Iron compounds + H2-receptor antagonists - Drug Interactions

Apart from a brief and unconfirmed report alleging that cimetidine reduced response to ferrous sulfate in three patients,there appears to be no other evidence that H2-receptor antagonists reduce absorption of iron to a clinically relevant extent

Clinical evidence,mechanism, importance and management

A brief report describes 3 patients taking cimetidine 1g and ferrous sulfate 600mg daily whose ulcers healed after 2 months,but their anaemia and altered iron metabolism persisted. When cimetidine was reduced to 400mg daily, but with same dose of iron, blood picture resolved satisfactorily within a month (See reference number 1). The author of report attributed this response to cimetidine-induced rise in gastric pH, which reduced absorption of iron. However, this suggested mechanism was subsequently disputed, as medicinal iron is already in most absorbable form, Fe(See reference number 2+), and so does not need an acidic environment to aid absorption (See reference number 2). A study in patients with iron deficiency, or iron-deficiency anaemia, found that concurrent use of famotidine, nizatidine, or ranitidine, did not affect their response to 2.4 g of iron succinyl-protein complex (equivalent to 60mg of iron twice daily) (See reference number 3). No special precautions would seem necessary on concurrent use.

In a series of 3 studies,healthy subjects were given a 300mg tablet of cimetidine with either a 300mg tablet of ferrous sulfate or 300mg of ferrous sulfate in solution. The reductions in AUC and maximum serum levels of cimetidine were small (less than 16%). In third experiment they were given famotidine 40mg with a 300mg tablet of ferrous sulfate. Again, AUC and maximum serum level reductions were also very small (10% or less). These small reductions are almost certainly due to formation of a weak complex between iron and these H2-receptor antagonists (See reference number 4). An in vitro study with ranitidine found that,while it also binds with iron, it forms a very weak complex, and is less likely to bind than cimetidine or famotidine (See reference number 4). It was concluded that no clinically relevant interaction occurs between ferrous sulfate and any of these H2-receptor antagonists (See reference number 4).

Esposito R. Cimetidine and iron-deficiency anaemia. Lancet (1977) ii,1132.

Rosner F. Cimetidine and iron absorption. Lancet (1978) i,95.

Bianchi FM,Cavassini GB, Leo P. Iron protein succinylate in the treatment of iron deficiency: Potential interaction with H2-receptor antagonists. Int J Clin Pharmacol Ther Toxicol (1993) 31, 209–17.

Partlow ES,Campbell NRC, Chan SC, Pap KM, Granberg K, Hasinoff BB. Ferrous sulfatedoes not reduce serum levels of famotidine or cimetidine after concurrent ingestion. Clin Pharmacol Ther (1996) 59, 389–93.