Hectorol (doxercalciferol)

Doxercalciferol dosage must be individualized carefully according to serum or plasma intact parathyroid hormone (iPTH) concentrations, with close monitoring of serum calcium and phosphorus concentrations. Serum calcium, phosphorus, and alkaline phosphatase, in addition to serum or plasma iPTH concentrations should be determined periodically; frequent monitoring may be necessary during doxercalciferol dosage adjustments. In patients undergoing dialysis, serum or plasma iPTH, serum calcium, and serum phosphorus concentrations should be determined prior to initiation of therapy with doxercalciferol and weekly during the early phase of therapy (i.e., the first 12 weeks). In predialysis patients, serum calcium, serum phosphorus, and plasma iPTH concentrations should be monitored at least every 2 weeks for 3 months after initiation of therapy or after subsequent dosage changes, then monthly for 3 months (once dosage is stabilized), and every 3 months thereafter.

The manufacturer recommends that dosage of doxercalciferol be titrated to reduce iPTH concentrations to within a target range; specific target ranges are recommended based on the degree of renal impairment. The manufacturer states that the iPTH target range for those with chronic kidney disease (CKD) stage 3 (glomerular filtration rate (GFR) 30-59 mL/minute per 1.73 m2), stage 4 (GFR 15-29 mL/minute per 1.73 m2), or stage 5 (GFR less than 15 mL/minute per 1.73 m2 or on dialysis) is 35-70, 70-110, or 150-300 pg/mL, respectively. However, the target ranges recommended by the manufacturer are based on the National Kidney Foundation's 2003 Kidney Disease Outcomes Quality Initiative (KDOQI) Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease. Nephrology experts currently state that the optimal iPTH concentration for patients with stage 3a (estimated GFR 45-59 mL/minute per 1.73 m2) to stage 5 CKD who are not undergoing dialysis is unknown, but modest increases in iPTH concentration may represent an appropriate adaptive response to declining renal function. For patients with stage 5 CKD undergoing dialysis, some experts suggest that iPTH concentrations may be maintained within a range of approximately 2-9 times the assay's upper limit of normal (ULN) (which may correspond to a range of approximately 130-600 pg/mL for commercially available assays ). Although some clinicians suggest that this range is too broad, available assays for PTH exhibit substantial variability; the previously recommended range of 150-300 pg/mL for patients with stage 5 CKD requiring dialysis was based on an assay that is no longer commercially available. Oversuppression of PTH may increase the risk of adynamic bone disease and should be avoided. (See Uses: Mineral and Bone Disorder Secondary to Chronic Renal Disease, in the Vitamin D Analogs General Statement 88:16.) Nephrology experts currently recommend that the individual values for serum calcium and phosphorus (evaluated together) be used instead of the mathematical construct of calcium times phosphorus product to guide clinical practice.

Doxercalciferol is administered orally without regard to meals. The drug also is administered by direct IV injection.

Specific drug interaction studies have not been conducted.

Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Oral Phosphates; Active Vitamin D Analogs/Burosumab

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Both burosumab and phosphates or vitamin D may increase serum phosphate levels. This combination may lead to greater increases in serum phosphate than anticipated.

CLINICAL EFFECTS: The combination of burosumab with oral phosphates or active vitamin D analogs may result in hyperphosphatemia and may increase the risk of nephrocalcinosis.(1)

PREDISPOSING FACTORS: Patients with renal impairment have alterations in mineral metabolism that may increase the risk of hyperphosphatemia.(1)

PATIENT MANAGEMENT: The concomitant use of burosumab with oral phosphates or active vitamin D analogs is contraindicated. Discontinue oral phosphate and/or active vitamin D analogs one week before starting burosumab.(1)

DISCUSSION: Burosumab restores dysfunctional renal phosphate reabsorption and renal production of 1,25-dihydroxyvitamin D to treat X-linked hypophosphatemia. Additional oral phosphates and/or active vitamin D analogs may raise serum phosphate higher than anticipated.

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

Tendency toward hypercalcemia.

Evidence of vitamin D toxicity.

Doxercalciferol injection is contraindicated in patients with known hypersensitivity to the drug or any ingredient in the formulation. (See Hypersensitivity Reactions under Warnings/Precautions: Sensitivity Reactions, in Cautions.)

• Hypercalcemia
• Hypervitaminosis D

• Hyperphosphatemia

• Disease of liver
• Hypoparathyroidism

In studies that evaluated use of oral doxercalciferol in patients with CKD requiring dialysis, adverse effects occurring in more than 2% of patients and more frequently than placebo include edema, headache, malaise, nausea/vomiting, dizziness, dyspnea, pruritus, bradycardia, anorexia, abscess, arthralgia, weight increase, constipation, and sleep disorder. In studies that evaluated oral doxercalciferol in predialysis patients with stage 3 or 4 CKD, adverse effects occurring in more than 5% of patients and more frequently than placebo include infection, chest pain, constipation, dyspepsia, anemia, dehydration, depression, hypertonia, insomnia, paresthesia, increased cough, dyspnea, and rhinitis.

Potential adverse effects of doxercalciferol generally are similar to those of excessive vitamin D intake, with early manifestations of such toxicity (in association with hypercalcemia) including weakness, headache, somnolence, nausea, dry mouth, constipation, muscle or bone pain, and metallic taste and late manifestations including polyuria, polydipsia, anorexia, weight loss, nocturia, calcific conjunctivitis, pancreatitis, photophobia, rhinorrhea, pruritus, hyperthermia, decreased libido, elevated BUN, albuminuria, hypercholesterolemia, elevated serum AST and ALT, ectopic calcification, hypertension, cardiac arrhythmias, and rarely overt psychosis.

More Frequent

• Dyspnea

Less Frequent

• Abscess
• Arthralgia
• Bradycardia
• Infection

Rare or Very Rare

• Anaphylaxis
• Angioedema
• Hypotension

More Frequent

• Chest pain
• Dizziness
• Edema
• Headache disorder
• Malaise
• Pruritus of skin
• Vomiting

Less Frequent

• Anorexia
• Cough
• Depression
• Dyspepsia
• Hyperphosphatemia
• Hypertonia
• Paresthesia
• Rhinitis
• Sleep disorder
• Weight gain

Rare or Very Rare

• Chest discomfort
• Constipation
• Hypercalcemia
• Nausea
• Stinging of skin

No enhanced messaging available.

Safety and efficacy not established in pediatric patients.

Category B. (See Users Guide.)

It is not known if doxercalciferol is distributed in milk; discontinue nursing or drug because of potential risk (e.g., hypercalcemia) in nursing infants.

No substantial differences in safety and efficacy relative to younger adults.