Pharmacokinetics, safety and preliminary clinical experiences using foscarnet in the treatment of cytomegalovirus infections in bone marrow and renal transplant recipients

Ringdén, Olle; Lönnqvist, B; Paulin, Thomas; Ahlmén, J; Klintmalm, Göran B.; Wahrén, Britta; Lernestedt, J.-O.

doi:10.1093/jac/17.3.373

Cited by 127 publications

(48 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The relationship of renal insufficiency to foscarnet use was considered possible in 4 of these 5 patients and was judged unevaluatable in the other. The frequency and severity ofrenal toxicity in our study was in the range ofthat in other studies ofallogeneic BMT recipients and AIDS patients [24,25,[28][29][30][31][32].…”

Section: Discussionsupporting

confidence: 63%

“…With one exception [17], earlier studies of foscarnet among BMT recipients used continuous intravenous infusions to administer the drug [13,19,28,29,[36][37][38]. In one of these studies that reported data on pharmacokinetics [29], the steady-state serum levels of foscarnet in 13 allogeneic BMT recipients who received a daily dose of foscarnet similar to the dose in our inpatient regimen were 273 ± 43~mol/ L (mean ± SE).…”

Section: Discussionmentioning

confidence: 88%

“…In one of these studies that reported data on pharmacokinetics [29], the steady-state serum levels of foscarnet in 13 allogeneic BMT recipients who received a daily dose of foscarnet similar to the dose in our inpatient regimen were 273 ± 43~mol/ L (mean ± SE). In our study, the median peak plasma concentrations of foscarnet obtained during the inpatient and outpatient regimens among autograft and allograft recipients ranged from 256 to 387~mol/L.…”

Section: Discussionmentioning

confidence: 90%

See 2 more Smart Citations

Phase I-II Trial of Foscarnet for Prevention of Cytomegalovirus Infection in Autologous and Allogeneic Marrow Transplant Recipients

Reusser

Gambertoglio

Lilleby

et al. 1992

Journal of Infectious Diseases

View full text Add to dashboard Cite

The safety and efficacy of foscarnet for prevention of cytomegalovirus (CMV) infection was evaluated in 19 CMV-seropositive bone marrow transplant (BMT) recipients. All patients received intermittent intravenous (iv) foscarnet: 40 mg/kg every 8 h from 7 days before to day 30 after BMT, then 60 mg/kg once a day until day 75. The main toxicity was transient renal dysfunction, with a >50 pmol/L increase in serum creatinine above baseline in 5 of the 7 autograft recipients and in 6 of the 12 allograft recipients. Only 4 allograft recipients developed CMV infection during foscarnet prophylaxis, and no patient showed evidence ofCMV disease. Because 3 allograft recipients receiving concomitant iv amphotericin B showed rapid impairment of renal function, foscarnet prophylaxis should not be given to allograft recipients requiring amphotericin B; otherwise, foscarnet prophylaxis at this dose appears safe after BMT.Infection due to cytomegalovirus (CMV) causes significant morbidity and mortality among bone marrow transplant (BMT) recipients [1]. In two published series, the probability ofCMV infection within the first 100 days after BMT among patients who were CMV-seropositive before transplant was up to 80%and 60%for allograft and autograft recipients, respectively [2,3]. Mortality was primarily related to CMV pneumonia, which developed in 37% of allograft and in 22% of autograft recipients who had evidence of active CMV infection [2,3]. Thus, the prevention of CMV infection and disease after BMT is of foremost importance.Antiviral chemotherapy aimed at preventing reactivation of latent virus may be the most promising approach to CMV prophylaxis both among CMV-seropositive autograft and allograft recipients and among seronegative allograft recipients who have a seropositive marrow donor. CMV drug prophylaxis should cover the early period after BMT in which a deficiency in CMV-specific immunity can contribute to the risk of severe CMV disease [4].The antiviral agent acyclovir given intravenously at high doses was shown to be partially effective in preventing CMV infection and disease among seropositive BMT recipients [5].

show abstract

Section: Discussionsupporting

confidence: 63%

Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 90%

See 1 more Smart Citation

Phase I-II Trial of Foscarnet for Prevention of Cytomegalovirus Infection in Autologous and Allogeneic Marrow Transplant Recipients

Reusser

Gambertoglio

Lilleby

et al. 1992

Journal of Infectious Diseases

View full text Add to dashboard Cite

show abstract

“…31 Patients with CMV infection were treated with ganciclovir or foscarnet. 32 Details about treatment have been published elsewhere. 21,23,33,34 …”

Section: Prophylaxis Against Infectionsmentioning

confidence: 99%

G-CSF given after haematopoietic stem cell transplantation using HLA-identical sibling donors is associated to a higher incidence of acute GVHD II–IV

Remberger

Naseh

Aschan

et al. 2003

Bone Marrow Transplant

View full text Add to dashboard Cite

Summary:The effect of granulocyte colony-stimulating factor (G-CSF), given after transplantation, was studied in 155 patients transplanted with haematopoietic stem cells (HSCT) from HLA-identical sibling donors at Huddinge University Hospital between 1993 and 2001. Only patients with haematological malignancies were included. Conditioning consisted of total-body irradiation in 118 and busulphan in 37 patients. They were all given methotrexate combined with cyclosporine as graft-versus-host disease (GVHD) prophylaxis. Of the 155 patients, 66 (43%) received G-CSF after HSCT. Those given G-CSF had a significantly shorter time to neutrophil engraftment (Po0.001). G-CSF treatment had no effect on erythrocyte transfusions, platelet engraftment and infections. However, patients treated with G-CSF had a significantly higher incidence of grades II-IV acute GVHD than those not given this treatment (34 vs 9%, Po0.001). The multivariate analysis showed that the effect of G-CSF was independent of other known risk factors for grades II-IV acute GVHD. Death from GVHD occurred in four and two cases (P ¼ 0.06) in the two groups, respectively. The cumulative incidences of transplant-related mortality, survival, chronic GVHD, relapse and relapse-free survival were similar in both groups. In conclusion, G-CSF given after HLA-identical sibling HSCT was associated with a higher risk of grades II-IV acute GVHD, but not transplant-related mortality.

show abstract

“…Foscarnet (trisodium phosphonoformate hexahydrate; PFA) is a drug which, like DHPG, inhibits viral DNA polymerase activity, leading to reversible suppression of viral replication (7,17). In clinical trials in allograft recipients with CMV disease, PFA treatment was associated with suppression of CMV replication and resolution of fever and thrombocytopenia in renal transplant recipients, but not bone marrow transplant recipients, with CMV interstitial pneumonitis (7,17).…”

mentioning

confidence: 99%

Synergistic effect of ganciclovir and foscarnet on cytomegalovirus replication in vitro

Manischewitz

Quinnan

Lane

et al. 1990

Antimicrob Agents Chemother

119

View full text Add to dashboard Cite

show abstract

Pharmacokinetics, safety and preliminary clinical experiences using foscarnet in the treatment of cytomegalovirus infections in bone marrow and renal transplant recipients

Cited by 127 publications

References 0 publications

Phase I-II Trial of Foscarnet for Prevention of Cytomegalovirus Infection in Autologous and Allogeneic Marrow Transplant Recipients

Phase I-II Trial of Foscarnet for Prevention of Cytomegalovirus Infection in Autologous and Allogeneic Marrow Transplant Recipients

G-CSF given after haematopoietic stem cell transplantation using HLA-identical sibling donors is associated to a higher incidence of acute GVHD II–IV

Synergistic effect of ganciclovir and foscarnet on cytomegalovirus replication in vitro

Contact Info

Product

Resources

About