Alfacalcidol: Indication, Dosage, Side Effect, Precaution

Generic Medicine Info Patient Medicine Information

This information is not country-specific. Please refer to the Malaysia prescribing information.

Generic Medicine Info

Indications and Dosage

Intravenous
Hyperparathyroidism, Hypoparathyroidism, Renal osteodystrophy

Adult: Initially, 1 mcg daily via bolus inj over approx 30 seconds, may be adjusted thereafter according to individual biochemical (e.g. plasma Ca levels), radiographic, or histological response. Usual maintenance dose: 0.25-1 mcg daily. Dose discontinuation may be required if hypercalcaemia occurs. Refer to detailed product guideline for further indication specific therapeutic measures.
Elderly: Initially, 0.5 mcg daily via bolus inj over approx 30 seconds, may be adjusted thereafter according to individual biochemical (e.g. plasma Ca levels), radiographic, or histological response. Usual maintenance dose: 0.25-1 mcg daily.
Child: In neonates and premature infants <1 month: Initially, 0.05-0.1 mcg/kg daily via bolus inj over approx 30 seconds; >1 month <20 kg: Initially, 0.05 mcg/kg daily via bolus inj over approx 30 seconds; >20 kg: Same as adult dose.

Intravenous
Osteomalacia, Rickets

Adult: In patients with nutritional and malabsorptive, hypophosphataemic vitamin D-resistant, and pseudo-deficiency (D-dependent) cases: Initially, 1 mcg daily via bolus inj over approx 30 seconds, may be adjusted thereafter according to individual biochemical (e.g. plasma Ca levels), radiographic, or histological response. Usual maintenance dose: 0.25-1 mcg daily. Dose discontinuation may be required if hypercalcaemia occurs. Refer to detailed product guideline for further indication specific therapeutic measures.
Elderly: Initially, 0.5 mcg daily via bolus inj over approx 30 seconds, may be adjusted thereafter according to individual biochemical (e.g. plasma Ca levels), radiographic, or histological response. Usual maintenance dose: 0.25-1 mcg daily.
Child: In neonates and premature infants <1 month: Initially, 0.05-0.1 mcg/kg daily via bolus inj over approx 30 seconds; >1 month <20 kg: Initially, 0.05 mcg/kg daily via bolus inj over approx 30 seconds; >20 kg: Same as adult dose.

Intravenous
Neonatal hypocalcaemia

Child: In neonates and premature infants: Initially, 0.05-0.1 mcg/kg daily via bolus inj over 30 seconds, followed by careful titration; doses up to 2 mcg/kg may be required in severe cases.

Oral
Hyperparathyroidism, Hypoparathyroidism, Renal osteodystrophy

Adult: As cap/oral drops: Initially, 1 mcg daily, adjust subsequent doses according to individual biochemical (e.g. plasma Ca levels), radiographic, or histological response. Dose increases may be done in increments of 0.25-0.5 mcg daily. Usual maintenance dose: 0.25-1 mcg daily. Dose discontinuation may be required if hypercalcaemia occurs. Refer to detailed product guideline for further indication specific therapeutic measures.
Elderly: As cap/oral drops: Initially, 0.5 mcg daily, adjust subsequent doses according to individual biochemical (e.g. plasma Ca levels), radiographic, or histological response. Dose increases may be done in increments of 0.25-0.5 mcg daily. Usual maintenance dose: 0.25-1 mcg daily.
Child: As cap/oral drops: In neonates and premature infants <1 month: Initially, 0.05-0.1 mcg/kg daily; >1 month <20 kg: Initially, 0.05 mcg/kg daily; >20 kg: Same as adult dose.

Oral
Neonatal hypocalcaemia

Child: As cap/oral drops: In neonates and premature infants: Initially, 0.05-0.1 mcg/kg daily, followed by careful titration; doses up to 2 mcg/kg may be required in severe cases.

Oral
Osteomalacia, Rickets

Adult: In patients with nutritional and malabsorptive, hypophosphataemic vitamin D-resistant, and pseudo-deficiency (D-dependent) cases: As cap/oral drops: Initially, 1 mcg daily, adjust subsequent doses according to individual biochemical (e.g. plasma Ca levels), radiographic, or histological response. Dose increases may be done in increments of 0.25-0.5 mcg daily. Usual maintenance dose: 0.25-1 mcg daily. Dose discontinuation may be required if hypercalcaemia occurs. Refer to detailed product guideline for further indication specific therapeutic measures.
Elderly: As cap/oral drops: Initially, 0.5 mcg daily, adjust subsequent doses according to individual biochemical (e.g. plasma Ca levels), radiographic, or histological response. Dose increases may be done in increments of 0.25-0.5 mcg daily. Usual maintenance dose: 0.25-1 mcg daily.
Child: As cap/oral drops: In neonates and premature infants <1 month: Initially, 0.05-0.1 mcg/kg daily; >1 month <20 kg: Initially, 0.05 mcg/kg daily; >20 kg: Same as adult dose.

Special Patient Group

Patients currently taking barbiturates and other anticonvulsants: May require larger doses to produce the desired effect.

Renal Impairment

Intravenous
Hypoparathyroidism; Renal osteodystrophy; Hyperparathyroidism; Rickets; Osteomalacia:
Patients undergoing haemodialysis: Initially, 1 mcg per dialysis, given into the return line from the haemodialysis machine at the end of each session. Max: 6 mcg per dialysis; 12 mcg/week.

Administration

Should be taken with food.

Contraindications

Hypercalcaemia, hyperphosphataemia, vitamin D toxicity, metastatic calcification.

Special Precautions

Patient with pulmonary tissue calcification, granulomatous diseases (e.g. sarcoidosis), nephrolithiasis, hypermagnesaemia. Concomitant treatment with digitalis glycosides; barbiturates and other anticonvulsants. Renal impairment. Children and elderly. Pregnancy and lactation.

Adverse Reactions

Significant: Hypercalcaemia (when prolonged may cause generalised vascular and soft tissue calcification, and exacerbated nephrolithiasis, arteriosclerosis or cardiac valve sclerosis); over suppression of PTH, hypercalciuria, hyperphosphataemia, adynamic bone disease; transient or long-lasting decreased kidney function.
Ear and labyrinth disorders: Vertigo.
Gastrointestinal disorders: Nausea, vomiting, diarrhoea, abdominal pain and discomfort, constipation.
General disorders and administration site conditions: Lassitude, asthenia, malaise, calcinosis.
Investigations: Increased plasma and urinary concentrations of Ca and phosphate, weight loss.
Metabolism and nutrition disorders: Anorexia, thirst.
Musculoskeletal and connective tissue disorders: Myalgia.
Nervous system disorders: Headache. Rarely, dizziness.
Psychiatric disorders: Confusional state.
Renal and urinary disorders: Polyuria, acute renal failure, nephrocalcinosis.
Skin and subcutaneous tissue disorders: Rash (e.g. maculo-papular, erythematous, pustular), pruritus, sweating, urticaria.

Monitoring Parameters

Monitor serum Ca and phosphate levels regularly, such as at least twice weekly, during treatment initiation and dose adjustments (particularly in children, patients with renal impairment, or taking high doses); PTH, alkaline phosphatase, and Ca x phosphate product as clinically indicated. Measurement frequency may be dependent on the presence and magnitude of abnormalities, and rate of disease progression.

Overdosage

Symptoms: Hypercalcaemia including nausea, vomiting, diarrhoea, anorexia, weight loss, thirst, polyuria, lassitude, headache, vertigo, and increased Ca and phosphate levels in the plasma and urine. Management: Supportive treatment. In acute cases, perform gastric lavage or administer mineral oil to reduce the absorption and promote faecal excretion. Ensure hydration by giving IV infusion of saline (forced diuresis). Monitor electrolytes, Ca and renal indices; assess for ECG abnormalities (particularly in patients on digitalis). May consider treatment with glucocorticosteroids, bisphosphonates, loop diuretics, calcitonin, and haemodialysis with low Ca content.

Drug Interactions

Increased risk of hypercalcaemia with thiazide diuretics, Ca-containing or other vitamin D-containing preparations. May precipitate cardiac arrhythmias with digitalis glycosides. Intestinal absorption may be impaired by colestyramine, colestipol, sucralfate, Al-based antacids (high dose), and mineral oil (prolonged use). May increase serum levels of Al in aluminium hydroxide, sucralfate or other Al-containing preparations. May increase metabolism with anticonvulsants (e.g. phenytoin, phenobarbital, carbamazepine, primidone). May cause hypermagnesaemia with Mg-based antacids or laxatives in dialysis patients.

Action

Description:
Mechanism of Action: Alfacalcidol is a precursor of calcitriol, which is an active metabolite of vitamin D. It promotes intestinal absorption of Ca and phosphorus, resorption of Ca from the bone, and possibly renal reabsorption of Ca.
Synonym: 1α-hydroxycholecalciferol.
Onset: 6 hours.
Duration: Effect on intestinal Ca absorption levels: 48 hours (1,25-dihydroxyvitamin D₃).
Pharmacokinetics:
Absorption: Time to peak plasma concentration: 1,25-dihydroxyvitamin D₃: Approx 12 hours (oral); 4 hours (IV).
Distribution: Enters breast milk. Plasma protein binding: Extensively to vitamin D-binding protein.
Metabolism: Rapidly and almost completely converted in the liver into 1,25-dihydroxyvitamin D₃ (calcitriol).
Excretion: Mainly via faeces; urine. Elimination half-life: Approx 35 hours; approx 3 hours (renal insufficiency).

Chemical Structure

Storage

Cap: Store between 15-25°C. Protect from direct sunlight. Oral drops/solution for inj: Store between 2-8°C. Protect from light and direct sunlight. Do not freeze.

MIMS Class

Agents Affecting Bone Metabolism

ATC Classification

A11CC03 - alfacalcidol ; Belongs to the class of vitamin D and analogues. Used as dietary supplements.

References

Alfacip Capsules (Cipla Malaysia Sdn Bhd). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my/. Accessed 03/06/2020.

AlfaD 1 microgram Capsules (Theramex Ireland Limited). MHRA. https://products.mhra.gov.uk/. Accessed 03/06/2020.

Anon. Alfacalcidol. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 03/06/2020.

Buckingham R (ed). Vitamin D Substances. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 03/06/2020.

Joint Formulary Committee. Alfacalcidol. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 03/06/2020.

LEO Pharma Ltd. One-Alpha 0.25 microgram Capsules, 1 microgram Capsules, 2 microgram/mL Oral Drops data sheet 26 April 2019. Medsafe. http://www.medsafe.govt.nz/. Accessed 03/06/2020.

One-Alpha (LEO Pharma). MIMS Singapore. http://www.mims.com/singapore. Accessed 03/06/2020.

One-Alpha 0.5 microgram Soft Capsules (LEO Laboratories Limited). MHRA. https://products.mhra.gov.uk/. Accessed 03/06/2020.

One-Alpha 2 microgram/mL Injection (LEO Laboratories Limited). MHRA. https://products.mhra.gov.uk/. Accessed 03/06/2020.

One-Alpha 2 microgram/mL Oral Drops (LEO Laboratories Limited). MHRA. https://products.mhra.gov.uk/. Accessed 03/06/2020.

Disclaimer: This information is independently developed by MIMS based on Alfacalcidol from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2024 MIMS. All rights reserved. Powered by MIMS.com