Olidetrim® pro

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT OLIDETRIM® PRO (OLIDETRIM PRO)

Composition:

Active substance: cholecalciferol;

1 soft capsule contains 50 μg of cholecalciferol, equivalent to 2000 IU of vitamin D3.

Excipients: capsule contents: purified safflower oil; capsule shell: gelatin, glycerol, purified water, medium-chain triglycerides (traces).

Pharmaceutical form. Soft capsules.

Main physicochemical properties: light-yellow, oval, soft capsules with a central seam line, filled with a light-yellow liquid.

Pharmacotherapeutic group. Vitamins. Vitamin D and analogues. Cholecalciferol.

ATC code A11C C05.

Pharmacological properties.

Pharmacodynamics.

Cholecalciferol (vitamin D3) is synthesized in the skin under the influence of ultraviolet radiation, including sunlight. In its biologically active form, vitamin D3 stimulates calcium absorption in the intestine, calcium penetration into the osteon, and calcium release from bone tissue. In the small intestine, it promotes both rapid and delayed calcium uptake. In addition, passive and active phosphate transport is stimulated. In the kidneys, it reduces excretion of calcium and phosphates by stimulating tubular reabsorption. The biologically active form of cholecalciferol directly inhibits parathyroid hormone production in the parathyroid glands. Parathyroid hormone secretion is further suppressed due to increased intestinal calcium absorption induced by biologically active vitamin D3.

Pharmacokinetics.

Absorption

Vitamin D, in the amounts present in food, is almost completely absorbed from the diet. It is absorbed together with dietary lipids and bile acids; therefore, administration of vitamin D during the main meal of the day may enhance its absorption.

Distribution

Cholecalciferol accumulates in adipocytes, and its biological half-life is approximately 50 days.

After a single oral dose of cholecalciferol, the maximum serum concentration of 25(OH)D3—the main storage form—is reached approximately 7 days later.

Biotransformation

Metabolic conversion of cholecalciferol occurs in the liver via microsomal hydroxylase, forming 25-hydroxycholecalciferol (25(OH)D3). This is subsequently converted in the kidneys into 1,25-dihydroxycholecalciferol, which is the biologically active form. Circulating metabolites are bound to a specific α-globulin.

Elimination

25(OH)D3 is eliminated slowly, with an apparent half-life in serum of approximately 50 days. Cholecalciferol and its metabolites are primarily excreted via bile and feces. After administration of vitamin D in high doses, serum concentrations of 25-hydroxycholecalciferol may remain elevated for several months. Hypercalcemia caused by overdose may persist for several weeks (see section "Overdose").

Clinical characteristics.

Indications.

• Prevention of vitamin D deficiency and conditions associated with vitamin D deficiency (e.g. rickets, osteomalacia) in adult patients and children aged 12 years and older with normal body weight.
• As an adjunct to specific osteoporosis therapy in adults.

Contraindications.

• Hypersensitivity to the active substance or to any of the excipients.
• Hypercalcaemia and/or hypercalciuria.
• Nephrolithiasis and/or nephrocalcinosis.
• Severe renal impairment.
• Hypervitaminosis D.
• Pseudohypoparathyroidism (vitamin D requirement may be lower than during normal vitamin sensitivity; risk of prolonged overdose).
• Sarcoidosis.
• Tuberculosis.
• Concomitant intake of vitamin D (may lead to overdose).
• Children under 12 years of age.

Interaction with other medicinal products and other forms of interaction.

Concomitant use of anticonvulsants (e.g. phenytoin) or barbiturates (and possibly other enzyme-inducing drugs) may lead to reduced effect of vitamin D3 due to metabolic inactivation.

When treating with thiazide diuretics, plasma calcium levels should be monitored due to reduced renal calcium excretion.

Glucocorticoids increase vitamin D metabolism, which may lead to reduced efficacy of vitamin D.

Oral intake of vitamin D together with cardiac glycosides may enhance the efficacy and toxicity of digoxin due to increased calcium levels (risk of cardiac arrhythmias). In such patients, regular ECG monitoring and measurement of plasma and urinary calcium levels are required, as well as determination of digoxin or digitoxin concentration, if possible.

Concomitant use of ion-exchange resins such as cholestyramine, colestipol hydrochloride, orlistat, or laxatives such as mineral oil, may reduce gastrointestinal absorption of vitamin D.

The cytotoxic agent actinomycin and imidazole antifungals may reduce the activity of vitamin D3 by inhibiting the conversion of 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol by renal enzymes, specifically 25-hydroxyvitamin D-1-hydroxylase.

Rifampicin may reduce the efficacy of cholecalciferol due to induction of hepatic enzymes.

Isoniazid may reduce the efficacy of cholecalciferol by inhibiting the metabolic activation of cholecalciferol.

Vitamin D may antagonize drugs used in the treatment of hypercalcaemia, such as calcitonin, etidronate, pamidronate.

Magnesium-containing preparations (e.g. antacids) should not be used during vitamin D therapy due to the risk of hypermagnesaemia.

Concomitant use of the product with antacids containing aluminium or magnesium may provoke toxic effects of aluminium on bone and hypermagnesaemia in patients with renal insufficiency.

Ketoconazole may reduce the biosynthesis and catabolism of 1,25(OH)2-cholecalciferol.

Concomitant use with medicinal products containing high doses of calcium and phosphorus increases the risk of hyperphosphataemia.

The use of cholecalciferol in combination with metabolites or analogues of vitamin D should be avoided. Concomitant administration of vitamin D3 with metabolites or analogues of vitamin D is possible only exceptionally and only under strict monitoring of serum calcium levels, as this increases the risk of toxic effects.

Other medicinal products or dietary supplements containing vitamin D should not be used during treatment with OLIDETRIM® PRO, except when such a treatment regimen has been specifically prescribed by a physician.

Special precautions for use

When using the medicinal product, additional intake of vitamin D should be taken into account (concomitant use of other vitamin D-containing preparations, duration of sun exposure, and amount of vitamin D consumed with certain foods). In Ukraine, cutaneous synthesis of vitamin D may be effective in healthy children and adults who expose their forearms and lower legs to sunlight without sunscreen for at least 15 minutes between 10:00 and 15:00 from May through September.

Vitamin D deficiency is defined as a 25-hydroxycholecalciferol (25(OH)D) level < 20 ng/mL (< 50 nmol/L); the target concentration to ensure optimal vitamin D effect is considered to be 30–50 ng/mL (75–125 nmol/L).

The medicinal product should be administered with special caution to patients with impaired renal function. In such patients, calcium and phosphate levels should be monitored. The risk of soft tissue calcification should be considered. Calcium and phosphate levels must be monitored in these patients.

Caution is required when prescribing to patients receiving treatment for cardiovascular diseases (see section "Interaction with other medicinal products and other forms of interactions").

Cholecalciferol should not be used in patients with sarcoidosis due to the risk of accelerated conversion of vitamin D into its active metabolites. In such patients, plasma and urinary calcium levels should be monitored.

In the general population, there are no specific indications for 25(OH)D3 testing.

Patients with excess body weight (adults – BMI ≥ 30 kg/m², children and adolescents – BMI > 90th percentile) should receive twice the recommended dose of vitamin D compared to patients with normal body weight.

There is no evidence of a direct causal relationship between vitamin D intake and kidney stone formation; however, such a risk is plausible, especially when calcium is co-administered. The need for additional calcium intake should be individually assessed for each patient. Additional calcium supplementation should be administered under strict medical supervision and only after determining plasma and urinary calcium levels.

If treatment is prolonged and the daily dose of vitamin D significantly exceeds the recommended dose, serum calcium levels should be monitored, and renal function should be monitored by measuring serum creatinine. Such monitoring is particularly important for elderly patients receiving concomitant therapy with cardiac glycosides or diuretics, as well as for patients at high risk of kidney stone formation.

In case of hypercalciuria (urinary calcium excretion exceeding 300 mg (7.5 mmol)/24 hours) or signs of impaired renal function, the dose should be reduced or treatment discontinued.

To prevent hypercalcemia during treatment, medical monitoring of plasma and urinary calcium levels is required.

Cholecalciferol is not recommended for individuals predisposed to calcium-containing kidney stones.

The medicinal product should be used with special caution in patients with impaired renal function who are receiving benzothiadiazine derivatives, as well as in immobilized patients (due to the risk of hypercalcemia and hypercalciuria). In patients with severe renal insufficiency, normal metabolic conversion of cholecalciferol is impaired; therefore, other forms of vitamin D should be used (see section "Contraindications").

Elderly patients

Age > 65 years

In a recent study in elderly individuals with a history of falls, an increased risk of falling was observed when administering 60,000 IU of vitamin D monthly. Therefore, the use of cholecalciferol in elderly patients is recommended only after careful benefit-risk assessment and only when clear indications exist. The dose should not exceed 24,000 IU per month. For elderly patients with a history of falls, daily vitamin D supplementation should be considered.

Age > 70 years

When treating with vitamin D using a loading-dose protocol, serum 25(OH)D3 levels should also be regularly monitored. Treatment should be discontinued if levels reach ≥ 50 ng/mL.

Use during pregnancy or breastfeeding

Pregnancy

Women planning pregnancy may take vitamin D, as for all adults, preferably under monitoring of plasma 25(OH)D3 concentration.

During confirmed pregnancy, vitamin D should be used only when necessary, if the expected benefit to the pregnant woman, in the physician's opinion, outweighs the potential risk to the fetus, at strictly recommended doses according to clinical guidelines.

During pregnancy, the woman should follow her physician's recommendations.

Breastfeeding

Vitamin D and its metabolites pass into breast milk; therefore, the medicinal product should be used during breastfeeding only under medical supervision and on prescription.

Fertility

No effects on reproductive function or fertility were observed in studies investigating the effects of cholecalciferol at therapeutic doses.

Ability to influence reaction rate when driving or operating machinery

No studies have been conducted on the effect of the medicinal product on the ability to drive or operate machinery. Adverse effects of cholecalciferol that could affect the ability to drive or operate machinery are unknown.

Dosage and Administration

Dosage

Prevention of vitamin D deficiency and conditions associated with vitamin D deficiency (e.g., rickets, osteomalacia) in adult patients and children aged 12 years and older with normal body weight

The usual recommended dose is 2000 IU/day for patients with normal body weight during the period from October to April, or throughout the year if effective cutaneous synthesis of vitamin D is not ensured during summer months (see section "Special precautions for use").

As an adjunct to specific osteoporosis therapy in adults

The usual recommended dose is 2000 IU/day, regardless of season.

The dose should not exceed the recommended amount, nor should the medication be used for longer than recommended. Additionally, do not take any other medicinal products, vitamin or mineral supplements containing calcium or vitamin D (cholecalciferol), calcitriol, or other vitamin D metabolites and analogs without consulting a physician. Plasma concentration of 25-hydroxyvitamin D (25(OH)D3) should be monitored according to clinical guidelines.

Patients with hepatic impairment

Dose adjustment is not required.

Patients with renal impairment

The medicinal product is contraindicated in patients with impaired kidney function (see section "Contraindications" and "Special precautions for use").

Administration

For oral use.

The capsule should be taken whole with sufficient amount of water, preferably during a main meal.

Children

OLIDEYTRIM® PRO, 2000 IU capsules, should not be used in children under 12 years of age.

Overdose

Symptoms

Acute and chronic overdose of vitamin D3 may cause hypercalcemia and increased levels of calcium in blood plasma and urine. Symptoms may be nonspecific and include nausea, vomiting, and diarrhea in the early stages; in later stages, constipation, anorexia, increased fatigue, headache, muscle and joint pain, muscle weakness, polydipsia, polyuria, kidney stone formation, nephrocalcinosis, renal failure, calcium deposition in tissues, ECG changes, arrhythmias, and pancreatitis. Isolated reports of fatal outcomes due to hypercalcemia have been reported.

Treatment

The primary measure is to discontinue vitamin D intake. Normalization of calcium levels after vitamin D intoxication-induced hypercalcemia may take several weeks.

Depending on the severity of hypercalcemia, a calcium-free or low-calcium diet may be used. High fluid intake is recommended, along with forced diuresis using furosemide, and administration of glucocorticoids and calcitonin.

Infusions of phosphates should not be used to reduce hypercalcemia in vitamin D hypervitaminosis due to the risk of metastatic calcification.

Side effects.

Frequency is defined as follows: uncommon (from ≥ 1/1000 to < 1/100); rare (from ≥ 1/10000 to < 1/1000); or frequency not known (cannot be estimated based on available data).

There have been isolated reports of fatal outcomes (see section "Overdose").

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after medicine authorization is of great importance. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients or their legal representatives are requested to report any suspected adverse reactions and lack of efficacy of the medicinal product via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life. 2 years.

Storage conditions.

Store at a temperature not exceeding 30°C. Keep in the original packaging to protect from light. Keep out of reach of children.

Packaging.

15 capsules per blister. 2, or 4, or 6 blisters per cardboard box.

Supply category.

Over-the-counter.

Manufacturer.

Pharmaceutical Works POLPHARMA S.A.

Pharmaceutical Works POLPHARMA S.A.

Manufacturer's address and site of manufacturing operations.

Medana Branch in Sieradz, 10, Wladyslawa Lokietka Str., 98-200 Sieradz, Poland