acyclovir and Kidney-Failure--Chronic

BACKGROUND The elderly population in the United States and the world is rapidly increasing. With aging, immunity and kidney function decrease, thus predisposing people to viral illnesses for which there is no effective prophylaxis. Herpes zoster afflicts the elderly and other immunocompromised patients, like those with end-stage renal disease, transplant recipients, and cancer patients, causing significant morbidity and sometimes mortality. Treating herpes zoster becomes problematic when the regular pharmacokinetics of the antiviral drugs are disturbed. CASE REPORT An 83-year-old African American man with end-stage kidney disease (ESRD) and on chronic peritoneal dialysis (PD) developed herpes zoster, for which he received the manufacturer-recommended intravenous dose of acyclovir. Shortly after taking the medication, he developed confusion, disorientation, and visual hallucinations. He was switched from PD to hemodialysis (HD), with successful recovery. Examination of the cerebrospinal fluid for meningitis and imaging studies of the head were negative. Serum levels of acyclovir were elevated. CONCLUSIONS Even when the acyclovir dose is properly adjusted for kidney function based on the current manufacturer's recommendations, it can cause neurotoxicity. Here, we discuss the pharmacokinetics of acyclovir and make some recommendations with regard to dose adjustment in patients with ESRD.

Topics: Acyclovir; Aged, 80 and over; Antiviral Agents; Humans; Kidney Failure, Chronic; Male; Neurotoxicity Syndromes; Peritoneal Dialysis

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

To develop a set of comprehensive, standardized, evidence-based guidelines for the use of antiviral therapy to prevent cytomegalovirus disease in adult patients having undergone renal transplantation.. The use of medication, at the time of induction therapy or at the earliest sign of viremia. Treatments were evaluated by patient and donor serologic groups and the induction regimen used.. The control of symptoms and features of cytomegalovirus disease over the first 6 mo to 1 yr after transplantation.. Articles, compiled using a MEDLINE search from 1976 to July 1997, were reviewed by representatives of nephrology, microbiology, pharmacy, and epidemiology. Additional information was obtained from recent review articles and conference abstracts, and from experts in the field.. The evidence-based methods and values of the Canadian Task Force on the Periodic Health Examinations were used. High value was placed on studies with a randomized controlled design and blinded outcome observers. Study quality was classified as poor when cointervention was present (especially with regard to immunosuppressive regimens), when more than 20% of patients were lost to follow-up, and when intention to treat analysis was not performed. Recommendations were made with a graded system (grades A and B: Use of the intervention advised, based on high or fair quality evidence, respectively; grades D and E: Use of the intervention not advised, based on high or fair quality evidence, respectively: grade C: No recommendation made because of insufficient or conflicting evidence).. (1) Seropositive recipient; donor seropositive or seronegative; immunosuppression with antilymphocyte products. Prophylaxis with antiviral therapy recommended (grade A recommendation). (2) Seronegative recipient; seropositive donor; immunosuppression with antilymphocyte products. Prophylaxis with antiviral therapy recommended (grade A recommendation) (3) Seronegative recipient; seropositive donor; conventional immunosuppression. Prophylaxis with antiviral therapy recommended (grade B recommendation). (4) Seronegative recipient; seronegative donor; any immunosuppressive regimen. No prophylaxis with antiviral therapy required (grade D/E recommendation). (5) Seropositive recipient: donor seropositive or seronegative; conventional immunosuppression. Prophylaxis left to the discrimination of the physician in charge (grade C recommendation).

Topics: Acyclovir; Adult; Antiviral Agents; Canada; Clinical Trials as Topic; Cost-Benefit Analysis; Cytomegalovirus Infections; Drug Costs; Female; Forecasting; Ganciclovir; Graft Rejection; Graft Survival; Humans; Immunization, Passive; Kidney Failure, Chronic; Kidney Transplantation; Male; Practice Guidelines as Topic; Prognosis; Tissue Donors

To alert practitioners to the danger of acyclovir neurotoxicity occurring in the presence of renal failure.. Two case reports of acyclovir neurotoxicity in the patients on continuous ambulatory peritoneal dialysis.. In one case neurotoxicity resulted from the use of a dosage regimen that would be appropriate in patients with normal renal function. In the other case, neurotoxicity occurred even though a reduced dose of acyclovir was given. Supportive management resulted in a complete recovery.. In patients with end stage renal failure with varicella zoster infections, when acyclovir is prescribed the loading dose should be 400 mg and the maintenance dose should be 200 mg twice daily.

Topics: Acyclovir; Aged; Antiviral Agents; Dose-Response Relationship, Drug; Female; Herpes Zoster; Humans; Kidney Failure, Chronic; Middle Aged; Nervous System; Peritoneal Dialysis, Continuous Ambulatory

Neurotoxicity associated with acyclovir use is infrequently encountered. However, the half-life of acyclovir is greatly prolonged in patients with end-stage renal disease, predisposing these patients to neurological side effects that are generally reversible but occasionally severe. In general, renal dialysis effectively decreases the serum level of acyclovir, which correlates with toxicity. We report an unusual case of delirium and coma in a patient undergoing hemodialysis who was receiving what appeared to be an appropriately adjusted dose of acyclovir.

Topics: Acyclovir; Aged; Coma; Delirium; Herpes Simplex; Humans; Kidney Failure, Chronic; Male; Penile Diseases; Renal Dialysis; Ulcer

Acyclovir produces neurologic symptoms that resemble extension of viral infection into the central nervous system. We discuss our observations in the cases of two patients with acyclovir neurotoxicity and review the findings of all previous reports in the English language literature. Systemic disease, most commonly renal dysfunction, preceded all 30 reported cases of acyclovir neurotoxicity. The most common symptoms were mental status disorder and involuntary movements. Measurement of serum acyclovir levels substantiated the diagnosis in only a subset of patients. Although all patients recovered, hemodialysis hastened the rate of recovery.

Topics: Acyclovir; Adult; Aged; Aged, 80 and over; Central Nervous System Diseases; Cytomegalovirus Infections; Female; Herpes Simplex; Herpes Zoster; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis

Renal dysfunction is a significant risk factor for acyclovir-induced neurotoxicity and altered mentation and myoclonic movements are the most common clinical symptoms observed. In majority of reported cases, neurological sequelae associated with acyclovir-induced neurotoxicity often mimic viral infections of the central nervous system and makes diagnosis of the former challenging. Although plasma concentrations of the drug may not always correlate with neurotoxic symptoms, obtaining serum levels of acyclovir may be helpful in confirming drug-induced neurotoxicity. Hemodialysis has been shown to significantly improve altered mentation in patients with suspected or confirmed acyclovir-induced neurotoxicity. Here, we report a definite case of acyclovir-induced neurotoxicity in a patient with end-stage renal disease. Clinical improvements in neurologic symptoms were observed following discontinuation of the drug and hemodialysis.

Topics: Acyclovir; Antiviral Agents; Central Nervous System Diseases; Humans; Kidney Failure, Chronic; Male; Middle Aged; Neurotoxicity Syndromes; Renal Dialysis

Granulomatosis polyangiitis (GPA) is an ANCA-related vasculitis (AAV) whose clinical manifestations mainly concern the respiratory tract (upper and lower) and the kidney. The treatment of GPA (as well as other AAV) includes the use of immunosuppressive drugs with numerous side effects; the most frequent complications are infectious and neoplastic. GPA frequently relapses. Epstein Barr Virus (EBV) is a ubiquitous virus; it is estimated that about 90% of the world’s population has BEEN EXPOSED TO with this pathogen and has subsequently developed a latent infection. Under certain conditions including immunosuppression EBV may reactivate. We report the clinical case of a 67-year-old woman who presented with GPA involving the upper respiratory tract and renal failure with the need for hemodialysis treatment. The fourth month of induction therapy with cyclophosphamide and methylprednisone she presented with dyspnea and respiratory failure. After excluding pulmonary embolism and heart failure, a series of investigations including high resolution tomography and fibroscopy with broncoalveolar lavage (BAL) were performed which excluded recurrence of pulmonary vasculitis including alveolar haemorrhage A BAL demonstrated EBV-DNA. On this basis EBV pneumonia was diagnosed, and antiviral therapy with acyclovir was begun, followed by clinical and radiological improvement. In patients with GPA treated with immunosuppressive drugs pulmonary involvement may not only be due to the underlying vasculitis, but also to opportunistic agents, which must always be considered.

Topics: Acyclovir; Aged; Antiviral Agents; Cyclophosphamide; Disease Susceptibility; Dyspnea; Epstein-Barr Virus Infections; Female; Granulomatosis with Polyangiitis; Herpesvirus 4, Human; Humans; Immunocompromised Host; Immunosuppressive Agents; Kidney Failure, Chronic; Pneumonia, Viral; Prednisone; Renal Dialysis; Respiratory Insufficiency

Topics: Acyclovir; Aged; Antiviral Agents; Female; Hemodiafiltration; Humans; Kidney Failure, Chronic; Neurotoxicity Syndromes; Recovery of Function; Renal Dialysis; Stomatitis, Herpetic; Treatment Outcome

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

Interstitial nephritis due to viruses is well-described after solid organ transplantation. Viruses implicated include cytomegalovirus; BK polyomavirus; Epstein-Barr virus; and, less commonly, adenovirus. We describe a rare case of hemorrhagic allograft nephritis due to herpes simplex virus type 1 at 10 days after living donor kidney transplantation. The patient had a favorable outcome with intravenous acyclovir and reduction of immunosuppression.

Topics: Acyclovir; Allografts; Antiviral Agents; Glomerular Filtration Rate; Graft Rejection; Graft Survival; Hemorrhage; Herpes Simplex; Herpesvirus 1, Human; Humans; Immunosuppression Therapy; Kidney Failure, Chronic; Kidney Function Tests; Kidney Transplantation; Male; Middle Aged; Nephritis; Prognosis; Risk Factors

Topics: Acyclovir; Aged; Antiviral Agents; Brain Diseases; Herpes Zoster; Humans; Kidney Failure, Chronic; Male; Renal Dialysis

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: Acute Disease; Acyclovir; Antiviral Agents; Confusion; Electroencephalography; Herpes Zoster; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis

Topics: Acyclovir; Akathisia, Drug-Induced; Baclofen; Continuity of Patient Care; Humans; Kidney Failure, Chronic; Male; Muscle Relaxants, Central; Myoclonus; Renal Dialysis; Tremor

Acyclovir is widely used in the treatment of herpes virus infections, particularly herpes simplex virus and varicella-zoster virus. Acyclovir, when given promptly upon the start of a herpes zoster eruption, speeds healing and diminishes acute pain.. Because acyclovir is a commonly used medication, it is crucial for health providers to be aware of appropriate dosing as well as possible side effects. We present this case to increase awareness of the potential for inappropriate dosing of acyclovir and the presentations of patients with toxic effects.. We report the case of a 65-year-old man with a past medical history significant for chronic kidney disease who presented to the Emergency Department with progressive confusion and ataxia over 2 days. Thorough questioning in the patient's native language revealed that he had recently started a medication for a "rash." Neither he nor his family knew the name of the new medication; further investigation revealed it to be acyclovir. Although other diagnoses were considered in the differential diagnosis for this patient with altered mental status, he was treated for presumed acyclovir toxicity and given prompt dialysis, upon which his symptoms resolved.. It is important for physicians to remember that even common medications such as acyclovir can have serious side effects and complications. In this case, renal dosing was not used in a patient on hemodialysis. Acyclovir must be renally dosed and carefully monitored through drug level measurement in patients with limited kidney function to prevent serious side effects, such as the neurological sequelae demonstrated in this case report. Emergency physicians should be aware of the potential for inappropriate dosing of this medication and the presentations of patients with toxic effects.

Topics: Acyclovir; Aged; Antiviral Agents; Ataxia; Confusion; Herpes Zoster; Humans; Kidney Failure, Chronic; Male; Mental Disorders; Renal Dialysis; Treatment Outcome

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

Topics: Acyclovir; Aged; Akathisia, Drug-Induced; Alcoholic Intoxication; Baclofen; Continuity of Patient Care; Diagnostic Errors; Drug Overdose; Emergencies; Herpes Zoster; Humans; Kidney Failure, Chronic; Male; Muscle Relaxants, Central; Myoclonus; Poisoning; Renal Dialysis; Tremor; Uremia

A probable acyclovir-associated hypersensitivity reaction resulting in severe facial angioedema and respiratory distress is reported.. A 51-year-old woman with human immunodeficiency virus (HIV) infection and end-stage renal disease arrived at the emergency department (ED) with a diffuse rash on the chest and back; she was diagnosed with varicella-zoster virus infection, received one dose of i.v. acyclovir, and was discharged home with a prescription for valacyclovir. After taking one dose of the drug, she became confused and agitated. The next day the patient returned to the ED; she was confused and unresponsive, with signs and symptoms suggesting viral encephalitis. After a workup including lumbar puncture fluid, she was treated empirically with i.v. acyclovir for viral encephalitis. Within one hour of receiving the acyclovir infusion, the patient developed angioedema of the lips, tongue, and periorbital areas requiring intubation and transfer to the intensive care unit. Further acyclovir therapy was withheld, and foscarnet therapy was initiated for the presumptive treatment of viral encephalitis. Over the next few days, the patient's angioedema completely resolved; her mental status gradually improved while she completed a 14-day course of foscarnet therapy. The application of the Naranjo scale indicated a probable adverse reaction to acyclovir, likely mediated by acyclovir-specific immunoglobulin E, highlighting the need to consider alternative antiviral agents without cross-reactivity to acyclovir in patients with confirmed or suspected viral encephalitis.. A 51-year-old woman with HIV infection developed probable acyclovir-induced angioedema after receiving i.v. acyclovir therapy for suspected viral encephalitis.

Topics: Acyclovir; Angioedema; Antiviral Agents; Encephalitis, Varicella Zoster; Face; Female; HIV Infections; Humans; Immunoglobulin E; Infusions, Intravenous; Kidney Failure, Chronic; Middle Aged; Respiration Disorders; Severity of Illness Index

Varicella zoster virus reactivation often occurs in the setting of impaired immunity, which is generally present in patients with end-stage renal disease (ESRD). Therapy for variceIla zoster virus infection is well established. However, it is often been forgotten that acyclovir dosage should be adjusted to renal function. We point to the problem encountered in clinical practice when ESRD patient presents with cutaneous herpes zoster and neurological symptoms. Clinical findings alone may prove inadequate to determine whether neurological deficit is caused by infection of the central nervous system or is a consequence of acyclovir induced neurotoxicity.

Topics: Acyclovir; Aged; Antiviral Agents; Female; Herpes Zoster; Herpesvirus 3, Human; Humans; Immunocompromised Host; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Virus Activation

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

Ramsay Hunt syndrome develops upon reactivation of a latent virus within the geniculate ganglion. The patient presents with acute facial paralysis, severe ear pain, and a vesicular eruption of the external auditory canal and concha. Varicella zoster virus seropositivity occurs among approximately 90% of members of society. In these persons, virus reactivation may occur especially with advancing age and immunosuppression. We present a case of Ramsay Hunt syndrome that developed in a 35-year-old male patient, who had undergone a renal transplantation 8 months prior and had received maintenance immunosuppression.

Topics: Acyclovir; Adult; Antiviral Agents; Dose-Response Relationship, Drug; Herpes Zoster Oticus; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Male; Methylprednisolone; Mycophenolic Acid; Postoperative Complications; Treatment Outcome

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

The U.S. end-stage renal disease (ESRD) population continues to increase. Adjustment of several drugs administered to dialysis patients is mandatory because of decreased--and sometimes totally absent--renal clearances. Gabapentin, a newer anticonvulsant increasingly used for several other clinical indications, is excreted in the urine unchanged. Its half-life of 5 - 9 hours is increased to up to 132 hours in anuric patients. Excretion of acyclovir an antiviral agent, occurs predominantly through the kidney (glomerular filtration and tubular secretion). Its normal plasma half-life is 2 - 3 hours; dosage modifications are obligatory in renal insufficiency. In 2008, we encountered 2 ESRD patients on dialysis who exhibited significant neurotoxicity with encephalopathy after gabapentin and acyclovir were given at the usual adult doses. Following prompt drug discontinuation and continued daily hemodialysis or peritoneal dialysis respectively, both patients were discharged home, in normal clinical condition, after 3 days. With the increasing ESRD (and CKD) populations, health care providers other than nephrologists will have increasing contact with these patients. Those providers must consider drug dose modifications according to residual renal function. Algorithms for appropriate renal drug dosing are available from various sources. Pragmatic tactics of this kind will avoid significant morbidity and mortality. In addition, this approach will save millions of now increasingly scarce health care dollars.

Topics: Acyclovir; Aged; Amines; Analgesics; Antiviral Agents; Cyclohexanecarboxylic Acids; Gabapentin; gamma-Aminobutyric Acid; Humans; Kidney Failure, Chronic; Male; Middle Aged; Neurotoxicity Syndromes; Renal Dialysis

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

Topics: Acyclovir; Aged; Antiviral Agents; Diagnostic Errors; Facial Paralysis; Female; Hematoma, Subdural, Intracranial; Humans; Kidney Failure, Chronic; Renal Dialysis

A 70-year-old man developed herpes zoster over the right L5-S2 region for 3 days and was admitted for acyclovir therapy. He had a medical history of rectal cancer status post-colostomy and end-stage renal disease undergoing thrice weekly hemodialysis. Without a prior loading dose, acyclovir 500 mg (7.7 mg/kg) daily was given intravenously in two divided doses. On the third dosage, the patient became confused and agitated and developed insomnia. Within the following 24 h, delirium, visual and auditory hallucinations, disorientation to place and time, as well as impaired recent memory occurred. At the same time, a transient low grade fever (38 degrees C) was noted but resolved spontaneously after ice pillow (Fig. 1). The etiology was vigorously explored. He had no history of any neurological or psychiatric disorders. Drug history was reviewed, but no other medications besides acyclovir were currently being used. Physical examination revealed neither meningeal signs nor focal neurological deficits. Serum blood urea nitrogen, glucose, and electrolytes were within normal limits except for an elevated creatinine level at 6.2 and 5.7 mg/dl (before and after neuropsychotic symptoms, respectively). Complete blood count with differentiation was also unremarkable. Cerebrospinal fluid examination was not possible as the patient's family refused the lumbar puncture. Moreover, an electroencephalograph study and head computed tomography scan disclosed no abnormalities. Acyclovir-induced neurotoxicity was suspected. Therefore, acyclovir was discontinued. Subsequently, serum acyclovir and CMMG were checked by enzyme-linked immunosorbent assay. Serum acyclovir level was 1.6 mg/l (normal therapeutic level, 0.12-10.8 mg/l) and CMMG level was 5 mg/l. Emergent hemodialysis (4-h/session) was given; the neuropsychotic symptoms, including agitation, delirium, and visual and auditory hallucinations, greatly abated after the second session. The patient fully recovered after three consecutive days of hemodialysis; the serum was rechecked and revealed that the acyclovir level was below 0.5 mg/l and the CMMG level was undetectable. At the same time, his herpetic skin lesions resolved well.

Topics: Acyclovir; Aged; Antiviral Agents; Delirium; Guanine; Hallucinations; Herpes Zoster; Humans; Kidney Failure, Chronic; Male; Renal Dialysis

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; Antiviral Agents; Brain Diseases; Female; Herpes Zoster; Humans; Kidney Failure, Chronic; Middle Aged

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

Topics: Acyclovir; Humans; Kidney Failure, Chronic; Nervous System Diseases; Prodrugs

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

Acyclovir (ACV) has been used for over two decades to treat herpes virus infections. Serious neurological adverse side effects have occurred during ACV treatment in patients with renal failure, but the cause of the symptoms remains unknown. We hypothesized that increased concentrations of the ACV main metabolite 9-carboxymethoxymethylguanine (CMMG) correlated to these symptoms.. We conducted an observational study from 1991 to mid 1999 based on samples sent for analysis of ACV concentration from various hospital departments in Sweden. Patients with neuropsychiatric symptoms (NS+, n=49) were compared with patients without symptoms (NS-, n=44). ACV and CMMG concentrations were analysed by HPLC. Medical records were analysed for symptoms and compared with pertinent cases identified from Medline.. The serum CMMG levels were significantly higher in the NS+ group (mean=34.1 micro mol/l, 95% confidence interval 23.4-46.1) compared with the NS- group (mean=4.7 micro mol/l, 95% confidence interval 3.3-6.6; P<0.001). CMMG was the strongest predictor in a receiver-operating characteristics curve analysis (ROC), based on 77 patients, of ACV-related neuropsychiatric symptoms. The ROC curve for CMMG demonstrated that neuropsychiatric symptoms could be predicted with a sensitivity of 91% and a specificity of 93% with the use of a cut-off value of 10.8 micro mol/l of CMMG. Thirty-five of 49 patients in the NS+ group showed levels exceeding this concentration compared with only three of 44 of patients in the NS- group (P<0.001). ACV exposure, ACV concentration, creatinine clearance and creatinine concentration were weaker but statistically significant predictors. Haemodialysis reduced CMMG and ACV levels and relieved the symptoms.. The determination of CMMG levels in serum may be a useful tool in supporting the diagnosis of ACV-associated neuropsychiatric symptoms. Furthermore, the monitoring of CMMG levels may prevent the emergence of symptoms.

Topics: Acyclovir; Adult; Aged; Antiviral Agents; Creatinine; Female; Guanine; Herpes Zoster; Humans; Kidney Failure, Chronic; Male; Mental Disorders; Middle Aged; Neurotoxicity Syndromes; ROC Curve; Sensitivity and Specificity

Nephrotoxicity is a well-known side effect of intravenous acyclovir treatment but occurs rarely by oral treatment. A 76-y-old healthy male, with normal baseline renal functions (blood creatinine 0.6 mg%), received oral acyclovir at a dose of 800 mg five times daily for 10 days for treatment of herpes zoster ophthalmicus. He developed renal failure with blood creatinine levels of 3 mg% and his renal function failed to improve within eight months of end of treatment. Affection of renal function has to be considered also in relation to oral acyclovir treatment, especially in elderly subjects.

Topics: Acyclovir; Administration, Oral; Aged; Antiviral Agents; Creatinine; Herpes Zoster Ophthalmicus; Humans; Kidney Failure, Chronic; Male

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

Topics: Acyclovir; Antiviral Agents; Confusion; Diabetes Mellitus, Type 1; Female; Herpes Labialis; Humans; Hypertension; Kidney Failure, Chronic; Middle Aged; Nausea

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

Because of the severe complications that may result from varicella zoster virus (VZV) infection following renal transplantation (Tx), transplanted varicella-susceptible children exposed to varicella are typically given varicella zoster immunoglobulin (VZIG) as prophylaxis or are admitted and treated with parenteral acyclovir if VZIG prophylaxis fails. As both VZIG and hospitalization are costly, prevention of varicella infection by vaccination could potentially result in significant cost savings in addition to decreasing morbidity and mortality. To test this hypothesis, we developed a decision-analysis model to evaluate the cost-effectiveness of vaccinating patients with chronic renal failure (CRF) against varicella prior to renal transplant. Under baseline assumptions, vaccination for varicella pretransplant was a cost-effective strategy, with a cost of $211 per patient vaccinated compared with $1,828 per patient not vaccinated. The magnitude of cost savings from vaccination was sensitive to variations in the cost of varicella vaccine, the percentage of patients hospitalized for treatment with acyclovir, and the percentage of patients exposed to varicella infection. One- and two-way sensitivity analyses confirmed that vaccination was the dominant cost-effective strategy under all conditions examined. We conclude that vaccination for varicella pretransplant is cost-effective for patients with CRF, and that the magnitude of cost savings is sensitive to the cost of hospitalization, the percentage of patients exposed to varicella, and the cost of varicella vaccination. Pending results of ongoing studies of the safety and efficacy of VZV vaccine in children with CRF, we recommend that VZV vaccine be given to all children with CRF.

Topics: Acyclovir; Chickenpox; Chickenpox Vaccine; Child; Child, Preschool; Cost-Benefit Analysis; gamma-Globulins; Herpes Zoster; Humans; Immunization; Kidney Failure, Chronic; Kidney Transplantation

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

Topics: Acyclovir; Adult; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antiviral Agents; Cyclosporine; Cytomegalovirus Infections; Daclizumab; Drug Therapy, Combination; Female; Graft Rejection; Humans; Immunoglobulin G; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Living Donors; Male; Retrospective Studies

Topics: Acyclovir; Antiviral Agents; Female; Herpes Zoster; Humans; Kidney Failure, Chronic; Middle Aged; Nervous System Diseases; Renal Dialysis

Topics: Acyclovir; Adult; Antiviral Agents; Brain Diseases; Herpes Zoster; Humans; Kidney Failure, Chronic; Male; Renal Dialysis; Skin Diseases, Viral

It is increasingly recognised that dose adjustment of oral acyclovir in continuous ambulatory peritoneal dialysis (CAPD) patients is necessary to avoid neurotoxicity. A single 800-mg oral dose of acyclovir was administered to 10 uninfected anuric patients who were treated by CAPD. Serial blood and CAPD bag samples were analysed for acyclovir during the 31 h after dosing. Serum acyclovir levels were measured using radioimmunoassay and the pharmacokinetic parameters were estimated by linear regression using the STRIPE computer programme. Peak plasma levels of 8.95 +/- 3.95 microM were achieved at 4.1 +/- 1.85 h with the T1/2 calculated to be 14.52 +/- 3 h. The mean predicted serum acyclovir levels at steady state after 1,600-, 800- and 600-mg daily doses were 13.76, 6.88 and 5.16 microM, respectively. The present recommended daily doses of acyclovir (1,600 mg) for end-stage renal disease patients leads to supratherapeutic levels therefore increasing the risk and incidence of neurotoxicity. Computer modelling of various dosage simulations suggests that daily doses of 800 and 600 mg will achieve therapeutic levels (4-8 microM).

Topics: Acyclovir; Administration, Oral; Adult; Aged; Antiviral Agents; Female; Half-Life; Humans; Kidney Failure, Chronic; Male; Metabolic Clearance Rate; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory

A 59-y-old with a history of chronic renal failure on hemodialysis was diagnosed with herpes zoster and begun on 800 mg acyclovir 5 times daily. Two days later the patient developed visual hallucinations, ataxia, confusion and memory loss along with focal myoclonus, nausea and vomiting. No fever, elevated WBC count or significant electrolyte imbalance was found. CT scan of the brain was unremarkable. The patient was then dialyzed for presumed acyclovir toxicity. Her acyclovir level was later found to have been 3.4 micrograms/ml (normal peak range 0.4-2 micrograms/ml) prior to dialysis. After 3 h of hemodialysis, her post-dialysis acyclovir level was 1.9 micrograms/ml. After a second course of hemodialysis the next day the patient's mental status improved, and she was discharged 5 d later. Due to its low volume of distribution (0.6 L/kg), low protein binding (about 15%) and water solubility, acyclovir is an example of the ideal drug that can be removed by hemodialysis. About 45% of the total body amount can be extracted through a 3-h course of hemodialysis with resultant improvement in symptoms.

Topics: Acyclovir; Antiviral Agents; Ataxia; Blood Chemical Analysis; Female; Hallucinations; Herpes Zoster; Humans; Kidney Failure, Chronic; Memory; Middle Aged; Myoclonus; Nausea; Renal Dialysis; Vomiting

Acute neurotoxicity following the administration of the recommended oral dose of acyclovir (800 mg twice daily) to dialysis-dependent patients is increasingly recognised. This suggests that the recommended dose is too high. Little is known of the pharmacokinetics of oral acyclovir in dialysis patients. We studied 7 patients with oliguric end stage renal failure receiving haemodialysis. Following haemodialysis, each patient received a single 800-mg tablet of acyclovir. Plasma acyclovir levels were monitored over the next 48 h as well as before and after the next routine dialysis. Peak plasma levels were achieved at 3 h (12.54 +/- 1.76 microM, range 8.5-17.5 microM) with the half-life calculated to be 20.2 +/- 4.6 h. Mean plasma level of 6.29 +/- 0.94 microM were within the quoted range to inhibit herpes zoster virus (4-8 microM) at 18 h. Haemodialysis (4-5 h) eliminated 51 +/- 11.5% of the acyclovir which remained at 48 h. Computer modelling of various dose modifications suggests that a loading dose of 400 mg and a maintenance dose of 200 mg twice daily is sufficient to maintain a mean plasma acyclovir level of 6.4 +/- 0.8 microM. A further loading dose (400 mg) after dialysis would raise the residual acyclovir concentration by 6.1 +/- 1.0 microM. Such a dose modification should prevent neurotoxicity, whilst the rapid elimination of acyclovir by a single haemodialysis treatment provides both a diagnostic and therapeutic tool when toxicity is suspected.

Topics: Acyclovir; Administration, Oral; Adult; Aged; Computer Simulation; Female; Half-Life; Humans; Kidney Failure, Chronic; Male; Middle Aged; Nervous System; Renal Dialysis; Virus Diseases

Topics: Acyclovir; Adult; Brain Diseases; Diagnosis, Differential; Herpes Zoster; Humans; Kidney Failure, Chronic; Male; Meningoencephalitis

A case of renal failure in a patient with severe central nervous system symptoms during oral acyclovir medication is reported. A 68-year-old man maintained on hemodialysis was given oral acyclovir 4,000 mg daily in divided doses because of herpes zoster affecting the left C3/5 dermatomes. He had vomiting and confusion 36 hours after administration. He had no focal neurological signs. The symptoms resolved 4 days after cessation of acyclovir administration and blood purification every day. Because of its high therapeutic index the use of acyclovir is associated with few side effects. In patients with renal failure the half-life of acyclovir is prolonged, this report indicates the importance of adhering to the dosage reductions in patients with renal failure.

Topics: Acyclovir; Administration, Oral; Aged; Central Nervous System Diseases; Herpes Zoster; Humans; Kidney Failure, Chronic; Male; Renal Dialysis

Oral infection with Herpes Simplex Virus (HSV) is a frequent and well documented complication in immunosuppressed individuals including patients on immunosuppressive medication. We report the development of severe oral infection with HSV type 1 in a 34 year old woman with type 1 diabetes mellitus and end stage renal disease (ESRD) following cadaveric renal transplantation at the Western General Hospital, Edinburgh. The role of acyclovir in therapy and chemoprophylaxis is discussed.

Topics: Acyclovir; Adult; Diabetes Mellitus, Type 1; Female; Herpes Labialis; Humans; Kidney Failure, Chronic; Kidney Transplantation; Postoperative Complications

Neurotoxicity associated with intravenous acyclovir therapy is well documented. We report 4 cases of acyclovir-induced neurotoxicity in dialysis patients receiving oral therapy at a reduced dose.

Topics: Acyclovir; Administration, Oral; Adult; Herpes Zoster; Humans; Kidney Failure, Chronic; Male; Middle Aged; Neurotoxins; Peritoneal Dialysis, Continuous Ambulatory; Renal Dialysis

Topics: Acyclovir; Coma; Female; Humans; Kidney Failure, Chronic; Middle Aged; Renal Dialysis

We report two cases of herpes-zoster in which the administration of acyclovir to patients with end-stage renal failure treated by continuous ambulatory peritoneal dialysis (CAPD) resulted in acyclovir neurotoxicity, even though the doses administered were within those recommended by the manufacturer's data sheet for patients with renal failure. Acyclovir removal was negligible with peritoneal dialysis and one patient died. The other patient was successfully treated with hemodialysis, which effectively reduced plasma concentrations, resulting in an improvement in conscious state. Acyclovir neurotoxicity should be considered in patients with renal failure who have been treated for viral infections, in whom the conscious state has deteriorated despite normal brain computed tomography (CT) scan and lumbar puncture investigations. Hemodialysis is the preferred treatment for the rapid removal of acyclovir.

Topics: Acyclovir; Adult; Aged; Brain; Consciousness; Female; Herpes Zoster; Humans; Kidney Failure, Chronic; Male; Peritoneal Dialysis, Continuous Ambulatory

Two patients on dialysis because of chronic renal failure who developed herpes zoster associated encephalitis are reported. Both developed overt encephalopathy despite treatment with oral acyclovir for the preceding herpes zoster eruption. The encephalopathy responded rapidly to intravenous acyclovir.

Topics: Acyclovir; Administration, Oral; Aged; Encephalitis; Female; Herpes Zoster; Humans; Injections, Intravenous; Kidney Failure, Chronic; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory

Topics: Acyclovir; Administration, Oral; Aged; Coma; Female; Herpes Zoster; Humans; Kidney Failure, Chronic

In subjects with normal renal function, acyclovir is rapidly removed from the body via the kidneys. In subjects with end-stage renal disease, the half-life is significantly prolonged. The half-life in subjects receiving hemodialysis and continuous ambulatory peritoneal dialysis (CAPD) is similarly prolonged (10.0 +/- 2.2 and 13.2 +/- 4.7 hours, respectively). After intravenous dosage, peritoneal clearance was 3.4 +/- 0.2 mL/min. Intraperitoneal dosing in subjects receiving CAPD resulted in a bioavailability of 61 +/- 10% and drug levels sufficient to inhibit herpes simplex virus (HSV) and varicella zoster virus (VZV). Intraperitoneal administration is an alternative route of administration in patients with poor vascular access.

Topics: Acyclovir; Adult; Biological Availability; Half-Life; Humans; Injections, Intraperitoneal; Injections, Intravenous; Kidney Failure, Chronic; Metabolic Clearance Rate; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Renal Dialysis

Topics: Acyclovir; Aged; Humans; Kidney Failure, Chronic; Male; Middle Aged; Nervous System Diseases; Peritoneal Dialysis, Continuous Ambulatory; Radioimmunoassay

Topics: Acyclovir; Aged; Female; Humans; Kidney Failure, Chronic; Nervous System Diseases

Once daily 60 min iv infusions of acyclovir at 2.5 mg/kg were administered to six uraemic patients (three male, three female of mean age 52 years and body weight 60 kg) treated by continuous ambulatory peritoneal dialysis (CAPD). Blood and dialysate samples were taken for analysis of acyclovir by radio-immunoassay. A three-compartment pharmacokinetic model was found necessary to explain the profiles obtained. Steady-state was reached by the third day, with little change in mean peak or trough plasma levels between day one (25 and 3 microM) and day five (29 and 4 microM). Mean total plasma clearance was 46 ml/h/kg, of which 12% was due to peritoneal dialysis. The model parameters predicted efficient transfer of acyclovir from the peritoneum to plasma, such that hypothetical peritoneal dosing might give 91% bioavailability. In patients treated by CAPD, iv acyclovir should be administered at 2.5 mg/kg/day.

Topics: Acyclovir; Adult; Aged; Ambulatory Care; Female; Half-Life; Humans; Kidney Failure, Chronic; Kinetics; Male; Metabolic Clearance Rate; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory

Acyclovir is an effective agent for the treatment of herpes virus infections, however, the pharmacokinetics of the drug are altered in renal failure. We studied this drug in a continuous ambulatory peritoneal dialysis (CAPD) patient who was immunocompromised and had cutaneous herpes infection. The elimination half-life (17.1 hours) was similar to that reported for end-stage renal disease (ESRD) patients, while the volume of the central compartment (29.6 L/1.73 m2), the steady state volume of distribution (68.1 L/1.73 m2), and the total body clearance (48.3 mL/min/1.73 m2) were greater. The mean CAPD clearance was only 4.4 mL/min, with less than 10% of an administered dose being recovered in the 24-hour dialysate. Further studies are needed to establish a dosing regimen for CAPD patients.

Topics: Acyclovir; Aged; Half-Life; Herpes Simplex; Humans; Infusions, Parenteral; Kidney Failure, Chronic; Kinetics; Male; Peritoneal Dialysis, Continuous Ambulatory

Topics: Acyclovir; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Psychoses, Substance-Induced; Renal Dialysis

Acyclovir (ACV) is almost entirely eliminated by the kidneys and has a terminal plasma half-life (t1/2) of 2 to 3 hr in subjects with normal renal function. To determine the drug's kinetics and tolerance in patients with severe renal failure, six anuric subjects on long-term hemodialysis were studied. Each received a 1-hr infusion of 2.5 mg/kg IV ACV. The kinetics are well described by a two-compartment open model. ACV terminal plasma t 1/2 and the total body clearance were 19.5 +/- 5.9 hr (mean +/- SD) and 28.6 +/- 9.5 ml/min/1.73 m2. Peak (end of infusion) and 8- and 24-hr plasma ACV concentrations were 37.5 +/- 23.3, 10.3 +/- 2.9, and 6.4 +/- 2.4 microM. Approximately 48 hr after the start of the infusion the subjects were hemodialyzed for 6 hr. The pre- and posthemodialysis ACV plasma levels were 2.74 +/- 1.38 and 1.11 +/- 0.60 microM. The terminal ACV t1/2 during hemodialysis was 5.7 +/- 0.85 hr. During hemodialysis paired arterial and venous samples showed that ACV was readily dialyzed, with a mean coefficient of extraction of 0.45 +/- 0.12. The dialysis clearance of acyclovir was 81.8 +/- 12.6 ml/min. None of the patients had any ACV-related adverse effects. Since ACV elimination is markedly reduced in end-stage renal failure and because ACV is readily hemodialyzible, dosage modification are needed to avoid cumulation and to replace dialyzed drug.

Topics: Acyclovir; Adult; Aged; Antiviral Agents; Female; Guanine; Humans; Kidney Failure, Chronic; Kinetics; Male; Middle Aged; Renal Dialysis; Time Factors

Topics: Acyclovir; Adult; Aged; Antiviral Agents; Female; Guanine; Humans; Kidney Failure, Chronic; Kinetics; Male; Middle Aged; Renal Dialysis; Statistics as Topic

The pharmacokinetic disposition of acyclovir was studied in six patients with chronic renal failure (CRF) and anuria. At the end of a one-hour intravenous infusion (2.5 mg/kg), the mean peak acyclovir plasma level (+/- SD), determined by radioimmunoassay, was 37.5 +/- 24.2 microM (8.4 +/- 5.4 microgram/ml), twice the level found at this dose in patients with normal renal function (NRF). In the CRF volunteers, significant plasma levels (3.0 +/- 1.4 microM) persisted at 47 hours after drug administration (before hemodialysis) whereas in the NRF patients levels dropped to less than 1 microM by 11 hours. Hemodialysis was started 47 hours after infusion and was continued for six hours. The pre-dialysis plasma drug level was reduced by 61.5 percent at 0.25 to 1.5 hours after the end of dialysis. The mean plasma t 1/2 during dialysis of 5.4 hours, the extraction ratio of 0.44, and the dialysis clearance for plasma of 113 ml/min indicate that acyclovir is efficiently removed by hemodialysis. One-half the suggested intravenous dose for a particular indication can be given every 24 hours and a similar replacement dose should be given after each dialysis.

Topics: Acyclovir; Antiviral Agents; Anuria; Guanine; Humans; Kidney Failure, Chronic; Kinetics; Renal Dialysis

Topics: Acyclovir; Adult; Female; Guanine; Herpes Simplex; Humans; Immunosuppression Therapy; Kidney Failure, Chronic; Kidney Transplantation