Ascorbic acid

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT ASCORBIC ACID (ASCORBIC ACID)

Composition:

Active substance: ascorbic acid;

1 ml of solution contains ascorbic acid 50 mg or 100 mg;

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

Pharmaceutical form. Injection solution.

Main physico-chemical properties: clear, colorless or slightly yellowish solution, practically free from particles.

Pharmacotherapeutic 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 supports optimal tissue metabolism. It actively participates in redox reactions, forming with dehydroascorbic acid a hydrogen proton transfer system, and exhibits antioxidant properties, thereby ensuring the stability of cellular membranes. Ascorbic acid is also involved in the synthesis of the ground substance of vascular wall connective tissue, 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 is involved 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. Ascorbic acid exerts an anti-anaemic effect through its influence on iron metabolism. It reduces trivalent iron to divalent iron, which is then transported in the bloodstream.

Pharmacokinetics. After parenteral administration, ascorbic acid readily penetrates leukocytes and platelets, and subsequently 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 breakdown of ascorbic acid (conversion into inactive metabolites), sharply reducing its body stores.

Clinical Characteristics

Indications. Hypovitaminosis C; scurvy; hemorrhages (uterine, pulmonary, nasal, hepatic); hemorrhagic diatheses; hemorrhages as a symptom of radiation sickness; various intoxications and infectious diseases; Addisonian crisis; anticoagulant overdose; bone fractures and poorly healing wounds; various dystrophies; increased cerebral tension and heavy physical exertion.

Contraindications. Hypersensitivity to ascorbic acid or to any of the excipients. Diabetes mellitus, increased blood coagulability, 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 interaction

Ascorbic acid increases blood concentrations of salicylates (increasing the risk of crystalluria), ethinylestradiol, benzylpenicillin, and tetracyclines, while decreasing blood levels of oral contraceptives. It enhances the excretion of drugs with alkaline properties (including alkaloids). In high doses, it increases renal excretion of mexiletine.

Tetracyclines and acetylsalicylic acid enhance urinary excretion of ascorbic acid.

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

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

Ascorbic acid 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 and primidone increases urinary excretion of ascorbic acid.

Simultaneous administration of ascorbic acid and deferoxamine increases iron-induced tissue toxicity, especially in cardiac muscle, potentially leading to circulatory decompensation. Vitamin C may be administered only 2 hours after deferoxamine injection.

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, adrenal function and arterial pressure should be monitored.

Prolonged administration of high doses may suppress the function of the islet apparatus of the pancreas; therefore, during long-term therapy, regular monitoring of pancreatic function is necessary.

High-dose therapy should not be prescribed to patients with a predisposition 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.

As a reducing agent, ascorbic acid may interfere with various laboratory tests, causing false-positive results in urine glucose tests and false-negative results in fecal occult blood tests. It may also reduce serum levels of lactate dehydrogenase and aminotransferases in laboratory assays.

Ascorbic acid should be administered in minimal doses to patients with increased iron levels in the body.

Administration of ascorbic acid to patients with rapidly proliferating and intensively metastasizing tumors may exacerbate disease progression. For 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 the lack of clinical data on potential interactions.

Important information about excipients. This medicinal product contains 0.3 mmol (7 mg/mL) of sodium (50 mg/mL dosage) or 0.6 mmol (13.8 mg/mL) of sodium (100 mg/mL dosage). Caution is required when administering to patients on a low-sodium diet. High doses of the drug should not be prescribed to such patients.

Use during pregnancy or breastfeeding

Vitamin C deficiency in the diet of pregnant women may be hazardous to the fetus; however, high-dose vitamin C administration 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 minimal daily requirement for ascorbic acid during the II–III 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, the drug should not be administered in increased doses during pregnancy, except when the potential benefit to the mother outweighs the possible risk to the fetus.

The minimal daily requirement for ascorbic acid during lactation is 80 mg. A mother's 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, the woman should discontinue breastfeeding.

Ability to influence reaction speed when driving or operating machinery. The medicinal product, at recommended doses, does not affect reaction speed.

Administration and Dosage

The medicinal product should be administered intravenously as a bolus or infusion, and intramuscularly.

For intravenous bolus administration, inject over 1–3 minutes. For intravenous infusion, dissolve a single dose of the medicinal product in 50–100 mL of 0.9% sodium chloride solution and administer as a slow intravenous infusion at a rate of 30–40 drops per minute.

For intramuscular administration, inject deeply into the muscle.

Dosages are determined individually, depending on the nature and severity of the disease.

Adults and children aged 12 years and older: The medicinal product is administered at a dose of 50–150 mg per day. The maximum single dose is 200 mg; the maximum daily dose is 1 g. In acute poisoning, the maximum daily dose is up to 500 mg.

Children under 12 years of age: The medicinal product is administered intravenously at a daily dose of 5–7 mg/kg body weight as a 5% solution (0.5–2 mL). Usual daily doses for children are: for children under 6 months of age — 30 mg; 6–12 months — 35 mg; 1–3 years — 40 mg; 4–10 years — 45 mg; 11–12 years — 50 mg. The maximum daily dose is 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 undergoing 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 "Administration and Dosage".

Overdose

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

In case of a single intake of excessive doses of the medicinal product, nausea, vomiting, bloating, abdominal pain, itching, skin rashes, and increased excitability may occur.

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

Treatment: Discontinue the drug; symptomatic therapy.

Adverse reactions

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

Gastrointestinal tract: nausea, diarrhea, stomach cramps.

Renal and urinary system: hyperoxaluria; with prolonged use in high doses — damage to the glomerular apparatus of the kidneys, formation of calcium oxalate kidney stones.

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

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

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, thrombus formation, erythrocytopenia, neutrophilic leukocytosis; in patients with glucose-6-phosphate dehydrogenase deficiency, the drug may cause hemolysis of erythrocytes.

Immune system: hypersensitivity reactions, including skin rash, skin hyperemia, pruritus, urticaria, anaphylactic shock.

General disorders and administration site reactions: hyperthermic syndrome; with intravenous administration, sensation of warmth and local reactions at the injection site may occur.

Pregnancy: with high-dose intravenous administration — risk of pregnancy termination.

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

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after drug registration is of great importance. It enables ongoing monitoring of the benefit-risk balance of the drug. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of drug efficacy via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life. 2 years.

Do not use the medicinal product after the expiry date stated on the packaging.

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

Keep out of reach of children.

Incompatibility. Due to its high redox potential, ascorbic acid may alter the chemical composition of other drugs. Therefore, when considering concomitant use with other medicinal products, compatibility must be confirmed.

Packaging. 2 ml in an ampoule; 5 ampoules in a blister pack, 1 or 2 blisters per cardboard box.

2 ml in an ampoule; 5 or 10 ampoules in a cardboard box with cardboard dividers.

Prescription status. Prescription only.

Manufacturer. JSC "Lubnifarm".

Manufacturer's address and location of operations. 16, Barvinkova St., Lubny, Poltava Oblast, 37500, Ukraine.