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Amoxicillin-potassium clavulanate interactions to avoid

Amoxicillin-potassium clavulanate interacts with certain birth control, warfarin, methotrexate, tetracycline antibiotics, and antigout agents
By | Oct. 27, 2023
Three Rx pill bottles: Amoxicillin-potassium clavulanate interactions to avoid
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Amoxicillin-potassium clavulanate is a widely used antibiotic from the penicillin family that is prescribed for bacterial infections of the sinuses, ears, lungs, and skin, as well as diverticulitis and urinary tract infections. Barring an allergy to penicillins, you stand a good chance of being prescribed amoxicillin-potassium clavulanate; its brand-name version, Augmentin; or the extended-release tablets. Although a commonly used antibiotic, it has potential drug interactions with birth control pills, tetracycline antibiotics, the gout prevention drugs probenecid and allopurinol, the autoimmune arthritis disease modifier methotrexate, and the anticoagulant warfarin. Unintended pregnancy, adverse effects, and hemorrhage could result from these interactions, so it is worth reading on to understand them better.

Key takeaways:

  • Clinical studies have raised concern that antibiotics like amoxicillin-potassium clavulanate could reduce the effectiveness of estrogen-based contraceptives, namely birth control pills, increasing the chance of unintended pregnancy.
  • Like most antibiotics, amoxicillin-potassium clavulanate increases the effectiveness of warfarin in thinning the blood, leading to a higher likelihood of bleeding.
  • The drug, like all penicillins, increases the concentration of methotrexate when co-administered, which means more potential for methotrexate toxicity.
  • Tetracyclines may reduce the effectiveness of amoxicillin-potassium clavulanate, and conversely, probenecid and allopurinol can increase the antibiotic’s side effect potential

Amoxicillin-potassium clavulanate-drug interactions

Drug interactions with amoxicillin-potassium clavulanic acid boil down to either diminished or heightened levels of either the antibiotic or other drug. As a result, the beneficial effects of the meds may be nullified, or negative effects may be magnified.

Estrogen-based contraceptives

In reviews of the topic, antibiotic usage in women on hormonal contraceptives has been associated with an increased rate of unintended pregnancy. However, this concern has not been fully substantiated, and other reviews have found no significant interaction. A change in treatment is not usually recommended, but using a barrier method of contraception, such as a condom, may be reasonable in addition to the estrogen-based contraceptive. Of course, using a condom also provides the extra advantage of some protection against sexually transmitted diseases.

Most commonly, estrogen-based contraceptives are taken in the form of birth control pills. Other varieties include patches and rings. Examples of these various versions include:

  • Junel (ethinyl estradiol and norethindrone pill)
  • Loestrin (ethinyl estradiol and norethindrone pill)
  • Xulane (ethinyl estradiol and norelgestromin weekly patch)
  • Zafemy (ethinyl estradiol and norelgestromin weekly patch)
  • Nuvaring (ethinyl estradiol and etonogestrel monthly vaginal ring)

Warfarin

Warfarin is an oral anticoagulant that thins the blood by blocking vitamin K-associated production of clotting proteins. Because vitamin K is absorbed after being produced by bacteria living in our intestines, antibiotics can reduce our vitamin K levels by killing these “good” bacteria. As a result, warfarin’s effectiveness can spike upward while taking antibiotics like amoxicillin-potassium clavulanate. This can mean more of a risk of bleeding. Your healthcare provider may want you to monitor warfarin closely while taking an antibiotic and seek immediate medical attention if you develop bleeding.

Methotrexate

Penicillins like amoxicillin-potassium clavulanate can increase the bodily concentrations of methotrexate. Because methotrexate has a number of potentially serious side effects, you should be aware of this interaction. Methotrexate can cause adverse effects on the skin, liver, kidney, and blood cell counts. Bring this concern up to your doctor if you are prescribed both drugs, and if taking both, seek medical attention for new symptoms, such as fatigue, rash, skin color change, and change in urination.

Tetracycline-class antibiotics

The family of tetracycline antibiotics is often used for tick-borne illnesses, as well as skin and respiratory tract infections. In some cases, when dual antibiotic treatment is recommended, or two different infections are treated, they can be used alongside amoxicillin-potassium clavulanate. A tetracycline antibiotic could potentially lower the antibacterial efficacy of penicillins via competing mechanisms of action. To date, this has only been found to be an issue during the treatment of meningitis. Common tetracyclines include:

Antigout agents 

Allopurinol and probenecid are two of the primary medicines for preventing attacks of gout. If you take allopurinol along with amoxicillin/clavulanate potassium, your risk of developing a skin rash may be higher. 

Probenecid, on the other hand, directly increases levels of amoxicillin-potassium clavulanate in the body, an effect that could be thought of as positive or negative. Limited studies on the topic have not been conclusive, with some demonstrating an advantage in treating infection, others an adverse outcome from side effects, and still others showing no difference. At this point, if you find yourself on one of these drug combinations, you should discuss the interaction with your prescribing healthcare professional.

Amoxicillin-potassium clavulanate-food interactions

Amoxicillin-potassium clavulanate is actually best taken with food and can even be mixed with milk or juice to facilitate a pediatric dose of oral suspension liquid. Significant food interactions are not a concern.

Other amoxicillin-potassium clavulanate interactions

Fortunately, this member of the penicillin family does not have many other interactions or contraindications. Nonetheless, a few are important to note.

Amoxicillin-potassium clavulanate and phenylketonuria

Phenylalanine can be present in some preparations of amoxicillin-potassium clavulanate. Accordingly, those with the metabolic disorder phenylketonuria should ask their pharmacists if phenylalanine is present to determine whether to avoid the drug.

Amoxicillin-potassium clavulanate and renal impairment

The drug is excreted in the urine, and if kidney function is severely impaired, the drug’s concentration could be too high. If you have kidney disease, you should get the medical advice of your healthcare team when prescribed amoxicillin-potassium clavulanate, or any new drug for that matter, to see if the dose should be adjusted for you.

Amoxicillin-potassium clavulanate and liver disease

While this antibiotic does not need to be avoided or adjusted in general with liver disease, amoxicillin-potassium clavulanate has been associated with some cases of drug-induced liver problems, specifically cholestatic hepatitis. These reactions are particular only to certain individuals, but enough cases occur to make amoxicillin-potassium clavulanate the most common cause of idiosyncratic drug-included liver injury. If you develop symptoms such as fatigue, dark urine, or jaundice, you should swiftly get medical care.

Amoxicillin-potassium clavulanate and mononucleosis

Besides the chance of an allergic reaction, a rash can also result if amoxicillin products are taken in the setting of mononucleosis, better known as mono. You can imagine that this is not uncommon, given that antibiotics are sometimes prescribed for sore throat, a symptom that can be from mono. To best avoid this, your healthcare provider may recommend a throat swab to determine if a bacterial infection, namely strep throat, is the cause of sore throat or not before prescribing any antibiotic.

How to minimize amoxicillin-potassium clavulanate interactions

Your best bet to avoid drug-drug interactions involving amoxicillin-potassium clavulanate is to communicate well with your medical providers. Keep an updated, accurate prescription drug list, including over-the-counter medications and supplements too, and review this list with your provider at each visit. Make sure that any provider who’s prescribing meds for you is aware of all of your underlying medical conditions. Periodically and when a new medication is prescribed, ask about any interactions with your existing therapies. 

When to talk to a healthcare provider about amoxicillin-potassium clavulanate interactions

If you are worried about a potential drug interaction, the time is now to ask about it. Taking an active role in your own care is essential for the best outcomes. By bringing up a potential interaction with amoxicillin-potassium clavulanate, you could avoid an adverse reaction or, at the very least, have peace of mind and a better understanding of why it is being prescribed for you.