Overview
11 DESCRIPTION Doxercalciferol Capsules contains doxercalciferol, which is a synthetic vitamin D 2 analog. Doxercalciferol undergoes metabolic activation in vivo to form 1α,25-dihydroxyvitamin D 2 (1α,25-(OH) 2 D 2 ), a naturally occurring, biologically active form of vitamin D 2 . Doxercalciferol is a colorless crystalline compound with a calculated molecular weight of 412.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Doxercalciferol is a synthetic vitamin D 2 analog that requires metabolic activation to form the active 1α,25-(OH) 2 D 2 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. 12.3 Pharmacokinetics Absorption In healthy volunteers, peak blood levels of 1α,25-(OH) 2 D 2 , the major metabolite of doxercalciferol, are attained at 8 hours after a single intravenous dose of doxercalciferol and at 11 to 12 hours following capsule doses.
Indications
- 1 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. Doxercalciferol Capsules is a synthetic vitamin D 2 analog: 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. ( 1 )
Common Doses
- 1 mcg
- 3.5 mcg
- 10 mcg
- 20 mcg
Dosage
2 DOSAGE AND ADMINISTRATION Before initiating treatment, ensure serum calcium is not above the upper limit of normal. ( 2.1 ) Dosage for doxercalciferol capsules in patients with: Stage 3 or 4 CKD: Initiate dosing at 1 mcg orally once daily. Maximum dose is 3.5 mcg once daily. ( 2.2 ) CKD on dialysis: Initiate dosing at 10 mcg orally three times weekly at dialysis (no more frequently than every other day). Maximum dose is 20 mcg three times weekly for a total of 60 mcg weekly. ( 2.
Contraindications
- 4 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 )].
Side Effects
- 6 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 )] The most common adverse reactions in patients with Stage 3 or 4 CKD (incidence >5%) were infection, urinary tract infection, chest pain, angina pectoris, constipation, dyspepsia, anemia, leukopenia, dehydration, edema, depression, hypertonia, insomnia, asthenia, paresthesia, cough increased,...
Interactions
- 7 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.