Olidetrim® pro

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT OLIDETRIM® PRO

Composition:

Active substance: cholecalciferol;

1 soft capsule contains 100 mcg of cholecalciferol, equivalent to 4000 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 A11CC05.

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 calcium and phosphate excretion by stimulating tubular reabsorption. The biologically active form of cholecalciferol directly inhibits parathyroid hormone production in the parathyroid glands. Parathyroid hormone secretion is additionally 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 a 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 after approximately 7 days.

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. osteomalacia, osteoporosis) in adults with obesity [body mass index (BMI) ≥ 30].

Contraindications.

• Hypersensitivity to the active substance or to any of the other excipients of the medicinal product.
• Hypercalcemia and/or hypercalciuria.
• Nephrolithiasis and/or nephrocalcinosis.
• Severe renal function impairment.
• Hypervitaminosis D.
• Pseudohypoparathyroidism (vitamin D requirement may be lower than during normal vitamin sensitivity; risk of prolonged overdose exists).
• Sarcoidosis.
• Tuberculosis.
• Additional intake of vitamin D (may lead to overdose).
• Age under 18 years.
• Pregnancy.

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 excretion of calcium.

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

Oral administration of vitamin D concomitantly 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 should be performed, and, if possible, serum concentrations of digoxin or digitoxin should be determined.

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 antifungal agents reduce the activity of vitamin D3 by inhibiting the conversion of 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol by renal enzymes, resulting in reduced activity of 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 hypercalcemia, such as calcitonin, etidronate, pamidronate.

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

Concomitant use of the product with antacids containing aluminum or magnesium may provoke toxic effects of aluminum on bone and hypermagnesemia 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 hyperphosphatemia.

The use of cholecalciferol in combination with metabolites or analogs of vitamin D should be avoided. Concomitant administration of vitamin D3 with metabolites or analogs 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 the 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 to September.

The medicinal product should be used with particular caution in 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 interaction").

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, specific indications for 25(OH)D3 testing have not been established.

Patients with obesity (adults – BMI ≥ 30 kg/m²) should receive twice the dose of vitamin D compared to the recommended dosage for patients with normal body weight.

There is no established direct causal link between vitamin D intake and kidney stone formation in the general population; however, such a risk is plausible, especially when calcium is co-administered. The need for additional calcium intake should be determined individually for each patient. Supplemental calcium intake should be prescribed under strict medical supervision and only after determining calcium levels in blood plasma and urine.

If treatment is prolonged and the daily dose of vitamin D significantly exceeds the recommended dose, serum calcium levels should be monitored, and kidney function should be assessed 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 kidney function, the dose should be reduced or treatment discontinued.

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

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

The medicinal product should be used with particular caution in patients with impaired renal function who are undergoing treatment with benzothiadiazine derivatives, as well as in immobilized patients (due to the risk of developing 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, elderly individuals with a history of falls showed an increased risk of falling when receiving monthly doses of 60,000 IU vitamin D. 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 according to a loading-dose protocol, serum 25(OH)D3 levels should also be regularly monitored. Treatment should be discontinued when levels reach ≥ 50 ng/mL.

Use during pregnancy or breastfeeding

Pregnancy

High doses (4,000 IU/day) of cholecalciferol are not recommended during pregnancy.

Breastfeeding

High doses (4,000 IU/day) of cholecalciferol are not recommended during breastfeeding.

Women who are breastfeeding should not take high doses of vitamin D. If vitamin D supplementation is indicated during breastfeeding, this should be taken into account when prescribing vitamin D to the infant.

Fertility

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

Ability to affect reaction speed when driving or operating machinery

Studies on the effect of the medicinal product on the ability to drive or operate machinery have not been conducted. Adverse effects of cholecalciferol that could impair the ability to drive or operate machinery are unknown.

Dosage and Administration

Prevention of vitamin D deficiency and conditions associated with vitamin D deficiency (e.g. osteomalacia, osteoporosis) in adults with obesity (BMI ≥ 30)

The usual recommended dose is 4000 IU/day from October to April, or throughout the year if effective cutaneous synthesis of vitamin D cannot be ensured during summer months (see section "Special precautions").

Do not take a higher dose or use the medication for longer than recommended. Also, do not take any other medicinal products, vitamin or mineral supplements containing calcium or vitamin D (cholecalciferol), calcitriol, or other metabolites and analogs of vitamin D 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 medication is contraindicated in patients with impaired renal function (see section "Contraindications" and "Special precautions").

Administration

For oral use.

The capsule should be swallowed whole with sufficient water, preferably during a main meal.

Children

OLIDEtrim® PRO, 4000 IU capsules should not be used in children (under 18 years of age).

Overdose

Symptoms

Acute and chronic overdose of vitamin D3 may cause hypercalcemia and increased calcium concentrations in blood plasma and urine. Symptoms may be non-specific and include nausea, vomiting, and diarrhea in the early stages, progressing in later stages to 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 hypercalcemia have been reported.

Treatment

As a primary measure, vitamin D intake must be discontinued; normalization of calcium levels following 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 a medicinal product is authorized is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients, as well as their legal representatives, should report any suspected adverse reactions and lack of efficacy through 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 and sight of children.

Packaging.

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

Availability.

Over-the-counter.

Manufacturer.

Pharmaceutical Works POLPHARMA S.A.

Pharmaceutical Works POLPHARMA S.A.

Manufacturer's address and location of operations.

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