Ascorutin

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT AСCORUTIN (ASCORUTIN)

Composition:

Active substances: Each tablet contains ascorbic acid (vitamin С) 50 mg, rutin (rutinoside trihydrate) 50 mg;

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

Pharmaceutical form. Tablets.

Main physico-chemical properties: round flat tablets with bevelled edges and a score line, light yellow with a greenish tint, with speckles.

Pharmacotherapeutic group. Capillary-stabilizing agents. Bioflavonoids.

ATC code С05С А51.

Pharmacological properties.

Pharmacodynamics.

A combined 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 via ascorbic acid.

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

In addition, rutin exhibits the following effects: reduction of exudation of the liquid portion 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, trophic disorders, and decreases or eliminates paresthesias 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 noticeably 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 within the cell. Ascorbic acid in tissues is located almost exclusively intracellularly 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, particularly in the adrenal glands; lower concentrations are found 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%—mainly 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 or as metabolites, predominantly 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 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 increase 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 impaired cardiac function (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). Such combination in these patient groups 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 efficacy 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 administered (this interaction has no clinical consequences when therapeutic doses are used).

Calcitonin: increased absorption rate of ascorbic acid.

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

Aluminum-containing antacids: it should be noted that ascorbic acid promotes intestinal absorption of aluminum, possibly 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 during prolonged use (over 4 weeks), as it may enhance their effects.

Ascorbic acid enhances the 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 absorption of ascorbic acid.

Special precautions for use.

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

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

During 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. Large doses of the medicinal product 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 late in the day.

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

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

Use during pregnancy or breastfeeding.

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

Based on available clinical data on the use of rutin and vitamin C as individual 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 medicinal products containing vitamin C and rutin in pregnant women have not been conducted. There are no reports of embryotoxicity of rutin or its penetration into breast milk. Vitamin C is excreted in breast milk; however, even doses 10 times higher than the recommended daily dose do not lead to a significant increase in its concentration in breast milk.

Ability to influence reaction rate while 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 administered orally after meals. Tablets should be swallowed whole with a small amount of water.

For therapeutic purposes: adults should take 1 tablet 2–3 times daily; children aged 3 years and older should take 1 tablet twice daily.

As a prophylactic agent: the recommended dosage is 1 tablet twice daily for adults and 1 tablet daily for children aged 3 years and older.

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

Children

The medicinal product 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, elevated arterial pressure, thrombosis. Exacerbation of adverse reactions may occur.

Overdose may lead to changes in renal excretion of ascorbic acid and uric acid during urine acidification, with a risk of precipitation of oxalate calculi.

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

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

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

Adverse reactions.

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

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

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

Gastrointestinal tract: prolonged use at high doses – gastrointestinal mucosa irritation, heartburn, stomach spasms, 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. 5 years.

Storage conditions.

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

Keep out of reach of children.

Packaging. 10 tablets in a blister; 5 blisters in a carton.

Availability. Over-the-counter.

Manufacturer. JSC "KYIV VITAMIN PLANT".

Manufacturer's address and location of business activity.

38 Kopilivska Street, Kyiv, 04073, Ukraine.

Web-site: www.vitamin.com.ua