acyclovir and Leukopenia

The median bioavailabilities of aciclovir after administration of aciclovir and its prodrug valaciclovir were 21.5 and 70.1%, respectively, in 12 patients with malignant hematological diseases with leukopenia after chemotherapy. The interindividual variations of the bioavailability were 48.5 and 21.0% after administration of aciclovir and valaciclovir, respectively. Neither the bioavailability nor the interindividual variation of area under the concentration-time curve of oral aciclovir or valaciclovir differed from that reported in healthy volunteers.

Topics: Acyclovir; Administration, Oral; Antiviral Agents; Biological Availability; Humans; Leukopenia; Prodrugs; Valacyclovir; Valine

Despite current approaches to prophylaxis, cytomegalovirus (CMV) continues to be a common cause of infection and disease in solid-organ-transplant patients. Thus, we conducted a controlled trial comparing long-term administration of ganciclovir with high-dose acyclovir for prevention of CMV infection and disease in liver transplant recipients. At the time of transplant, patients were randomised to receive either ganciclovir (6 mg/kg body weight per day intravenously from postoperative day 1 to day 30, then 6 mg/kg per day Monday through Friday until day 100) or acyclovir (10 mg/kg intravenously every 8 h from postoperative day 1 to day of discharge, then 800 mg orally four times a day until day 100). Patients were followed for development of CMV infection, CMV disease, and drug-related toxicity by frequent cultures, serological tests, laboratory measurements, and tissue biopsies. During the first 120 days after transplant, CMV infection occurred in 48 of 126 (38%) acyclovir patients but in only 6 of 124 (5%) ganciclovir patients (p < 0.0001). Similarly, symptomatic CMV disease developed in 12 of 126 (10%) acyclovir patients but in only 1 of 124 (0.8%) ganciclovir patients (p = 0.002). Ganciclovir reduced the incidence of CMV infection in both CMV antibody positive (37 vs 4%, p = 0.001) and negative patients (42 vs 11%, p = 0.06). In a multivariate analysis of donor-recipient CMV antibody status and other risk factors, prophylactic ganciclovir was the most significant factor protecting against CMV infection (p < 0.0001) and disease (p = 0.001). Ganciclovir and acyclovir were generally well-tolerated. Incidences of leukopenia, thrombocytopenia, renal failure, and other adverse events were similar in the two groups. CMV can be eliminated almost completely as a significant pathogen in liver transplant recipients by the long-term administration of prophylactic ganciclovir. In addition, the treatment is safe.

Topics: Acyclovir; Administration, Oral; Adult; Aged; Antibodies, Viral; Cytomegalovirus; Cytomegalovirus Infections; Drug Administration Schedule; Female; Follow-Up Studies; Ganciclovir; Humans; Incidence; Injections, Intravenous; Leukopenia; Liver Transplantation; Male; Middle Aged; Multivariate Analysis; Thrombocytopenia

Sixty-four patients received systemic alpha-interferon (10 million units subcutaneously daily) and 63 received systemic acyclovir (5 mg/kg body weight intravenously thrice daily) in a randomized study of acute herpes zoster. Start of healing, complete healing, development of new skin lesions in the primarily affected and in other dermatomes, and degree and duration of pain were evaluated. Both drugs proved equally clinically efficient without statistically different findings between the two groups; herpes zoster neuralgia was not prevented by either interferon or acyclovir therapy. Minor clinical side effects occurred slightly more frequently during interferon treatment and included fever and nausea. Transient and moderate leukopenia was observed in nearly all patients in the interferon group.

Topics: Acyclovir; Aged; Clinical Trials as Topic; Female; Fever; Herpes Zoster; Humans; Interferon Type I; Leukopenia; Male; Middle Aged; Nausea; Random Allocation; Recombinant Proteins

Shingles is the cutaneous expression of the reactivation of latent varicella zoster virus infection in sensory ganglia. It presents as vesicles in the corresponding dermatome. The condition is called disseminated herpes zoster (DHZ) when more than 2 contiguous dermatomes are affected, more than 20 vesicles are observed outside the initial dermatome, or involvement is systemic. DHZ is rare and most frequently occurs in immunocompromised patients.. To describe the epidemiology, predisposing factors, clinical presentation, laboratory findings, and clinical course of patients with DHZ, and to compare the findings in immunocompromised and immunocompetent patients.. We analyzed a retrospective case series of adults hospitalized between February 2010 and October 2015.. Forty-one patients with virologically confirmed manifestations of DHZ were included. Stress as a trigger factor was detected in 39% and immunodepression in 58.5%. Immunocompromised patients were younger than the immunocompetent patients (mean ages, 60.5 vs 82 years, P<.01). The 8 immunocompetent patients with no detectable trigger factors were older (mean age, 85 years). In 95% of cases, DHZ was initially limited to a single dermatome and then spread to other dermatomes or became disseminated. Thrombocytopenia was detected in 56% of cases. Complication rates were similar in immunocompromised and immunocompetent patients (54% vs 59%, P>.01). Six patients died; there was no difference in mortality between the 2 groups.. This study provides evidence on the relationship between DHZ, the presence of underlying immunodepression, and complications. Immunosenescence may play an important role in the onset of this disease in older immunocompetent patients.

Topics: Acyclovir; Aged; Aged, 80 and over; Anemia; Antiviral Agents; Female; Herpes Zoster; Humans; Immunocompetence; Leukopenia; Male; Middle Aged; Neuralgia, Postherpetic; Retrospective Studies; Risk Factors; Spain; Stress, Psychological; Superinfection; Treatment Outcome

Immunosuppressive agents (azathioprine, methotrexate) are increasingly being used in the treatment of inflammatory bowel disease. The use of immunosuppressive agents is associated with a greater risk of opportunistic infections, the most frequent of which are those caused by cytomegalovirus and varicella zoster virus. We present four cases of opportunistic infections due to Herpesviruses in patients undergoing immunosuppressive treatment with azathioprine for Crohn's disease. We also review the literature published on this topic. Two patients presented cutaneous varicella complicated by pneumonia and esophagitis respectively, one patient had cutaneous herpes zoster and the other had fatal pneumonia possibly caused by the Herpesvirus. In the first three the clinical course of the infection was favorable after withdrawing immunosuppressant treatment and initiating treatment with aziclovir. In patients Crohn's disease azathioprine treatment increases the risk of opportunistic infection by Herpesvirus. However, in the absence of other factors that increase immunosuppression, these infections usually have a benign course with specific antiviral therapy.

Topics: Acyclovir; Adult; Aged; Antiviral Agents; Azathioprine; Chickenpox; Crohn Disease; Disease Susceptibility; Esophageal Diseases; Fatal Outcome; Female; Ganciclovir; Hepatitis, Viral, Human; Herpes Zoster; Herpesviridae Infections; Humans; Immunosuppressive Agents; Leukopenia; Lymphopenia; Male; Opportunistic Infections; Pneumonia, Viral

The efficacy of oral acyclovir, a purine nucleoside analogue with activity against human herpes viruses, is limited as a result of its low bioavailability. Valacyclovir, the L-valyl ester of acyclovir, has been developed as a pro-drug to improve the bioavailability. The aim of the present study was to compare the pharmacokinetics of acyclovir after intravenous administration and after oral administration of valacyclovir.. The pharmacokinetics of acyclovir were studied in 18 children aged 1.4-18.1 years (median: 6.9 years; 9 females) after intravenous infusion (1 hr; median dose: 10.5 mg/kg). In 10 of the children the pharmacokinetics of acyclovir were also studied after oral administration of valacyclovir (median dose: 34.1 mg/kg). Quantification of acyclovir in serum was performed by reversed-phase liquid chromatography with fluorometric detection. The pharmacokinetic analysis was performed by pharmacokinetic modelling.. The serum concentration versus time curves of acyclovir were described by the two compartment model after intravenous administration and by the one compartment model with a zero- or first-order absorption phase after oral administration of valacyclovir. The bioavailability of acyclovir after oral administration of valacyclovir was 45% (median value; 95% CI: 37-55%).. It is possible to substitute intravenous acyclovir therapy by oral valacyclovir therapy in children with leukopenia and mucositis after chemotherapy. This finding can at present not be fully implemented in clinical practice, since a commercial pharmaceutical formulation of valacyclovir aimed for children not able to swallow intact tablets is lacking. Crushed valacyclovir tablets have a very unpleasant taste, but can be administered to children through nasogastric tubes.

Topics: Acyclovir; Administration, Oral; Adolescent; Antineoplastic Agents; Antiviral Agents; Biological Availability; Child; Child, Preschool; Female; Herpes Simplex; Humans; Immunocompromised Host; Infant; Infusions, Intravenous; Leukopenia; Male; Mouth Mucosa; Prodrugs; Stomatitis; Valacyclovir; Valine

Topics: Acyclovir; Agranulocytosis; Antibodies, Viral; Central Nervous System Diseases; Chickenpox; Child; Herpesvirus 3, Human; Humans; Leukopenia; Liver Diseases; Male; Neutropenia

The efficacy and toxicity of ganciclovir given by intravenous or intravenous plus intravitreal injection were studied in nine patients with cytomegalovirus (CMV) retinitis; seven with AIDS and two with drug induced immunodeficiency. Five patients had retinitis with macular involvement in six sighted eyes; six patients had only peripheral retinitis in seven eyes. In two patients (two eyes) with macular involvement intravenous plus intravitreal injection of ganciclovir preserved sight; intravenous infusion alone did not in four eyes of three other patients. In seven eyes (six patients) with peripheral retinitis vision was retained regardless of the route of ganciclovir treatment. Following intravenous ganciclovir drug levels in the vitreous fluid were 1.4-2.2 mmol/l, that is, 44 and 65% of the concomitant serum concentration. Clinically and at necropsy three eyes showed no evidence of toxicity from intravitreal injection of ganciclovir. All of five patients with AIDS who received intravenous ganciclovir for more than one week developed leucopenia. CMV retinitis of the macula may be benefited with minimal drug toxicity by intravitreal injection of ganciclovir. Treatment of peripheral CMV retinitis in patients with AIDS may be optional.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Antiviral Agents; Cytomegalovirus Infections; Ganciclovir; Humans; Immunosuppression Therapy; Injections, Intravenous; Leukopenia; Retinitis; Visual Acuity; Vitreous Body

Out of 80 kidney graft recipients treated with cyclosporin A and low dose steroids 19 (23.8%) developed herpes virus infection and from these 15 (18.8%) herpetic stomatitis. Evaluation of enhancing factors for herpetic stomatitis suggested a role of cyclosporin A rather than of steroids and a probable relation to preceding CMV infection. Acyclovir treatment was effective on the course of stomatitis and pain in 12 of the 15 patients. No serious side effects were observed. Leukopenia as a possible hazard was discussed.

Topics: Acyclovir; Cyclosporins; Humans; Immunosuppression Therapy; Kidney Transplantation; Leukocyte Count; Leukopenia; Stomatitis, Herpetic