AN INVESTIGATION OF THE NEPHROTOXICITY AND EFFICACY OF
CIDOFOVIR FOR THE TREATMENT OF CYTOMEGALOVIRUS INFECTION
AND DISEASE AFTER ALLOGENEIC STEM CELL TRANSPLANTATION
Nick Duncan, Neil Masters
Pharmacy Department, Queen Elizabeth Hospital, Birmingham
Nick Duncan
Haematology pharmacist
Pharmacy Department
Queen Elizabeth Hospital
Edgbaston
Birmingham
B 15 2TH
Tele - 0121 627 2323
Fax - 0121 627 2324
Nick.Duncan@uhb.nhs.uk
AN INVESTIGATION OF THE NEPHROTOXICITY AND EFFICACY OF
CIDOFOVIR FOR THE TREATMENT OF CYTOMEGALOVIRUS INFECTION
AND DISEASE AFTER ALLOGENEIC STEM CELL TRANSPLANTATION
Nick Duncan, Neil Masters
Pharmacy Department, Queen Elizabeth Hospital, Birmingham
Introduction
Cytomegalovirus (CMV) infection and disease are important complications of
allogeneic stem cell transplantation (SCT).1 Recognised treatment options include
ganciclovir, foscarnet and cidofovir. Of these, cidofovir has shown promising efficacy
as a salvage therapy2 but is associated with nephrotoxicity and its use is contraindicated in renal impairment (CrCl ≤55ml/min).3 We have previously reported our
experience with cidofovir in a small cohort of SCT patients.4 The aims of the current
study were to investigate further the nephrotoxicity and efficacy of this agent in a larger
cohort of patients, including those with pre-existing renal impairment.
Methods
Data were collected for all haematology patients at the Queen Elizabeth Hospital who
received cidofovir as an anti-CMV agent between January 2006 – February 2008. The
drug was given at a dose of 5mg/kg every 1-2 weeks. Doses were adjusted for renal
impairment where necessary.5
Results
13 patients received 18 courses of cidofovir. 6 patients had pre-existing renal
impairment (CrCl ≤55ml/min). The median number of doses per course was 4.5 (range
1-9). Serum creatinine data are presented in table 1. Two patients developed a
doubling of serum creatinine during treatment and a 1.5 fold increase was seen in a
further four patients. No patient stopped treatment due to nephrotoxicity.
Table 1 Serum creatinine measurements in patients receiving cidofovir
Baseline
Mean
Serum
creatinine
(µmol/l)
Mean increase in creatinine
114
Maximum during
treatment
165
End of
treatment
149
-
+47%
+32%
In terms of efficacy, ten patients received cidofovir for CMV infection unresponsive to
ganciclovir. None of these patients subsequently developed CMV disease. Of the three
patients who received the drug for CMV disease, one patient subsequently died of
CMV pneumonitis.
Conclusions
We have shown that cidofovir has a manageable nephrotoxicity profile and can be
safely given to patients with pre-existing renal impairment. This drug should be
considered as an alternative to foscarnet as a second-line agent for the treatment of
CMV infection and disease.
References
1.
Ljungman P et al. Management of CMV infections: recommendations form
the infectious diseases working party of the EBMT. Bone Marrow
Transplant 2004; 33: 1075-1081
2.
Ljungman P et al. Cidofovir for cytomegalovirus infection and disease in
allogeneic stem cell transplant recipients. The Infectious Diseases Working
Party of the EBMT. Blood. 2001; 97:388-92.
3.
http://www.medicines.org.uk/. Accessed 25/6/08.
4.
Todd S, Duncan N. The use of cidofovir in the management of viral
infections in patients with haematological malignancies. BOPA 2004
5.
Ashley C, Currie A (eds). The Renal Drug Handbook (2nd ed.), 2004.
Radcliffe Medical Press, Oxford.