Ascorutin

I N S T R U C T I O N for medical use of the medicinal product AСCORUTIN (ASCORUTINUM)

Composition:

Active substances: ascorbic acid; rutin;

One tablet contains ascorbic acid 50 mg, rutin 50 mg;

Excipients: potato starch; sugar; calcium stearate; talc.

Medicinal form. Tablets.

Main physico-chemical properties: tablets of light greenish-yellow color with insignificant specks, with flat surface, beveled edges and a score line.

Pharmacotherapeutic group. Capillary-stabilizing agents. Bioflavonoids.

ATC code C05C A51.

Pharmacological Properties

Pharmacodynamics

A combination medicinal product whose action is determined by the effects of its constituent components.

Rutin (vitamin P) promotes the conversion of ascorbic acid into dehydroascorbic acid and prevents further transformation of the latter into diketogulonic acid. Therefore, most of the effects of rutin are mediated through ascorbic acid.

Rutin in combination with ascorbic acid reduces capillary permeability and fragility, strengthens the cellular wall, decreases platelet aggregation, exerts an anti-inflammatory effect (including by inhibition of hyaluronidase activity), and demonstrates antioxidant properties. It also participates in redox processes.

In addition, rutin has the following effects: reduction of exudation of the liquid component of blood plasma and diapedesis of blood cells through the vascular wall; choleretic and mild antihypertensive effects.

In patients with chronic venous insufficiency, rutin reduces edema and pain syndromes, improves trophic disorders, and decreases or eliminates paresthesia and muscle cramps. It helps reduce the severity of adverse effects associated with radiation therapy (cystitis, enteroproctitis, dysphagia, skin erythema) and also slows the progression of diabetic retinopathy.

Pharmacokinetics

Each vitamin contained in the formulation undergoes its characteristic transformations. Ascorbic acid is rapidly absorbed primarily in the duodenum and small intestine. Within 30 minutes after administration, the concentration of ascorbic acid in the blood significantly increases, and tissue uptake begins. Ascorbic acid is initially converted into dehydroascorbic acid, which penetrates through cell membranes without energy expenditure and is rapidly reduced inside the cell. Ascorbic acid in tissues is located almost exclusively intracellularly and is present in three forms: ascorbic acid, dehydroascorbic acid, and ascorbigen (bound ascorbic acid). It is unevenly distributed among organs. High concentrations are found in endocrine glands, particularly in the adrenal glands; lower concentrations are present in the brain, kidneys, liver, and cardiac and skeletal muscles. The concentration of ascorbic acid in leukocytes and platelets is higher than in blood plasma. It is metabolized and excreted by the kidneys up to 90%, primarily as oxalate, and partially in free form.

Rutin, after absorption in the gastrointestinal tract, promotes the transport and deposition of ascorbate. It is excreted unchanged and as metabolites, primarily via bile and to a lesser extent in urine.

The elimination half-life is 10–25 hours.

Clinical characteristics.

Indications.

• Deficiency of rutin and ascorbic acid.
• Diseases associated with increased vascular permeability – as part of complex therapy.
• Prevention of colds and reduction of flu symptoms.
• Immune system enhancement.

Contraindications.

Hypersensitivity to the components of the drug. Hypercoagulability, thrombophlebitis, predisposition to thrombosis; diabetes mellitus; gout, urolithiasis with urate stone formation, cystinuria, hypokalemia and hypercalcemia, oxaluria; severe kidney diseases; concomitant use with sulfonamides or aminoglycosides; fructose intolerance, glucose-galactose malabsorption syndrome.

Interaction with other medicinal products and other forms of interaction.

Acetylsalicylic acid, oral contraceptives: reduced absorption of the drug.

Ascorbic acid at doses ≥1 g increases the bioavailability of oral contraceptives (estrogens, including ethinylestradiol), increases blood concentration of salicylates, enhancing their adverse effects (risk of crystalluria, effect on gastric mucosa).

Acetylsalicylic acid, barbiturates, tetracyclines: increased urinary excretion of ascorbic acid.

Penicillin (including benzylpenicillin), tetracyclines, iron preparations: high doses of ascorbic acid may enhance their absorption and blood concentration.

Deferoxamine (desferrioxamine): increased iron absorption and urinary excretion; increased tissue toxicity of iron, particularly cardiotoxicity, which may lead to circulatory decompensation. Cases of cardiac dysfunction (usually reversible after discontinuation of vitamin C) have been reported in patients with idiopathic hemochromatosis and thalassemia who received deferoxamine and high doses of ascorbic acid (more than 500 mg per day). This combination requires caution and careful monitoring of cardiac function in these patients. Ascorbic acid should be taken only 2 hours after deferoxamine injection.

Heparin, indirect anticoagulants, phenothiazines, fluphenazine, sulfonamide drugs, aminoglycoside antibiotics: reduced effectiveness of these drugs.

Cyclosporine A: possible reduction in its bioavailability.

Vitamins of the B group: mutual enhancement of therapeutic effect. High doses of ascorbic acid affect vitamin B₁₂ resorption.

Corticosteroids, paracetamol: increased half-life of these agents when high doses of ascorbic acid are administered (this interaction has no clinical consequences when therapeutic doses are used).

Calcitonin: increased absorption rate of ascorbic acid.

Amphetamine: increased renal excretion when high doses of ascorbic acid are used.

Aluminum-containing antacids: it should be noted that ascorbic acid promotes intestinal absorption of aluminum, potentially increasing urinary elimination of aluminum. Concomitant use of antacids and ascorbic acid is not recommended, especially in patients with renal insufficiency.

The drug should not be prescribed simultaneously with cardiac glycosides, antihypertensive agents, or nonsteroidal anti-inflammatory drugs for prolonged use (over 4 weeks), as it may potentiate their effects.

Ascorbic acid enhances excretion of oxalates in urine, thereby increasing the risk of calcium oxalate stone formation in urine.

Combined use of very high doses of ascorbic acid with amygdalin (complementary medicine) may increase the risk of cyanide toxicity.

Smoking, alcohol: reduce plasma ascorbate concentration.

Disulfiram: long-term intake of large doses of ascorbic acid inhibits the disulfiram-alcohol reaction.

High-dose ascorbic acid (over 2 g/day) may interfere with biochemical assays of creatinine, uric acid, and glucose levels in blood and urine samples, as well as with determination of inorganic phosphate, liver enzymes, and bilirubin levels in blood. Fecal occult blood screening tests may yield false-negative results.

Concomitant use with alkaline drinks or consumption of fresh fruit or vegetable juices reduces ascorbic acid absorption.

Special precautions.

Concomitant use of the drug with alkaline drinks, fresh fruit or vegetable juices reduces the absorption of vitamin C. The 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 for patients with hemochromatosis, thalassemia, polycythemia, leukemia, and sideroblastic anemia. Patients with high iron levels in the body should use the drug in minimal doses.

Ascorbic acid should be used with caution in patients with glucose-6-phosphate dehydrogenase deficiency and in patients with a history of kidney disease.

During prolonged administration of high doses of ascorbic acid, kidney function, arterial blood pressure, and pancreatic function should be monitored.

In patients with urolithiasis, the daily dose of ascorbic acid should not exceed 1 g. High doses of the drug should not be prescribed to patients with increased blood coagulation.

Since ascorbic acid has a mild stimulating effect, it is not recommended to take the drug at the end of the day.

Due to the presence of ascorbic acid in the drug formulation, it may alter the results of several laboratory tests (see section "Interaction with other medicinal products and other types of interactions").

The drug contains sugar, which should be taken into account in patients with diabetes mellitus.

Use during pregnancy or breastfeeding.

During pregnancy, the drug may be used only as prescribed by a physician. The drug is contraindicated in the first trimester of pregnancy. In the second and third trimesters of pregnancy or during breastfeeding, the drug should be prescribed considering the benefit/risks ratio for the woman and the fetus/child, provided that recommended doses and treatment duration are strictly followed.

According to available clinical data on the use of rutin and vitamin C as individual medicinal products during pregnancy, no significant risks to the fetus have been identified. However, adequate and well-controlled clinical studies on the safety of combined preparations containing vitamin C and rutin in pregnant women have not been conducted.

There are no reports of embryotoxicity of rutin or its passage into breast milk.

Vitamin C is excreted in breast milk; however, even doses 10 times higher than the recommended daily dose did not lead to a significant increase in its concentration in breast milk.

Ability to affect reaction rate when driving vehicles or operating machinery.

There is no data on the effect of Ascorutin on the ability to drive vehicles or operate machinery.

Dosage and Administration.

The drug should be administered orally after meals. Tablets should be swallowed whole with a small amount of water.

For therapeutic purposes, the recommended dose is 1 tablet 2–3 times daily for adults and 1 tablet 2 times daily for children aged 3 years and older. As a prophylactic agent, the recommended dose is 1 tablet 2 times daily for adults and 1 tablet once daily for children aged 3 years and older.

The duration of treatment is 3–4 weeks, depending on the nature of the disease and treatment efficacy.

Children.

The drug is indicated for children aged 3 years and older.

Overdose.

Symptoms: epigastric pain, nausea, vomiting, diarrhea, itching and skin rashes, increased nervous system excitability, headache, increased arterial pressure, thrombosis. Exacerbation of adverse reactions may occur.

Overdose may lead to altered renal excretion of ascorbic and uric acids during urine acidification, with a risk of precipitation of oxalate stones.

Prolonged use in high doses may result in suppression of the pancreatic islet apparatus function and impaired kidney function.

Ascorbic acid in doses exceeding 3 g/day may cause acidosis or hemolytic anemia in individuals with glucose-6-phosphate dehydrogenase deficiency.

Treatment: gastric lavage, use of sorbents, symptomatic therapy.

Side effects.

Central nervous system: headache, fatigue; with prolonged use at high doses – sleep disturbances, increased excitability of the central nervous system.

Renal and urinary system: acidification of urine, hyperoxaluria in patients at risk when doses exceed 1 g/day; with prolonged use at high doses – damage to the glomerular apparatus of the kidneys, formation of urate and oxalate stones in the urinary tract, renal failure. Doses of ascorbic acid exceeding 600 mg/day have a diuretic effect.

Hematological system: with prolonged use at high doses – thrombocytosis, hyperprothrombinemia, thrombosis, erythrocytopenia, neutrophilic leukocytosis, hemolytic anemia in some individuals with glucose-6-phosphate dehydrogenase deficiency.

Metabolic effects: hypervitaminosis C, impaired tissue trophism; with prolonged use at high doses – suppression of pancreatic islet function (hyperglycemia, glucosuria) and glycogen synthesis, sodium and fluid retention, disturbances in zinc and copper metabolism.

Cardiovascular system: with prolonged use at high doses – myocardial dystrophy, increased arterial pressure, development of microangiopathies.

Gastrointestinal tract: with prolonged use at high doses – irritation of the gastrointestinal mucosa, heartburn, nausea, vomiting, diarrhea.

Immune system: hypersensitivity reactions, including skin hyperemia, skin rashes, eczema, pruritus, angioedema (Quincke's edema), urticaria, anaphylactic shock, respiratory hypersensitivity reactions.

Shelf life.

4 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging.

10 tablets in a blister.

10 tablets in a blister; 2 blisters per pack.

10 tablets in a blister; 5 blisters per pack.

10 tablets in a blister; 10 blisters per pack.

Prescription status.

Over-the-counter.

Manufacturer. JSC « Monfarm ».

Manufacturer's address and place of business.

8, Zavodska St., Avramivka, Uman District, Cherkasy Oblast, 19161, Ukraine.