valacyclovir and Kidney-Failure--Chronic

Valacyclovir (VACV) is used increasingly to treat herpes zoster, although neuropsychiatric symptoms [VACV neurotoxicity (VAN) or acyclovir neurotoxicity], may accompany use of this drug. To promote awareness of this rare condition, we describe here two clinical cases of VAN we previously reported and review 20 cases from the literature. In all cases, chronic or acute renal failure preceded VAN. The symptoms of VAN varied, but disturbances of consciousness and hallucination occurred most commonly. When acute renal failure was due to the drug, recovery from both the disturbance of consciousness and renal failure followed within several days after discontinuation of VACV. Early recognition and diagnosis will ensure effective treatment of VAN.

Topics: Acute Kidney Injury; Acyclovir; Adult; Aged; Antiviral Agents; Consciousness Disorders; Female; Hallucinations; Herpes Zoster; Humans; Kidney Failure, Chronic; Male; Middle Aged; Neurotoxicity Syndromes; Valacyclovir; Valine

Polyomavirus BK (BKV) is the cause of polyomavirus-associated nephropathy resulting in premature graft loss. There are limited data regarding the role of cytomegalovirus (CMV) infection and its prevention in developing BKV viremia and PVAN. In a prospective study, we analyzed 207 consecutive renal transplant recipients previously enrolled in 2 randomized trials evaluating different CMV prevention regimens with routine screening for BKV and CMV. Of these, 59 received valganciclovir and 100 valacyclovir prophylaxis; 48 patients were managed by preemptive therapy. At 3 years, the incidence of BKV viremia and PVAN was 28% and 5%, respectively. CMV DNAemia developed in 55% and CMV disease in 6%. Both BKV viremia (42% vs 23% vs 21%, P = .006) and PVAN (12% vs 2% vs 2%, P = .011) were increased in patients treated with valganciclovir prophylaxis compared to valacyclovir and preemptive therapy. Using multivariate Cox proportional hazard regression, valganciclovir prophylaxis was independent predictor of BKV viremia (hazard ratio [HR] = 2.38, P = .002) and PVAN (HR = 4.73, P = .026). In contrast, the risk of subsequent BKV viremia was lower in patients with antecedent CMV DNAemia (HR = 0.50, P = .018). These data suggest valganciclovir prophylaxis may be associated with increased risk of BKV viremia and PVAN. CMV DNAemia did not represent a risk for BKV.

Topics: Adult; BK Virus; Cytomegalovirus; Cytomegalovirus Infections; Female; Graft Survival; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Multivariate Analysis; Polyomavirus Infections; Premedication; Proportional Hazards Models; Prospective Studies; Randomized Controlled Trials as Topic; Risk Factors; Treatment Outcome; Tumor Virus Infections; Valacyclovir; Valganciclovir; Viremia

We report a 57-year-old woman with end-stage renal disease (ESRD) on maintenance peritoneal dialysis (PD), who presented to the emergency room (ER) by ambulance with complaints of confusion and altered sensorium for 48 hours. She had been reviewed in a walk-in clinic 72 hours earlier and had been prescribed the standard 1000 mg three times per day of valacyclovir for an acute attack of shingles instead of 500 mg once a day on ESRD. In the ER, she received further 500 mg of intravenous acyclovir as herpes encephalitis was clinically suspected. CT of the brain and lumbar puncture were non-contributory to the diagnosis. Valacyclovir and acyclovir were discontinued when the diagnosis of valacyclovir-associated neurotoxicity became clinically evident. As the patient's Glasgow Coma Scale declined, we intensified her PD regimen from one to six exchanges per day and 24 hours later there was a significant neurological improvement.

Topics: Acyclovir; Administration, Intravenous; Antiviral Agents; Confusion; Consciousness Disorders; Diagnosis, Differential; Encephalitis, Herpes Simplex; Female; Herpes Zoster; Humans; Kidney Failure, Chronic; Middle Aged; Neurotoxicity Syndromes; Peritoneal Dialysis; Valacyclovir; Valine

An 81-year-old woman suffering from sarcoidosis, chronic renal failure caused by hypertention was treated by valacyclovir 500 mg/day, for the diagnosis of herpes zoster of her right back. Her consciousness gradually became worse, and 3 days after taking the drug, she was sent to the emergency department of the hospital. Her conscious level was E2V2M5 (Glasgow Coma Scale) and myoclonus especially in her lower extremities occurred. Head CT and MRI show no obvious, acute abnormal findings other than chronic ischemic lesions, while an electroencephalogram (EEG) shows periodic synchronous discharges (PSDs) and disorganized background activity. Based on these findings, she was diagnosed as valacyclovir-associated acute encephalopathy. After conservative therapy of maintenance hemodialysis, her consciousness gradually improved, and PSDs disappeared accordingly and background activity of EEG became improved. In this case report, we presented valacyclovir-associated neurotoxicity with PSDs in EEG as potentially a surrogate marker. We should be cautious to use valaciclovir which may cause drug-induced encephalopathy especially in elderly or patients with renal failure even though the dose was adjusted in advance.

Topics: Acute Disease; Acyclovir; Aged, 80 and over; Antiviral Agents; Brain Diseases; Electroencephalography; Female; Herpes Zoster; Humans; Kidney Failure, Chronic; Periodicity; Valacyclovir; Valine

Valacyclovir induced neurotoxicity is a life-threatening complication, usually starting 24-48 h after drug-peak serum concentrations. The elderly with impaired renal function seem to be the most susceptible group to valacyclovir neurotoxicity. Although hemodialysis is considered the best method for rapid drug removal, our case showed that intensive peritoneal dialysis regimen leads to the recovery of neurotoxicity after 3 days.

Topics: Acute Kidney Injury; Acyclovir; Aged; Antiviral Agents; Female; Follow-Up Studies; Herpes Zoster; Humans; Kidney Failure, Chronic; Kidney Function Tests; Peritoneal Dialysis, Continuous Ambulatory; Risk Assessment; Treatment Outcome; Valacyclovir; Valine

Topics: Acyclovir; Antiviral Agents; Female; Herpes Zoster; Humans; Kidney Failure, Chronic; Middle Aged; Neurotoxicity Syndromes; Renal Dialysis; Valacyclovir; Valine

We followed up 550 primary kidney transplant recipients in an observational retrospective cohort to evaluate the impact of three consecutive cytomegalovirus (CMV) prevention strategies. In period 1 (1996-2000; n = 190), no anti-CMV prophylaxis was given; in period 2 (2000-2004; n = 173), 6-month valacyclovir was given and in period 3 (>2004; n = 187), 6-month valganciclovir was given. Cytomegalovirus disease significantly decreased from 33.2% in period 1 to 13.9% in period 2 and to 8.6% in period 3; onset was significantly prolonged with valganciclovir (228 days) compared with valacyclovir (93 days) and with no prophylaxis (33 days). After Cox regression adjustments, both valganciclovir and valacyclovir were similarly protective factors for CMV disease. Cytomegalovirus diseases encountered in both valacyclovir and valganciclovir groups were primary infections (79.2 and 93.8% respectively) as compared with a significant low number (39.7%) in the nonprophylaxis group. Two cases of valganciclovir resistance were recorded in the valganciclovir group and no resistance was seen with valacyclovir. A significantly reduced incidence of other herpes viruses was only observed with valganciclovir. Valganciclovir was better tolerated than valacyclovir and this long-term prophylaxis was applicable to 85% of patients. Longer follow-up of valganciclovir or valacyclovir prophylaxis is still required to appreciate its impact on graft and patient survivals, as well as other indirect effects, in the mycophenolate mofetil and calcineurin inhibitor immunosuppressive era.

Topics: Acyclovir; Antiviral Agents; Cytomegalovirus Infections; Female; Follow-Up Studies; Ganciclovir; Graft Survival; Humans; Incidence; Injections, Intravenous; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Prodrugs; Retrospective Studies; Survival Rate; Time Factors; Treatment Outcome; Valacyclovir; Valganciclovir; Valine

The patient was a 67-year-old man with a 2-year history of peritoneal dialysis for end-stage renal disease due to hypertensive nephropathy. He presented to a dermatologist with a complaint of pain in the right femoral region. He was diagnosed as having herpes zoster and valacyclovir, 1,000 mg/day, was prescribed. After 5 days of taking valacyclovir orally, he felt fretful and hallucinations appeared. He was admitted to our hospital and was hospitalized in our urology ward. We diagnosed his condition as neurotoxicity caused by an overdose of valacyclovir. As his general condition was stable, he was treated only by continuation of peritoneal dialysis. After 7 days of hospitalization, the neurotoxicity completely disappeared and he left the hospital. His serum acyclovir concentration at admission was 20.20 μg/l, and was reduced to 0.7 μg/l when he left the hospital. This supported our diagnosis of valacyclovir-induced neurotoxicity. In this case, valacyclovir should have been reduced to 500 mg/day, considering his renal function. Although we could treat the patient only by continuation of peritoneal dialysis, hemodialysis seems to be an effective treatment method in the case of unstable general condition or severe adverse effects, because it can eliminate the serum acyclovir.

Topics: Acyclovir; Aged; Antiviral Agents; Humans; Kidney Failure, Chronic; Male; Mental Disorders; Peritoneal Dialysis; Valacyclovir; Valine

Topics: Acyclovir; Adult; Antiviral Agents; Arm; Ecchymosis; Female; Giant Cells; Herpes Zoster; Histological Techniques; Humans; Kidney Failure, Chronic; Lupus Nephritis; Purpura; Thrombocytopenia; Valacyclovir; Valine

This study was performed to investigate the pharmacokinetics of valaciclovir (VACV), aciclovir (ACV) and 9-(carboxymethoxy)methylguanine (CMMG) in Japanese chronic hemodialysis patients following a single oral administration of 1000 mg VACV and the influence of genetic polymorphisms of aldehyde dehydrogenase-2 (ALDH2) on their pharmacokinetics. A total of eighteen individuals genotyped as ALDH2*1/*1, ALDH2*1/*2 or ALDH2*2/*2 were enrolled in this study. Blood samples were obtained pre-dose and up to 48 hour post-dose. ACV t(1/2) was significantly affected by ALDH2 genotype and prolonged in the order of ALDH2*1/*1 (18.1 hr)

Topics: Acyclovir; Administration, Oral; Adult; Aged; Aldehyde Dehydrogenase; Aldehyde Dehydrogenase, Mitochondrial; Female; Guanine; Half-Life; Humans; Kidney Failure, Chronic; Male; Middle Aged; Polymorphism, Genetic; Prodrugs; Renal Dialysis; Valacyclovir; Valine

Valaciclovir (VACV) has been reported to induce adverse neuropsychiatric effects (ANE), especially in patients with renal failure, but few data are available for renal transplant recipients (RTR).. We conducted a retrospective study in RTR given VACV as cytomegalovirus prophylaxis, from January 1999 to December 2000, to define the incidence rate, type and outcome of VACV-induced ANE, and to identify risk factors for ANE. The VACV-induced ANE were defined as neuropsychiatric disorders justifying VACV dose reduction or withdrawal. Patients with and without VACV-induced ANE were compared by univariate and multivariate analysis.. In all, 167 RTR were included, of whom 25 (15%) displayed VACV-induced ANE (mainly hallucinations and confusion), which occurred with a mean of 4 days after the start of VACV. ANE were reversible in all cases. Multivariate analysis showed that delayed graft function (DGF) was the main risk factor for VACV-induced ANE [Odds ratio (OR): 12.1; 95% CI = 3.4-43.4; P = 0.0001]. All VACV doses given to patients with ANE were in accordance with the current recommended adaptation to estimated glomerular filtration rate (GFR).. In RTR, VACV-induced ANE are significantly frequent but reversible. DGF occurrence is the main risk factor for these ANE. In RTR with DGF, the recommended doses for GFR below 10 ml/min might be too high. Several strategies, in RTR with DGF, might lower the risk of ANE, including reduction of the currently recommended VACV dosage, delayed VACV introduction until improvement of renal function, or use of another anti-cytomegalovirus drug.

Topics: Acyclovir; Adult; Age Distribution; Analysis of Variance; Behavioral Symptoms; Cohort Studies; Cytomegalovirus Infections; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; France; Graft Rejection; Humans; Incidence; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Neuropsychological Tests; Probability; Prognosis; Retrospective Studies; Risk Assessment; Sex Distribution; Valacyclovir; Valine

Little is known about the implications of performing a renal transplant on a patient who is already pregnant. This case study reports a successful outcome of pregnancy, diagnosed coincidentally following renal transplantation at 13 weeks gestation. The recipient was a 23-year-old woman with chronic kidney disease who received a live-related renal transplant from her father. Pregnancy was discovered at routine ultrasound scanning of the renal allograft at 5 days posttransplant and estimated at 13 weeks gestation. She received ciclosporin monotherapy as immunosuppression throughout the pregnancy, and was given valacyclovir as prophylaxis against cytomegalovirus (CMV) infection. Renal function remained stable throughout the pregnancy, which progressed normally, resulting in the vaginal delivery of a healthy, liveborn male infant at 37 weeks gestation. This case study demonstrates that transplantation during pregnancy can have a successful outcome.

Topics: Acyclovir; Adult; Cyclosporine; Family Health; Female; Humans; Immunosuppressive Agents; Infant, Newborn; Kidney; Kidney Failure, Chronic; Kidney Transplantation; Living Donors; Male; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Pregnancy, High-Risk; Time Factors; Treatment Outcome; Valacyclovir; Valine

Topics: Acyclovir; Aged; Aged, 80 and over; Anticonvulsants; Antiviral Agents; Female; Herpes Zoster; Humans; Kidney Failure, Chronic; Status Epilepticus; Treatment Outcome; Valacyclovir; Valine

Cytomegalovirus (CMV) is a major pathogen in renal transplant patients causing significant post-transplant morbidity and mortality. Prophylactic antiviral therapy, currently implemented in most kidney transplant centres, has significantly reduced the incidence of CMV infection after transplantation. Oral ganciclovir has been shown to be an effective prophylactic agent in preventing CMV disease and infection with a demonstrated superior efficacy over oral acyclovir. Valacyclovir, a prodrug of acyclovir with a higher level of bioavailability than acyclovir, has also been shown to be effective in preventing CMV disease when given as prophylactic treatment.. In a retrospective analysis of 150 renal transplant recipients in our centre, we compared the efficacy of oral ganciclovir with valacyclovir in preventing CMV infection. Seventy-seven consecutive renal transplant recipients prophylactically treated with oral ganciclovir for 12 weeks after transplant were compared with 73 consecutive recipients treated with oral valacylovir for an equal length of time.. No difference was noted in the incidence of CMV infection between the two treatment groups (5.1 vs 5.4%) after a 6 month follow-up. Likewise, the incidence of acute rejection was similar in both groups (11.6 vs 6.8%). All cases of CMV infection occurred in high-risk patients (donor positive/recipient negative).. The prophylactic use of oral valacylovir is as effective as oral ganciclovir in reducing CMV infection and disease after kidney transplantation.

Topics: Acyclovir; Administration, Oral; Adult; Cytomegalovirus Infections; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Ganciclovir; Graft Rejection; Graft Survival; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Opportunistic Infections; Preoperative Care; Probability; Retrospective Studies; Risk Assessment; Treatment Outcome; Valacyclovir; Valine

Topics: Acyclovir; Aged; Humans; Kidney Failure, Chronic; Male; Seizures; Valacyclovir; Valine

Topics: Acyclovir; Aged; Antiviral Agents; Dose-Response Relationship, Drug; Humans; Kidney Failure, Chronic; Male; Neurotoxicity Syndromes; Peritoneal Dialysis, Continuous Ambulatory; Valacyclovir; Valine

In continuous ambulatory peritoneal dialysis (CAPD) patients, acyclovir-induced neurotoxicity is reported to be associated with high serum drug levels even when following the recommended reduced doses for this renal failure population. In view of the high oral bioavailability of valaciclovir (the L-valyl ester of acyclovir) the risk of neurotoxicity becomes more prominent. The present study was conducted in 12 CAPD patients who were administered a single oral dose of 500 mg valaciclovir. Acyclovir was analyzed by high-performance liquid chromatography. Relative pharmacokinetic parameters were estimated based on acyclovir concentrations at 8, 12 and 24 h post-dose. High inter-patient variations were observed with acyclovir apparent total clearance 7.238 +/- 4 l/h and half-life (T1/2) 22.27 +/- 16.82 h. However, dosage simulations confirmed supratherapeutic acyclovir concentrations for all participants when following the recommended dose of 1,000 mg valaciclovir/24 h for varicella zoster infections.

Topics: Acyclovir; Aged; Antiviral Agents; Biological Availability; Female; Herpes Zoster; Humans; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Valacyclovir; Valine

Topics: 2-Aminopurine; Acyclovir; Aged; Aged, 80 and over; Chorea; Drug Interactions; Famciclovir; Herpes Zoster; Humans; Kidney Failure, Chronic; Male; Renal Dialysis; Valacyclovir; Valine