Prescription Drugs

CLINICAL PHARMACOLOGY Dihydrotachysterol is hydroxylated in the liver to 25-hydroxydihydrotachysterol, which is the major circulating active form of the drug. It does not undergo further hydroxylation by the kidney and therefore is the analogue of 1, 25-dihydroxyvitamin D. Dihydrotachysterol is effective in the elevation of serum calcium by stimulating intestinal calcium absorption and mobilizing bone calcium in the absence of parathyroid hormone and of functioning renal tissue. Dihydrotachysterol also increases renal phosphate excretion. In contrast to parathyroid extract, dihydrotachysterol is active when taken orally, exerts a slow but persistent effect, and may be used for long periods without increasing the dosage or causing tolerance. Dihydrotachysterol is faster-acting than pharmacologic doses of vitamin D and is less persistent after cessation of treatment, thus decreasing the risk of accumulation and of hypercalcemia.

DHT™ Tablets (Dihydrotachysterol Tablets USP): 0.125mg, 0.4mg DESCRIPTION Each tablet contains: Dihydrotachysterol 0.125 mg, 0.2 mg, or 0.4 mg. Each mL of Intensol TM Oral Solution (Concentrate) contains: Dihydrotachysterol.............................. 0.2 mg Alcohol 20% Dihydrotachysterol is a synthetic reduction product of tachysterol, a close isomer of vitamin D. Chemically dihydrotachysterol is 9, 10-Secoer-gosta-5, 7,22-tri-en-3b-ol, which can be represented by the following molecular formula C28H46O with a molecular weight of 398.65. Its chemical structure is: Dihydrotachysterol acts as a blood calcium regulator. Inactive ingredients: The tablets contain butylated hydroxyanisole, FD&C Red No. 3 (0.2 mg only), lactose, magnesium stearate, propyl gallate, starch, and sucrose.

INDICATIONS Dihydrotachysterol is indicated for the treatment of acute, chronic, and latent forms of postoperative tetany, idiopathic tetany, and hypoparathyroidism. DOSAGE AND ADMINISTRATION The dosage depends on the nature and seriousness of the disorder and should be adapted to each individual patient. Serum calcium levels should be maintained between 9 to 10 mg per 100 mL. The following dosage schedule will serve as a guide: Initial dose: 0.8 mg to 2.4 mg daily for several days. Maintenance dose: 0.2 mg to 1.0 mg daily as required for normal serum calcium levels. The average maintenance dose is 0.6 mg daily. This dose may be supplemented with 10 to 15 grams of calcium lactate or gluconate by mouth daily. HOW SUPPLIED DHTTM Dihydrotachysterol Tablets USP 0.125 mg white tablets (Tablets identified 54 280). NDC 0054-8172-25: Unit dose, 10 tablets per strip, 10 strips per shelf pack, 10 shelf packs per shipper. NDC 0054-4190-19: Bottles of 50 Tablets 0.2 mg pink tablets (Identified 54 903). NDC 0054-8182-25: Unit dose, 10 tablets per strip, 10 strips per shelf pack, 10 shelf packs per shipper. NDC: 0054-4189-25: Bottles of 100 Tablets 0.4 mg white tablets (Tablets Identified 54 772). NDC 0054-4191-19: Bottles of 50 Tablets DHTTM Dihydrotachysterol IntensolTM 0.2 mg per mL NDC 0054-3170-44: Bottles of 30 mL with calibrated dropper (graduated 0.25 mL to 1.0 mL). Caution: Federal law prohibits dispensing without prescription.

PATIENT INFORMATION See WARNINGS,PRECAUTIONS and CONTRAINDICATIONS.

OVERDOSE The effects of dihydrotachysterol can persist for up to one month after cessation of treatment. Manifestations: Toxicity associated with dihydrotachysterol is similar to that seen with large doses of vitamin D. Overdosage is manifested by symptoms of hypercalcemia, i.e., weakness, headache, anorexia, nausea, vomiting, abdominal cramps, diarrhea, constipation, vertigo, tinnitus, ataxia, hypotonia, lethargy, depression, amnesia, disorientation, hallucinations, syncope, and coma. Impairment of renal function may result in polyuria, polydipsia, and albuminuria. Widespread calcification of soft tissues, including heart, blood vessels, kidneys, and lungs, can occur. Death can result from cardiovascular or renal failure. Treatment: Treatment of overdosage consists of withdrawal of dihydrotachysterol, bed rest, liberal intake of fluids, a low-calcium diet, and administration of a laxative. Hypercalcemic crisis with dehydration, stupor, coma, and azotemia requires more vigorous treatment. The first step should be hydration of the patient. Intravenous saline may quickly and significantly increase urinary calcium excretion. A loop diurectic (furosemide or ethacrynic acid) may be given with the saline infusion to further increase renal calcium excretion. Other reported therapeutic measures include dialysis or the administration of citrates, sulfates, phosphates, corticosteroids, EDTA (ethylenediaminetetraacetic acids), and mithramycin via appropriate regimens. CONTRAINDICATIONS Contraindicated in patients with hypercalcemia, abnormal sensitivity to the effects of vitamin D, and hypervitaminosis D.

SIDE EFFECTS No information provided. DRUG INTERACTIONS Administration of thiazide diuretics to hypoparathyroid patients who are concurrently being treated with dihydrotachysterol may cause hypercalcemia.

WARNINGS No information provided. PRECAUTIONS General The difference between therapeutic dose and intoxicating dose may be small in any patient and therefore dosage must be individualized and periodically reevaluated. In patients with renal osteodystrophy accompanied by hyperphosphatemia, maintenance of a normal serum phosphorus level by dietary phosphate restriction and/or administration of aluminum gels as intestinal phosphate binders is essential to prevent metastatic calcification. Because of its effect on serum calcium, dihydrotachysterol should be administered to pregnant patients or to patients with renal stones only when, in the judgment of the physician, the potential banefits outweigh the possible hazards. Laboratory Tests To prevent hypercalcemia, treatment should always be controlled by regular determinations of blood calcium level, which should be maintained within the normal range. Drug Interactions Administration of thiazide diuretics to hypoparathyroid patients who are concurrently being treated with dihydrotachysterol may cause hypercalcemia. Pregnancy Teratogenic Effects -Pregnancy Category C: Animal reproduction studies have shown fetal abnormalities in several species associated with hypervitaminosis D. These are similar to the supravalvular aortic stenosis syndrome described in infants by Black in England (1963). This syndrome was characterized by supravalvular aortic stenosis, elfin facies, and mental retardation. There are no adequate and well-controlled studies in pregnant women. Dihydrotachysterol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Nursing Mothers It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when dihydrotachysterol is a administered to a nursing woman.