Usage
Alfacalcidol + Calcium is primarily prescribed for conditions characterized by calcium deficiency or impaired calcium metabolism. These include:
- Chronic Kidney Disease (CKD), especially with secondary hyperparathyroidism: In CKD, the kidneys’ ability to convert vitamin D to its active form is impaired, leading to low calcium levels and bone disease (renal osteodystrophy). Alfacalcidol helps to correct this deficiency.
- Hypoparathyroidism: This condition results in low levels of parathyroid hormone, leading to hypocalcemia. Alfacalcidol helps increase calcium levels.
- Osteoporosis: Alfacalcidol can improve bone density and reduce fracture risk in osteoporosis, especially when combined with calcium.
- Vitamin D-resistant Rickets and Osteomalacia: These conditions involve softening of the bones due to impaired vitamin D metabolism. Alfacalcidol can improve calcium absorption and bone mineralization.
Pharmacological Classification: Vitamin D analog, calcium regulator.
Mechanism of Action: Alfacalcidol is a prohormone converted in the liver to calcitriol (1,25-dihydroxyvitamin D3), the active form of vitamin D. Calcitriol binds to vitamin D receptors in the intestine, kidneys, and bone, increasing calcium absorption, reducing calcium excretion, and promoting bone mineralization. It also suppresses parathyroid hormone (PTH) secretion, which further helps regulate calcium levels.
Alternate Names
- Alfacalcidol is the generic name.
- 1α-hydroxyvitamin D3
- 1α-hydroxycholecalciferol
Brand Names: One-Alpha®, Bondiol®, Alfaget®
How It Works
Pharmacodynamics: Alfacalcidol’s primary effect is to increase serum calcium levels. It achieves this by enhancing calcium absorption from the intestine, decreasing renal calcium excretion, and mobilizing calcium from bone. It also decreases serum alkaline phosphatase and PTH levels in patients with CKD.
Pharmacokinetics:
- Absorption: Alfacalcidol is readily absorbed from the gastrointestinal tract. Food does not significantly affect absorption.
- Metabolism: It is rapidly metabolized in the liver to calcitriol, its active form.
- Elimination: Calcitriol is eliminated primarily through the bile and feces, with a small amount excreted in the urine.
Mode of Action: Alfacalcidol’s active metabolite, calcitriol, binds to the vitamin D receptor (VDR), a nuclear receptor. This complex then interacts with specific DNA sequences, regulating the expression of genes involved in calcium transport and bone metabolism.
Receptor Binding: Binds to the Vitamin D Receptor (VDR).
Elimination Pathways: Primarily hepatic, biliary excretion, with some renal excretion.
Dosage
Standard Dosage
Adults:
Initial: 0.5–1 mcg daily, adjusted according to serum calcium levels.
Maintenance: 0.25–1 mcg daily.
Children:
<20 kg: 0.05 mcg/kg/day.
≥20 kg: Similar to adult dosing, starting at the lower end of the range.
Special Cases:
- Elderly Patients: Start with 0.5 mcg daily. Titrate cautiously.
- Patients with Renal Impairment: Dose adjustment is usually not necessary, as alfacalcidol bypasses the need for renal activation. Close monitoring of calcium levels is essential.
- Patients with Hepatic Dysfunction: Use with caution, as hepatic metabolism is essential for activation. Monitor calcium levels carefully.
- Patients with Comorbid Conditions: Careful monitoring is necessary, especially in patients with conditions that predispose to hypercalcemia.
Clinical Use Cases
Alfacalcidol’s dosage in specific clinical settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations should be individualized based on the patient’s condition, calcium levels, and other relevant factors. There is no standardized dosing protocol for these settings.
Dosage Adjustments
Dose adjustments should be based on serum calcium levels and clinical response. Hypercalcemia requires dose reduction or temporary discontinuation.
Side Effects
Common Side Effects:
Hypercalcemia (high calcium levels), nausea, vomiting, constipation, weakness, headache.
Rare but Serious Side Effects:
Cardiac arrhythmias, kidney stones, confusion, pancreatitis.
Long-Term Effects:
Nephrocalcinosis (calcium deposits in the kidneys), vascular calcification.
Adverse Drug Reactions (ADR):
Severe hypercalcemia requiring hospitalization.
Contraindications
- Hypercalcemia
- Hyperphosphatemia
- Vitamin D toxicity
- Hypersensitivity to alfacalcidol or any components of the formulation
Drug Interactions
- Thiazide diuretics: May increase the risk of hypercalcemia.
- Digoxin: Hypercalcemia can exacerbate digoxin toxicity.
- Magnesium-containing antacids: May increase the risk of hypermagnesemia.
- Cholestyramine: May reduce the absorption of alfacalcidol.
Pregnancy and Breastfeeding
Alfacalcidol should be used with caution during pregnancy and breastfeeding. It is classified as Pregnancy Category C, meaning that animal studies have shown adverse effects on the fetus, but there are no adequate and well-controlled studies in humans. Alfacalcidol is excreted in breast milk.
Drug Profile Summary
- Mechanism of Action: Vitamin D analog, promotes calcium absorption and bone mineralization.
- Side Effects: Hypercalcemia, nausea, vomiting, constipation.
- Contraindications: Hypercalcemia, vitamin D toxicity.
- Drug Interactions: Thiazide diuretics, digoxin, magnesium antacids.
- Pregnancy & Breastfeeding: Use with caution.
- Dosage: Adults: 0.5–1 mcg/day initially, adjusted based on serum calcium.
- Monitoring Parameters: Serum calcium, phosphate, PTH, alkaline phosphatase.
Popular Combinations
Alfacalcidol is often used in combination with calcium supplements to ensure adequate calcium intake, especially in patients with CKD and osteoporosis.
Precautions
- General Precautions: Monitor serum calcium, phosphate, PTH, and alkaline phosphatase levels regularly.
- Specific Populations: Use with caution in pregnancy, breastfeeding, and patients with hepatic impairment.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Alfacalcidol + Calcium?
A: Alfacalcidol is typically started at 0.5-1 mcg daily for adults and 0.05 mcg/kg/day for children under 20kg, adjusted based on calcium levels. Calcium supplementation should be individualized to meet daily requirements.
Q2: How does alfacalcidol differ from regular vitamin D?
A: Alfacalcidol is activated in the liver, while vitamin D requires activation in the kidneys. This makes alfacalcidol suitable for patients with kidney disease.
Q3: What are the most common side effects of alfacalcidol?
A: Hypercalcemia, nausea, vomiting, and constipation are the most common side effects.
Q4: What are the signs of hypercalcemia?
A: Signs of hypercalcemia include nausea, vomiting, constipation, weakness, confusion, and cardiac arrhythmias.
Q5: What should be done if hypercalcemia occurs?
A: Discontinue alfacalcidol, restrict dietary calcium, and consult a physician.
Q6: Can alfacalcidol be used during pregnancy?
A: Use with caution during pregnancy and breastfeeding, and only if the potential benefits outweigh the risks.
Q7: How is alfacalcidol administered?
A: Alfacalcidol is available as oral capsules and drops and is usually taken once daily.
Q8: What monitoring is necessary during alfacalcidol therapy?
A: Regular monitoring of serum calcium, phosphate, PTH, and alkaline phosphatase levels is necessary.
Q9: What is the role of calcium supplementation with alfacalcidol?
A: Calcium supplementation is often used with alfacalcidol to ensure adequate calcium intake for optimal bone health.
Q10: Are there any drug interactions I should be aware of with alfacalcidol?
A: Yes, potential interactions exist with thiazide diuretics, digoxin, and magnesium-containing antacids, among others. Consult a physician or pharmacist about specific drug interactions.
