Ascorbic acid

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT ASCORBIC ACID

Composition:

Active substance: ascorbic acid (vit C);

1 ml of solution contains 50 mg of ascorbic acid;

Excipients: sodium hydrogencarbonate, anhydrous sodium sulfite (E 221), water for injections.

Medicinal form. Solution for injection.

Main physicochemical properties: clear colorless or slightly yellowish liquid.

Pharmaco-therapeutic group. Simple ascorbic acid preparations. Ascorbic acid (vitamin C). ATC code A11G A01.

Pharmacological properties.

Pharmacodynamics.

Ascorbic acid (vitamin C) is a water-soluble vitamin that promotes optimal tissue metabolism. It actively participates in redox reactions, forming a hydrogen proton transfer system together with dehydroascorbic acid, exhibits antioxidant properties, thereby ensuring the stability of cellular membranes. It participates in the synthesis of the ground substance of connective tissue in the vascular wall, thus preventing the development of hemorrhagic diathesis. It is not synthesized in the human body. With insufficient intake of ascorbic acid from food, bleeding from the gums and mucous membranes develops. Ascorbic acid participates in glucose metabolism, cholesterol catabolism, and synthesis of steroid hormones. During stress reactions, the content of ascorbic acid in the body and particularly in adrenal gland tissue decreases significantly, confirming the involvement of ascorbic acid in adaptation responses. It is capable of exerting an anti-anemic effect by influencing iron metabolism. It reduces trivalent iron to divalent iron, which is then transported by the bloodstream.

Pharmacokinetics.

After parenteral administration, ascorbic acid readily penetrates leukocytes and platelets, and then distributes into all tissues. It accumulates mainly in organs with high metabolic activity, particularly in adrenal gland tissue. In tissues, it exists both in free form and as bound compounds. It is excreted from the body in urine, both unchanged and as metabolites.

Alcohol consumption and smoking 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, various intoxications and infectious diseases, Addisonian crisis, anticoagulant overdose, bone fractures and slowly healing wounds, various dystrophies, increased cerebral strain, and heavy physical exertion.

Contraindications. Hypersensitivity to ascorbic acid or any of the excipients. Diabetes mellitus, increased blood coagulation, predisposition to thrombosis, thrombophlebitis, urolithiasis (including hyperoxaluria), renal insufficiency, progressive malignant diseases, hemochromatosis, thalassemia, polycythemia, leukemia, sideroblastic anemia, sickle cell anemia, glucose-6-phosphate dehydrogenase deficiency.

Interaction with other medicinal products and other forms of interactions. Ascorbic acid increases blood concentrations of salicylates (increasing the risk of crystalluria), ethinylestradiol, benzylpenicillin, and tetracyclines, while reducing blood levels of oral contraceptives. It increases the excretion of drugs with alkaline reaction (including alkaloids). In high doses, it increases renal excretion of mexiletine.

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

Concomitant use with salicylates and short-acting sulfonamides increases the risk of urinary stone formation.

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

It reduces the anticoagulant effect of coumarin derivatives and heparin, as well as the efficacy of antibiotics.

It enhances detoxification and total clearance of ethanol.

It reduces the chronotropic effect of isoprenaline and the therapeutic effect of phenothiazine derivatives.

Concomitant use with barbiturates or primidone increases urinary excretion of ascorbic acid.

Simultaneous administration of ascorbic acid and deferoxamine increases tissue toxicity of iron, particularly in the myocardium, potentially leading to circulatory decompensation. Vitamin C may be taken only 2 hours after deferoxamine injection.

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

Special precautions for use.

When used in large doses, monitoring of kidney function, blood pressure (due to stimulation by ascorbic acid of corticosteroid production), and pancreatic function (due to inhibition of the islet apparatus) is required.

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

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

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

This medicinal product contains less than 1 mmol (23 mg) of sodium per dose, i.e., it is practically sodium-free. High doses of the drug should not be prescribed to patients on a low-sodium diet.

Administration of ascorbic acid to patients with rapidly proliferating and intensively metastasizing tumors may exacerbate the course of the disease. In patients undergoing chemotherapy, the drug should be administered no earlier than 1–3 days after chemotherapy (depending on the half-life of the antineoplastic agent), due to lack of clinical data on potential interactions.

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.

The minimum daily requirement of ascorbic acid during the second and third trimesters of pregnancy is approximately 60 mg. Ascorbic acid crosses the placental barrier. It should be noted that the fetus may adapt to high doses of ascorbic acid taken by the pregnant woman, and subsequently, scurvy (ascorbic acid deficiency) may develop in the newborn as a withdrawal reaction. Therefore, high doses of the drug should not be administered during pregnancy, except when the potential benefit to the mother outweighs the possible risk to the fetus.

The minimum daily requirement of ascorbic acid during breastfeeding is 80 mg. A maternal diet containing adequate amounts of ascorbic acid is sufficient to prevent deficiency in the infant. Ascorbic acid is excreted in breast milk. 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 of the drug are required, breastfeeding should be discontinued.

Ability to influence reaction rate while driving or operating machinery. The drug, when used at recommended doses, does not affect the ability to drive or operate machinery.

Method of Administration and Dosage.

Administer intravenously as a bolus or by infusion, and intramuscularly.

For intravenous bolus administration, inject over 1–3 minutes. For intravenous infusion, dissolve a single dose of the drug 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.

Dosage should be determined individually, taking into account the nature and severity of the disease.

Adults and children aged 12 years and older: the usual daily dose is 50–150 mg. 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 – 30 mg; 6–12 months – 35 mg; 1–3 years – 40 mg; 4–10 years – 45 mg; 11–12 years – 50 mg.

Maximum daily dose – 100 mg.

Special patient groups. For patients with recurrent kidney stone formation, the daily dose of ascorbic acid should not exceed 100–200 mg. For patients with severe or terminal renal insufficiency (patients on dialysis), the daily dose of ascorbic acid should not exceed 50–100 mg. For patients with glucose-6-phosphate dehydrogenase deficiency, the daily dose of ascorbic acid should not exceed 100–500 mg.

Children. Dosage for children is described in the section "Method of Administration and Dosage".

Overdose. Large doses of ascorbic acid may cause gastrointestinal disturbances, including diarrhea, and may lead to hyperoxaluria and formation of oxalate calculi. Doses exceeding 600 mg per day may produce a diuretic effect.

After single administration of excessive doses, nausea, vomiting, bloating, abdominal pain, itching, skin rashes, and increased excitability may occur.

When administered intravenously in high doses, there is a risk of pregnancy termination.

Treatment: discontinue the drug and provide symptomatic therapy.

Adverse Reactions. Ascorbic acid is generally well tolerated, but the following adverse effects may occur.

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

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

Gastrointestinal disorders: nausea, diarrhea, stomach cramps.

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

Skin and subcutaneous tissue disorders: very rarely – skin rashes, skin hyperemia, pruritus, urticaria.

Metabolism and nutritional disorders: 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.

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

General disorders: with intravenous administration, possible sensation of warmth, increased body temperature, local reactions at the injection site.

Pregnancy: when administered intravenously in high doses – risk of pregnancy termination.

Immune system disorders: very rarely – hypersensitivity reactions, including anaphylactic shock.

The presence of sodium sulfite (E 221) as an excipient in the drug formulation may rarely cause hypersensitivity reactions and bronchospasm.

Shelf life. 2 years.

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

Keep out of reach of children.

Incompatibility. Ascorbic acid has a high redox potential and may alter the chemical composition of other drugs. Therefore, compatibility with other medicinal products must be verified before considering concomitant use.

Packaging. 1 mL or 2 mL in ampoules, 10 in a pack; 10, 5×2 in blisters in a pack.

Prescription status. Prescription only.

Manufacturer.

Limited Liability Company "Research Plant "GNCLS".

LIMITED LIABILITY COMPANY "CORPORATION "ZDOROVIYA".

Manufacturer's address and place of business.

8 Vorobiova Street, Kharkiv, Kharkiv Region, Ukraine.

(Limited Liability Company "Research Plant "GNCLS")

22 Shevchenka Street, Kharkiv, Kharkiv Region, 61013, Ukraine.

(LIMITED LIABILITY COMPANY "CORPORATION "ZDOROVIYA")