Estradiol with Doxycycline Interaction Details

Brand Names Associated with Estradiol

Brand Names Associated with Doxycycline

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 13, 2023

Interaction Effect

Decreased contraceptive effectiveness

Interaction Summary

Concomitant use of doxycycline and oral combination contraceptives (OC) may reduce contraceptive efficacy because tetracyclines alter intestinal flora which, in turn, may alter enterohepatic circulation of the contraceptive. In a review of 163 cases of OC failure in reliable pill takers, 23% were attributed to concurrent use of antibiotics; 4% included a concurrent tetracycline . Absence of interaction was shown in a study (N=15) of concurrent use of ethinyl estradiol/etonogestrel vaginal ring contraceptive and doxycycline . A retrospective review (N=356) showed no difference in OC failure rates among women who received OC with or without concomitant antibiotics, including tetracyclines. Failure rate 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 a patient, an additional form of contraception is recommended .

Severity

Major

Onset

Delayed

Evidence

Theoretical

How To Manage Interaction

Concomitant use of doxycycline and combination oral contraceptives (OC) may result in decreased contraceptive efficacy. Although there was no increased risk of OC failure in a study of women with acne (n=34) who used OC concomitantly with antibiotics, including tetracyclines, tetracycline and its derivatives may interact with low-dose estrogen contraceptives. Absence of interaction was also shown in a study (N=15) of concurrent use of ethinyl estradiol/etonogestrel vaginal ring combination contraceptive and doxycycline . A retrospective review (N=356) showed no difference in 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 is recommended .

Mechanism Of Interaction

Alteration in gut flora, leading to decreased estrogen reabsorption

Literature Reports

A) Systemic exposure of ethinyl estradiol/etonogestrel with use of the vaginal ring contraceptive was not affected by concomitant use of doxycycline in a randomized, 2-way crossover study in healthy volunteers (n=15). Following synchronization of menstrual cycles by 21 to 28 days and a 7-day ring-free period, volunteers received the vaginal ring for 21 days with or without doxycycline 200 mg orally on day 1 then, 100 mg daily for 10 days. After a 7-day ring-free washout period, subjects crossed over to the opposite treatment arm. With administration of the vaginal ring alone, the mean AUC of ethinyl estradiol, measured at 24 hours, day 9 to 10, day 10, and day 21, was 0.638 nanograms x hr/mL, 0.538 nanograms x hr/mL, 5.51 nanograms x hr/mL, and 11.2 nanograms x hr/mL, respectively. With administration of the ring plus doxycycline, the mean AUC of ethinyl estradiol was 0.6 nanograms x hr/mL, 0.512 nanograms x hr/mL, 5.35 nanograms x hr/mL, and 10.9 nanograms x hr/mL, respectively. The AUC interaction/control ratio (ring with doxycycline to ring alone) also showed absence of drug interaction. At 24 hours, day 9 to 10, day 10, and day 21, the interaction/control ratio was 0.95, 0.92, 0.95, and 0.95, respectively. The etonogestrel plasma concentrations and interaction/control ratio demonstrated similar findings at all time points .

B) 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 .

C) 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-dose 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 .

D) The effect of doxycycline on serum levels of estradiol and norethindrone was studied in 24 women taking oral contraceptives. The subjects had been taking an oral contraceptive containing 1 mg norethindrone and 35 mcg ethinyl estradiol for at least 2 months prior to the study. Administration of doxycycline 100 mg daily for 7 days starting on day 14 of the 28-day cycle had no significant effect on the average serum levels of estradiol and norethindrone, however, there was substantial variability. Progesterone levels indicated that ovulation had not occurred in any of these subjects . Although no significant effect was observed in this study, antibiotics may have an effect in patients with unusually low oral contraceptive hormone levels.

E) 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 .

F) The interaction between oral contraceptives and tetracyclines 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 .

Estradiol Overview

• Estrogen is used to treat hot flushes ('hot flashes'; sudden strong feelings of heat and sweating) in women who are experiencing menopause ('change of life', the end of monthly menstrual periods). Some brands of estrogen are also used to treat vaginal dryness, itching, or burning, or to prevent osteoporosis (a condition in which the bones become thin and weak and break easily) in women who are experiencing or have experienced menopause. However, women who need a medication only to treat vaginal dryness or only to prevent osteoporosis should consider a different treatment. Some brands of estrogen are also to relieve symptoms of low estrogen in young women who do not produce enough estrogen naturally. Some brands of estrogen are also used to relieve the symptoms of certain types of breast and prostate (a male reproductive gland) cancer. Estrogen is in a class of medications called hormones. It works by replacing estrogen that is normally produced by the body.

Doxycycline Overview

• Doxycycline is used to treat a variety of infections caused by certain types of bacteria. Doxycycline is also used to treat or prevent anthrax (a serious infection that may be spread on purpose as part of a bioterror attack) in people who may have been exposed to anthrax in the air and to treat plague and tuleramia (serious infections that may be spread on purpose as part of a bioterror attack). It is also used to prevent malaria. Doxycycline is also used along with other medications to treat acne and rosacea (a skin disease that causes redness, flushing, and pimples on the face). Doxycycline (Oracea) is used only to treat pimples and bumps caused by rosacea. Doxycycline is in a class of medications called tetracycline antibiotics. It works to treat infections by preventing the growth and spread of bacteria. It works to treat acne by killing the bacteria that infects pores and decreasing a certain natural oily substance that causes acne. It works to treat rosacea by decreasing the inflammation that causes this condition.

• Antibiotics such as doxycycline will not work for colds, flu, or other viral infections. Using antibiotics when they are not needed increases your risk of getting an infection later that resists antibiotic treatment.

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Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.