Drug Interaction Study Between Linezolid and Clarithromycin in Tuberculosis Patients

University Medical Center Groningen (UMCG)

Status and phase: Completed; Phase 4

Conditions: Multidrug-resistant Tuberculosis; Extensively Drug-resistant Tuberculosis

Treatments: Drug: Addition of different doses of clarithromycin.

Study type: Interventional

Funder types: Other

Identifiers

NCT01521364

2011-000513-39 (EudraCT Number)

NL35534.042.11

Details and patient eligibility

About

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.

Enrollment: 7 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

7 participants in 1 patient group

0mg, 250mg, and 500mg claritromycin

Other group

Description:

Patients receive 300mg linezolid twice a day during entire study. After one week, 250mg claritromycin once daily is added for a duration of two weeks. After another two weeks, 250mg claritromycin is replaced by 500mg claritromycin once daily for another two weeks. After this, there is a wash-out period of one week during which no claritromycine is administered.

Treatment:

Drug: Addition of different doses of clarithromycin.