Approval date: April 18, 2007

Revision date: December 28, 2012

　　　　　July 1, 2013

Alfacalcitol Soft Capsules Instructions

Please read the instructions carefully and use under the supervision of a physician

Drug Name

　　Generic Name: Alfacalcitol Soft Capsules

　　Trade name: IANFAN

　　English name: Alfacalcidol Soft Capsules

　　Hanyu Pinyin: Afaguhuachun Ruan Jiaonang

Ingredients  

　　Alfacalcidol is the main ingredient of this product.

　　Chemical name: (5Z,7E)-9,10-open ring cholesta-5,7,10(19)-triene-1α,3β-diol

　　Chemical structural formula:

　　Molecular formula: C27H44O2

　　Molecular weight: 400.6

Properties

　　This product is a soft capsule containing light yellow oily liquid.

Indications

　　This product is used for the treatment of calcium metabolism disorders caused by insufficient production of endogenous 1,25-dihydroxyvitamin D3. For example, renal osteodystrophy, postoperative or idiopathic hypoparathyroidism, pseudohypoparathyroidism, as an adjuvant therapy for tertiary hyperthyroidism, anti-vitamin D rickets or osteochondrosis, vitamin D-dependent rickets, neonatal hypocalcemia or rickets, calcium malabsorption, osteoporosis, malabsorption and nutritional rickets and osteochondrosis.

Specification】（1）0.25μg （2）1μg

Usage and dosage

　　Starting dose:

　　Adults and children weighing more than 20 kilograms: 1μg /day

　　Children weighing less than 20 kilograms: 0.05μg/kg/day

　　Neonates: 0.1μg /kg/day

　　Dosage should be adjusted according to the results of biochemical tests to avoid hypercalcemia. Indicators of efficacy include: serum calcium level, alkaline phosphatase level, parathyroid hormone level, urinary calcium excretion, as well as imaging and histologic examinations. Most patients with severe bone disease (except for those with renal failure) can tolerate higher doses without hypercalcemia. However the failure of serum calcium to rise in a timely manner in patients with osteochondrosis does not mean that a larger dose is needed, as the absorbed calcium may be integrated into the demineralized bone. The effective therapeutic dose for most patients is 1-3 μg daily, which may be reduced when there is biochemical or imaging evidence of bone healing in patients with osteochondrosis, or when serum calcium levels normalize in patients with hypoparathyroidism. Maintenance dose is usually 0.25-2 μg /day. Patients taking barbiturates or other anticonvulsant medications may require a higher dose of alfacalcitol softgels to achieve the desired effect.

[Adverse Reactions

　　Except for hypercalcemia, no other adverse reactions have been identified.

Contraindications

　　This product is contraindicated in patients with known hypersensitivity to 1α-hydroxyvitamin D3, vitamin D and its analogs or derivatives, in patients with evidence of biochemical indicators of hypercalcemia, and in patients with evidence of excess vitamin D overdose.

[PRECAUTIONS

　　Periodic serum calcium checks are required throughout the course of alfacalcitol soft gelatin capsules therapy, and alfacalcitol soft gelatin capsules can only be used safely if serum calcium and other appropriate biochemical indicators are monitored.

　　Frequency of monitoring: Depending on the degree of improvement of the patient, plasma calcium should be checked weekly or monthly, with additional monitoring required early in treatment (especially in patients with high plasma calcium) and later in the course of treatment when evidence of bone healing has occurred. Plasma calcium should also be monitored regularly during initial therapy in the absence of significant bone-involving disease such as hypoparathyroidism. If hypercalcemia occurs, use of Alfacalcitol Soft Capsules should be discontinued immediately until serum calcium returns to normal (approximately one week), and then therapy should be restarted at half the original dose.The risk of hypercalcemia depends on a number of factors such as the extent of mineralization defects, renal function, and the dose of Alfacalcitol Soft Capsules. When biochemical evidence of bone healing is present (e.g., normalization of plasma alkaline phosphatase), hypercalcemia may occur if the dose of Alfacalcitol Soft Capsules is inappropriately reduced. Longer-term hypercalcemia should be avoided, especially in patients with chronic renal insufficiency.

　　In patients with renal bone disease, Alfacalcitol Soft Capsules should be administered concomitantly with a phosphorus-binding agent to prevent hyperphosphatemia, which may increase the risk of metastatic calcification.

[For pregnant and lactating women

　　Alfacalcitol Soft Capsules may be used in pregnant and lactating women only if deemed necessary by a physician.

For children

　　See other items in this instruction manual, or as directed by a physician.

Geriatric Use

　　There is no specific experience with the use of medication in elderly patients, and there are no additional recommendations for precautions and dose adjustments.

Drug Interactions

　　Patients taking barbiturates or other anticonvulsant drugs may require a higher dose of Alfacalcitol Softgels to achieve the desired effect.

[Drug Overdose].

　　Hypercalcemia may be corrected by discontinuing Alfacalcitol Softgels; severe hypercalcemia may require further treatment with diuretics, intravenous fluid replacement and corticosteroids.

[Pharmacology and Toxicology

　　Alfacalcitol (1α-hydroxyvitamin D3) is rapidly converted in the liver to 1,25-dihydroxyvitamin D3. this substance is an active metabolite of vitamin D3, which can regulate the calcium-phosphorus balance in the body. Inadequate production of endogenous 1,25-dihydroxyvitamin D3 in the kidneys can lead to disturbances in mineral metabolism. This is seen in renal bone disease, hypoparathyroidism and vitamin D-dependent rickets. These disorders require high doses of vitamin D to correct, but only small amounts of alfacalcitol softgels are needed. The main advantage of alfacalcitol softgels over vitamin D is that the effect is faster and reversible. This allows for more accurate dosage adjustment and reduces the risk of medication-induced hypercalcemia.

Pharmacokinetics

　　Alfacalcitol is fat-soluble with oral bioavailability close to 100%. After absorption, it is rapidly converted in the liver to 1,25-dihydroxyvitamin D3. Alfacalcitol has a plasma half-life of 3 hours. Alfacalcitol has a plasma half-life of 3 hours and 1,25-dihydroxyvitamin D3 is present in plasma within 30 minutes of oral administration. Serum levels of 1,25-dihydroxyvitamin D3 peak 8-12 hours after a single dose of alfacalcitol is given.The half-life of 1,25-dihydroxyvitamin D3 is about 35 hours. The metabolism of alfacalcitol is similar to that of vitamin D3.

Storage】closed, moisture-proof, shielded from light, stored at 15℃-25℃.

Packaging】Capsules are packed in blister plates, which are made of aluminum/PVC vesicles and polyamine/aluminum cover material. 10 capsules, 30 capsules/box.

Effective period: 24 months

【Executive Standard

　　Import drug registration standard: JX20020272

【Approval Document Number

　　Imported Drug Registration No.: H20130513 (Specification: 0.25μg)                     

　　Import Drug Registration No.: H20130514 (Specification: 1μg)     

【Manufacturer

　　Company name: LEO Pharma A/S

　　　　　　　LEO Pharma Denmark Ltd.

　　Address: 55 Industriparken, DK-2750 Ballerup, Denmark