Vitamin D Analog

Reduction of elevated intact parathyroid hormone (iPTH) in the management of secondary hyperparathyroidism in patients on chronic hemodialysis

B

Reproduction in animals (usual and high dose) do not reveal teratogenic or fetotoxic effects. Studies in humans are lacking. Excretion in breast milk is unknown. Other vitamin D derivatives are excreted in breast milk and are compatible with breast-feeding.

History of hypercalcemia or evidence of vitamin D toxicity; hyperphosphatemia should be corrected before initiating therapy

Other forms of vitamin D should be discontinued when doxercalciferol is started. Overdose from vitamin D is dangerous and needs to be avoided. Careful dosage titration and monitoring can minimize risk. Hyperphosphatemia exacerbates secondary hyperparathyroidism, diminishing the effect of doxercalciferol. Hyperphosphatemia needs to be corrected for best results. Use with caution in patients with hepatic impairment. Safety and efficacy have not been established in pediatrics.

Some of the signs and symptoms of hypercalcemia include anorexia, nausea, vomiting, constipation, polyuria, weakness, fatigue, confusion, stupor, and coma.

Central nervous system: Headache (28%), malaise (28%), dizziness (11.5%)

Cardiovascular: Edema (34.4%)

Gastrointestinal: Nausea/vomiting (34%)

Respiratory: Dyspnea (11.5%)

1% to 10%:

Central nervous system: Sleep disorder (3.3%)

Cardiovascular: Bradycardia (6.6%)

Neuromuscular & skeletal: Arthralgia (4.9%)

Gastrointestinal: Anorexia (4.9%), constipation (3.3%), dyspepsia (4.9%)

Dermatologic: Pruritus (8.2%)

Miscellaneous: Abscess (3.3%)

Doxercalciferol, in excess, can cause hypercalcemia, hypercalciuria, hyperphosphatemia and oversuppression of PTH secretion. Some of the signs and symptoms of hypercalcemia include anorexia, nausea, vomiting, constipation, polyuria, weakness, fatigue, confusion, stupor, and coma. Following withdrawal of the drug and calcium supplements, hypercalcemia treatment consists of a low calcium diet and monitoring. Adjustments of calcium in the dialysis bath can also be made if necessary. When calcium levels normalize, then doxercalciferol can be restarted. Reduce each dose by at least 2.5 mcg. Monitor serum calcium levels closely.

Decreased effect: Cholestyramine, mineral oil (both reduce absorption)

Increased toxicity: Concurrent use of other vitamin D supplements, magnesium containing antacids and supplements (hypermagnesemia)

Store at controlled room temperature (15°C to 30°C/59°F to 86°F)

Doxercalciferol is metabolized to the active form of vitamin D. The active form of vitamin D controls the intestinal absorption of dietary calcium, the tubular reabsorption of calcium by the kidneys, and in conjunction with PTH, the mobilization of calcium from the skeleton.

Metabolism: Hepatically via CYP 27

Half-life: Active metabolite: 32-37 hours; up to 96 hours

Adults: Oral:

If the iPTH >400 pg/mL, then the initial dose is 10 mcg 3 times/week at dialysis. The dose is adjusted at 8-week intervals based upon the iPTH levels.

If the iPTH level is decreased by 50% and >300 pg/mL, then the dose can be increased to 12.5 mcg 3 times/week for 8 more weeks. This titration process can continue at 8-week intervals up to a maximum dose of 20 mcg 3 times/week. Each increase should be by 2.5 mcg/dose.

If the iPTH is between 150-300 pg/mL, maintain the current dose.

If the iPTH is <100 pg/mL, then suspend the drug for 1 week. Resume doxercalciferol at a reduced dose. Decrease each dose (not weekly dose) by at least 2.5 mcg.

Dosage adjustment in renal impairment: No adjustment required

Dosage adjustment in hepatic impairment: Use caution in these patients; no guidelines for dosage adjustment

Before initiating, check iPTH, serum calcium and phosphorus. Check weekly thereafter until stable. Serum iPTH, calcium, phosphorus, and alkaline phosphatase should be monitored.

Serum calcium times phosphorus product should be less than 70

No information available to require special precautions

No effects or complications reported

Be clear on dose and directions for taking. Stop other vitamin D products. Do not miss doses. Avoid magnesium-containing antacids and supplements. Report headache, dizziness, weakness, sleepiness, severe nausea, vomiting, and difficulty thinking or concentrating to your health care provider. Do not take over-the-counter medicines or supplements without first consulting your health care provider. Follow diet and calcium supplements as directed by your health care provider.

Capsule: 2.5 mcg