Amoxicillin with Levonorgestrel Interaction Details

Brand Names Associated with Amoxicillin

Brand Names Associated with Levonorgestrel

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Mar 03, 2024

Interaction Effect

Decreased contraceptive effectiveness

Interaction Summary

Amoxicillin may alter intestinal flora, possibly leading to lower estrogen reabsorption and decreased oral combination contraceptive efficacy[1]. Concomitant use has been associated with unintended pregnancies and menstrual changes [2][3][4]. However, systemic exposure to ethinyl estradiol/etonogestrel was not different when the vaginal ring was used with or without a 10-day course of amoxicillin during a randomized, crossover study (n=15) [5]. Furthermore, 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.. The OC failure rate in both groups did not exceed a typical contraceptive failure rate of 1% to 3%. If a 1% to 3% contraceptive failure rate is unacceptable, recommend an additional form of contraception [6].

Severity

Major

Onset

Delayed

Evidence

Theoretical

How To Manage Interaction

Concomitant use of amoxicillin and combination contraceptives may result in decreased contraceptive efficacy[1]; however, significant differences in contraceptive failure rates were not demonstrated during a study of oral contraceptives with or without antibiotics [6] and no significant difference in exposure was observed with the use of the vaginal ring with or without amoxicillin [5]. If a typical failure rate of 1% to 3% is a concern for the patient, consider additional or alternative forms of birth control.

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 amoxicillin in a randomized, 2-way crossover study in healthy women 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 amoxicillin 875 mg orally twice daily for 10 days (mean age, 29.9 +/- 5.8 years). 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 12 hours, day 9 to 10, day 10, and day 21, was 0.328 +/- 0.092 nanograms x hr/mL, 0.266 +/- 0.0874 nanograms x hr/mL, 5.86 +/- 1.77 nanograms x hr/mL, and 11.7 +/- 3.86 nanograms x hr/mL, respectively. With administration of the ring plus amoxicillin, the mean AUC of ethinyl estradiol was 0.328 +/- 0.0757 nanograms x hr/mL, 0.252 +/- 0.0935 nanograms x hr/mL, 5.49 +/- 1.67 nanograms x hr/mL, and 11.3 +/- 3.57 nanograms x hr/mL, respectively. The AUC interaction/control ratio (ring with amoxicillin to ring alone) also showed absence of drug interaction. At 12 hours, day 9 to 10, day 10, and day 21, the interaction/control ratio was 1.01 (90% CI, 0.87 to 1.18), 0.96 (90% CI, 0.84 to 1.09), 0.95 (90% CI, 0.85 to 1.06), and 0.98 (90% CI, 0.88 to 1.09), respectively. The etonogestrel plasma concentrations and interaction/control ratio demonstrated similar findings at all time points [5].

B) 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 [6].

References

1 ) Product Information: amoxicillin oral capsules, oral suspension, oral chewable tablets, amoxicillin oral capsules, oral suspension, oral chewable tablets. Teva Pharmaceuticals USA (per DailyMed), Sellersville, PA, 2013.

2 ) Szoka PR & Edgren RA: Drug interactions with oral contraceptives: compilation and analysis of an adverse experience report database. Fertil Steril 1988; 49(5 suppl 2):31S-38S.

3 ) Back DJ, Breckenridge AM, Crawford FE, et al: Interindividual variation and drug interactions with hormonal steroid contraceptives. Drugs 1981; 21:46-61.

4 ) True RJ: Interactions between antibiotics and oral contraceptives (letter). JAMA 1982; 247:1408.

5 ) Dogterom P, van den Heuvel MW, & Thomsen T: Absence of pharmacokinetic interactions of the combined contraceptive vaginal ring NuvaRing with oral amoxicillin or doxycycline in two randomised trials. Clin Pharmacokinet 2005; 44(4):429-438.PubMed Abstract: http://www.ncbi.nlm.nih.gov/...

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 Abstract: http://www.ncbi.nlm.nih.gov/...

Amoxicillin Overview

• Amoxicillin is used to treat certain infections caused by bacteria, such as pneumonia; bronchitis (infection of the airway tubes leading to the lungs); and infections of the ears, nose, throat, urinary tract, and skin. It is also used in combination with other medications to eliminate H. pylori, a bacteria that causes ulcers. Amoxicillin is in a class of medications called penicillin-like antibiotics. It works by stopping the growth of bacteria.

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

Levonorgestrel Overview

• Levonorgestrel is used to prevent pregnancy after unprotected sexual intercourse (sex without any method of birth control or with a birth control method that failed or was not used properly [e.g., a condom that slipped or broke or birth control pills that were not taken as scheduled]). Levonorgestrel should not be used to prevent pregnancy on a regular basis. This medication is to be used as an emergency contraceptive or backup in case regular birth control fails or is used incorrectly. Levonorgestrel is in a class of medications called progestins. It works by preventing the release of an egg from the ovary or preventing fertilization of the egg by sperm (male reproductive cells). It also may work by changing the lining of the uterus (womb) to prevent development of a pregnancy. Levonorgestrel may prevent pregnancy, but it will not prevent the spread of human immunodeficiency virus (HIV, the virus that causes acquired immunodeficiency syndrome [AIDS]) and other sexually transmitted diseases.

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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.