Doxerol 4 mcg/2 ml

INDICATIONS

Doxercalciferol injection is indicated for the treatment of secondary hyperparathyroidism in adult patients with CKD on dialysis.

PHARMACOLOGY

Doxercalciferol is a synthetic vitamin D2 analog. It requires metabolic activation to form the active 1α, 25-dihydroxyvitamin D2 (1α,25-(OH)2D2) 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 PTH levels by inhibiting PTH synthesis and secretion.

DOSAGE & ADMINISTRATION

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 meg 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 meg to 2 meg if intact PTH is not lowered by 50% and fails to reach the target range. The maximum dose is 18 meg 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 meg lower.

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

INTERACTION

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 excretion of calcium in the urine. Monitor serum calcium concentrations more frequently and adjust doxercalciferol dose as needed. Doxercalciferol can cause hypercalcemia which can potentiate the risk of digitalis toxicity. Monitor patients for signs and symptoms and increase 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 active doxercalciferol moiety. If a patient initiates or discontinues therapy with a cytochrome P450 inhibitor, dose adjustment of doxercalciferol may be necessary. Monitor intact 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.

SIDE EFFECTS

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

PREGNANCY & LACTATION

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.

PRECAUTIONS & WARNINGS

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 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 and treat if indicated. Adynamic bone disease may develop and increase risk of fractures if intact PTH levels are suppressed to abnormally low levels. Monitor intact PTH levels to avoid oversuppression and adjust dose if needed. More frequent monitoring of intact PTH, calcium and phosphorus levels should be done in patients with hepatic impairment.

STORAGE CONDITIONS

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