Detriol

Package leaflet: Information for the patient

Detriol, 0.5 micrograms, soft capsules
Calcitriolum
For use in adults
Please read all of this leaflet carefully before taking this medicine, as it contains
important information for you.

• Keep this leaflet, so that you can read it again if necessary.
• If you have any questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm someone else, even if their symptoms are the same.
• If you experience any adverse effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Leaflet contents

1. What Detriol is and what it is used for
2. Important information before taking Detriol
3. How to take Detriol
4. Possible side effects
5. How to store Detriol
6. Contents of the pack and other information

1. What Detriol is and what it is used for

Calcitriol, the active substance in Detriol, is a metabolite of vitamin D. It is the biologically active
form of vitamin D, also known as vitamin D hormone (calcium metabolism regulator).
Detriol is used for the treatment of adult patients with:
˗ severe or progressive secondary hyperparathyroidism (overactivity of the parathyroid glands)
leading to renal osteodystrophy (bone disorders) associated with moderate or severe chronic
renal insufficiency.
˗ hypocalcaemia (low calcium levels) due to hypoparathyroidism.
Hypoparathyroidism may occur:
˗ after surgery (post-surgical hypoparathyroidism),
˗ without an identifiable cause (idiopathic hypoparathyroidism), or
˗ due to disturbances in phosphate metabolism (pseudohypoparathyroidism).
˗ hereditary (or familial) hypophosphataemic rickets [HPDR], a form of rickets unresponsive to vitamin D.

2. Important information before taking Detriol

When not to take Detriol

• if the patient is allergic to calcitriol, other substances from the same class (vitamin D or its
  metabolites), peanuts, soy or any of the other ingredients of this medicine (listed in section 6),
• if the patient has any disorder associated with increased calcium levels in blood or urine (hypercalcemia or hypercalciuria),
• if the patient has familial hypophosphatemic rickets associated with increased calcium levels in urine,
• if the patient is suspected of vitamin D intoxication (hypervitaminosis D),
• if the patient has metastatic calcification (tissue calcification),
• if the patient has nephrocalcinosis (renal calcification) or kidney stones (nephrolithiasis).

Warnings and precautions
Before starting treatment with Detriol, consult your doctor or pharmacist.

Treatment with Detriol may increase calcium levels in blood (hypercalcemia). The effect of Detriol is closely related to diet, especially calcium intake. For example, elevated blood calcium levels may also result from changes in dietary habits (increased consumption of dairy products) or uncontrolled use of calcium supplements.

Therefore, it is essential to strictly follow the diet prescribed by the doctor and take calcium supplements only as directed by the physician.

Since the active substance in Detriol is the most biologically active metabolite of vitamin D, other vitamin D supplements (including analogs or metabolites of vitamin D) or vitamin D-fortified foods should not be taken during treatment with Detriol, as this may lead to vitamin D overdose and elevated blood calcium levels.

During treatment with Detriol, serum calcium levels will be monitored regularly to avoid incorrect dosing and to prevent elevated calcium levels in blood (hypercalcemia) or urine (hypercalciuria) (see section 3 “How to take Detriol”).

Regular laboratory tests should also include measurements of serum phosphate, magnesium, alkaline phosphatase, and urinary phosphate levels.

• Particular caution is required when treating patients receiving thiazide diuretics (certain medicines used to increase urine output), patients with sarcoidosis, a history of kidney stones, or immobilization (e.g. after surgery), as these conditions increase the risk of elevated calcium levels in blood (hypercalcemia) or urine (hypercalciuria).
• Chronic hypercalcemia may lead to generalized calcification of blood vessels, kidney calcification, and other soft tissue calcifications; therefore, treatment must be discontinued.
• Calcitriol increases serum inorganic phosphate levels. While this effect is beneficial in patients with low blood phosphate levels (hypophosphatemia), caution is required in patients with chronic kidney disease due to the risk of ectopic calcifications. In such cases, serum phosphate levels should be maintained within the normal range through oral phosphate binders and a low-phosphate diet.
• In patients with both familial hypophosphatemic rickets and low serum phosphate levels, oral phosphate therapy should be continued. However, the required dose of oral phosphate may be reduced, as Detriol enhances intestinal phosphate absorption.
• When switching from ergocalciferol (vitamin D) to calcitriol therapy, it may take several months for ergocalciferol blood levels to return to baseline.
• If kidney function is normal, ensure adequate fluid intake during treatment with Detriol.

Early diagnosis and treatment of magnesium imbalance should be emphasized, due to its critical role in regulating calcium levels in blood and urine.

Children and adolescents
Detriol is not recommended for use in children and adolescents.

Interaction of Detriol with other medicines
Inform your doctor or pharmacist about all medicines currently used, recently used, or planned for use.

• There is a risk of increased blood calcium levels (hypercalcemia) in patients also taking thiazide diuretics (certain medicines used to increase urine output).
• In patients taking cardiac glycosides (heart medications), Detriol should be administered with caution, as elevated blood calcium levels may lead to cardiac arrhythmias.
• Concomitant use of glucocorticoids may reduce the effectiveness of Detriol, as glucocorticoids inhibit calcium absorption.
• In patients undergoing kidney dialysis, medications containing magnesium (e.g. acid-binding agents known as antacids) should not be taken during Detriol treatment, as this may lead to increased magnesium levels in blood.
• If the patient is also taking phosphate binders (e.g. aluminium hydroxide or aluminium carbonate), dosage should be based on serum phosphate levels.
• If the patient is also taking enzyme inducers such as phenobarbital (active ingredient in sleep-inducing medicines) or phenytoin (a medicine used to treat seizures), the effect of Detriol may be reduced. Enzyme inducers accelerate the breakdown of calcitriol, so higher doses of Detriol may be required.
• Detriol may be less effective when taken simultaneously with substances that bind bile acids, such as cholestyramine or sevelamer. These may limit the absorption of fat-soluble vitamins from the intestine and impair calcitriol absorption.
• If the patient is taking orlistat (a medicine used to treat obesity), laxatives containing liquid paraffin, or cholestyramine (a medicine used to lower high cholesterol levels), absorption of vitamin D from the gastrointestinal tract may be reduced.

Detriol with food and drink
Always follow the recommended calcium diet. Avoid sudden increases in calcium intake due to dietary changes (e.g. increased consumption of dairy products) or uncontrolled use of calcium supplements.

Pregnancy and breastfeeding
If the patient is pregnant, breastfeeding, suspects she may be pregnant, or is planning to become pregnant, she should consult her doctor or pharmacist before using this medicine.

There is no experience with the use of calcitriol during pregnancy and breastfeeding.

Pregnancy
Calcitriol should be used during pregnancy only if clearly indicated and under strict medical supervision.

Overdose of calcitriol may harm the unborn child (risk of physical and mental impairment, as well as heart and eye disorders).

Serum calcium levels in pregnant women treated with Detriol must be closely monitored, and monitoring should continue into the postpartum period (see section 3 “How to take Detriol”).

Breastfeeding
Calcitriol is expected to pass into breast milk. During treatment with Detriol in breastfeeding women, serum calcium levels should be monitored regularly in both the mother and the infant.

Driving and operating machinery
Detriol has no or negligible effect on the ability to drive and operate machinery. No studies have been conducted.

Detriol contains alcohol and sorbitol
This medicine contains 0.869 mg of alcohol (ethanol) per capsule. The amount of alcohol in 1 capsule is equivalent to less than 1 mL of beer or 1 mL of wine. The small amount of alcohol in this medicine will not cause noticeable effects.

Detriol contains 6 mg of sorbitol per dose, which corresponds to 2 mg of fructose in the body.

Detriol contains peanut oil (from peanuts)
Do not use if hypersensitivity to peanuts or soy has been diagnosed.

3. How to take Detriol

This medicine should always be taken as directed by your doctor or pharmacist. If in doubt,
consult your doctor or pharmacist.
Note:
The optimal daily dose of Detriol is carefully determined individually for each patient
according to serum calcium levels. If necessary, Detriol treatment may be supplemented
with calcium supplements. To avoid elevated calcium levels in the blood, always follow your
doctor's instructions regarding supplementary calcium dosing.
Detriol 0.5 microgram capsules are used only in patients whose maintenance dose is 0.5 micrograms
or more per day. Treatment should always be initiated with 1 capsule of Detriol 0.25 micrograms.
Serum and urinary calcium levels should be monitored regularly during treatment. If elevated calcium
levels in the blood (hypercalcemia) or urine (hypercalciuria) occur, Detriol should be discontinued
immediately until calcium levels return to normal. A reduction in dietary calcium intake should also
be considered.

Severe or advanced secondary hyperparathyroidism (overactivity of the parathyroid glands)
leading to renal osteodystrophy (bone changes) associated with moderate or severe chronic
renal insufficiency
Initial treatment dose is 1 soft capsule of Detriol 0.25 micrograms daily. In patients with normal or
only slightly reduced serum calcium levels, 1 soft capsule of Detriol 0.25 micrograms every other day
may be sufficient.
If no satisfactory clinical and biochemical response is observed within 2 to 4 weeks, the dose may be
increased every 2 to 4 weeks by 0.25 micrograms of calcitriol (1 soft capsule of Detriol 0.25 micrograms)
per day.
Most patients respond to a daily dose of 0.5 to 1.0 micrograms of calcitriol.
The maximum weekly dose of 12 micrograms must not be exceeded.

Hypocalcemia (low calcium levels) due to hypoparathyroidism
The recommended initial dose is 1 soft capsule of Detriol 0.25 micrograms daily.
If no improvement in clinical symptoms or laboratory parameters is observed, the dose may be
increased every 2 to 4 weeks by 0.25 micrograms of calcitriol.

Hereditary (or familial) hypophosphatemic rickets (HPDR)
Treatment should be initiated with 0.25 micrograms of calcitriol daily and must be closely monitored.

Elderly patients
No dose adjustment is required in elderly patients.

Liver function disorders
No data are available.

Use in children and adolescents
Detriol is not recommended for use in children and adolescents under 18 years of age. The safety and
efficacy of calcitriol capsules have not been sufficiently studied to allow dose recommendations. In
children under 6 years of age, there is a risk of choking due to the pharmaceutical form (capsule).

Method of administration
Oral use.
Soft capsules should be swallowed whole (do not chew), with a small amount of liquid, in the morning
with breakfast. Patients requiring higher doses should take the total daily dose divided into 2 or 3
individual doses, all taken with meals.

Duration of treatment
The duration of treatment depends on disease symptoms and laboratory parameters. Therefore, it must
be determined individually for each patient by the treating physician.

Accidental overdose of Detriol
No cases of acute poisoning with Detriol have been reported to date. Based on theoretical
considerations, a single overdose is unlikely to cause any adverse symptoms.
If symptoms of overdose occur (see section 4 "Possible side effects"), consult your doctor immediately.

Missed dose of Detriol
Do not take a double dose to make up for a missed dose. Continue taking the medicine as directed.

Stopping Detriol treatment
Do not interrupt or discontinue treatment without consulting your doctor.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
The most commonly reported adverse reaction was increased blood calcium levels (hypercalcemia).

Very common (may affect more than 1 in 10 patients):
Increased blood calcium levels (hypercalcemia).

Common (may affect up to 1 in 10 patients):
Headache, abdominal pain, nausea, rash, urinary tract infections.

Uncommon (may affect up to 1 in 100 patients):
Decreased appetite, vomiting, increased blood creatinine levels.

Rare (may affect up to 1 in 1,000 patients):
Severe allergic reactions caused by peanut oil.

Frequency not known (frequency cannot be estimated from available data):
Hypersensitivity, urticaria, increased thirst, dehydration, weight loss, apathy, psychiatric disorders, muscle weakness, sensory disturbances, somnolence, cardiac arrhythmias, constipation, intestinal obstruction due to paralysis of intestinal muscles (paralytic ileus), skin redness (erythema), itching, delayed growth, increased urine volume, nocturnal urination, pathological calcium salt deposits in the skin and internal organs (calcinosis), fever, thirst.

Since calcitriol exhibits vitamin D activity, possible adverse reactions are comparable to symptoms of vitamin D overdose, i.e. various symptoms of elevated blood calcium levels (hypercalcemia syndrome) or calcium poisoning (depending on the severity and duration of elevated blood calcium levels).

Due to the short biological half-life of calcitriol, pharmacokinetic studies have shown that elevated serum calcium levels normalize within a few days after dose reduction or discontinuation—significantly faster than with vitamin D supplementation.

Chronic adverse reactions may include: muscle weakness, weight loss, sensory disturbances, fever, thirst or increased sensation of thirst, increased urine volume, dehydration, apathy, delayed growth, and urinary tract infections.

Concomitant elevation of both calcium and phosphate levels in the blood may lead to soft tissue calcification visible on X-ray.

Allergic reactions (itching, rash, urticaria, and very rarely serious skin disorders associated with redness) may occur in sensitive patients.

In patients with normal kidney function, persistent elevation of blood calcium levels (chronic hypercalcemia) may be associated with increased serum creatinine levels.

No clinically significant differences in the types of adverse reactions are expected in specific patient groups, e.g. elderly patients.

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181C
02-222 Warsaw
Tel.: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl

Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps to gather more information on the safety of the medicine.

5. How to store Detriol

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and bottle following:
"EXP". The expiry date refers to the last day of the stated month.
Do not store above 25°C.
Keep the bottle tightly closed and in the outer packaging to protect from light.
Shelf life after first opening the bottle: 4 months.

6. Contents of the pack and other information

What Detriol contains

• The active substance is: calcitriol
• The other ingredients are: Content of the capsule: Arachis oil (peanut oil), purified, butylated hydroxyanisole, butylated hydroxytoluene, ethanol, anhydrous.

Capsule shell:
Gelatin, glycerol 85%, sorbitol 70%, non-crystallizing, iron oxide red (E 172).
Detriol 0.5 microgram soft capsules contain arachis oil (peanut oil), sorbitol,
and alcohol (ethanol) (see section 2).

What Detriol looks like and contents of the pack
Detriol 0.5 microgram soft capsules are opaque, red, oval, soft capsules.
Detriol is available in packs containing 90 or 100 soft capsules.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
SUN-FARM Sp. z o.o.
ul. Dolna 21
05-092 Łomianki
tel. +48 22 350 66 69

Manufacturer
mibe GmbH Arzneimittel
Münchener Straße 15
06796 Brehna
Germany