The 25-hydroxylated form of vitamin D is known as calcifediol, and it must undergo an additional hydroxylation in the kidneys in order to be fully active.  Adults with vitamin D deficiency or insufficiency and stage 3 to 4 chronic renal disease can use it to treat secondary hyperparathyroidism. It is not advisable  to prescribe calcifediol to patients with more severe kidney disease (such as those with stage 5 CKD, ESRD, and those receiving hemodialysis), as  its activation is inhibited and it is ineffective.

Calcifediol Dose in Adults

Use in the treatment of Secondary hyperparathyroidism:

• 30 mcg taken orally once daily before bed.
• If the intact PTH is above the desired range after three months, increase the dose to 60 mcg once day at bedtime.
• The total blood calcium level should be less than 9.8 mg/dL prior to starting treatment.
• The maintenance dose should target the following goals:
  • Total 25-hydroxyvitamin D levels: 30 - 100 ng/mL
  • Intact Parathyroid hormone levels within desired range
  • Serum calcium of 9.8 mg/dL or less
  • Serum phosphorus of 5.5 mg/dL or less.

Calcifediol Dose in Childrens

 Safety and efficacy have not been established in children. 

Pregnancy Risk Factor C

• Although it crosses the placental boundary, the cord levels are generally lower that the maternal plasma levels.

Calcifediol use during breastfeeding:

• Although it is not well excreted in breast milk, the concentrations may rise if supplementation is given.
• Lactating women should use it with caution

Calcifediol Dose in Renal Disease:

• Adjustment in the dose is not necessary.

Calcifediol Dose in Liver Disease:

• The manufacturer has not provided any adjustment in the dose in patients with liver disease. 

Common side Effects Of Calcifediol Include:

• Hematologic & oncologic:
  • Abnormal phosphorus levels

Less Common Side Effects Of Calcifediol Include:

• Cardiovascular:
  • Cardiac failure
• Endocrine & metabolic:
  • Hypercalcemia
  • Hyperkalemia
  • Hyperuricemia
• Hematologic & oncologic:
  • Anemia
  • Bruise
• Neuromuscular & skeletal:
  • Osteoarthritis
• Renal:
  • Increased serum creatinine
• Respiratory:
  • Nasopharyngitis
  • Cough
  • Dyspnea
  • Bronchitis
  • Chronic obstructive pulmonary disease
  • Pneumonia

Contraindication to Calcifediol include:

Contraindications are not listed on the label.

Warnings and Precautions

• Hypervitaminosis D:
  • People who consume too much vitamin D can develop hypercalcemia and hyperphosphatemia as well as renal stones.
  • They may also experience suppression of the parathyroid hormone, which could lead to a dynamic bone disease.
• Hypercalcemia:
  • A high level of vitamin D may lead to acute and progressive hypercalcemia, which can increase the risk of seizures and cardiac arrhythmias.
  • A chronic elevation in calcium levels can lead to generalized vascular or soft-tissuecalcification, which may eventually lead to nephrolithiasis.
  • Patients with chronic renal disease who have hypercalcemia have a higher mortality rate.
  • Concomitant medications like thiazide diuretics may increase the risk of hypercalcemia.
• Hyperphosphatemia
  • Before starting therapy with vitamin D, it is important to monitor serum phosphate levels.

Calcifediol: 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:

Monitor the following parameters within 3 months of the start of the therapy or following a dose change, and then at least every 6 to 12 months after that.

• Serum calcium and signs and symptoms of hypercalcemia:
• Serum phosphorus
• Serum total 25-hydroxyvitamin D
• Intact PTH levels

KDIGO recommendations:

• CKD stage 3a-3b:
  • Monitor Serum calcium and phosphate every 6 - 12 months.
• CKD stage 4:
  • Monitor Serum calcium and phosphate every 3 to 6 months
  • Intact PTH every 6 - 12 months
• CKD stage 5 and 5D:
  • Monitor Serum calcium and phosphate every 1 - 3 months
  • Intact PTH every 3 - 6 months

How to administer Calcifediol?

• The drug should be administered at bedtime.
• The capsule should not be crushed or chewed and swallowed as a whole.

Mechanism of action of Calcifediol:

• Calcifediol or 25 Hydroxycholecalciferol or 25 hydroxyvitamin D is a prohormone. 
• To be converted into the activated form of 1, 25 hydroxyvitaminD or calcitriol, it must be further hydroxylated in the kidneys.
• Calcitriol, in its activated form binds to vitamin D receptors in target tissue.
• This results in greater intestinal absorption of calcium as well as a decrease in parathyroid hormone production.

It has beenStart of actionIn approximately 2 weeks. (The maximum effect can be seen in three months). The drug contains more than 98%. protein-boundIt isMetabolizedBy the enzyme 1-alpha hydroxylase found in the kidneys to convert calcitriol.

It has been ahalf-life eliminationIt is found in healthy adults for 11 days, but it can be increased to 25 days in stage 4 or 5 kidney disease. It is excreted from the feces.

International Brands of Calcifediol:

• Caldiol
• Dedrogyl
• Hidroferol
• Vulsora

Calcifediol brands in Pakistan: