Alfacalcidol

• Treatment and Prevention of Hypocalcemia associated with chronic renal failure (including dialysis patients).
• Management of Renal Osteodystrophy: Improves abnormal bone metabolism due to renal insufficiency.
• Vitamin D Deficiency and Related Disorders: Including hypoparathyroidism, rickets, and osteomalacia caused by vitamin D deficiency or impaired metabolism.
• Management of Secondary Hyperparathyroidism: In patients with chronic kidney disease.
• Other Uses: Sometimes used in osteoporosis treatment when vitamin D metabolism is impaired, or in certain cases of hypophosphatemia.

• Adults:
• Typical dose: 1–2 micrograms daily orally, adjusted based on serum calcium and phosphate levels.
• For renal osteodystrophy: 1–4 micrograms daily orally or intravenously depending on severity and clinical response.
• Elderly: Same as adults; dose adjustment may be required based on renal function and calcium status.
• Pediatrics:
• Dose usually ranges from 1–3 micrograms daily orally, adjusted carefully with medical supervision.
• Administration:
• Oral tablets or capsules, taken with or without food.
• Intravenous administration is reserved for specific clinical situations under supervision.
• Special Populations:
• Renal impairment: Dosing must be individualized; frequent monitoring necessary.
• Hepatic impairment: No specific dose adjustment recommended.

Alfacalcidol is a prodrug of the active hormone calcitriol (1,25-dihydroxyvitamin D3). It is rapidly converted in the liver to calcitriol, which binds to vitamin D receptors in the intestines, bones, kidneys, and parathyroid glands. This binding enhances intestinal absorption of calcium and phosphate, promotes bone mineralization, modulates parathyroid hormone secretion, and facilitates calcium mobilization from bone. The overall effect corrects hypocalcemia and improves bone metabolism in patients with impaired vitamin D activation or deficiency.

• Absorption: Well absorbed orally with peak plasma concentrations within 3–6 hours.
• Distribution: Widely distributed in plasma, highly bound to vitamin D binding proteins.
• Metabolism: Converted in the liver to active calcitriol; further metabolized in kidneys and other tissues.
• Half-life: Approximately 3–6 hours for alfacalcidol; active metabolite calcitriol half-life is ~15 hours.
• Elimination: Primarily excreted in bile and urine as inactive metabolites.

• Pregnancy: No well-controlled studies in humans; animal studies show no teratogenic effects at therapeutic doses. Use only if clearly needed and benefits outweigh risks.
• Lactation: Excreted in breast milk in small amounts; caution advised during breastfeeding, monitor infant for hypercalcemia.

• Primary Class: Vitamin D analog
• Subclass: Prodrug of active vitamin D (calcitriol)
• Pharmacologic: Bone metabolism regulator and calcium homeostasis agent

• Known hypersensitivity to alfacalcidol or any excipients.
• Hypercalcemia or hypercalciuria.
• Vitamin D toxicity.
• Untreated vitamin D deficiency causing hypercalcemia.
• Severe renal impairment without appropriate medical supervision.

• Risk of hypercalcemia and hypercalciuria: Monitor serum calcium and phosphate regularly.
• Use cautiously in patients with renal impairment; monitor renal function.
• Avoid vitamin D overdose to prevent toxicity symptoms.
• Monitor for symptoms of vitamin D toxicity: nausea, vomiting, weakness, polyuria.
• Use caution in patients with granulomatous diseases (e.g., sarcoidosis) that may increase vitamin D sensitivity.
• Not a substitute for calcium supplementation when dietary intake is insufficient.

• Common: Hypercalcemia (nausea, vomiting, constipation, headache, weakness), hypercalciuria.
• Less common: Thirst, dry mouth, metallic taste, muscle weakness.
• Rare/Serious: Nephrocalcinosis, renal failure due to hypercalcemia, allergic reactions (rash, pruritus, angioedema).

• Thiazide diuretics: May increase risk of hypercalcemia.
• Digitalis glycosides: Risk of arrhythmia increased with hypercalcemia.
• Magnesium-containing antacids: Risk of hypermagnesemia, especially in renal impairment.
• Corticosteroids: May reduce vitamin D efficacy.
• Phenytoin, phenobarbital, rifampicin: May increase metabolism of vitamin D derivatives, reducing efficacy.
• No significant involvement of CYP450 enzyme system in alfacalcidol metabolism.

• Recent nephrology guidelines emphasize individualized dosing and monitoring of vitamin D analogs like alfacalcidol to optimize mineral balance and reduce secondary hyperparathyroidism in CKD.
• Recommendations highlight the importance of correcting vitamin D deficiency early to prevent bone complications.
• Safety advisories underline the need for vigilant monitoring to avoid hypercalcemia and toxicity.

• Store at 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep container tightly closed.
• No refrigeration required.
• Protect from freezing.