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iron sulfate makes up for the lack of iron in the body. as part of the protoporphyrin hemoglobin prosthetic group, iron (ii) plays an important role in the binding and transport of oxygen and carbon dioxide.
In the protoporphyrin group of cytochrome enzymes, iron plays a key role in electron transport processes. In these processes, the absorption and release of electrons is carried out by the reverse transformation of Fe (II) –Fe (III).
Large amounts of iron can also be detected in muscle myoglobin molecules.
Vitamin C increases the absorption of iron in the intestine and is involved in redox processes.
Pharmacokinetics Iron is absorbed in the duodenum and proximal jejunum. The absorption rate of hemoglobin-bound iron is ≈20%, while hemoglobin-bound iron is ≈10%. For better absorption, iron should be in the form of Fe (II). Hydrochloric acid in the stomach and vitamin C promote the absorption of iron by reducing Fe (III) to Fe (II).
Iron Fe (II) - ferro, entering the intestinal epithelial cells, is oxidized to iron Fe (III) - ferri and binds to apoferritin. One part of apoferritin enters the bloodstream, the other remains temporarily in the intestinal epithelial cells in the form of ferritin, which either enters the bloodstream after 1-2 days, or is excreted along with feces along with desquamated epithelium. Nearly 1/3 iron entering the bloodstream binds to apotransferrin, due to which the molecule turns into 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 of Fe (III) is reduced to flavoproteins.
The method of manufacture of coated tablets provides a continuous release of iron (II) ions. When they pass through the gastrointestinal tract, iron (II) ions are continuously released from the porous matrix for 6 hours. Slow release of the active substance prevents dangerously high concentrations of iron, so that irritation of the intestinal epithelium can be avoided.
Prevention and treatment of iron deficiency anemia.
To prevent anemia, adults and children over the age of 12 years are prescribed 1 tablet of sorbifer durules per day. for the treatment of anemia, adults and children over 12 years of age are prescribed 1 tablet 2 times a day. tablets should be swallowed whole, without chewing, with a glass of water, at least 30 minutes before a meal. in case of adverse reactions, the dose can be reduced by 50% (1 tablet per day).
During the first 6 months of pregnancy, the recommended dose is 1 tablet per day, in the third 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 normalizing the level of hemoglobin, the administration of the drug must be continued until the iron reserves are fully saturated (≈2 months). In the presence of symptoms of iron deficiency anemia, the average duration of treatment is 3–6 months.
Hypersensitivity to the components of the drug; esophageal stenosis and / or other obstructive gastrointestinal diseases; intestinal diverticulum; intestinal obstruction; conditions accompanied by increased accumulation of iron (hemochromatosis, hemosiderosis); repeated blood transfusion; other types of anemia not caused by iron deficiency (e.g. hemolytic anemia caused by vitamin b12 deficiency); violation of the mechanisms of incorporation of iron into hemoglobin (anemia caused by lead poisoning); siderohrestical anemia; thrombosis, tendency to thrombosis, thrombophlebitis, severe kidney disease; simultaneous use of parenteral forms of iron; disorder of iron excretion mechanisms (thalassemia); diabetes; urolithiasis (with the use of ascorbic acid 1 g / day); fructose intolerance.
From the digestive tract: nausea, diarrhea, constipation, pain in the stomach, ulcers of the esophagus, stenosis of the esophagus. with prolonged use of ascorbic acid in high doses of 1 g / day - irritation of the mucous membrane of the digestive tract, heartburn.
Allergic reactions are possible (including itching, redness of the skin, anaphylaxis), as well as Quinckes edema, anaphylactic shock in the presence of sensitization.
From the urinary system: damage to the glomerular apparatus of the kidneys, crystalluria, the formation of urate, cystine and / or oxalate calculi in the kidneys and urinary tract.
From the endocrine system: damage to the insular apparatus of the pancreas (hyperglycemia, glucosuria) and impaired glycogen synthesis up to the onset of diabetes mellitus.
From the cardiovascular system: AH, myocardial dystrophy.
From the hematopoietic system: thrombocytosis, hyperprothrombinemia, erythrocytopenia, neutrophilic leukocytosis; in patients with deficiency of glucose-6-phosphate dehydrogenase, blood cells can cause erythrocyte hemolysis.
From the nervous system: increased irritability, sleep disturbance, headache.
From the side of metabolism: metabolic imbalance of zinc, copper.
The drug is effective only with iron deficiency. a diagnosis of iron deficiency should be established (plasma iron level, high total ability of iron to bind in blood plasma) before the initial appointment of the drug.
The drug is ineffective in other types of anemia that are not associated with iron deficiency (infectious anemia, anemia caused by chronic diseases). Inflammatory and peptic ulcer diseases of the gastrointestinal tract can worsen with oral administration of the drug. When treated with the drug, feces may become black.
Iron preparations are used with caution in people with the following diseases: leukemia, chronic liver and kidney diseases, inflammatory diseases of the gastrointestinal tract, gastric and duodenal ulcers, intestinal diseases (enteritis, ulcerative colitis, Crohns disease).
With the course application, a systematic monitoring of the indicators of iron and hemoglobin in the blood serum is necessary.
It should be borne in mind that ascorbic acid at a dose of 1 g / day is contraindicated in patients with urolithiasis.
When taking the drug in high doses and for a long time, it is necessary to control renal function and blood pressure, as well as the function of the pancreas.
Do not prescribe the drug in high doses to patients with high levels of blood coagulation.
The simultaneous use of the drug with alkaline drink reduces the absorption of ascorbic acid, so you should not drink the drug with alkaline mineral water. Also, the absorption of ascorbic acid can be impaired with intestinal dyskinesia, enteritis and achilia.
Used with caution for 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 levels of glucose, bilirubin, transaminase activity, LDH, etc.
The ability to influence the reaction rate when driving vehicles or working with other mechanisms. Use the drug with caution while driving and working with other mechanisms, given the possibility of adverse reactions from the central nervous system.
Use during pregnancy or lactation. The drug can be used by pregnant women and women who are breastfeeding, both for prevention and for the treatment of iron deficiency anemia.
Children. The drug is used in children over the age of 12 years.
It is necessary to avoid the combined use of sorbifer durules:
- with ciprofloxacin, since absorption of ciprofloxacin is reduced by ≈50% and there is a risk that the concentration of ciprofloxacin in the blood plasma will remain below the therapeutic level;
- with levofloxacin, since the absorption of levofloxacin is reduced;
- with moxifloxacin, since the bioavailability of moxifloxacin is reduced by ≈40%, therefore, if necessary, the combined use of these drugs, the interval between their doses should be at least 6 hours;
- with norfloxacin, since the absorption of norfloxacin decreases by ≈75%;
- with ofloxacin, since the absorption of ofloxacin decreases by ≈30%.
The combined use of Sorbifer Durules and the following drugs requires dose adjustment of these drugs, and the interval between their doses should be at least 2 hours.
Calcium- and magnesium-containing food additives, aluminum hydroxide, and calcium- or magnesium-containing antacids form a complex with iron salts, due to which they reduce the absorption of each other.
Captopril: with combined use, the AUC of captopril decreases (by ≈37%), possibly as a result of a chemical reaction in the gastrointestinal tract.
Zinc: with combined use, the absorption of zinc salts is reduced.
Clodronate: In vitro studies have shown that iron-containing preparations form a complex with clodronate. Although in vivo interaction studies have not been conducted, it can be concluded that with the simultaneous use of these drugs, the absorption of clodronate decreases.
Deferoxamine: The combined use of these drugs reduces the absorption of both deferoxamine and iron due to complex formation.
Levodopa: when used with levodopa or carbidopa, iron sulfate reduces the bioavailability of a single dose of levodopa by ≈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 (iron sulfate or iron gluconate), the bioavailability of methyldopa is reduced, possibly due to the formation of a chelate complex, which can lead to a decrease in the severity of the hypotensive effect.
Penicillinamine: with the combined use of penicillinamine and iron salts, the absorption of both penicillinamine and iron salts decreases due to the formation of a chelate complex.
Risedronate: In vitro studies have shown that iron-containing preparations form a complex with risedronate. Although in vivo interaction studies have not been conducted, it can be assumed that the combined use of these drugs reduces the absorption of risedronate.
Tetracyclines: with combined use, the absorption of both iron and tetracyclines is reduced, so if you need to use these drugs simultaneously, the interval between their doses should be at least 3 hours.
Thyroid hormones: the simultaneous use of iron and thyroxine preparations can reduce the absorption of the latter.
Tocopherol: the activity of both drugs decreases.
Pancreatin, colestyramine, D-penicillamine: there is a decrease in iron absorption in the digestive tract.
GCS: perhaps increased stimulation of erythropoiesis.
Ethanol: increased absorption and the risk of toxic complications.
Ascorbic acid: iron absorption is enhanced.
When using Sorbifer Durules, together with cimetidine, the secretion of hydrochloric acid in the stomach is reduced, since cimetidine reduces the absorption of iron. Therefore, the interval between taking these drugs should be at least 2 hours.
With the simultaneous use of tea, coffee, eggs, bread, foods rich in plant fibers, the absorption of iron may decrease.
The simultaneous use of chloramphenicol can slow the development of the clinical effect of iron.
The absorption of ascorbic acid is reduced with the combined use of oral contraceptives, the use of fruit or vegetable juices, alkaline drinking.Oral ascorbic acid increases the absorption of penicillin, tetracycline, iron, reduces the effectiveness of heparin and indirect anticoagulants, and increases the risk of crystalluria during treatment with salicylates. The simultaneous administration of ascorbic acid and deferoxamine increases the 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 injection of deferoxamine. Long-term use of the drug in high doses by persons who are treated with disulfiramine inhibits the disulfiram-alcohol reaction. The drug in high doses reduces the effectiveness of tricyclic antidepressants, antipsychotics - phenothiazine derivatives, tubular reabsorption of amphetamine, disrupts the excretion of mexiletine by the kidneys.
Preparations of the quinoline series, calcium chloride, salicylates, GCS with prolonged use reduce the reserves of ascorbic acid in the body.
Iron salts reduce the resorption of concomitantly administered drugs such as tetracycline, DNA gyrase inhibitors (e.g. ciprofloxacin, levofloxacin, norfloxacin, ofloxacin), diphosphonates, penicillamine, levodopa, carbidopa and methyldopa, penicillin, sulfasalazine.
Symptoms the initial symptoms of an iron overdose are nausea, vomiting, diarrhea, bloody bowel movements, abdominal pain, drowsiness, shock. dehydration, metabolic acidosis, hyperglycemia, tachycardia, arterial hypotension may also develop.
In severe cases, after an obvious improvement in the duration of 6-24 hours, a relapse may occur, characterized by coagulopathy, vascular insufficiency (due to heart failure associated with myocardial damage), hyperthermia, hypoglycemia, liver and kidney failure, seizures and coma. There is a risk of gastrointestinal perforation, as well as the development of Yersinia enterocolica sepsis. Later (after a few weeks, sometimes months), liver cirrhosis and pyloric stenosis may develop.
In some sensitive patients (glucose-6-phosphate dehydrogenase deficiency), an overdose of vitamin C (ascorbic acid) can cause severe acidosis and hemolytic anemia.
Treatment. Drink milk or liquid that causes vomiting.
Rinse the stomach with rheum of deferoxamine (2 g / l), then inject 50-100 ml of water containing 5 g of deferoxamine and leave it in the stomach. For adults, it may be helpful to drink mannitol or sorbitol to ease gastric motility. Induction of diarrhea can be very dangerous for children and especially for young children, so it should be avoided. The patient should be closely monitored for the timely identification of possible aspiration.
The tablets absorb x-rays, so by x-ray examination of the abdominal cavity, you can identify the number of tablets that could remain in the digestive tract after forced vomiting and gastric lavage.
In case of severe intoxication: in case of shock and / or coma and with a high level of iron in the blood plasma (90 μmol / L in children and 142 μmol / L in adults), intensive maintenance therapy should immediately be started and deferoxamine should be prescribed (15 mg / kg / h by slow infusion, the maximum dose is 80 mg / kg / day). Too high a rate of administration can lead to arterial hypotension.
With less severe intoxication, you can introduce deferoxamine / m (50 mg / kg, the maximum total dose is 4 g).
During the entire period of intoxication, it is recommended to control the level of iron in the blood plasma.
At a temperature not exceeding 25 ° c.