What medication should not be taken with Keflex? A guide to drug interactions

October 12, 2025 •

4 min read

Before starting treatment with the antibiotic Keflex (cephalexin), it is critical to be aware of potential drug interactions that can affect its efficacy or lead to serious side effects. Certain medications, such as the blood thinner warfarin and the diabetes drug metformin, require careful monitoring or avoidance to prevent adverse health events when you are prescribed Keflex.

Quick Summary

This guide details important drug, supplement, and lifestyle interactions with Keflex (cephalexin), a common antibiotic. Key warnings involve anticoagulants like warfarin, diabetes medications such as metformin, and certain diuretics or gout treatments. Patients with allergies to penicillin or other cephalosporins should also avoid this medication.

Key Points

Blood Thinners and Keflex: Never combine Keflex with warfarin without close medical supervision, as it significantly increases the risk of bleeding.
Diabetes Medication Alert: Keflex can raise metformin levels, increasing the risk of low blood sugar and potentially dangerous lactic acidosis.
Gout Treatment Interference: The gout drug probenecid can block the kidneys from clearing Keflex, leading to higher antibiotic levels and increased side effects.
Kidney Health Concern: Taking Keflex with diuretics like furosemide can increase the risk of kidney damage, especially for those with existing kidney problems.
Avoid Allergic Reactions: Do not take Keflex if you have a known allergy to cephalosporin or penicillin antibiotics due to the risk of cross-hypersensitivity.
Timing is Everything: Separate mineral supplements containing zinc by at least three hours to prevent them from reducing Keflex's absorption and effectiveness.
Limit Alcohol Consumption: While generally not a contraindication, it is best to avoid alcohol during your course of Keflex to prevent worsening gastrointestinal side effects and to help your body fight the infection effectively.

What is Keflex (Cephalexin)?

Keflex is a brand name for the antibiotic cephalexin, which belongs to a class of drugs called cephalosporins. It is prescribed to treat various bacterial infections, including those affecting the urinary tract, skin, respiratory tract, ears, and bones. Like all antibiotics, it works by inhibiting the growth and spread of bacteria, but it is ineffective against viral infections like the common cold or flu. Before taking Keflex, it is crucial to review your complete medical history and current medication list with your doctor or pharmacist, as several substances can cause significant interactions.

Medications with Major or Significant Interactions

Several medications have notable interactions with Keflex, and your healthcare provider may need to adjust your dosage or choose an alternative treatment if you are taking any of the following:

Warfarin (Coumadin): This is one of the most significant interactions to monitor. Warfarin is a blood thinner, and Keflex can potentially amplify its anticoagulant effects, increasing the risk of bleeding. The mechanism for this may involve Keflex altering the gut bacteria that produce vitamin K, a crucial clotting factor. If you are on warfarin, your doctor will likely recommend more frequent monitoring of your INR (International Normalized Ratio) and may adjust your warfarin dosage.
Metformin: For individuals with type 2 diabetes, the co-administration of Keflex and metformin can be problematic. Keflex can cause metformin concentrations in the blood to increase, which raises the risk of metformin side effects, including dangerous lactic acidosis. You may need to monitor your blood sugar levels more closely, and your doctor might adjust your metformin dose during Keflex therapy.
Probenecid (Probalan): This medication is used to treat gout. Probenecid inhibits the renal excretion of Keflex, which can cause the level of Keflex to build up in your blood. This elevated concentration can increase the risk of side effects from Keflex, such as nausea and diarrhea, especially in patients with pre-existing kidney issues. Your doctor will typically need to adjust your Keflex dosage if you are also taking probenecid.
Loop Diuretics (e.g., Furosemide/Lasix): Combining Keflex with powerful diuretics can increase the risk of kidney problems. Patients with impaired renal function are particularly susceptible, and kidney function may need to be monitored more frequently.
Aminoglycoside Antibiotics (e.g., Gentamicin): When used concurrently with Keflex, aminoglycosides can further increase the risk of kidney-related complications. Regular laboratory tests are often required to monitor kidney function in these cases.

Other Potential Interactions

Beyond the major interactions, several other substances can affect how Keflex works or cause adverse effects:

Birth Control Pills: Some combined oral contraceptives may be less effective when taken with cephalexin. This potential interaction is not universal, but patients should be aware of the possibility and consider alternative birth control methods during the antibiotic course.
Live Oral Vaccines (Typhoid, Cholera): Because Keflex is an antibiotic, it can render live bacterial vaccines, such as those for typhoid and cholera, less effective by killing the weakened bacteria. It is advisable to consult a doctor about the timing of any vaccinations relative to your Keflex treatment.
Mineral Supplements (e.g., Zinc, Iron): Certain mineral supplements can interfere with the absorption of cephalexin, potentially making the antibiotic less effective. To minimize this, it is recommended to take Keflex at least three hours before or after taking supplements containing zinc.
Alcohol: While there is no direct chemical interaction between cephalexin and alcohol that renders the antibiotic ineffective, it's advisable to avoid alcohol during treatment. Both Keflex and alcohol can cause similar side effects like nausea, vomiting, and stomach upset, and combining them may intensify these issues. Furthermore, alcohol can suppress the immune system, slowing down your body's ability to fight the infection.

Hypersensitivity and Allergies

One of the most critical contraindications for Keflex use is a pre-existing hypersensitivity to cephalexin or other cephalosporin antibiotics. Due to a documented risk of cross-hypersensitivity, patients with a known allergy to penicillin should use Keflex with extreme caution. Allergic reactions can be severe and may include hives, angioedema (swelling), and even anaphylaxis.

Comparison Table: Key Keflex Interactions


Interacting Substance	Potential Risk	Mechanism	Management Action
Warfarin	Increased bleeding risk	Alters gut flora, affecting vitamin K production	Monitor INR closely, adjust warfarin dosage
Metformin	Increased metformin levels; risk of lactic acidosis	Inhibits metformin's renal tubular secretion	Monitor blood sugar, adjust metformin dosage
Probenecid	Increased Keflex blood levels; risk of side effects	Inhibits renal excretion of Keflex	Adjust Keflex dosage
Loop Diuretics	Increased risk of kidney damage	Potential combined effect on kidney function	Monitor kidney function
Oral Contraceptives	Decreased contraceptive effectiveness	Can affect hormone levels	Consider back-up birth control during antibiotic course
Mineral Supplements (Zinc)	Reduced absorption and effectiveness of Keflex	Binding of Keflex by minerals	Space doses at least 3 hours apart
Alcohol	Worsened GI side effects, delayed recovery	Overlapping side effects and immune system suppression	Avoid or minimize alcohol consumption

Conclusion

While Keflex is a widely used and effective antibiotic for many bacterial infections, it is not without potential drug and supplement interactions. The most serious risks involve combining it with anticoagulants like warfarin or diabetes medications such as metformin, which require careful monitoring and potential dosage adjustments by a healthcare provider. Other important considerations include interactions with probenecid, diuretics, certain vaccines, and mineral supplements. Additionally, individuals with a penicillin or cephalosporin allergy should avoid Keflex altogether. It is always best to consult your doctor or pharmacist about all medications and supplements you are taking before beginning a course of Keflex to ensure your safety and the medication's effectiveness.

For more detailed, professionally vetted information, the U.S. FDA drug label for Keflex is an authoritative source.

Frequently Asked Questions

You should use Keflex with extreme caution if you have a penicillin allergy, as there is a documented risk of cross-hypersensitivity. Inform your doctor about any drug allergies before starting treatment so they can assess the risk and consider an alternative antibiotic if necessary.

Yes, Keflex may reduce the effectiveness of some combined oral contraceptives. Discuss this with your doctor and consider using a backup birth control method during your antibiotic course.

While there's no major direct interaction, it is recommended to avoid or minimize alcohol consumption while taking Keflex. Combining them can worsen gastrointestinal side effects like nausea and vomiting and may hinder your immune system's ability to fight the infection.

No, you should not take mineral supplements like zinc at the same time as Keflex. To ensure proper absorption, separate the doses by at least three hours.

If you are on warfarin, your doctor will likely prescribe Keflex with caution and recommend closer monitoring of your INR levels. You should also watch for any unusual bruising or bleeding and report it to your doctor immediately.

Yes, Keflex can increase the concentration of metformin in your blood, which can raise your risk of developing dangerously low blood sugar levels or lactic acidosis. Your doctor may need to adjust your metformin dosage.

Yes, some over-the-counter products, especially those containing minerals like zinc or iron in multivitamins, can interact with Keflex. Always inform your healthcare provider about any over-the-counter medications, vitamins, or supplements you are taking.