Linezolid with Rifampin Interaction Details

Brand Names Associated with Linezolid

Brand Names Associated with Rifampin

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 13, 2023

Interaction Effect

Subtherapeutic linezolid serum concentrations and potentially decreased efficacy

Interaction Summary

Concomitant administration of linezolid and rifampin has resulted in decreased linezolid Cmax and AUC concentrations in studies in healthy males. Coadministration of linezolid and rifampin was associated with decreased linezolid serum levels in a 31-year-old critically ill patient . Caution is advised if these agents are coadministered and monitor patients closely for loss of linezolid efficacy.

Severity

Moderate

Onset

Delayed

Evidence

Established

How To Manage Interaction

Clinicians should be aware that concomitant administration of linezolid and rifampin may result in decreased linezolid serum levels, thereby resulting in loss of linezolid efficacy.

Mechanism Of Interaction

Altered linezolid metabolism due to hepatic enzyme induction

Literature Reports

A) In a pharmacokinetic study, concomitant administration of linezolid and rifampin resulted in decreased linezolid concentrations. Healthy adult males (n=16) were administered oral linezolid 600 mg twice daily for 5 doses with and without rifampin 600 mg once daily for 8 days. Concomitant administration led to a 21% decrease in linezolid Cmax (90% CI 15% to 27%) and a 32% decrease in linezolid AUC (90% CI 27% to 37%). The exact mechanism for this is not known but may be related to induction of hepatic enzymes .

B) In a small study in healthy males (n=8), concurrent administration of linezolid and rifampin led to reduced linezolid plasma levels compared with administration of linezolid alone. Subjects received a one-time dose of IV linezolid 600 mg. A day later, they were given concurrent doses of IV linezolid 600 mg and IV rifampin 600 mg. Six hours after the initial dose of linezolid and rifampin, linezolid serum levels were at 90%, and dropped to 80% and 65% after 9 hours and 12 hours, respectively. Up-regulation of linezolid intestinal secretion was proposed as a possible explanation for the increased linezolid clearance .

C) Concomitant administration of linezolid and rifampin led to decreased linezolid serum levels in a 31-year-old female. Within 24 hours of admission, this critically ill patient presented with community-acquired methicillin-resistant staphylococcus aureus (MRSA). She was treated with intravenous drotrecogin alfa, norepinephrine, vasopressin, piperacillin-tazobactam, vancomycin, and clindamycin. Based on culture results, piperacillin-tazobactam and clindamycin were discontinued. On day 6, blood cultures still showed positive for MRSA. Vancomycin was discontinued, and intravenous linezolid 600 mg every 12 hours with rifampin 300 mg every 8 hours were initiated. Three days after linezolid and rifampin initiation, blood cultures were negative for MRSA growth. During treatment with linezolid and rifampin (19 days; day 6 to 25 of admission), the patient developed daily fevers and nosocomial candidemia. Caspofungin was started and later changed to fluconazole. Escherichia coli bacteremia was initially treated with meropenem and later, therapy was changed to levofloxacin. The patient was also restarted on sertraline which she had been taking at home for depression. Additionally, hydroxychloroquine was initiated to treat systemic lupus erythematosus which was diagnosed around day 40 of admission. On day 35 (ie, 10 days after stopping rifampin), linezolid trough levels were reported as trace. Linezolid dose was increased to 600 mg every 8 hours, and rifampin was restarted on day 36. On day 37, linezolid peak (7.29 mcg/mL) and trough levels (2.04 mcg/mL) were obtained. Rifampin was discontinued on day 44, and linezolid peak and trough levels on day 52 had increased to 12.46 mcg/mL and 5.03 mcg/mL. Subsequently, the patient made steady progress and was discharged on day 86 .

Linezolid Overview

• Linezolid is used to treat infections, including pneumonia, and infections of the skin . Linezolid is in a class of antibacterials called oxazolidinones. It works by stopping the growth of bacteria.

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

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.