Doxercalciferol (2 brand names, 2 dosage forms, 2 routes)
Available dosage forms: INJECTABLE, CAPSULE.
Routes of administration: INJECTION, ORAL.
Brand Names
- DOXERCALCIFEROL
- HECTOROL
Indications and Usage
Doxercalciferol capsules are indicated for the treatment of secondary hyperparathyroidism in adult patients with Stage 3 or Stage 4 chronic kidney disease (CKD) and adult patients with CKD on dialysis.
Contraindications
Doxercalciferol is contraindicated in patients with: Hypercalcemia [see Warnings and Precautions ( 5.1)] Vitamin D toxicity [see Warnings and Precautions ( 5.1)] Known hypersensitivity to doxercalciferol or any of the inactive ingredients of doxercalciferol capsules; serious hypersensitivity reactions including anaphylaxis and angioedema have been reported [see Warnings and Precautions ( 5.3), Adverse Reactions ( 6.2)].
Adverse Reactions
The following adverse reactions are discussed in greater detail in another section of the label: Hypercalcemia [see Warnings and Precautions ( 5.1)] Serious Hypersensitivity Reactions [see Warnings and Precautions ( 5.3)] Adynamic Bone Disease [see Warnings and Precautions ( 5.4)]
Drug Interactions
Tables 3 and 4 include clinically significant drug interactions with doxercalciferol. Table 3: Clinically Significant Drug Interactions with Doxercalciferol Capsules Drugs that May Increase the Risk of Hypercalcemia Clinical Impact 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. Examples Calcium-containing products, other vitamin D compounds or thiazide diuretics Intervention Monitor serum calcium concentrations more frequently and adjust doxercalciferol dose as needed [see Warnings and Precautions ( 5.1)]. Digitalis Compounds Clinical Impact Doxercalciferol can cause hypercalcemia which can potentiate the risk of digitalis toxicity. Intervention Monitor patients for signs and symptoms of digitalis toxicity and increase frequency of serum calcium monitoring when initiating or adjusting the dose of doxercalciferol in patients receiving digitalis compounds [see Warnings and Precautions ( 5.2)]. Cytochrome P450 Inhibitors Clinical Impact Doxercalciferol is activated by CYP 27 in the liver. Cytochrome P450 inhibitors may inhibit the 25-hydroxylation of doxercalciferol and thus reduce the formation of active doxercalciferol moiety [see Clinical Pharmacology ( 12.3)]. Examples Ketoconazole and erythromycin Intervention 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 Clinical Impact Doxercalciferol is activated by CYP 27 in the liver. Enzyme inducers may affect the 25-hydroxylation of doxercalciferol [see Clinical Pharmacology ( 12.3)]. Examples Glutethimide and phenobarbital Intervention If a patient initiates or discontinues therapy with an enzyme inducer, dose adjustment of doxercalciferol may be necessary. Monitor i
Mechanism of Action
Doxercalciferol is a synthetic vitamin D 2analog that requires metabolic activation to form the active 1α,25-(OH) 2D 2metabolite, 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.
Overdosage
Overdosage of doxercalciferol may lead to hypercalcemia, hypercalciuria, and hyperphosphatemia [see Warnings and Precautions ( 5.1)] . The treatment of acute overdosage should consist of supportive measures and discontinuation of doxercalciferol administration. Serum calcium levels should be measured until normal. Based on similarities between doxercalciferol and its active metabolite, 1α,25-(OH) 2D 2, it is expected that doxercalciferol is not removed from the blood by dialysis.