Pharmacokinetics and Safety of Moxifloxacin
Pharmacokinetics and Safety of Moxifloxacin
The main objective of this prospective clinical trial is to compare pharmacokinetics and
 safety and tolerability of a standard dose (400 mg) with an escalated dose (600 mg; 800 mg)
 of moxifloxacin (MFX). This clinical trial will provide important safety information on MFX
 in a higher dosage in TB patients.
Moxifloxacin (MFX) is a fluoroquinolone with a high in vitro and in vivo bactericidal
 activity against Mycobacterium tuberculosis. A daily dose of 600-800 mg MFX should be
 considered for optimal killing of the involved mycobacteria and suppression of drug
 resistance, which is higher than the currently used dose of 400 mg once daily. In general,
 safety data to support switching to the suggested higher dose are limited.

 For this purpose, twenty tuberculosis patients will start on a standard dose of MFX 400 mg
 once daily. After 8 days the dose will be increased to 600 mg once daily and on the 15th day
 of treatment, the dose of MFX will be escalated to 800 mg. In patients who have been treated
 with rifampicin (RIF) in the past three weeks prior to start of MFX treatment an additional
 washout period of 3 weeks to reduce the rifampicin induced enzymatic activity will precede
 the dose escalation.
Inclusion Criteria:

 -  Patients with TB, with Mycobacterium tuberculosis (or M. africanum) by culture

 -  Starting treatment with MFX in a dose of 400 mg as part of their TB treatment

 Exclusion Criteria:

 -  Contra-indication for MFX

 -  Baseline QTc-interval > 450 msec

 -  History of resuscitation

 -  History of ventricular tachycardia (including Torsades de Pointes)

 -  Family history of sudden cardiac death or Torsades de Pointes

 -  Additional risk factors for Torsades de Pointes (including known heart failure, Left
 ventricular hypertrophy)

 -  Use of concomitant treatment with QT/QTc prolonging drugs (including anti-dysrhythmics
 class IA and III, antipsychotics, tricyclic antidepressants or the antihistaminic drug
 terfenadine)

 -  Abnormal electrolytes (K, Mg, Na, Ca)

 -  Abnormal cardiac repolarisation on screening/baseline ECG

 -  History of adverse events to fluoroquinolones

 -  HIV co-infection

 -  RIF treatment during last 3 weeks before start of the study. After a washout period of
 3 weeks the patient can be included.