INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT Duovit® (Duovit®)

Composition:

Active substances:

1 red coated tablet contains:

vitamin A (retinol palmitate) 5000 IU;

vitamin D3 (cholecalciferol) 200 IU;

vitamin C (ascorbic acid) 60 mg;

vitamin PP (nicotinamide) 13 mg;

vitamin E (α-tocopheryl acetate) 10 mg;

calcium pantothenate 5 mg;

vitamin B6 (pyridoxine hydrochloride) 2 mg;

vitamin B2 (riboflavin) 1.2 mg;

vitamin B1 (thiamine nitrate) 1 mg;

folic acid 0.4 mg;

vitamin B12 (cyanocobalamin) 3 μg;

Excipients: lactose monohydrate, orange flavor, polysorbate 80, glycerin, castor oil, sorbitol (E 420), glucose solution, magnesium stearate, capol 600 pharma (containing yellow wax, carnauba wax, shellac), anti-adherent agent, Opalux AS-F-2833G (containing Yellow Sunset FCF (E 110), povidone, sucrose, Ponceau 4R (E 124), titanium dioxide, sodium benzoate (E 211), purified water), sucrose, mannitol (E 421);

Active substances:

1 blue coated tablet contains:

magnesium (Mg²⁺ as magnesium lactate) 20 mg;

calcium (Ca²⁺ as calcium hydrogen phosphate) 15 mg;

phosphorus (P⁵⁺ as calcium hydrogen phosphate) 12 mg;

iron (Fe²⁺ as iron fumarate) 10 mg;

zinc (Zn²⁺ as zinc sulfate) 3 mg;

copper (Cu²⁺ as copper sulfate) 1 mg;

manganese (Mn²⁺ as manganese sulfate) 1 mg;

molybdenum (Mo⁶⁺ as sodium molybdate) 0.1 mg;

Excipients: lactose monohydrate, orange flavor, polysorbate 80, glycerin, castor oil, sorbitol (E 420), glucose solution, magnesium stearate, capol 600 pharma (containing yellow wax, carnauba wax, shellac), anti-adherent agent, mineral oil, povidone, Opalux AS-20912 Blue (containing indigocarmine, povidone, sucrose, titanium dioxide, sodium benzoate (E 211), purified water), sucrose.

Pharmaceutical form. Coated tablets.

Main physicochemical properties: hard, smooth red coated tablets with a sweet-sour taste and possible specks on the surface; hard, smooth blue coated tablets with possible specks on the surface.

Pharmacotherapeutic group. Multivitamins with trace elements. ATC code: A11A A04.

Pharmacological properties.

Pharmacodynamics.

Duovit®, coated tablets, contain vitamins and trace elements. Vitamins and minerals are closely related in their functional activity and exhibit an additive effect. Some vitamins and minerals cannot coexist, which is why they are separated into red (vitamins) and blue (minerals) tablets of Duovit®.

Vitamins of group B (B1, B2, B6, pantothenic acid, and nicotinamide) participate in carbohydrate, protein, and fat metabolism, as well as in the functioning of the nervous system. Vitamin B12 is involved in erythropoiesis and supports normal nervous system function. Vitamin A is necessary for epithelial cell development and for synthesis of visual pigment. Vitamin D3 regulates calcium absorption and promotes proper mineralization of bones and teeth. Vitamin C controls iron absorption and participates in numerous redox processes in the body. Vitamin E, a physiological antioxidant, protects cell membranes from damage and maintains their functional integrity.

Mineral substances and trace elements are extremely important for the body. They are structural components of tissues or activators and integral parts of enzymes and hormones. Calcium and phosphorus play an important role in the mineralization of bones and teeth. Calcium ions activate many enzymes, participate in the regulation of cardiac muscle tone, in nerve impulse transmission, and regulate cell membrane permeability. Iron and copper, together with B-complex vitamins, are essential for erythrocyte formation. Magnesium, manganese, zinc, and molybdenum serve as enzymatic components in numerous reactions vital for the body.

Pharmacokinetics.

There are no available data on the pharmacokinetics of Duovit® tablets. However, scientific literature contains information on the absorption, distribution, and elimination of certain vitamins and minerals.

Water-soluble vitamins (B-complex vitamins, vitamin C) are absorbed within daily requirements. Excess amounts not absorbed by tissues are excreted in urine, and in some cases also in feces. These vitamins are present in the body in very small quantities, so their adequate levels must be maintained regularly.

After oral administration, fat-soluble vitamins A and D3 are absorbed in the small intestine in the presence of fats. Absorption of vitamin E is relatively low (from 25% to 85% of the dose). These vitamins are stored in larger amounts in the liver, making them more potentially toxic than water-soluble vitamins.

Clinical characteristics.

Indications.

Duovit®, coated tablets, are recommended:

in cases of physical and mental overload (during studying, work or at home);
during participation in active sports and active recreation;
in disorders of nutrient absorption (due to alcohol consumption, smoking, in elderly individuals);
in inadequate and unbalanced nutrition;
during dieting (weight loss and other types of diets);
during seasonal periods of fruit and vegetable deficiency in the diet;
in significant loss of minerals (due to vomiting, diarrhea, excessive menstruation, increased sweating).

Contraindications.

Hypersensitivity to the components of the medicinal product, hypervitaminosis of vitamins A, E and D3, renal insufficiency, pronounced renal function disorders. Concomitant use of retinoids. Nephrolithiasis, gout, hyperuricemia, erythremia, erythrocytosis, thrombophlebitis, thromboembolism, fructose intolerance, glucose-galactose malabsorption syndrome, disorders of iron or copper metabolism, hypercalcemia, hypercalciuria, hypermagnesemia, thyrotoxicosis, chronic glomerulonephritis, chronic heart failure, history of sarcoidosis, peptic ulcer of the stomach and duodenum in the stage of exacerbation (due to possible increase in gastric juice acidity), active forms of tuberculosis.

Do not use in children (under 18 years of age).

Interaction with other medicinal products and other forms of interaction.

The medicinal product is recommended to be taken 2 hours before or 2 hours after taking other medicinal products.

It is not recommended to use the drug together with medicinal products containing aromatic rings (tetracycline, quinolines, cholestyramine) and antacids.

Absorption of iron and calcium, tetracycline antibiotics and fluoroquinolones is reduced when used simultaneously.

Some antacid agents containing aluminum, magnesium or calcium reduce the absorption of minerals (iron).

Cholestyramine reduces iron absorption. Calcium may interfere with levothyroxine absorption. If combined use of these drugs is necessary for treatment, the interval between administration should be 2 hours before taking Duovit® and 4–6 hours after taking it. Some food products (e.g., those containing oxalic acid, phosphates or phytic acid) may reduce calcium absorption.

Vitamins A and E mutually enhance their effects and are synergists. Due to the possible development of vitamin A hypervitaminosis, simultaneous use of Duovit®, coated tablets, with other products containing vitamin A or oral retinoids is not recommended. Vitamin E should be avoided in patients taking oral anticoagulants such as dicoumarol and neodicoumarol due to increased risk of bleeding. Vitamin E should not be used together with drugs containing large amounts of iron and silver due to their inhibitory effect on the vitamin. Alpha-tocopherol acetate enhances the effect of steroid and non-steroidal anti-inflammatory agents (sodium diclofenac, ibuprofen, prednisolone).

When vitamin D3 is used concomitantly with thiazide diuretics, the risk of hypercalcemia increases. Ion-exchange resins such as cholestyramine and laxatives (paraffin oil) may reduce vitamin D3 absorption. Due to metabolic activation, the activity of vitamin D3 may be reduced when used simultaneously with phenytoin or barbiturates. Since oral administration of a combination of calcium and vitamin D3 enhances the effect of cardiac glycosides, medical supervision and ECG monitoring are required during their concomitant use.

During therapy with sulfonamides, to prevent crystalluria, large amounts of vitamin C should be avoided. Vitamin C slows down the absorption of beta-adrenoblockers and indirect-acting anticoagulants. Concurrent use of vitamin C and deferoxamine increases tissue iron toxicity, especially in cardiac muscle, which may lead to circulatory decompensation. Vitamin C may be administered only 2 hours after deferoxamine injection. Prolonged use of high doses of ascorbic acid (more than 1 g) in individuals treated with disulfiram inhibits the "disulfiram–alcohol" reaction. Calcium chloride, salicylates, and corticosteroids reduce ascorbic acid stores in the body when used long-term. Absorption of ascorbic acid is reduced when used concomitantly with oral contraceptives, consumption of fruit or vegetable juices, and alkaline drinks. Vitamin B1 may affect the action of curare preparations. Vitamin B2 reduces the absorption and effectiveness of antibiotics (streptomycin, doxycycline). It should be taken at least 3 hours before or 3 hours after the antibiotic dose. Tricyclic antidepressants may reduce riboflavin levels.

Vitamin B6 reduces the effect of levodopa if the patient is taking levodopa alone. Pyridoxine prevents or reduces toxic manifestations observed during isoniazid and other antituberculosis drug therapy.

H2-receptor antagonists, potassium preparations, alcohol (especially with prolonged use), and para-aminosalicylic acid (PAS) reduce vitamin B12 absorption.

Folic acid reduces plasma concentrations of phenytoin; with other antiepileptic agents, mutual reduction of clinical efficacy is possible.

Special precautions.

Duovit® tablets should be taken after a meal in the first half of the day; otherwise, they may cause discomfort in the stomach.

Patients with diabetes mellitus may use Duovit®; however, they should be aware that each daily dose contains 1.6 g of sugar. Each coated tablet contains 0.8 g of sugar.

Use with caution in patients with liver impairment, history of peptic ulcer of the stomach or duodenum, acute nephritis, decompensated cardiac function, gallstone disease, chronic pancreatitis, allergic conditions, idiosyncrasy, diabetes mellitus, and in patients with neoplasms.

Women who have taken high doses of retinol (over 10,000 IU) should not plan pregnancy earlier than 6–12 months after discontinuation. This is due to the risk of fetal developmental abnormalities caused by high levels of vitamin A in the body during this period.

Discoloration of urine to a yellow color may occur, which is completely harmless and is due to the presence of riboflavin in the drug.

The drug should not be prescribed together with other multivitamins, as this may lead to vitamin overdose.

Absorption of ascorbic acid may be impaired in intestinal dyskinesia, enteritis, and achylia. Since ascorbic acid enhances iron absorption, its use in high doses may be dangerous for patients with hemochromatosis, thalassemia, polycythemia, leukemia, and sideroblastic anemia. As a reducing agent, ascorbic acid may interfere with laboratory test results, such as glucose, bilirubin, transaminase activity, and lactate dehydrogenase levels.

Special warnings regarding inactive ingredients

Duovit® contains lactose, sorbitol, glucose, and sucrose. This medication is contraindicated in patients with rare hereditary forms of fructose or galactose intolerance, lactase deficiency, or glucose-galactose malabsorption.

Azo dyes E 124 and E 110 may cause allergic reactions.

Use during pregnancy or breastfeeding.

Since studies on the safety of the drug during pregnancy and breastfeeding have not been conducted, it should not be used in these patient groups. Animal studies have shown that vitamin A in high doses (100–1000 times higher than the recommended daily human dose) has teratogenic effects.

Ability to influence reaction rate when driving or operating machinery.

There have been no reports indicating that the drug affects the ability to drive or operate machinery.

Method of Administration and Dosage

Take 1 red vitamin tablet and 1 blue mineral tablet once daily.

The tablets should be swallowed whole after breakfast with liquid.

Children

Do not use in children.

Overdose

No intoxication is expected at the recommended dosage. The likelihood of overdose is minimal. In case of overdose, the listed adverse reactions may intensify, and abdominal bloating (meteorism) may occur.

Prolonged use of high doses may lead to hypervitaminosis A and D3. Overdose of vitamin D3 may cause weakness, anorexia, nausea, vomiting, diarrhea, weight loss, fever, convulsions, and cardiovascular and renal disorders. Hypercalcemia may develop due to hypersensitivity to vitamin D3. Symptoms of hypercalcemia include anorexia, polyuria, nausea, vomiting, general weakness, headache, apathy, and thirst.

Overdose of vitamin A may lead to headache, dizziness, sleep disturbances, nausea, vomiting, drowsiness, photophobia, and convulsions. If the above symptoms occur, discontinue use of the product and seek medical advice immediately. When very high doses of vitamin E are taken, headache, increased fatigue, nausea, diplopia, muscle weakness, slight creatinuria, and gastrointestinal disturbances may occur.

Iron overdose may cause nausea, vomiting, diarrhea, abdominal pain, hematemesis, rectal bleeding, lethargy, and acute vascular insufficiency. Hyperglycemia and acidosis may occur. High doses of calcium may lead to constipation and urinary stone formation.

Prolonged use of high doses of ascorbic acid may suppress the function of the islet apparatus of the pancreas; therefore, its functional capacity should be monitored. Overdose may alter renal excretion of ascorbic and uric acids during urine acidification, increasing the risk of oxalate stone formation. High-dose ascorbic acid may cause heartburn. When recommended doses are significantly exceeded (vitamin C dose exceeding 1 g per day), renal failure, sleep disturbances, sensation of heat, increased fatigue, disturbances in zinc and copper metabolism, increased excitability, erythrocytopenia, and neutrophilic leukocytosis may occur.

In case of overdose symptoms, administration of Duovit® should be discontinued. If necessary, treatment should be initiated. Induce vomiting and administer large amounts of fluid.

If hypercalcemia is detected, a diet restricted in calcium and vitamin D3 should be followed. Further treatment is symptomatic.

Adverse reactions.

Adverse effects that may occur during the use of Duovit® are classified by frequency:

very common: > 1/10,
common: > 1/100, < 1/10,
uncommon: > 1/1000, < 1/100,
rare: > 1/10,000, < 1/1000,
very rare: < 1/10,000,
frequency unknown (cannot be estimated from available data).

Within each frequency group, adverse effects are listed in order of decreasing severity.

If Duovit® tablets are taken as directed, they do not usually cause adverse effects.

From the immune system:

very rare: hypersensitivity reactions (allergic) to individual components of the medicinal product;

frequency unknown: anaphylactic reactions, angioedema, bronchospasm.

If hypersensitivity reactions occur, treatment should be discontinued and medical advice should be sought. In case of anaphylactic reactions, immediate medical attention is required.

From metabolism and nutrition:

frequency unknown: hypercalcemia, calcinosis.

From the nervous system:

frequency unknown: headache, dizziness, drowsiness.

From blood and lymphatic system:

frequency unknown: decreased blood coagulation.

From the eye:

frequency unknown: visual disturbances.

From the gastrointestinal tract:

rare: dyspepsia, nausea, vomiting, stomach pain, belching, constipation, diarrhea, increased gastric juice secretion.

From the skin and subcutaneous tissue:

very rare: skin rashes, urticaria, pruritus, erythema, eczema.

From the kidneys and urinary bladder:

uncommon: discoloration of urine;

frequency unknown: hypercalciuria, glomerular apparatus damage of the kidneys.

General disorders:

frequency unknown: hyperthermia, increased excitability, increased sweating.

Adverse effects occurring with prolonged use at high doses

From metabolism and nutrition:

frequency unknown: hyperuricemia, decreased glucose tolerance, hyperglycemia, impaired glycogen synthesis.

From the nervous system:

frequency unknown: paresthesia.

From the heart:

frequency unknown: cardiac arrhythmias, arterial hypertension, myocardial dystrophy.

From blood and lymphatic system:

frequency unknown: thrombocytosis, hyperprothrombinemia, thrombosis.

Administration of ascorbic acid in doses exceeding 1 g per day in patients with glucose-6-phosphate dehydrogenase deficiency may cause hemolysis of erythrocytes (hemolytic anemia).

From the gastrointestinal tract:

very rare: gastrointestinal disturbances.

From the skin and subcutaneous tissue:

frequency unknown: dryness and cracking of palms and soles, hair loss, seborrheic eruptions.

From the kidneys and urinary bladder:

frequency unknown: renal failure, crystalluria, formation of urate, cystine and/or oxalate calculi.

Investigations:

frequency unknown: transient increase in aspartate aminotransferase (AST), lactate dehydrogenase, alkaline phosphatase activity; changes in urine parameters; increased levels of calcium in blood and urine; hyperglycemia; glucosuria.

Shelf life.

3 years.

Storage conditions.

Store at a temperature not exceeding 25 °C in the original packaging to protect from light and moisture.

Keep out of reach and sight of children.

Packaging.

5 red and 5 blue tablets in a blister, 4, 6, or 8 blisters per cardboard box.

Pharmaceutical category. Over-the-counter (without prescription).

Manufacturer.

KRKA, d.d., Novo mesto, Slovenia / KRKA, d.d., Novo mesto, Slovenia.

Manufacturer's address.

Smarjeska cesta 6, 8501 Novo mesto, Slovenia / Smarjeska cesta 6, 8501 Novo mesto, Slovenia.