What is the interaction between Rifampicin (Rifampin) and Levothyroxine (Euthyrox, T4)?

From the Guidelines

Rifampicin significantly reduces the effectiveness of levothyroxine (Euthyrox) and requires careful management, with patients typically needing a dose increase of levothyroxine while on rifampicin therapy. This interaction is due to rifampicin being a potent inducer of liver enzymes that accelerate the metabolism of levothyroxine, resulting in lower thyroid hormone levels 1. The American Thoracic Society guidelines highlight the importance of monitoring serum TSH levels and potentially increasing the dose of levothyroxine when co-administered with rifampicin 1.

Some key points to consider in managing this interaction include:

• Monitoring thyroid function tests (TSH and free T4) within 2-4 weeks after starting rifampicin and again 4-8 weeks after completing the antibiotic course, with dose adjustments made accordingly 1
• Patients should take these medications at least 4 hours apart to minimize direct interference with absorption
• After discontinuing rifampicin, the levothyroxine dose will likely need to be reduced back to the original amount to prevent hyperthyroidism
• The interaction is particularly important for patients on tuberculosis treatment regimens containing rifampicin, as the full course typically lasts 6 months or longer, potentially causing prolonged thyroid hormone instability if not properly managed 1

It is essential to closely monitor patients taking both rifampicin and levothyroxine to ensure that thyroid hormone levels remain within the normal range, and to adjust the levothyroxine dose as needed to prevent hypothyroidism or hyperthyroidism 1.

From the FDA Drug Label

Table 7 Drugs That May Alter Hepatic Metabolism of T4 (Hypothyroidism) Potential impact: Stimulation of hepatic microsomal drug-metabolizing enzyme activity may cause increased hepatic degradation of levothyroxine, resulting in increased levothyroxine sodium requirements. Drug or Drug Class Effect Phenobarbital Rifampin Phenobarbital has been shown to reduce the response to thyroxine Phenobarbital increases L-thyroxine metabolism by inducing uridine 5’-diphospho-glucuronosyltransferase (UGT) and leads to a lower T4 serum levels. Changes in thyroid status may occur if barbiturates are added or withdrawn from patients being treated for hypothyroidism. Rifampin has been shown to accelerate the metabolism of levothyroxine.

Rifampicin may interact with Euthyrox (levothyroxine) by accelerating its metabolism, potentially leading to increased levothyroxine sodium requirements 2.

• Key points:
  • Rifampin accelerates the metabolism of levothyroxine
  • This may result in increased hepatic degradation of levothyroxine
  • Patients may require increased levothyroxine sodium doses
• Clinical decision: Closely monitor thyroid hormone parameters in patients taking rifampicin and levothyroxine concomitantly.

From the Research

Rifampicin and Euthyrox Interaction

• The interaction between rifampicin and levothyroxine (euthyrox) has been studied in several clinical settings 3, 4, 5.
• Rifampicin is a potent inducer of hepatic enzymes and can decrease circulating levels of thyroid hormone, while having no effect on thyroid-stimulating hormone (TSH) in normal volunteers 4.
• In patients receiving levothyroxine, serum thyroid function test should be performed after starting rifampicin treatment, as rifampicin can increase the required dose of levothyroxine 3.
• The effects of rifampicin on levothyroxine absorption can be variable, with one study showing a significant increase in total plasma thyroxine (T4) concentrations when coadministered with rifampicin 5.

Clinical Relevance

• The interaction between rifampicin and levothyroxine can have significant clinical implications, particularly in patients with hypothyroidism or thyroid cancer 3, 4.
• Clinicians should be aware of the potential for rifampicin to induce drug-metabolising enzymes and transporters, leading to reduced therapeutic responses or toxic reactions 6, 7.
• Close monitoring of thyroid function and adjustment of levothyroxine dose may be necessary when rifampicin is initiated or discontinued 3, 4.

Mechanism of Interaction

• Rifampicin induces cytochrome P450 (CYP) 3A4 and P-glycoprotein, leading to increased metabolism and transport of levothyroxine 7.
• The induction of drug-metabolising enzymes and transporters by rifampicin can take approximately 1 week to develop and 2 weeks to dissipate after discontinuation of rifampicin 7.