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BMJ (Clinical Research Ed.) Dec 2007report two cases of Cotard’s syndrome that occurred as an adverse drug reaction to aciclovir and its prodrug valaciclovir
report two cases of Cotard’s syndrome that occurred as an adverse drug reaction to aciclovir and its prodrug valaciclovir
Topics: Acyclovir; Adult; Antiviral Agents; Attitude to Death; Bipolar Disorder; Delusions; Female; Herpes Labialis; Herpes Zoster; Humans; Male; Middle Aged; Syndrome
PubMed: 18156240
DOI: 10.1136/bmj.39408.393137.BE -
Clinical Microbiology and Infection :... Jul 2006Ganciclovir and its prodrug, valganciclovir, are more effective than acyclovir in preventing cytomegalovirus (CMV) infection and disease in solid-organ transplant...
Ganciclovir and its prodrug, valganciclovir, are more effective than acyclovir in preventing cytomegalovirus (CMV) infection and disease in solid-organ transplant recipients. However, the indirect effects of prophylactic use of ganciclovir and acyclovir are comparable, and the greater effectiveness of ganciclovir may be compensated for by less drug-related toxicity with acyclovir or valacyclovir. No conclusive data exist concerning the best technique and duration of surveillance for CMV infection in patients for whom active surveillance for late-onset CMV should be performed, i.e., those reaching the end of prophylaxis. Only large randomised controlled trials, with long follow-up periods, will provide definitive conclusions regarding the comparative prophylactic roles of the major antiviral agents in this population, and how their use fits with a strategy of active surveillance and pre-emptive therapy.
Topics: Acyclovir; Antiviral Agents; Cytomegalovirus Infections; Ganciclovir; Humans; Organ Transplantation; Valacyclovir; Valganciclovir; Valine
PubMed: 16774555
DOI: 10.1111/j.1469-0691.2006.01405.x -
The Cochrane Database of Systematic... Dec 2016Infectious mononucleosis (IM) is a clinical syndrome, usually caused by the Epstein Barr virus (EPV), characterised by lymphadenopathy, fever and sore throat. Most cases... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Infectious mononucleosis (IM) is a clinical syndrome, usually caused by the Epstein Barr virus (EPV), characterised by lymphadenopathy, fever and sore throat. Most cases of symptomatic IM occur in older teenagers or young adults. Usually IM is a benign self-limiting illness and requires only symptomatic treatment. However, occasionally the disease course can be complicated or prolonged and lead to decreased productivity in terms of school or work. Antiviral medications have been used to treat IM, but the use of antivirals for IM is controversial. They may be effective by preventing viral replication which helps to keep the virus inactive. However, there are no guidelines for antivirals in IM.
OBJECTIVES
To assess the effects of antiviral therapy for infectious mononucleosis (IM).
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 3, March 2016), which contains the Cochrane Acute Respiratory Infections (ARI) Group's Specialised Register, MEDLINE (1946 to 15 April 2016), Embase (1974 to 15 April 2016), CINAHL (1981 to 15 April 2016), LILACS (1982 to 15 April 2016) and Web of Science (1955 to 15 April 2016). We searched the World Health Organization (WHO) International Clinical Trials Registry Platform and ClinicalTrials.gov for completed and ongoing trials.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) comparing antivirals versus placebo or no treatment in IM. We included trials of immunocompetent participants of any age or sex with clinical and laboratory-confirmed diagnosis of IM, who had symptoms for up to 14 days. Our primary outcomes were time to clinical recovery and adverse events and side effects of medication. Secondary outcomes included duration of abnormal clinical examination, complications, viral shedding, health-related quality of life, days missing from school or work and economic outcomes.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed studies for inclusion, assessed the included studies' risk of bias and extracted data using a customised data extraction sheet. We used the GRADE criteria to rate the quality of the evidence. We pooled heterogeneous data where possible, and presented the results narratively where we could not statistically combine data.
MAIN RESULTS
We included seven RCTs with a total of 333 participants in our review. Three trials studied hospitalised patients, two trials were conducted in an outpatient setting, while the trial setting was unclear in two studies. Participants' ages ranged from two years to young adults. The type of antiviral, administration route, and treatment duration varied between the trials. The antivirals in the included studies were acyclovir, valomaciclovir and valacyclovir. Follow-up varied from 20 days to six months. The diagnosis of IM was based on clinical symptoms and laboratory parameters.The risk of bias for all included studies was either unclear or high risk of bias. The quality of evidence was graded as very low for all outcomes and so the results should be interpreted with caution. There were statistically significant improvements in the treatment group for two of the 12 outcomes. These improvements may be of limited clinical significance.There was a mean reduction in 'time to clinical recovery as assessed by physician' of five days in the treatment group but with wide confidence intervals (CIs) (95% CI -8.04 to -1.08; two studies, 87 participants). Prospective studies indicate that clinical signs and symptoms may take one month or more to resolve and that fatigue may be persistent in approximately 10% of patients at six-month follow-up, so this may not be a clinically meaningful result.Trial results for the outcome 'adverse events and side effects of medication' were reported narratively in only five studies. In some reports authors were unsure whether an adverse event was related to medication or complication of disease. These results could not be pooled due to the potential for double counting results but overall, the majority of trials reporting this outcome did not find any significant difference between treatment and control groups.There was a mean reduction in 'duration of lymphadenopathy' of nine days (95% CI -11.75 to -6.14, two studies, 61 participants) in favour of the treatment group.In terms of viral shedding, the overall effect from six studies was that viral shedding was suppressed while on antiviral treatment, but this effect was not sustained when treatment stopped.For all other outcomes there was no statistically significant difference between antiviral treatment and control groups.
AUTHORS' CONCLUSIONS
The effectiveness of antiviral agents (acyclovir, valomaciclovir and valacyclovir) in acute IM is uncertain. The quality of the evidence is very low. The majority of included studies were at unclear or high risk of bias and so questions remain about the effectiveness of this intervention. Although two of the 12 outcomes have results that favour treatment over control, the quality of the evidence of these results is very low and may not be clinically meaningful. Alongside the lack of evidence of effectiveness, decision makers need to consider the potential adverse events and possible associated costs, and antiviral resistance. Further research in this area is warranted.
Topics: Acute Disease; Acyclovir; Adolescent; Adult; Antiviral Agents; Child; Child, Preschool; Female; Guanine; Humans; Infectious Mononucleosis; Male; Randomized Controlled Trials as Topic; Valacyclovir; Valine; Young Adult
PubMed: 27933614
DOI: 10.1002/14651858.CD011487.pub2 -
The American Journal of Case Reports Dec 2018BACKGROUND The elderly population in the United States and the world is rapidly increasing. With aging, immunity and kidney function decrease, thus predisposing people... (Review)
Review
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
PubMed: 30531673
DOI: 10.12659/AJCR.911520 -
Australian Family Physician May 2014
Topics: Acyclovir; Adult; Antiviral Agents; Blister; Diagnosis, Differential; Female; Hand Dermatoses; Herpes Simplex; Humans; Prodrugs; Real-Time Polymerase Chain Reaction; Recurrence; Valacyclovir; Valine
PubMed: 24791774
DOI: No ID Found -
Alimentary Pharmacology & Therapeutics Apr 1997Three patients developed acute colitis, either de novo, or as an exacerbation of pre-existing colitis, following the use of oral acyclovir, prescribed for Herpes zoster...
Three patients developed acute colitis, either de novo, or as an exacerbation of pre-existing colitis, following the use of oral acyclovir, prescribed for Herpes zoster or Herpes simplex infection. Rechallenge with oral acyclovir was performed in one patient, and resulted in a recurrence of colitic symptoms. It is speculated that acyclovir can have a direct irritant effect on large bowel mucosa.
Topics: Acyclovir; Adult; Antiviral Agents; Colitis, Ulcerative; Herpes Simplex; Herpes Zoster; Humans; Male; Middle Aged
PubMed: 9146784
DOI: 10.1046/j.1365-2036.1997.147323000.x -
AAPS PharmSciTech Mar 2013Investigations on thermal behavior of drug samples such as acyclovir and zidovudine are interesting not only for obtaining stability information for their processing in...
Investigations on thermal behavior of drug samples such as acyclovir and zidovudine are interesting not only for obtaining stability information for their processing in pharmaceutical industry but also for predicting their shelf lives and suitable storage conditions. The present work describes thermal behaviors and decomposition kinetics of acyclovir and zidovudine in solid state, studied by some thermal analysis techniques including differential scanning calorimetry (DSC) and simultaneous thermogravimetry-differential thermal analysis (TG/DTA). TG analysis revealed that thermal degradation of the acyclovir and zidovudine is started at the temperatures of 400°C and 190°C, respectively. Meanwhile, TG-DTA analysis of acyclovir indicated that this drug melts at about 256°C. However, melting of zidovudine occurred at 142°C, which is 100°C before starting its decomposition (242°C). Different heating rates were applied to study the DSC behavior of drug samples in order to compute their thermokinetic and thermodynamic parameters by non-isothermal kinetic methods. Thermokinetic data showed that both drugs at the room temperature have slow degradation reaction rates and long shelf lives. However, acyclovir is considerably more thermally stable than zidovudine.
Topics: Acyclovir; Antiviral Agents; Calorimetry, Differential Scanning; Drug Stability; Kinetics; Thermogravimetry; Zidovudine
PubMed: 23299688
DOI: 10.1208/s12249-012-9916-y -
Skin Therapy Letter Feb 2005The Herpesviridae family (Types 1-8) continues to inflict considerable morbidity and social stigma upon humanity. Once infected with the herpes viruses, especially Types... (Review)
Review
The Herpesviridae family (Types 1-8) continues to inflict considerable morbidity and social stigma upon humanity. Once infected with the herpes viruses, especially Types 1-3, they establish permanent residence within our nervous system and reactivate during periods of stress, trauma, and/or other precipitating factors. To date, there is no cure for herpes viral infections but antivirals can attenuate the symptoms and duration of episodic outbreaks. Prophylactic therapy can suppress recurrences. The first antiviral with selective activity against virus-infected cells is considered to be acyclovir. Our article will highlight the clinical indications of the current generation, valacyclovir, which is a prodrug of acyclovir. We consider valacyclovir as a second-generation antiviral, having taken into account the initial selectivity and safety profile of its progenitor, acyclovir.
Topics: Acyclovir; Antiviral Agents; Herpesviridae Infections; Humans; Prodrugs; Valacyclovir; Valine
PubMed: 15776202
DOI: No ID Found -
Molecules (Basel, Switzerland) Nov 2017Acyclovir (ACV) and penciclovir (PNV) have been commonly used during the last few decades as potent antiviral agents, especially for the treatment of herpes virus...
Acyclovir (ACV) and penciclovir (PNV) have been commonly used during the last few decades as potent antiviral agents, especially for the treatment of herpes virus infections. In the present research their binding properties with human serum albumin (HSA) were studied using different advanced spectroscopic and in-silico methods. The interactions between ACV/PNV and HSA at the three investigated temperatures revealed a static type of binding. Extraction of the thermodynamic parameters of the ACV-HSA and PNV-HSA systems from the measured spectrofluorimetric data demonstrated spontaneous interactions with an enthalpy change (∆⁰) of -1.79 ± 0.29 and -4.47 ± 0.51 kJ·mol for ACV and PNV, respectively. The entropy change (∆⁰) of 79.40 ± 0.95 and 69.95 ± 1.69 J·mol·K for ACV and PNV, respectively, hence supported a potential contribution of electrostatic binding forces to the ACV-HSA and PNV-HSA systems. Putative binding of ACV/PNV to HSA, using previously reported site markers, showed that ACV/PNV were bound to HSA within subdomains IIA and IIIA (Sudlow sites I and II). Further confirmation was obtained through molecular docking studies of ACV-HSA and PNV-HSA binding, which confirmed the binding site of ACV/PNV with the most stable configurations of ACV/PNV within the HSA. These ACV/PNV conformers were shown to have free energies of -25.61 and -22.01 kJ·mol for ACV within the HSA sites I and II and -22.97 and -26.53 kJ·mol for PNV in HSA sites I and II, with hydrogen bonding and electrostatic forces being the main binding forces in such conformers.
Topics: Acyclovir; Antiviral Agents; Binding Sites; Guanine; Humans; Hydrogen Bonding; Models, Molecular; Molecular Docking Simulation; Molecular Structure; Protein Binding; Protein Domains; Serum Albumin, Human; Thermodynamics
PubMed: 29113080
DOI: 10.3390/molecules22111906 -
The Cochrane Database of Systematic... Aug 2016Genital herpes is incurable, and is caused by the herpes simplex virus (HSV). First-episode genital herpes is the first clinical presentation of herpes that a person... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Genital herpes is incurable, and is caused by the herpes simplex virus (HSV). First-episode genital herpes is the first clinical presentation of herpes that a person experiences. Current treatment is based around viral suppression in order to decrease the length and severity of the episode.
OBJECTIVES
To determine the effectiveness and safety of the different existing treatments for first-episode genital herpes on the duration of symptoms and time to recurrence.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (from inception to April 2016), MEDLINE (from inception to April 2016), the Specialised Register of the Cochrane Sexually Transmitted Infections Review Group (from inception to April 2016), EMBASE (from inception to April 2016), PsycINFO (from inception to April 2016), CINAHL (from inception to April 2016), LILACS (from inception to April 2016), AMED (from inception to April 2016), and the Alternative Medicines Specialised Register (from inception to April 2016). We handsearched a number of relevant journals, searched reference lists of all included studies, databases of ongoing trials, and other Internet databases.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) on participants with first-episode genital herpes. We excluded vaccination trials, and trials in which the primary objective assessed a complication of HSV infection.
DATA COLLECTION AND ANALYSIS
All studies written in English were independently assessed by at least two review authors for inclusion, risk of bias for each trial, and to extract data. Studies requiring translation were assessed for inclusion, trial quality, and data extraction by external translators.
MAIN RESULTS
We included 26 trials with 2084 participants analysed. Most of the studies were conducted in the United Kingdom (UK) and United States (US), and involved men and women experiencing their first episode of genital herpes, with the exception of three studies which included only women. We rated the majority of these studies as having an unclear risk of bias; largely due to lack of information supplied in the publications, and due to the age of the trials. This review found low quality evidence from two studies of oral acyclovir, when compared to placebo, reduced the duration of symptoms in individuals undergoing their first episode of genital herpes (mean difference (MD) -3.22, 95% confidence interval (CI) -5.91 to -0.54; I(2) = 52%). In two studies (112 participants), intravenous acyclovir decreased the median number of days that patients with first-episode herpes suffered symptoms. Oral valaciclovir (converted to acyclovir) also showed a similar length of symptom duration when compared to acyclovir in two studies.There is currently no evidence that topical acyclovir reduces symptoms (MD -0.61 days, 95% CI -2.16 to 0.95; 3 RCTs, 195 participants, I(2) statistic = 56%). There is also no current evidence that the topical treatments of cicloxolone cream, carbenoxolone sodium cream, adenosine arabinoside, idoxuridine in dimethyl sulfoxide, when compared to placebo reduced the duration of symptoms in people undergoing their first episode of herpes.Two studies reported no evidence of a reduction in the number of median days to recurrence following treatment with oral acyclovir versus placebo. Adverse events were generally poorly reported by all of the included studies and we were unable to quantitatively analyse this outcome. For those taking acyclovir, there were no serious adverse events; the most common adverse events reported for oral acyclovir were coryza, dizziness, tiredness, diarrhoea and renal colic. For intravenous acyclovir these were phlebitis, nausea and abnormal liver function tests and for topical acyclovir there was pain with the topical application.Those undergoing interferon treatment had significantly more adverse events compared to those taking placebo.
AUTHORS' CONCLUSIONS
There is low quality evidence from this review that oral acyclovir reduced the duration of symptoms for genital herpes. However, there is low quality evidence which did not show that topical antivirals reduced symptom duration for patients undergoing their first episode of genital herpes. This review was limited by the inclusion of skewed data, resulting in few trials that we were able to meta-analyse.
Topics: Acyclovir; Administration, Oral; Antiviral Agents; Female; Herpes Genitalis; Humans; Injections, Intravenous; Male; Randomized Controlled Trials as Topic; Recurrence; Valacyclovir; Valine
PubMed: 27575957
DOI: 10.1002/14651858.CD010684.pub2