Consumer medicine information

Calcitriol AN Capsules



Brand name

Calcitriol AN Capsules

Active ingredient





Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Calcitriol AN Capsules.

What is in this leaflet

This leaflet answers some common questions about Calcitriol AN capsules.

It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking Calcitriol AN capsules against the benefits they expect it will have for you.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine.

You may need to read it again.

What Calcitriol AN is used for

Calcitriol AN contains the active ingredient calcitriol, one of the naturally occurring and biologically active forms of Vitamin D. Calcitriol acts in the body in a similar manner to Vitamin D.

Calcitriol AN is used to treat people with osteoporosis, a disease where the bones of the body weaken, and in the prevention of osteoporosis in people taking oral corticosteroids.

Calcitriol AN capsules are also prescribed for patients who have low blood calcium levels due to osteodystrophy (a type of bone disease), hypoparathyroidism (a condition where the parathyroid glands have decreased function) and rickets.

Calcitriol AN increases calcium absorption in the intestine and stimulates healthy bone growth. There are many different types of medicines used to treat bone conditions. Calcitriol AN belongs to a group of medicines known as vitamin D compounds.

Your doctor may have prescribed Calcitriol AN for another purpose.

Ask your doctor if you have any questions why Calcitriol AN has been prescribed for you.

This medicine is available only with a doctor's prescription.

Calcitriol AN is not addictive.

Before you take Calcitriol AN

When you must not take it

Do not take Calcitriol AN if:

  • You have had an allergic reaction to Calcitriol AN, calcitriol or any ingredients listed in the Ingredients section of this leaflet
  • You have high blood calcium levels (hypercalcaemia)
  • You have vitamin D toxicity
  • You are breastfeeding or wish to breastfeed.
    Calcitriol AN may pass into the breast milk and have unwanted effects in the baby.

Do not take Calcitriol AN if the package shows signs of tampering or if the capsules do not look quite right.

Do not take Calcitriol AN if the expiry date (EXP) printed on the bottle has passed.

If you take this medicine after the expiry date has passed, it may not work as well.

If you are not sure if you should be taking Calcitriol AN, talk to your doctor.

Before you start to take it

You must tell your doctor if:

  • You are allergic to any other medicines, foods, dyes or preservatives
  • You have any other health problems including:
    - kidney problems.
    - you are bedridden or in a wheelchair
    - Vitamin D resistant rickets
    - an abnormal heartbeat
  • You are pregnant or intend to become pregnant.
    Your doctor will discuss the risks and benefits of taking Calcitriol AN when pregnant.

If you have not told your doctor about any of the above, tell them before you take any Calcitriol AN.

Taking other medicines

Tell your doctor if you are taking any other medicines including any that you have bought from a pharmacy, supermarket or health food shop.

Some medicines and Calcitriol AN may interfere with each other. These include:

  • medicines, vitamin tablets or health supplements containing vitamin D or calcium
  • cholestyramine
  • antacids containing magnesium
  • digoxin
  • thiazide diuretics
  • phenytoin
  • phenobarbital
  • corticosteroids

These medicines may be affected by Calcitriol AN, or may affect how well it works. You may need to take different amounts of your medicine, or you may need to take different medicines. Your doctor will advise you.

Your doctor and pharmacist have a complete list of medicines to be careful with or avoid while taking Calcitriol AN.

Ask your doctor or pharmacist if you are not sure about this list of medicines.

Use in Children

When children are taking Calcitriol AN for a long time, the dose should be well controlled and blood levels of calcium should be monitored so that kidney stones don’t develop.

How to take Calcitriol AN

How much to take

Your doctor will tell you how many Calcitriol AN capsules to take each day. This will vary depending on the nature of your illness, the level of calcium in your blood and your individual response to Calcitriol AN. Your doctor will need to make regular measurements of the calcium level in your blood while you are taking Calcitriol AN.

Osteoporosis Patients
Generally the daily dose for adults is 0.25 micrograms (one capsule) taken twice daily.

Osteodystrophy, Hypoparathyroidism & Rickets
Generally the initial daily dose for adults is 0.25 micrograms (one capsule) given in the morning. If calcium levels have not improved significantly after 2 to 4 weeks treatment with Calcitriol, your doctor may gradually increase the dose in 0.25 microgram steps until a satisfactory calcium level in your blood is achieved.

For Infants & Small Children with Hypoparathyroidism
As for adults, the correct dose of Calcitriol must be determined by your doctor. For children between 1 and 5 years of age the recommended daily dose is 0.25 to 0.75 micrograms (one to three capsules).

How to take it

Capsules should be swallowed whole with a glass of water.

Do not open the capsules and do not take any capsules that are damaged.

When to take it

Calcitriol AN can be taken at any time of day with or without food.

How long to take Calcitriol AN

Calcitriol AN is usually taken continuously for long term treatment.

Always tell your doctor if you want to stop taking Calcitriol AN as stopping suddenly can lead to a rapid fall in calcium levels.

If you forget to take Calcitriol AN

Do not take an extra dose. Wait until the next dose and take your normal dose then. Do not try to make up for the dose that you missed by taking more than one dose at a time.

In case of an overdose

Immediately telephone your doctor or Poisons Information Centre (telephone 13 11 26) for advice or go to Accident and Emergency at your nearest hospital if you think that you or anyone else may have taken too much Calcitriol AN, even if there are no signs of discomfort or poisoning.

You may need urgent medical attention. Signs of overdosage include loss of appetite, headache, excessive thirst, feeling sick, vomiting and constipation.

Keep telephone numbers for these places handy.

If you are not sure what to do, contact your doctor or pharmacist.

While you are taking Calcitriol AN

Things you must do

Tell all doctors, dentists and pharmacists who are treating you that you are taking Calcitriol AN.

Do not take any other medicines whether they require a prescription or not without first telling your doctor. Tell your doctor if you become pregnant while taking Calcitriol AN.

Tell your doctor if, for any reason, you have not taken your medicine exactly as prescribed.

Otherwise, your doctor may think that it was not effective and change your treatment unnecessarily.

Tell your doctor if you feel the capsules are not helping your condition.

Be sure to keep all of your appointments with your doctor so that your progress can be checked.

Always discuss with your doctor any problems or difficulties during or after taking Calcitriol AN capsules.

Calcitriol AN and Diet

You should discuss your diet with your doctor and adhere strictly to your dietary recommendations.

Sudden changes in diet, particularly the amount of dairy products, may lead to increased calcium in your blood. If this happens, you may feel sick, vomit, be confused, experience weakness, be constipated and experience increased urination.

Calcitriol AN and Laboratory Tests

Make sure that you keep all blood test appointments with your doctor.

These are to check your blood calcium levels while you are taking Calcitriol AN. Your doctor will discuss your specific needs with you.

Things you must not do

Do not suddenly stop taking Calcitriol AN or change the dose without first checking with your doctor. Your doctor will tell you the best way to slowly reduce the amount of Calcitriol AN you are taking before stopping completely.

Do not let yourself run out of medicine over the weekend or on holidays.

Do not give Calcitriol AN to anyone else even if their symptoms seem similar to yours.

Do not use Calcitriol AN to treat other complaints unless your doctor says to.

Things to be careful of

Your ability to drive a car or operate machinery may be affected by medicines. Normally, your ability to drive a car or operate machinery will not be affected by Calcitriol AN.

Side Effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking Calcitriol AN.

Calcitriol AN helps most people but it may have unwanted side effects in a few. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

Tell your doctor if you notice any of the following and they worry you:

  • not feeling hungry (loss of appetite)
  • feeling sick
  • headache
  • fever
  • vomiting or stomach ache
  • constipation
  • weakness or muscle weakness
  • dry mouth or thirst
  • irregular and/or rapid heart beat
  • urinary tract infection

These are all symptoms of high levels of calcium in your blood. If you experience any of these, tell your doctor immediately. This is not a complete list of all possible side effects. Others may occur in some people and there may be some side effects not yet known.

Other side effects not listed above may also occur in some patients. Tell your doctor if you notice anything else that is making you feel unwell.

Ask your doctor or pharmacist if you do not understand anything in this list.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

After taking Calcitriol AN


Keep your capsules in the bottle until it is time to take them.

If you take the capsules out of the bottle they may not keep well.

Keep Calcitriol AN in a cool dry place where the temperature stays below 25°C. Do not store it, or any other medicine, in a bathroom or near a sink.

Do not leave it in the car or on window sills.

Heat and dampness can destroy some medicines.

Keep Calcitriol AN where young children cannot reach it.

A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.


If your doctor tells you to stop taking Calcitriol AN, or the capsules have passed their expiry date, ask your pharmacist what to do with any capsules that are left over.

Product Description

What Calcitriol AN looks like

Calcitriol AN capsules are red coloured, oval soft gelatin capsules containing a clear oily liquid.


Active ingredient - calcitriol Each Calcitriol AN capsule contains 0.25 micrograms of calcitriol.

Inactive ingredients - The capsules also contain:

  • butylated hydroxyanisole
  • butylated hydroxytoluene
  • fractionated coconut oil
  • gelatin
  • glycerol
  • sorbitol
  • titanium dioxide
  • iron oxide red
  • iron oxide yellow

Calcitriol AN is available in bottles (AUST R 99717) or blisters (AUST R 230366) of 100 capsules.

Name and address of sponsor

Amneal Pharma Australia Pty Ltd
12 River Street
South Yarra 3141

Date of Preparation

January 2015


Brand name

Calcitriol AN Capsules

Active ingredient





Name of the medicine



Butylated hydroxyanisole, butylated hydroxytoluene, fractionated coconut oil, gelatin, glycerol, sorbitol (70 percent, noncrystallising), iron oxide red and iron oxide yellow.


Chemical name: 1,25-dihydroxycholecalciferol. Molecular formula: C27H44O3. MW: 416.65. CAS: 32222-06-3.
Calcitriol is a white, crystalline compound, which occurs naturally in humans. It is soluble in organic solvents but practically insoluble in water.
Calcitriol is available as soft gelatin capsules containing 0.25 micrograms of calcitriol. Each capsule also contains butylated hydroxyanisole, butylated hydroxytoluene, fractionated coconut oil, gelatin, glycerol, sorbitol (70 percent, non-crystallising), iron oxide red and iron oxide yellow.



Calcitriol is the most important active metabolite of vitamin D3. It is normally formed in the kidney from its precursor 25-hydroxycholecalciferol (25-HCC). Physiological daily production is normally 0.5-1.0 microgram and is somewhat higher during periods of increased bone synthesis (e.g. growth or pregnancy).
The natural supply of vitamin D in humans depends mainly on exposure to ultraviolet rays of the sun for conversion of 7-dehydrocholesterol in the skin to vitamin D3 (cholecalciferol). Vitamin D3 must be metabolically activated in the liver and the kidney before it is fully active as a regulator of calcium and phosphorus metabolism at target tissues. The initial transformation of vitamin D3 is catalysed by a vitamin D3-25-hydroxylase enzyme (25-OHase) present in the liver, and the product of this reaction is 25-hydroxyvitamin D3 [25-(OH) D3]. Hydroxylation of 25-(OH) D3 occurs in the mitochondria of kidney tissue, activated by the renal 25-hydroxyvitamin D3-1 alpha-hydroxylase (alpha-OHase), to produce 1,25-(OH)2 D3 (calcitriol), the active form of vitamin D3.
Calcitriol binds to an intracellular receptor, a member of the steroid receptor superfamily. The calcitriol receptor complex interacts with specific DNA sequences that regulate transcription and protein synthesis in a variety of cells including osteoblasts, mucosal cells of the intestine, renal tubular cells and parathyroid cells. The changes in protein synthesis induced in these cells by calcitriol are responsible for its profound physiological effects. A vitamin D resistant state exists in uremic patients because of the failure of the kidney to convert precursors to the active compound. The uremic state may also inhibit the binding of the calcitriol receptor to its specific DNA responsive elements.
The key role of calcitriol in the regulation of bone and calcium homeostasis, which includes stimulating effects on osteoblastic activity in the skeleton, provides a sound pharmacological basis for its therapeutic effects in osteoporosis. Treatment of established osteoporosis with calcitriol is associated with an increase in bone density and a reduction in new vertebral fractures. Established osteoporosis is defined as the finding of: bone mineral density measurements of 2 or more standard deviations below the gender specific peak bone mass; or the presence or history of osteoporotic fracture. Calcitriol also reduces bone loss associated with corticosteroid therapy.
In patients with marked renal impairment, synthesis of endogenous calcitriol is correspondingly limited or may even cease altogether. This deficiency plays a key role in the development of renal osteodystrophy. In patients with renal osteodystrophy, administration of calcitriol normalises reduced intestinal absorption of calcium, hypocalcemia, increased serum alkaline phosphatase and serum parathyroid hormone concentration.
In patients with hypophosphataemic rickets and hypophosphataemia, treatment with calcitriol reduces tubular elimination of phosphates and, in conjunction with concurrent phosphate treatment, corrects some skeletal abnormalities.



Calcitriol is rapidly absorbed from the intestine. Peak serum concentrations (above basal values) were reached within 3 to 6 hours following oral administration of single doses of 0.25 to 1.0 microgram of calcitriol.
Peak plasma concentrations (above basal values) were reached within 2-6 hours following oral administration of a steady state dose of 1 microgram per day.


Following a single oral dose of 0.5 microgram mean serum concentrations of calcitriol rose from a baseline value of 40.0 ± 4.4 (S.D.) picogram/mL to 60.0 ± 4.4 pg/mL at 2 hours and declined to 53.0 ± 6.9 at 4 hours, 50 ± 7.0 at 8 hours, 44 ± 4.6 at 12 hours and 41.5 ± 5.1 at 24 hours.
Following a steady state dose of 1 microgram per day the peak plasma concentrations of calcitriol rose from a baseline value of 47.9 ± 14.6 (SD) picogram/mL to 83.0 ± 17.2 (SD) picogram/mL after 4 hours.
Calcitriol and other vitamin D metabolites are transported approximately 99.9% bound to specific plasma proteins in the blood.


Several metabolites of calcitriol, each exerting different vitamin D activities, have been identified: 1α,25-dihydroxy-24-oxo-cholecalciferol; 1α,23,25-trihydroxy-24-oxo- cholecalciferol; 1α,24R,25-trihydroxycholecalciferol; 1α,25R-dihydroxycholecalciferol-26,23S- lactone; 1α,25S,26-trihydroxycholecalciferol; 1α25-dihydroxy-23-oxo-cholecalciferol; 1α,25R,26-trihydroxy-23-oxo-cholecalciferol and 1α-hydroxy-23-carboxy-24,25,26,27-tetranorcholecalciferol. 1α,25R-dihydroxycholecalciferol-26,23S-lactone is the major metabolite in humans.


The elimination half-life of calcitriol from serum was found to range from 3 to 6 hours. However, the pharmacological effect of a single dose of calcitriol lasts about three to five days. Enterohepatic recycling and biliary excretion occur. Following intravenous administration of radiolabelled calcitriol in normal subjects, approximately 27% and 7% of the radioactivity appeared in the faeces and urine respectively, within 24 hours. When a 1 microgram oral dose of radiolabelled calcitriol was administered to normals, approximately 10% of the total radioactivity appeared in urine within 24 hours. Cumulative excretion of radioactivity on the sixth day following intravenous administration of radiolabelled calcitriol averaged 16% in urine and 49% in faeces.
There is evidence that maternal calcitriol may enter the fetal circulation.
A bioequivalence study comparing Douglas Calcitriol AN capsules with Roche Rocaltrol capsules in a single 1 microgram dose is summarized in Table 1 and Table 2.

Clinical Trials

Females with osteoporosis.

The pathophysiology of osteoporosis is essentially the same in females and males. There are few data on the safety and efficacy of calcitriol on fracture rates and bone mineral density in premenopausal women.

Postmenopausal osteoporosis.

Calcitriol versus calcium.

The pivotal evidence for the efficacy of calcitriol in postmenopausal osteoporosis is provided by a three year, open label multicentre randomized comparison of calcitriol versus calcium in 432 patients (calcitriol n = 213, calcium n = 219). Vertebral fracture rate was assessed by X-ray evidence. Treatment with calcitriol 0.25 microgram twice daily for three years resulted in a threefold reduction in the rate of new vertebral fractures in women with postmenopausal osteoporosis compared with calcium supplementation of 1000 mg daily. There was a reduction in the number of patients with new fractures, the number of new fractures per se and the fracture rate expressed as fractures per 100 patient years in the calcitriol group when compared to the calcium group. The differences between calcitriol and calcium groups increased over the three year study period, reaching significance by the second year. Serum calcium and creatinine were monitored regularly and dosage was halved if levels became elevated. Hypercalcemia was reported in two patients.

Calcitriol versus placebo.

A randomised, double blind, placebo controlled trial was conducted in 40 patients (calcitriol n = 18, placebo n = 22). Calcitriol was increased from an initial dose of 0.25 microgram twice daily until hypercalcemia developed, at which point the dosage was adjusted and calcium intake reduced to maintain stable serum and urinary calcium. Dietary calcium was maintained at 1000 mg per day and 400 IU vitamin D was administered to each patient. After two years, calcitriol treated patients had an increase in spine bone density of 1.94% measured by dual photon absorptiometry compared to a decrease of 3.92% in patients on placebo (p = 0.001). The sample size was too small to show positive data on fracture rate after two years.
Phase II studies of calcitriol in postmenopausal osteoporosis were undertaken in the USA and involved a total of 93 patients. The primary endpoint was effect on vertebral fracture rates. Dose titration resulted in a mean dose of 0.5 to 0.6 microgram/day. Two studies were very similar, with an initial two month placebo treatment for all patients, followed by a ten month double blind comparison of calcitriol and placebo, with a subsequent extension of 12 to 30 months during which all patients received calcitriol. The third study compared calcitriol with placebo in an initial six month single blind evaluation, with a subsequent open phase of up to 24 months calcitriol treatment. Dietary calcium was supplemented to 600 mg per day in the two double blind trials. A highly significant reduction was noted in the fracture rate in patients treated with calcitriol in comparison with placebo in the three double blind studies. Overall, there was a statistically significant association between calcitriol treatment and the suppression of fractures. Calcium absorption was significantly increased in the calcitriol groups in all three studies.

Males with osteoporosis.

There are few data on the safety and efficacy of calcitriol on fracture rates and bone mineral density in osteoporotic men.

Calcitriol versus calcium.

A randomised double blind, placebo controlled pilot trial assessed the efficacy of calcitriol 25 microgram twice daily versus calcium 500 mg twice daily for 24 months in men with osteoporosis. Twenty one men were randomised to receive calcitriol and 20 to receive calcium. Due to the size of the study no valid conclusions were drawn regarding the efficacy in terms of bone mineral density (BMD) and vertebral fracture rates.

Corticosteroid induced osteoporosis.

A randomised, double blind, placebo and comparator controlled trial was conducted in 103 enrolled male and female patients with rheumatic, immunological or respiratory disease. The subjects enrolled within four weeks of starting long-term corticosteroid therapy. The three treatment groups were the placebo group (n = 29, calcium 1000 mg/day), calcitriol group (n = 34, oral calcium 1000 mg/day, calcitriol 0.5-1 microgram/day) and the calcitriol plus calcitonin group (n = 29, oral calcium 1000 mg/day, calcitriol 0.5-1 microgram/day, intranasal calcitonin 400 IU/day). Each treatment group received active treatment for 12 months and was followed up for a further 12 months.
The primary efficacy endpoint was bone mineral density measured at the lumbar spine, femoral neck and distal radius by photon absorptiometry. Serum levels of parathyroid hormone, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and osteocalcin and urinary levels of calcium, hydroxyproline and creatinine were also measured. The bone density measurements and biochemical analyses were made at baseline and then every four months for two years. Serum calcium was measured at one, three and five weeks and every two months thereafter.
After the first year both treatment groups showed a similar and statistically significant reduction in bone loss at the lumbar spine but not at the femoral neck or distal radius compared to the placebo group. In the second year, this reduction in bone loss was no longer apparent in the calcitriol group. However, this group did receive a higher cumulative dose of corticosteroids during the second year.
The study medications were generally well tolerated with few adverse effects. The most frequent events were hypercalcemia and rhinorrhea. Hypercalcemia was seen in one placebo group patient, one calcitriol group patients and eight calcitriol plus calcitonin group patients. Other less frequently reported adverse events included rash, headache and gastrointestinal symptoms.


Calcitriol AN is indicated for the treatment of established osteoporosis diagnosed by objective measuring techniques, such as densitometry, or by radiographic evidence of atraumatic fracture.
Calcitriol AN is also indicated for the prevention of corticosteroid induced osteoporosis in patients commencing oral steroid therapy in a dose and regimen expected to result in a significant bone loss.
Calcitriol AN is indicated in the treatment of hypocalcemia in patients with uremic osteodystrophy, hypoparathyroidism and in hypophosphataemic rickets.


Hypercalcemia or vitamin D toxicity.
Hypersensitivity to calcitriol or any of the excipients in Calcitriol AN.


Concomitant therapy with other vitamin D compounds.

Since Calcitriol AN is the most potent metabolite of vitamin D available, other vitamin D compounds should be withheld during treatment in order to avoid the development of hypervitaminosis D.
If patients are changed over from ergocalciferol to calcitriol it may take many months for blood levels of ergocalciferol to return to pretreatment values. Overdosage of any form of vitamin D is dangerous (see also Overdosage). Chronic hypercalcemia can lead to generalised vascular calcification, nephrocalcinosis and other soft tissue calcification.


A strong relationship exists between calcitriol therapy and the development of hypercalcemia. In some trials in uremic osteodystrophy, up to 40% of patients receiving calcitriol treatment became hypercalcemic.
Sudden increases in calcium consumption due to dietary change (e.g. dairy products) or injudicious calcium supplements may precipitate hypercalcemia. Patients and relatives should receive instruction in dietary management, be informed about the symptoms of hypercalcemia, and be warned of the consequences of not adhering to dietary recommendations. Although an adequate dietary intake of calcium is important in patients with postmenopausal osteoporosis, calcitriol does increase calcium absorption in these patients and calcium supplements may lead to hypercalcemia and are not recommended unless the dietary intake is clearly inadequate (see Dosage and Administration, Information for the patient and Adverse Effects).
In patients with normal renal function, chronic hypercalcemia may be associated with an increase in serum creatinine.

Serum phosphate levels.

Calcitriol AN raises serum inorganic phosphate levels. While this is a desirable effect in patients with hypophosphataemic states, caution must be taken in patients with renal failure. (See Precautions, Ectopic calcification.)

Hypophosphataemic rickets.

Patients with hypophosphataemic rickets (familial hypophosphatemia) should pursue their oral phosphate therapy. However, the possible stimulation of intestinal phosphate absorption may modify the requirement for phosphate supplements. During the stabilisation phase of treatment with Calcitriol AN, serum calcium levels should be checked at least twice weekly (see Dosage and Administration, Laboratory monitoring).

Ectopic calcification.

Calcitriol AN may increase plasma phosphate levels. While this effect is desirable in hypophosphataemic osteomalacia, it may cause ectopic calcification, especially in patients with renal failure. Plasma phosphate levels should be kept normal in such patients by the oral administration of phosphate binding agents.
Patients with normal renal function who are taking Calcitriol AN should avoid dehydration. Adequate fluid intake should be maintained.


Patients immobilised after surgical procedures are more at risk of developing hypercalcemia, therefore more frequent monitoring is recommended.

Use in patients with impaired renal function.

Special care should be taken when administering Calcitriol AN to patients with renal dysfunction. More frequent monitoring in these patients is appropriate (see Dosage and Administration).

Use in children.

Paediatric patients on long-term treatment with calcitriol are at risk of development of nephrocalcinosis. The younger the age at the commencement of therapy, and the higher the dose of calcitriol needed, the greater the risk. The drug should be used only if the benefits clearly outweigh the risks.

Use in the elderly.

It is advised that in elderly patients suffering from ischemic heart disease, serum calcium levels should be carefully monitored. If hypercalcemia is observed, calcitriol therapy should be suspended immediately. It should also be remembered that geriatric patients receive many other drugs and that their compliance may not be ideal.

Carcinogenicity/ mutagenicity.

Long-term animal studies have not been conducted to evaluate the carcinogenic potential of calcitriol. Calcitriol AN is not mutagenic in vitro in the Ames test. No significant effects of calcitriol on fertility and or general reproductive performances were observed in a study in rats at oral doses of up to 0.3 microgram/kg (approximately 3 times the maximum recommended dose based on body surface area).

Use in pregnancy.

(Category B3)
There are no adequate and well controlled studies in pregnant women. Calcitriol AN has been found to be teratogenic in rabbits when given at doses of 0.08 and 0.3 microgram/kg (approximately 1 and 5 times the maximum recommended dose based on mg/m2). All 15 fetuses in 3 litters at these doses showed external and skeletal abnormalities. However, none of the other 23 litters (156 fetuses) showed external and skeletal abnormalities compared to controls. Teratogenicity studies in rats up to 0.3 microgram/kg (approximately twice the maximum recommended dose based on mg/m2) showed no evidence of teratogenic potential.
Calcitriol AN should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Australian categorisation definition of category B3: drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans.

Use in lactation.

It should be assumed that exogenous calcitriol passes into the breast milk. In view of the possible adverse effects on the infant, mothers should not breastfeed while taking Calcitriol AN.


Since calcitriol is one of the most important active metabolites of vitamin D3, pharmacological doses of vitamin D and its derivatives should be withheld during treatment with Calcitriol AN to avoid possible additive effects and hypercalcemia.
In patients being treated for osteoporosis, calcium containing preparations should be avoided unless required for specific dietary purposes.
Cholestyramine has been reported to reduce intestinal absorption of fat soluble vitamins; as such, it may impair intestinal absorption of Calcitriol AN.
A relationship of functional antagonism exists between vitamin D analogues, which promote calcium absorption, and corticosteroids, which inhibit it.
Magnesium containing antacids and Calcitriol AN should not be used concomitantly, because such use may lead to the development of hypermagnesemia.
Calcitriol AN should be given cautiously to patients on digitalis because hypercalcemia in such patients may precipitate cardiac arrhythmias.
The concomitant use of thiazide diuretics may precipitate hypercalcemia.
Since Calcitriol AN also has an effect on phosphate transport in the intestine, kidneys and bones, the dosage of phosphate binding agents must be adjusted in accordance with the serum concentration (normal value: 0.6-1.6 mmol/L).
Administration of enzyme inducers such as phenytoin or phenobarbital may lead to increased metabolism and hence reduced serum concentrations of calcitriol. Therefore, higher doses of calcitriol may be necessary if these drugs are administered simultaneously.

Effects on laboratory tests.

Calcitriol AN affects serum calcium levels and serum phosphate levels (see Precautions, Hypercalcaemia and serum phosphate levels and Dosage and Administration, Laboratory monitoring). It is essential that regular monitoring of serum calcium concentration be performed during therapy with Calcitriol AN.

Adverse Effects

Since Calcitriol AN exerts vitamin D activity in the body, adverse effects are, in general, similar to those encountered with excessive vitamin D intake.
Hypercalcaemia related to mechanism of action is the most important side effect and is manageable by dose modification. Hypercalcaemia has been demonstrated not to be an issue for calcitriol in the treatment of postmenopausal osteoporosis at the recommended dosage of 0.25 microgram twice daily.
Acute hypercalcemia may give rise to cardiac arrhythmia and/or arrest.
Signs and symptoms of vitamin D intoxication associated with hypercalcaemia include the following.


Weakness, headache, somnolence, nausea, vomiting, dry mouth, constipation, muscle pain, bone pain and metallic taste.


Polyuria, polydipsia, anorexia, weight loss, nocturia, conjunctivitis (calcific), pancreatitis, photophobia, rhinorrhea, hyperthermia, decreased libido, elevated BUN, albuminuria, hypercholesterolemia, elevated AST and ALT, ectopic calcification, hypertension, cardiac arrhythmias and, rarely, overt psychosis. Prolonged chronic hypercalcemia or concurrent hypercalcemia and hyperphosphatemia of > 1.9 mmol/L can result in metastatic calcification of soft tissues; this can be seen radiographically. In patients with normal renal function, chronic hypercalcemia may be associated with an increase in serum creatinine.
The following adverse reactions have been reported in clinical trials involving calcitriol therapy.

Serious or life threatening reactions.

Severe dehydration.

More common reactions.



Central nervous system.

Drowsiness, weakness.



Less common reactions.


Pruritus (associated with hypercalcemia).

Gastrointestinal tract.

Diarrhoea, constipation.


Impairment of renal function.


Metastatic or ectopic calcification.
Hypersensitivity reactions may occur in susceptible individuals.

Dosage and Administration

The optimal daily dose of Calcitriol AN must be carefully determined for each patient and indication. Dosage optimisation should be accompanied by regular monitoring of serum calcium concentration. If hypercalcemia occurs, the drug should be immediately discontinued until normocalcemia ensues.



Established osteoporosis.

The recommended dose of Calcitriol AN is 0.25 microgram twice daily. If a satisfactory response is not obtained with this dose, it may be increased, with regular serum calcium monitoring, to a maximum of 0.5 microgram twice daily. This increased dose should rarely be necessary.

Corticosteroid induced osteoporosis.

The recommended dose is 0.25 microgram twice daily for steroid doses equivalent to < 10 mg/day of oral prednisone increasing to 0.75 microgram/day for steroid doses > 10 mg/day oral prednisone.
Dietary calcium intake should not exceed 1000 mg/day (see Precautions, Hypercalcemia).

Other indications.

Uremic osteodystrophy.

The recommended initial dose of Calcitriol AN is 0.25 microgram/day. If a satisfactory response in the biochemical parameters and clinical manifestations of the disease state is not observed, dosage may be increased by 0.25 microgram/day at intervals of two to four weeks. Patients with normal or only slightly reduced serum calcium levels may respond to Calcitriol AN doses of 0.25 microgram every other day. Most patients undergoing hemodialysis respond to doses between 0.5 and 1 microgram daily.

Hypoparathyroidism and rickets.

The recommended initial dose of Calcitriol AN is 0.25 microgram per day given in the morning. If a satisfactory response in the biochemical parameters and clinical manifestations of the disease are not observed, the dose may be increased at intervals of two to four weeks.
Malabsorption is occasionally noted in patients with hypoparathyroidism, therefore larger doses of Calcitriol AN may be needed.


The doses are similar to those used in adults with greater variability between subjects. Patients in the one to five year age group with hypoparathyroidism have usually been given 0.25 to 0.75 microgram daily.


No dosage adjustment is necessary in elderly patients. (See Precautions, Use in the elderly.)

Information for the patient.

It is recommended that patients receive instruction in dietary management and that they be warned of the consequences and implications of not adhering strictly to the diet recommendations in relation to intake of calcium and vitamin D (see Precautions, Hypercalcemia). Patients should also be informed of the symptoms of hypercalcemia, which include weakness, nausea and vomiting.


When the optimal dosage of Calcitriol AN has been determined, the serum calcium levels should be checked regularly. As soon as serum calcium nears hypercalcemic levels (1 mg per 100 mL [0.25 mmol/L] above normal 9-11 mg per 100 mL [2.25-2.75 mmol/L] on average), the dosage of Calcitriol AN should be substantially reduced or treatment stopped altogether until normocalcemia ensues. Withdrawal of additional doses of calcium can also be of benefit in bringing about rapid normalisation of serum calcium levels. Careful consideration should also be given to lowering the dietary calcium intake.
Should hypercalcemia occur, Calcitriol AN should be suspended immediately and serum calcium and phosphate levels must be determined daily. When normal levels have been attained, the treatment with Calcitriol AN can be continued, at a daily dose 0.25 microgram lower than that previously used.

Laboratory monitoring.

For safety reasons, it is essential that regular monitoring of serum calcium concentration be performed during therapy with Calcitriol AN. Blood samples should be taken without a tourniquet where possible to minimise local calcium effects.

Osteoporosis, including corticosteroid induced osteoporosis.

Patients should be monitored at the commencement of therapy, at 2 to 4 weeks, and thereafter at 2 to 3 monthly intervals.

Hypocalcemia/ uremic osteodystrophy/ hypoparathyroidism/ hypophosphataemic.

Rickets Serum calcium, phosphorus, magnesium and alkaline phosphatase and 24 hour urinary calcium and phosphorus should be determined periodically. During the initial phase of the medication, serum calcium should be determined at least twice weekly. Subsequently, monitoring should also be undertaken at 2 to 4 weeks and at 2 to 3 monthly intervals thereafter.


Since calcitriol is a derivative of vitamin D, the symptoms of overdose are the same as for an overdose of vitamin D. Administration of Calcitriol AN to patients in excess of their daily requirements can cause hypercalcaemia, hypercalciuria and hyperphosphataemia. High intake of calcium and phosphate concomitant with Calcitriol AN may lead to similar abnormalities. In patients with uremic osteodystrophy, high levels of calcium in the dialysate bath may contribute to the hypercalcemia.


Acute symptoms.

Acute symptoms of vitamin D intoxication include anorexia, headache, vomiting and constipation.

Chronic symptoms.

Chronic symptoms include dystrophy (weakness, loss of weight), sensory disturbances, possibly fever with thirst, polyuria, dehydration, apathy, arrested growth and urinary tract infections. Hypercalcaemia ensues with metastatic calcification of the renal cortex, myocardium, lungs and pancreas.


Accidental overdosage.

The treatment of acute accidental overdosage of Calcitriol AN should consist of general supportive measures. If drug ingestion is discovered within a relatively short time, induction of emesis or gastric lavage may be of benefit in preventing further absorption. Serial serum electrolyte determinations (especially calcium), rate of urinary calcium excretion and assessment of electrocardiographic abnormalities due to hypercalcemia should be obtained. Such monitoring is critical in patients receiving digitalis.
Discontinuation of supplemental calcium and a low calcium diet are also indicated in accidental overdosage.
Due to the relatively short duration of the pharmacological action of calcitriol, further measures are probably unnecessary. However, should persistent and markedly elevated serum levels occur, there are a variety of therapeutic alternatives that may be considered, depending on the patient's underlying condition. These include the use of drugs such as phosphates and corticosteroids as well as measures to induce an appropriate forced diuresis. The use of peritoneal dialysis against a calcium free dialysate has also been reported.

Hypercalcemia and overdosage.

General treatment of hypercalcemia (greater than 1 mg/100 mL [0.25 mmol/L] above the upper limit of the normal range) consists of immediate discontinuation of Calcitriol AN therapy, institution of a low calcium diet and withdrawal of calcium supplements. Serum calcium levels should be determined daily until normocalcemia ensues. Hypercalcaemia frequently resolves in two to seven days. When serum calcium levels have returned to within normal limits, Calcitriol AN therapy may be reinstituted at a dose of 0.25 microgram/day less than prior therapy. Serum calcium levels should be obtained at least twice weekly after all dosage changes and subsequent dosage titration. Persistent or markedly elevated serum calcium levels in dialysis patients may be corrected by dialysis against a calcium free dialysate.


Calcitriol AN 0.25 microgram is supplied as soft red coloured, oval soft gelatine capsule containing a clear oily liquid.
Calcitriol AN is available in bottles (HDPE with PP closures) and blisters (PVC/Aluminium) of 100 capsules.


Bottles and blisters: store below 25°C. Protect from light.

Poison Schedule