INSTRUCTIONS for medical use of the medicinal product PikoVit® (Pikovit®)

Composition:

Active ingredients: 1 tablet contains:

600 IU retinol (vitamin A as retinyl palmitate),
80 IU cholecalciferol (vitamin D3),
10 mg ascorbic acid (vitamin C),
3 mg nicotinamide,
1.2 mg calcium pantothenate,
0.3 mg riboflavin (vitamin B2),
0.3 mg pyridoxine hydrochloride (vitamin B6),
0.25 mg thiamine nitrate (vitamin B1),
0.04 mg folic acid,
0.2 mcg cyanocobalamin (vitamin B12),
12.5 mg calcium (Ca2+ as calcium hydrogen phosphate),
10 mg phosphorus (P5+ as calcium hydrogen phosphate);

Excipients: lactose monohydrate, flavoring agent orange oil, polysorbate 80, glycerin, purified castor oil, citric acid, sorbitol (E 420), glucose solution, magnesium stearate, Caprol 600 Pharma, mineral oil, povidone, anti-adherent agent, titanium dioxide (E 171), yellow coloring agent West FCF (E 110), quinoline yellow coloring agent (E 104), indigo carmine blue coloring agent (E 132), mannitol (E 421), Ponceau 4R coloring agent (E 124), sucrose.

Medicinal form. Film-coated tablets.

Main physicochemical properties: film-coated tablets in red, yellow, green and orange colors.

Pharmacotherapeutic group. Multivitamins with minerals. ATC code A11A A03.

Pharmacological properties.

Pharmacodynamics.

Pikovit®, coated tablets, contains vitamins in combination with calcium and phosphorus. Vitamins are substances that participate in the regulation of many biochemical processes in the body. The effects of vitamins and minerals in the body are primarily physiological rather than pharmacodynamic.

Vitamins of group B (B1, B2, B6, B12, pantothenic acid, and nicotinamide) are involved in carbohydrate, protein, and fat metabolism, and also play an important role in the functioning of the nervous system. Vitamin A is necessary for epithelial cell development and for the 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 oxidation-reduction processes in the body.

Minerals are essential for the body. They form components of connective tissue and act as activators and components of enzymes.

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.

Pharmacokinetics.

There are no data available on the pharmacokinetics of Pikovit®, coated tablets. Due to the complex composition of the product and the fact that vitamins and minerals are normally present in the diet, studying such low doses of vitamins contained in Pikovit®, coated tablets, is not feasible.

Water-soluble vitamins (B-complex vitamins and vitamin C) are well absorbed in amounts corresponding to daily requirements. Excess amounts are excreted in urine and, in some cases, in feces. These vitamins are stored in the body only in limited quantities; therefore, they should be administered regularly to maintain adequate tissue concentrations.

Fat-soluble vitamins A and D3, when administered orally, are well absorbed in the small intestine in the presence of fats. When administered in large amounts, these vitamins are stored in the liver and thus are more toxic than water-soluble vitamins.

Calcium ions are absorbed in the small intestine via active transport and passive diffusion. 45% of calcium is protein-bound in blood plasma. Excess calcium is primarily excreted in urine and feces. Phosphate is absorbed from the gastrointestinal tract via active transport and passive diffusion and is distributed throughout plasma, extracellular fluid, cell membranes, collagen, and bones. Most phosphate is absorbed in the small intestine and predominantly excreted in urine.

Clinical characteristics.

Indications.

The product is intended for children:

with reduced appetite;
with physical and mental overloads in schoolchildren;
with delayed development;
as an adjunctive agent during antibiotic therapy;
with seasonal deficiency of fruits and vegetables in the diet.

Contraindications.

Hypersensitivity to the active substances or to any excipient; hypervitaminosis of vitamins A and D3; nephrolithiasis; gout; hyperuricemia; erythremia; erythrocytosis; thrombophlebitis; thromboembolism; fructose intolerance, glucose-galactose malabsorption syndrome, sucrase-isomaltase deficiency; disorders of iron and copper metabolism; hypercalcemia; hypercalciuria; thyrotoxicosis; chronic glomerulonephritis; chronic heart failure; history of sarcoidosis; gastric and duodenal ulcer (due to possible increase in gastric juice acidity); pulmonary tuberculosis; renal insufficiency; concomitant use of retinoids; untreated cobalamin deficiency; malignant anemias; malignant neoplasms.

Interaction with other medicinal products and other forms of interaction.

Due to the possibility of developing hypervitaminosis A, concomitant use of Pиковіт® coated tablets with other products containing vitamin A or with oral retinoids is not recommended. Vitamin A should not be administered together with oral retinoids, as their combination may be toxic. Retinol may reduce the anti-inflammatory effect of glucocorticoids. Concomitant use with nitrates and cholestyramine is not recommended, as they impair retinol absorption.

When treating with sulfonamides, high doses of vitamin C should be avoided to prevent crystalluria. Vitamin C enhances iron absorption, but slows down the absorption of beta-adrenergic blockers and indirect-acting anticoagulants. Concurrent use of vitamin C and deferoxamine increases tissue iron toxicity, especially in the myocardium, 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, equivalent to the content of 100 Pиковіт® tablets) by patients treated with disulfiram inhibits the disulfiram-alcohol reaction. Calcium chloride, salicylates, and corticosteroids reduce ascorbic acid reserves in the body when used long-term. Absorption of ascorbic acid is reduced when taken simultaneously with fruit or vegetable juices, alkaline drinks, or when Pиковіт® coated tablets are used by adults concomitantly with oral contraceptives.

Pyridoxine reduces the effectiveness of levodopa if the patient is taking levodopa alone. Vitamin B6 prevents or reduces toxic manifestations observed during treatment with isoniazid and other antituberculosis drugs. Thiamine may weaken curare-like effects. PAS, cimetidine, potassium preparations, and alcohol reduce the absorption of vitamin B12. Riboflavin is incompatible with streptomycin and reduces the effectiveness of antibacterial agents (oxytetracycline, doxycycline, erythrocycline, tetracycline, and lincomycin). It should be taken at least 3 hours before or 3 hours after the dose of antibiotic. Tricyclic antidepressants, imipramine, and amitriptyline inhibit riboflavin metabolism, especially in cardiac tissues. When used concomitantly with quinine, hemorrhages may be intensified.

Concomitant use of vitamin D3 and thiazide diuretics increases the risk of hypercalcemia. Ion-exchange resins such as cholestyramine and laxatives (paraffin oil) may reduce vitamin D3 absorption. Due to metabolic activation, vitamin D3 activity may be reduced when used concomitantly with phenytoin or barbiturates. Therefore, the product is recommended to be taken 2 hours before or 2 hours after other medicinal products. Since concomitant oral administration of calcium- and vitamin D3-containing products enhances the effect of cardiac glycosides, medical supervision and ECG monitoring are required during their concomitant use.

In patients with folate deficiency, folic acid administration may reduce plasma phenobarbital levels and provoke epileptic seizures. Ethanol, cycloserine, glutethimide, and methotrexate may affect folate metabolism. Folic acid absorption is reduced when used concomitantly with analgesics, anticonvulsants, antacids, sulfonamides, antibiotics, and cytostatics. Cases of reduced or altered absorption may occur when cholestyramine and folic acid are used concomitantly. Therefore, the product should be taken 1 hour before or 4–6 hours after cholestyramine. It should not be used together with mineral acids, alkaline substances, or reducing agents, as folic acid inactivation occurs.

Special precautions.

If any hypersensitivity reactions occur during treatment, the drug should be discontinued. Prior to concomitant use of other vitamin, mineral, or vitamin-mineral preparations, consultation with a physician is mandatory. The drug is not recommended to be prescribed together with other multivitamins, as overdose is possible. Do not exceed the recommended dose.

Patients with diabetes mellitus may use Pиковіт®; however, they should be aware that each coated tablet contains 0.6 g of sugar, and the daily dose contains from 2.4 g to 4.2 g of sugar.

Use with caution in patients with a history of kidney or liver disease, acute nephritis, cardiac decompensation, cholelithiasis, chronic pancreatitis, allergic disorders, idiosyncrasy, neoplasms, or predisposition to thrombosis and bleeding (hemophilia, thrombocytopenia, thrombopathies).

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

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

The drug should be administered with caution in patients with anemias of unknown etiology, as folic acid may interfere with the diagnosis of pernicious anemia by improving hematological manifestations of the disease, while allowing neurological complications to progress. Blood analysis should be systematically performed during treatment of anemias with folic acid. Prolonged use of the drug is not recommended (especially in high doses) due to the possible decrease in vitamin B12 concentration.

Special information about some of the excipients

Pиковіт® contains lactose, sucrose, glucose, and sorbitol (E 420); therefore, patients with rare hereditary forms of fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase deficiency should not take this drug. Pиковіт® contains azo dyes E 110 and E 124, which may cause allergic reactions.

Patients with known intolerance to certain sugars should consult their physician before taking this medicinal product.

Use during pregnancy or breastfeeding.

The drug is intended for use in children.

Women during pregnancy or breastfeeding may take vitamins and minerals only after mandatory consultation with a physician. Pregnancy should not be planned earlier than 6–12 months after high-dose retinol therapy (over 10,000 IU) due to the risk of embryonic abnormalities caused by high vitamin A levels in the body.

Ability to influence reaction rate while driving or operating machinery.

The drug is intended for use in children.

Method of Administration and Dosage.

For the prevention of vitamin deficiency:

children aged 4 to 6 years – 1 coated tablet 1–2 times daily;

children aged 7 to 14 years – 1 coated tablet 2–3 times daily.

For the treatment of vitamin deficiency:

children aged 4 to 6 years – 1 coated tablet 4–5 times daily;

children aged 7 to 14 years – 1 coated tablet 5–7 times daily.

Coated tablets should be sucked in the mouth.

In cases of reduced appetite, Pиковіt® is recommended for use over 2 months; for other indications – as needed, depending on the duration and frequency of symptoms, after consultation with a physician.

Children.

The medication is intended for children aged 4 years and older.

Overdose.

No intoxication is expected when recommended doses are taken. In case of overdose, the likelihood of the adverse reactions listed increases; abdominal bloating (meteorism) may occur.

Prolonged use of high doses may lead to hypervitaminosis A and D3, although overdose with Pиковіt® coated tablets is unlikely. Overdose of vitamin D3 may cause weakness, anorexia, nausea, vomiting, diarrhea, weight loss, fever, convulsions, and cardiovascular and kidney disorders. Hypercalcemia may develop due to hypersensitivity to vitamin D3. Symptoms of hypercalcemia include anorexia, polyuria, nausea, vomiting, general weakness, headache, apathy, and thirst. Vitamin A overdose may lead to headache, dizziness, sleep disturbances, nausea, vomiting, drowsiness, photophobia, and convulsions. If any of the above symptoms occur, discontinue the medication and seek medical advice immediately.

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 intake may cause heartburn. Significant overdose (if vitamin C intake exceeds 1 g per day, equivalent to 100 Pиковіt® coated tablets) may lead to renal failure, sleep disturbances, sensation of heat, increased fatigue, disturbances in zinc and copper metabolism, increased excitability, erythrocytopenia, and neutrophilic leukocytosis.

If signs of overdose occur, discontinue the medication. If possible, initiate treatment. Induce vomiting and ensure adequate hydration. In case of hypercalcemia, follow a diet restricted in calcium and vitamin D3. Further treatment is symptomatic. Very high doses of folic acid may increase central nervous system excitability and provoke convulsions.

Side effects

Immune system disorders: possible hypersensitivity reactions to the components of the drug, including anaphylactic reaction, anaphylactic shock, bronchospasm, Quincke's edema.

If hypersensitivity reactions (allergic reactions) occur, treatment should be discontinued and medical advice should be sought. In case of anaphylactic reaction, immediate emergency medical assistance should be sought.

Metabolism and nutrition disorders: hypercalcemia, calcinosis.

Nervous system disorders: headache, dizziness, drowsiness, increased excitability.

Eye disorders: visual disturbances.

Gastrointestinal disorders: dyspepsia, nausea, vomiting, belching, stomach pain, constipation, diarrhea, increased gastric juice secretion, heartburn.

Skin and subcutaneous tissue disorders: rash, urticaria, itching, redness, eczema.

Renal and urinary disorders: change in urine color, hypercalciuria, glomerular apparatus kidney damage.

Other: hyperthermia, increased sweating.

With prolonged use at high doses, the following adverse effects may occur.

Metabolism and nutrition disorders: hyperuricemia; impaired glucose tolerance, hyperglycemia, impaired glycogen synthesis, anorexia.

Nervous system disorders: paresthesia.

Cardiac disorders: cardiac arrhythmias, arterial hypertension, myocardial dystrophy, arterial hypotension.

Blood and lymphatic system disorders: thrombocytosis, hyperprothrombinemia, thrombus formation.

Administration of ascorbic acid in doses exceeding 1 g per day (more than 100 Pиковит® coated tablets) in patients with glucose-6-phosphate dehydrogenase deficiency may cause hemolysis of erythrocytes (hemolytic anemia).

Gastrointestinal disorders: irritation of the gastrointestinal mucosa, flatulence, bitter taste in mouth.

Skin and subcutaneous tissue disorders: dryness and cracking of palms and soles, hair loss, seborrheic eruptions.

Renal and urinary disorders: renal failure, crystalluria, formation of urate, cystine and/or oxalate calculi.

Investigations: transient increase in aspartate aminotransferase, lactate dehydrogenase, alkaline phosphatase activity; increased levels of calcium in blood and urine, 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 of children.

Packaging

15 tablets in a blister pack; 2 blisters in a cardboard box.

Availability: Over-the-counter.

Manufacturer

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

Manufacturer's address and place of business

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