Calcifediol (semiactivated Vitamin D, high dose) available by prescription in Australia

Calcifediol high-strength formulation for vitamin D deficiency

Active ingredient: calcifediol

Brand name (sponsor): Vistella (Aspen Pharmacare)

Presentation: 255-microgram soft gelatin capsules

Route of administration: oral

Approved indication: treatment of vitamin D deficiency in adults, and maintenance treatment as required

Background: Vitamin D3 (colecalciferol) promotes absorption of calcium and phosphate in the gut and plays an important role in bone health. It is primarily synthesised in the skin through exposure to sunlight, with a smaller contribution from dietary sources. Tobecome active, vitamin D3 is first converted in theliver to calcifediol (25-hydroxyvitamin D), the form ofvitamin D that is measured in the serum, before beingconverted in the kidneys to calcitriol, the biologicallyactive form. Calcifediol is available over the counter as a 10-microgram capsule. Vistella, a prescription-only product, is the first high-strength calcifediol preparation, for intermittent administration (usually monthly), to be approved in Australia.

Clinical trials: Two clinical studies have evaluated the efficacy and safety of oral calcifediol using the same dosage regimen approved in Australia (255 micrograms once monthly or sometimes fortnightly).

Postmenopausal women with vitamin D deficiency:

In a double-blind, randomised controlled trial in postmenopausal women with vitamin Ddeficiency (25-hydroxyvitamin D concentrations below 50 nanomol/L), participants (n=303)were randomised to one of three groups: oral calcifediol 255 micrograms monthly for 12 months, oral calcifediol 255 micrograms monthly for 4 months followed by placebo for 8 months, ororal colecalciferol 25,000 units (625 micrograms)monthly for 12 months.1 The primary efficacy endpointwas the percentage of participants achievingserum 25-hydroxyvitamin D concentrations above75 nanomol/L at 4 months.1,2 At month 4, 35% of participants who received calcifediol achieved target 25-hydroxyvitamin D concentrations versus 8.2% of participants who received colecalciferol. 2 After 12 months of continuous treatment, the proportions of participants who achieved target 25-hydroxyvitamin D concentrations were 21.6% with calcifediol 255 micrograms once a month,versus 9.2% with colecalciferol 625 micrograms once a month. In participants who had calcifediolwithdrawn after 4 months, a significant decrease in25-hydroxyvitamin D was observed, with 86.7% fallingbelow 50 nanomol/L by month 12.1Younger adults with no comorbidities: Calcifediol wasalso studied in younger adults aged 18 to 50 yearsin a phase 1 clinical trial (n=101, 66% female).3 Thestudy comprised a 4-month open-label treatmentphase followed by a 5-month double-blind, placebocontrolled phase.During the open-label phase, participants with 25-hydroxyvitamin D concentrations below 25 nanomol/L (n=7) received fortnightly calcifediol,while those with concentrations between 25 and 50 nanomol/L (n=94) received monthly calcifediol. After 1 month of treatment, 57% of participantsachieved target 25-hydroxyvitamin D concentrations(above 50 nanomol/L), increasing to 83% after4 months.At the end of the open-label phase, participants with target 25-hydroxyvitamin D concentrations were randomised to receive either calcifediol or placebo, taken monthly for 5 months. At the endof the study, 89% of those who received calcifediolmaintained target concentrations compared with 49%on placebo.3

Adverse effects: The main adverse effects ofcalcifediol are those associated with excessivevitamin D supplementation and hypercalcaemia .When taken at the approved dose and frequency, calcifediol is usually well tolerated.4 A serum25-hydroxyvitamin D concentration above 375 nanomol/L is associated with an increased incidence of adverse effects.5

Dosage and administration: The standard dosage of calcifediol is 255 micrograms (one capsule) once a month, taken orally. More frequent doses may be needed for severe vitamin D deficiency; however, the dose should not exceed one capsule every 2 weeks and the frequency should be lowered once vitamin Dconcentrations have stabilised.5

Precautions: In patients with severe renal impairment(creatinine clearance less than 30 mL/min), there may be a significant reduction in efficacy because calcifediol is activated in the kidneys.In patients with prolonged immobilisation, a dose reduction may be needed to avoid hypercalcemia . 5Vistella capsules contain the colouring agent sunset yellow, which can cause allergic reactions and asthma, especially in patients allergic to acetylsalicylic acid. 5Calcifediol concentrations may be reduced if administered with drugs that induce cytochrome P450 3A4 (e.g., phenytoin). Other drugs that can interact with calcifediol include orlistat, digoxin, verapamil and corticosteroids 5

Use in pregnancy and breastfeeding: Calcifediolis is classified as Therapeutic Goods Administration pregnancy category B3 and should not be used during pregnancy. It is excreted into breastmilk andshould not be used during breastfeeding.5

Place in therapy:

Calcifediol 255-microgram(Vistella) capsules provide another option for the treatment of vitamin D deficiency in adults. There is some evidence that calcifediol may increase vitamin D concentrations more rapidly than colecalciferol; however, no clinical trials to date have compared the approved calcifediol dosage regimen with colecalciferol dosage regimens commonly used in Australia for the initial treatment of vitamin D deficiency (e.g., 75 to 125 micrograms daily for 6 to12 weeks6). It is important to note that colecalciferol and calcitriol cannot be therapeutically compared microgram to microgram.7 Pharmacokinetic studies and a 2024 international consensus statement suggest calcifediol may have an advantage over colecalciferol in certain groups, such as people with vitamin D malabsorption or obesity,8,9, and it may be beneficial in patients requiring rapid correction of deficiency.9 Monthly (or in some cases fortnightly)dosing may be more convenient than daily supplementation for some people, but may be prone to dosing errors and over-supplementation if taken more frequently than recommended. Vistella is not listed on the Pharmaceutical Benefits Scheme and is more expensive than colecalciferol.

Practice points:

Monitor 25-hydroxyvitamin D concentrations while on treatment and monitor for hypercalcaemia. Patients should be advised on the importance of adhering to the recommended treatment frequency, and recommendations around diet and co-administration of calcium supplements to minimise the risk of toxicity. Patients should also be educated on the signs and symptoms of hypercalcaemia (e.g. weakness, fatigue, drowsiness, headache, nausea, vomiting, abdominal cramps).

PDF

REFERENCES

  1. Perez-Castrillon JL, Duenas-Laita A, Gomez-Alonso C,Jodar E, Del Pino-Montes J, Brandi ML, et al. Long-TermTreatment and Effect of Discontinuation of Calcifediolin Postmenopausal Women with Vitamin D Deficiency:A Randomized Trial. J Bone Miner Res 2023;38:471-9.https://doi.org/10.1002/jbmr.47762.

  2. Perez-Castrillon JL, Duenas-Laita A, Brandi ML, Jodar E,Del Pino-Montes J, Quesada-Gomez JM, et al. Calcifediol is superior to cholecalciferol in improving vitamin D status in postmenopausal women: a randomized trial. J Bone Miner Res2021;36:1967-78. https://doi.org/10.1002/jbmr.43873.

  3. Guerra Lopez P, Urroz Elizalde M, Vega-Gil N,Sanchez Santiago B, Zorrilla Martinez I, Jimenez-Mercado M,et al. Efficacy and Safety of Calcifediol in Young Adults with Vitamin D Deficiency: A Phase I, Multicentre, Clinical TrialPOSCAL Study. Nutrients 2024;16. https://doi.org/10.3390/nu160203064.

  4. Therapeutic Goods Administration. Australian Public Assessment Report for Vistella. Department of Health, Disability and Ageing; 2025. https://www.tga.gov.au/resources/auspar/vistella [cited 2025 Sep 22]

  5. Therapeutic Goods Administration. Australian Product Information - VISTELLA calcifediol (as monohydrate)capsule blister. Department of Health, Disability and Ageing;2025. https://www.tga.gov.au/resources/artg/413380[cited 2025 Sep 19]6. Australian Medicines Handbook Pty Ltd.

  6. Australian Medicines Handbook 2025 (online). Adelaide; 2025. https://amhonline.amh.net.au/ [cited 2025 Oct 28]

  7. Sosa Henriquez M, Gomez de Tejada Romero MJ.Cholecalciferol or Calcifediol in the Management of Vitamin D Deficiency. Nutrients 2020;12. https://doi.org/10.3390/nu120616178.

  8. Charoenngam N, Kalajian TA, Shirvani A, Yoon GH, Desai S, McCarthy A, et al. A pilot-randomized, double-blind crossover trial to evaluate the pharmacokinetics of orally administered 25-hydroxyvitamin D3 and vitamin D3 in healthy adults with differing BMI and in adults with intestinal malabsorption. Am J Clin Nutr 2021;114:1189-99. https://doi.org/10.1093/ajcn/nqab1239.

  9. Giustina A, Bilezikian JP, Adler RA, Banfi G, Bikle DD, Binkley NC, et al. Consensus Statement on Vitamin D Status Assessment and Supplementation: Whys, Whens, and Hows.Endocr Rev 2024;45:625-54. https://doi.org/10.1210/endrev/bnae009

Created December 2025