Phase 4
N=7
Drug Interaction Study Between Linezolid and Clarithromycin in Tuberculosis Patients
Multidrug-resistant Tuberculosis · Extensively Drug-resistant Tuberculosis
Bottom Line
View on ClinicalTrials.gov: NCT01521364 ↗Enrolled (actual)
7
Serious AEs
0.0%
Results posted
Jul 2013
Primary outcome: Primary: Area Under the Time Concentration Curve (AUC0-12h) of Linezolid in Plasma After Addition of 0mg, 250mg, or 500mg Clarithromycin (CLA). — 36.3; 61.0; 67.2 mg*h/L
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 4
- Interventions
- Addition of different doses of clarithromycin. (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- University Medical Center Groningen
- Primary completion
- Oct 2012
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Area Under the Time Concentration Curve (AUC0-12h) of Linezolid in Plasma After Addition of 0mg, 250mg, or 500mg Clarithromycin (CLA). |
36.3; 61.0; 67.2 | — |
| SECONDARY Linezolid (LIN) and Clarithromycin (CLA) Pharmacokinetic Parameters, e.g. Tmax, Cmax, Cmin, T1/2, Cl. |
— | — |
| SECONDARY Number of Patients With Adverse Events (AEs) |
0; 0; 0 | — |
| SECONDARY Pharmacokinetic Parameters, e.g. Tmax, T1/2, Cmax, Cmin, Cl, of Anti-TB Drugs That Are Co-administered as Part of the Continued Standard Care. |
— | — |
| SECONDARY Area Under the Time Concentration Curve (AUC0-12h) of Linezolid in Saliva. |
— | — |
Summary
Future patients might benefit from a combination of linezolid (LIN) and clarithromycin (CLA) in the treatment of Multidrug-resistant and Extensively Drug-resistant Tuberculosis (MDR/XDR-TB) due to possible synergistic activity as shown in in vitro experiments in different Mycobacteria strains. The investigators observed increased LIN serum levels in three cases after combining LIN and CLA of which the investigators described one in a case report (Bolhuis et al). The investigators suggest to conduct a prospective pharmacokinetic study in MDR- and XDR-TB patients to quantify the above described interaction between LIN and CLA.
Eligibility Criteria
Inclusion Criteria
- Age ≥18 years old
- Signed informed consent
- Diagnosis of MDR/XDR-TB confirmed with standard microbiological criteria (culture-based, molecular or both)
- Treatment with linezolid 300mg twice daily per os.
Exclusion Criteria
- Hypersensitivity to: linezolid, clarithromycin, erythromycin, or any macrolide antibiotics, or any of the excipients of linezolid or clarithromycin.
- Concomitant use with astemizole, cisapride, ergotamine derivatives (dihydroergotamine, ergotamine), monoamine oxidase inhibitors (phenelzine, isocarboxazid, selegiline, or moclobemide), pimozide, or terfenadine.
- Pregnancy or breast-feeding.
- Hypokalemia
- Concomitant use of other P-gp inhibitors/inducers, e.g. amiodarone, verapamil, digoxin, tipranavir/ritonavir, lovastatin, tariquidar, itraconazole, dipyridamol, erythromycin, ritonavir, quinidine.
Data sourced from ClinicalTrials.gov (NCT01521364). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.