Summary

Rifampin significantly reduces bortezomib plasma concentrations through CYP3A4 enzyme induction, potentially compromising the anticancer efficacy of bortezomib. This interaction requires careful monitoring and possible dose adjustments or alternative antibiotic selection.

Introduction

Bortezomib (Velcade) is a proteasome inhibitor primarily used to treat multiple myeloma and mantle cell lymphoma. It works by blocking the proteasome complex, leading to cancer cell death. Rifampin is a potent antibiotic belonging to the rifamycin class, commonly used to treat tuberculosis, atypical mycobacterial infections, and as prophylaxis for certain bacterial infections. Rifampin is known for its strong enzyme-inducing properties, particularly affecting cytochrome P450 enzymes.

Mechanism of Interaction

The interaction between bortezomib and rifampin occurs through rifampin's potent induction of cytochrome P450 3A4 (CYP3A4) enzymes. Bortezomib is primarily metabolized by CYP3A4, CYP2C19, and CYP1A2 enzymes. When rifampin induces CYP3A4, it significantly increases the metabolism of bortezomib, leading to reduced plasma concentrations and potentially decreased therapeutic efficacy. This enzyme induction effect can persist for several days to weeks after rifampin discontinuation due to the time required for enzyme levels to return to baseline.

Risks and Symptoms

The primary clinical risk of this interaction is reduced bortezomib efficacy due to significantly decreased plasma concentrations. This could lead to suboptimal cancer treatment outcomes, including reduced response rates, shorter progression-free survival, and potential treatment failure in patients with multiple myeloma or mantle cell lymphoma. The interaction is considered clinically significant and may compromise the patient's oncological treatment plan. Additionally, patients may experience breakthrough infections if alternative antibiotics are less effective than rifampin for their specific indication.

Management and Precautions

Key management strategies include: 1) Avoid concurrent use when possible by selecting alternative antibiotics that do not induce CYP3A4, such as fluoroquinolones or macrolides without enzyme-inducing properties. 2) If rifampin use is essential, consider increasing bortezomib dose under close oncological supervision, though specific dose adjustment guidelines are limited. 3) Monitor bortezomib therapeutic response more closely through regular assessment of disease markers and clinical response. 4) Consider therapeutic drug monitoring if available. 5) Coordinate care between oncology and infectious disease specialists to optimize both cancer treatment and infection management. 6) Allow adequate washout period (2-3 weeks) after rifampin discontinuation before resuming standard bortezomib dosing.

Rifampin interactions with food and lifestyle

Rifampin should be taken on an empty stomach, at least 1 hour before or 2 hours after meals, as food can significantly reduce its absorption and effectiveness. Alcohol consumption should be avoided or limited while taking rifampin, as both rifampin and alcohol can cause liver toxicity, and the combination may increase the risk of hepatotoxicity. Patients should be counseled to take rifampin consistently either with or without food (preferably without) to maintain consistent blood levels.