Usage
Alfacalcidol is prescribed for various medical conditions related to calcium and phosphate metabolism, often arising from vitamin D deficiency or insufficiency. This includes:
- Renal osteodystrophy: Bone disease associated with chronic kidney disease.
- Hypoparathyroidism: Low levels of parathyroid hormone, leading to hypocalcemia.
- Pseudohypoparathyroidism: Resistance to parathyroid hormone, also resulting in hypocalcemia.
- Vitamin D-resistant rickets and osteomalacia: Softening of the bones due to impaired vitamin D metabolism.
- Vitamin D-dependent rickets: Genetic disorders affecting vitamin D metabolism.
- Hypocalcemia: Low blood calcium levels.
- Postmenopausal osteoporosis: Loss of bone density in postmenopausal women.
Pharmacological Classification: Vitamin D analog, specifically a synthetic precursor of 1,25-dihydroxyvitamin D3 (calcitriol), the active form of vitamin D.
Mechanism of Action: Alfacalcidol is rapidly converted in the liver to calcitriol, which regulates calcium and phosphate homeostasis by promoting their absorption in the intestines and reabsorption in the kidneys. It also influences bone metabolism.
Alternate Names
How It Works
Pharmacodynamics: Alfacalcidol’s primary effect is to increase serum calcium and phosphate levels. Calcitriol (the active form) binds to vitamin D receptors in the intestines, kidneys, and bone, modulating gene transcription related to calcium and phosphate transport.
Pharmacokinetics:
- Absorption: Alfacalcidol is well-absorbed orally. Food can slightly enhance absorption.
- Metabolism: Rapidly converted to calcitriol in the liver.
- Elimination: Excreted mainly in bile and feces, with a small amount in urine.
Mode of Action: Alfacalcidol is a prodrug of calcitriol, the active form of vitamin D. Calcitriol binds to the vitamin D receptor (VDR), a nuclear receptor that heterodimerizes with the retinoid X receptor (RXR). This complex then binds to vitamin D response elements (VDREs) in the DNA, regulating the transcription of genes involved in calcium and phosphate transport.
Receptor Binding: Vitamin D receptor (VDR).
Elimination Pathways: Primarily hepatic (biliary and fecal), with some renal excretion.
Dosage
Standard Dosage
Adults:
Initial: 1 mcg/day orally. Maintenance: 0.25–1 mcg/day, adjusted according to serum calcium and phosphate levels.
Children:
Dosing is weight-based. Consult pediatric dosing guidelines for specific recommendations and safety considerations.
Special Cases:
- Elderly Patients: Initial: 0.5 mcg/day, with careful titration based on serum calcium levels.
- Patients with Renal Impairment: Dosage adjustments are necessary based on the degree of impairment. For hemodialysis patients, the dose is typically administered into the return line of the dialysis machine.
- Patients with Hepatic Dysfunction: Use with caution; dosage adjustment may be required.
- Patients with Comorbid Conditions: Careful monitoring for drug interactions and adjustments as needed, particularly with thiazide diuretics, calcium supplements, and anticonvulsants.
Clinical Use Cases
Dosage in specific clinical settings is individualized based on the underlying condition and response to therapy. The information provided in the sources primarily focus on chronic conditions like renal osteodystrophy and hypoparathyroidism rather than acute settings.
Dosage Adjustments
Dosage should be titrated based on serum calcium, phosphate, and parathyroid hormone levels, along with clinical response. Frequent monitoring is essential, particularly during initial therapy and dose adjustments. Genetic polymorphisms affecting drug metabolism have not been specifically mentioned.
Side Effects
Common Side Effects:
- Nausea
- Vomiting
- Headache
- Constipation
- Weakness
- Skin rash
- Itching
- Abdominal pain
Rare but Serious Side Effects:
- Hypercalcemia (high calcium levels) leading to:
- Cardiac arrhythmias
- Confusion
- Muscle weakness
- Generalized vascular and soft tissue calcification
- Nephrocalcinosis
Long-Term Effects: Long-term hypercalcemia can contribute to nephrolithiasis (kidney stones) and renal impairment.
Contraindications
- Hypercalcemia
- Hyperphosphatemia (except in hypoparathyroidism)
- Hypervitaminosis D
- Hypersensitivity to alfacalcidol or any components of the formulation
- Evidence of vitamin D toxicity
- Metastatic calcification
Drug Interactions
- Thiazide diuretics: Increased risk of hypercalcemia.
- Calcium supplements: Increased risk of hypercalcemia.
- Anticonvulsants (e.g., phenytoin, phenobarbital, carbamazepine): Increased alfacalcidol metabolism, potentially requiring higher doses.
- Magnesium-containing antacids: Increased risk of hypermagnesemia.
- Aluminum-containing preparations: Increased risk of aluminum toxicity.
- Mineral oil: Decreased alfacalcidol absorption.
- Bile acid sequestrants (e.g., cholestyramine): Decreased alfacalcidol absorption.
- Digitalis glycosides: Hypercalcemia can potentiate the effects of digitalis, increasing the risk of cardiac arrhythmias.
- Ketoconazole: May inhibit calcitriol metabolism.
Pregnancy and Breastfeeding
- Pregnancy: Alfacalcidol is generally not recommended during pregnancy due to the risk of hypercalcemia in the mother and potential adverse effects on the fetus.
- Breastfeeding: Alfacalcidol may be excreted in breast milk and could affect calcium metabolism in the infant. Breastfeeding during treatment should be avoided.
Drug Profile Summary
- Mechanism of Action: Converted to calcitriol, which regulates calcium and phosphate homeostasis.
- Side Effects: Nausea, vomiting, headache, constipation, hypercalcemia.
- Contraindications: Hypercalcemia, hypervitaminosis D, vitamin D toxicity.
- Drug Interactions: Thiazide diuretics, calcium supplements, anticonvulsants.
- Pregnancy & Breastfeeding: Generally avoided.
- Dosage: Adult initial: 1 mcg/day; maintenance 0.25–1 mcg/day. Pediatric: weight-based.
- Monitoring Parameters: Serum calcium, phosphate, PTH, alkaline phosphatase, urinary calcium.
Popular Combinations
While the provided sources do not list specific popular combinations, alfacalcidol may be prescribed alongside calcium supplements, particularly in cases of severe hypocalcemia.
Precautions
- Monitor serum calcium, phosphate, and PTH levels regularly.
- Monitor for signs of hypercalcemia.
- Use with caution in patients with pre-existing conditions like sarcoidosis, granulomatous diseases, and nephrolithiasis.
- Assess renal and hepatic function before and during treatment.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Alfacalcidol?
A: Adults: Initial dose is 1 mcg/day orally. Maintenance dose is 0.25–1 mcg/day, adjusted based on serum calcium and phosphate levels. Children: Dosing is weight-based; consult pediatric guidelines. Elderly: Initial dose is usually 0.5 mcg/day, titrated carefully.
A: Alfacalcidol is a synthetic analog of vitamin D and a direct precursor to calcitriol (the active form), requiring less metabolic activation. This makes it faster acting than other forms like vitamin D3 (cholecalciferol).
Q3: What are the most serious side effects of Alfacalcidol?
A: Hypercalcemia is the most serious side effect and can lead to cardiac arrhythmias, confusion, muscle weakness, and even nephrocalcinosis if prolonged.
Q4: Can Alfacalcidol be used in patients with kidney disease?
A: Yes, it is often used to treat renal osteodystrophy associated with chronic kidney disease. Dosage adjustments are necessary depending on the degree of renal impairment. For hemodialysis patients, it’s administered via the dialysis machine.
Q5: Can I take Alfacalcidol with calcium supplements?
A: It can be prescribed concurrently with calcium supplements, especially in severe hypocalcemia. However, careful monitoring of calcium levels is crucial to avoid hypercalcemia.
Q6: What are the contraindications to using Alfacalcidol?
A: Contraindications include hypercalcemia, hypervitaminosis D, vitamin D toxicity, hypersensitivity to alfacalcidol, and evidence of metastatic calcification.
Q7: What should patients know about taking Alfacalcidol?
A: Patients should take the medication as prescribed, undergo regular monitoring of calcium levels, and report any symptoms of hypercalcemia promptly. Alcohol should be limited, as it can interfere with calcium absorption.
Q8: Can Alfacalcidol be used during pregnancy or breastfeeding?
A: Alfacalcidol is generally avoided during pregnancy and breastfeeding due to the risk of hypercalcemia in the mother and potential adverse effects on the fetus or infant.
Q9: What should I do if I miss a dose of Alfacalcidol?
A: If you miss a dose, take it as soon as you remember. However, if it is close to the time for your next dose, skip the missed dose and resume your regular schedule. Do not double the dose.
