Serum cipro, enoxacin, norfloxactn and pefloxacin (but not ofloxacin) levels can be reduced below therapeutic concentrations by the concurrent use of aluminium and magnesium antacids.
Clinical evidence
10 patients on dialysis (CAPD) because of renal failure were given given 250 mg cipro four times daily The steady-state serum cipro levels of three of them con currently taking alummium-containing antacids (Maalox, Mahnal) as phosphate binders were reduced by approximately two-thirds (peak serum levels fell from 3 69 to 1 25 ig/ml), whereas the serum levels of three others taking a calcium carbonate containing antacid (Titralac) for the same reason were unaffected.
A further study found that peak serum cipro levels and the AUC (area under the curve) were reduced 90% or more by the use of aluminium and magnesium-containing antacids. A later study found that the bioavailabihty of cipro was reduced 77-85% when Maalox was given within 2 h before the antibiotic n Reductions in serum levels of 50-98% in serum enoxacin, cipro, norfloxacin and pefloxacin levels have been described in other studies and case involving aluminium and magnesium containing antacids However no clinically important interaction was seen in a study of ofloxacin with a chewing tablet of Maalox. Another study found that calcium supplementa tion with calcium carbonate caused a 40% reduction in cipro bioavailability.
Mechanism
It is believed that certain functional groups (3-carbonyl and 4-oxo) on the antibiotics form insoluble chelates with aluminium and magnesium ions in the gut which reduces absorption. In addition these chelates appear to be relatively inactive as antibactenals.
Importance and management
The aluminium/magnesium antacid-cipro interaction is established and clinically important Serum antibiotic levels may become subtherapeutic against organisms such as staphylococci and Pseudomonas aeruginosa. Do not give the antacid and antibiotic at the same time Separating the dosages as much as possible reduces the effects of this interaction but it is difficult to assess the best time scheduling Giving the antacid 2-4 h before the antibiotic to avoid mixing m the gut results in reductions in absorption of 30-75%. One study suggests that the absorption is reduced 20-40% if the antacid is given 2-4 h after the antibiotic, whereas another suggests that no interaction occurs if given 2 h after the antibiotic u The makers of cipro advise avoidance within 4 h of these antacids Remember also that some antacids can raise the urinary pH The solubility of cipro decreases as the pH rises and excessive urinary alkalinity should be avoided to prevent crystalluna and possible kidney damage.
Much less is known about enoxacin, norfloxacin and pefloxacin but they seem to interact like cipro and the same precautions should be followed An alternative is possibly to use ofloxacin which appears not to interact.