FERROUS SULFATE
Chemistry - An orally available iron supplement, ferrous sulfate occurs as odorless, pale-bluish-green, crystals or granules having a saline, styptic taste. In dry air the drug is efflorescent. If exposed to moisture or moist air, the drug is rapidly oxidized to a brownish-yellow ferric compound which should not be used medicinally. Exposure to light or an alkaline medium will enhance the conversion from the ferrous to ferric state.
Ferrous sulfate is available commercially in two forms, a "regular" and a "dried" form. Regularferrous sulfate contains 7 molecules of water of hydration and is freely soluble in water and insoluble in alcohol. Ferrous sulfate contains approximately 200 mg of elemental iron per gram.
Dried ferrous sulfate consists primarily of the monohydrate with some tetrahydrate. It is slowlysoluble in water and insoluble in water. Dried ferrous sulfate contains 300 mg of elemental iron pergram. Ferrous sulfate, dried may also be know as ferrous sulfate, exsiccated.
Ionized iron is also a component in the enzymes cytochrome oxidase, succinic dehydrogenase, andxanthine oxidase.
Uses, Indications - While iron is a necessary trace element in all hemoglobin-utilizing animals, theuse of therapeutic dosages of ferrous sulfate (or other oral iron) preparations in veterinary medicineis limited primarily to the treatment of iron-deficiency anemias in dogs (usually due to chronicblood loss), although it may occasionally be used in other species. Injectable iron products areusually used in the treatment of iron deficiency anemias associated with newborn animals.
Food in the GI tract may reduce the amount absorbed.
After absorption, the ferrous iron is immediately bound to transferrin, and is transported to thebone marrow and eventually incorporated into hemoglobin. Iron metabolism occurs in a nearlyclosed system. Because iron liberated by the destruction of hemoglobin is reused by the body andonly small amounts are lost by the body via hair and nail growth, normal skin desquamation and GItract sloughing, normal dietary intake usually is sufficient to maintain iron homeostasis.
While lethal doses are not readily available in domestic species, as little as 400 mg (of elementaliron) is potentially fatal in a child. Initial symptoms of acute iron poisoning usually present as anacute onset of gastrointestinal irritation and distress (vomiting¯possibly hemorrhagic, abdominalpain, diarrhea). The onset of these effects may be seen within 30 minutes of ingestion, but also canbe delayed for several hours. Peripheral vascular collapse may rapidly follow with symptoms ofdepression, weak and/or rapid pulse, hypotension, cyanosis, ataxia, and coma possible. Somepatients do not exhibit this phase of toxicity and may be asymptomatic for 12-48 hours afteringestion, when another critical phase may occur. This phase may be exhibited by pulmonaryedema, vasomotor collapse, cyanosis, pulmonary edema, fulminant hepatic failure, coma and death.
Animals who survive this phase may exhibit long-term sequelae, including gastric scarring andcontraction and have persistent digestive disturbances.
Because an acute onset of gastroenteritis may be associated with a multitude of causes, diagnosisof iron intoxication may be difficult unless the animal has been observed ingesting the product orphysical evidence suggests ingestion. Ferrous sulfate (and gluconate) tablets are radiopaque, andoften can be observed on abdominal radiographs. Serum iron levels and total iron binding capacity(TIBC) may also be helpful in determining the diagnosis, but must be done on an emergency basisto have any clinical benefit.
Treatment of iron intoxication must be handled as an emergency. In humans who have ingested 10mg/kg or more of elemental iron within 4 hours of presentation, the stomach is emptied, preferablyusing gastric lavage with a large bore tube to remove tablet fragments. It is generally recommendedto avoid using emetics in patients who already have had episodes of hemorrhagic vomiting. Thesepatients are lavaged using tepid water or 1-5% sodium bicarbonate solution.
In dogs, one author (Mount 1989), has recommended using oral milk of magnesia to help bind thedrug, administering apomorphine if appropriate to help dislodge tablets, and to instill a gastriclavage slurry of 50% sodium bicarbonate with a portion left in the stomach.
Deferoxamine is useful in chelating iron that has been absorbed. After chelation, a water solublecomplex forms that is rapidly eliminated by the kidneys. Dosage recommendations for ironintoxicated dogs are:
a) In severely affected animals: 40 mg/kg IV at a rate not exceeding 15 mg/kg/hr (avoidinghypotension); repeat every 4-12 hours at 20 mg/kg as determined by animal's response.
In less acutely afflicted animals: 20 mg/kg q4-12h IM or SQ q3-12h.
Three days of therapy may be required in severely poisoned animals. (Mount 1989)
b) Initially, 10 mg/kg IM or IV for 2 doses, 2 hours apart. After the second dose has beengiven, the urine should be examined. If no color change is seen after the second doseand the animal is not exhibiting clinical signs or symptoms or intoxication, no furthertreatment is required. If the urine is a reddish-orange color, a significant amount of ironhas been ingested and treatment should continue at 10 mg/kg q8h for 24 hours. Do notexceed 80 mg/kg total dose of deferoxamine in 24 hours. Continue to monitor carefully, particularly for shock. (Papich 1990)
In addition to chelation therapy, other supportive measures may be necessary, including treatmentof acidosis, prophylactic antibiotics, oxygen, treatment for shock, coagulation abnormalities, seizures and/or hyperthermia. After the acute phases have resolved, dietary evaluation andmanagement may be required.
Because chloramphenicol may delay the response to iron administration, avoid using chloramphenicol in patients with iron deficiency anemia.
Iron can decrease the efficacy of penicillamine, probably by decreasing its absorption. Doses ofthe two drugs should be spaced as far apart as possible, should both be required.
Antacids, eggs, or milk administered concurrently with oral iron preparations can reduce thebioavailability of the iron. Separate iron doses from these items as far apart as possible.
Iron salts may precipitate phosphate in the GI tract.
Drug/Laboratory Interactions - Large doses of oral iron can color the feces black and causefalse-positives with the guiaic test for occult blood in the feces. Iron does not usually affect thebenzidine test for occult blood.
Ferrous sulfate is available commercially in two forms, a "regular" and a "dried" form. Regularferrous sulfate contains 7 molecules of water of hydration and is freely soluble in water and insoluble in alcohol. Ferrous sulfate contains approximately 200 mg of elemental iron per gram.
Dried ferrous sulfate consists primarily of the monohydrate with some tetrahydrate. It is slowlysoluble in water and insoluble in water. Dried ferrous sulfate contains 300 mg of elemental iron pergram. Ferrous sulfate, dried may also be know as ferrous sulfate, exsiccated.
Storage, Stability, Compatibility
Unless otherwise instructed, store ferrous sulfate preparationsin tight, light-resistant containers.Pharmacology - FERROUS SULFATE
Iron is necessary for myoglobin and hemoglobin in the transport and utilizationof oxygen. While neither stimulating erythropoiesis nor correcting hemoglobin abnormalities notcaused by iron deficiency, iron administration does correct both physical symptoms and decreasedhemoglobin levels secondary to iron deficiency.Ionized iron is also a component in the enzymes cytochrome oxidase, succinic dehydrogenase, andxanthine oxidase.
Uses, Indications - While iron is a necessary trace element in all hemoglobin-utilizing animals, theuse of therapeutic dosages of ferrous sulfate (or other oral iron) preparations in veterinary medicineis limited primarily to the treatment of iron-deficiency anemias in dogs (usually due to chronicblood loss), although it may occasionally be used in other species. Injectable iron products areusually used in the treatment of iron deficiency anemias associated with newborn animals.
Pharmacokinetics - FERROUS SULFATE
Oral absorption of iron salts is complex and is determined by a variety offactors, including diet, iron stores present, degree of erythropoiesis, and dose. Iron is thought to beabsorbed throughout the GI tract, but is most absorbed in the duodenum and proximal jejunum.Food in the GI tract may reduce the amount absorbed.
After absorption, the ferrous iron is immediately bound to transferrin, and is transported to thebone marrow and eventually incorporated into hemoglobin. Iron metabolism occurs in a nearlyclosed system. Because iron liberated by the destruction of hemoglobin is reused by the body andonly small amounts are lost by the body via hair and nail growth, normal skin desquamation and GItract sloughing, normal dietary intake usually is sufficient to maintain iron homeostasis.
Contraindications, Precautions, Reproductive Safety
Ferrous sulfate (or other oral iron products) are considered contraindicated in patients with hemosiderosis, hemochromotosis, hemolyticanemias, or known hypersensitivity to any component of the product. Because of the GI irritatingproperties of the drugs, oral iron products are also considered contraindicated by some clinicians inpatients with GI ulcerative diseases.Adverse Effects, Warnings
Adverse effects associated with non-toxic doses are usually limitedto mild gastrointestinal upset. Division of the daily dosage may reduce this effect, but dosage reduction may also be necessary in some animals.Overdosage, Acute Toxicity
Ingestion of iron containing products may result in serious toxicity.While lethal doses are not readily available in domestic species, as little as 400 mg (of elementaliron) is potentially fatal in a child. Initial symptoms of acute iron poisoning usually present as anacute onset of gastrointestinal irritation and distress (vomiting¯possibly hemorrhagic, abdominalpain, diarrhea). The onset of these effects may be seen within 30 minutes of ingestion, but also canbe delayed for several hours. Peripheral vascular collapse may rapidly follow with symptoms ofdepression, weak and/or rapid pulse, hypotension, cyanosis, ataxia, and coma possible. Somepatients do not exhibit this phase of toxicity and may be asymptomatic for 12-48 hours afteringestion, when another critical phase may occur. This phase may be exhibited by pulmonaryedema, vasomotor collapse, cyanosis, pulmonary edema, fulminant hepatic failure, coma and death.
Animals who survive this phase may exhibit long-term sequelae, including gastric scarring andcontraction and have persistent digestive disturbances.
Because an acute onset of gastroenteritis may be associated with a multitude of causes, diagnosisof iron intoxication may be difficult unless the animal has been observed ingesting the product orphysical evidence suggests ingestion. Ferrous sulfate (and gluconate) tablets are radiopaque, andoften can be observed on abdominal radiographs. Serum iron levels and total iron binding capacity(TIBC) may also be helpful in determining the diagnosis, but must be done on an emergency basisto have any clinical benefit.
Treatment of iron intoxication must be handled as an emergency. In humans who have ingested 10mg/kg or more of elemental iron within 4 hours of presentation, the stomach is emptied, preferablyusing gastric lavage with a large bore tube to remove tablet fragments. It is generally recommendedto avoid using emetics in patients who already have had episodes of hemorrhagic vomiting. Thesepatients are lavaged using tepid water or 1-5% sodium bicarbonate solution.
In dogs, one author (Mount 1989), has recommended using oral milk of magnesia to help bind thedrug, administering apomorphine if appropriate to help dislodge tablets, and to instill a gastriclavage slurry of 50% sodium bicarbonate with a portion left in the stomach.
Deferoxamine is useful in chelating iron that has been absorbed. After chelation, a water solublecomplex forms that is rapidly eliminated by the kidneys. Dosage recommendations for ironintoxicated dogs are:
a) In severely affected animals: 40 mg/kg IV at a rate not exceeding 15 mg/kg/hr (avoidinghypotension); repeat every 4-12 hours at 20 mg/kg as determined by animal's response.
In less acutely afflicted animals: 20 mg/kg q4-12h IM or SQ q3-12h.
Three days of therapy may be required in severely poisoned animals. (Mount 1989)
b) Initially, 10 mg/kg IM or IV for 2 doses, 2 hours apart. After the second dose has beengiven, the urine should be examined. If no color change is seen after the second doseand the animal is not exhibiting clinical signs or symptoms or intoxication, no furthertreatment is required. If the urine is a reddish-orange color, a significant amount of ironhas been ingested and treatment should continue at 10 mg/kg q8h for 24 hours. Do notexceed 80 mg/kg total dose of deferoxamine in 24 hours. Continue to monitor carefully, particularly for shock. (Papich 1990)
In addition to chelation therapy, other supportive measures may be necessary, including treatmentof acidosis, prophylactic antibiotics, oxygen, treatment for shock, coagulation abnormalities, seizures and/or hyperthermia. After the acute phases have resolved, dietary evaluation andmanagement may be required.
Drug Interactions
Oral iron preparations can bind to orally administered tetracyclines, therebydecreasing the absorption of both compounds. If both drugs are necessary, give the tetracyclinedose 2 hours before or 3 hours after the iron dose.Because chloramphenicol may delay the response to iron administration, avoid using chloramphenicol in patients with iron deficiency anemia.
Iron can decrease the efficacy of penicillamine, probably by decreasing its absorption. Doses ofthe two drugs should be spaced as far apart as possible, should both be required.
Antacids, eggs, or milk administered concurrently with oral iron preparations can reduce thebioavailability of the iron. Separate iron doses from these items as far apart as possible.
Iron salts may precipitate phosphate in the GI tract.
Drug/Laboratory Interactions - Large doses of oral iron can color the feces black and causefalse-positives with the guiaic test for occult blood in the feces. Iron does not usually affect thebenzidine test for occult blood.