Ascorutin

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT ASCORUTIN (ASCORUTIN)

Composition:

Active substances: ascorbic acid (vitamin C), rutin;

1 tablet contains ascorbic acid (vitamin C) equivalent to 100% substance
50 mg, rutin trihydrate equivalent to 100% anhydrous substance 50 mg;

Excipients: white sugar, potato starch, corn starch, magnesium stearate, talc.

Pharmaceutical form. Tablets.

Main physicochemical properties: single-layer tablets, round-shaped, light yellow with a greenish tint, flat upper and lower surfaces, edges of surfaces beveled. Speckles on the tablet surface are permissible. Under magnification, the cross-section reveals a relatively homogeneous structure.

Pharmacotherapeutic group. Capillary stabilizing agents. Bioflavonoids. Rutin combinations. ATC code C05CA51.

Pharmacological properties.

Pharmacodynamics.

A combined medicinal product, whose action is determined by the effects of the components included in its composition.

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

Rutoside in combination with ascorbic acid reduces capillary permeability and fragility, strengthens the cell wall, decreases platelet aggregation, exerts anti-inflammatory effects (including by inhibiting hyaluronidase activity), possesses antioxidant properties, and participates in redox processes.

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

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

Pharmacokinetics.

Each vitamin contained in the medicinal product 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 its uptake by tissues begins. During this process, it 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 almost exclusively intracellular and is found 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, especially in the adrenal glands; lower concentrations are found in the brain, kidneys, liver, and in 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%, mainly in the form of oxalate, and partially in free form.

Rutoside, after absorption in the gastrointestinal tract, promotes the transport and deposition of ascorbate. It is excreted unchanged and as metabolites, mainly 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.
• As part of complex therapy for diseases accompanied by increased vascular permeability.
• Prevention of colds and reduction of flu symptoms.
• For immune system enhancement.

Contraindications.

• Hypersensitivity to any component of the drug.
• Increased blood coagulation, thrombophlebitis, predisposition to thrombosis.
• Gout, urolithiasis with urate stone formation, cystinuria, hypokalemia and hypercalcemia, oxaluria.
• Diabetes mellitus.
• Severe kidney diseases.
• Concomitant use with sulfonamides or aminoglycosides.
• Fructose intolerance, glucose-galactose malabsorption syndrome.

Interaction with other medicinal products and other types of interactions.

Acetylsalicylic acid, oral contraceptives: reduced drug absorption.

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 (deferoxamine): increased iron absorption and urinary excretion; increased tissue toxicity of iron, especially 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 in such patients requires caution and careful monitoring of cardiac function. 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 of its bioavailability.

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

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

Calcitonin: increased rate of ascorbic acid absorption.

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

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

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

Ascorbic acid increases 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 use of large doses of ascorbic acid inhibits the disulfiram–alcohol reaction.

High-dose ascorbic acid (over 2 g/day) may affect biochemical test results for creatinine, uric acid, and glucose levels in blood and urine samples, as well as tests for inorganic phosphates, liver enzymes, and bilirubin 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 absorption of ascorbic acid.

Special precautions.

Concomitant use of the medicinal product with alkaline drinks, fresh fruit or vegetable juices reduces the absorption of vitamin C. The 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 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.

With prolonged use 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 administered to patients with increased blood coagulation.

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

Due to the presence of ascorbic acid in the formulation, the drug 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 after consultation with 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 administered 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 separate medicinal products in pregnant women, no significant risks to the fetus have been identified. However, adequate and well-controlled clinical studies on the safety of combined products 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 influence reaction rate when driving or operating machinery.

There are no data on the effect of Ascorutin on the ability to drive a vehicle or operate machinery.

Dosage and Administration

The medicinal product should be taken orally after meals. Tablets should be swallowed whole with a small amount of water.

For therapeutic purposes, the recommended dose is: adults—1 tablet 2–3 times daily; children aged 3 years and older—1 tablet twice daily. As a prophylactic agent, the recommended dosage is: adults—1 tablet twice daily; children aged 3 years and older—1 tablet daily.

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 changes in 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.

Blood 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 disturbances: hypervitaminosis C, impaired tissue trophism; with prolonged use at high doses – suppression of the pancreatic islet apparatus 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, gastric spasms, nausea, vomiting, diarrhea.

Immune system: hypersensitivity reactions, including skin hyperemia, skin rashes, eczema, pruritus, angioedema, 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; 5 blisters in a carton.

10 tablets in a blister; 80 blisters in a cardboard box.

50 tablets in containers; 1 container in a carton.

Dispensing category.

Over-the-counter.

Manufacturer.

JSC "Tekhnolog".

Manufacturer's address and location of business activity.

8 Staroprizhna St., Uman, Cherkasy region, 20300, Ukraine.