiting, abdominal cramps, constipation, diarrhea, vertigo, tinnitus, ataxia, exanthema, myalgia, arthralgia, and irritability. Polyuria, photophobia, anorexia, rhinorrhea, hyperthermia, cardiac arrhythmias, and hypertension are all late symptoms of hypercalcemia. Dihydrotachysterol should be discontinued if symptoms become severe. Therapy with dihydrotachysterol should be started at the lowest dose and serum calcium levels monitored throughout treatment. Dietary calcium intake also should be estimated and adjusted, if necessary, to avoid hypercalcemic effects. In conditions of hypercalcemia, reduction in calcium intake in the diet is advocated along with an increase in fluid intake. Vitamin D increases the absorption of phosphorus and may cause hyperphosphatemia, especially in those with renal failure. Dosage adjustments may be required for patients receiving aluminum-containing antacids for the treatment of hyperphosphatemia

Dihydrotachysterol DHT�, Hytakerol�