Doxercalciferol (Hectorol) is a synthetic vitamin D2 (analog of ergocalciferol) that is activated inside the body. It is used in the management of secondary hyperparathyroidism.

Doxercalciferol (Hectorol) Uses:

• Secondary hyperparathyroidism (patients on dialysis):

  • Treatment options for secondary hyperparathyroidism in CKD patients receiving oral or intravenous injections include dialysis.

• Secondary hyperparathyroidism (patients not on dialysis):

  • Oral: Treatment for stage 3 or stage 4 CKD patients with secondary hyperparathyroidism.

Adult dose:

Doxercalciferol Dose in the treatment of chronic kidney disease (CKD) patients on dialysis :

• Note: According to KDIGO recommendations, parathyroid hormone (PTH) levels should be kept intact between 2 and 9 times the upper normal limit for the assay. 
• Caution is advised to avoid hypercalcemia or elevated phosphate levels.
• Initial:

  • IV:

    • After dialysis, 4 mcg three times per week (no more frequently than every other day)

  • Oral:

    • Dialysis 10 mcg three times each week (no more frequently than every other day)

• Dose titration:

  • Ensure serum calcium is within normal limits before increasing the dose.

  • Oral:

    • Titrate the dose by 2.5 mcg/dose every 8 weeks to achieve a target plasma PTH level.
    • 20 mcg maximum, three times per week at dialysis (60 mcg weekly).
    • Hold therapy or reduce dose if PTH is persistently and abnormally low or if corrected serum calcium is constantly above the upper normal range; If doxercalciferol is stopped, it is possible to resume taking it after one week at a dose that is at least 2.5 micrograms less than the one before.

    IV:

    • If plasma PTH is not reduced by 50% and the desired plasma PTH level is not reached after 8 weeks, titrate the dose by 1 to 2 mcg/dose.
    • Maximum: 18 mcg weekly.
    • Hold therapy or reduce dose if PTH is persistently and abnormally low or if corrected serum calcium is constantly above upper normal range; if doxercalciferol is held, may resume at a dose that is at least 1 microgram less than the prior dose after a week.

Doxercalciferol Dose in the treatment of CKD patients not on dialysis (CKD stage ≥G3):

• Note: KDIGO recommendations advise against routinely administering vitamin D analogues, such as doxercalciferol, to patients with CKD stages G3 to G5, who are not on dialysis.
• For patients with severe and worsening hyperparathyroidism and CKD stages G4 or G5, it could make sense to reserve use.
• Caution is advised to avoid hypercalcemia or elevated phosphate levels (KDIGO 2017).

• Initial:

  • Oral: 1 mcg once daily

• Dose titration:

  • Oral:
    • Titrate the dose by 0.5 mcg/dose at every 2-week intervals to achieve a target plasma PTH level.
    • Maximum: 3.5 mcg once daily.
    • Ensure serum calcium is within normal limits before increasing the dose.
    • Hold therapy or reduce dose if PTH is persistently and abnormally low or if corrected serum calcium is constantly above upper normal range; Alternatively, doxercalciferol may be resumed after a week at a dose that is at least 0.5 micrograms less than the preceding dose.

Dose in children:

Not recommended for use in children. 

Pregnancy Risk Category: B

• In animal reproduction studies, adverse events have not been reported

Doxercalciferol use during breastfeeding:

• It is unknown if doxercalciferol can be found in breast milk.
• The drug manufacturer advises that breastfeeding during therapy should be considered in light of the risks to infant exposure and the benefits to the mother.
• Monitor the breastfed infant for hypercalcemia signs and symptoms.

Renal dose:

Doxercalciferol Dose in Kidney disease:

• No dosage adjustment is necessary. The major metabolite, 1α,25-(OH) D, is not removed by hemodialysis.

Doxercalciferol Dose in Liver disease:

• There are no dosage adjustments provided in the drug manufacturer’s labeling. Use with care and assume considering checking iPTH, calcium, and phosphate levels more frequently.

Common Side Effects of Doxercalciferol (Hectorol):

• Hematologic & Oncologic:

  • Anemia

• Cardiovascular:

  • Edema

• Gastrointestinal:

  • Constipation
  • Nausea And Vomiting

• Infection:

  • Infection

• Respiratory:

  • Rhinitis
  • Cough
  • Dyspnea

• Central Nervous System:

  • Insomnia
  • Paresthesia
  • Headache
  • Malaise
  • Dizziness
  • Hypertonia

• Neuromuscular & Skeletal:

  • Asthenia

Less Common Side Effects Of Doxercalciferol (Hectorol):

• Hematologic & Oncologic:

  • Leukopenia

• Cardiovascular:

  • Angina Pectoris
  • Bradycardia
  • Chest Pain

• Dermatologic:

  • Pruritus

• Endocrine & Metabolic:

  • Dehydration
  • Weight Gain

• Gastrointestinal:

  • Dyspepsia
  • Anorexia

• Central Nervous System:

  • Depression
  • Sleep Disorder

• Genitourinary:

  • Urinary Tract Infection

• Infection:

  • Abscess

• Neuromuscular & Skeletal:

  • Arthralgia

• Respiratory:

  • Sinusitis

Rare side effects of Doxercalciferol:

• Endocrine & metabolic:

  • Hypercalcemia
  • Hyperphosphatemia

Contraindications to Doxercalciferol (Hectorol):

• Allergy or hypersensitivity to doxercalciferol or any other ingredient in the formulation
• Limited evidence exists of cross-reactivity between vitamin D analogues and allergenic substances.
• Hypercalcemia
• Cross-sensitivity is possible due to the likelihood of chemical structure or pharmacologic effects.
• Vitamin D toxicities

Warnings and precautions

• Vitamin D excess:

  • This can then lead to hypercalcemia, hypercalciuria and hyperphosphatemia as well as dynamic bone disease.
  • Vitamin-D supplementation may lead to excessive suppression of parathyroid hormones (PTH).

• Hypercalcemia:

  • Patients with chronic renal disease should be aware of their calcium levels.
  • Patients with hypercalcemia should not be used.
  • Concomitant use of calcium-containing supplements or medications that increase serum calcium (eg thiazide diuretics) may increase the risk of hypercalcemia.
  • Hypercalcemia is more common in patients with high calcium levels (>10.5 mg/dL before treatment).
  • Cardiac arrhythmias, seizures, generalised vascular calcification, and other soft-tissue calcification are all risks that can be increased by acute and gradual hypercalcemia.
  • This could exacerbate nephrolithiasis, which has been associated with a higher mortality rate in those with chronic renal disease (CKD).
  • Hypercalcemia can be treated with a lower dose or discontinue treatment.

• Hypersensitivity

  • Severe Allergic Reactions (some fatal), such as anaphylaxis, angioedema and dyspnea, chest discomfort, cardiopulmonary arrest, heart attack, and unresponsiveness have all been studied using IV doxercalciferol.
  • If you start IV treatment, be sure to monitor for hypersensitivity. Stop immediately if this happens.

• Hepatic impairment

  • Hepatic impairment can make it difficult for patients to properly metabolize doxercalciferol.
  • Patients with hepatic impairment should be cautious; they may need more frequent iPTH, Calcium, and Phosphate monitoring.

• Hyperphosphatemia

  • Hyperphosphatemia is more common in patients with high phosphate levels before treatment (>6.9 mg/dL).
  • Do not correct before you start therapy. Secondary hyperparathyroidism can exacerbate, which will reduce the effectiveness of doxercalciferol.

Doxercalciferol: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

• Parathyroid hormone (PTH): The frequency of measurement may depend on the existence and severity of abnormalities, the rate at which chronic kidney disease (CKD) is progressing, and the usage of therapies for CKD-related mineral and bone disorders.
• Serum calcium and phosphate

• CKD stage G4:

  • Serum calcium and phosphate: Every 3 to 6 months interval;
  • PTH: Every 6 to 12 months

• In dialysis patients,

  • iPTH, serum calcium, and phosphate should be determined before starting therapy and weekly thereafter for the first 12 weeks.

• CKD stage G5 and G5D:

  • Serum calcium and phosphate: Every 1 to 3 months interval;
  • PTH: Every 3 to 6 months

• CKD stage G3a to G3b:

  • Serum calcium and phosphate: Every 6 to 12 months intervals;
  • PTH: Frequency based on baseline level and progression of CKD

• For predialysis patients,

  • Every two weeks for three months following the start of therapy or after dose modifications, then monthly for three months, and then every three months moving forward, serum calcium and phosphate levels, as well as plasma levels of iPTH, should be evaluated.
  • Every 12 months or more frequently in the presence of increased PTH, periodic 24-hour urine calcium, phosphate, magnesium, and alkaline phosphatase measurements should be performed.
  • Depending on the severity of the CKD, creatinine, BUN, albumin, and intact parathyroid hormone (iPTH) every three to twelve months.

How to administer Doxercalciferol (Hectorol)?

• Injection: Administer as an IV bolus.

Mechanism of action of Doxercalciferol (Hectorol):

• The kidneys' tubular reabsorption of calcium, the intestinal absorption of dietary calcium, and, in conjunction with PTH, the mobilisation of calcium from the skeleton are all regulated by the active form of vitamin D.
• The metabolite of doxercalciferol is the active form of vitamin D.

Half-life elimination:

• Major metabolite: ~32 to 37 hours (range: up to 96 hours)

Metabolism:

• Hepatic via CYP27 to active metabolites, 1α,25-(OH) D (major) and 1α,24dihydroxyvitamin D (minor).

Time to peak:

• Major metabolite: 8 hours injection form; 11 to 12 hours by oral.

International Brands of Doxercalciferol:

• Hectorol
• Vitcalciferol

Doxercalciferol Brand Names in Pakistan:

No Brands Available in Pakistan.