Background: Two pharmacokinetic studies were performed to investigate whether there is any interaction between etonogestrel or ethinylestradiol released from the combined contraceptive vaginal ring NuvaRingR and concomitant treatment with orally administered amoxicillin or doxycycline. Methods: In one study, healthy women were randomised to receive either NuvaRingR alone for 21 days or NuvaRingR for 21 days plus amoxicillin on days 1-10. After a 7-day ring-free washout period, women were crossed over to the alternate regimen for a further 21-day treatment period. The other study used an identical design except that women received doxycycline instead of amoxicillin. The amoxicillin study measured serum etonogestrel and ethinylestradiol levels and area under the serum concentration-time curve (AUC) values over the initial 12 hours on days 1 (AUC<inf>12</inf>) and 10 (AUC <inf>216-228</inf>) and the whole of days 1-11 (AUC<inf>240</inf>) and 1-22 (AUC<inf>504</inf>). The doxycycline study measured AUC values over the initial 24 hours on days 1 (AUC<inf>24</inf>) and 10 (AUC<inf>216-240</inf>) and the whole of days 1-11 (AUC<inf>240</inf>) and 1-22 (AUC<inf>504</inf>). Results: No differences in etonogestrel or ethinylestradiol serum concentrations were observed between subjects using NuvaRingR alone versus those receiving the ring plus either of the antibiotics. Calculation of etonogestrel and ethinylestradiol interaction/control ratios confirmed the absence of pharmacokinetic interactions. Conclusion: The results from these studies demonstrate the absence of pharmacokinetic interactions between etonogestrel and ethinylestradiol released from NuvaRingR and the oral antibiotics amoxicillin and doxycycline, suggesting that contraceptive efficacy would also be unaffected. < copyright > 2005 Adis Data Information BV. All rights reserved

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

Over 700 alleged OC/drug interactions were reported for antituberculous drugs, other antibiotics, anticonvulsants, antidepressants, and analgesics. Fewer than ten reports of OC/drug interactions were found involving antihistamines, thyroid hormone, vitamin C, antacids, ulcer medication, or diuretics. These may represent a set of OC/drug interaction problems that need to brought into medical awareness. Pregnancy is the first event reported when OCs appear to interact with another drug. However, menstrual disturbances are reported more often. BTB is the most frequently reported menstrual disturbance: it has been considered a warning signal that OC efficacy may be compromised. In such circumstances, contraceptive backup may be warranted. Reports of interference with OC efficacy have been most common for drugs used to treat tuberculosis, epilepsy, and depression, so patients and their physicians should be aware of potential problems. However, the average woman is more likely to encounter antibiotics, analgesics, and antihistamines, and current package inserts contain appropriate warnings. In recent years, prescriptions for low-estrogen OCs have outnumbered those for high-dose preparations. Many physicians became concerned that there was an increased risk of OC drug failure with the low-dose products. The database does not seem to suggest that this has happened. The dose of estrogen is not correlated with total adverse experience reports, time of appearances of the first adverse experience reports, or rate of reporting of the interactions. Likewise, reports of potential interactions with menstrual disturbances are not correlated with lower estrogen doses in OCs. There is, however, an association between low-estrogen OCs and recently reported pregnancies attributed to OC/drug interactions.(ABSTRACT TRUNCATED AT 250 WORDS)

There is considerable variation in opinion about the importance of drug interactions between the combined oral contraceptive pill (COCP) and broad-spectrum antibiotics. Clinical practice varies widely, especially between doctors in Europe and those in the US. Rifampicin and griseofulvin induce hepatic enzymes and do appear to have a genuine interaction with the COCP, leading to reduced efficacy. The situation with the broad-spectrum antibiotics is less clear. There are relatively few prospective studies of the pharmacokinetics of concurrent COCP and antibiotic use and few, if any, demonstrate a convincing basis for any reduced contraceptive efficacy. There is evidence, however, that variable contraceptive steroid handling could make some women, at some times, more susceptible to COCP failure. Given the serious consequences of unwanted pregnancy, the cautious approach of using additional or alternative contraception during short courses of broad-spectrum antibiotics and the initial weeks of long-term antibiotic administration may be justified to safeguard the few unidentifiable women who may be at risk. Conflicting opinion and advice is potentially confusing to both professionals and patients, and instructions for additional precautions during and after concurrent COCP and antibiotic use are complicated. Many women are ignorant of, or confused about, the circumstances that can cause OC to fail. Health professionals who prescribe the COCP must continue to strive to educate women about the mode of action and about the times when there is the greatest danger of failure. Professionals who feel that concurrent antibiotic use represents a real threat to contraceptive efficacy of the COCP should be prepared to present the advice for additional contraceptive precautions in a simple and consistent way, backed up with written information and reinforced at regular intervals

All tetracycline derivatives are bacteriostatics and their concentration in serum should not fall during the therapy below the generally accepted minimum therapeutic concentration of 0.5 to 1.5 mug/ml. Tetracyclines have a high affinity to form chelates with polyvalent metallic cations such as Fe+++, Fe++, Al+++, Mg++ and Ca++. Many of these tetracycline-metal complexes are either insoluble or otherwise poorly absorbable from the gastro-intestinal tract. Milk and other dairy products, antacids containing polyvalent cations, as well as various iron salts ingested simultaneously with tetracycline derivatives, might interfere with their absorption by 50 to 90% or even more. The severity of interaction depends both on the nature of the tetracycline derivative and of the cation, on the doses used, on pharmaceutical factors, and on time schedules in dosing. An interval of 3 hours between the ingestion of tetracyclines and cations prevents the interaction. The pharmacokinetic interactions in absorption of tetracyclines likely to be clinically significant in cases where the infecting pathogens are moderately resistant to tetracyclines and relatively high serum concentrations are needed for proper bacteriostasis

BACKGROUND: Despite anecdotal evidence of a possibility of decreased effectiveness of oral contraceptives (OCs) with some antibiotics, it is not known whether antibiotic use in dermatologic practices engenders any increased risk of accidental pregnancy. OBJECTIVE: Our purpose was to examine the effect of commonly prescribed oral antibiotics (tetracyclines, penicillins, cephalosporins) on the failure rate of OCs. METHODS: The records from three dermatology practices were reviewed, and 356 patients with a history of combined oral antibiotic/OC use were surveyed retrospectively. Of these patients, 263 also provided 'control' data (during the times they used OCs alone). An additional 162 patients provided control data only. RESULTS: Five pregnancies occurred in 311 woman-years of combined antibiotic/OC exposure (1.6% per year failure rate) compared with 12 pregnancies in 1245 woman-years of exposure (0.96% per year) for the 425 control patients. This difference was not significant (p = 0.4), and the 95% confidence interval on the difference (-0.81, 2.1) ruled out a substantial difference (> 2.1% per year). There was also no significant difference between OC failure rates for the women who provided data under both conditions, nor between the two control groups. All our data groups had failure rates below the 3% or higher per year, which are typically found in the United States. CONCLUSION: The difference in failure rates of OCs when taken concurrently with antibiotics commonly used in dermatology versus OC use alone suggests that these antibiotics do not increase the risk of pregnancy. Physicians and patients need to recognize that the expected OC failure rate, regardless of antibiotic use, is at least 1% per year and it is not yet possible to predict in whom OCs may fail

OBJECTIVE: The pharmacokinetics of norelgestromin, the primary active metabolite of norgestimate, plus ethinyl estradiol (EE), delivered by the once-weekly contraceptive patch (Ortho Evra/Evra), have been studied in eight trials. This overview summarizes the relevant pharmacokinetic data for the contraceptive patch. DESIGN: Review article. RESULT(S): The amount of norelgestromin and EE absorbed from the patch is proportional to patch size: the 20-cm(2) patch (Ortho Evra) delivers norelgestromin, 150 microg/d, and EE, 20 microg/d, to the systemic circulation. After single and multiple applications of the contraceptive patch, daily serum concentrations (area under the serum concentration-versus-time curve) of norelgestromin and EE were within the ranges generally seen with oral norgestimate, 250 microg/EE 35 microg (Ortho-Cyclen/Cilest), but without the peaks and troughs characteristic of oral dosing. Moreover, the contraceptive patch maintains serum concentrations of norelgestromin and EE within these ranges for up to 10 days, suggesting that clinical efficacy would be maintained even if a scheduled change is missed for as long as two full days. Regardless of the location of patch application (abdomen, buttock, upper outer arm, or torso [excluding breasts]) and even under conditions of heat, humidity, exercise, and cool-water immersion, efficacious concentrations of norelgestromin and EE are achieved. Coadministration of the patch with tetracycline did not affect the pharmacokinetics of norelgestromin and EE. CONCLUSION(S): The contraceptive patch exhibits an excellent pharmacokinetic profile, maintaining efficacious serum hormone concentrations under varying conditions

kvinde i microgyn behandling bliver gravid. Mistanke om graviditet grundet tetracyclin behandling fra 1.-4. cyclusdag.

Doxycycline and other antibiotics have been implicated in oral contraceptive (OC) failure, but information is sparse and studies of a doxycycline-OC interaction are nonexistent. Because an interaction between doxycycline and OCs, especially those containing low-dose estrogen, could result in an unplanned and unwanted pregnancy, a controlled clinical trial of the effects of doxycycline on OC hormone concentrations was performed. Twenty-four women aged 18-35 years were recruited as volunteers from among the patients seen in a University-based family planning clinic. While they were on a steady dose of the OC Ortho-Novum 1/35, serum concentrations of ethinyl estradiol, norethindrone, and endogenous progesterone were measured on days 18, 19, and 20 of the menstrual cycle (control phase). These measurements were repeated on days 18, 19, and 20 of the following menstrual cycle while the patient was taking doxycycline, 100 mg twice daily (treatment phase). No statistically significant differences in serum levels of ethinyl estradiol, norethindrone, or endogenous progesterone were seen between the control and treatment phases. However, there was large inter-patient and intra-patient variability in ethinyl estradiol and norethindrone levels. No elevations of endogenous progesterone occurred to suggest ovulation during antibiotic administration in either phase. It is not known what effects longer or earlier administration of doxycycline during the OC cycle would have on serum hormone concentrations or ovulation. Pregnancies attributed to failure of OCs because of tetracycline use could in fact be due to other causes or could represent a true interaction that only manifests itself in a small proportion of women at risk

Despite the widespread use of tetracycline for treatment of dermatologic disorders and sexually transmitted diseases, the pharmacodynamics of oral contraceptive use in the presence of tetracycline has not been studied. Seven normal women ingested an oral contraceptive containing ethinyl estradiol 35 micrograms and norethindrone 1 mg in the follicular phase of the menstrual cycle. On day 0 baseline ethinyl estradiol and norethindrone levels were obtained at 0, 1/2, 3/4, 1, 2, 4, 12, and 24 hours after oral contraceptive administration. On day 1 tetracycline 500 mg was given orally every 6 hours while the oral contraceptive was continued. Tetracycline, ethinyl estradiol, and norethindrone levels were determined at the same time intervals as on day 0. Oral contraceptive and tetracycline were continued for up to 10 days, and additional concentrations of ethinyl estradiol, norethindrone, and tetracycline were determined between days 5 and 10. Four additional normal women ingested tetracycline for 5 to 10 days. Tetracycline levels were determined at the time intervals noted above on day 1 and days 5 to 10. No significant decrease in plasma ethinyl estradiol or norethindrone concentration was seen with either short-term (24 hours) or long-term (5 to 10 days) ingestion of tetracycline. Similarly, levels of tetracycline do not significantly decrease with ingestion of a low-dose oral contraceptive