Ferric Citrate – Uses, Dosage, Side Effects, Interactions

Ferric ammonium citrate is a yellowish brown to red solid with a faint ammonia odor. It is soluble in water. The primary hazard is the threat to the environment. Immediate steps should be taken to limit its spread to the environment. It is used in medicine, in making blueprints, and as a feed additive.

Indications

• Fexeric is indicated for the control of hyperphosphataemia in adult patients with chronic kidney disease (CKD).
• Source of iron in treating iron-deficiency anemias. It is less constipating than Inorg forms of iron. It is free from astringent & irritant properties. However, the ferric ion is less well absorbed than the ferrous ion, so its supposed advantages are outweighed by its lesser efficacy, and it is considered to be an obsolete preparation. In the forms presently marketed, a unit dose provides only the recommended daily allowance of iron (15 mg).
• Investigated by ESR spectroscopy.
• Control of serum phosphorous levels in patients with chronic kidney disease on dialysis.
• Treatment of iron deficiency anemia in patients with chronic kidney disease not on dialysis.

Contraindications

• Excess of iron (hemosiderosis, hemochromatosis);
• Non-iron deficiency anemia (eg, erythropoiesis, hemolytic anemia due to a deficiency in the body of vitamin B12, megaloblastic anemia, bone marrow hypoplasia);
• Impaired iron utilization (eg, thalassemia, sideroachrastic anemia, late porphyria of the skin, lead anemia);
• Hypersensitivity to the components of the drug.
• Infectious hepatitis;
• Osler-Randu-Weber Syndrome;
• Chronic polyarthritis;
• Uncontrolled hyperparathyroidism;
• Infectious diseases of the kidneys (in the acute course);
• Bronchial asthma;
• Decompensated hepatic cirrhosis;
• Intravenous introduction;
• The first trimester of pregnancy.

When taking the drug inside, because of the need to assign smaller doses, premature infants Maltofer is recommended to use in the form of drops, and children under 12 years of age – in the form of syrup. The drug in the form of a solution for injection is not recommended for children up to 4 months (due to lack of data on the safety and efficacy of its use in this category of patients).

Dosage

Usual Adult Dose for Hyperphosphatemia of Renal Failure:

• Each tablet contains ferric iron 210 mg equivalent to ferric citrate 1 g
• Initial dose: 2 tablets orally 3 times a day with meals. Adjust dose in increments/decrements of 1 to 2 tablets per day per week or longer intervals to maintain serum phosphorous at target levels
• Average dose: 8 to 9 tablets per day
• Maximum dose: 12 tablets per day

Usual Adult Dose for Anemia Associated with Chronic Renal Failure:

Each tablet contains ferric iron 210 mg equivalent to ferric citrate 1 g

• Initial dose: 1 tablet orally 3 times a day with meals. Adjust dose as needed to achieve and maintain target hemoglobin levels
• Average dose: 5 tablets per day
• Maximum dose: 12 tablets per day

Usual Adult Dose for Iron Deficiency Anemia:

Each tablet contains ferric iron 210 mg equivalent to ferric citrate 1 g

• Initial dose: 1 tablet orally 3 times a day with meals. Adjust dose as needed to achieve and maintain target hemoglobin levels
• Average dose: 5 tablets per day
• Maximum dose: 12 tablets per day

Side Effects

Most Common

• Inhalation of dust irritates the nose and throat. Ingestion irritates the mouth and stomach. Dust irritates the eyes and causes mild irritation of the skin on prolonged contact.
• Inhalation of dust irritates the nose and throat. Ingestion irritates the mouth and stomach. Dust irritates the eyes and causes mild irritation of the skin.
• Inhalation of ferric salts as dust and mists is irritating to the respiratory tract. Ferric salts are regarded as skin irritants
• If inhaled, iron is a local irritant to the lung and gastrointestinal tract.
• Abdominal or stomach discomfort
• low blood pressure,
• Tablets should not be chewed or crushed because it may cause discoloration of mouth and teeth.
• difficult, burning, or painful urination
• increased potassium blood levels (hyperkalemia),
• low blood sugar (hypoglycemia), and
• diarrhea
• symptoms of weakness, muscle pain (myalgia)
• abdominal pain (GI complaints), lactic acidosis (rare)
• low blood levels of vitamin B-12
• nausea, vomiting
• chest discomfort
• chills, dizziness
• bloating/abdominal distention
• constipation
• heartburn

More common

• chest pain;
• Abdominal or stomach discomfort
• a cough or hoarseness
• decreased appetite
• diarrhea
• fast or shallow breathing
• feeling like you might pass out;
• swelling in your hands, ankles, or feet;
• trouble breathing; or
• dangerously high blood pressure (a severe headache, blurred vision, buzzing in your ears, anxiety, confusion, chest pain, shortness of breath, uneven heartbeats, seizure)
• lower back or side pain
• muscle pain or cramping
• painful or difficult urination

Less common

• muscle cramps;
• weakness, tired feeling;
• dizziness, anxiety, headache;
• nausea, vomiting, stomach pain;
• diarrhea, constipation;
• ear pain;
• sore throat, sinus pain or congestion;
• decreased sense of taste;
• joint pain; or
• pain, swelling, burning, or irritation around the IV needle.
• Bloating or swelling of the face, arms, hands, lower legs, or feet
• blurred vision
• chest pain or tightness in the chest
• confusion
• difficult or labored breathing
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• nervousness
• pounding in the ears
• rapid weight gain

Drug Interaction

• Acidic salts, such as FERRIC AMMONIUM CITRATE, are generally soluble in water. The resulting solutions contain moderate concentrations of hydrogen ions and have pHs of less than 7.0. They react as acids to neutralize bases. These neutralizations generate heat, but less or far less than is generated by the neutralization of inorganic acids, inorganic oxoacids, and carboxylic acid.
• They usually do not react as either oxidizing agents or reducing agents but such behavior is not impossible. Many of these compounds catalyze organic reactions. Special Hazards of Combustion Products: Toxic oxides of nitrogen or ammonia gas may be formed in fires
• The present study has investigated whether melatonin can alter the proportion of neurons that die in the 24 hr period following 1.0 microL intracortical injections of 1.0 mM ferric ammonium citrate (FAC) or 0.9% saline. Rats that received systemic infusions of melatonin (5 mg/kg bw/day) displayed a 40% reduction (P=0.019) in the proportion of neurons killed by FAC.
• By contrast, the reduction of endogenous melatonin by continuous light exposure did not significantly affect the extent of neuronal death. Furthermore, elevated or reduced melatonin levels did not alter the number of neurons killed by saline injections.
• Specific pathogen-free male Fischer-344-rats received daily intraperitoneal injections of ferric-ammonium-citrate (FAC) at 40 mg/kg bw at 1 mL/kg or an equal volume of saline. Beginning on day four, rats were simultaneously exposed to an aerosol of beryllium-sulfate (BeSO4) for 2 hr/day through nose-only inhalation.
• By day 15, mortality was 80% in the BeSO4 plus saline group as compared to 33% in the BeSO4 plus FAC group. Exposure was then discontinued. By day 18, all rats in the BeSO4 plus saline group had died, while the cumulative mortality for the BeSO4 plus FAC group was only 66%. By day 19, mortality in this group had reached a maximum of 76%.
• Senile plaques, the major neuropathological lesions of Alzheimer’s disease (AD), are composed primarily of amyloid-beta … peptide and contain high concentrations of iron (1.0 mM). /It was/ previously shown that intracortical injections of 1.0 mM iron to adult rats produce significantly more neuronal loss than control injections of saline vehicle, whereas injections of /amyloid-beta/ do not. Because iron has been shown to increase the in vitro toxicity of /amyloid-beta/, the present study was undertaken to determine whether iron can make /amyloid-beta/ neurotoxic in vivo. /Amyloid-beta/ and 1.0 mM iron (as ferric ammonium citrate) were coinjected into rat cerebral cortex, and the neuronal loss was compared with that produced by pure /amyloid-beta/ or pure iron. The human and rat variants of /amyloid-beta/1-42 were compared to determine whether they produce the same amount of neuronal loss when combined with iron. Coinjection of iron with either /amyloid-beta/ variant caused significantly more neuronal loss than /amyloid-beta/ peptide alone, suggesting that iron may contribute to the toxicity associated with senile plaques. Rat /amyloid-beta/1-42 combined with iron was as toxic as iron alone, whereas iron combined with human /amyloid-beta/1-42 was significantly less toxic.
• To investigate the effects of sodium ferricitrate complex (sodium ferrous citrate) on the relative bioavailability of ciprofloxacin taken alone or with ascorbic acid, 3 healthy volunteers first received a single oral dose of 600 mg of ciprofloxacin alone or with 100 mg of oral sodium ferricitrate complex, and then 2 healthy volunteers received a single oral dose of 600 mg of ciprofloxacin alone, with 100 mg of oral sodium ferricitrate complex alone, or with sodium ferricitrate complex and 1500 mg of oral ascorbic acid; blood samples were taken frequently and analyzed for pharmacokinetic parameters. Cmax and area under the serum concentration-time curve decreased significantly with the coadministration of sodium ferricitrate complex. Relative bioavailability was 33.1%. In the second study, the area under the curve for both volunteers was improved with concomitant administration of ascorbic acid. However, the bioavailability did not significantly change.
• The effect of common baby food, strained pears, on the absorption of Fe from human milk was measured. Five adult subjects were initially fed 1 dL of human milk that contained added ferrous citrate 59Fe; the same subjects were later fed human milk and one jar of baby food. The incorporation of 59Fe into red blood cells averaged approximately 1/4 of the administered Fe from the human milk. When the milk was combined with the baby food, incorporation was significantly decreased. The addition of supplemental food to the diet of the breastfed infant impairs the bioavailability of the Fe from human milk.
• Intraneural infusion of lower dose manganese (4.2 nmol) in the present study did not significantly alter dopamine levels in rat striatum. Moreover, manganese completely suppressed both acute lipid peroxidation in substantia nigra and chronic degeneration of the nigrostriatal neurons induced by intraneural infusion of ferrous citrate (4.2 nmol).

Pregnancy and Lactation

• US FDA pregnancy category: Not assigned

  Risk Summary: There are no data available on the use of this drug during pregnancy to inform a drug-associated risk of major birth defects or miscarriage; an overdose of iron in pregnant women may carry a risk for spontaneous abortion, gestational diabetes and fetal malformation.

• Iron is a normal component of human milk. Studies on various forms of iron indicate that breastmilk levels are not increased greatly after exogenous administration. No special precautions are necessary. Holder pasteurization reduces the concentration of iron in milk by about 6.5%.

FAQ

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