ANTIBIOTICS
AND ORAL CONTRACEPTIVES.
DeRossi
SS, Hersh EV. Dent Clin North Am 2002 Oct;46(4):653-64
With
the exception of rifampin-like drugs, there is a lack of scientific evidence
supporting the ability of commonly prescribed antibiotics, including all those
routinely employed in outpatient dentistry, to either reduce blood levels and/or
the effectiveness of oral contraceptives. To date, all clinical trials studying
the effects of concomitant antibiotic therapy (with the exception of rifampin
and rifabutin) have failed to demonstrate an interaction. Like all drugs, oral
contraceptives are not 100% effective with the failure rate in the typical
United States population reported to be as high as 3%. It is thus possible that
the case reports of unintended pregnancies during antibiotic therapy may simply
represent the normal failure rate of these drugs. Considering that both drug
classes are prescribed frequently to women of childbearing potential, one would
expect a much higher rate of oral contraceptive failure in this group of
patients if a true drug:drug interaction existed. On the other hand, if the
interaction does exist but is a relatively rare event, occurring in, say, 1 in
5000 women, clinical studies such as those described in this article would not
detect the interaction. The pharmacokinetic studies of simultaneous antibiotic
and oral contraceptive ingestion, and the retrospective studies of pregnancy
rates among oral contraceptive users exposed to antibiotics, all suffer from
one potential common weakness, i.e., their relatively small sample size. Sample
sizes in the pharmacokinetic trials ranged from 7 to 24 participants, whereas
the largest retrospective study of pregnancy rates still evaluated less than
800 total contraceptive users. Still, the incidence of such a rare interaction
would not differ from the accepted normal failure rate of oral contraceptive
therapy. The medico-legal ramifications of what looks like at best a rare
interaction remains somewhat "murky." On one hand, we have
medico-legal experts advising the profession to exercise caution and warn all
oral contraceptive users of a potential reduction in efficacy during antibiotic
therapy. These opinions are not evidence-based and rely heavily on one or two
legal proceedings that cannot even be substantiated. On the other hand, there
is one recently published legal proceeding in which the outcome was in favor of
the oral surgeon. There is clearly a need for additional scientific research in
oral contraceptive users that incorporates larger sample sizes, different time
courses (prophylactic use versus standard 7-10 day use versus extended use),
and different delivery systems (systemic administration versus local-controlled
delivery) of antibiotic therapy. Though experts on this topic still recommend
informing oral contraceptive users of the potential for a rare interaction, and
for clinicians to advise them to employ additional barrier techniques of birth
control during antibiotic therapy and for at least 1 week beyond the last dose
[40], it is hoped that a set of guidelines regarding this controversy will
eventually be published that is evidence-based, and not solely the results of
anecdotal reports, expert opinions, and legal proceedings.
ORAL
CONTRACEPTIVE EFFICACY AND ANTIBIOTIC INTERACTION: A MYTH DEBUNKED.
Archer
JS, Archer DF. J Am Acad Dermatol 2002 Jun;46(6):917-23
The
purpose of this study was to review the pharmacokinetic and clinical literature
regarding the efficacy of oral contraceptives when used concomitantly with
antibiotic therapy. Relevant literature was identified by searching MEDLINE and
EMBASE. Other sources were located by consulting the bibliographies of the
material collected from MEDLINE and EMBASE. Pharmacokinetic evidence
demonstrates that plasma levels of oral contraceptive steroids are unchanged
with the concomitant administration of antibiotics, including ampicillin,
ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin,
roxithromycin, temafloxacin, and tetracycline. However, reduced steroid levels
have been reported in women taking rifampin with oral contraceptives. Clinical
reports of contraceptive failure with antibiotic use are retrospective, have
multiple potential biases, and are not supported by pharmacokinetic data.
Available scientific and pharmacokinetic data do not support the hypothesis
that antibiotics (with the exception of rifampin) lower the contraceptive
efficacy of oral contraceptives.
DRUG
INTERACTIONS BETWEEN ORAL CONTRACEPTIVES AND ANTIBIOTICS.
Dickinson
BD, et al. Obstet Gynecol 2001 Nov;98(5 Pt 1):853-60
OBJECTIVE:
To evaluate the evidence on possible drug interactions between antibiotics and
oral contraceptives (OCs) that may lead to OC failure.
DATA
SOURCES: MEDLINE and Lexis/Nexis Medical Library searches for 1966-1999 using
the key word "oral contraceptives," cross-indexed with the terms
"antibiotics," "adverse effects," and
"pregnancy," and MEDLINE search using the additional MeSH term
"drug interactions." No language restrictions were used.
METHODS
OF STUDY SELECTION: A total of 167 articles were retrieved for analysis.
Another 32 articles were identified by review of the references cited in these
publications. Articles were selected based on their ability to provide
information on the relationship between antibiotic therapy and OC efficacy in
otherwise compliant users (defined as women with unplanned pregnancies who
reported compliance with their OC regimen). Additionally, studies that either
directly measured the effects of antibiotics on the pharmacokinetics of OC
components, or that analyzed the effects of antibiotics on measures of ovulation
in OC users were accepted.
TABULATION,
INTEGRATION, AND RESULTS: At least 30 cases have been reported of pregnancies
occurring in women taking OCs and antibiotics, particularly rifampin.
Approximately 20% of pregnant women reporting to family planning or abortion
clinics reported concomitant OC and antibiotic use. Information from adverse
event reporting databases generally mirrors the types of information gleaned
from these case reports and clinical surveys and accounts for approximately
one-third of reported cases. Retrospective surveys, primarily from
dermatology-based practices, also have reported 24 pregnancies in OC users who
concomitantly received therapy with antibiotics, most commonly tetracyclines
and penicillins. Apparent OC failure rates in clinical surveys were within the
usual range expected for patterns of typical use. In pooled results obtained
from relatively small populations, oral antibiotics, with the exception of
rifampin, have not significantly affected the pharmacokinetics of ethinyl
estradiol, levonorgestrel, and norethindrone or reduced the serum
concentrations of gonadotropins. However, individual patients have been
identified who experienced significant decreases in the plasma concentration of
these components of OCs and who appeared to ovulate.
CONCLUSION:
Rifampin impairs the effectiveness of OCs. Pharmacokinetic studies of other
antibiotics have not shown any systematic interaction between antibiotics and
OC steroids. However, individual patients do show large decreases in the plasma
concentrations of ethinyl estradiol when they take certain other antibiotics,
notably tetracycline and penicillin derivatives. Because it is not possible to
identify these women in advance, a cautious approach is advised.