Levothyroxine with Rifampin Interaction Details

Brand Names Associated with Levothyroxine

Brand Names Associated with Rifampin

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

Interaction Effect

Decreased efficacy of levothyroxine

Interaction Summary

Coadministration of levothyroxine and rifampin may increase clearance of levothyroxine. Rifampin may induce levothyroxine metabolism, causing biochemical hypothyroidism. A decrease in serum thyroxine levels and free thyroxine index, along with an increase in the serum thyrotropin levels may occur . Increased clearance of levothyroxine induced by rifampin may return the patient to a hypothyroid state with a compensatory rise in the thyroid-stimulating hormone (TSH) level . However, in 1 study (n=8), thyroxine AUC was increased by 25% with coadministration of oral levothyroxine 1000 mcg and rifampin 600 mg (p=0.003). Closer monitoring of thyroid status may be warranted . Administer levothyroxine at least 4 hours before or after drugs that are known to interfere with absorption .

Severity

Moderate

Onset

Delayed

Evidence

Probable

How To Manage Interaction

Coadministration of levothyroxine and rifampin may cause increased clearance of levothyroxine, resulting in increased levothyroxine requirements . Administer levothyroxine at least 4 hours before or after drugs that are known to interfere with absorption and closely monitor thyroid status in patients receiving concurrent rifampin and levothyroxine therapy .

Mechanism Of Interaction

Induction of levothyroxine metabolism by rifampin

Literature Reports

A) During a prospective, double-blind, randomized study in healthy adult volunteers (n=8), mean baseline-corrected thyroxine (T4) AUC was significantly increased (25%; p=0.003) with coadministration of rifampin and levothyroxine compared with crossover treatment with placebo and levothyroxine (p=0.035). Study doses were levothyroxine 1000 mcg orally and rifampin 600 mg orally. The washout period between study days was at least 4 weeks. Total plasma T4 concentrations were measured over a 6-hour period after dosing. This effect of rifampin was unexpected and the exact mechanism of the interaction was unknown .

B) A 31-year old female with Turner's syndrome was maintained on levothyroxine 0.1 mg daily following a total thyroidectomy. When nafcillin could not eradicate a staphylococcus aureus infection, rifampin 300 mg every 12 hours was added to therapy. Although the dose of levothyroxine stayed constant during the course of hospitalization, the serum thyroxine levels and free thyroxine index decreased during rifampin therapy and the serum thyrotropin levels increased. The patient did not develop any symptoms of hypothyroidism. These effects were attributed to an increased metabolic clearance of levothyroxine caused by rifampin. The administration of rifampin in normal-thyroid patients will not induce hypothyroidism because the basal and stimulated serum thyrotropin levels remain unchanged. However, in this patient, the increase in levothyroxine clearance induced by rifampin resulted in a marked increased in serum thyrotropin because the patient did not have an intact thyroid .

C) A 50-year-old male with a thyroid-stimulating hormone (TSH) level of 8.52 mIU/L was started on levothyroxine 0.025 mg daily. Two and four months later, his TSH level was 3.67 mIU/L and 4.67 mIU/L, respectively. At approximately the same time, the patient experienced a methicillin resistant staphylococcus aureus wound infection following coronary artery bypass surgery. Despite aggressive and long-term treatment with vancomycin, the infection persisted. Oral rifampin 600 mg daily was added to the vancomycin regimen for synergy and a total of 14 days of combination therapy was completed. Three days after rifampin was discontinued, the TSH was measured at 9.44 mIU/L, although the patient did not show signs of hypothyroidism. The levothyroxine dose was increased to 0.05 mg daily, and the TSH level dropped to 4.34 mIU/L nine days after rifampin was stopped .

Levothyroxine Overview

• Levothyroxine is used to treat hypothyroidism (condition where the thyroid gland does not produce enough thyroid hormone). It is also used with surgery and radioactive iodine therapy to treat thyroid cancer. Levothyroxine is in a class of medications called hormones. It works by replacing thyroid hormone that is normally produced by the body.

• Without thyroid hormone, your body cannot function properly, which may result in poor growth, slow speech, lack of energy, excessive tiredness, constipation, weight gain, hair loss, dry, thick skin, increased sensitivity to cold, joint and muscle pain, heavy or irregular menstrual periods, and depression. When taken correctly, levothyroxine reverses these symptoms.

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.