The first step involved in the activation of vitamin D3 is a 25-hydroxylation which is catalysed by the 25-hydroxylase in the liver and then by other enzymes. The mitochondrial sterol 27-hydroxylase catalyses the first reaction in the oxidation of the side chain of sterol intermediates. The active form of vitamin D3 (calcitriol) binds to intracellular receptors that then function as transcription factors to modulate gene expression. Like the receptors for other steroid hormones and thyroid hormones, the vitamin D receptor has hormone-binding and DNA-binding domains. The vitamin D receptor forms a complex with another intracellular receptor, the retinoid-X receptor, and that heterodimer is what binds to DNA. In most cases studied, the effect is to activate transcription, but situations are also known in which vitamin D suppresses transcription. Calcitriol increases the serum calcium concentrations by: increasing GI absorption of phosphorus and calcium, increasing osteoclastic resorption, and increasing distal renal tubular reabsorption of calcium. Calcitriol appears to promote intestinal absorption of calcium through binding to the vitamin D receptor in the mucosal cytoplasm of the intestine. Subsequently, calcium is absorbed through formation of a calcium-binding protein.

Alfacalcidol is indicated in:

• It is used to increase the amount of vitamin D in your body. This often increases calcium levels as well which can help in treatment of certain illnesses.
• In general this drug is used to treat diseases where the amount of calcium and phosphate (which is controlled by the level of vitamin D) in your body needs changing.
• Benefits of being on this drug can include control of the levels of calcium and phosphate in your body.
• Treat and prevent bone conditions that are caused by kidney failure (osteodystrophy)
• Treat illnesses and abnormalities affecting the parathyroid glands which make a substance called the parathyroid hormone.
• Correct low levels of calcium in the blood of newborn babies (hypocalcaemia)
• Treat the softening and deformity of the bones due to lack of calcium (rickets or osteomalacia)

Adults: The usual starting dose is 1 microgram each day. People usually take between 1 and 3 micrograms each day. Most people take between 0.25 and 1 microgram each day once the blood test results show the medicine is working.

If you have very low levels of calcium in your blood, your doctor may prescribe between 3 and 5 microgram each day. Your doctor may prescribe another medicine called a calcium supplement to take as well as Alfacalcidol. This will help to keep the right amount of calcium level in your blood.

Elderly: The usual starting dose is 0.5 microgram each day.

Children:

• Newborn and premature babies: The usual starting dose is 0.05 to 0.1 microgram per kilogram of body weight each day. If the level of calcium in their blood is very low, up to 2 micrograms per kilogram of body weight may be needed each day. A dose of 0.1 microgram per kilogram body weight each day is used to stop low blood calcium levels in premature babies.
• Children weighing less than 20 kilograms: The usual starting dose is 0.05 microgram per kilogram body weight each day.
• Children weighing more than 20 kilograms: The usual starting dose is 1 microgram each day.

Should be taken with food.

Hypercalcaemia, metastatic calcification, hyperphosphataemia (except when occurring with hypoparathyroidism), hypermagnesaemia.

Anorexia, nausea, vomiting, diarrhoea, lassitude, polyuria, sweating, headache, thirst, vertigo, pruritus, rash, urticaria. Hypercalcaemia, hypercalciuria and ectopic calcification.

In case of renal impairment, hyperphosphataemia. In hypercalcaemic dialysis patients, possibility of calcium influx from the dialysate should be considered.

Pregnancy & Lactation

FDA has not yet classified the drug into a specified pregnancy category.

Precautions & Warnings

Pregnancy, lactation, renal impairment, infants, elderly. Monitor serum levels of calcium in patients with renal failure. Caution in hypercalciuria in those with history of renal calculi. Avoid in patients with hypersensitivity to inj. containing propylene glycol.