What are the main uses of ferrous sulfate. How should ferrous sulfate be dosed for different conditions. What are the potential side effects of taking ferrous sulfate. How can ferrous sulfate be used safely during pregnancy.

Understanding Ferrous Sulfate: An Essential Iron Supplement

Ferrous sulfate is a vital iron supplement used to prevent and treat iron deficiency anemia. This mineral compound plays a crucial role in supporting various bodily functions, particularly in the production of hemoglobin, the protein in red blood cells responsible for carrying oxygen throughout the body.

What is ferrous sulfate?

Ferrous sulfate is an iron salt that contains approximately 20% elemental iron. It is one of the most commonly prescribed forms of iron supplementation due to its high bioavailability and relatively low cost. The compound comes in various formulations, including tablets, liquid solutions, and delayed-release capsules.

Primary Uses of Ferrous Sulfate

Ferrous sulfate serves several important purposes in maintaining health and treating various conditions. Here are the main uses:

• Treatment of iron deficiency anemia
• Prevention of anemia in high-risk individuals
• Management of anemia associated with chronic renal failure
• Vitamin and mineral supplementation
• Supporting pregnancy and lactation

How does ferrous sulfate work in the body?

When ingested, ferrous sulfate is absorbed in the small intestine. The iron is then incorporated into hemoglobin in red blood cells, myoglobin in muscle tissue, and various enzymes throughout the body. This process helps maintain proper oxygen transport, energy production, and overall cellular function.

Dosage Guidelines for Ferrous Sulfate

The appropriate dosage of ferrous sulfate varies depending on the condition being treated, age, and individual needs. It’s crucial to follow the prescribed dosage carefully to avoid potential side effects or complications.

What is the typical adult dosage for iron deficiency anemia?

For adults with iron deficiency anemia, the usual initial dose is 600 mg of ferrous sulfate (equivalent to 120 mg of elemental iron) per day, divided into 1 to 3 doses. This regimen is typically continued for three months to replenish iron stores.

How should ferrous sulfate be dosed for children?

Pediatric dosing varies by age and condition:

• 0 to 5 years: 15 to 30 mg/kg/day of ferrous sulfate (3 to 6 mg/kg/day elemental iron)
• 5 to 12 years: 300 mg ferrous sulfate (60 mg/day elemental iron)
• 12-18 years: Dosage ranges from 300 to 600 mg/day ferrous sulfate, depending on gender and specific needs

These doses are typically divided and administered 1 to 3 times daily.

Ferrous Sulfate in Special Populations

Certain groups may require special considerations when taking ferrous sulfate.

Is ferrous sulfate safe during pregnancy?

Ferrous sulfate is generally considered safe and often recommended during pregnancy to prevent iron deficiency anemia. However, dosage may need to be adjusted:

• For vitamin supplementation/prevention of anemia: 110 to 135 mg/day ferrous sulfate (22 to 27 mg/day elemental iron)
• For treatment of anemia: 300 to 600 mg ferrous sulfate (60 to 120 mg/day elemental iron)

It’s essential to consult with a healthcare provider for personalized dosing during pregnancy.

How should ferrous sulfate be used in patients with chronic renal failure?

For patients with anemia associated with chronic renal failure, the initial dose is typically 1000 mg/day ferrous sulfate (200 mg/day elemental iron) taken in divided doses. If oral supplementation doesn’t achieve desired results after 1 to 3 months, intravenous iron supplementation may be considered.

Potential Side Effects and Precautions

While ferrous sulfate is generally well-tolerated, it can cause side effects in some individuals.

What are common side effects of ferrous sulfate?

Common side effects may include:

• Gastrointestinal discomfort (nausea, constipation, diarrhea)
• Darkening of stools
• Temporary tooth staining (with liquid formulations)
• Stomach upset

These effects are often mild and may diminish over time. Taking the supplement with food or using a delayed-release formulation can help minimize gastrointestinal side effects.

Are there any serious risks associated with ferrous sulfate?

While rare, serious risks can occur, particularly with overdose. The US FDA requires a boxed warning on ferrous sulfate products stating that accidental overdose of iron-containing products is a leading cause of fatal poisoning in children under 6. It’s crucial to keep iron supplements out of reach of children and seek immediate medical attention in case of suspected overdose.

Optimizing Ferrous Sulfate Absorption

To maximize the benefits of ferrous sulfate supplementation, it’s important to understand factors that can affect its absorption.

What enhances iron absorption from ferrous sulfate?

Several factors can improve iron absorption:

• Vitamin C: Taking ferrous sulfate with a source of vitamin C (e.g., orange juice) can significantly enhance absorption
• Acidic foods: Consuming ferrous sulfate with acidic foods can also boost absorption
• Empty stomach: Taking the supplement on an empty stomach (1 hour before or 2 hours after meals) can improve absorption, though this may increase the likelihood of gastrointestinal side effects

What inhibits iron absorption from ferrous sulfate?

Certain substances can interfere with iron absorption:

• Calcium: Avoid taking calcium supplements or calcium-rich foods within 2 hours of ferrous sulfate
• Tannins: Found in tea, coffee, and some fruits, tannins can significantly reduce iron absorption
• Phytates: Present in whole grains and legumes, phytates can bind to iron and reduce absorption
• Certain medications: Antacids, proton pump inhibitors, and some antibiotics can interfere with iron absorption

To optimize absorption, it’s best to take ferrous sulfate at least 2 hours apart from these potential inhibitors.

Monitoring and Long-term Use of Ferrous Sulfate

Proper monitoring and management are crucial for safe and effective long-term use of ferrous sulfate.

How is the effectiveness of ferrous sulfate supplementation monitored?

Healthcare providers typically monitor the effectiveness of ferrous sulfate supplementation through regular blood tests. These may include:

• Complete blood count (CBC) to assess hemoglobin and red blood cell levels
• Serum ferritin to evaluate iron stores
• Transferrin saturation to assess iron transport capacity

The frequency of monitoring may vary depending on the individual’s condition and response to treatment.

Can ferrous sulfate be used long-term?

While ferrous sulfate can be used long-term for certain conditions, such as chronic anemia or ongoing iron deficiency, it’s important to do so under medical supervision. Long-term use should be based on documented need and regular monitoring to prevent iron overload, which can lead to organ damage.

Interactions and Contraindications

Understanding potential interactions and contraindications is crucial for safe use of ferrous sulfate.

What medications interact with ferrous sulfate?

Several medications can interact with ferrous sulfate:

• Levothyroxine: Ferrous sulfate can reduce the absorption of thyroid hormones
• Tetracycline antibiotics: Iron can decrease the effectiveness of these antibiotics
• Levodopa: Iron may reduce the absorption of this Parkinson’s disease medication
• Quinolone antibiotics: Iron can interfere with the absorption of these antibiotics

To avoid interactions, it’s generally recommended to take ferrous sulfate at least 2 hours before or after these medications.

Are there any conditions where ferrous sulfate is contraindicated?

Ferrous sulfate may be contraindicated or require special consideration in certain conditions:

• Hemochromatosis: A condition of iron overload
• Hemosiderosis: Iron accumulation in tissues
• Peptic ulcer disease: Iron may exacerbate symptoms
• Inflammatory bowel disease: Iron may worsen inflammation in some cases

Individuals with these conditions should consult their healthcare provider before using ferrous sulfate supplements.

Alternative Forms of Iron Supplementation

While ferrous sulfate is a common and effective form of iron supplementation, there are alternatives available for those who may not tolerate it well or have specific needs.

What are other forms of iron supplements?

Alternative forms of iron supplementation include:

• Ferrous gluconate: Generally better tolerated but contains less elemental iron
• Ferrous fumarate: Similar to ferrous sulfate in elemental iron content
• Iron amino acid chelates: May have fewer gastrointestinal side effects
• Carbonyl iron: A form of elemental iron that may be safer in cases of accidental ingestion
• Intravenous iron: Used in cases of severe deficiency or when oral supplements are not tolerated

The choice of iron supplement should be based on individual needs, tolerability, and healthcare provider recommendations.

How do these alternatives compare to ferrous sulfate?

While all forms of iron can be effective in treating deficiency, they differ in several aspects:

• Absorption: Ferrous forms (including sulfate) are generally better absorbed than ferric forms
• Side effects: Some forms, like iron amino acid chelates, may cause fewer gastrointestinal side effects
• Cost: Ferrous sulfate is often the most cost-effective option
• Dosing: The amount of elemental iron varies between forms, affecting dosing requirements

Your healthcare provider can help determine the most appropriate form of iron supplementation based on your specific situation.

Ferrous Sulfate Dosage Guide with Precautions

Medically reviewed by Drugs.com. Last updated on March 22, 2021.

Applies to the following strengths: 300 mg/5 mL; 300 mg; 160 mg; (as elemental iron) 45 mg; 525 mg; 325 mg; 195 mg; (as elemental iron) 15 mg/mL; 75 mg/0.6 mL; 90 mg/5 mL; 190 mg; 250 mg; 220 mg/5 mL; 159 mg; 324 mg; (as elemental iron) 15 mg/1.5 mL; 200 mg

Usual Adult Dose for:

Usual Pediatric Dose for:

Additional dosage information:

Usual Adult Dose for Iron Deficiency Anemia

Initial dose: 600 mg/day ferrous sulfate (120 mg/day elemental iron) for 3 months
-Give in divided doses (1 to 3 times daily)

Usual Adult Dose for Anemia Associated with Chronic Renal Failure

Initial dose: 1000 mg/day ferrous sulfate (200 mg/day elemental iron) orally in divided doses (1 to 3 times daily)

Comments:
-If goals are not met with oral iron after 1 to 3 months, consider IV iron supplementation.
-Smaller daily doses may be better tolerated.

Usual Adult Dose for Vitamin/Mineral Supplementation

Initial dose: 1 tablet orally once a day

or

Initial dose: 30 to 90 mg/day ferrous sulfate (FeSO4) (6 to 18 mg/day elemental iron) orally, in divided doses (1 to 3 times daily)

51 and over: 25 to 40 mg/day FeSO4 (5 to 8 mg/day elemental) orally, in divided doses (1 to 3 times daily)

Usual Pediatric Dose for Iron Deficiency Anemia

0 to 5 years: 15 to 30 mg/kg/day ferrous sulfate (FeSO4) (3 to 6 mg/kg/day elemental iron)
5 to 12 years: 300 mg FeSO4 (60 mg/day elemental)
12-18 years male: Two 300 mg FeSO4 (60 mg elemental) tablets orally daily
12-18 years female: 300 to 600 mg/day FeSO4 (60 to 120 mg/day elemental)
-Give in divided doses (1 to 3 times daily)

Usual Pediatric Dose for Vitamin/Mineral Supplementation

Preterm infant (less than 37 weeks gestation), 0 to 12 months: 10 mg/kg/day ferrous sulfate (FeSO4) (2 mg/kg/day elemental iron)
0 to 6 months: 1 to 1.35 mg/day FeSO4 (0.2 to 0.27 mg/day elemental)
7 to 12 months: 35 to 55 mg/day FeSO4 (7 to 11 mg/day elemental)
1 to 3 years: 20 to 45 mg/day FeSO4 (4 to 9 mg/day elemental)
4 to 8 years: 20 to 50 mg/day FeSO4 (4 to 10 mg/day elemental)
9 to 13 years: 30 to 40 mg/day FeSO4 (6 to 8 mg/day elemental)
14 to 18 years: 40 to 75 mg/day FeSO4 (8 to 15 mg/day elemental)
-Give in divided doses (1 to 3 times daily)

or

Tablets (325 mg FeSO4, 65 mg elemental iron)
12 years and older: 1 tablet orally once a day

Renal Dose Adjustments

No adjustment recommended

Liver Dose Adjustments

No adjustment recommended

Dose Adjustments

Vitamin supplementation/Prevention of anemia:
14 to 18 years: Pregnancy: 115 to 135 mg/day ferrous sulfate (FeSO4) (23 to 27 mg/day elemental iron)
14 to 18 years: Lactation: 35 to 50 mg/day FeSO4 (7 to 10 mg/day elemental)
19 to 50 years: Pregnancy: 110 to 135 mg/day FeSO4 (22 to 27 mg/day elemental)
19 to 50 years: Lactation: 32.5 to 45 mg/day FeSO4 (6.5 to 9 mg/day elemental)
Maximum dose: 225 mg FeSO4 (45 mg/day elemental)

Treatment of anemia:
Pregnancy: 300 to 600 mg FeSO4 (60 to 120 mg/day elemental)

Precautions

US BOXED WARNING:
-Accidental overdose of iron-containing products is a leading cause of fatal poisoning in children under 6.
-Keep out of reach of children.
-In case of accidental overdose, call a doctor or poison center immediately.

Consult WARNINGS section for additional precautions.

Dialysis

Iron supplementation is routinely provided to peritoneal dialysis and hemodialysis patients for prevention or treatment of anemia associated with chronic renal failure.

Other Comments

Administration advice:
-Coffee, tea, milk, cereal, dietary fiber, and phosphate containing carbonated drinks decrease iron absorption.
-Supplements containing calcium, zinc, manganese, or copper decrease iron absorption.
-Antacids, h3 blockers, and proton pump inhibitors decrease iron absorption; do not use within 1 to 2 hours of iron administration.
-Vitamin C and acidic foods increase iron absorption.
-Delayed release and enteric coated formulations are better tolerated, but are not as well absorbed.

Patient advice:
-Accidental overdose of iron-containing products is a leading cause of fatal poisoning in children under 6.
-Keep out of reach of children.
-In case of accidental overdose, call a doctor or poison center immediately.

Frequently asked questions

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Medical Disclaimer

Ferrous sulfate Use During Pregnancy

Ferrous sulfate is also known as: Chem-Sol, Fe 50, Fe Caps, Feosol Original, Fer-Gen-Sol, Fer-In-Sol, Fer-Iron, Feratab, Fero-Gradumet Filmtab, FeroSul, Ferra T.D. Caps, Ferra-TD, Ferro-Bob, Ferro-Time, Ferrospace, Ferrousal, Iron Sulfate, Lydia E. Pinkham, Mol-Iron, MyKidz Iron 10, Slow Fe, Slow Release Iron, Yieronia

Medically reviewed by Drugs.com. Last updated on March 22, 2021.

Ferrous sulfate Pregnancy Warnings

Use is considered acceptable.

AU TGA pregnancy category: Exempt
US FDA pregnancy category: Not assigned

Comments:
-Routine screening for anemia, including in asymptomatic patients, is generally recommended.
-Routine supplementation during pregnancy is recommended by many organizations.

Maternal anemia increases the risk of low birthweight, premature delivery, and impaired cognitive and behavioral development. Randomized trials show that supplementation can prevent iron deficiency anemia and related adverse consequences to the infant. Recent studies have linked high serum iron with an increased risk of gestational diabetes.

AU Exempt: Medications exempted from pregnancy classification are not absolutely safe for use in pregnancy in all circumstances. Some exempted medicines, for example the complementary medicine, St John’s Wort, may interact with other medicines and induce unexpected adverse effects in the mother and/or fetus.

US FDA pregnancy category Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D, and X are being phased out.

See references

Ferrous sulfate Breastfeeding Warnings

Use is considered acceptable.

Excreted into human milk: Yes

Comments:
-Iron in breast milk is very bioavailable, but amounts are generally not sufficient for infants older than 4 months; iron supplementation of the mother does not change this situation.
-Iron content of breast milk is not affected by the mother’s nutritional status.

See references

References for pregnancy information

1. NIH Office of Dietary Supplements “Iron Dietary Supplement Fact Sheet. Available from: URL: https://ods.od.nih.gov/factsheets/Iron-HealthProfessional/?print=1” ([2016, Feb 01]):
2. World Health Organization (WHO) “Iron Deficiency Anaemia. Assessment, Prevention, and Control, A guide for programme managers
   Available from: URL: http://www.who.int/nutrition/publications/en/ida_assessment_prevention_control.pdf.” ([2001]):
3. Bao W, Chavarro JE, Tobias DK, et.al “Long-term risk of type 2 diabetes in relation to habitual iron intake in women with a history of gestational diabetes: a prospective cohort study.” Am J Clin Nutr 103 (2016): 375-81
4. Rawal S, Hinkle SN, Bao W, et.al “A longitudinal study of iron status during pregnancy and the risk of gestational diabetes: findings from a prospective, multiracial cohort.” Diabetologia 60 (2017): 249-57
5. McDonagh M, Cantor A, Bougatsos C, et al. “Routine Iron Supplementation and Screening for Iron Deficiency Anemia in Pregnant Women: A Systematic Review to Update the U.S. Preventive Services Task Force Recommendation [Internet] Available from: URL: https://www.ncbi.nlm.nih.gov/books/NBK285987/” ([2015, Mar]):
6. Scholl TO, Reilly T “Anemia, Iron and Pregnancy Outcome.” J Nutr 130 (2000): 443S-7S

References for breastfeeding information

1. Picciano MF “Pregnancy and Lactation: Physiological Adjustments, Nutritional Requirements and the Role of Dietary Supplements.” J Nutr 133 (2003): 1997S-2002S
2. Cerner Multum, Inc. “UK Summary of Product Characteristics.” O 0
3. NIH Office of Dietary Supplements “Iron Dietary Supplement Fact Sheet. Available from: URL: https://ods.od.nih.gov/factsheets/Iron-HealthProfessional/?print=1” ([2016, Feb 01]):
4. Allen LH “Multiple micronutrients in pregnancy and lactation: an overview.” Am J Clin Nutr 81(S) (2005): 1206S-12S

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Medical Disclaimer

Ferrous sulfate: medicine for treating iron deficiency anaemia

If you or your child are prescribed ferrous sulfate, follow a doctor’s instructions about how and when to take it.

If you buy ferrous sulfate from a pharmacy, follow the instructions that come with the packet.

Ferrous sulfate comes as 200mg tablets or as drops that you swallow.

The drops contain 125mg of ferrous sulfate in each 1ml.

The drops may be easier for children and people who find it difficult to swallow tablets.

How much will I take?

The dose of ferrous sulfate depends on why you’re taking it and whether you have tablets, capsules or drops.

For children under the age of 18 years, the doctor will use your child’s age, weight and blood results to work out the right dose.

To treat anaemia

The usual dose for adults is:

• tablets: one 200mg tablet, taken 2 to 3 times a day
• drops: 4ml, taken once or twice a day

To prevent anaemia

The usual dose for adults is:

• tablets: one 200mg tablet, taken once a day
• drops: 2.4ml to 4.8ml daily

How to take it

Ferrous sulfate works best when you take it on an empty stomach. However, if it upsets your stomach, you can take it with or after food.

A doctor (or a pharmacist) may recommend taking ferrous sulfate with orange juice or a vitamin C supplement. Vitamin C is believed to increase the amount of iron absorbed by the body.

Swallow the tablet or capsule whole with a glass of water. Do not suck, chew or keep the tablet in your mouth as this can cause mouth ulcers or stain your teeth.

Do not take it with tea, coffee, eggs, dairy products and soybean products, as they can reduce the amount of iron that gets into your system. When you take ferrous sulfate (or when you eat foods that are high in iron), leave a 2-hour gap before having these foods or drinks.

If you have difficulty swallowing the tablets tell your doctor or pharmacist.

If you’re taking ferrous sulfate as drops, it will come with a plastic syringe or dropper to help you measure out the right dose.

If you do not have one, ask a pharmacist for one. Do not use a kitchen teaspoon as it will not give you the right amount of medicine.

What if I forget to take it?

If you forget a dose, take another as soon as you remember. If it’s almost time to take the next dose, then do not take the missed dose at all.

Do not take a double dose to make up for a forgotten dose.

If you often forget doses, it may help to set an alarm to remind you. You could also ask your pharmacist for advice on other ways to remember your medicine.

What if I take too much?

If you go to A&E do not drive yourself. Get someone else to drive you, or call an ambulance.

Take the ferrous sulfate packet or the leaflet inside it with you and any remaining medicine.

Ferrous sulfate | DrugBank Online

Ferrous sulfate oral solution in young children with iron deficiency anemia: An open-label trial of efficacy, safety, and acceptability

Background:

This study evaluated the efficacy, safety, and acceptability of a new ferrous sulfate oral solution (Tardyferon® 20 mg/mL) in young children with mild or moderate iron deficiency anemia (IDA).

Methods:

This was a multicenter, national, single-arm, open-label study. Children aged 6-53 months presenting with mild or moderate IDA (i.e., blood hemoglobin (Hb) ranging from 7.0 to 10.9 g/dL and serum ferritin <12 ng/mL) were eligible for inclusion. The ferrous sulfate heptahydrate solution (2 mg/kg/day) was administered orally for 3 months. If normalization of either Hb or ferritin was not achieved at month 3 the treatment was continued for another 3 months.

Results:

Of the 100 children screened, 21 aged 6-17 months were included and received the study treatment, and 19 were analyzed for hematologic outcomes at month 3. Only one patient continued treatment for the additional 3 months. At month 3, mean ± SD Hb and ferritin levels were 12.0 ± 0.7 g/dL and 31.5 ± 19.4 ng/mL, respectively. Hemoglobin and ferritin levels were normalized in 95% (18/19) and 84% (16/19) of the patients, respectively. Treatment compliance and levels of satisfaction of both the parents and the investigators were high. Overall, 33.3% of patients (7/21) experienced at least one adverse event. Only one patient (4.8%) experienced a drug-related adverse event (upper abdominal pain).

Conclusions:

A 2 mg/kg daily dose of the new oral ferrous sulfate heptahydrate solution provides substantial therapeutic benefit with high levels of tolerability in young children who have mild or moderate IDA.

Keywords:

ferrous sulfate; infant; iron deficiency anemia; preschool child.

Ferrous Sulfate Side Effects – Iron

What Is Ferrous Sulfate?

Iron, or ferrous sulfate (Feosol®, Slow FE®) is a mineral that your body needs to produce red blood cells. When the body does not get enough iron, it cannot produce enough red blood cells to keep itself healthy. This is called iron-deficiency anemia. Lack of iron can cause tiredness, shortness of breath, and decreased physical performance. It also can increase the chance of a liver transplant patient getting infections.

Ferrous sulfate uses include treating or preventing low levels of iron in the blood; it treats or prevents iron-deficiency anemia.

Foods rich in iron include lean red meat, beans, nuts, asparagus, oatmeal, and dried peaches. Vitamin C can increase the absorption of iron, which can be found in citrus fruits and fresh vegetables. Ferrous sulfate might be prescribed if your child is not able to maintain a healthy level of iron through diet alone after a liver transplant.

Ferrous Sulfate Dosage

Ferrous sulfate medication is taken by mouth. It is available in liquid form, as caplets, and as 300- and 324-mg tablets.

How to Properly Take Ferrous Sulfate

Ferrous sulfate should be taken on an empty stomach and with water or fruit juice. However, if the medication upsets your child’s stomach, he or she can take ferrous sulfate with food.

Missed Doses

If your child misses a dose of ferrous sulfate, take it as soon as you or your child remembers. If you remember within two hours of your next scheduled dose, skip the missed dose and resume your child’s usual dosing schedule. Do not double the dose to catch up.

Ferrous Sulfate Side Effects

Some people do experience stomach discomfort that ranges from heartburn to nausea and vomiting, but taking ferrous sulfate with food instead may help avoid or lessen it. Constipation or stools that are black or green also occur. (The unusual coloring is because of absorbed iron, and is not harmful.)

In rare cases, ferrous sulfate side effects include:

• Diarrhea
• Stomach pain
• Chest pain
• Dark urine

If your child has trouble with any of these side effects, inform your doctor or transplant coordinator.

Ferrous Sulfate Drug Interactions

Tell your transplant coordinator about all the medication your child uses, whether over-the-counter or prescription, so you can be warned of undesirable interactions and prevent them.

Precautions for Children

Take ferrous sulfate as prescribed. Eggs, milk, dairy products, coffee, tea, spinach, fiber, and antacids can decrease iron absorption. Your child should take iron tablets one to two hours after eating these foods or taking other medication.

Ferrous Sulfate Availability

Most pharmacies stock ferrous sulfate.

Drug information changes periodically. For the most updated information on drugs, visit www.drugs.com.

Ferrous sulfate for iron-deficiency anaemia

Ferrous sulfate for iron-deficiency anaemia

This leaflet is about the use of ferrous sulfate (ferrous sulphate), which is a form of iron, for the prevention or treatment of iron-deficiency anaemia.

This leaflet has been written specifically for parents and carers about the use of this medicine in children. The information may differ from that provided by the manufacturer. Please read this leaflet carefully. Keep it somewhere safe so that you can read it again.

Do not give ferrous sulfate to your child unless a doctor has told you to. If your child’s anaemia is not due to an iron deficiency, they could end up with too much iron, which can be dangerous.
 

Name of drug

Ferrous sulfate (ferrous sulphate)
Brand name: Ironorm® Drops

Why is it important for my child to take this medicine?

Anaemia is a blood condition where there is a lack of a protein called haemoglobin. Haemoglobin is needed to carry oxygen in the blood and transport it around the body.

Children with anaemia are often pale, feel tired, have little energy, and may not grow or develop properly.

Ferrous sulfate is a form of iron that can be taken by mouth. It helps the body to make more haemoglobin and so treat the anaemia. It can also be used to prevent anaemia in children who are at risk of it or, for example, before surgery.

What is ferrous sulfate available as?

• Tablets: 200 mg (65 mg of iron)
• Oral drops: 125 mg (25 mg of iron) in 1 mL

When should I give ferrous sulfate?

This depends on whether it is being used to prevent or treat anaemia. Your doctor will tell you how often to give ferrous sulfate.

If ferrous sulfate is being used to prevent anaemia, it is usually given once each day. This can be in the morning OR the evening.

If ferrous sulfate is being used to treat anaemia, it is usually given twice or three times each day.

• Twice a day: this should be once in the morning and once in the evening. Ideally, these times are 10–12 hours apart, for example some time between 7 and 8 am, and between 7 and 8 pm.
• Three times a day: this should be once in the morning, once in the early afternoon and once in the evening. Ideally, these times are at least 6 hours apart, for example 8 am, 2 pm and 8 pm.

Give the medicine at about the same time(s) each day so that this becomes part of your child’s daily routine, which will help you to remember.

How much should I give?

Your doctor will work out the amount of ferrous sulfate (the dose) that is right for your child. The dose will be shown on the medicine label. The dose may be given as a number of drops or as millilitres (mL).

It is important that you follow your doctor’s instructions about how much to give.

How should I give it?

Tablets should be swallowed with a glass of water or juice, but not milk. Your child should not chew the tablet. Do not crush these tablets.

Oral drops: Measure out the right amount (you will be told this in either drops or mL) from the dropper bottle or by using an oral syringe. You can get these from your pharmacist. Do not use a kitchen teaspoon as it will not give the right amount.

Ferrous sulfate works best when given on an empty stomach. Try to give it 30 minutes before or 2 hours after food. However, if this upsets your child’s stomach, you can give it with a little food.

When should the medicine start working?

Ferrous sulfate takes some time to work. If it is being used to treat anaemia, you might notice an improvement in your child when they have been taking the medicine for 3–4 weeks. They may be less pale, have more energy and have less shortness of breath. Your child will need to take ferrous sulfate regularly for at least 3 months for it to have its full benefits. If your child is taking ferrous sulfate to prevent anaemia, you will not see any difference in your child, but the medicine will still be working to improve your child’s levels of iron and stop them getting anaemia.

What if my child is sick (vomits)?

• If your child is sick less than 30 minutes after having a dose of ferrous sulfate, give them the same dose again.
• If your child is sick more than 30 minutes after having a dose of ferrous sulfate, you do not need to give them another dose. Wait until the next normal dose.

What if I forget to give it?

• If you usually give it once a day: Give the missed dose when you remember, as long as this is at least 12 hours before the next dose is due. You do not need to wake up a sleeping child to give a missed dose.
• If you usually give it twice a day: If you remember up to 4 hours after you should have given a dose, give your child the missed dose. For example, if you usually give a dose at about 7 am, you can give the missed dose at any time up to 11 am. If you remember after that time, do not give the missed dose. Give the next dose as usual.
• If you usually give it three times a day: Do not give the missed dose. Just give the next dose as usual.

Never give a double dose of ferrous sulfate. If you are not sure whether to give a missed dose, don’t give it. Giving an extra dose of ferrous sulfate by mistake is more likely to do harm than missing a dose.

What if I give too much?

It may be dangerous to give too much ferrous sulfate. Never give your child more than the doctor has advised. 

If your child has one or more of the following symptoms, they may have had too much ferrous sulfate:

• stomach pains
• being repeatedly sick (vomiting)
• diarrhoea
• their vomit or stools (poo) are blood stained, or green or grey.

Children who have had too much ferrous sulfate might not show any symptoms or only have mild symptoms. If you think your child has had too much ferrous sulfate, contact your doctor or NHS Direct (0845 4647 in England and Wales; 08454 24 24 24 in Scotland) or take your child to hospital.

If your child appears very unwell or drowsy call for an ambulance straight away.

Take the medicine container or packaging with you, even if it is empty. This will be useful to the doctor. Have the medicine or packaging with you if you telephone for advice.

Are there any possible side-effects?

We use medicines to make our children better, but sometimes they have other effects that we don’t want (side-effects).

• Your child may feel sick or be sick. It may help to give ferrous sulfate after some food.
• Your child might get indigestion, constipation (difficulty doing a poo) or diarrhoea/loose stools (poo).
• If these side-effects are a problem or do not wear off, contact your doctor or pharmacist, as they may suggest a different iron preparation or a lower dose. Do not reduce the dose without discussing with your doctor first.

There may, sometimes, be other side-effects that are not listed above. If you notice anything unusual and are concerned, contact your doctor.

Can other medicines be given at the same time as ferrous sulfate?

• You can give your child medicines that contain paracetamol or ibuprofen, unless your doctor has told you not to.
• Ferrous sulfate should not be taken with some medicines that you get on prescription. Tell your doctor and pharmacist about any other medicines your child is taking before giving ferrous sulfate.
• If your child needs to take any medicines for indigestion, do not give these with ferrous sulfate. Give the two medicines at different times of the day.
• Check with your doctor or pharmacist before giving any other medicines to your child, other products that contain iron, and any products that contain zinc or magnesium. This includes multivitamin preparations and herbal or complementary medicines.

Is there anything else I need to know about this medicine?

• The packaging for ferrous sulfate may include the warning, ‘Important warning: Contains iron. Keep out of the reach and sight of children, as overdose may be fatal’. However, iron is not harmful when given in the amounts recommended by your doctor. You must not give your child more than this.

Keep ferrous sulfate out of the reach of young children.

• Your child’s stool (poo) may appear darker than usual while taking ferrous sulfate. This is very common and you do not need to worry about it. However, if you are concerned, your pharmacist or doctor will be able to give you more advice.
• Your doctor will do blood tests to measure how much iron is in your child’s blood and to make sure that the medicine is working.
• Separate leaflets on other medicines containing iron for the treatment and prevention of anaemia are available on www.medicinesforchildren.org.uk

General advice about medicines

• Try to give medicines at about the same times each day, to help you remember.
• If you are not sure a medicine is working, contact your doctor but continue to give the medicine as usual in the meantime. Do not give extra doses, as you may do harm.
• Only give this medicine to your child. Never give it to anyone else, even if their condition appears to be the same, as this could do harm.

If you think someone else may have taken the medicine by accident, contact your doctor straight away.

• Make sure that you always have enough medicine. Order a new prescription at least 2 weeks before you will run out.
• Make sure that the medicine you have at home has not reached the ‘best before’ or ‘use by’ date on the packaging. Give old medicines to your pharmacist to dispose of.

Where I should keep this medicine?

• Keep the medicine in a cupboard, away from heat and direct sunlight. It does not need to be kept in the fridge.
• Make sure that children cannot see or reach it.
• Keep the medicine in the container it came in.

Who to contact for more information

Your doctor, pharmacist or nurse will be able to give you more information about ferrous sulfate and about other medicines used to treat iron-deficiency anaemia.

Therapy “Comparative evaluation of chronic iron overload with the use of iron preparations in subtoxic doses

Comparative assessment of chronic iron overload with the use of iron preparations in subtoxic doses

O.A. Nazarenko, O.A. Gromova, V.I. Demidov, I. Yu. Torshin, I.K. Tomilova, E.L. Aleksakhina

FGBOU VO “Ivanovo State Medical Academy”, 1 Department of Pharmacology and Clinical Pharmacology,
2 research center, 4 departments of chemistry, g.Ivanovo
3 FSBEI HE “Moscow Institute of Physics and Technology (State University)”, Department of Intelligent Systems,
Dolgoprudny

Iron preparations used for the treatment of iron deficiency anemia differ in different safety levels. Unlike organic iron salts, such inorganic iron compounds as oxides, hydroxides and sulfates do not have high bioavailability and significantly increase the load of tissues with insoluble iron oxides. In this work, an experimental study of iron preparations based on iron hydroxide in the composition of the polymaltose complex (Maltofer®) and iron sulfate has been carried out.Oral administration of iron sulfate for 2 months caused chronic iron overload (systemic hemosiderosis), manifested as histological damage by hemosiderin to the parenchyma of the liver, kidneys and brain, and an increase in blood alanine aminotransferase levels and urinary protein levels. Compared with ferrous sulfate, Maltofer has advantages with long-term use: there were no hemosiderin deposits in the tissues of the kidneys and brain; in the liver, small deposits of hemosiderin were observed only in the intralobular sinus capillaries, but not in hepatocytes.

Literature

1. Dvoretsky L.I. Iron deficiency anemia. M .: Nyudiamed, 1998.37 p.
2. Stuklov N.I., Chistyakova A.V. Diagnostics and choice of treatment tactics for iron deficiency anemia in gastroenterological patients. Breast cancer. 2015; 13: 781-7.
3. Vorobiev A.I. Guide to Hematology. M .: Medicine, 1985.368 p.
4. Vorobiev P.A. Anemic syndrome in clinical practice. M .: Nyudiamed, 2001.168 p.
5. Gromova O.A., Torshin I.Yu., Khadzhidis A.K. Undesirable effects of ferrous sulfate in obstetric, pediatric and therapeutic practice. Zemsky doctor. 2010; 2: 1-8.
6. Gromova O.A., Torshin I.Yu., Minushkin O.N., Dibrova E.A., Karimova I.M. Kustov. E.V. On the effectiveness and molecular mechanisms of action of Laennec in the treatment of liver pathological conditions associated with iron deposition in the liver. Medical journal “Business of Life”. 2015; 1 (1): 44–51.
7. Tokarev Yu.N., Settarova D.A., Smetanina N.S., Maksimov V.A., Rumyantsev A.G. Iron overload diseases (hemochromatosis). Hands. for doctors. Ed. A.G. Rumyantseva, Yu.N. Tokarev. M .: Medpraktika-M, 2004.328 p.
8. Gromova O.A., Torshin I.Yu., Grishina T.R., Tomilova I.K. The value of using iron preparations and its molecular synergists for the prevention and treatment of iron deficiency anemia in pregnant women. Russian Bulletin of Obstetrician-Gynecologist. 2015; 4: 85–94.
9. Sullivan J.L., Mascitelli L. Current status of the iron hypothesis of cardiovascular diseases.Recenti. Prog. Med. 2007; 98 (7-8): 373-7.
10. Geisser P., Baer M., Schaub E. Structure / histotoxicity relationship of parenteral iron preparations. Arzneimittelforschung. 1992; 42 (12): 1439–52.
11. WHO / NHD. Iron Deficiency Anaemia. Assessment, Prevention and Control: A guide for program managers, 2001.
12. Milovanova L., Milovanov Y., Kozlovskaya L. Iron (III) hydroxide polymaltozoate is a new generation drug for the treatment of iron deficiency anemia. Doctor. 2013; 1: 54-7.
13. Gromova O.A., Rakhteeenko A.Yu., Gromova M.A. Outpatient doctor’s reference book. Chapter “Iron deficiency anemia”. Moscow: Bionika-Media, 2015.573 p.

About the Authors / Correspondence

Olga Nazarenko, PhD, Associate Professor of the Department of Pharmacology and Clinical Pharmacology, Ivanovo State Medical Academy. Address: 153012, Ivanovo, Sheremetevsky pr., 8 Phone: (4932) 41-65-25

Gromova Olga Alekseevna, d.MD, Professor of the Department of Pharmacology and Clinical Pharmacology, Ivanovo State Medical Academy. Address: 153012, Ivanovo, Sheremetevsky pr., 8. Phone: (4932) 41-65-25. E-mail: [email protected]

Demidov Vadim Igorevich, Candidate of Medical Sciences, Senior Researcher Research Center of the Federal State Budgetary Educational Institution of Higher Education “Ivanovo State Medical Academy”. Address: 153012, Ivanovo, Sheremetevsky prospect, 8. Phone: (4932) 41-65-25

Torshin Ivan Yurievich, Ph.D. -technical Institute (State University) “.Address: 141701, Moscow region, Dolgoprudny, Institutskiy per., 9. Phone: (499) 135-24-89

Aleksakhina Elena Lvovna, Ph.D., scientific consultant of the Research Center, associate professor of the department chemistry FSBEI HE “Ivanovo State Medical Academy”. Address: 153012, Ivanovo, Sheremetevsky prospect, 8. Phone: (4932) 41-65-25

Tomilova Irina Konstantinovna, MD, head. Department of Chemistry, Ivanovo State Medical Academy. Address: 153012, g.

iron in obstetric, pediatric and therapeutic

practice

O.A. Gromova1, I. Yu. Torshin1, A.K. Hadjidis2

ARSC Institute of Micronutrients UNESCO, Moscow,

2GOU HPE “St. Petersburg State Pediatric Academy”

Iron deficiency anemia is a common occurrence in children, pregnant women, middle-aged and elderly people.Although mild forms of anemia are often almost asymptomatic, neglect of this condition leads to serious complications, reduces the quality and duration of life. For the treatment of iron deficiency anemia, it is necessary to use effective and safe iron preparations. This article analyzes the safety of the use of various generations of iron-containing drugs; provides the latest evidence from clinical studies on the adverse effects of obsolete pharmaceutical preparations based on ferrous sulfate.ha – anemia) implies a decrease in the concentration of hemoglobin in the blood, often against the background of a decrease in the number of red blood cells. In addition to the characteristic drops in hemoglobin and erythrocyte levels, anemias are characterized by a wide range of clinical manifestations: general weakness, rapid fatigue, tinnitus, headaches, dizziness, fainting, shortness of breath, palpitations. Attention is drawn to pallor and trophic disorders of the skin, hair loss, and increased tooth decay.

Anemia occurs in patients of all ages and conditions.Iron deficiency anemia is much more common in women than in men. This is due to menstruation and the fact that iron stores in the body of women are three times less than that of men. During pregnancy and lactation, a woman’s body requires iron in another

large quantities and iron deficiency anemia accounts for 75-95% of all anemias in pregnant women [1]. In newborns and young children, anemia is a consequence of the mother’s anemia during pregnancy.In preschool children and schoolchildren, anemia can develop for nutritional reasons (first of all, a lack of iron in the diet and helminthic invasion) and also as a result of a violation of the regime (insufficient stay in the fresh air, smoking parents, living in ecologically unfavorable areas, etc.) … In middle-aged and elderly people, even moderate anemia is associated with an increased risk of complications, which include cognitive and immune dysfunctions [2], cardiovascular diseases, decreased bone density (and, as a result, fractures) and, in general, increased mortality [2-5 ].

The clinical manifestations of iron deficiency anemia (IDA) are due to the biological roles of iron in the body. It is generally known that iron is an essential part of heme, a cofactor for many proteins. First of all, heme is a part of hemoglobin – the main transport protein of oxygen, which reversibly binds to oxygen in the capillaries of the lungs. In addition, heme forms the active center of numerous redox enzymes (cytochromes, etc.)). Since heme promotes redox processes, tissue hypoxia – anemia – prevails in patients with iron deficiency.

Analysis of the physiological context of oxygen transport in the body [6] indicates several possible mechanisms of anemia (ie, from a physiological point of view, functional oxygen deficiency): iron deficiency, disorders

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biosynthesis of heme, violation of the formation of red blood cells (erythropoiesis), too rapid destruction of red blood cells (hemolysis), blood loss, which inevitably leads to the loss of red blood cells, etc.e. Anemia is also common in patients with chronic inflammatory diseases [7].

Since there are a number of parallel mechanisms of the pathogenesis of anemia, therapy with iron preparations should be carried out only after the diagnosis of iron deficiency states. Mild anemia is diagnosed only by laboratory parameters, when the clinical signs characteristic of IDA are not expressed or absent at all. The most important biochemical indicator of iron deficiency is hemoglobin level.At screening, a mild degree of iron deficiency anemia in pregnant women is characterized by a decrease in hemoglobin to 110-90 g / l, an average – from 89 to 70 g / l, a severe one – 69 g / l or less.

Establishing an iron deficiency in a patient requires the appointment of special iron-containing preparations. A fairly popular misconception regarding iron supplements is the assertion that a drug for the treatment of IDA simply must contain iron and it does not matter in what form.In modern pharmacology, at least three generations of iron-containing preparations are known. It should be especially noted that the use of outdated forms of 1st generation iron, such as inorganic sulfate, chloride, hydroxide, is associated with significant side effects. This article discusses the fundamentals of the pharmacology of iron preparations.

Obsolete pharmacological forms of iron

Among the various forms of iron, sulfate has the highest toxicity [8].In 1991, the US Academy of Toxicology reported 3578 cases of iron sulfate poisoning in children under 6 years of age, with a mortality rate of 25%. Of course, in this case we are talking about ultra-high doses of ferrous sulfate (grams). However, as the studies cited below show, the toxic effects of ferrous sulfate are observed at much lower doses.

MEDLINE has more than 200 studies from 1983 to 2010 reporting unwanted side effects and complications when taking ferrous sulfate (ferrous sulfate).Side effects were observed in a very wide range of clinical manifestations, from diarrhea and nausea to allergies and anaphylactic shock, with dyspeptic disorders being the most common. It is known that when taken orally, ferrous sulfate can cause damage to the esophagus [9-12], including

injury to the sphincter [13], pronounced ulceration of the oral cavity [14], provocation of infectious diseases [15], severe skin complications – rash [16], and in isolated cases – anaphylactic shock [17].

Ferrous sulfate is a harsh irritant of the gastrointestinal tract, causing intense desquamation and necrosis of the intestinal epithelium. A study of 6 healthy volunteers showed that even a single dose of iron sulfate at a dose of 80 mg leads to oxidative damage to the small intestine [18]. When taking ferrous sulfate, inhibition of the production of protective gastric mucus was noted [19]. A study of 36 biopsies of the gastrointestinal tract from patients receiving ferrous sulfate revealed that 89% of biopsies showed the presence of glandular deposits on the epithelium of the gastrointestinal tract, 83% of biopsies showed the presence of ulcerative lesions of the mucosal layer [20].

Due to the fact that ferrous sulfate causes severe irritation and in some cases burns the gastrointestinal tract, such “therapy” can lead to increased bleeding of the gastrointestinal mucosa and further loss of iron through microbleeds. Such hemorrhages are especially dangerous in the elderly, as they provoke severe anemia.

A study of such hepatocytotoxic substances as doxorubicin, butylhydropyroxide, ferrous sulfate and sulfamaxol showed that all these agents worsen cell survival, reduce the levels of ATP, lactate dehydrogenase, caspase, aspart-aminotransferase, glutamate dehydrogenase [21].

A clinical study of 150 pregnant women aged 16-20 weeks showed that ferrous sulfate often causes diarrhea and epigastric pain. This effect is dose dependent [22]. Nausea, vomiting and constipation when using vitamin-mineral complexes with iron sulfate led to the fact that many women stopped taking such drugs. A follow-up of 453 women taking iron supplements in the II and III trimester of pregnancy showed that ferrous sulfate had the greatest number of side effects, including constipation and nausea: for this reason, 83 women stopped taking the drug [23].

In the light of the results of numerous studies cited above, the statements that “iron sulfate is a reference agent in terms of efficacy and safety, intended for the prevention of both latent and overt iron deficiency anemia” seem very unconvincing. Firstly, as such, the prevention of IDA was canceled a long time ago, even at the WHO level, and is currently considered a violation of patient management.Secondly, such statements are never, as a rule, confirmed even by citing any research publications.

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Congenital malformations, heart defects, dysmorphism can be a direct consequence of the use of ferrous sulfate during pregnancy. Data on the teratogenic effect of ferrous sulfate on the developing fetus are given in the work of the head of the Federal Center for Monitoring the Safety of Medicines V.K. Lepakhin [24]. When conducting tests for toxicity of ferrous sulfate according to the GLP system, the dose of 50% lethality (LD50) for rats when taking ferrous sulfate orally is ~ 320 mg / kg (according to the CAS database, www.cas.org). For comparison: a compound such as protein iron succinylate (see below) is 12.5 times less toxic – LD50 in rats was 4000 mg / kg when taken orally, according to the CAS database.

A study of the effects of ferrous sulfate on the behavior of adult rats showed that even very moderate doses (3 mg / kg for 5 days) led to a decrease in neurological parameters in the maze, open field and learning tests.Animal brain studies have shown significant accumulation of inorganic iron in the hippocampus and basal ganglia. Thus, even a moderate intake of ferrous sulfate in a short course disrupts the protection of the brain from intoxication with inorganic iron, which leads to behavioral disturbances and changes in the emotional background due to the development of neurological deficits [25].

Thus, ferrous sulfate should be treated as a potential toxicant.Due to the high toxicity since 2009, preparations for pregnant women containing ferrous sulfate are no longer registered in Russia.

Pharmacotherapy for iron deficiency states

It is obvious that the pathogenetic therapy of IDA is the use of iron preparations. However, as shown by our earlier analysis [6], the biological functions of iron can be inhibited in the absence of a number of micronutrients (especially Zn, Mn, Cu, Mo, Cr, I, vitamins C, B2, B6, Bc, B12).Therefore, in order to carry out the most successful and safe pharmacotherapy of iron deficiency states, both the interactions between these micronutrients and the most acceptable pharmaceutical forms of iron should be considered.

Firstly, there is an obvious synergy, that is, an increase in efficiency when iron and these micronutrients are used together. In particular, ascorbic acid activates the absorption of iron preparations by more than 30%.Since vitamins such as B2, B6, C, necessary to maintain the functions of iron, are present in most vitamin-mineral complexes (IUDs), it is recommended to supplement therapy with iron preparations with standard IUDs,

produced from high quality pharmaceutical substances.

Secondly, despite the synergy between trace elements at the level of physiological systems and specific proteins, there is also a certain pharmacokinetic antagonism between iron, zinc, copper, molybdenum and manganese.Iron, copper, magnesium impair zinc absorption. Molybdenum increases urinary copper loss, and zinc can compete with copper for absorption [27]. From these pharmacokinetic antagonisms, it is clear that the combined intake of iron, copper and manganese is most acceptable (pharmacokinetic antagonism is minimal), and zinc and molybdenum should be taken separately from iron, copper and manganese.

Third, when choosing an iron supplement, remember the fundamental difference between the three ferrous iron.For more than 100 years, an indisputable fact has been known in chemistry: in solution, ferrous iron is a reducing agent, and ferric iron is an oxidizing agent [28]. Under normal conditions, +3 is the highest oxidation state of iron in solution, so that ferric iron can never be a reducing agent in the body. Studies of cells in culture showed that the levels of antioxidant enzymes superoxide dismutase and glutathione were much higher in cells treated with ferrous rather than ferric iron [29]. In addition, ferrous iron was absorbed more efficiently than trivalent (p <0.05), since enterocytes absorb iron through the previously mentioned proteins - ferrous metal transporters [30].Therefore, ferric iron must be reduced to ferrous (for example, when taken together with ascorbic acid), which will allow it to be more efficiently absorbed by cells.

Fourthly, one should remember about the most acceptable pharmaceutical forms of iron and other trace elements. Sulfates and other inorganic compounds of iron, copper, manganese and other macro- and microelements represent the first generation of element-containing preparations [31].More advanced drugs are based on organic compounds (usually salts), which have a higher digestibility and better tolerance. Examples of iron preparations of various generations are given in table. 1, more detailed information on iron preparations is presented in table. 2.

Unfortunately, as can be seen from the table. 1 and 2, most drugs use ferrous sulfate, which is not highly bioavailable and, as noted earlier, is characterized by numerous side effects.Therefore, WHO currently strongly recommends that pregnant women and children, patients with gastrointestinal tract pathology, elderly people with anemia use gluconate-based drugs,

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magazine “Zemsky Doctor” No. 2-2010 41

Table 1. Generations of iron-containing preparations

Generation Peculiarities of preparations Examples of preparations

I Inorganic forms (salts, oxides) Aktiferrin, Hemofer Polongatum, Tardiferon, Sorbifer durules, Hemofer, Conferon, Maltofer, Ferbitol, Ferrocal, Ferroplex, Ferrum-lek

II Organic salts of Iron gluconate, Ferronate, Heferol

III Organic forms of trace elements in combination with synergistic components Hemostimullin, Totem, Ferlatum

ferrous fumarate or other safe organic iron salts [24].Preparations based on ferrous sulfate are partially (categories of patients: pregnant women, children suffering from gastrointestinal diseases) are prohibited in France, Sweden, Switzerland, Finland. Since 2009, ferrous sulfate preparations for use in pregnant women have also been banned from registration in Russia, since it causes congenital fetal anomalies and gastrointestinal disorders in pregnant women and in women with gastrointestinal tract pathology [24].

Fifth, oral iron preparations are preferred over copper –

parenteral chambers.The therapeutic effect of iron preparations prescribed physiologically, that is, pei os, occurs somewhat later than when administered intravenously or intramuscularly, but side effects when administered orally occur much less frequently.

Sixth, the dosage of the drug is naturally of great importance for the effectiveness and safety of therapy. In the norms of the Russian Federation * 2008, in the physiological course of pregnancy and in the absence of anemia, all pregnant women in the second half of pregnancy, starting from the 18-20th week, are recommended to take iron preparations at a dose of 15-18 mg / day, with the established IDA, iron consumption may be higher (30-180 mg / day).

It is necessary to distinguish between drugs that have a real biological basis and inept counterfeits for biology. For example, the combination of iron hydroxide with polymaltose has been known for a long time. Such a mixture is a first generation drug, since (1) potentially toxic inorganic iron compounds (hydroxide or oxides) are used, which (2) are intended for use in a mixture with polysaccharides. Iron against the background of polysaccharides is a combination unknown in biology, since in natural food iron is supplied and absorbed against a background of a high concentration of proteins, and not against a background of a high concentration of fats or carbohydrates.The ineffectiveness of oral drugs such as a mixture of polymaltose with iron hydroxide was illustrated in the series

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Table. 2. Iron preparations for the treatment of iron deficiency anemia

Preparation Pharmacological form of iron Element. iron, mg Dosing regimen

I generation

Ferroplex 50 mg iron (II) sulfate 16 1-2 pills / day

Aktiferrin 11.85 mg iron (II) sulfate 34.5 1 caps.2-3 r / day

Fefol 150 mg iron (II) sulfate 50 1 caps / day

Conferon 250 mg ferrous sulfate (II) 50 1-2 caps. 3 r / day

Ferrocal 200 mg of iron (II) sulfate 67 2-6 tablets / day

Tardiferon 256 mg iron (II) sulfate 80 1-2 tab. 1-2 p / day

Sorbifer durules 320 mg of iron (II) sulfate 100 1 pills 1-2 r / day

Ferrogradumet 325 mg of iron (II) sulfate 105 1 tab./ day

Hemofer 325 mg of iron (II) sulfate 105 1 tablet / day

II generation

Ferronate 200 mg ferrous fumarate 67 1 caps. 3 r / day

Heferol 350 mg ferrous fumarate 115 1 caps. 3 r / day

III generation

Ferlatum 800 mg iron protein succinylate 40 1 amp./ day

Totem 360 mg iron gluconate, in a synergistic composition with manganese gluconate and copper gluconate 50 2-4 amp. / Day

Hemostimullin 246 mg iron lactate 60 1 tab. 3 r / day

* Norms of physiological needs for energy and nutrients for various groups of the population of the Russian Federation, Methodological recommendations MR 2.3.1.2432-08, approved Head of the Federal Service for Supervision of Consumer Rights Protection and Human Welfare, Chief State Sanitary Doctor of the Russian Federation G.G. Onishchenko. M., 2008, 43 p.

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de studies even in the case of iron deficiency anemia, when, it would seem, the absorption of any form of iron should increase [32, 33].

Conclusion

Iron is a vital micronutrient.The provision of iron, as well as other essential micronutrients, is the basis of a healthy diet at any age: for children, adults and the elderly. With an established iron deficiency, the patient needs not only diet correction, but also treatment using effective and safe drugs. A normal iron supply in such patients improves the quality and longevity of life.

Due to its low cost and inertia, ferrous sulfate is widely used in preparations for the treatment of IDA and in vitamin-mineral complexes.However, the accumulated data on the undesirable effects of taking drugs based on ferrous sulfate leads to the fact that the world medical community is moving away from prescribing ferrous sulfate to pregnant women, therefore, outdated drugs based on it fill the Russian market.

Currently, there is a move away from the use of outdated forms of inorganic iron, which cause numerous undesirable effects, primarily dyspeptic. In pediatrics and obstetrics, an active transition to the use of safer and more effective preparations based on organic iron (protein succinylate, iron lactate, iron gluconate, etc.) is especially noted.). Some progress is also observed in the accompaniment of therapy for iron deficiency anemia with synergistic iron micronutrients: copper, manganese, vitamin C, pyridoxine, etc.

Literature

1. Gromova O.A. Vitamins and minerals in pregnant and lactating women. UNESCO training programs. M., 2007.140 s.

2. Penninx B.W., Guralnik J.M., Onder G., Ferrucci L., Wallace R.B., Pahor M. Anemia and decline in physical performance among older persons // Am J Med. 2003; 115 (2): 104-110.

3. Balducci L. Epidemiology of anemia in the elderly: information on diagnostic evaluation // J Am Geriatr Soc. 2003; 51 (3) Suppl: S2-S9.

4. Eisenstaedt R /, Penninx B.W., Woodman R.C. Anemia in the elderly: current understanding and emerging concepts // Blood Rev.2006; 20 (4): 213-26.

5. Kanadys W.M. Postpartum body weight change // Ginekol Pol. 1998; 69 (7): 570-574.

6. Gromova O.A., Torshin I.Yu., Khadzhidis A.K. Systematic analysis of the molecular mechanisms of the effects of iron, copper, manganese in the pathogenesis of iron deficiency anemia // Clinical Pharmacology. 2010. No. 3.

7. Portillo K., Belda J., Anton P, Casan P High frequency of anemia in COPD patients admitted in a tertiary hospital // Rev Clin Esp. 2007; 207 (8): 383-387.

8. Markova I.V., Afanasyev V.V., Tsybulkin E.K. Clinical toxicology of children and adolescents. SPb .: Intermedika, 1999.399 p.

9. Cerezo A., Costan G., Gonzale A., Galvez C., Garcia V., Iglesias E., Reye A., DE

Dios J.F Severe esophagitis due to overdose of iron tablets // Gastroenterol Hepatol. 2008; 31 (8): 551-552.

10. Areia M., Gradiz R., Souto P, Camacho E., Silva M.R., Almeida N., Rosa A., Xavier da Cunha M.F., Leitao M.C. Iron-induced esophageal ulceration // Endoscopy. 2007; 39 Suppl 1: E326.

11. Zhang S.T., Wong W.M., Hu W.H., Trendell-Smith N.J., Wong B.C. Esophageal injury as a result of ingestion of iron tablets // J Gastroenterol Hepatol.2003; 18 (4): 466-467.

12. Jaspersen D. Drug-induced oesophageal disorders: pathogenesis, incidence, prevention and management // Drug Saf. 2000; 22 (3): 237-249.

13. Belavic J.M. A new treatment option for type 2 diabetes // Nurse Pract. 2010; 35 (1): 51-52.

14. Jones T.A., Parmar S.C. Oral mucosal ulceration due to ferrous sulphate tablets: report of a case // Dent Update.2006; 33 (10): 632-633.

15. Eisenhut M. Exacerbation of infectious diseases by iron supplementation // J Pediatr (Rio J). 2007; 83 (1): 95; author reply 95.

16. Rogkakou A., Guerra L., Scordamaglia A., Canonica G.W., Passalacqua G. Severe skin reaction due to excipients of an oral iron treatment // Allergy. 2007; 62 (3): 334-335.

17.de Barrio M., Fuentes V., Tornero P, Sanchez I., Zubeldia J., Herrero T. Anaphylaxis to oral iron salts. desensitization protocol for tolerance induction // J Investig Allergol Clin Immunol. 2008; 18 (4): 305-308.

18. Troost FJ., Saris W.H., Haenen G.R., Bast A., Brummer R.J. New method to study oxidative damage and antioxidants in the human small bowel: effects of iron application // Am J Physiol Gastrointest Liver Physiol. 2003; 285 (2): G354-9 Epub 2003 Ap.

19. Ji H., Yardley J.H. Iron medication-associated gastric mucosal injury // Arch Pathol Lab Med. 2004; 128 (7): 821-822.

20. Abraham S.C., Yardley J.H., Wu T.T. Erosive injury to the upper gastrointestinal tract in patients receiving iron medication: an underrecognized entity // Am J Surg Pathol. 1999; 23 (10): 1241-1247.

21.Gerets H. H., Hanon E., Cornet M., Dhalluin S., Depelchin O., Canning M., Atienzar FA. Selection of cytotoxicity markers for the screening of new chemical entities in a pharmaceutical context: a preliminary study using a multiplexing approach // Toxicol In Vitro. 2009; 23: 319-32.

22. Souza A.I., Batista Filho M., Bresani C.C., Ferreira L.O., Figueiroa J.N. Adherence and side effects of three ferrous sulfate treatment regimens on anemic pregnant women in clinical trials // Cad Saude Publica.2009; 25 (6): 1225-1233.

23. Melamed N., Ben-Haroush A., Kaplan B., Yogev Y Iron supplementation in preg-nancy-does the preparation matter? // Arch Gynecol Obstet. 2007; 276 (6): 601-4.

24. Astakhova A.V., Lepakhin V.K. Medicines. ADVERSE REACTIONS AND SAFETY CONTROLS. Series: Professional Medicine. M., Eksmo, 2008.

25.Maaroufi K., Ammari M., Jeljeli M., Roy V., Sakly M., Abdelmelek H. Impairment of emotional behavior and spatial learning in adult Wistar rats by ferrous sulfate // Physiol Behav. 2009; 96 (2): 343-9 Epub 2008 Nov,

26. Cheney K., Gumbiner C., Benson B., Tenenbein M. Survival after a severe iron poisoning treated with intermittent infusions of deferoxamine // J Clin Toxicol. 1995; 33 (1): 61-6.

27.Rebrov V.G., Gromova O.A. Vitamins, macro- and microelements. M .: Geo-tarMed, 2008, 956 p.

28. Khomchenko GP. Chemistry manual for university applicants. M .: Novaya Volna, 2007.

29. He W.L., Feng Y, Li X.L., Wei YY, Yang X.E. Availability and toxicity of Fe (II) and Fe (III) in Caco-2 cells // J Zhejiang Univ Sci B. 2008 Sep; 9 (9): 707-12.

30.Thomas C., Oates PS. Differences in the uptake of iron from Fe (II) ascorbate and Fe (III) citrate by IEC-6 cells and the involvement of ferroportin / IREG-1 / MTP-

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1 / SLC40A1 // Pflugers Arch. 2004 Jul; 448 (4): 431-7. Epub 2004 Apr 28.

31. Gromova O.A., Kudrin A.V. Neurochemistry of macro- and microelements. M .: Alev-V, 2001.230 p.

32. Ruiz-Arguelles G.J., Diaz-Hernandez A., Manzano C., Ruiz-Delgado G.J. Ineffectiveness of oral iron hydroxide polymaltose in iron-deficiency anemia // Hematology. 2007; 12 (3): 255-256.

33. Nanivadekar A.S. Ineffectiveness of iron polymaltose in treatment of iron deficiency anemia // J Assoc Physicians India.2003; 51: 928-9; author reply.

Adverse effects of iron sulfate in obstetrics, pediatrics and therapeutics

O.A. Gromova1,1.Yu. Torshin1, A.K. Hadzhidis2

‘Russian Satellite Center of UNESCO Institute of microelements, Moscow

2St. Petersburg State Pediatric Academy, St.Petersburg

Iron deficiency anemia is a frequent condition in children, pregnant women, people of middle and old age. Although mild forms of anemia often exist almost without symptoms, neglect of this condition leads to severe complications, reduces the quality and length of life. For treatment of iron deficiency anemia must use effective and safe iron-containing drugs. This article analyzes the safety of the various generations of iron-containing products and contains the latest findings from clinical studies on adverse effects of outdated pharmaceuticals based on iron sulphate.s ———

Outcomes of the III Global Incontinence Forum

At the end of April this year, the III Global Forum on Incontinence was held in Prague, the participants of which identified a common problem: the prevention and treatment of urinary incontinence is still not given adequate attention. According to experts, insufficient funding for various kinds of urological programs leads to a decrease in the level of medical literacy of the population and the lack of clear preventive measures.In addition, the forum participants noted that poor understanding of incontinence issues is observed among health workers themselves, as a result of which doctors prescribe ineffective treatment to patients.

Incontinence: economic and moral losses

Urinary incontinence is a serious global problem, affecting up to 25% of women (over 35 years old) worldwide and 5% of men. With age, the number of patients increases.However, in the health sector, the issue of incontinence continues to receive insufficient attention.

“Incontinence has serious consequences,” says Diane Newman, co-director of the Center for Pelvic and Excretory Health in the Department of Urology at the University of Pennsylvania Medical Center (USA).

According to Lyudmila Dmitrievna Serova, professor, doctor of medical sciences, deputy director of the Russian Gerontological Research and Clinical Center, “In Russia, the problem of incontinence is very poorly resolved.Alas, in most cases our women suffering from this ailment simply do not know where to turn for help. ”

Research

In March this year, commissioned by SCA Hygiene Products, the world’s leading manufacturer of lich-

hygiene, a study was conducted to find out how primary care physicians feel about incontinence and what treatments they have.More than 500 therapists from France, Poland and the UK took part in the study. As a result, it was found that only 5% of those surveyed have extensive experience and knowledge of the problem of incontinence and are confident in prescribing treatment. At the same time, more than half of the respondents noted that today, in their opinion, there is no integrated incontinence treatment program that they could follow.

Among the main reasons hindering the development and improvement of the quality of medical services in this area, the research participants named the following:

• lack of access to social services;

• small number of experts in the field of urinary incontinence;

• lack of education and professionals in this

area.

Diane Newman commented on the results of the study: “It is absolutely clear that therapists need a clear treatment regimen for incontinence, which has not yet been worked out.”

Continuing the theme raised by D. Newman, L.D. Serova noted that “the topic of incontinence is very sensitive, today it removes the patient from society. However, with a proper approach to this problem, it can be successfully solved by joint efforts. “Further, Lyudmila Dmitrievna Serova cited the example of the Russian Gerontological Research and Clinical Center, in which special consulting rooms have been opened, where the patient himself and his relatives can receive the necessary knowledge and skills on how to cope with the disease.

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PHARMATEKA »Comparative assessment of chronic iron overload when using iron preparations in subtoxic doses

Iron preparations used for the treatment of iron deficiency anemia differ in their safety.Unlike organic iron salts, such inorganic iron compounds as oxides, hydroxides and sulfates do not have high bioavailability and significantly increase the load on tissues with insoluble iron oxides. In this work, an experimental study of iron preparations based on iron hydroxide in the composition of the polymaltose complex and iron sulfate has been carried out. Oral administration of ferrous sulfate for 2 months caused chronic iron overload (systemic hemosiderosis), manifested as histological damage by hemosiderin to the parenchyma of the liver, kidneys and brain, and an increase in blood alanine aminotransferase levels and urinary protein levels.Compared with ferrous sulfate of iron (III), polymaltose hydroxide has advantages in long-term use: there were no hemosiderin deposits in the tissues of the kidneys and brain; in the liver, small deposits of hemosiderin were observed only in the intralobular sinus capillaries, but not in hepatocytes.

Introduction

Anemia is established when the hemoglobin concentration is less than 120 g / l in non-pregnant women and less than 130 g / l in men. According to the World Health Organization, 2 billion people worldwide suffer from anemia, 80–90% of these conditions are associated with iron deficiency (iron deficiency syndromes), and more than half is iron deficiency anemia (IDA).

In Russia, according to the Ministry of Health, 15% of the population suffers from anemia [1, 2].

For the treatment of IDA, preparations containing iron are prescribed: organic salts (for example, ferrous fumarate, etc.), inorganic salts (for example, ferrous sulfate, so-called ferrous sulfate), polymaltose complexes with iron hydroxides, etc. At the same time over the past decades, the practice of long-term intake (months and years) of multicomponent micronutrient complexes containing ferrous sulfate has developed. We can say that IDA scared doctors so much that a kind of mania for the universal use of micronutrient complexes (usually containing iron sulfate) arose in order to prevent non-existent IDA [3, 4].

However, it is well known from clinical practice that iron-containing (ferrous sulfate) preparations can cause various side effects – constipation or, conversely, diarrhea, epigastric pain, nausea, vomiting, and sometimes liver dysfunction [5].

Bivalent iron (Fe2 +) in the composition of iron sulfate is easily oxidized to prooxidant ferric iron (Fe3 +), which, spreading throughout the body, contributes to the increased formation of hemosiderosis (i.e. non-physiological and insoluble deposits of iron oxides in tissues, i.e.n. hemosiderin) [6].

Hemosiderosis affects organs in the following sequence: liver, myocardium, skeletal muscles, kidneys, brain, organs of vision, joints [7]. Thus, the liver suffers from hemosiderosis in the first place. Normally, the liver is a depot of iron, in which it is stored in the form of tightly packed ferritin granules, excluding the contact of Fe2 + ions with oxidizing agents and with hepatocyte membranes.

When using inorganic forms of iron, Fe2 + ions are oxidized to Fe3 + with the formation of hemosiderin, a dark yellow pigment that includes a mixture of iron oxides with denatured proteins.Denatured proteins activate autoimmune reactions, which, along with the prooxidant properties of ferric iron, supports chronic inflammation, causes damage to the liver parenchyma and its replacement with dysfunctional fibrous tissue. Excessive accumulation of iron in the liver in the form of hemosiderin significantly slows down the process of liver regeneration, which provokes the development of liver cirrhosis and damage to other organs (heart, kidneys, brain, etc.).

The purpose of this study was a comparative assessment of the development of chronic iron overload with long-term use of drugs based on iron sulfate and polymaltose iron complex.

Material and methods

The study was carried out on 30 white rats weighing 200-250 g, divided into 3 groups. Group 1 (n = 10) served as an intact control. Group 2 (n = 10) received ferrous sulfate in the actiferrin syrup, which was selected for the convenience of probing. The syrup was introduced into the stomach through a tube at a dose of 0.6 ml / kg. Group 3 (n = 10) received iron (III) hydroxide polymaltose in the form of a syrup at a dose of 0.5 ml / kg into the stomach through a tube. Iron preparations were administered daily for 2 months.

2 months after the administration of the preparations, the animals were placed for a day in exchange cells to determine the excretory function of the kidneys, after which they were guillotined. On day 0 and day 60, the activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST), the levels of bilirubin, total protein and creatinine were determined in the blood, and the protein concentration in urine (using standard kits). On day 61, the liver, kidneys and brain were taken for histological examination; in the pathological laboratory, iron in the tissue was determined using the Prussian blue reaction.After craniotomy, the entire brain was removed, and the liver and kidneys were also eviscerated.

For histological analyzes, all organs were fixed in a 10% solution of neutral formalin. The tissue was guided according to the standard scheme (dehydration in ethyl alcohol, xylene), followed by the manufacture of paraffin blocks. Histological sections with a thickness of 6 µm prepared on a Microm microtome were stained with hematoxylin and eosin. Duplicate sections were stained according to Perls using the Biovitrum reagent kit to detect ferric iron in the tissues.The result of the reaction was the formation of an insoluble colored iron salt, the so-called. Prussian blue (4Fe³ + 3K4Fe (CN) 6 → Fe4 (Fe (CN) 6) 3). The morphological examination of histological sections was carried out on an image analyzer “BioVision” (Austria), micrographs were obtained using a research microscope “Micros MC 200” and a digital eyepiece camera DCM 900. Statistical processing of the obtained data was carried out using the Statistica 6 program. Differences between the groups were considered statistically significant at p <0.05.The data in the table are presented as M ± m.

Research results

On day 0, no differences were found between groups in all biochemical parameters studied. A biochemical blood test performed on day 60 showed that long-term use of iron sulfate has a damaging effect on hepatocytes, which is confirmed by a significant increase in ALT activity (see table, Fig. 1), while the use of polymaltose iron complex did not increase ALT levels.

In addition, while taking iron sulfate, renal function also changed: there was a slight increase in urine output when using iron (III) hydroxide polymaltose (possibly of a compensatory nature – to accelerate the excretion of iron salts), as well as proteinuria, which was statistically significant. Thus, the use of ferrous sulfate has been associated with impaired liver function.

Histological examination of the sectional material (liver, kidneys, brain) confirmed the results of biochemical studies and showed significant damage to the liver parenchyma against the background of hemosiderosis.

Histological examination of the tissues of intact animals showed that the formation of Prussian blue was not observed in the brain and kidneys during the Perls reaction. Histological examination of liver tissue showed that in all 10 samples the cytoplasm of hepatocytes contained evenly distributed fine iron-containing granules, which is most likely explained by the normal metabolism of hepatocytes with the formation of transferrin (Fig. 2).

In 10 out of 10 animals treated with ferrous sulfate, pronounced pathohistological changes in liver tissue were found.Despite the plethora of the central veins and sinusoids, the precentral zone of the hepatic lobules, hepatocytes were in a state of moderately pronounced hydropic (vacuole) dystrophy (Fig. 3A, 3B). The Perls reaction made it possible to reveal large inclusions of Prussian blue crystals in the parenchyma and partially in the cytoplasm of hepatocytes located near the central vein (Fig. 3B).

In animals treated with ferrous sulfate, examination of the brain using the Perls reaction revealed focal formation of Prussian blue in the subependymal region (paraventricular zone) of the left cerebral hemisphere (Fig.4A). In the kidneys of 2 out of 10 animals, the Pearls reaction gave a weakly positive result, which was expressed by the formation of fine granules of Prussian blue in the cytoplasm of the nephrocytes of the proximal convoluted tubules (Figs. 4B and 4C).

Pathohistological changes in the liver in rats receiving iron (III) hydroxide polymaltose at the maximum dose were characterized by focal vacuolar degeneration of hepatocytes in the central zone of the hepatic lobule. The Perls reaction turned out to be weakly positive and was expressed by staining with Prussian blue of the walls of intralobular sinusoidal blood capillaries (diffuse spots of Prussian blue), single small granules of Prussian blue in the parenchyma (Fig.five). In the study using the Pearls reaction of the brain and kidneys of rats treated with iron (III) hydroxide polymaltose, the formation of Prussian blue was not observed in any of the animals.

Thus, histological examination showed that long-term (within 2 months) use of ferrous sulfate led to severe hemosiderosis of the parenchyma of the liver, brain and kidneys. Severe hemosiderosis of the liver parenchyma with prolonged use of iron sulfate was accompanied by more noticeable degenerative changes in hepatocytes.When taking iron (III) hydroxide polymaltose, there was a very low deposition of hemosiderin in the liver, less damage to the liver (lower ALT levels) and kidney (less pronounced proteinuria), which confirms the low toxicity of polymaltose complexes [10].

Conclusion

Due to the wide range of biological roles of iron, iron deficiency in the body must necessarily be compensated. Unfortunately, at present, two radical positions prevail in the scientific and medical environment, which can be conditionally called “ultra-right” and “ultra-left”.

The “ultra-left” position, presented mainly in Western literature, appeals to the complete rejection of the appointment of any iron-containing drugs, since “Iron overloads the body and shortens the life span” and in general – “there is enough iron in food.” In this case, no distinction is made between the pharmacological forms of iron. This “ultra-left” approach gives rise to massive phobias in relation to iron preparations and, naturally, contributes to the widest spread of IDA, especially among pregnant women, children and elderly patients.

For example, in the medical press one can even come across downright extremist proposals about the need for “complete depletion of iron for the primary prevention of cardiovascular diseases in elderly patients” [9]. It is surprising how often the fundamental provisions of cardiology and neurology that “ischemia is a lack of oxygen” can be forgotten …

The “ultra-right” position is intimidation by iron deficiency to such an extent that widespread long-term “prophylactic” prescription of iron preparations is carried out (again, without considering the differences between the pharmacological forms of iron).As a result of such “prevention”, especially with the use of rather toxic iron sulfate, there is a real “overload” of the body with iron, i.e. the formation of hemosiderosis in various tissues of the body.

The present study shows the inconsistency of this “ultra-right” position and emphasizes the importance of accounting for differences between the pharmacological forms of iron preparations. The use of such an outdated pharmacological form of iron as ferrous sulfate necessarily leads to the deposition of hemosiderin in hepatocytes along the sinusoidal capillaries, and also to dystrophic changes in hepatocytes.Damage to the liver parenchyma by iron sulfate is confirmed by an increase in the level of the hepatic enzyme ALT in the blood.

In a number of cases, hepatic hemosiderosis is accompanied by systemic hemosiderosis affecting the parenchyma of the kidneys, brain, etc. The polymaltose form of iron, when used even at maximum doses and with prolonged use, has an advantage in terms of safety: no damage to hepatocytes, liver dysfunction, no hemosiderosis in brain and kidney, thus, the drug has a favorable safety profile for different categories of patients.

1. Butler L. I. Iron deficiency anemia. M., 1998.37 p.

2. Stuklov N.I. Chistyakova A.V. Diagnostics and choice of treatment tactics for iron deficiency anemia in gastroenterological patients. Breast cancer. 2015; 13: 781–87.

3. Vorobiev A.I. Guide to Hematology. M., 1985.

4. Vorobiev P.A. Anemic syndrome in clinical practice. M., 2001.168 p.

5. Gromova O.A., Torshin I.Yu., Khadzhidis A.K. Undesirable effects of ferrous sulfate in obstetric, pediatric and therapeutic practice.Zemsky doctor. 2010; 2: 1-8.

6. Gromova OA, Torshin I.Yu., Minushkin O.N., Dibrova E.A., Karimova I.M. Kustov. E.V. On the effectiveness and molecular mechanisms of action of the drug “Laennec” in the treatment of pathological conditions of the liver associated with the deposition of iron in the liver. Medical journal “Business of Life”. 2015; 1 (1): 44–51.

7. Tokarev Yu.N., Settarova D.A., Smetanina N.S., Maksimov V.A., Rumyantsev A.G. Iron overload diseases (hemochromatosis). Guidelines for Physicians / Ed.A.G. Rumyantseva, Yu.N. Tokarev. M., 2004.328 p.

8. Gromova O.A., Torshin I.Yu., Grishina T.R., Tomilova I.K. The value of using iron preparations and its molecular synergists for the prevention and treatment of iron deficiency anemia in pregnant women. Russian Bulletin of Obstetrician-Gynecologist. 2015; 4: 85–94.

9. Sullivan J.L., Mascitelli L. Current status of the iron hypothesis of cardiovascular diseases. Recenti. Prog. Med. 2007; 98 (7-8): 373-77.

10. Geisser P., Baer M., Schaub E. Structure / histotoxicity relationship of parenteral iron preparations. Arzneimittelforschung. 1992; 42 (12): 1439–52.

O.A. Gromova – Doctor of Medical Sciences, Prof. Department of Pharmacology and Clinical Pharmacology, Ivanovo State Medical Academy, Ministry of Health of the Russian Federation, Russian Collaborating Center of the Institute of Microelements under the auspices of UNESCO at the State Budgetary Educational Institution of Higher Professional Education RNMU named after N.I. Pirogov of the Ministry of Health of the Russian Federation; e-mail: [email protected]

489 02.11.2012 – ClinLine

P-Monofer-CKD-02 protocol

Protocol name
A randomized, open-label Phase III study comparing intravenous iron isomaltoside 1000 (Monofer®) given as an infusion or repeated bolus injections and oral ferrous sulfate in patients with dialysis-independent chronic renal failure and anemia with chronic renal failure

Therapeutic area

Nephrology

CI start and end date
02.11.2012 – 30.06.2014

RCT number and date
No. 489 dated 02.11.2012

Drug name
Monofer® (Iron Isomaltoside 1000)

Dosage form and dosage
10% solution in 5 ml vials

Cities
Moscow, Petrozavodsk, Rostov-on-Don, St. Petersburg

Developer country
Denmark

Organization involved by the drug developer
LLC “EastHorn Clinical Sevises in SII”, 191002, St.St. Petersburg, st. Marata, house 47-49, letter A

CI phase
III

KI type
IMCI

The purpose of CI
The main objective of the study: • To demonstrate that intravenous iron isomaltoside 1000 (Monofer®) is as effective as oral ferrous sulfate in reducing renal anemia in subjects with dialysis-independent chronic renal failure (DN-CRF), with efficacy defined as ability increase Hb levels Additional Study Objectives: • To assess other relevant hematologic and biochemical parameters throughout the study.• Assess quality of life (QOL) based on a linear analogue scale (LAS). • Evaluate the safety of intravenous iron isomaltoside 1000 (Monofer®) versus oral iron sulfate. • Assess RLS symptoms and changes in these symptoms over the course of the study

Number of medical institutions
nine

Number of patients
140

Iron supplement

Iron , also known as iron salts and iron tablets , are a range of iron compositions used to treat and prevent iron deficiency including iron deficiency anemia.For prevention, they are only recommended for those with poor absorption, heavy menstrual periods, pregnancy, hemodialysis, or a diet low in iron. Prophylaxis can also be applied to low birth weight infants. They are taken orally, injected into a vein, or injected into a muscle. While benefits can be seen within a few days, it can take up to two months for iron levels to return to normal.

Common side effects include constipation, abdominal pain, dark stools, and diarrhea.Other side effects that can occur with overuse include iron overload and iron toxicity. Black salts used as oral supplements include ferrous fumarate, ferrous gluconate, ferrous succinate, and ferrous sulfate. Injectable forms include gland dextrans and iron sucrose. They work by providing iron for the production of red blood cells.

Iron tablets have been used in medicine since at least 1681, and an easy-to-use formulation was created in 1832.They are included in the World Health Organization’s List of Essential Medicines. Iron salts are available as a generic medicine and without a prescription. Slow-release formulations, although available, are not recommended. In 2017, ferrous sulfate was the 92nd most commonly prescribed drug in the United States, with over eight million prescriptions.

Medical use

Iron supplements are used to treat iron deficiency and iron deficiency anemia; parenteral irons can also be used to treat functional iron deficiency when iron requirements exceed the body’s ability to supply iron, such as in inflammatory conditions.The main criterion is that other causes of anemia have also been investigated, such as vitamin B ₁₂ or folate deficiency caused by drugs or other poisons such as lead, as often anemia has several underlying causes.

Iron deficiency anemia is usually microcytic hypochromic anemia. Typically in the UK, oral medications are tested before parenteral delivery. except in cases where a rapid response is required, a previous intolerance to oral iron, or the likely ineffectiveness of the response.Intravenous iron can reduce the need for blood transfusions, but it increases the risk of infections compared to oral iron. A 2015 Cochrane Collaboration review found that daily oral iron supplementation during pregnancy reduces the risk of maternal anemia and that the impact on the baby and other outcomes for the mother is unclear. Another review found preliminary evidence that intermittent oral iron supplementation is similar for mothers and babies to daily supplements with fewer side effects.Oral supplements should be taken on an empty stomach, with a small amount of food if desired, to reduce discomfort.

Athletes

Athletes may be at increased risk of iron deficiency and therefore benefit from supplementation, but circumstances vary from person to person and dosage should be based on tested ferritin levels as supplements can be harmful in some cases.

Side effects

Side effects of oral iron intake are most commonly diarrhea or constipation and epigastric abdominal discomfort.When taken after meals, side effects are reduced, but the risk of interactions with other substances increases. Side effects are dose dependent and the dose may be adjusted.

The patient may notice that his stool turns black. This is completely harmless, but patients should be warned about this in order to avoid unnecessary fears. When iron supplements are given in liquid form, teeth can be reversibly discolored (this can be avoided by using a straw). Intramuscular injection can be painful and brownish discoloration may be seen.

Treatment with iron (II) sulfate has a higher incidence of adverse events than iron (III) hydroxide polymaltose complex (MIC) or iron bis-glycinate chelate.

Iron overdose has been one of the leading causes of death in children under 6 years of age from toxicological agents.

Iron poisoning can cause death or short and long term illness.

Risk of contamination

Since one of the functions of elevated ferritin (acute phase response protein) in acute infections is thought to be to sequester iron from bacteria, it is generally believed that iron supplementation (which bypasses this mechanism) should be avoided in patients with active bacterial infections.infections. Replacing iron stores is rarely such an emergency that any such acute infection cannot be treated.

Several studies have shown that iron supplementation can increase the incidence of infectious diseases in regions where bacterial infections are common. For example, children who receive iron-fortified foods have an increased incidence of diarrhea in general and excretion of enteropathogens. Iron deficiency protects against infection by creating an unfavorable environment for bacteria to grow.However, while iron deficiency can reduce infection caused by certain pathogenic diseases, it also results in decreased resistance to other strains of viral or bacterial infections, such as Salmonella typhimurium or Entamoeba histolytica . In general, it is sometimes difficult to decide whether iron supplementation would be beneficial or harmful to humans in an environment that is prone to many infectious diseases; however, this is a different question than supplementation for people who already have a bacterial infection.

Children living in areas prone to malaria infections are also at risk of developing anemia. It was believed that iron supplementation in these children could increase the risk of contracting malaria. A Cochrane systematic review published in 2016 found high-quality evidence that iron supplementation does not increase the risk of clinical malaria in children.

Contraindications.

Contraindications often depend on the substance in question.Confirmed hypersensitivity to any ingredient and anemia without proper evaluation (i.e., documentary evidence of iron deficiency) is common to all drugs. Some of them can be used for iron deficiency, others require iron deficiency anemia. Some are also contraindicated in rheumatoid arthritis.

Hemochromatosis

Humans may be genetically predisposed to excessive absorption of iron, as is the case with hereditary hemochromatosis HFE.In the general population, 1 in 400 people have a homozygous form of this genetic trait, and 1 in every 10 people have its heterozygous form. People who are homozygous or heterozygous should not take iron supplements.

Interactions

Neprohema iron forms an insoluble complex with several other drugs, resulting in decreased absorption of both iron and other drug. Examples include tetracycline, penicillamine, methyldopa, levodopa, bisphosphonates, and quinolones.The same can happen with elements in food, such as calcium. Iron absorption is better at low pH (i.e. in an acidic environment), and absorption is reduced when antacids are taken concomitantly.

Many other substances reduce the rate of absorption of non-heme iron. Examples are tannins from foods such as tea and saw palmetto, phytic acid, and roughage. Because plant-based iron is more difficult to absorb than animal-based heme iron, vegetarians and vegans should have slightly higher daily iron intakes than those who eat meat, fish, or poultry.

Taking after meals causes fewer side effects, but also less absorption due to interactions and changes in pH. Typically, a 2–3 hour interval between iron and other medications is appropriate, but it is less convenient for patients and may affect adherence.

Brand Name

It is marketed in India under the trade name Bizfer XT (fixed dose combination of iron bisglycinate, IP folic acid, zinc bisglycinate and methylcobalamin.

History

The first tablets were commonly known as the Bloud tablets, named after P. Bloud of Bocker, the French physician who introduced and began to use these drugs to treat patients with anemia.

Administration

Oral

Iron can be ingested in various forms such as iron (II) sulfate. It is the most common and well-studied soluble iron salt sold under brand names such as Feratab, Fer-Iron, and Slow-FE.It is in a complex with gluconate, dextran, carbonyl iron and other salts. Ascorbic acid, a vitamin C, increases the absorption of non-heme sources of iron.

Heme iron polypeptide (HIP) (eg Proferrin ES and Proferrin Forte) can be used when conventional iron supplements such as ferrous sulfate or ferrous fumarate are not tolerated or absorbed. A clinical study found that HIP increased serum iron levels 23 times more than ferrous fumarate, on a milligram per milligram basis.

Another alternative is colored glycine sulfate or ferroglycine sulfate , which have fewer gastrointestinal side effects than standard drugs such as iron fumarate. Among oral preparations with iron supplements, it is unusual in that the iron in this preparation has a very high oral bioavailability, especially in liquid preparations. This option should be evaluated before resorting to parenteral therapy.It is especially useful in iron deficiency anemia associated with autoimmune gastritis and gastritis caused by Helicobacter pylori , where it usually has a satisfactory effect.

Since the body’s iron stores are generally depleted, there is a limit to what the body can process (about 2-6 mg / kg body weight per day; that is, for a person weighing 100 kg / 220 lbs, this is the maximum). dose 200-600 mg / day) without iron poisoning, this is a chronic therapy that can last 3-6 months.

Due to frequent oral iron intolerance and slow improvement, parenteral iron administration is recommended for many indications.

By injection

Iron therapy (intravenous or intramuscular) is indicated when oral therapy fails (cannot be tolerated), oral absorption is severely impaired (due to illness or when the person cannot swallow), benefit from oral therapy cannot be expected, or rapid improvement is required …(for example, before a planned operation). Parenteral therapy is more expensive than oral iron and is not appropriate during the first trimester of pregnancy.

There are cases where parenteral iron administration is preferable to oral iron. These are cases where oral iron is not tolerated, when hemoglobin needs to be rapidly increased (eg, in the postpartum period, after surgery, after blood transfusion), in the presence of an underlying inflammatory condition (eg, inflammatory bowel disease), or in patients with kidney disease, benefits parenteral iron far outweighs the risks.In many cases, intravenous iron, such as ferric carboxymaltose, has a lower risk of side effects than blood transfusion and is a better alternative as long as the patient is stable. Ultimately, this always remains a clinical decision based on local guidelines, although national guidelines increasingly require intravenous iron for certain patient populations.

Soluble iron salts carry a significant risk of side effects and can cause toxicity due to damage to cellular macromolecules.When iron is given parenterally, various molecules are used to limit this. These include dextrans, sucrose, carboxymaltose and, more recently, isomaltoside 1000.

One of the parenteral iron preparations is iron dextran, which covers the older high molecular weight preparations (trade name DexFerrum ) and the much safer low molecular weight iron dextrans (trade names including Cosmofer and Infed).

Iron sucrose has an occurrence of allergic reactions of less than 1 in 1000. A common side effect is a change in taste, especially a metallic taste in the mouth, occurring in the range of 1 in 10 and 1 in 100 patients. According to the SPC, the maximum dose is 200 mg for each case, but it is prescribed in doses of 500 mg. Doses can be administered up to 3 times a week.

Iron carboxymaltose is marketed as Ferinject , Injectafer and Iroprem in various countries.The most common side effects are headaches, which occur in 3.3%, and hypophosphatemia, which occurs in more than 35%.

Iron Isomaltoside 1000 (trade name Monofer ) is a novel parenteral iron formula with a matrix structure that results in very low levels of free and labile iron. It can be administered in high doses – 20 mg / kg per visit – with no upper dose limit. The advantage of this drug is that it provides a complete iron correction in one visit.

Follow

Observation is necessary to ensure adherence to treatment and an adequate response to therapy. The observation interval can largely depend on both the method of administration and the underlying pathology. For a parenteral iron, it is recommended to take 4 weeks before the re-blood test to allow the body to use the iron. For oral iron supplementation this can take significantly longer, so wait three months.

See also

Recommendations

90,000 contraindications, side effects, dosages, composition – tablets, cover.shell in the reference book of medicines

Sorbifer ™ Durules® should not be combined with the following drugs:

– ciprofloxacin : when used together, the absorption of ciprofloxacin is reduced by 50%, so there is a danger that its plasma concentration will not reach the therapeutic level;

– levofloxacin : when used together, the absorption of levofloxacin decreases;

– moxifloxacin : when used together, the bioavailability of moxifloxacin is reduced by 40%.With the simultaneous use of moxifloxacin and Sorbifer ™ Durules®, the maximum possible time interval of at least 6 hours should be maintained between taking these drugs;

– norfloxacin : when used together, the absorption of norfloxacin decreases by about 75%;

– ofloxacin : when used together, the absorption of ofloxacin decreases by about 30%;

– mycophenolate mofetil : a sharp decrease in absorption by 90% of mycophenolate mofetil was observed when combined with preparations containing iron.

Combinations to avoid

– Iron (salts) (parenteral route of administration)

Possible lipothymia, even shock, which is explained by the rapid release of iron from its complex form and transferrin saturation.

Therefore, the combined use of oral and parenteral iron preparations should be avoided; the same goes for repeated blood transfusions.

Combinations to be taken into account

– Acetohydroxamic acid

Decreased absorption of both drugs as a result of complexation.

Combinations that are used with precautionary measures

– Bisphosphonates

Decrease in the absorption of bisphosphonates due to the formation of poorly absorbed complexes with iron.

It is recommended to observe the interval between the intake of iron salt and bisphosphonates (from 30 minutes to 2 hours or more, if possible, depending on the bisphosphonate).

– Entacapon

Decrease in the absorption of entacapone and iron due to its chelation with entacapone.

It is recommended to observe the interval between the intake of iron salt and entacapone (if possible, more than 2 hours).

– Strontium

It is recommended to observe the interval between the intake of iron salt and strontium (if possible, more than 2 hours).

– Proton pump inhibitors

May decrease absorption of oral iron. Therefore, dose adjustment or replacement with intravenous iron may be required.

– Nonsteroidal anti-inflammatory drugs (e.g. salicylates and phenylbutazone)

When administered orally, an irritating effect on the mucous membrane of the gastrointestinal tract can be observed.

– Dimercaprol

Forms a toxic complex with iron and should not be used concomitantly with iron preparations.

– Cholestyramine

Iron absorption is impaired.

The potential interactions mentioned above can be reduced by maintaining at least a 2-hour interval between each drug.

Oral administration of ferrous sulfate preparations can lead to false positive stool occult blood test results.

When Sorbifer ™ Durules® is used together with the following drugs, it may be necessary to change their dose.

Between taking Sorbifer ™ Durules® and any of these drugs, the maximum possible time interval should be maintained, at least 2-3 hours:

– Food additives containing calcium or magnesium, as well as antacids containing aluminum, calcium or magnesium : These form complexes with iron salts, thus impairing the absorption of each other.

– Captopril : when used simultaneously with captopril, its area under the concentration-time curve decreases by an average of 37%, probably due to a chemical reaction in the gastrointestinal tract.

– Zinc: with simultaneous use, the absorption of zinc salts decreases.

– Clodronate and Risendronate : In vitro studies found that preparations containing iron form a complex with clodronate.Despite the fact that studies of in vivo have not been conducted, it can be assumed that when used together, the absorption of clodronate decreases.

– Deferoxamine : when used together, the absorption of both deferoxamine and iron decreases due to the formation of complexes.

– Levodopa, carbidopa : with the combined use of iron sulfate with levodopa and carbidopa – probably due to the formation of complexes – the bioavailability of levodopa in healthy volunteers decreases by 50%, and carbidopa – by 75%.

– Methyldopa (levorotatory) : with the combined use of iron salts (ferrous sulfate and gluconate) with methyldopa – probably due to the formation of chelate complexes – the bioavailability of methyldopa decreases, which can worsen its hypotensive effect.

– Penicillamine : when penicillamine is used together with iron salts – probably due to the formation of chelate complexes – the absorption of both penicillamine and iron salts is reduced.

– Alendronate : In study in vitro , preparations containing iron formed complexes with alendronate, reducing the absorption of the latter.There are no results under conditions of in vivo .

– Tetracycline : when used together, the absorption of both tetracycline and iron decreases, therefore, with combined use, the maximum possible time interval should be maintained, which is at least 3 hours between doses. The use of iron-containing drugs worsens the enterohepatic cycle of doxycycline, both when taken orally and when administered intravenously, therefore, the combined use of these drugs should be avoided.

– Thyroid hormones : with the combined use of iron-containing drugs and thyroxine, the absorption of the latter may decrease, which can lead to the failure of replacement therapy.

– Cimetidine : when Sorbifer ™ Durules® is used together with cimetidine, the decrease in gastric acidity caused by cimetidine reduces the absorption of iron. Therefore, for combined use, the maximum possible time interval should be maintained, which is at least 2 hours.

– Chloramphenicol : The effect of iron therapy appears later. The formation of red blood cells is suppressed and the level of hemoglobin decreases.

When Sorbifer ™ Durules® is used with tea, coffee, eggs, dairy products, wholemeal bread, cereal or fiber-rich foods, iron absorption may be reduced.

Interactions related to ascorbic acid

Increases the concentration of salicylates in the blood (increases the risk of crystalluria), ethinylestradiol, benzylpenicillin, and tetracyclines.Reduces the concentration of oral contraceptives . Increases the activity of norepinephrine . Reduces the anticoagulant effect of coumarin derivatives , heparin . Improves absorption in the intestine of iron preparations , as well as iron from food (by converting ferric iron to bivalent). Increases the total clearance of ethyl alcohol . May affect the effectiveness of disulfiram in the treatment of chronic alcoholism.The simultaneous use of ascorbic acid and deferoxes does not increase the excretion of iron.

Acetylsalicylic acid, oral contraceptives, fresh juices and alkaline drinks reduce absorption and assimilation of ascorbic acid.

Ascorbic acid increases renal excretion amphetamine .

Plasma ascorbate concentration decreases with smoking and oral contraceptives .

Simultaneous reception of acetylsalicylic acid and ascorbic acid can interfere with the absorption of ascorbic acid.The renal excretion of salicylate is not affected and does not lead to a decrease in the anti-inflammatory effect of acetylsalicylic acid.

Simultaneous reception of aluminum-containing antacids can increase the excretion of aluminum in the urine. The simultaneous administration of antacids and ascorbic acid is not recommended, especially in patients with renal insufficiency.

Concomitant use with amygdalin (alternative therapy) may cause cyanide toxicity.

Simultaneous administration of ascorbic acid with deferoxamine enhances urinary excretion of iron and can lead to cases of cardiomyopathy and heart failure in patients with idiopathic hemochromatosis and thalassemia receiving deferoxamine, who are subsequently given ascorbic acid.Ascorbic acid should be used with caution in these patients and cardiac function should be monitored.

Ascorbic acid can interfere with the biochemical determination of creatinine, uric acid and glucose in blood and urine samples.

Treatment of iron deficiency anemia in women after childbirth

Anemia is a condition when the hemoglobin content in the blood is less than normal (low hemoglobin), which is reflected in blood tests. Hemoglobin is a molecule in red blood cells and requires iron to carry oxygen.Insufficient iron intake / absorption and iron loss (eg, through bleeding) can lead to iron deficiency anemia. Symptoms of anemia include tiredness / fatigue, shortness of breath, and dizziness. Women can lose a lot of blood during childbirth, and many pregnant women already have anemia, which can progress as a result of bleeding. Severe anemia can be associated with maternal mortality. Postpartum iron deficiency anemia is more common in low-income countries.

Treatment for iron deficiency anemia includes tablets containing iron or a solution that is injected into a vein (intravenously). Another treatment option is to restore red blood cells with a donor transfusion or stimulate red blood cell formation with erythropoietin. It is important to investigate which method is best in reducing the symptoms of anemia and whether these treatment options are safe.