Randomized Comparison of Safety and Pharmacokinetics of Caspofungin, Liposomal Amphotericin B, and the Combination of Both in Allogeneic Hematopoietic Stem Cell Recipients

Groll AH, Silling G, Young C, Schwerdtfeger R, Ostermann H, Heinz WJ, Gerss J, Kolve H, Lanvers-Kaminsky C, Pinheiro JP, Gammelin S, et al. (2010)
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY 54(10): 4143-4149.

Journal Article | Published | English

No fulltext has been uploaded

Author
; ; ; ; ; ; ; ; ; ; ;
All
Abstract
The combination of liposomal amphotericin B (LAMB) and caspofungin (CAS) holds promise to improve the outcome of opportunistic invasive mycoses with poor prognosis. Little is known, however, about the safety and pharmacokinetics of the combination in patients at high risk for these infections. The safety and pharmacokinetics of the combination of LAMB and CAS were investigated in a risk-stratified, randomized, multicenter phase II clinical trial in 55 adult allogeneic hematopoietic stem cell recipients (aHSCT) with granulocytopenia and refractory fever. The patients received either CAS (50 mg/day; day 1, 70 mg), LAMB (3 mg/kg of body weight/day), or the combination of both (CASLAMB) until defervescence and granulocyte recovery. Safety, development of invasive fungal infections, and survival were assessed through day 14 after the end of therapy. Pharmacokinetic sampling and analysis were performed on days 1 and 4. All three regimens were well tolerated. Premature study drug discontinuations due to grade III/IV adverse events occurred in 1/18, 2/20, and 0/17 patients randomized to CAS, LAMB, and CASLAMB, respectively. Adverse events not leading to study drug discontinuation were frequent but similar across cohorts, except for a higher frequency of hypokalemia with CASLAMB (P < 0.05). Drug exposures were similar for patients receiving combination therapy and those randomized to monotherapy. There was no apparent difference in the occurrence of proven/probable invasive fungal infections and survival through day 14 after the end of therapy. CASLAMB combination therapy in immunocompromised aHSCT patients was as safe as monotherapy with CAS or LAMB and had similar plasma pharmacokinetics, lending support to further investigations of the combination in the management of patients with invasive opportunistic mycoses.
Publishing Year
ISSN
eISSN
PUB-ID

Cite this

Groll AH, Silling G, Young C, et al. Randomized Comparison of Safety and Pharmacokinetics of Caspofungin, Liposomal Amphotericin B, and the Combination of Both in Allogeneic Hematopoietic Stem Cell Recipients. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY. 2010;54(10):4143-4149.
Groll, A. H., Silling, G., Young, C., Schwerdtfeger, R., Ostermann, H., Heinz, W. J., Gerss, J., et al. (2010). Randomized Comparison of Safety and Pharmacokinetics of Caspofungin, Liposomal Amphotericin B, and the Combination of Both in Allogeneic Hematopoietic Stem Cell Recipients. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 54(10), 4143-4149.
Groll, A. H., Silling, G., Young, C., Schwerdtfeger, R., Ostermann, H., Heinz, W. J., Gerss, J., Kolve, H., Lanvers-Kaminsky, C., Pinheiro, J. P., et al. (2010). Randomized Comparison of Safety and Pharmacokinetics of Caspofungin, Liposomal Amphotericin B, and the Combination of Both in Allogeneic Hematopoietic Stem Cell Recipients. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY 54, 4143-4149.
Groll, A.H., et al., 2010. Randomized Comparison of Safety and Pharmacokinetics of Caspofungin, Liposomal Amphotericin B, and the Combination of Both in Allogeneic Hematopoietic Stem Cell Recipients. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 54(10), p 4143-4149.
A.H. Groll, et al., “Randomized Comparison of Safety and Pharmacokinetics of Caspofungin, Liposomal Amphotericin B, and the Combination of Both in Allogeneic Hematopoietic Stem Cell Recipients”, ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, vol. 54, 2010, pp. 4143-4149.
Groll, A.H., Silling, G., Young, C., Schwerdtfeger, R., Ostermann, H., Heinz, W.J., Gerss, J., Kolve, H., Lanvers-Kaminsky, C., Pinheiro, J.P., Gammelin, S., Cornely, O.A., Wuerthwein, G.: Randomized Comparison of Safety and Pharmacokinetics of Caspofungin, Liposomal Amphotericin B, and the Combination of Both in Allogeneic Hematopoietic Stem Cell Recipients. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY. 54, 4143-4149 (2010).
Groll, Andreas H., Silling, Gerda, Young, Charlotte, Schwerdtfeger, Rainer, Ostermann, Helmut, Heinz, Werner J., Gerss, Joachim, Kolve, Hedwig, Lanvers-Kaminsky, Claudia, Pinheiro, Joao Paulo, Gammelin, Sibylle, Cornely, Oliver A., and Wuerthwein, Gudrun. “Randomized Comparison of Safety and Pharmacokinetics of Caspofungin, Liposomal Amphotericin B, and the Combination of Both in Allogeneic Hematopoietic Stem Cell Recipients”. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY 54.10 (2010): 4143-4149.
This data publication is cited in the following publications:
This publication cites the following data publications:

15 Citations in Europe PMC

Data provided by Europe PubMed Central.

Tolerability and outcome of once weekly liposomal amphotericin B for the prevention of invasive fungal infections in hematopoietic stem cell transplant patients with graft-versus-host disease.
Luu Tran H, Mahmoudjafari Z, Rockey M, Henry D, Grauer D, Aljitawi O, Abhyankar S, Ganguly S, Lin T, McGuirk J., J Oncol Pharm Pract 22(2), 2016
PMID: 25471252
Physiology-based pharmacokinetics of caspofungin for adults and paediatrics.
Stader F, Wuerthwein G, Groll AH, Vehreschild JJ, Cornely OA, Hempel G., Pharm. Res. 32(6), 2015
PMID: 25522788
Pharmacokinetics of caspofungin in ICU patients.
Muilwijk EW, Schouten JA, van Leeuwen HJ, van Zanten AR, de Lange DW, Colbers A, Verweij PE, Burger DM, Pickkers P, Bruggemann RJ., J. Antimicrob. Chemother. 69(12), 2014
PMID: 25139840
The Eagle-like effect of echinocandins: what's in a name?
Vanstraelen K, Lagrou K, Maertens J, Wauters J, Willems L, Spriet I., Expert Rev Anti Infect Ther 11(11), 2013
PMID: 24134556
Pharmacokinetics of posaconazole within epithelial cells and fungi: insights into potential mechanisms of action during treatment and prophylaxis.
Campoli P, Perlin DS, Kristof AS, White TC, Filler SG, Sheppard DC., J. Infect. Dis. 208(10), 2013
PMID: 23908482
Newer antifungal agents.
Larru B, Zaoutis TE., Curr. Opin. Pediatr. 25(1), 2013
PMID: 23263025
Safety and interactions of new antifungals in stem cell transplant recipients.
Girmenia C, Iori AP., Expert Opin Drug Saf 11(5), 2012
PMID: 22913714
Minimization of the preanalytical error in pharmacokinetic analyses and therapeutic drug monitoring: focus on IV drug administration.
Kontny NE, Boos J, Wurthwein G, Hempel G, Boddy AV, Groll AH, Krischke M., Ther Drug Monit 34(4), 2012
PMID: 22660605
Invasive aspergillosis: resistance to antifungal drugs.
Hadrich I, Makni F, Neji S, Abbes S, Cheikhrouhou F, Trabelsi H, Sellami H, Ayadi A., Mycopathologia 174(2), 2012
PMID: 22327841
Population pharmacokinetics of liposomal amphotericin B and caspofungin in allogeneic hematopoietic stem cell recipients.
Wurthwein G, Young C, Lanvers-Kaminsky C, Hempel G, Trame MN, Schwerdtfeger R, Ostermann H, Heinz WJ, Cornely OA, Kolve H, Boos J, Silling G, Groll AH., Antimicrob. Agents Chemother. 56(1), 2012
PMID: 22083471
Concentration of antifungal agents within host cell membranes: a new paradigm governing the efficacy of prophylaxis.
Campoli P, Al Abdallah Q, Robitaille R, Solis NV, Fielhaber JA, Kristof AS, Laverdiere M, Filler SG, Sheppard DC., Antimicrob. Agents Chemother. 55(12), 2011
PMID: 21930891
Liposomal amphotericin B twice weekly as antifungal prophylaxis in paediatric haematological malignancy patients.
Bochennek K, Tramsen L, Schedler N, Becker M, Klingebiel T, Groll AH, Lehrnbecher T., Clin. Microbiol. Infect. 17(12), 2011
PMID: 21895857
Safety analysis of liposomal amphotericin B in adult patients: anaemia, thrombocytopenia, nephrotoxicity, hepatotoxicity and hypokalaemia.
Shigemi A, Matsumoto K, Ikawa K, Yaji K, Shimodozono Y, Morikawa N, Takeda Y, Yamada K., Int. J. Antimicrob. Agents 38(5), 2011
PMID: 21885259

51 References

Data provided by Europe PubMed Central.


AUTHOR UNKNOWN, 2009

Export

0 Marked Publications

Open Data PUB

Web of Science

View record in Web of Science®

Sources

PMID: 20660670
PubMed | Europe PMC

Search this title in

Google Scholar