Ascorbic acid-darnitsa

INSTRUCTIONS for medical use of the medicinal product ASCORBIC ACID-DARNITSA (ASCORBIC ACID-DARNITSA)

Composition:

Active ingredient: ascorbic acid;

1 ml of solution contains 50 mg of ascorbic acid;

Excipients: sodium hydrocarbonate, sodium metabisulfite (E 223), disodium edetate, water for injections.

Medicinal form. Solution for injection.

Main physicochemical properties: clear colorless or slightly yellowish liquid.

Pharmacotherapeutic group.
Simple ascorbic acid (vitamin C) preparations. ATC code A11G A01.

Pharmacological Properties

Pharmacodynamics.

Ascorbic acid, or vitamin C, belongs to the group of water-soluble vitamins. It participates in redox reactions and numerous metabolic processes, including regulation of carbohydrate metabolism, metabolism of aromatic amino acids and thyroxine, synthesis of catecholamines, steroid hormones, and insulin. It is an essential component in blood coagulation, collagen and procollagen synthesis, and regeneration of connective and bone tissues. It regulates capillary permeability (by inhibiting hyaluronidase) and participates in iron absorption and hemoglobin synthesis.

With the participation of ascorbic acid, inactivation of free radicals occurs; therefore, ascorbic acid prevents cell membrane damage, particularly of lymphocytes, caused by lipid peroxidation. This action leads to a range of immunomodulatory effects, including enhanced chemotaxis, synthesis and release of interferon, and improved lymphocyte migration.

It enhances both non-specific and immune resistance of the body.

Ascorbic acid is not synthesized in the human body. Insufficient intake with food leads to the development of hypovitaminosis or avitaminosis.

Pharmacokinetics.

Protein binding in plasma – 25%. Normal plasma concentration of ascorbic acid is approximately 10–20 μg/mL, with total body stores of about 1.5 g. Time to reach maximum plasma concentration after intramuscular administration (Tmax) is 15–20 minutes. Ascorbic acid readily penetrates leukocytes and platelets, and then distributes into all tissues; it accumulates in the posterior pituitary, adrenal cortex, ocular epithelium, intermediate cells of the seminal glands, ovaries, liver, spleen, pancreas, lungs, kidneys, intestinal wall, heart, muscles, and thyroid gland. It crosses the placental barrier. The concentration of ascorbic acid in leukocytes and platelets is higher than in erythrocytes and blood plasma. In deficiency states, the concentration in leukocytes decreases later and more slowly, thus being considered a better indicator of deficiency than plasma concentration. Metabolism occurs predominantly in the liver. Excretion is via the kidneys, intestine, and sweat; it passes into breast milk in the form of unchanged ascorbate and metabolites. At high doses, when plasma concentration exceeds 1.4 mg/dL, excretion is markedly increased, and elevated excretion persists even after discontinuation of intake. Smoking and alcohol consumption accelerate the degradation of ascorbic acid (conversion into inactive metabolites), sharply reducing its body stores.

Clinical characteristics.

Indications.

Vitamin C deficiency, scurvy, hemorrhages (uterine, pulmonary, nasal, hepatic), hemorrhagic diatheses, bleeding as a symptom of radiation sickness, intoxications and infectious diseases, nephropathy in pregnancy, Addisonian crisis, overdose of anticoagulants, bone fractures and sluggish granulating wounds, various dystrophies, pregnancy and lactation.

Contraindications.

Hypersensitivity to components of the drug, diabetes mellitus, increased blood coagulation, predisposition to thrombosis, thrombophlebitis, urolithiasis (including hyperoxaluria) when administered in doses exceeding 1 g, severe renal insufficiency, progressive malignant diseases, hemochromatosis, thalassemia, polycythemia, leukemia, sideroblastic anemia, glucose-6-phosphate dehydrogenase deficiency, sickle cell anemia.

Interaction with other medicinal products and other types of interactions.

When used concomitantly with short-acting salicylates, sulfonamides, the risk of urinary stone formation increases.

When used concomitantly, ascorbic acid increases blood concentrations of salicylates, ethinylestradiol, benzylpenicillin, and tetracyclines.

When used concomitantly with ascorbic acid, the effectiveness of coumarin derivatives and heparin, antibiotics is reduced.

High doses of ascorbic acid may lower urine pH, thereby decreasing tubular reabsorption of concurrently administered amphetamines and tricyclic antidepressants.

When used concomitantly, ascorbic acid reduces the effectiveness of oral contraceptives.

Tetracyclines and acetylsalicylic acid enhance the urinary excretion of ascorbic acid.

When used concomitantly with barbiturates, pyrimethamine, the urinary excretion of ascorbic acid increases.

Increases detoxification and total clearance of ethanol.

Increases excretion of drugs with alkaline reaction (including alkaloids).

In high doses, increases renal excretion of mexiletine.

Increases iron excretion in patients taking deferoxamine.

Concomitant administration of ascorbic acid and deferoxamine increases iron tissue toxicity, especially in myocardial tissue, which may lead to circulatory decompensation. Vitamin C may be taken only 2 hours after deferoxamine injection.

Reduces chronotropic effect of isoprenaline and therapeutic effect of phenothiazine derivatives.

When high doses of ascorbic acid are used concomitantly with alcohol consumption, disulfiram-like reactions may develop.

Special precautions for use.

Due to the stimulating effect of ascorbic acid on the synthesis of corticosteroid hormones, kidney function and arterial pressure should be monitored.

With prolonged use of high doses, suppression of the pancreatic islet apparatus function is possible; therefore, it should be regularly monitored during treatment.

Patients with increased iron levels in the body should use ascorbic acid in minimal doses.

Administration of ascorbic acid to patients with rapidly proliferating and intensively metastasizing tumors may intensify the process.

For patients undergoing chemotherapy, the medicinal product should be administered no earlier than 1–3 days (depending on the half-life of the antineoplastic agent) after chemotherapy, due to lack of clinical data on possible interactions.

High-dose ascorbic acid may affect the results of certain laboratory tests: false-positive urine glucose tests, false-negative fecal occult blood tests, and decreased serum lactate dehydrogenase and aminotransferase levels.

High-dose therapy should not be administered to patients prone to recurrent urolithiasis. In patients with renal insufficiency, adequate fluid intake (1.5–2 liters per day) should be ensured to reduce the risk of crystalluria.

Patients on a low-sodium diet should not be prescribed high doses of this medicinal product.

This medicinal product contains sodium metabisulfite (E 223), which may rarely cause hypersensitivity reactions and bronchospasm.

Use during pregnancy or breastfeeding.

Vitamin C deficiency in the diet of pregnant women may be hazardous to the fetus; however, its use in high doses may adversely affect fetal development and may also increase the risk of pregnancy termination. Therefore, ascorbic acid should be prescribed only when the expected benefit to the mother outweighs the potential risk to the fetus.

Ascorbic acid crosses the placental barrier.

The minimal daily requirement for ascorbic acid during the II–III trimesters of pregnancy is approximately 60 mg. It should be noted that the fetus may adapt to high doses of ascorbic acid taken by the pregnant woman, and subsequently, the newborn may develop scurvy as a withdrawal syndrome. (Ascorbic acid should not be taken in elevated doses during pregnancy, except when the expected benefit to the mother exceeds the potential risk to the fetus.)

The minimal daily requirement during breastfeeding is 80 mg. Ascorbic acid passes into breast milk; therefore, vitamin C should be taken during breastfeeding only under medical supervision. There is a theoretical risk to the infant when the mother takes high doses of ascorbic acid. (During breastfeeding, exceeding the daily requirement of ascorbic acid is not recommended.) If higher doses are necessary, breastfeeding should be discontinued.

A maternal diet containing adequate amounts of ascorbic acid is sufficient to prevent vitamin C deficiency in the infant.

Ability to affect the speed of reaction while driving or operating machinery.

The effect of the medicinal product at recommended doses on reaction speed while driving or operating machinery is unlikely.

Administration and Dosage.

The medicinal product "Ascorbic Acid-Darnitsya" should be administered intramuscularly or intravenously, either as a bolus or by infusion.

For intravenous bolus administration, inject over 1–3 minutes. For intravenous infusion, dissolve the single dose in 50–100 mL of 0.9% sodium chloride solution and administer by slow intravenous infusion at a rate of 30–40 drops per minute. For intramuscular administration, inject deeply into the muscle. Dosages should be individually determined, taking into account the nature and severity of the disease.

Adults and children aged 12 years and older: 50–150 mg daily (1–3 mL of 5% solution). In cases of poisoning, the daily dose may be increased up to 500 mg. Maximum single dose – 200 mg; maximum daily dose – 1 g.

Children under 12 years of age: administer intravenously at a daily dose of 5–7 mg/kg body weight as a 5% solution (0.5–2 mL). Typical daily doses for children are:

under 6 months of age – 30 mg;

6 to 12 months of age – 35 mg;

1 to 3 years of age – 40 mg;

4 to 10 years of age – 45 mg;

11 to 12 years of age – 50 mg.

Maximum daily dose for children under 12 years of age – 100 mg.

Special patient groups. For patients with recurrent kidney stone formation, the daily dose of ascorbic acid should not exceed 100–200 mg.

Children.

The medicinal product can be used in children.

Overdose.

Symptoms. Large doses of ascorbic acid may cause gastrointestinal disturbances, including diarrhea, and may lead to hyperoxaluria and formation of oxalate calculi. After single excessive doses, nausea, vomiting, bloating, abdominal pain, itching, skin rashes, and increased excitability may occur. Intravenous administration of high doses may pose a risk of pregnancy termination. Doses exceeding 600 mg daily may produce a diuretic effect.

Treatment. Discontinue the medicinal product, perform gastric lavage, administer alkaline drinks, activated charcoal, or other adsorbents, and provide symptomatic therapy.

Adverse Reactions

Ascorbic acid is generally well tolerated; however, adverse reactions may occur.

Gastrointestinal tract: stomach cramps, nausea, diarrhea.

Renal and urinary system: hyperoxaluria; with prolonged use in high doses – glomerular apparatus kidney damage, formation of oxalate kidney stones.

Metabolism and metabolic processes: hypervitaminosis C; with prolonged use in high doses – suppression of pancreatic islet apparatus function (hyperglycemia, glucosuria) and glycogen synthesis, sodium and fluid retention, disturbances in zinc and copper metabolism.

Nervous system: headache, increased fatigue; with prolonged use in high doses – sleep disturbances, increased central nervous system excitability.

Cardiovascular system: decreased capillary permeability, impaired tissue trophism; with prolonged use in high doses – myocardial dystrophy, increased arterial pressure, development of microangiopathies.

Blood and lymphatic system: with prolonged use in high doses – thrombocytosis, hyperprothrombinemia, thrombosis, erythrocytopenia, neutrophilic leukocytosis.

Immune system: hypersensitivity reactions, including bronchospasm, anaphylactic shock.

Skin and subcutaneous tissue: very rarely – skin rashes, skin hyperemia, pruritus, urticaria, increased body temperature.

General disorders and administration site reactions: local site reactions; with intravenous administration – sensation of warmth, chills; with intravenous administration in high doses – risk of pregnancy termination.

Reporting of suspected adverse reactions.

Reporting of suspected adverse reactions after marketing authorization is an important procedure. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are required to report any suspected adverse reactions through the national reporting system.

Shelf life. 2 years.

Storage conditions.

Store in the original packaging at a temperature between 2 °C and 8 °C.

Keep out of reach of children.

Incompatibilities.

The medicinal product is incompatible with iron salts, oxidizing agents, heavy metal salts, especially copper. There are reports that ascorbic acid injections are incompatible with aminophylline, bleomycin sulfate, erythromycin, sodium nafcillin, sodium nitrofurantoin, conjugated estrogens, sodium bicarbonate, sulfafurazole diethanolamine. Occasionally, depending on pH or concentration, incompatibility with chloramphenicol may occur.

Packaging.

2 ml in a vial; 5 vials in a blister pack; 2 blister packs in a carton.

Prescription status. Prescription only.

Manufacturer. JSC "Pharmaceutical Company "Darnytsia".

Manufacturer's address and location of operations.

13, Boryspylska Street, Kyiv, 02093, Ukraine.