Drug Interaction Report

ADDITIONAL CONTRACEPTION RECOMMENDED: The effectiveness of estrogen-containing oral contraceptives may be impaired by concomitant treatment with antimicrobial agents. However, the risk appears to be small, and supportive data are primarily limited to anecdotal evidence from case reports and findings from uncontrolled or poorly controlled studies. Most antimicrobials, with the exception of the rifamycins and possibly griseofulvin, do not induce hepatic enzymes and have not been shown to significantly increase the clearance of oral contraceptive estrogens. Some investigators believe that antimicrobials interfere with the enterohepatic recirculation of estrogens by decreasing bacterial hydrolytic enzymes in the gastrointestinal tract that are responsible for regenerating parent estrogen molecules following first-pass metabolism. It is possible that a small number of women may be more susceptible to contraceptive failure and, consequently, are more sensitive to the effects of antimicrobials on estrogen disposition in vivo, but risk factors or genetic predispositions have yet to be identified.

MANAGEMENT: Until further data are available, women using oral contraceptives should be advised of the risk of breakthrough bleeding and unintended pregnancy during concomitant antimicrobial therapy. Alternative or additional methods of birth control should be considered during and for at least one week beyond the last dose of short-term antimicrobial therapy, and for at least the initial weeks of long-term antimicrobial therapy when risk may be the greatest.

ADJUST DOSING INTERVAL: The non-hormonal placebo pills included in some oral contraceptive preparations may contain iron, usually ferrous fumarate. Concomitant administration of these iron pills may significantly decrease the gastrointestinal absorption of antibiotics such as cefdinir. The proposed mechanism is chelation of cefdinir by the iron cation, forming a complex that is poorly absorbed from the gastrointestinal tract. According to product labeling, concomitant administration of cefdinir with a therapeutic iron supplement containing 60 mg of elemental iron (as ferrous sulfate) or vitamins supplemented with 10 mg of elemental iron resulted in a reduction of cefdinir absorption by 80% and 31%, respectively.

MANAGEMENT: To minimize potential interaction with iron, the product labeling recommends that cefdinir be taken at least 2 hours before or 2 hours after administration of iron-containing products.

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Coadministration with grapefruit juice may increase the bioavailability of oral estrogens. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits. In a small, randomized, crossover study, the administration of ethinyl estradiol with grapefruit juice (compared to herbal tea) increased peak plasma drug concentration (Cmax) by 37% and area under the concentration-time curve (AUC) by 28%. Based on these findings, grapefruit juice is unlikely to affect the overall safety profile of ethinyl estradiol. However, as with other drug interactions involving grapefruit juice, the pharmacokinetic alterations are subject to a high degree of interpatient variability. Also, the effect on other estrogens has not been studied.

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The central nervous system effects and blood levels of ethanol may be increased in patients taking oral contraceptives, although data are lacking and reports are contradictory. The mechanism may be due to enzyme inhibition. Consider counseling women about this interaction which is unpredictable.

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