Metformin with Rifampin Interaction Details

Brand Names Associated with Metformin

Brand Names Associated with Rifampin

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 05, 2023

Interaction Effect

Increased metformin plasma concentrations; enhanced glucose lowering effects of metformin

Interaction Summary

Use caution when prescribing rifampin to patients who are taking metformin. In a pharmacokinetic study (n=16) with healthy volunteers, concurrent administration of rifampin increased metformin plasma concentrations and enhanced the glucose lowering effects of metformin. Consider monitoring patients for increased metformin adverse effects whenever rifampin is added to metformin therapy. Closely monitor blood glucose levels and for signs and symptoms of hypoglycemia in patients taking metformin and rifampin concurrently.

Severity

Moderate

Onset

Rapid

Evidence

Established

How To Manage Interaction

Use caution when prescribing rifampin to patients who are taking metformin. Concomitant administration of metformin and rifampin may increase metformin plasma concentrations and enhance the glucose lowering effects of metformin. Consider monitoring patients for increased metformin adverse effects whenever rifampin is added to metformin therapy. Closely monitor blood glucose levels and for signs and symptoms of hypoglycemia in patients taking metformin and rifampin concurrently.

Mechanism Of Interaction

Increased organic cation transporter (OCT1) expression and hepatic uptake of metformin

Literature Reports

A) In a pharmacokinetic study (n=16) in healthy volunteers, concurrent administration of rifampin increased metformin plasma concentrations and enhanced the glucose lowering effects of metformin. Participants received 2 doses of metformin (1750 mg total) on days 1 and 2, and again on days 13 and 14 after a 10-day course of rifampin. Oral glucose tolerance testing was performed before and after each dose of metformin to assess glucose-lowering effects. The difference in maximum glucose level before and after metformin treatment was increased by 41.9% with rifampin treatment (31 +/- 14 mg/dL or 1.72 +/- 0.77 mmol/L vs 44 +/- 14 mg/dL or 2.44 +/- 0.77 mmol/L), respectively; p=0.024). Also, the difference in partial area under the plasma concentration-time curve for glucose (0 to 60 minutes after ingestion) before and after metformin treatment was increased by 54.5% with rifampin treatment (914 +/- 510 mg/dL x min vs 1412 +/- 555 mg/dL x min, respectively; p=0.02). Rifampin increased metformin plasma concentrations by 23% (p=0.002) and 13% (p=0.036) at 0.5 and 1 hour, respectively. Rifampin significantly increased the clearance of metformin by 16% (p=0.008) while the elimination half-life of metformin was not significantly changed. Rifampin treatment increased organic cation transporter (OCT1) mRNA levels by approximately 4.1-fold; however, no OCT2 mRNA was detected in the peripheral blood cells .

Metformin Overview

• Metformin is used alone or with other medications, including insulin, to treat type 2 diabetes (condition in which the body does not use insulin normally and, therefore, cannot control the amount of sugar in the blood). Metformin is in a class of drugs called biguanides. Metformin helps to control the amount of glucose (sugar) in your blood. It decreases the amount of glucose you absorb from your food and the amount of glucose made by your liver. Metformin also increases your body's response to insulin, a natural substance that controls the amount of glucose in the blood. Metformin is not used to treat type 1 diabetes (condition in which the body does not produce insulin and therefore cannot control the amount of sugar in the blood).

• Over time, people who have diabetes and high blood sugar can develop serious or life-threatening complications, including heart disease, stroke, kidney problems, nerve damage, and eye problems. Taking medication(s), making lifestyle changes (e.g., diet, exercise, quitting smoking), and regularly checking your blood sugar may help to manage your diabetes and improve your health. This therapy may also decrease your chances of having a heart attack, stroke, or other diabetes-related complications such as kidney failure, nerve damage (numb, cold legs or feet; decreased sexual ability in men and women), eye problems, including changes or loss of vision, or gum disease. Your doctor and other healthcare providers will talk to you about the best way to manage your diabetes.

Rifampin Overview

• Rifampin is used with other medications to treat tuberculosis (TB; a serious infection that affects the lungs and sometimes other parts of the body). Rifampin is also used to treat some people who have Neisseria meningitidis (a type of bacteria that can cause a serious infection called meningitis) infections in their noses or throats. These people have not developed symptoms of the disease, and this treatment is used to prevent them from infecting other people. Rifampin should not be used to treat people who have developed symptoms of meningitis. Rifampin is in a class of medications called antimycobacterials. It works by killing the bacteria that cause infection.

• Antibiotics such as rifampin 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:

• 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.