Iron diminishes absorption of ACE inhibitors (Schaefer et al. 1998). In a double-blind, place-controlled, cross-over study, seven healthy adult volunteers took captopril (25 mg) concomitantly with either ferrous sulphate (300 mg) or placebo. Coadministration of iron salts with captopril resulted in a 37% decrease in area under the curve plasma levels for unconjugated captopril. This decrease may be due to an interaction in the gastrointestinal tract when these substances are ingested together.

Iron salts may reduce the bioavailability of carbidopa and levodopa. However, the clinical relevance of this potential interaction is not known (PDR 2000).

Iron absorption is dependent upon gastric pH; therefore, medications that affect gastric pH may interfere with absorption of iron (PDR 2000). Iron can bind cimetidine in the gastrointestinal tract and reduce the absorption of this drug (Campbell et al. 1993). The bioavailability of the bound iron may also be decreased. Iron supplements should not be taken with cimetidine; doses of either substance should be staggered by 2 hours before or after administration of the other.

In vitro investigations have demonstrated that cholestyramine and colestipol both bind iron citrate (Leonard et al. 1979). The amount of iron citrate bound by colestipol ranged from 95 to 98%. Cholestyramine bound 24 to 97% of the iron citrate in a pH-dependent manner.

Iron may decrease the effectiveness of levothyroxine. A case report describes a patient who became hypothyroid when ferrous sulfate was added to the medication regimen; increasing the dose of levothyroxine countered these effects (Shakir et al. 1997). However, when the ferrous sulfate was discontinued, the patient became hyperthyroid at the higher levothyroxine dose. Thyroid function should be monitored in patients taking iron salts and levothyroxine concomitantly.

Oral contraceptives have been shown to increase the levels of iron in women (Tyrer 1984).

Quinolone antibiotics form chelates with metal cations, such as aluminum, magnesium, calcium, iron, zinc, copper, and manganese (Kara et al. 1991; Li et al. 1999), which significantly reduces the absorption of these medications (Balfour and Wiseman 1999; Brouwers 1992; Campbell and Hasinoff 1991). In a clinical trial with 12 healthy volunteers, ferrous sulfate (325 mg po tid) produced a 65% reduction in the absorption of orally administered ciprofloxacin (Polk 1989). This reduction in bioavailability has also been observed when iron salts were coadministered with levofloxacin, norfloxacin, and ofloxacin (Akerele and Okhamafe 1991; Okhamafe et al. 1991). Dietary supplements and antacids containing aluminum and magnesium should be taken two to four hours before or after administration of these antibiotics (Hines Burnham et al. 2000; Li et al. 1999).

Tetracyclines form chelates with divalent and trivalent cations, including iron, aluminum, magnesium, and calcium (Neuvonen 1976). These chelates are poorly soluble and can significantly reduce the absorption and efficacy of tetracyclines (Hines Burnham et al. 2000; Neuvonen 1976). Iron salts should be taken at least 3 hours before or 2 hours after tetracyclines (Hines Burnham et al. 2000).

Akerele JO, Okhamafe AO. Influence of oral co-administered metallic drugs on ofloxacin pharmacokinetics. J Antimicrob Chemother. 1991;28:87-94.

Balfour JA, Wiseman LR. Moxifloxacin. Drugs. 1999;57(3):363-374.

Brouwers J. Drug interactions with quinolone antibacterials. Drug Safety. 1992;7(4):268-281.

Campbell NR, Hasinoff BB. Iron supplements: a common cause of drug interactions. Br J Clin Pharmacol. 1991;31(3):251-255.

Campbell NR, Hasinoff BB, Meddings JB, Anderson WD, Robertson S, Granberg K. Ferrous sulfate reduces cimetidine absorption. Dig Dis Sci. 1993;38(5):950-954.

Hines Burnham T, et al, eds. Drug Facts and Comparisons. St. Louis, MO:Facts and Comparisons;2000:1294.

Kara M, Hasinoff BB, McKay DW, et al. Clinical and chemical interactions between iron preparations and ciprofloxacin. Br J Clin Pharmacol. 1991;31(3):257-261.

Leonard JP, Desager JP, Beckers C, Harvengt C. In vitro binding of various biological substances by two hypocholesterolaemic resins. Cholestyramine and colestipol. Arzneim Forsch/Drug Res. 1979;29:979-981.

Li RC, Lo KN, Lam JS, et al. Effects of order of magnesium exposure on the postantibiotic effect and bactericidal activity of ciprofloxacin. J Chemother. 1999;11(4):243-247.

Neuvonen PJ. Interactions with the absorption of tetracyclines. Drugs. 1976;11(1):45-54.

Okhamafe AO, Akerele JO, Chukuka CS. Pharmacokinetic interactions of norfloxacin with some metallic agents. Int J Pharmaceutics. 1991;68:11-16.

Physicians' Desk Reference, 54^th ed. Montvale, NJ: Medical Economics Company; 2000.

Polk RE. Drug-drug interactions with ciprofloxacin and other fluoroquinolones. Am J Med. 1989;87(Suppl5A):76-81.

Schaefer JP, Tam Y, Hasinoff BB, et al. Ferrous sulphate interacts with captopril. Br J Clin Pharmacol. 1998;46(4):377-381.

Shakir KM, Chute JP, Aprill BS, Lazarus AA. Ferrous sulfate-induced increase in requirement for thyroxine in a patient with primary hypothyroidism. South Med J. 1997;90(6):637-639.

Tyrer LB. Nutrition and the pill. J Reprod Med. 1984;29(7 Suppl):547-550.