Ascorbic acid-darnitsa

INSTRUCTION for medical use of the medicinal product Ascorbic Acid-Darnitsa (Ascorbicacid-Darnitsa)

Composition:

active substance: ascorbic acid;

1 ml of solution contains ascorbic acid 100 mg;

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

Pharmaceutical form. Solution for injection.

Main physicochemical properties: clear colorless or slightly colored liquid.

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 promotes optimal tissue metabolism. It actively participates in redox reactions, forming a proton-hydrogen transfer system together with dehydroascorbic acid, exhibits antioxidant properties, thereby ensuring the stability of cell membranes. It is 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. It 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 significantly decreases, confirming the involvement of ascorbic acid in adaptation responses. It can exert an anti-anemic effect by influencing iron metabolism. It reduces trivalent iron to divalent iron, which is transported in the bloodstream.

Pharmacokinetics.

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

Alcohol consumption and smoking accelerate the destruction of ascorbic acid (conversion into inactive metabolites), sharply reducing its reserves in the body.

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; nephropathy in pregnancy; Addisonian crisis; anticoagulant overdose; bone fractures and slowly healing wounds; various dystrophies; increased cerebral tension and heavy physical exertion.

Contraindications.

Hypersensitivity to the active substance or to other components of the drug; 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.

With benzylpenicillin, tetracycline, salicylates – increased concentration of these drugs in blood;

with ethinylestradiol (ascorbic acid at a dose of 1 g/day) – increased concentration of ethinylestradiol (including that contained in oral contraceptives) in blood;

with oral contraceptives – decreased concentration of these drugs in blood;

with tetracycline and acetylsalicylic acid – enhanced urinary excretion of ascorbic acid;

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

with deferoxamine – increased iron excretion;

with heparin, indirect anticoagulants, antipsychotic agents, phenothiazine derivatives – reduced efficacy of these drugs;

with isoprenaline – reduced chronotropic effect of the drug;

with short-acting sulfonamides – increased risk of crystalluria;

with drugs having an acidic reaction – slowed renal excretion of these drugs;

with drugs having an alkaline reaction, mexiletine, amphetamine, tricyclic antidepressants – accelerated renal excretion of these drugs;

with acetylsalicylic acid – increased urinary excretion of ascorbic acid and decreased excretion of acetylsalicylic acid;

with barbiturates, primidone – increased urinary excretion of ascorbic acid;

with quinolone derivatives, calcium chloride, salicylates, glucocorticosteroids – prolonged use may deplete ascorbic acid stores;

with ethanol – increased overall ethanol clearance, which in turn reduces ascorbic acid concentration in the body;

with disulfiram – prolonged use or use in high doses may interfere with the disulfiram-ethanol interaction.

Ascorbic acid increases blood concentrations of salicylates (increases the risk of crystalluria).

It participates in the metabolism of phenylalanine, tyrosine, folic acid, norepinephrine, and histamine.

Concomitant administration of ascorbic acid and deferoxamine increases tissue iron toxicity, particularly in the myocardium, which may lead to circulatory decompensation.

Special precautions for use.

Ascorbic acid, being a reducing agent, may distort the results of various laboratory tests, including false-positive glucose tests in urine and false-negative occult blood tests in feces, as well as reduced serum levels of lactate dehydrogenase and aminotransferases.

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

With prolonged use of high doses, suppression of the endocrine apparatus of the pancreas may occur; therefore, during long-term treatment, pancreatic function should be regularly monitored.

High-dose therapy should not be administered 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.

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

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 the lack of clinical data on possible interactions.

Use during pregnancy or breastfeeding.

The minimum 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 scurvy as a withdrawal reaction may develop in the newborn. Therefore, the drug should not be administered in doses exceeding the recommended daily intake during pregnancy, except when the potential benefit to the mother outweighs the possible risk to the fetus.

The minimum daily requirement for ascorbic acid during breastfeeding is 80 mg. A maternal diet containing an adequate amount of ascorbic acid is sufficient to prevent deficiency in the infant. Ascorbic acid is excreted into 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 for ascorbic acid is not recommended). If higher doses of the drug are necessary, breastfeeding should be discontinued.

Ability to affect reaction speed when driving or operating machinery.

Does not affect reaction speed at recommended doses.

Method of Administration and Dosage.

The medicinal product is administered intravenously by bolus or infusion, and intramuscularly.

Intravenous bolus injection should be given over 1–3 minutes. For intravenous infusion, a single dose of the medicinal product should be dissolved in 50–100 mL of 0.9% sodium chloride solution and administered by slow intravenous infusion at a rate of 30–40 drops per minute.

Intramuscular administration should be performed as a deep intramuscular injection.

Dosage is 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 (0.5–1.5 mL of a 10% solution) per day. The maximum single dose is 200 mg (2 mL of a 10% solution), and the maximum daily dose is 1 g (10 mL of a 10% solution). In acute poisonings, the maximum daily dose may be up to 500 mg (50 mL of a 10% solution).

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: 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.

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 end-stage 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.

The medicinal product can be used in pediatric practice.

Overdose.

Acute poisoning with ascorbic acid has not been reported. High 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. Intravenous administration of high doses may pose a risk of pregnancy termination. Acute overdose may result in nausea, vomiting, bloating, abdominal pain, itching, skin rashes, and increased excitability.

Treatment: discontinue the medicinal product, symptomatic therapy.

Side effects.

Gastrointestinal disorders: nausea, diarrhea, stomach cramps.

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

Metabolic and nutritional 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 disorders: headache, dizziness, fatigue; with prolonged use in high doses – sleep disturbances, increased excitability of the central nervous system.

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

Blood and lymphatic system disorders: with prolonged use in high doses – thrombocytosis, hyperprothrombinemia, thrombosis, erythrocytopenia, neutrophilic leukocytosis; in patients with glucose-6-phosphate dehydrogenase deficiency of blood cells may cause hemolysis of erythrocytes.

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

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

Pregnancy: with intravenous administration in high doses – risk of pregnancy termination.

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. Do not freeze.

Keep out of reach of children.

Incompatibility.

Ascorbic acid has a high redox potential; therefore, it may alter the chemical composition of other medicinal products. When considering the possibility of concomitant use with other medicinal products, their compatibility must be confirmed.

Packaging.

2 ml in an ampoule; 5 ampoules in a blister pack; 2 blister packs in a carton.

Prescription status. Prescription only.

Manufacturer. JSC "Pharmaceutical Company "Darnytsia".

Manufacturer's name and address of manufacturing site.

13 Borispilska Street, Kyiv, 02093, Ukraine.