Ethinyl Estradiol; Norethindrone with Tetracycline Interaction Details
Brand Names Associated with Tetracycline
- Achromycin V®
- Sumycin®
- Tetracycline
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 12, 2023
Interaction Effect
Decreased contraceptive effectiveness
Interaction Summary
Concomitant use of tetracycline and combination oral contraceptives may result in decreased contraceptive efficacy. The mechanism of interaction is thought that tetracyclines may alter intestinal flora which, in turn, may alter the enterohepatic circulation of combination contraceptives . 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 . 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 .
Severity
Major
Onset
Delayed
Evidence
Theoretical
How To Manage Interaction
Concomitant use of tetracycline and combination oral contraceptives may result in decreased contraceptive efficacy; however, evidence from a large retrospective chart review showed 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 .
Mechanism Of Interaction
Alteration in gut flora, leading to decreased estrogen reabsorption
Literature Reports
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 .
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 .
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 .
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 .
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 .
Tetracycline Overview
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Tetracycline is used to treat infections caused by bacteria including pneumonia and other respiratory tract infections; ; certain infections of skin, eye, lymphatic, intestinal, genital and urinary systems; and certain other infections that are spread by ticks, lice, mites, and infected animals. It is also used along with other medications to treat acne. Tetracycline is also used to treat plague and tuleramia (serious infections that may be spread on purpose as part of a bioterror attack). It can also be used in patients who cannot be treated with penicillin to treat certain types of food poisoning, and anthrax (a serious infection that may be spread on purpose as part of a bioterror attack). Tetracycline is in a class of medications called tetracycline antibiotics. It works by preventing the growth and spread of bacteria.
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Antibiotics such as tetracycline 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:
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.