Is It Safe To Take Keflex (Cephalexin) With Birth Control?

The pharmacist discusses whether or not Keflex (cephalexin) interacts with or reduces the effectiveness of birth control.


My Dr. put me on 500mg of cephalexin 3 times a day and 150mg of fluconazole. I am currently taking Estarylla birth control pills. I'm terrified that the medication my Dr. gave me will interfere with the birth control and I will end up pregnant, especially with all the controversy about antibiotics and birth control pills. My Dr. said I would be fine if I had unprotected sex but I'm not so sure. So is it really ok if I have unprotected sex?

Asked by Kenzie On Aug 27, 2022

Answered by
Medical Content Reviewed By HelloPharmacist Staff

Published Aug 27, 2022
Last updated Aug 27, 2022

Key points

  • Studies suggest that most antibiotics, with the exception of the rifampin family of antibiotics, don't significantly affect oral contraceptives (i.e. birth control tablets).
  • However, some studies have shown that a very small percentage of individuals may be affected by antibiotics and it would be prudent to use backup birth control while on antibiotic therapy, just to be safe.


Whether or not antibiotics, like Keflex (cephalexin), reduce the effectiveness of birth control is uncertain to some degree. However, most studies suggest that the vast majority of antibiotics do not significantly reduce birth control effectiveness, with the exception being the rifamycin family of antibiotics.

Nevertheless, as the consequences of unintended pregnancy are significant, and there isn't conclusive data regarding just how Keflex may affect hormone concentrations in birth control in all women, it would be prudent to use backup contraception when taking the antibiotic.

Interaction In Detail

Historically, it was thought that antibiotics could reduce the effectiveness of birth control pills by altering the bacterial flora in our gastrointestinal tract, which was thought to decrease overall estrogen levels. The mechanism behind this interaction is as follows:

  • The estrogen (Ethinyl estradiol) in oral contraceptives is primarily metabolized in the liver to the metabolite 2-hydroxy-ethinylestradiol and other hydroxylated and methylated metabolites.
  • These estrogen metabolites undergo what is known as enterohepatic recirculation. This means that these estrogen metabolites are recirculated into the GI tract after being processed by the liver.
  • The bacteria in our GI tract can change the metabolized estrogen back into the active, parent compound, Ethinyl estradiol, which increases overall absorption and concentrations of estrogen.
  • Antibiotics, like Keflex, theoretically eliminate much of our normal GI flora. Therefore, less of the metabolized estrogen is able to be converted back into the active compound, reducing overall concentrations and protection from pregnancy.

While the above may be the mechanism behind the potential antibiotic-birth control interaction, it doesn't appear to be significant for most people.

What Do The Studies Say?

The vast majority of studies on the matter conclude that most antibiotics do not significantly alter the concentrations of hormones from birth control pills and therefore do not reduce the effectiveness of birth control. Antibiotics that have little evidence of this interaction include:

  • Ampicillin
  • Penicillin (conflicting data)
  • Cephalexin
  • Ciprofloxacin
  • Clarithromycin
  • Doxycycline
  • Metronidazole
  • Tetracycline (conflicting data)

The only antibiotics that have been definitively shown to decrease hormone concentrations are anti-tuberculosis drugs like rifampin, which interact with oral hormones via an entirely different mechanism (by speeding up metabolism of estrogen).

However, and this is an important point, one large study, published in Obstetrics and Gynecology, reported that a small number of individual patients, who are difficult to accurately identify, did experience significant decreases in hormone concentrations from birth control pills when taking antibiotics and these individuals ovulated (which birth control pills are supposed to suppress). 

The study concluded the following:

"Pharmacokinetic studies of other antibiotics have not shown any systematic interaction between antibiotics and OC [oral contraceptive] steroids. However, individual patients do show large decreases in the plasma concentrations of ethinyl estradiol when they take certain other antibiotics, notably tetracycline and penicillin derivatives. Because it is not possible to identify these women in advance, a cautious approach is advised."


So overall, if you aren't taking a rifampin-type antibiotic, which Keflex is not, the effectiveness of your birth control will probably not be significantly affected. However, as there may be some individuals more susceptible to the interaction, and because unplanned pregnancy has life-changing consequences, backup birth control (e.g. condoms) is recommended.

In terms of how long to wait after taking antibiotics to stop backup contraception, the most common recommendation is for 7 days after you finish your antibiotic. This allows time for the bacteria in your gut to "re-grow" and for hormone concentrations from the birth control pills to return to a normal level.


  • Drug interactions between oral contraceptives and antibiotics, PubMed
  • Keflex Prescribing Information, AccessFDA
  • Oral contraceptive efficacy and antibiotic interaction: a myth debunked, PubMed

About the Pharmacist

Dr. Brian Staiger, PharmD

Dr. Brian has been practicing pharmacy for over 11 years and has wide-ranging experiences in many different areas of the profession. From retail, clinical and administrative responsibilities, he's your knowledgeable and go-to source for all your pharmacy and medication-related questions! Feel free to send him an email at! You can also connect with Dr. Brian Staiger on LinkedIn.

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