Rifampicin-Moxifloxacin Interaction
Rifampicin significantly reduces moxifloxacin plasma concentrations by approximately 27-39% through induction of hepatic metabolic enzymes, requiring dose adjustment or careful monitoring when these drugs are co-administered. 1, 2, 3
Mechanism of Interaction
- Rifampicin is a potent inducer of hepatic microsomal enzymes, specifically cytochrome P450 (CYP) enzymes and phase II metabolic pathways including glucuronidation and sulfation, which are responsible for moxifloxacin metabolism 1, 3
- The FDA label explicitly states that rifampicin induces multiple drug metabolizing enzymes and transporters (CYP1A2, 2B6, 2C8, 2C9, 2C19, 3A4, UDP-glucuronyltransferases, and P-glycoprotein), thereby decreasing exposure to co-administered drugs 1
- Moxifloxacin exposure (AUC0-24h) decreases by 27-39% when co-administered with rifampicin, with the sulfate conjugate metabolite of moxifloxacin increasing twofold 2, 3, 4
Clinical Significance
- In tuberculosis patients receiving rifampicin 600mg with moxifloxacin 400mg, only 65% achieved the target AUC/MIC ratio >100 compared to 78% receiving moxifloxacin alone 2
- Peak moxifloxacin concentrations (Cmax) are reduced by approximately 19-32% when combined with rifampicin 2, 3, 4
- Time to peak concentration is prolonged from 1 hour to 2.5 hours with rifampicin co-administration 3
Management Recommendations
Increase moxifloxacin dose to 600mg daily when co-administered with rifampicin to compensate for the drug-drug interaction. 2
- Seven out of eight patients (87.5%) receiving moxifloxacin 600mg with rifampicin achieved the target AUC/MIC >100, compared to only 65% with the standard 400mg dose 2
- Monitor clinical response monthly during tuberculosis treatment, specifically questioning patients about symptoms associated with treatment failure 1
- Therapeutic drug monitoring should be considered to ensure adequate moxifloxacin exposure, particularly in patients with isoniazid-resistant tuberculosis where moxifloxacin is a critical component 2
Clinical Context for Use
Moxifloxacin combined with rifampicin is recommended as a second-line option for specific mycobacterial infections:
- For rifampicin-resistant M. kansasii or intolerance to first-line antibiotics, moxifloxacin should be used as part of a second-line regimen 5
- For M. xenopi pulmonary disease, a multidrug regimen including moxifloxacin or macrolide with rifampicin and ethambutol is suggested 5
- Moxifloxacin may be used in tuberculosis patients with hepatotoxicity from first-line agents, as it lacks hepatotoxic effects 5
Important Caveats
- Despite the pharmacokinetic interaction, clinical effectiveness data from prosthetic joint infections showed moxifloxacin/rifampicin was as effective as levofloxacin/rifampicin (89% vs 87.5% success rates), suggesting the interaction may not always translate to treatment failure 6
- However, this reassuring data comes from non-tuberculosis infections with lower bacterial burden; tuberculosis treatment requires more aggressive dosing strategies 2
- The FDA label requires baseline hepatic enzymes, bilirubin, serum creatinine, complete blood count, and platelet count before initiating rifampicin, with monthly monitoring during therapy 1
- Rifampicin's enzyme induction develops gradually during treatment and persists for approximately 2 weeks after discontinuation 1