ALPHADOL 0.25 MCG CAPSULES

Indications

• Hypophosphataemic rickets
• Persistent hypocalcaemia due to hypoparathyroidism
• Vitamin D dependent rickets
• Persistent neonatal hypocalcaemia
• Prevention of vitamin D deficiency in renal or cholestatic liver disease

Dosage

Children: Child 1 month–11 years: 25–50 nanograms/kg once daily; Child 12–17 years: 1 microgram once daily; Neonate: 50–100 nanograms/kg once daily, adjusted as necessary.

Adults: Initially, 1 microgram once daily, adjusted as necessary. Maximum dose is 1 microgram per day.

Mechanism of action

Alfacalcidol is converted to calcitriol in the liver and kidneys, which increases intestinal absorption of calcium and phosphate, promotes bone mineralization, and regulates parathyroid hormone levels.

Pharmacodynamics

Alfacalcidol acts as a potent regulator of calcium and phosphate homeostasis, enhancing the absorption of calcium from the gastrointestinal tract and influencing bone metabolism.

Pharmacokinetics

Alfacalcidol is absorbed rapidly after oral administration, with peak plasma concentrations occurring within a few hours. It is metabolized in the liver to its active form, calcitriol, and has a half-life of approximately 3 to 5 hours. It is excreted primarily in the bile and urine.

Adverse effects

• Dizziness
• Weight decreased
• Confusion
• Renal impairment
• Muscle weakness
• Paralytic ileus
• Polydipsia
• Psychiatric disorder
• Sensory disorder
• Urinary disorders

Interactions

• Vitamin D substances

Precautions

• Nephrolithiasis
• Care to ensure correct dose in infants
• Monitor plasma-calcium concentration in renal impairment
• Monitor plasma calcium, phosphate, and creatinine during dosage titration

Pregnancy

Alfacalcidol is generally considered safe in pregnancy; however, caution is advised and monitoring of calcium levels is recommended.

Breast-feeding

Alfacalcidol is excreted in breast milk; caution should be exercised when administering to nursing mothers.

Storage

Store below 25°C, protect from light.

Formulations

• Alfacalcidol 2 micrograms/ml oral drops
• Alfacalcidol 250 nanogram capsules
• Alfacalcidol 500 nanogram capsules
• Alfacalcidol 1 microgram capsules

Mechanism of action

In conditions like chronic renal failure, renal bone disease, hypoparathyroidism, and vitamin D dependent rickets, the kidneys' capacity for 1α-hydroxylation is impaired, leading to reduced production of endogenous 1,25-dihydroxyvitamin D and aberrated mineral metabolism. As an active and potent analog of vitamin D, alfacalcidol works to restore the functions and activities of endogenous 1,25-dihydroxyvitamin D.

Pharmacodynamics

Alfacalcidol works to increase serum levels of calcium by stimulating intestinal calcium absorption, reabsorption of calcium from bone, and possibly the renal reabsorption of calcium. It also modestly promotes intestinal phosphorus absorption. In patients with renal failure, alfacalcidol increased intestinal calcium and phosphorus absorption in a dose-related manner. This increase in calcium and phosphorus levels occurs within three days following drug administration: this effect was reversed within three days of drug discontinuation. In patients with chronic renal failure, serum calcium levels were elevated while parathyroid hormone and alkaline phosphatase levels returned to normal levels within five days following alfacalcidol administration. Since alfacalcidol suppresses parathyroid hormone, a reduction in parathyroid hormone levels is achieved more rapidly in patients on intermittent intravenous therapy, with significant reductions occurring within three months of therapy. In patients receiving daily oral therapy of alfacalcidol, the time it takes alfacalcidol to normalize plasma calcium levels may be up to several months, possibly reflecting calcium being utilized for bone mineralization. In patients with nutritional osteomalacia, alfacalcidol increased calcium absorption with six hours of oral administration and the effects peaked at 24 hours.