Gastrointestinal |
3.8.2) CLINICAL EFFECTS
A) DRUG-INDUCED GASTROINTESTINAL DISTURBANCE 1) In a small study, 5 healthy volunteers given carbonyl iron had slightly more episodes of abdominal cramping and diarrhea, as compared to the ferrous sulfate group (Gordeuk et al, 1986). The effects were not considered statistically significant.
2) CASE SERIES/INCIDENCE: In a comparison study of healthy female blood donors given iron supplementation daily for 56 days in the form of either carbonyl iron or ferrous sulfate, gastrointestinal side effects were similar for both groups (Gordeuk et al, 1987). However, the carbonyl dose was 10 times higher than the ferrous sulfate dose (600 mg vs 300 mg ferrous sulfate {equivalent to 60 mg Fe++}).
3) COMPARISON STUDY: In a comparison study of carbonyl iron and ferrous sulfate supplementation, healthy females with hematocrits less than 35% were given equivalent amounts of iron (100 mg) daily for 12 weeks, and developed relatively the same rate of gastrointestinal effects (e.g., constipation, diarrhea, heartburn, nausea, epigastric pain, abdominal cramps) (Devasthali et al, 1991).
4) SEVERE IRON OVERDOSE: Severe overdose has not been reported with carbonyl iron, and the need for it to be solubilized prior to absorption may make severe toxicity unlikely. If a large amount were absorbed, severe toxic effects would include severe vomiting, diarrhea, gastrointestinal hemorrhage, and late onset gastrointestinal strictures (Tenenbein et al, 1990; Carlsson et al, 2008; Wu et al, 2003). Refer to IRON management for more information.
B) TASTE SENSE ALTERED 1) Unpleasant taste was described by most anemic patients (n=32) during a clinical trial with carbonyl iron (Gordeuk et al, 1986), and thought to be secondary to eructation (Gordeuk et al, 1987).
2) In another study, unpleasant taste was reported in almost twice as many patients receiving carbonyl iron, as compared to ferrous sulfate (Devasthali et al, 1991). Its suggested that it may be a result of hydrogen gas formation during solubilization of the carbonyl iron.
3.8.3) ANIMAL EFFECTS
A) ANIMAL STUDIES 1) LACK OF EFFECT a) CHRONIC EXPOSURE 1) In rat studies, animals fed 13 mg of carbonyl iron/day for 6 months (60 times their daily requirement) did not develop toxicity. Siderosis of the spleen was the only reported finding at necropsy, with no iron reported in the duodenum, pancreas, or liver (Sacks & Houchin, 1978).
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Hepatic |
3.9.2) CLINICAL EFFECTS
A) INJURY OF LIVER 1) In a small study of healthy volunteers, hepatic function was not altered by the oral administration of carbonyl iron. In the same study, anemic patients received a total of 607-patient-days of therapy with NO hepatotoxicity reported (Gordeuk et al, 1986).
2) Severe overdose has not been reported with carbonyl iron, and the need for it to be solubilized prior to absorption may make severe toxicity unlikely. If a large amount were absorbed, hepatotoxicity may occur , but this has not been reported after carbonyl iron overdose (Tenenbein, 2001). Refer to IRON management for more information.
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Summary Of Exposure |
A) USES: Carbonyl iron is used in various industrial processes and as a dietary supplement.
B) PHARMACOLOGY: Carbonyl iron (Fe(CO)5) is an uncharged insoluble iron powder and greater than 98% elemental iron. It is complexed with dextran. Carbonyl iron is manufactured by a process that heats gaseous iron pentacarbonyl which deposits metallic iron as submicroscopic crystals. Absorption of carbonyl iron requires ionization and solubilization by gastric acid which can result in a prolonged rate of absorption and accounts for its reduced toxicity. However, once solubilized, the pathway of absorption via the intestinal mucosa, as well as the extent of absorption, is similar to that of ferrous sulfate. Thus, theoretically it behaves pharmacologically similar to an extended-release preparation of iron.
C) TOXICOLOGY: Iron is involved in various redox reactions that contribute to oxidative stress with the formation of reactive oxygen species. Also, iron causes direct mucosal injury to the gastrointestinal tract epithelium and disrupts oxidative phosphorylation.
D) EPIDEMIOLOGY: Carbonyl is not commonly used medically and severe toxicity has not been reported.
E) WITH THERAPEUTIC USE
1) Gastrointestinal effects were the most commonly reported adverse event following carbonyl iron use, and occurred at a similar rate to ferrous sulfate. Constipation, diarrhea, abdominal cramping, nausea, heartburn, epigastric pain, and abnormal tastes were reported with therapeutic use.
F) WITH POISONING/EXPOSURE
1) MILD TO MODERATE TOXICITY: There are no reports of overdose with carbonyl iron. Nausea, vomiting, diarrhea, and abdominal pain would be expected after an overdose.
2) SEVERE TOXICITY: Severe overdose has not been reported with carbonyl iron, and the need for it to be solubilized prior to absorption may make severe toxicity unlikely. If a large amount were absorbed, severe toxic effects would include severe vomiting, diarrhea, lethargy, metabolic acidosis, shock, gastrointestinal hemorrhage, coma, seizures, hepatotoxicity, and late onset gastrointestinal strictures.
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Neurologic |
3.7.2) CLINICAL EFFECTS
A) CENTRAL NERVOUS SYSTEM DEFICIT 1) WITH POISONING/EXPOSURE a) Severe overdose has not been reported with carbonyl iron, and the need for it to be solubilized prior to absorption may make severe toxicity unlikely. If a large amount were absorbed, lethargy, restlessness and confusion may occur, but this has not been reported after carbonyl iron overdose (Carlsson et al, 2008; Chyka & Butler, 1993). Refer to IRON management for more information.
B) SEIZURE 1) WITH POISONING/EXPOSURE a) Severe overdose has not been reported with carbonyl iron, and the need for it to be solubilized prior to absorption may make severe toxicity unlikely. If a large amount were absorbed, seizures may occur, but this has not been reported after carbonyl iron overdose (Chyka & Butler, 1993). Refer to IRON management for more information.
C) COMA 1) WITH POISONING/EXPOSURE a) Severe overdose has not been reported with carbonyl iron, and the need for it to be solubilized prior to absorption may make severe toxicity unlikely. If a large amount were absorbed, coma may occur, but this has not been reported after carbonyl iron overdose (Chyka & Butler, 1993). Refer to IRON management for more information.
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Genitourinary |
3.10.2) CLINICAL EFFECTS
A) NORMAL RENAL FUNCTION 1) LACK OF EFFECT a) In a small study of healthy volunteers, renal function was not altered by the ingestion of carbonyl iron. In the same study, anemic patients received a total of 607 patient-days of therapy with NO renal toxicity reported (Gordeuk et al, 1986).
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Acid-Base |
3.11.2) CLINICAL EFFECTS
A) METABOLIC ACIDOSIS 1) WITH POISONING/EXPOSURE a) Severe overdose has not been reported with carbonyl iron, and the need for it to be solubilized prior to absorption may make severe toxicity unlikely. If a large amount were absorbed, anion gap metabolic acidosis may occur, but this has not been reported after carbonyl iron overdose . Refer to IRON management for more information. 1) IRON OVERDOSE: Anion gap metabolic acidosis is a common early finding in significant ingestions (Carlsson et al, 2008; Schonfeld & Haftel, 1989; Wu et al, 1998). Severe metabolic acidosis may persist for days in severe overdoses.
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Hematologic |
3.13.2) CLINICAL EFFECTS
A) HEMATOLOGY FINDING 1) LACK OF EFFECT a) No evidence of hematologic toxicity was reported in a group of anemic patients who had received a total of 607 patient-days of therapy with carbonyl iron (Gordeuk et al, 1986). Similar findings were reported in a group of females given high-dose (600 mg Fe three times daily) carbonyl iron for iron deficiency anemia (Gordeuk et al, 1987).
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