Instructions for Sorbifer Durules film-coated tablets with modified release, bottle No. 30
Composition
active ingredients: ferrous sulfate, ascorbic acid;
1 tablet contains: 320 mg of anhydrous ferrous sulfate (corresponding to 100 mg of bivalent iron), 60 mg of ascorbic acid;
excipients: povidone, polyethylene powder, carbomers, magnesium stearate;
shell composition: hypromellose, macrogols, titanium dioxide (E 171), iron oxide yellow
(E 172), paraffin.
Dosage form
Modified-release film-coated tablets.
Main physicochemical properties:
Lenticular, slightly biconvex tablets, coated with an ocher-yellow coating, engraved with "Z" on one side, with a characteristic odor.
Pharmacotherapeutic group
Antianemic agents. Iron preparations, various combinations.
ATX code B03A E10.
Pharmacological properties
Pharmacodynamics.
Ferrous sulfate replenishes the iron deficiency in the body. As part of the protoporphyrin prosthetic group of hemoglobin, iron (II) plays an important role in the binding and transport of oxygen and carbon dioxide.
Within the protoporphyrin group of cytochrome enzymes, iron plays a key role in electron transport processes. In these processes, electron uptake and release are carried out through the reverse transformation (Fe(II) <–––> Fe(III).
Large amounts of iron can also be found in the myoglobin molecules of muscles.
Vitamin C increases the absorption of iron in the intestinal tract and participates in redox processes.
Pharmacokinetics.
Iron is absorbed from the duodenum and proximal jejunum. The absorption rate of heme-bound iron is approximately 20%, while
heme-bound iron – approximately 10%. For better absorption, iron must be in the form of Fe(II). Hydrochloric acid in the stomach and vitamin C promote iron absorption by reducing Fe(III) to Fe(II).
Iron (Fe (II) – ferro), entering the epithelial cells of the intestine, is oxidized to iron Fe (III) – ferri and binds to apoferritin. One part of apoferritin enters the bloodstream, the other remains temporarily in the epithelial cells of the intestine in the form of ferritin, which either enters the bloodstream after 1–2 days, or is excreted with feces together with the exfoliated epithelium. Almost 1/3r of the iron entering the bloodstream binds to apotransferrin, due to which the molecule is converted to transferrin. Iron is transported to target organs in the form of transferrin, which, after binding to extracellular receptors, enters the cytoplasm by endocytosis. Here, iron is separated from transferrin and binds to apoferritin again. Under the influence of apoferritin, iron is oxidized and the oxidized form [Fe (III)] is reduced to flavoprotein.
The method of manufacturing the coated tablets ensures a continuous release of iron (II) ions. During their passage through the gastrointestinal tract, iron (II) ions are continuously released from the porous matrix for 6 hours. The slow release of the active substance prevents dangerously high iron concentrations, which can avoid irritation of the intestinal epithelium.
Indication
Prevention and treatment of iron deficiency anemia.
Contraindication
Hypersensitivity to any component of the drug; esophageal stenosis and/or other obstructive diseases of the gastrointestinal tract; peptic ulcer, ulcerative colitis in the acute phase; intestinal diverticulum; intestinal obstruction; conditions accompanied by increased iron accumulation (hemochromatosis, hemosiderosis); repeated blood transfusion; other types of anemia not caused by iron deficiency (for example, aplastic and hemolytic anemia, chronic hemolysis, anemia caused by vitamin B12 deficiency); disorders of the mechanisms of iron incorporation into hemoglobin (anemia caused by lead poisoning); sideroachrestic anemia; thrombosis, tendency to thrombosis, thrombophlebitis, severe kidney disease; simultaneous use of parenteral forms of iron; disorders of iron excretion mechanisms (thalassemia); diabetes mellitus; urolithiasis (when using ascorbic acid more than 1 g per day); fructose intolerance.
Interaction with other medicinal products and other types of interactions
Interactions related to iron.
Fluoroquinolones: the simultaneous use of Sorbifer Durules should be avoided:
with ciprofloxacin, as the absorption of ciprofloxacin is reduced by approximately 50% and the plasma concentration of ciprofloxacin may be below therapeutic levels;
with levofloxacin, as the absorption of levofloxacin is reduced;
with moxifloxacin, as the bioavailability of moxifloxacin is reduced by approximately 40%, therefore, if it is necessary to use these drugs together, the interval between their administrations should be at least 6 hours.
with norfloxacin, as the absorption of norfloxacin is reduced by approximately 75%;
with ofloxacin, as the absorption of ofloxacin is reduced by approximately 30%;
with gatifloxacin as the absorption of the drug is reduced by 30–90%.
Iron preparations and other medications containing iron: iron accumulation in the liver is possible, increasing the likelihood of iron overdose.
Oral forms of iron salts, due to the formation of chelate compounds, inhibit the absorption of many drugs. Therefore, there should be a certain interval between taking iron preparations and the following drugs.
The combined use of Sorbifer Durules and the following drugs requires correction of the doses of these drugs, and the interval between their administrations should be at least 2 hours.
Calcium and magnesium-containing food supplements, aluminum hydroxide, and calcium or magnesium-containing antacids form a complex with iron salts, as a result of which they reduce the absorption of each other;
oral preparations of zinc, calcium, aluminum, magnesium, cholestyramine, pancreatin, proton pump inhibitors, trientine: reduced absorption of iron from the digestive tract;
entacapone, sulfasalazine: iron salts may reduce the bioavailability of these drugs;
Captopril: with concomitant use, the area under the concentration-time curve of captopril decreases (by approximately 37%), possibly due to a chemical reaction in the gastrointestinal tract;
zinc: when used together, the absorption of zinc salts decreases;
Clodronate: in vitro studies have shown that iron-containing drugs form a complex with clodronate. Although in vivo interaction studies have not been conducted, it can be concluded that the simultaneous administration of these drugs reduces the absorption of clodronate;
deferoxamine: combined use of these drugs reduces the absorption of both deferoxamine and iron due to complex formation;
Levodopa: when used with levodopa or carbidopa, ferrous sulfate reduces the bioavailability of a single dose of levodopa by approximately 50% and the bioavailability of a single dose of carbidopa by almost 75%, possibly due to the formation of a chelate complex;
methyldopa: with the combined use of methyldopa and iron salts (ferrous sulfate or ferrous gluconate), the bioavailability of methyldopa is reduced, possibly due to the formation of a chelate complex, which may lead to a decrease in the hypotensive effect;
Penicillinamine: with the combined use of penicillinamine and iron salts, the absorption of both penicillinamine and iron salts is reduced due to the formation of a chelate complex;
Risedronate: In vitro studies have shown that iron-containing drugs form a complex with risedronate. Although in vivo interaction studies have not been conducted, it can be assumed that co-administration of these drugs reduces the absorption of risedronate;
tetracyclines: when used together, the absorption of both iron and tetracyclines decreases, therefore, if simultaneous use is necessary, Sorbifer Durules should be taken at least 3 hours before or 2 hours after taking them;
thyroid hormones: absorption of thyroxine is reduced, which may affect the results of treatment. The interval between taking thyroxine and Sorbifer Durules should be at least 2 hours. Patients should have their thyroid function checked regularly;
Mycophenolate mofetil: Oral iron preparations significantly reduce the absorption of mycophenolate mofetil;
tocopherol: the activity of both drugs decreases;
D-penicillamine: with the combined use of penicillamine and iron salts, the absorption of both penicillamine and iron salts is reduced due to the formation of a chelate complex;
Glucocorticosteroids: possible increased stimulation of erythropoiesis;
ethanol: absorption and risk of toxic complications increase;
Ascorbic acid and citric acid: increases iron absorption.
When Sorbifer Durules is used together with cimetidine, the secretion of hydrochloric acid in the stomach decreases, since cimetidine reduces the absorption of iron. Therefore, the interval between taking these drugs should be at least 2 hours.
Foods: simultaneous consumption of foods high in phytates, phosphates, oxalates and tannins, found in plant products, milk and its derivatives, coffee, tea, eggs, whole grains, bread, may reduce iron absorption. Fish and foods high in ascorbic acid and fruit acids promote iron absorption. Iron supplements should not be taken within 1 hour before or 2 hours after taking these foods.
When taking the drug, a false-positive result of a stool test for occult blood is possible.
Chloramphenicol: Delay in the development of the clinical effect of iron preparations. Chloramphenicol slows down the plasma clearance of iron and its incorporation into erythrocytes, thus inhibiting erythropoiesis.
Bisphosphonates: absorption of the latter may be impaired. The time interval between taking the drugs should be at least 2 hours.
Nonsteroidal anti-inflammatory drugs: possible increased irritating effect of iron on the mucous membrane of the digestive tract.
Dimercaprol: formation of toxic complexes with iron; concomitant use should be avoided.
Allopurinol: increased iron absorption with the risk of hemosiderosis.
Acetohydroxamic acid: decreased activity of both drugs.
Etidronic acid: the activity of etidronic acid is reduced. It should be taken no earlier than 2 hours after taking Sorbifer Durules.
Absorption of ascorbic acid is reduced with simultaneous use of oral contraceptives, consumption of fruit or vegetable juices, alkaline drinks. Ascorbic acid when taken orally increases the absorption of penicillin, tetracycline, iron, reduces the effectiveness of heparin and indirect anticoagulants, increases the risk of crystalluria during treatment with salicylates. Simultaneous administration of ascorbic acid and deferoxamine increases tissue toxicity of iron, especially in the heart muscle, which can lead to decompensation of the circulatory system. The drug can be taken only 2 hours after the injection of deferoxamine.
Long-term administration of large doses by persons treated with disulfiram inhibits the disulfiram-alcohol reaction. Large doses of the drug reduce the effectiveness of tricyclic antidepressants, neuroleptics - phenothiazine derivatives, tubular reabsorption of amphetamine, and disrupt the renal excretion of mexiletine.
Quinoline drugs, calcium chloride, salicylates, and corticosteroids, when used for long periods of time, reduce the body's stores of ascorbic acid.
Iron salts reduce the resorption of concomitantly taken drugs, such as tetracycline, DNA gyrase inhibitors (e.g. ciprofloxacin, levofloxacin, norfloxacin, ofloxacin), diphosphonate, penicillamine, levodopa, carbidopa and methyldopa, penicillin, sulfasalazine.
Application features
The drug is effective only in iron deficiency anemia and is not effective in anemias not associated with iron deficiency. Before starting treatment, it is necessary to establish
diagnosis of iron deficiency (serum iron level, high total serum iron binding capacity) and to exclude specific causes of iron deficiency (e.g., gastric erosions or colon carcinoma).
It is not advisable to use it in cases of reduced serum iron concentration/anemia caused by chronic/acute inflammatory processes or neoplasms, since iron introduced into the body accumulates in the reticuloendothelial system and begins to be used by the body only after the underlying disease is cured.
To avoid possible overdose, special care must be taken when using food or other supplements containing iron salts.
Iron preparations should be used with caution in leukemia, rheumatoid arthritis, chronic liver and kidney diseases, in the remission phase of gastric and duodenal ulcers, inflammatory diseases of the gastrointestinal tract and intestinal diseases (enteritis, ulcerative colitis, Crohn's disease).
Patients who have both anemia and Crohn's disease may develop a state of iron overload and the symptoms of anemia will not resolve. Such patients require careful evaluation and concurrent treatment of anemia and Crohn's disease.
Inflammatory and ulcerative diseases of the digestive tract may be exacerbated by oral administration of the drug.
Iron supplements are believed to increase the pathogenicity of some microorganisms and may negatively affect the prognosis of infectious diseases in HIV-infected patients. Therefore, iron supplements should not be prescribed to HIV-infected patients who do not have iron deficiency anemia.
During course use, it is necessary to periodically (approximately every 4 weeks) monitor serum iron and hemoglobin levels, erythrocyte count, erythrocyte volume, mean erythrocyte hemoglobin content, and reticulocyte count. Determination of serum ferritin allows for an assessment of the amount of stored iron; a serum ferritin level < 15 μg/l indicates a lack of iron stores in the body. Treatment should not be discontinued immediately after normalization of hemoglobin and erythrocyte counts in the blood. Premature discontinuation of treatment usually leads to a relapse of iron deficiency anemia.
To improve the absorption of iron from the intestines, while taking the drug, you should eat a full diet, including meat products, vegetables, and fruits.
Simultaneous use of the drug with alkaline drinks, fresh fruit or vegetable juices reduces the absorption of ascorbic acid. Absorption of ascorbic acid may be impaired in intestinal dyskinesias, enteritis and achilia.
Iron absorption is slowed down by products made from cereals (bread, millet and wheat porridge, cereals), legumes (soybeans, peas), rice, seafood, dairy products, eggs. The time interval between taking the drug and consuming these products should be at least 2 hours. The drug should not be washed down with strong tea, coffee, milk.
You should not drink alcohol during treatment with the drug.
Large doses of the drug should not be prescribed to patients with increased blood clotting.
Preparations containing ascorbic acid should be used with caution in the treatment of patients with glucose-6-phosphate dehydrogenase deficiency and patients with a history of kidney disease.
It should be noted that ascorbic acid in doses exceeding 1 g per day is contraindicated in patients with urolithiasis.
When taking high doses and long-term use of the drug, it is necessary to monitor kidney function and blood pressure, as well as pancreatic function.
Since ascorbic acid has a mild stimulating effect, it is not recommended to take the drug at the end of the day.
The drug may cause dark stool coloration, which is not clinically significant. This is due to the excretion of unabsorbed iron. To prevent staining of tooth enamel, the tablets should be swallowed without chewing. To avoid constipation, the drug should be washed down with plenty of water.
When taking the drug, a false-positive result of a stool test for occult blood is possible.
Simultaneous administration of the drug with alkaline drinks reduces the absorption of ascorbic acid, so you should not wash down the drug with alkaline mineral water. Also, the absorption of ascorbic acid may be impaired in intestinal dyskinesias, enteritis, and achilia.
Use with caution in the treatment of patients with glucose-6-phosphate dehydrogenase deficiency.
Ascorbic acid as a reducing agent can affect the results of laboratory tests, for example, when determining the blood content of glucose, bilirubin, transaminase activity, lactate dehydrogenase, etc.
Accidental inhalation of iron-containing drugs into the respiratory tract can lead to irreversible bronchial necrosis. Therefore, in case of accidental inhalation of fragments of the drug tablets, you should immediately consult a doctor.
Use during pregnancy or breastfeeding
The drug can be used by pregnant and breastfeeding women, both for the prevention and treatment of iron deficiency anemia.
Ability to influence reaction speed when driving vehicles or other mechanisms
The drug should be used with caution when driving or operating other machinery, due to the possibility of adverse reactions from the central nervous system.
Method of administration and doses
For the prevention of anemia, adults and children over 12 years of age are prescribed 1 tablet per day. For the treatment of anemia, adults and children over 12 years of age are prescribed 1 tablet 2 times a day. The tablets should be swallowed whole, without chewing, with a glass of water, at least 30 minutes before meals. In case of adverse reactions, the daily dose can be reduced by 50% (1 tablet per day).
During the first 6 months of pregnancy, the recommended dose of the drug is 1 tablet per day, in the last trimester of pregnancy, as well as during breastfeeding - 1 tablet 2 times a day. The duration of treatment depends on the individual results of checking the iron content in the blood plasma. After normalization of the hemoglobin level, the drug should be administered until the iron stores are fully saturated (approximately 2 months).
If symptoms of iron deficiency anemia are present, the average duration of treatment is 3–6 months.
Children
The drug is used in children over 12 years of age.
Overdose
Symptoms. Ingestion of 20 mg/kg of elemental iron is considered a potentially toxic dose, and 200–250 mg/kg is considered potentially lethal. The course of acute iron overdose can be divided into several stages. In the first stage (up to 6 hours after ingestion), symptoms may include tachycardia, hypotension, abdominal pain, nausea,
vomiting, diarrhea, melena and/or hematemesis, in more severe cases – coma, convulsions, shock. The second stage (6–24 hours after ingestion) is characterized by temporary remission or clinical stabilization. The third stage is characterized by recurrence of gastrointestinal toxicity (vomiting, diarrhea, gastrointestinal bleeding). Symptoms of overdose may also include severe drowsiness (lethargy) or coma, dehydration, vascular insufficiency/severe shock (due to heart failure associated with hypovolemia or direct cardiotoxicity), hepatic insufficiency/hepatocellular necrosis with jaundice, coagulation and bleeding disorders, hypoglycemia, encephalopathy, metabolic acidosis, convulsions, hyperthermia, renal failure (due to decreased tissue perfusion) and pulmonary edema. There is a risk of gastrointestinal perforations, as well as the development of Yersinia enterocolica sepsis. In the fourth stage (2–5 weeks after administration), partial or complete gastrointestinal obstruction (due to cicatricial strictures/pyloric stenosis) and cirrhosis of the liver may develop.
In some sensitive patients (with glucose-6-phosphate dehydrogenase deficiency), an overdose of ascorbic acid can cause severe acidosis and hemolytic anemia.
Treatment depends on symptoms, dose, and time since ingestion of a potentially hazardous dose. Supportive and symptomatic measures include inducing vomiting, ingestion of milk or raw eggs (to form an iron-protein complex), gastric lavage with 1% sodium hydroxide solution (to form sparingly soluble iron carbonate), gastric lavage with deferoxamine solution (2 g/l), and administration of deferoxamine solution into the stomach via a gastric tube (5–10 g of deferoxamine dissolved in 100 ml of isotonic sodium chloride solution), as well as ensuring adequate pulmonary ventilation, monitoring cardiac activity with an ECG, monitoring blood pressure and diuresis, intravenous access, and ensuring adequate hydration. Serum iron levels should be monitored throughout the period of intoxication.
In adults, mannitol or sorbitol may be helpful to increase gastric motility. Inducing diarrhea can be very dangerous in children, especially young children, and should be avoided. The patient should be closely monitored for aspiration.
Tablets absorb X-rays, so an X-ray of the abdominal cavity can detect the number of tablets that may have remained in the gastrointestinal tract after forced vomiting and gastric lavage.
If the serum iron concentration is > 3–5 mg/l (55–90 μmol/l) and tends to rise, parenteral administration of desferrioxamine should be considered. In severe intoxication: shock and/or coma and high serum iron levels (> 90 μmol/l in children and > 142 μmol/l in adults), intensive supportive care and intravenous deferoxamine (15 mg/kg/h by slow infusion, maximum dose 80 mg/kg/day) should be initiated immediately. Too high an infusion rate may lead to hypotension.
In less severe intoxication, deferoxamine can be administered intramuscularly (50 mg/kg, maximum total dose 4 g).
Hemodialysis is ineffective for iron removal, but can be used to accelerate the elimination of the iron-desferrioxamine complex and is also indicated for oliguria or anuria. Peritoneal dialysis may be used.
Adverse reactions
Gastrointestinal: abdominal discomfort, dyspepsia, gastrospasm, vomiting, anorexia, epigastric/abdominal pain, gastritis, flatulence. Prolonged use of high doses of oral iron preparations, especially in elderly patients, may cause constipation, sometimes leading to coprostasis.
When using large doses, gastrointestinal erosions/ulcers (including the esophagus), bleeding, and esophageal stenosis are possible as a result of contact irritation of the digestive tract mucosa with ferrous sulfate tablets.
With prolonged use of ascorbic acid in high doses of more than 1 g per day - irritation of the mucous membrane of the digestive tract, heartburn.
On the part of the immune system: hypersensitivity reactions, including rash, eczema, itching, urticaria, skin hyperemia, anaphylactic reactions, including sore throat, angioedema, anaphylactic shock in the presence of sensitization, respiratory hypersensitivity reactions.
From the urinary system: acidification of urine, hyperoxaluria in patients at risk at doses of ascorbic acid exceeding 1 g/day; with prolonged use in high doses - damage to the glomerular apparatus of the kidneys, crystalluria, formation of urate, cystine and/or oxalate stones in the kidneys and urinary tract, renal failure. Doses of ascorbic acid exceeding 600 mg/day have a diuretic effect.
Metabolic: with prolonged use in high doses (the drug contains ascorbic acid) - hypervitaminosis C, deterioration of tissue trophism, inhibition of the function of the insular apparatus of the pancreas (hyperglycemia, glucosuria), impaired glycogen synthesis, diabetes mellitus, sodium and fluid retention, impaired zinc and copper metabolism.
From the cardiovascular system: arterial hypertension, myocardial dystrophy, feeling of squeezing behind the sternum, feeling of heat, development of microangiopathies.
From the hematopoietic system: thrombocytosis, thrombocytopenia, hyperprothrombinemia, erythrocytopenia, neutrophilic leukocytosis; in patients with glucose-6-phosphate dehydrogenase deficiency of blood cells, hemolysis of erythrocytes is possible.
From the nervous system: increased excitability, sleep disturbances, headache, dizziness, weakness, irritability, fatigue.
Expiration date
3 years.
Storage conditions
Store at a temperature not exceeding 25 °C out of the reach of children.
Packaging
30 or 50 tablets in a glass bottle; 1 bottle in a cardboard box.
Vacation category
According to the recipe.
Producer
CJSC Pharmaceutical Plant EGIS, Hungary.
Location
9900, Kermend, Matyas Kirai Street 65, Hungary.
