Plasma levels of norethisterone (NET), ethinyl estradiol (EE), Ampicillin or Metronidazole were estimated in 16 women, who were taking low-dose oral combination contraceptive pills (containing norethisterone acetate 1 mg and ethinyl estradiol 30 microgram) and in whom concurrently, either Ampicillin (6 women) or Metronidazole therapy (10 women) was given. Neither Ampicillin nor Metronidazole therapy altered the ´peak´ or 24-hour plasma levels and area under the curve, for NET and EE. Furthermore, oral contraceptive treatment did not alter the ´peak´ levels of Ampicillin or Metronidazole. Progesterone (P) levels were in the anovulatory range in all Ampicillin treated cycles. However, in Metronidazole treated group, two out of 10 women showed a P rise of more than 4 ng/ml. The study was expanded to include another group of 15 women treated with Metronidazole, where only one women showed a P rise of more than 4 ng/ml. The occurrence of ´escape ovulation´ as suggested by P rise of more than 4 ng/ml in three out of 25 Metronidazole treated women is either a chance incidence due to a different pharmacological response in them, or most probably due to the default in the regular intake of pills in these women. This is supported by the observation that one out of three women showing a P rise (greater than 4 ng/ml( during concurrent Metronidazole therapy, also showed ovulatory P values in oral contraceptive-only treated cycles. Furthermore, in the control group also, one out of 10 women had ovulatory P levels (greater than 4 ng/ml) in oral contraceptive-only treated cycles

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

Antibacterial drugs, such as quinolones, macrolides, rifampin, isoniazid, and trimethoprim-sulfamethoxazole, can interact with other drugs in a wide variety of clinically significant ways. They are frequently administered with other prescription and nonprescription medications. Antibacterial agents may interact by causing a change in the pharmacokinetics or pharmacodynamics of a second drug. In other cases, the antimicrobial may be affected by the action of another drug. Interactions involving antimicrobials often result from alterations in the absorption of the antimicrobial from the gastrointestinal tract or changes in the hepatic metabolism or renal elimination of the drugs concurrently administered. While certain classes of antibacterial drugs are known to interact with many other drugs, the interaction potential of most classes of antimicrobials is not uniform among members of the class. This diversity in interaction potential provides the clinician with an opportunity to avoid potential interactions by means of appropriate drug selection. An understanding of the common, clinically significant drug interactions involving antibacterial agents will enable the physician to avoid unnecessary adverse drug reactions

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

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

Earlier studies have shown that ampicillin produces 50% lower-and therefore very likely less adequate-plasma levels in pregnant than in nonpregnant women. The present investigation compares levels of ampicillin in plasma and urine produced by a single oral dose administered to 10 healthy women taking oral contraceptives on the 21st and on the 28th day of the menstruation cycle. Plasma levels of ampicillin were lower on the 21st day than on the 28th, i.e. a difference in the same direction as between pregnant and nonpregnant women although the difference was not significant. Contrary to what was found for pregnant women the dose of ampicillin to women taking oral contraceptives does not have to be doubled in order to compensate for lower plasma levels

The effectiveness of oral contraceptives with concomitant use of ampicillin has been questioned. Eleven volunteer subjects were studied during 2 consecutive menstrual cycles; they were given Demulen with placebo or ampicillin during each of the cycles. Serum estradiol (E2), progesterone (P4), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were evaluated on days 13 and 19 of each cycle. Testosterone-binding globulin (TeBG) capacity and ferning of cervical mucus were evaluated on day 13 of each cycle. Subjective symptoms were recorded. All cycles appeared to be anovulatory. Steroid suppression was present in 10 of 11 patients during both cycles. Estrogen-dependent TeBG was not affected by ampicillin. It is possible that cervical mucus ferning was improved by concurrent ampicillin administration. Ampicillin appears unlikely to diminish the effectiveness of the oral contraceptive studied

1 Thirteen women taking long term oral contraceptive steroids were studied while taking ampicillin (500 mg three times daily) and compared to a control cycle while not taking ampicillin. 2 There were no significant changes in the plasma concentrations of ethinyloestradiol, levonorgestrel, follicle stimulating hormone or progesterone, although lower concentrations of ethinyloestradiol were noted in two women. 3 We conclude that most patients taking oral contraceptive steroids do not need to take alternative contraceptive precautions while taking ampicillin