Bacampicillin and Estradiol Topical: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Estradiol Topical
Bacampicillin
No brand names on record
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
Decreased contraceptive effectiveness
Interaction Deep Dive
Contraceptive effectiveness may be reduced when oral contraceptives are coadministered with antibiotics. The mechanism of interaction is thought that penicillins may alter intestinal flora which, in turn, may alter the enterohepatic circulation of combination contraceptives. This could result in unintended pregnancies and menstrual changes345. However, in a large retrospective chart review, there was no significant difference in oral contraceptive (OC) failure rates among women who received OC with or without concomitant antibiotics, including penicillins; and the OC failure rate in both groups did not exceed a typical contraceptive failure rate of 1% to 3%. If at any time, a 1% to 3% contraceptive failure rate is unacceptable to the patient, an additional form of contraception should be recommended 1.
Why it happens (mechanism)
Alteration in gut flora, leading to decreased estrogen reabsorption
Literature reports
5 reports — tap to read
a) There was no significant difference in oral contraceptive (OC) failure rates among women who received OC with or without concomitant antibiotics, including penicillins; and the OC failure rate in both groups did not exceed a typical contraceptive failure rate of 1% to 3% in a retrospective chart review and follow-up survey. Of 356 women who received antibiotics and OC concurrently over 311.2 woman-years, 5 pregnancies occurred yielding a rate of 1.6 pregnancies per 100 woman-years or a 1.6%/year failure rate. Of 425 control patients who received OC without antibiotics for 1244.9 woman-years, 12 pregnancies occurred yielding a rate of 0.96 pregnancies per 100 woman-years or 0.96%/year failure rate. The difference in failure rate between these groups was not significant (95% CI on the difference, -0.81 to 2.1; p=0.4) and ruled out a substantial difference (greater than 2.1% per year). The women in the control group consisted of 263 women who received OC but did not concomitantly use OC with antibiotics and 162 OC users who never concomitantly used antibiotics. Among women who never concomitantly used antibiotics (n=162) over 551.2 woman-years, 7 pregnancies occurred, yielding a rate of 1.3 pregnancies per 100 woman-years or 1.3%/year failure rate 1.
b) Concomitant ampicillin and oral contraceptive therapy has been reported to result in menstrual irregularity and unplanned pregnancy, as well as reduced urinary excretion of endogenous estrogens 7891011.
c) Ampicillin had no significant effect on plasma levels of ethinyl estradiol, levonorgestrel, follicle-stimulating hormone, or progesterone when given in combination with oral contraceptives. The authors indicate that alternative contraceptive methods are not required during combined therapy 6.
d) The interaction between oral contraceptives and ampicillin may be due to an alteration of the gut flora. The normal gut flora is thought to be responsible for the hydrolysis of the glucuronide moiety (estrogen metabolite found in the bile) to free drug. When the gut flora is altered, enterohepatic recirculation is reduced and the metabolite is simply excreted. This causes a decrease in body levels of the estrogen and reduced effectiveness 5.
e) In a study of 11 regularly menstruating women, ages 21 to 39 years, concurrent ampicillin administration appeared not to diminish the effectiveness of the oral contraceptive studied. Demulen(R) (1 mg ethynodiol diacetate and 50 mcg ethinyl estradiol) was given to each subject for 2 consecutive menstrual cycles, 21 days on and 7 days off. Ampicillin 250 mg or placebo was given 4 times a day from day 1 through day 16 of each study cycle. Two subjects experienced breakthrough bleeding while taking ampicillin. One subject reported spotting with Demulen(R)/placebo combination, but not with Demulen(R)/ampicillin. There was no difference in quantity of menstrual flow between the two study cycles. One subject reported mid-cycle abdominal pain while on Demulen(R)/ampicillin. All cycles appeared to be anovulatory with no significant difference in follicle-stimulating hormone, luteinizing hormone, and steroid hormone levels in patients on Demulen(R)/ampicillin compared with patients on Demulen(R)/placebo 2.
Common questions
Can I take Bacampicillin and Estradiol Topical together?
Decreased contraceptive effectiveness Always confirm with your pharmacist or prescriber before making any change.
How serious is the Bacampicillin and Estradiol Topical interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of Bacampicillin or Estradiol Topical need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (11)
- Helms SE, Bredle DL, Zajic J, et al: Oral contraceptive failure rates and oral antibiotics. J Am Acad Dermatol 1997; 36(5 Pt 1):705-710. PubMed
- Friedman CI, Huneke AL, Kim MH, et al: The effect of ampicillin on oral contraceptive effectiveness. Obstet Gynecol 1980; 55:33-37.
- Back DJ, Breckenridge AM, Crawford FE, et al: Interindividual variation and drug interactions with hormonal steroid contraceptives. Drugs 1981; 21:46-61. PubMed
- Bainton R: Interaction between antibiotic therapy and contraceptive medication. Oral Surg Oral Med Oral Pathol 1986; 61:453-455. DOI
- True RJ: Interactions between antibiotics and oral contraceptives (letter). JAMA 1982; 247:1408. DOI
- Back DJ, Breckenridge AM, MacIver M, et al: The effects of ampicillin on oral contraceptive steroids in women. Br J Clin Pharmacol 1982; 14:43-48.
- Trybuchowski H: Effect of ampicillin in the urinary output of steroidal hormones in pregnant and non-pregnant women. Clin Chim Acta 1973; 45:9-18.
- Boehm FH, DiPietro DL, & Goss DA: The effect of ampicillin administration on urinary estriol and serum estradiol in the normal pregnant patient. Am J Obstet Gynecol 1974; 119:98-103. PubMed
- Sybulski S & Maughan GB: Effect of ampicillin administration on estradiol, estriol, and cortisol levels in maternal plasma and on estriol levels in urine. Am J Obstet Gynecol 1976; 124:379-381. DOI
- Adlercreutz H, Martin F, Lehtinen T, et al: Effect of ampicillin administration on plasma conjugated and unconjugated estrogen and progesterone levels in pregnancy. Am J Obstet Gynecol 1977; 128:266-271. DOI
- Back DJ, Grimmer SF, Orme ML, et al: Evaluation of Committee on Safety of Medicines yellow card reports on oral contraceptive-drug interactions with anticonvulsants and antibiotics. Br J Clin Pharmacol 1988; 25:527-532. PubMed
Keep reading about Estradiol Topical
Keep reading about Bacampicillin
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