New Zealand - English - Medsafe (Medicines Safety Authority)
Calcitriol 0.25µg and 0.5µg soft gel capsules
What is in this leaflet
This leaflet answers some common questions about Calcitriol-AFT soft gel 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 your
taking Calcitriol-AFT against the benefits they expect it will have for you.
If you have any concerns about taking this medicine, ask your doctor or
Keep this leaflet with the medicine. You may need to read it again.
What Calcitriol-AFT is used for
Calcitriol occurs naturally in humans and is a biologically active form of vitamin D.
Calcitriol-AFT is used to treat people with postmenopausal osteoporosis (bone-
thinning) and to prevent osteoporosis in people taking oral corticosteroids. Calcitriol-
AFT is also for the treatment of low blood calcium in patients with renal
hypoparathyroidism from various causes (reduced function of the parathyroid
glands), hyperparathyroidism (excessive levels of the parathyroid hormone in the
body) and rickets (Vitamin D deficiency).
Calcitriol-AFT works by improving absorption of calcium from the intestine and by
stimulating growth of healthy bones.
This medicine is available only with a doctor's prescription. Your doctor may have
prescribed Calcitriol-AFT for another purpose.
Ask your doctor if you have any questions why Calcitriol-AFT has been
prescribed for you.
Before you take Calcitriol-AFT
When you must not take it
Do not take Calcitriol-AFT if:
you have had an allergic reaction to calcitriol or any other Vitamin D-like
substances, or any ingredients listed in the Ingredients section of this leaflet
you have high levels of calcium in your blood (called hypercalcaemia)
you have high levels of vitamin D in your blood
the package is torn or shows signs of tampering
the expiry date printed on the pack has passed
If you take this medicine after the expiry date has passed, it may not work as well
Before you start to take Calcitriol-AFT
You must tell your doctor if:
you are pregnant or plan to become pregnant.
It is not known whether Calcitriol-AFT is harmful to an unborn baby when taken
by a pregnant woman. If there is a need to take Calcitriol-AFT when you are
pregnant your doctor will discuss the risks and benefits to you and the unborn
you are breastfeeding or plan to breastfeed.
Mothers may breastfeed while taking Calcitriol-AFT provided that the blood
calcium levels of the mother and infant are monitored.
you have any other health problems, especially the following:
you are bedridden or in a wheelchair
Vitamin D resistant rickets (familial hypophosphataemia)
you are allergic to any other medicines, foods, dyes or preservatives
you are taking any other medicines including any that you have bought from a
pharmacy, supermarket or healthfood shop.
Some medicines may be affected by or interfere with how well Calcitriol-AFT works.
You may need to take different amounts of your medicine, or you may need to take
different medicines. Your doctor will advise you.
These medicines include:
medicines or vitamin tablets containing vitamin D or calcium
cholestyramine (Questran Light
if you are undergoing dialysis, antacids containing magnesium (e.g. Mylanta
thiazide diuretics (e.g. Chlotride
antihypertensives with thiazide diuretics (Accuretic
methylprednisolone, betamethasone, cortisone, dexamethasone, budesonide,
Ask your doctor or pharmacist if you are not sure about this list of medicines.
How to use the Medicine
How much to take
Your doctor will tell you how much Calcitriol-AFT to take each day. Sometimes
Calcitriol-AFT does not need to be taken every day. This will vary depending on the
nature of your condition, the calcium level in your blood and your individual response
to the medicine.
Generally the daily dose for adults ranges from 0.25 to 1.00 micrograms
How to take it
Calcitriol-AFT capsules should be swallowed whole with a glass of water. Do not
open or bite the capsules and do not take any capsules that are damaged.
When to take it
Calcitriol-AFT can be taken with or without food.
How long to take Calcitriol-AFT
Continue taking Calcitriol-AFT until your doctor tells you to stop.
If you forget to take Calcitriol-AFT
If it is almost time for your next dose, skip the dose you missed and take your next
dose when you are meant to.
Otherwise, take it as soon as you remember and then go back to taking it as you
If you are not sure what to do ask your doctor or pharmacist.
If you have trouble remembering your dose, ask your pharmacist for some hints.
Things you must do
Tell all doctors, dentists and pharmacists who are treating you that you are taking
Tell your doctor if you become pregnant while taking Calcitriol-AFT.
Do not take any other medicines or dietary supplements whether they require a
prescription or not, without first telling your doctor. You must be especially
careful with medicines or dietary supplements that contain Vitamin D, calcium or
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 Calcitriol-AFT is not helping your condition.
Be sure to keep all of your appointments with your doctor so that your progress can
be checked. Your doctor will need to make regular measurements of the calcium
level in your blood while you are taking Calcitriol-AFT.
Calcitriol-AFT and Diet:
You should discuss your diet with your doctor and adhere strictly to your
Sudden changes in diet, particularly the amount of calcium containing foods, such as
dairy products, may lead to increased calcium in your blood. If this happens, you may
urination, headache, loss of interest in everyday activities or loss of appetite.
Calcitriol-AFT and Laboratory Tests:
Make sure that you keep all blood test appointments with your doctor.
These are to check your blood calcium levels (and possibly some other blood factors)
while you are taking Calcitriol-AFT. Your doctor will discuss your specific needs with
Things you must not do
Do not stop taking Calcitriol-AFT or change the dose without first checking
with your doctor.
Stopping suddenly can lead in a rapid fall in blood calcium levels.
Your doctor will tell you the best way to slowly reduce the amount of Calcitriol-AFT
you are taking before stopping completely.
Do not let yourself run out of medicine over the weekend or on holidays.
Do not give Calcitriol-AFT to anyone else even if their symptoms seem similar to
Do not use Calcitriol-AFT to treat other complaints unless your doctor says to.
Things to be careful of
Be careful driving or operating machinery until you know how Calcitriol-AFT affects
However, Calcitriol-AFT is not expected to affect your ability to drive a car or operate
Tell your doctor or pharmacist as soon as possible if you do not feel well while you
are taking Calcitriol-AFT.
Calcitriol-AFT helps most people but it may have unwanted side effects.
All medicines can have side effects. Sometimes they are serious. 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:
loss of appetite
stomach ache, constipation.
Tell you doctor immediately or go to your nearest Accident and Emergency centre if
you notice any of the following:
sight or hearing disturbances
fever and a dry mouth, thirst
frequent urination and/or pain on urination
loss of interest in everyday events
These are all symptoms of high levels of calcium in your blood. These may be
serious side effects and you may need urgent medical attention.
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.
Tell your doctor if you notice anything else that is making you feel unwell, even
if it is not on this list.
Ask your doctor or pharmacist any questions you may have or 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
Immediately telephone your doctor or National Poisons Information Centre
(telephone 0800 POISON or 0800 764 766) for advice or go to an Accident and
Emergency centre if you think that you or anyone else may have taken too
much Calcitriol-AFT, even if there are no signs of discomfort or poisoning. You
may need urgent medical attention.
The following are some symptoms, which may or may not occur:
loss of appetite
Keep telephone numbers for these places handy.
If you are not sure what to do, contact your doctor or pharmacist.
Keep your medicine in the original container until it is time to take it.
If you take the medicine out of the original container Calcitriol-AFT capsules may not
Keep Calcitriol-AFT capsules in a cool dry place where the temperature stays
Do not store them, or any other medicine, in a bathroom or near a sink. Do not leave
them in the car or on window sills. Heat and moisture can destroy some medicines.
Keep Calcitriol-AFT 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-AFT, or it has passed its expiry date,
ask your pharmacist what to do with any medicine that is left over.
0.25µg strength capsule contains also contains red iron oxide as a colourant while
the 0.5µg strength capsule contains both red and yellow iron oxides as colourants.
hydroxytoluene (BHT) and medium-chain triglycerides.
AFT Pharmaceuticals Ltd.,
Date of Preparation:
19 November 2015
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NEW ZEALAND DATA SHEET
CALCITRIOL – AFT
Calcitriol – AFT capsules 0.25 μg
Calcitriol – AFT capsules 0.5 μg
QUALITATIVE AND QUANTITATIVE COMPOSITION
Calcitrol – AFT 0.25 μg: Each capsule contains 0.25μg of synthetic calcitriol, a biologically active
form of vitamin D3.
Calcitrol – AFT 0.5 μg: Each capsule contains 0.25μg of synthetic calcitriol, a biologically active
form of vitamin D3.
Excipients with known effect:
For the full list of excipients, see section 6.1.
Capsule, liquid filled.
Calcitrol - AFT are oval, orange soft-gel capsules.
Established postmenopausal osteoporosis.
Renal osteodystrophy in patients with chronic renal failure, particularly those undergoing
Secondary hyperparathyroidism in patients with moderate to severe chronic renal failure (pre-
Vitamin D-dependent rickets.
Hypophosphataemic vitamin D-resistant rickets.
Prevention of corticosteroid induced osteoporosis
Dose and method of administration
The optimal daily dose of Calcitriol-AFT must be carefully determined for each patient on the basis
of the serum calcium level. Calcitriol-AFT therapy should always be started at the lowest possible
dose and should not be increased without careful monitoring of serum calcium (see Patient
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A prerequisite for optimal efficacy of Calcitriol-AFT is adequate but not excessive calcium intake
(in adults: approximately 800mg daily) at the beginning of therapy. Calcium supplements may be
Because of improved calcium absorption from the gastrointestinal tract, some patients on Calcitriol-
AFT may be maintained on a lower calcium intake. Patients who tend to develop hypercalcaemia
may require only low doses of calcium or no supplementation at all.
The total daily calcium intake (i.e. from food, and, where applicable, from medicines) should
average approximately 800mg and should not exceed 1000mg.
During the stabilization phase of treatment with Calcitriol-AFT, serum calcium levels should be
checked at least twice weekly. When the optimal dosage of Calcitriol-AFT has been determined,
serum calcium levels should be checked every month (or as given below for individual indications).
Samples for serum calcium estimation should be taken without a tourniquet.
As soon as the serum calcium levels rise to 1 mg/100ml (250μmol/l) above normal (9 to 11mg/100
ml, or 2250-2750μmol/l), or serum creatinine rises to > 120μmol/l, treatment with Calcitriol-AFT
should be stopped immediately until normocalcaemia ensues.
During the periods of hypercalcaemia, serum calcium and phosphate levels must be determined
daily. When normal levels have been attained, the treatment with Calcitriol-AFT can be continued,
at a daily dose 0.25μg lower than that previously used. An estimate of daily dietary calcium intake
should be made and the intake adjusted when indicated.
Special dosage instructions
The recommended dosage for Calcitriol-AFT is 0.25μg twice daily.
Serum calcium and creatinine levels should be determined at 1, 3 and 6 months and at 6-month
Renal osteodystrophy (dialysis patients)
The initial daily dose is 0.25μg. In patients with normal or only slightly reduced serum calcium
levels, doses of 0.25μg every other day are sufficient. If no satisfactory response in the biochemical
parameters and clinical manifestations of the disease is observed within 2 - 4 weeks, the daily
dosage may be increased by 0.25μg at two to
four-week intervals. During this period, serum calcium levels should be determined at least twice
weekly. Most patients respond to between 0.5μg and 1.0μg daily.
An oral Calcitriol-AFT pulse therapy with an initial dosage of 0.1μg/kg/week split into two or three
equal dosages given at night was found to be effective even in patients refractory to continuous
therapy. A maximum total cumulative dosage of 12μg per week should not be exceeded.
Secondary hyperparathyroidism (pre-dialysis patients)
hyperparathyroidism and resultant metabolic bone disease in patients with moderate to severe renal
failure i.e. creatinine clearance (Ccr) 15 to 55ml/min, is 0.25μg/day in adults and in paediatric
patients 3 years of age or older (corrected for a surface area of 1.73m2). This dosage may be
increased if necessary to 0.5μg/day.
The recommended initial dose of Calcitriol-AFT is 0.25μg/day given in the morning. If a
satisfactory response in the biochemical parameters and clinical manifestations of the disease is not
observed, the dose may be increased at two to four-week intervals. During this period, serum
calcium levels should be determined at least twice weekly. If hypercalcaemia is noted, Calcitriol-
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AFT should be immediately discontinued until normocalcaemia ensues. Careful consideration
should also be given to lowering the dietary calcium intake.
Malabsorption is occasionally noted in patients with hypoparathyroidism; hence, larger doses of
Calcitriol-AFT may be needed.
If the physician decides to prescribe Calcitriol-AFT to a pregnant woman with hypoparathyroidism,
an increased dose may be required during the latter half of gestation, with dose reduction postpartum
or during lactation.
Prevention of corticosteroid induced osteoporosis
The recommended dosage range for the prevention of corticosteroid induced osteoporosis is 0.5-
0.75μg per day. Serum calcium and creatinine levels should be obtained at 2-4 weeks after initiating
treatment then at 3 and 6 months and every 6 months thereafter. If hypercalcaemia is noted, the
medicine should be immediately discontinued until normocalcemia ensues. While an adequate
dietary calcium intake is important, ordinarily it is more convenient to titrate medicine dosage
around the customary calcium intake of the patient.
No specific dosage modifications are required in elderly patients. The general recommendations for
monitoring serum calcium and creatinine should be observed.
Infants and children
During the first 2 years of life, a daily dosage of 0.01-0.1μg/kg bodyweight is recommended as a
Calcitriol-AFT is contraindicated in all diseases associated with hypercalcaemia.
Use of Calcitriol-AFT in patients with known hypersensitivity to calcitriol or medicines of the
same class and any of the constituent excipients is contraindicated.
Calcitriol-AFT is contraindicated if there is evidence of vitamin D toxicity.
Special warnings and precautions for use
hypercalcaemia. An abrupt increase in calcium intake as a result of changes in diet (e.g. increased
consumption of dairy products) or uncontrolled intake of calcium preparations may trigger
hypercalcaemia. Patients and their families should be advised that strict adherence to the prescribed
hypercalcaemia. As soon as the serum calcium levels rise to 1mg/100 ml (250μmol/l) above normal
(9-11mg/100 ml, or 2250-2750μmol/l), or serum creatinine rises to >120μmol/l, treatment with
Calcitriol-AFT should be stopped immediately until normocalcaemia ensues (see Dosage and
Immobilised patients, e.g. those who have undergone surgery, are particularly exposed to the risk
Calcitriol increases inorganic phosphate levels in serum. While this is desirable in patients with
hypophosphatemia, caution is called for in patients with renal failure because of the danger of
ectopic calcification. In such cases, the plasma phosphate level should be maintained at the normal
level (2-5mg/100ml or 0.65-1.62mmol/l) by the oral administration of appropriate phosphate-
binding agents and low phosphate diet.
The serum calcium times phosphate (Ca x P) product should not be allowed to exceed 70mg2/dl2.
Patients with vitamin D-resistant rickets (familial hypophosphatemia) who are being treated with
Calcitriol-AFT must continue their oral phosphate therapy. However, possible stimulation of
Page 4 of 8
intestinal absorption of phosphate by Calcitriol-AFT should be taken into account since this effect
may modify the need for phosphate supplementation. The regular laboratory investigations that are
phosphatase and of the calcium and phosphate content in 24-hour urine. During the stabilisation
phase of treatment with Calcitriol-AFT, serum calcium levels should be checked at least twice
weekly (see Dosage Administration).
Since calcitriol is the most effective vitamin D metabolite available, no other vitamin D preparation
should be prescribed during treatment with Calcitriol-AFT, thereby ensuring that the development
of hypervitaminosis D is avoided.
If the patient is switched from ergocalciferol (vitamin D2) to calcitriol, it may take several months
for the ergocalciferol level in the blood to return to the baseline value (see Overdosage).
Patients with normal renal function who are taking Calcitriol-AFT should avoid dehydration.
Adequate fluid intake should be maintained.
Interaction with other medicines and other forms of interaction
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-AFT to
avoid possible additive effects and hypercalcaemia.
Dietary instructions, especially concerning calcium supplements, should be strictly observed, and
uncontrolled intake of additional calcium-containing preparations avoided.
Concomitant treatment with a thiazide diuretic increases the risk of hypercalcaemia. Calcitriol
A relationship of functional antagonism exists between vitamin D analogues, which promote
calcium absorption, and corticosteroids, which inhibit it.
Magnesium-containing medicines (e.g. antacids) may cause hypermagnesemia and should therefore
not be taken during therapy with Calcitriol-AFT by patients on chronic renal dialysis.
Since Calcitriol-AFT 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 phosphate
concentration (normal values: 2-5mg/100ml, or 0.65-1.62mmol/l).
Patients with vitamin D-resistant rickets (familial hypophosphatemia) should continue their oral
phosphate therapy. However, possible stimulation of intestinal phosphate absorption by calcitriol
should be taken into account since this effect may modify the requirement for phosphate
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 medicines are administered simultaneously.
Cholestyramine can reduce intestinal absorption of fat-soluble vitamins and therefore may impair
intestinal absorption of calcitriol.
Fertility, pregnancy and lactation
Supravalvular aortic stenosis has been produced in foetuses by near-fatal oral doses of vitamin D
in pregnant rabbits. There is no evidence to suggest that vitamin D is teratogenic in humans even at
very high doses. Calcitriol-AFT should be used during pregnancy only if the benefits outweigh the
potential risk to the foetus.
It should be assumed that exogenous calcitriol passes into the breast milk. In view of the potential
for hypercalcaemia in the mother and for adverse reactions from Calcitriol-AFT in nursing infants,
mothers may breastfeed while taking Calcitriol-AFT, provided that the serum calcium levels of the
mother and infant are monitored.
Page 5 of 8
Effects on ability to drive and use machines
On the basis of the pharmacodynamic profile of reported adverse events, this product is presumed
to be safe or unlikely to adversely affect such activities.
Since calcitriol exerts vitamin D activity, adverse effects may occur which are similar to those found
when an excessive dose of vitamin D is taken, i.e. hypercalcaemia syndrome or calcium intoxication
(depending on the severity and duration of hypercalcaemia) (See Dosage and Administration and
Warnings and Precautions). Occasional acute symptoms include anorexia, headache, nausea,
vomiting, abdominal pain or stomach ache and constipation.
Because of the short biological half-life of calcitriol, pharmacokinetic investigations have shown
normalisation of elevated serum calcium within a few days of treatment withdrawal, i.e. much faster
than in treatment with vitamin D3 preparations.
Chronic effects may include dystrophy, sensory disturbances, fever with thirst, thirst/polydipsia,
polyuria, dehydration, apathy, arrested growth and urinary tract infections.
The number of adverse effects reported from clinical use of calcitriol over a period of 15 years in
all indications is very low with each individual effect, including hypercalcaemia, occurring at a rate
of 0.001% or less.
In concurrent hypercalcaemia and hyperphosphatemia of > 6mg/100ml or > 1.9mmol/l, soft-tissue
calcification may occur; this can be seen radiographically.
In patients with normal renal function, chronic hypercalcaemia may be associated with an increase
in serum creatinine.
Hypersensitivity reactions (pruritis, rash, urticaria, and very rarely severe erythematous skin
disorders) may occur in susceptible individuals.
Treatment of asymptomatic hypercalcaemia: see Dosage and administration.
Since calcitriol is a derivative of vitamin D, the symptoms of overdose are the same as for an
overdose of vitamin D. Intake of high doses of calcium and phosphate together with Calcitriol-AFT
may give rise to similar symptoms. The serum calcium times phosphate (Ca x P) product should
not be allowed to exceed 70mg2/dl2. A high calcium level in the dialysate may contribute to the
development of hypercalcaemia.
Acute symptoms of vitamin D intoxication: anorexia, headache, vomiting, constipation.
Chronic symptoms: 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.
The following measures should be considered in treatment of accidental overdosage: immediate
gastric lavage or induction of vomiting to prevent further absorption. Administration of liquid
paraffin to promote faecal excretion. Repeated serum calcium determinations are advisable. If
elevated calcium levels persist in the serum, phosphates and corticosteroids may be administered
and measures instituted to bring about adequate diuresis.
Calcitriol is one of the most important active metabolites of vitamin D3. It is normally formed in
the kidney from its precursor, 25-hydroxycholecalciferol (25-HCC). Physiological daily production
is normally 0.5-1.0μg and is somewhat higher during periods of increased bone synthesis (e.g.
growth or pregnancy). Calcitriol promotes intestinal absorption of calcium and regulates bone
mineralisation. The pharmacological effect of a single dose of calcitriol lasts about 3-5 days.
Page 6 of 8
The key role of calcitriol in the regulation of calcium homeostasis, which includes stimulating
effects on osteoblastic activity in the skeleton, provides a sound pharmacological basis for its
therapeutic effects in osteoporosis.
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
In patients with renal osteodystrophy, oral administration of Calcitriol-AFT normalises reduced
intestinal absorption of calcium, hypocalcaemia, increased serum alkaline phosphatase and serum
parathyroid hormone concentration. It alleviates bone and muscle pain and corrects the histological
alterations that occur in osteitis fibrosa and other mineralisation defects.
In patients with postsurgical hypoparathyroidism, idiopathic hypoparathyroidism, and pseudohypo-
parathyroidism, hypocalcaemia and its clinical manifestations are alleviated by Calcitriol-AFT
In patients with vitamin D-dependent rickets, serum levels of calcitriol are low or absent. As the
endogenous production of calcitriol in the kidney is insufficient, Calcitriol-AFT is considered as a
In patients with vitamin D-resistant rickets and hypophosphatemia in whom plasma calcitriol levels
are reduced, treatment with Calcitriol-AFT reduces tubular elimination of phosphates and, in
conjunction with concurrent phosphate treatment, normalises bone development.
Patients with various other forms of rickets, e.g. in association with neonatal hepatitis, biliary
atresia, cystinosis and dietary calcium and vitamin D deficiency, have also benefited from
The two known sites of action of calcitriol are intestine and bone.
A calcitriol receptor-binding protein appears to exist in the mucosa of human intestine. Additional
evidence suggests that calcitriol may also act on the kidney and the parathyroid glands. Calcitriol
is the most active known form of vitamin D3 in stimulating intestinal calcium transport. In acutely
uremic rats calcitriol has been shown to stimulate intestinal calcium absorption.
The kidneys of uremic patients cannot adequately synthesize calcitriol, the active hormone formed
from precursor Vitamin D. Resultant hypocalcaemia and secondary
hyperparathyroidism are a major cause of the metabolic bone disease of renal failure. However,
other bone-toxic substances which accumulate in uremia (e.g., aluminium) may also contribute.
The beneficial effect of Calcitriol-AFT in renal osteodystrophy appears to result from correction of
produces other independent beneficial effects.
Calcitriol is rapidly absorbed from the intestine. Peak serum concentrations following a single oral
administration, serum calcitriol levels reached a steady state within 7 days, with a relationship to
the dose of calcitriol administered.
After a single oral dose of 0.5μg Calcitriol-AFT, the average serum concentrations of calcitriol rose
from a baseline value of 40.0 ± 4.4pg/ml to 60.0 ± 4.4pg/ml after two hours, and then fell to 53.0 ±
6.9 after four hours, to 50.0 ± 7.0 after eight hours, to 44 ± 4.6 after twelve hours and to 41.5 ±
5.1pg/ml after 24 hours. During transport in the blood, calcitriol and other vitamin D metabolites
are bound to specific plasma proteins.
It can be assumed that exogenous calcitriol passes from the maternal blood into the foetal
bloodstream and breast milk.
Page 7 of 8
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-
oxo-cholecalciferol and 1α-hydroxy-23-carboxy-24,25,26,27-tetranorcholecalciferol.
The elimination half-life of calcitriol in serum is 9 - 10 hours.
However, the pharmacological effect of a single dose of calcitriol lasts at least 7 days. Calcitriol is
excreted in the bile and is subject to enterohepatic circulation.
After i.v. administration of radioactive calcitriol in healthy subjects, about 27% of the radioactivity
is found in the faeces and about 7% in the urine within 24 hours.
After oral administration of 1μg radioactive calcitriol in healthy subjects, about 10% of the entire
radioactivity was found in the urine within 24 hours. On the sixth day after i.v. administration of
radioactive calcitriol, urine and faeces accounted for an average of 16% and 49% respectively of
the cumulative excretion of radioactivity.
Pharmacokinetics in special clinical situations
In patients with nephrotic syndrome or in those undergoing haemodialysis, serum levels of calcitriol
were reduced and time to peak levels was prolonged.
Preclinical safety data
Acute toxicity studies in mice and rats indicated that the oral approximate lethal dose of calcitriol
ranged from 1.35 to 3.9mg/kg. These values are several orders of magnitude higher than the
proposed clinical dose of 0.25μg twice daily (approximately 8 - 10ng/kg/day).
Subchronic toxicity studies in rats and dogs indicated that calcitriol at an oral dose of 20ng/kg/day
(twice the usual human dosage) for up to 6 months produced no or minimal adverse effects. A dose
of 80ng/kg/day (8 times the usual human dosage) for up to 6 months produced moderate adverse
effects; changes seen appeared to be primarily the result of prolonged hypercalcaemia.
Reproductive toxicity studies in rats indicated that oral doses up to 300ng/kg/day (30 times the
usual human dose) did not adversely affect reproduction. In rabbits, calcitriol produced some
maternal and foetotoxic effects at an oral dose of 300ng/kg/day, but did not show any adverse effect
at 20 or 80ng/kg/day (8 times the usual human dose).
List of excipients
Gelatin 69.45mg, glycerol 15.78mg, iron oxide red 0.368mg, sodium ethyl hydroxybenzoate
0.316mg, sodium propyl hydroxybenzoate 0.151mg, sorbitol 16.668mg (70% solution), titanium
dioxide 0.971 mg.
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Special precautions for storage
Do not store above 25°C. Store in the original container.
Nature and contents of container
Packs of 100 capsules.
Special precautions for disposal
No special requirements.
AFT Pharmaceuticals Ltd
PO Box 33-203
Phone: 0800 423 823
DATE OF FIRST APPROVAL
12 January 2006
DATE OF REVISION OF THE TEXT
25 February 2019
SUMMARY TABLE OF CHANGES
Reformat consistent with new Medsafe Data Sheet