Teicoplanin in patients with acute leukaemia and febrile neutropenia: a special population benefiting from higher dosages.
OBJECTIVE
To define the optimal dosage regimen of teicoplanin that ensures early therapeutically relevant trough concentrations (C(min)) [>10 mg/L at 24 hours and possibly close to 20 mg/L at 48 hours] in patients with acute leukaemia who develop febrile neutropenia after chemotherapy.


METHODS
Prospective observational pharmacokinetic study.


METHODS
Adult patients (n = 33) with normal renal function previously treated with antineoplastic chemotherapy because of acute lymphocytic or acute nonlymphocytic leukaemia, and subsequently developing febrile neutropenia treated with empirical antimicrobial therapy.


METHODS
First, the standard dosage group (n = 11) was administered standard loading and maintenance doses of teicoplanin (400 mg every 12 hours for three doses followed by 400 mg once daily). Blood samples were collected at defined times as part of routine monitoring and assessed for teicoplanin plasma concentration by fluorescence polarisation immunoassay. Secondly, the high dosage group (n = 22) received a high loading regimen (800 + 400 mg 12 hours apart on day 1, 600 + 400mg 12 hours apart on day 2) followed by a high maintenance regimen (400 mg every 12 hours) from day 3 on.


RESULTS
In the standard dosage group, no patient had the recommended teicoplanin C(min) of >or=10 mg/L within the first 72 hours, and only five of the 11 patients (45%) had a C(min) of >or=10 mg/L after 120 hours. No patient had a C(min) of >or=20 mg/L. In the high dosage group, teicoplanin C(min) averaged >or=10 mg/L within 24 hours, and this value was achieved within 48 hours in all but one patient. Of note, C(min) at 72 hours exceeded 20 mg/L in ten of the 22 patients (45%). No patient experienced significant impairment of renal function.


CONCLUSIONS
In this patient group, therapeutically relevant C(min) may be achieved very early in the treatment period with loading doses of 12 mg/kg and 6 mg/kg 12 hours apart on day 1, and 9 mg/kg and 6 mg/kg 12 hours apart on day 2, regardless of renal function. Subsequently, in patients with normal renal function a maintenance dosage of 6 mg/kg every 12 hours may be helpful in ensuring C(min) close to 20 mg/L. Assessment of C(min) after 48-72 hours may be useful to individualise teicoplanin therapy. Factors increasing volume of distribution and/or renal clearance of teicoplanin (fluid load, hypoalbuminaemia, leukaemic status) may explain the need for higher dosages.
Pea
Federico
F
Department of Experimental and Clinical Pathology and Medicine, Medical School, Institute of Clinical Pharmacology and Toxicology, University of Udine, Udine, Italy. federico.pea@med.uniud.it
Viale
Pierluigi
P
Candoni
Anna
A
Pavan
Federica
F
Pagani
Leonardo
L
Damiani
Daniela
D
Casini
Marco
M
Furlanut
Mario
M
D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005334:Fever / Q000139:chemically induced / Q000188:drug therapy; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced / Q000188:drug therapy*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D011446:Prospective Studies; D017334:Teicoplanin / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D017334:Teicoplanin