Probenecid
Amoxicillin Interactions
The administration of amiloride 2 hours before a dose of amoxicillin oral suspension reduced the bioavailability of amoxicillin by 27% and its Cmax by 25%. No change in the renal clearance of amoxicillin was noted. Although the significance of this pharmacokinetic interaction is unclear, clinicians should avoid administering doses of these two drugs within 2 hours of the other. Staggering the administration times further may avoid this interaction.
Probenecid inhibits renal tubular secretion of amoxicillin, thereby causing higher, prolonged serum levels of the drug. In clinical practice, these two drugs routinely are administered together to treat gonorrhea. In general, this drug interaction should not pose a clinical problem.
Although concomitant use of amoxicillin with the aminoglycosides provides synergistic activity against enterococci and group B streptococci, the drugs cannot be administered at the same time or physically mixed together because they are chemically and physically incompatible. Some penicillins are known to inactivate aminoglycosides when mixed in intravenous; oral neomycin may reduce the oral absorption of the oral penicillins if administered concomitantly.
Concomitant use of amoxicillin with clavulanic acid improves the activity of amoxicillin against some beta-lactamase-producing bacteria such as H. influenzae. (NOTE: amoxicillin and clavulanic acid are marketed together as Augmentin®.)
Penicillins in large doses inhibits renal tubular secretion of methotrexate, thereby causing higher, prolonged serum levels of methotrexate.
Use of amoxicillin with allopurinol can increase the incidence of drug-related skin rash.
It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Nifedipine may increase the oral absorption of amoxicillin by enhancing the active transport of amoxicillin across the intestinal epithelium. However, the interaction is unlikely to be of clinical significance.
Chloramphenicol, macrolides, sulfonamides, and tetracyclines may interfere with bactericidal effects of penicillins. In vitro data support this, however, the clinical significance of these interactions are unknown.
[ Last revised: 8/30/2004 11:25:00 AM ]
References
. Amoxil® (amoxicillin) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2004 Jan.
. Zyloprim® (allopurinol) package insert. San Diego, CA: Prometheus Laboratories Inc.; 2001 July.
. Rheumatrex® (methotrexate) package insert. Cranbury, NJ: STADA Pharmaceuticals, Inc.; 2003 Feb.
. McLaughlin JE, et al. Clinical and laboratory evidence for inactivation of gentamicin by carbenicillin. Lancet 1971;1:261.
. Thompson MI, Russo ME, Saxton BJ, et al. Gentamicin inactivation by piperacillin or carbenicillin in patients with end-stage renal disease. Antimicrob Agents Chemother 1982;21:268 - 73.
. Halstenson CE, Hirata CA, Heim-Duthoy KL, et al. Effect of concomitant administration of piperacillin on the dispositions of netilmicin and tobramycin in patients with end-stage renal disease. Antimicrob Agents Chemother 1990;34:125 - 33.
. Uber WE, Brundage RC, White RL, et al. In vivo inactivation of tobramycin by piperacillin. DICP, Ann Pharmacother 1991;25:357.
. Roberts GW, Nayion RL, Jarvinen AO, et al. An in vivo assessment of the tobramycin/ticarcillin interaction in cystic fibrosis patients. Br J Clin Pharmacol 1993;36:372 - 5.
. Archer JSM, Archer DF. Oral contraceptive efficacy and antibiotic interaction: A myth debunked. J Am Acad Dermatol 2002;46:917 - 23.
. Dickinson BD, Altman RD, Nielsen NH, Sterling ML, for the Council on Scientific Affairs, American Medical Association (AMA). Drug interactions between oral contraceptives and antibiotics. Obstet Gynecol 2001;98:853 - 60. Review.
. Westphal JF, Jehl F, Brogard JM, et al. Amoxicillin intestinal absorption reduction by amiloride: possible role of the Na(+) -H+ exchanger. Clin Pharmacol Ther 1995;57:257 - 64.
. Augmentin® (amoxicillin and clavulanate potassium) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2004 Jun.
. Westphal JF, Trouvin JH, Deslandes A, et al. Nifedipine enhances amoxicillin absorption kinetics and bioavailability in humans. J Pharmacol Exp Ther 1990;255:312 - 7.
. Cheng SH, White A. Effect of orally administered neomycin on the absorption of penicillin V. N Engl J Med 1962;267:1296 - 7.
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