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Ferrous Sulfate

The Elephant Formulary
© 2003-06 Susan K. Mikota DVM and Donald C. Plumb, Pharm.D.
Published by Elephant Care International -
www.elephantcare.org


Elephant specific information, if available, is in blue.

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. Regular ferrous 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 slowly soluble in water and insoluble in water. Dried ferrous sulfate contains 300 mg of elemental iron per gram. Ferrous sulfate, dried  may also be know as ferrous sulfate, exsiccated .

 

Storage/Stability/Compatibility - Unless otherwise instructed, store ferrous sulfate preparations in tight, light-resistant containers.

 

Pharmacology - Iron is necessary for myoglobin and hemoglobin in the transport and utilization of oxygen. While neither stimulating erythropoiesis nor correcting hemoglobin abnormalities not caused by iron deficiency, iron administration does correct both physical symptoms and decreased hemoglobin levels secondary to iron deficiency.

 

Ionized iron is also a component in the enzymes cytochrome oxidase, succinic dehydrogenase, and xanthine oxidase.

 

Uses/Indications - While iron is a necessary trace element in all hemoglobin-utilizing animals, the use of therapeutic dosages of ferrous sulfate (or other oral iron) preparations in veterinary medicine is limited primarily to the treatment of iron-deficiency anemias in dogs (usually due to chronic blood loss), although it may occasionally be used in other species. Injectable iron products are usually used in the treatment of iron deficiency anemias associated with newborn animals.

 

Pharmacokinetics - Oral absorption of iron salts is complex and is determined by a variety of factors, including diet, iron stores present, degree of erythropoiesis, and dose. Iron is thought to be absorbed 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 the bone marrow and eventually incorporated into hemoglobin. Iron metabolism occurs in a nearly closed system. Because iron liberated by the destruction of hemoglobin is reused by the body and only small amounts are lost by the body via hair and nail growth, normal skin desquamation and GI tract 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, hemolytic anemias, or known hypersensitivity to any component of the product. Because of the GI irritating properties of the drugs, oral iron products are also considered contraindicated by some clinicians in patients with GI ulcerative diseases.

 

Adverse Effects/Warnings - Adverse effects associated with non-toxic doses are usually limited to 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 elemental iron) is potentially fatal in a child. Initial symptoms of acute iron poisoning usually present as an acute onset of gastrointestinal irritation and distress (vomiting—possibly hemorrhagic, abdominal pain, diarrhea). The onset of these effects may be seen within 30 minutes of ingestion, but also can be delayed for several hours. Peripheral vascular collapse may rapidly follow with symptoms of depression, weak and/or rapid pulse, hypotension, cyanosis, ataxia, and coma possible. Some patients do not exhibit this phase of toxicity and may be asymptomatic for 12-48 hours after ingestion, when another critical phase may occur.

 

This phase may be exhibited by pulmonary edema, vasomotor collapse, cyanosis, pulmonary edema, fulminant hepatic failure, coma and death. Animals who survive this phase may exhibit long-term sequelae, including gastric scarring and contraction and have persistent digestive disturbances.

 

Because an acute onset of gastroenteritis may be associated with a multitude of causes, diagnosis of iron intoxication may be difficult unless the animal has been observed ingest­ing the product or physical evidence suggests ingestion. Ferrous sulfate (and gluconate) tablets are radiopaque, and often 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 basis to have any clinical benefit.

 

Treatment of iron intoxication  must be handled as an emergency. In humans who have ingested 10 mg/kg or more of elemental iron within 4 hours of presentation, the stomach is emptied, preferably using gastric lavage with a large bore tube to remove tablet fragments. It is generally recommended to avoid using emetics in patients who already have had episodes of hemorrhagic vomiting. These patients 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 the drug, administering apomorphine if appropriate to help dislodge tablets, and to instill a gastric lavage 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 soluble complex forms that is rapidly eliminated by the kidneys. Dosage recommendations for iron intoxicated dogs are:

a)   In severely affected animals: 40 mg/kg IV at a rate not exceeding 15 mg/kg/hr (avoiding hypotension); 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 been given, the urine should be examined. If no color change is seen after the second dose and the animal is not exhibiting clinical signs or symptoms or intoxication, no further treatment is required. If the urine is a reddish-orange color, a significant amount of iron has been ingested and treatment should continue at 10 mg/kg q8h for 24 hours. Do not exceed 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 treatment of acidosis, prophylactic antibiotics, oxygen, treatment for shock, coagulation abnormalities, seizures and/or hyperthermia. After the acute phases have resolved, dietary evaluation and management may be required.

 

Drug Interactions - Oral iron preparations can bind to orally administered tetracyclines, thereby decreasing the absorption of both compounds. If both drugs are necessary, give the tetracycline dose 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 of the 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 the bioavailability 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 cause false-positives with the guiaic test for occult blood in the feces. Iron does not usually affect the benzidine test for occult blood.

 

Doses - Caution: Unless otherwise noted, doses are for ferrous sulfate (regular—not dried). Dosing of oral iron products can be confusing; some authors state doses in terms of the iron salt and some state doses in terms of elemental iron. For the doses below, assume that the doses are for ferrous sulfate and not elemental iron, unless specified.

Horses:

As a hematinic:

a)   2 - 8 g PO per day for 2 weeks or more. (Adams 1988a)

 

 

Monitoring Parameters -

1)    Efficacy; adverse effects

a)   hemograms

b)   serum iron and total iron binding capacity, if necessary. Normal serum iron values for dogs and cats are reported as 80-180 micrograms/dl and 70-140 micro­grams/dl, respectively. Total iron binding for dogs and cats are reported as 280-340 micrograms/dl and 270-400 micrograms/dl, respectively. (Morgan 1988)

 

Client Information - Because of the potential for serious toxicity when overdoses of oral iron-containing products are ingested by either children or animals, these products should be kept well out of reach of children and pets.

 

Dosage Forms/Preparations/FDA Approval Status/Withholding Times -

 

Veterinary-Approved Products: No veterinary-approved products containing only ferrous sulfate could be located, but there are many multivitamin with iron containing products available.

 

Human-Approved Products:

Ferrous Sulfate Tablets  (20% elemental iron) 195 mg (39 mg iron), 300 mg (60 mg iron), 324 mg (65 mg iron);  Mol-Iron® (Schering-Plough); Feratab® (Upsher-Smith); generic (OTC)

Ferrous Sulfate Caplets: 160 mg (50 mg iron); Fe50 ® (Northampton) (OTC)

 

Ferrous Sulfate Capsules: 250 mg (50 mg iron);Ferospace® (Hudson); generic, (OTC)

 

Ferrous Sulfate Tablets Timed-Release 525 mg (105 mg iron); Fero-Gradumet® Filmtabs®  (Abbott) (OTC)

 

Ferrous Sulfate Syrup 18 mg/ml (3.6 mg iron/ml) in pints; Fer-In-Sol®  (Mead Johnson Nutritionals); (OTC)

 

Ferrous Sulfate Elixir 44 mg/ml (8.8 mg iron/ml) in pints and gallons 220 mg (44 mg iron) per 5 ml in pints and gallons

Feosol®  (SKBeecham); (OTC); generic (OTC)

 

Ferrous Sulfate Drops 125 mg/ml (25 mg iron/ml) in 50 ml Fer-In-Sol ® (Mead Johnson Nutritionals), Fer-Iron®  (various generics), (OTC)

 

Ferrous Sulfate, Dried (exissicated) Capsules 190 mg (60 mg iron); Fer-In-Sol® (Mead Johnson Nutritionals); (OTC)

 

Ferrous Sulfate, Dried (exissicated) Capsules Timed-Release 159 mg (50 mg iron); 250 mg dried ferrous sulfate equivalent (50 mg iron); Feosol®  (SK-Beecham); Ferralyn Lanacaps® (Lannett); Ferra-TD® (Goldline); generic (OTC)

 

Ferrous Sulfate, Dried (exissicated) Tablets 200 mg (65 mg iron); Feosol®  (SK-Beecham); (OTC)

 

Ferrous Sulfate, Dried (exissicated) Tablets, Slow-Release 160 mg (50 mg iron); Slow FE®  (Ciba Consumer); (OTC)

 

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