Doxercalciferol injection is indicated for the treatment of secondary hyperparathyroidism in adult patients with chronic kidney disease (CKD) on dialysis.

Doxercalciferol is a synthetic vitamin D analog. It requires metabolic activation to form the active 1α,25-dihydroxyvitamin D (1α,25-(OH)₂D) metabolite, which binds to the vitamin D receptor (VDR) to result in the selective activation of vitamin D responsive pathways. Vitamin D and doxercalciferol have been shown to reduce parathyroid hormone (PTH) levels by inhibiting PTH synthesis and secretion.

Route of administration: Doxercalciferol injection should be administered intravenously. Ensure serum calcium is not above the upper limit of normal before initiating treatment with Doxercalciferol injection.

Administration instructions:

• Administer Doxercalciferol injection intravenously as a bolus dose at the end of dialysis.

• Inspect Doxercalciferol injection visually prior to administration; the solution should appear clear and colorless.

• Do not use if the solution is not clear or particles are present.

Dosage recommendations:

• Initiate Doxercalciferol injection at a dose of 4 mcg given by bolus intravenous administration three times weekly at the end of dialysis (no more frequently than every other day).

• Target the maintenance dose of Doxercalciferol to intact parathyroid hormone (PTH) levels within the desired therapeutic range and serum calcium within normal limits.

• Monitor serum calcium, phosphorus and intact PTH levels weekly after initiation of therapy or dose adjustment.

• Titrate the dose of Doxercalciferol injection based on intact PTH. The dose may be increased at 8-week intervals by 1 mcg to 2 mcg if intact PTH is not lowered by 50% and fails to reach the target range. The maximum dose is 18 mcg weekly. Prior to raising the dose, ensure serum calcium is within normal limits.

• Suspend or decrease the dose if intact PTH is persistently and abnormally low to reduce the risk of adynamic bone disease or if serum calcium is consistently above the normal range to reduce the risk of hypercalcemia. If suspended, the drug should be restarted one week later at a dose that is at least 1 mcg lower.

Use in children and adolescents: The safety and effectiveness of doxercalciferol in pediatric patients have not been established.

Drug interaction with medication: Concomitant administration of high doses of calcium-containing preparations or other vitamin D compounds may increase the risk of hypercalcemia. Thiazide diuretics are known to induce hypercalcemia by reducing urinary calcium excretion. Monitor serum calcium concentrations more frequently and adjust the doxercalciferol dose as needed. Doxercalciferol can cause hypercalcemia, which may potentiate the risk of digitalis toxicity. Monitor patients for signs and symptoms, and increase the frequency of serum calcium monitoring when initiating or adjusting the dose of doxercalciferol in patients receiving digitalis compounds. Cytochrome P450 inhibitors may inhibit the 25-hydroxylation of doxercalciferol and thus reduce the formation of the active doxercalciferol moiety. If a patient initiates or discontinues therapy with a cytochrome P450 inhibitor, dose adjustment of doxercalciferol may be necessary. Monitor intact parathyroid hormone (PTH) and serum calcium concentrations closely. Enzyme inducers (e.g., glutethimide and phenobarbital) may affect the 25-hydroxylation of doxercalciferol. If a patient initiates or discontinues therapy with an enzyme inducer, dose adjustment of doxercalciferol may be necessary. Concomitant administration of doxercalciferol and high doses of magnesium-containing products may increase the risk of hypermagnesemia. Avoid use of magnesium-containing products and doxercalciferol in patients on chronic renal dialysis.

This combination is contraindicated in patients with known hypersensitivity to doxercalciferol or any other components of this product. It is also contraindicated in hypercalcemia and vitamin D toxicity.

The most common side effects are infection / bacterial infection / viral infection, constipation, rhinitis, anemia, cough, dyspnea, paresthesia, asthenia, insomnia, hypertonia, and angina pectoris.

The limited available data with doxercalciferol in pregnant women are insufficient to identify a drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for doxercalciferol and any potential adverse effects on the breastfed infant from doxercalciferol or from the underlying maternal condition.

Hypercalcemia can occur during treatment with doxercalciferol and can lead to cardiac arrhythmias and seizures. Severe hypercalcemia may require emergency attention. Monitor serum calcium prior to initiation and during treatment, and adjust the dose accordingly. Anaphylaxis, with symptoms of angioedema, hypotension, unresponsiveness, chest discomfort, shortness of breath, and cardiopulmonary arrest, has been reported in hemodialysis patients after administration of doxercalciferol. Monitor patients upon treatment initiation for hypersensitivity reactions. Should a hypersensitivity reaction occur, discontinue the drug and treat if indicated. Adynamic bone disease may develop and increase the risk of fractures if intact parathyroid hormone (PTH) levels are suppressed to abnormally low levels. Monitor intact PTH levels to avoid oversuppression, and adjust the dose if needed. More frequent monitoring of intact PTH, calcium, and phosphorus levels should be performed in patients with hepatic impairment.

Overdosage of doxercalciferol may lead to hypercalcemia, hypercalciuria, and hyperphosphatemia. The treatment of acute overdosage should consist of supportive measures and discontinuation of doxercalciferol administration. Serum calcium levels should be measured until normal. It is expected that doxercalciferol is not removed from the blood by dialysis.

Keep out of the reach of children. Store in a cool (below 25°C) and dry place, protected from light. After first use, the unused portion can be stored for 3 days in a refrigerator at 2°C to 8°C if required.