Tetracycline and Levonorgestrel: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Levonorgestrel
Tetracycline
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
Concomitant use of tetracycline and combination oral contraceptives may result in decreased contraceptive efficacy4. The mechanism of interaction is thought that tetracyclines may alter intestinal flora which, in turn, may alter the enterohepatic circulation of combination contraceptives 3. Although there was no increased risk of contraceptive failure in a study of women with acne (n=34) who used OC concomitantly with antibiotics, including tetracycline, the data suggests that tetracycline and its derivatives may interact with low-dose estrogen contraceptives 2. 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 tetracyclines; 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 tetracyclines; 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) There was no increased risk of contraceptive failure with concomitant antibiotic use in a study of 34 patients with acne who used oral antibiotics, including tetracycline (n=17) and erythromycin (n=20), concomitantly with low estrogen oral contraceptives for a total period of 71 women-years. The calculated contraceptive failure rate was 1.4 per 100 women-years for the study, which was not significantly different than an accepted and documented contraceptive failure rate of 0.27 per 100 women-years (p=0.17). Of the 34 patients, one became pregnant while using the norethindrone, ethinyl estradiol, and mestranol combination concomitantly with oral tetracycline (12 months duration of use); the patient stated that she did not miss any doses of the contraceptive combination or had any changes in her menstrual cycle. Two other patients reported menstrual irregularities; one reported spotting while using the ethinyl estradiol and ethynodiol diacetate combination concomitantly with terfenadine and minocycline treatment, and another reported heavy cramping while using the norethindrone acetate and ethinyl estradiol combination concomitantly with tetracycline. Although this study determined that there was no increased risk of contraceptive failure with concomitant antibiotic use, the data suggests that tetracycline and its derivatives may interact with low-dose estrogen contraceptives 2.
c) The interaction between oral contraceptives and tetracycline has been suggested to 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 3.
d) A study which documented 163 cases of oral contraceptive failure in reliable pill takers found that 23% (37 cases) of these failures were associated with antibiotic use. Of these 163 cases, 6 were attributed to the use of tetracyclines, including doxycycline, minocycline, and lymecycline. The authors recommended a 7-day abstinence period or a barrier method of contraceptive following a course of antibiotics 5.
e) In a pharmacokinetic study, oral administration of tetracycline 500 mg four times daily for 3 days prior to and 7 days during use of the norelgestromin and ethinyl estradiol combination transdermal did not significantly affect the pharmacokinetics of norelgestromin or ethinyl estradiol 6.
Common questions
Can I take Tetracycline and Levonorgestrel together?
Decreased contraceptive effectiveness Always confirm with your pharmacist or prescriber before making any change.
How serious is the Tetracycline and Levonorgestrel 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 "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
Questions for your pharmacist
- Does my dose of Tetracycline or Levonorgestrel 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 (6)
- 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
- London BM & Lookingbill DP: Frequency of pregnancy in acne patients taking oral antibiotics and oral contraceptives. Arch Dermatol 1994; 130(3):392-393. DOI
- True RJ: Interactions between antibiotics and oral contraceptives (letter). JAMA 1982; 247:1408. DOI
- Product Information: tetracycline HCl oral capsule, tetracycline HCl oral capsule. Barr Laboratories, Inc (per DailyMed), Pomona, NY, 2006. DailyMed
- Sparrow MJ: Pill method failures. N Z Med J 1987; 100:102-105.
- Product Information: ORTHO EVRA(R) transdermal system patch, norelgestromin ethinyl estradiol transdermal system patch. Ortho Women’s Health & Urology (per FDA), Raritan, NJ, 2011.
Keep reading about Levonorgestrel
Keep reading about Tetracycline
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