FERROTONE

Indications

• Iron deficiency anemia
• Prophylaxis of iron deficiency in at-risk populations
• Epithelial tissue changes such as atrophic glossitis and koilonychia

Dosage

Children: For children aged 1 month to 11 years: 0.25 mL per kilogram twice daily, with the total daily dose possibly given in 3 divided doses, not exceeding 20 mL per day. For children aged 12-17 years: 10 mL once daily.

Adults: The dose is calculated according to body weight and the iron deficit, specifying both the iron salt and formulation. For specific dosing, consult product literature.

Mechanism of action

Iron is necessary for the production of hemoglobin. Iron deficiency can lead to decreased production of hemoglobin and a microcytic, hypochromic anemia. Ferrous fumarate releases iron in the gastrointestinal tract, facilitating its absorption and subsequent incorporation into hemoglobin, thus alleviating anemia.

Pharmacodynamics

The major activity of supplemental iron, including ferrous fumarate, is in the prevention and treatment of iron deficiency anemia. Iron also has putative immune-enhancing, anticarcinogenic, and cognition-enhancing activities, supporting overall health and functionality.

Pharmacokinetics

Ferrous fumarate is absorbed in the gastrointestinal tract, with absorption being optimal in an acidic environment. The bioavailability can be influenced by dietary factors, such as the presence of certain foods or medications that may inhibit iron absorption. Once absorbed, iron is transported in the blood bound to transferrin and is stored in tissues as ferritin and hemosiderin. The elimination half-life of iron is variable and depends on the individual's iron status and the amount of iron stored.

Contra-indications

• Iron overload syndromes
• Repeated blood transfusions
• Porphyria cutanea tarda

Adverse effects

• Asthenia
• Drowsiness
• Urine discoloration
• Cold sweat
• Confusion
• Decreased level of consciousness
• Thrombophlebitis
• Headache
• Joint stiffness
• Pain in extremities
• Skin reactions
• Small intestinal bacterial overgrowth
• Thirst
• Nausea
• Constipation
• Diarrhea
• Decreased appetite

Interactions

• Iron absorption may be affected by antacids and certain medications that alter gastric pH.

Precautions

• Monitor iron status to avoid iron overload.
• Caution in patients with intestinal strictures or diverticular disease.
• Care in elderly patients and those on high doses.

Pregnancy

Iron is generally considered safe during pregnancy, but supplementation should be monitored to avoid overload.

Breast-feeding

Iron supplementation may be necessary for exclusively breast-fed infants if maternal iron stores are low.

Storage

Store in a cool, dry place, away from direct sunlight. Keep out of reach of children.

Formulations

• Solution for injection (Iron as Iron sucrose 20 mg per 1 ml)
• Capsules containing iron formulations

Indications

• Iron-deficiency anemia (therapeutic)
• Iron-deficiency anemia (prophylactic)

Dosage

Children: For children aged 1 month to 11 years: 0.25 mL/kilogram twice daily. For children aged 12 to 17 years: 10 mL once daily.

Adults: 280 mg twice daily.

Mechanism of action

Ferrous sulfate acts as a source of iron, which is essential for the synthesis of hemoglobin, the protein in red blood cells that carries oxygen. Iron is absorbed in the intestines, where it is converted into a form that can be incorporated into hemoglobin. The mechanism involves transport proteins that facilitate iron uptake and incorporation into the heme group of hemoglobin.

Pharmacodynamics

The pharmacodynamic effect of ferrous sulfate is the increase in hemoglobin levels and improvement in symptoms of anemia, such as fatigue and weakness. Iron supplementation leads to increased erythropoiesis (red blood cell production) in the bone marrow, effectively correcting the deficit in iron stores and enhancing oxygen-carrying capacity.

Pharmacokinetics

Ferrous sulfate is absorbed in the gastrointestinal tract, particularly in the duodenum and proximal jejunum. The bioavailability of iron from ferrous sulfate can be affected by dietary factors, with enhanced absorption in acidic environments. Peak plasma concentrations typically occur within 2 to 6 hours post-administration. Iron is primarily stored in the liver and bone marrow, and any excess iron is excreted through feces, urine, and sweat.

Contra-indications

• Hypersensitivity to ferrous sulfate or any of its excipients
• Hemochromatosis
• Hemosiderosis
• Thalassemia
• Other anemias not due to iron deficiency

Adverse effects

• Gastrointestinal disturbances (nausea, constipation, diarrhea, abdominal pain)
• Dark stools
• Staining of teeth (with liquid formulations)
• Allergic reactions (rare)

Interactions

• Antacids may reduce the absorption of iron
• Tetracycline antibiotics may interfere with iron absorption
• Ascorbic acid (vitamin C) may enhance iron absorption
• Certain foods and beverages (e.g., tea, coffee, dairy) can decrease iron absorption

Precautions

• Use with caution in patients with peptic ulcer disease
• Monitor for signs of iron overload
• Assess the cause of anemia before initiation of therapy
• Keep out of reach of children to prevent accidental overdose

Pregnancy

Ferrous sulfate is generally considered safe for use during pregnancy to prevent or treat iron-deficiency anemia.

Breast-feeding

Ferrous sulfate is excreted in breast milk in small amounts but is considered safe for breastfeeding mothers.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Formulations

• Ferrous sulfate 200 mg tablets
• Ferrous sulfate 325 mg modified-release tablets
• Ferrous sulfate oral solution 140 mg/5 mL
• Ferrous sulfate drops

Indications

• Iron deficiency anemia
• Iron deficiency due to inadequate dietary intake
• Anemia associated with chronic disease
• Pregnancy-related anemia

Dosage

Children: Refer to the BNF for Children for specific dosing recommendations based on age and weight.

Adults: Refer to the BNF for specific dosing recommendations, generally, adults may require 100-200 mg of elemental iron daily divided into several doses.

Mechanism of action

Ferrous ions (Fe2+) play a vital role in hemoglobin production by participating in the synthesis of heme, the iron-containing compound essential for oxygen transport in the blood. In addition, iron is a cofactor for various enzymes involved in metabolic pathways, including those related to DNA synthesis and energy production.

Pharmacodynamics

The pharmacodynamic effects of ferrous include increased hemoglobin synthesis, improved oxygen transport, and enhanced cellular energy metabolism. Supplementation leads to an increase in serum ferritin levels and replenishment of iron stores in the body, which is particularly beneficial in cases of iron deficiency anemia.

Pharmacokinetics

Ferrous iron is absorbed primarily in the duodenum and upper jejunum of the small intestine. The absorption rate can be influenced by various factors, including the presence of food, the form of iron, and individual patient characteristics. Once absorbed, ferrous is transported in the bloodstream bound to transferrin, and it is stored in the liver, spleen, and bone marrow as ferritin. The elimination half-life of iron is not well-defined as it is not excreted directly but rather recycled in the body.

Pregnancy

Not contraindicated, but iron supplementation should be done under medical supervision.

Breast-feeding

Iron is excreted in breast milk, but supplementation is generally considered safe.

Storage

Store in a cool, dry place away from sunlight. Keep out of reach of children.

Mechanism of action

Folic acid is biochemically inactive until it is converted into active forms, primarily tetrahydrofolic acid and methyltetrahydrofolate, by the enzyme dihydrofolate reductase (DHFR). These active forms are essential for maintaining normal erythropoiesis, synthesizing nucleic acids, interconverting amino acids, and generating formate. They participate in critical one-carbon transfer reactions necessary for DNA synthesis and methylation processes. Folic acid, in conjunction with vitamin B12, helps normalize elevated homocysteine levels by facilitating its remethylation to methionine, a process that is crucial for various metabolic pathways.

Pharmacodynamics

Folic acid is an essential cofactor for enzymes involved in nucleic acid synthesis and amino acid metabolism. It is particularly significant in preventing megaloblastic anemia, which arises from impaired DNA synthesis due to folate deficiency. The synthesis of thymidylate, necessary for DNA formation, is directly influenced by folate availability. Folic acid's role is especially crucial during periods of rapid cellular division, and it has protective effects against certain cancer developments. As humans cannot synthesize folic acid endogenously, adequate dietary intake is essential for maintaining normal physiological functions.

Pharmacokinetics

Folic acid is absorbed in the small intestine and is then converted into its active forms within the body. The bioavailability of folic acid is influenced by factors such as food composition and the presence of certain gastrointestinal conditions. Once absorbed, it is transported in the bloodstream, mainly as 5-methyltetrahydrofolate. The distribution of folate occurs within various tissues, with significant

Adverse effects

• Allergic reactions
• Gastrointestinal disturbances
• Skin rash
• Altered sleep patterns

Interactions

• Anticonvulsants may reduce the effectiveness of folic acid
• Methotrexate may interfere with folic acid metabolism
• Trimethoprim-sulfamethoxazole can enhance the effects of folic acid deficiency

Precautions

• Monitor for signs of anemia in patients with malabsorption syndromes
• Use cautiously in patients with a history of hypersensitivity to folic acid
• Assess for vitamin B12 deficiency before initiating treatment, as folic acid can mask symptoms

Pregnancy

Folic acid is essential during pregnancy to prevent neural tube defects and support fetal development. Supplementation is recommended before conception and during the first trimester.

Breast-feeding

Folic acid passes into breast milk, and adequate maternal intake is important to ensure sufficient levels for the nursing infant.

Storage

Store in a cool, dry place away from light. Keep out of reach of children.

Formulations

• Tablets
• Oral solutions
• Injectable forms

Indications

• Vitamin deficiency syndromes (e.g., scurvy for vitamin C deficiency, rickets for vitamin D deficiency)
• Support for immune function
• Antioxidant support
• Bone health maintenance
• Vision health
• Energy metabolism support

Dosage

Children: Refer to the BNF for Children for specific vitamin dosing guidelines, which depend on age and nutritional requirements.

Adults: Refer to specific vitamin guidelines as dosage varies significantly depending on the type of vitamin and individual needs.

Mechanism of action

Vitamins function primarily as coenzymes or precursors for coenzymes in enzymatic reactions. For instance, B vitamins are involved in energy metabolism, while vitamins A, C, D, E, and K support various physiological functions including vision, antioxidant activity, calcium regulation, and blood clotting. Each vitamin has a unique mechanism of action based on its structure and role in the body.

Pharmacodynamics

Vitamins exert their effects at the cellular level, influencing metabolic pathways, gene expression, and immune responses. For example, vitamin D regulates calcium and phosphate homeostasis, while vitamin A is crucial for vision and immune function. Deficiencies in vitamins can lead to a range of disorders, highlighting their importance in maintaining health.

Pharmacokinetics

The pharmacokinetics of vitamins vary widely. Fat-soluble vitamins (A, D, E, and K) are stored in liver and adipose tissues and can be released into circulation as needed. Water-soluble vitamins (B-complex and C) are not stored and must be consumed regularly, with excess amounts excreted in urine. Absorption rates, half-lives, and distribution can also differ based on the specific vitamin and individual metabolic factors.

Interactions

• tretinoin+vitamin: Severe (increases risk of vitamin toxicity)
• retinoids+vitamin: Severe (increases risk of vitamin toxicity)
• retinoids+vitamin: Moderate (increases risk of toxicity)
• carbamazepine+vitamin: Unknown (decreases effects)
• cobicistat+vitamin: Unknown (increases exposure)
• vitamin D substances+digoxin: Unknown (increases risk of toxicity)
• idelalisib+vitamin: Unknown (increases exposure)
• clarithromycin+vitamin: Unknown (increases exposure)

Pregnancy

Consult healthcare professional before use. Vitamin supplementation during pregnancy should be carefully managed to avoid hypervitaminosis.

Breast-feeding

Consult healthcare professional before use. Some vitamins can pass into breast milk and may affect the infant.

Storage

Store in a cool, dry place, away from direct sunlight. Ensure it is kept out of reach of children.

Formulations

• {'name': 'Vitamin A', 'form': 'Capsule', 'strength': '10000 IU'}
• {'name': 'Vitamin D', 'form': 'Tablet', 'strength': '1000 IU'}
• {'name': 'Vitamin E', 'form': 'Softgel', 'strength': '400 IU'}

Mechanism of action

Iron is necessary for the production of hemoglobin. Iron-deficiency can lead to decreased production of hemoglobin and a microcytic, hypochromic anemia.

Pharmacodynamics

The major activity of supplemental iron is in the prevention and treatment of iron deficiency anemia. Iron has putative immune-enhancing, anticarcinogenic and cognition-enhancing activities.

Mechanism of action

Iron is necessary for the production of hemoglobin. Iron-deficiency can lead to decreased production of hemoglobin and a microcytic, hypochromic anemia.

Pharmacodynamics

The major activity of supplemental iron is in the prevention and treatment of iron deficiency anemia. Iron has putative immune-enhancing, anticarcinogenic and cognition-enhancing activities.

Mechanism of action

Folic acid, as it is biochemically inactive, is converted to tetrahydrofolic acid and methyltetrahydrofolate by dihydrofolate reductase (DHFR). These folic acid congeners are transported across cells by receptor-mediated endocytosis where they are needed to maintain normal erythropoiesis, synthesize purine and thymidylate nucleic acids, interconvert amino acids, methylate tRNA, and generate and use formate. Using vitamin B12 as a cofactor, folic acid can normalize high homocysteine levels by remethylation of homocysteine to methionine via methionine synthetase. Folic acid, after conversion to tetrahydrofolic acid, is necessary for normal erythropoiesis, synthesis of purine and thymidylates, metabolism of amino acids such as glycine and methionine, and the metabolism of histidine. The principal biochemical function of folates is the mediation of one-carbon transfer reactions. 5-Methyltetrahydrofolate donates a methyl group to homocystine, in the conversion of homocystine to L-methionine. ... 5,10-Methyltetrahydrofolate is regenerated from tetrahydrofolate via the enzyme serine hydroxymethyltransferase, a reaction, which in addition to producing 5,10-methyltetrahydrofolate, yields glycine. ... 5,10-methyltetrahydrofolate, supplies the one carbon group for the methylation of deoxyuridylic acid to form the DNA precursor thymidylic acid. This reaction is catalyzed by thymidylate synthase and the folate product of the reaction is dihydrofolate. Dihydrofolate is converted to tetrahydrofolate via the enzyme dihydrofolate reductase ...

Pharmacodynamics

Folic acid is a water-soluble B-complex vitamin found in foods such as liver, kidney, yeast, and leafy, green vegetables. Also known as folate or Vitamin B9, folic acid is an essential cofactor for enzymes involved in DNA and RNA synthesis. More specifically, folic acid is required by the body for the synthesis of purines, pyrimidines, and methionine before incorporation into DNA or protein. Folic acid is the precursor of tetrahydrofolic acid, which is involved as a cofactor for transformylation reactions in the biosynthesis of purines and thymidylates of nucleic acids. Impairment of thymidylate synthesis in patients with folic acid deficiency is thought to account for the defective deoxyribonucleic acid (DNA) synthesis that leads to megaloblast formation and megaloblastic and macrocytic anemias. Folic acid is particularly important during phases of rapid cell division, such as infancy, pregnancy, and erythropoiesis, and plays a protective factor in the development of cancer. As humans are unable to synthesize folic acid endogenously, diet and supplementation is necessary to prevent deficiencies. In order to function properly within the body, folic acid must first be reduced by the enzyme dihydrofolate reductase (DHFR) into the cofactors dihydrofolate (DHF) and tetrahydrofolate (THF). This important pathway, which is required for de novo synthesis of nucleic acids and amino acids, is disrupted by anti-metabolite therapies such as [DB00563] as they function as DHFR inhibitors to prevent DNA synthesis in rapidly dividing cells, and therefore prevent the formation of DHF and THF. In general, folate serum levels below 5 ng/mL indicate folate deficiency, and levels below 2 ng/mL usually result in megaloblastic anemia.