brivudine and Herpes-Zoster

There is lack of consensus from randomized controlled trials on the efficacy of antivirals in the management of herpes zoster. Therefore, a systematic review and meta-analysis was undertaken to provide better understanding of effectiveness of antivirals in management of herpes zoster.. A total of 12 randomized controlled trials with 7,277 patients were included in the review. Trials compared one antiviral to another (aciclovir, valaciclovir, famciclovir or brivudin) for a minimum of 7 days in immunocompetent patients presenting with herpes zoster diagnosed within 72 h of symptom onset. Primary outcome was reduction in pain.. Compared with aciclovir, valaciclovir showed significant reduction in herpes-zoster-associated pain up to 112 days. The largest risk reduction in pain (36%) was seen at 21-30 days (relative risk [RR] 0.64, 95% CI 0.59, 0.70) with number needed to treat to benefit (NNT) of 3 (95% CI 2.7, 3.8). Famciclovir was also superior to aciclovir with a 46% reduction in risk of pain at 28-30 days (RR 0.54, 95% CI 0.48, 0.68) with NNT of 3 (95% CI 2, 5). Time to lesion healing and adverse effect profile was comparable.. Evidence from quality trials have shown significant reduction in risk of pain with valaciclovir and famciclovir for management of herpes zoster including ophthalmicus. Valaciclovir or famciclovir should be preferred treatment options in patients with herpes zoster as they both provide significant reduction in risk of herpes-zoster-associated pain. Furthermore, the superior pharmacokinetics and more convenient dosing regimens with the use of valaciclovir and famciclovir clearly make them the preferred treatment option.

Topics: 2-Aminopurine; Acyclovir; Antiviral Agents; Bromodeoxyuridine; Famciclovir; Herpes Zoster; Herpesvirus 3, Human; Humans; Pain Management; Randomized Controlled Trials as Topic; Valacyclovir; Valine

A 66-year-old woman with metastatic mammary carcinoma, who was being treated with capecitabine, contracted a herpes zoster infection that was treated with the antiviral drug brivudin. A drug-drug interaction between brivudin and capecitabine caused medullar aplasia, serious toxic effects to the intestinal mucous membrane, hand-foot syndrome, onycholysis and dental pigmentation.. Physical examination, blood analysis, blood cultures, chest X-ray, bone marrow aspiration and biopsy.. Serious adverse event secondary to inhibition of dihydropyrimidine dehydrogenase by a drug-drug interaction between capecitabine and brivudin.. Intravenous hydration, imipenem, red blood cell and platelet transfusions, filgrastim, omeprazole, care of the mouth and feet, topical anesthetics, systemic analgesics and parenteral nutrition.

Topics: Aged; Anemia, Aplastic; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Antiviral Agents; Breast Neoplasms; Bromodeoxyuridine; Capecitabine; Carcinoma, Ductal, Breast; Combined Modality Therapy; Deoxycytidine; Dihydrouracil Dehydrogenase (NADP); Drug Interactions; Fatal Outcome; Female; Fluorouracil; Herpes Zoster; Humans; Onycholysis; Palliative Care; Peripheral Nervous System Diseases; Salvage Therapy; Stomatitis; Tooth Discoloration

The objective of this article is to provide evidence-based recommendations for the management of patients with herpes zoster (HZ) that take into account clinical efficacy, adverse effects, impact on quality of life, and costs of treatment. Systematic literature reviews, published randomized clinical trials, existing guidelines, and the authors' clinical and research experience relevant to the management of patients with HZ were reviewed at a consensus meeting. The results of controlled trials and the clinical experience of the authors support the use of acyclovir, brivudin (where available), famciclovir, and valacyclovir as first-line antiviral therapy for the treatment of patients with HZ. Specific recommendations for the use of these medications are provided. In addition, suggestions are made for treatments that, when used in combination with antiviral therapy, may further reduce pain and other complications of HZ.

Topics: 2-Aminopurine; Acyclovir; Analgesics; Anti-Inflammatory Agents; Antiviral Agents; Bromodeoxyuridine; Famciclovir; Herpes Zoster; Herpesvirus 3, Human; Humans; Immunocompetence; Immunocompromised Host; Valacyclovir; Valine

Topics: 2-Aminopurine; Acute Disease; Acyclovir; Administration, Oral; Adult; Age Factors; Analgesics, Non-Narcotic; Analgesics, Opioid; Anticonvulsants; Antidepressive Agents, Tricyclic; Antiviral Agents; Bromodeoxyuridine; Child; Drug Therapy, Combination; Famciclovir; Female; Herpes Zoster; Herpesvirus 3, Human; Herpesvirus Vaccines; Humans; Male; Middle Aged; Neuralgia, Postherpetic; Pain; Prodrugs; Risk Factors; Sex Factors; Time Factors; Vaccination; Valacyclovir; Valine

The overall incidence of herpes zoster in Europe is approximately 3 per 1000 people per year and more than 10 per 1000 people per year in those aged >80 years. Post herpetic neuralgia (PHN) is a common debilitating complication of herpes zoster, particularly in patients aged >50 years, in persons with severe pain or rash at presentation, and in those with significant prodromal symptoms. Antiviral drugs can effectively control acute symptoms and, if used early enough in the course of the illness, can help prevent the development of PHN and other complications. However, despite this, many patients do not receive such treatment. The economic impact of zoster and PHN is largely underestimated in Europe. Furthermore, there is considerable variation throughout Europe in the management of herpes zoster. Use of antiviral therapy including the newer potent antiviral agents such as brivudin, which requires less frequent administration than acyclovir, is improving patient outcomes in some European countries. However, in many countries, patient awareness of herpes zoster and, as a result, overall antiviral use is low. Guidelines recommending the use of antiviral agents, particularly in patients at risk of developing PHN, are available but are not widely used. More needs to be done to educate the general public and increase awareness among primary healthcare providers of the benefits of timely and appropriate pharmacological therapy in patients with herpes zoster.

Topics: Age Distribution; Aged; Aged, 80 and over; Antiviral Agents; Bromodeoxyuridine; Dose-Response Relationship, Drug; Drug Administration Schedule; Europe; Female; Herpes Zoster; Humans; Male; Middle Aged; Neuralgia, Postherpetic; Pain Measurement; Prognosis; Recurrence; Risk Assessment; Severity of Illness Index; Sex Distribution; Treatment Outcome

Brivudin is an oral thymidine analogue indicated for the early treatment of acute herpes zoster in immunocompetent adults. It has high, selective activity against varicella zoster virus (VZV), inhibiting VZV replication, possibly through competitive inhibition of viral DNA polymerase, or by acting as an alternative substrate to deoxythymidine triphosphate, causing viral DNA strand breakage. In a large, 7-day, phase III trial in immunocompetent patients with herpes zoster, once-daily brivudin 125mg was significantly more effective than oral acyclovir 800mg five times daily in reducing the mean time from start of treatment to last vesicular eruption, and was as effective as acyclovir at healing lesions and alleviating acute zoster-related pain. The likelihood of developing post-herpetic neuralgia (PHN) in immunocompetent patients aged > or =50 years was significantly lower with brivudin than with acyclovir. Brivudin was as effective as oral famciclovir 250mg three times daily in terms of the prevalence of PHN, the time to last vesicular eruption and lesion healing in another large, 7-day, phase III study in immunocompetent patients with herpes zoster. Oral brivudin is generally well tolerated, with a similar tolerability profile to those of oral acyclovir or famciclovir. Nausea was the most commonly reported adverse event.

Topics: Acute Disease; Antiviral Agents; Bromodeoxyuridine; Herpes Zoster; Humans; Randomized Controlled Trials as Topic

This Commentary is dedicated to the memory of Dr. Jacques Gielen, the late Editor of Biochemical Pharmacology, whom I have known as both an author and reviewer for the Journal for about 25 years. This is, quite incidentally, about the time it took for bringing brivudin (BVDU) [(E)-5-(2-bromovinyl)-2'-deoxyuridine] from its original description as an antiviral agent to the market place (in a number of European countries, including Germany and Italy) for the treatment of herpes zoster in immunocompetent persons. BVDU is exquisitely active and selective against varicella-zoster virus (VZV) and herpes simplex virus type 1 (HSV-1). BVDU owes this high selectivity and activity profile to a specific phosphorylation by the virus-encoded thymidine kinase, followed by a potent interaction with the viral DNA polymerase. The (E)-5-(2-bromovinyl)-substituent can be considered as the hallmark for the activity of BVDU against VZV and HSV-1. Extensive clinical studies have indicated that BVDU as a single (oral) daily dose of 125 mg (for no more than 7 days) is effective in the treatment of herpes zoster, as regards both short-term (suppression of new lesion formation) and long-term effects (prevention of post-herpetic neuralgia). In this sense, BVDU is as efficient and/or convenient, if not more so, than the other drugs (acyclovir, valaciclovir, famciclovir) that have been licensed for the treatment of herpes zoster. There is one caveat; however, BVDU should not be given to patients under 5-fluorouracil therapy, as the degradation product of BVDU, namely (E)-5-(2-bromovinyl)uracil (BVU), may potentiate the toxicity of 5-fluorouracil, due to inhibition of dihydropyrimidine dehydrogenase, the enzyme involved in the catabolism of 5-fluorouracil.

Topics: Antimetabolites; Antiviral Agents; Bromodeoxyuridine; Drug Interactions; Europe; Fluorouracil; Herpes Zoster; Herpesvirus 3, Human; Humans; Virus Replication

Herpes zoster has been known since ancient times. It is a ubiquitous disease, occurring sporadically without any seasonal preference and is caused by the varicella-zoster virus. It may be defined as an endogenous relapse of the primary infection varicella. Herpes zoster is characterised by typical efflorescences in the innervation region of a cranial or spinal nerve and starts and ends with pain of varying intensity. Currently, several antiviral drugs are approved and many studies have shown that antiviral therapy, started early in the course of disease, can significantly reduce the risk and the duration of postherpetic neuralgia in elderly patients. The effects of all antivirals discussed in this article, given either orally or intravenously, are comparable with regards to the resolution of virus replication, prevention of dissemination of skin lesions and reduction of acute herpes zoster pain. Valaciclovir (valacyclovir), famciclovir and brivudine (brivudin) are comparably effective in the reduction of the incidence and/or prevention of zoster-associated pain and postherpetic neuralgia. Brivudine 125mg once daily is as effective as famciclovir 250mg three times daily in reducing the prevalence and the duration of zoster-associated pain and postherpetic neuralgia, especially if therapy is combined with a structured-pain therapy. The intensity of the therapy for pain should depend on the intensity of the pain that it is treating. Famciclovir and brivudine offer an advantage over other antivirals because they are administered less frequently; this is particularly relevant for elderly patients who may already be taking a number of medications for other diseases. Therefore, antiviral therapy in combination with adequate pain management should be given to all elderly patients as soon as herpes zoster is diagnosed.

Topics: 2-Aminopurine; Acyclovir; Age Factors; Aged; Analgesics; Antiviral Agents; Bromodeoxyuridine; Drug Therapy, Combination; Famciclovir; Herpes Zoster; Humans; Neuralgia; Pain Measurement; Valacyclovir; Valine

Antiviral treatment of herpesvirus infections is rapidly changing since the advent of new drugs with improved oral availability. The efficacy of valaciclovir, the prodrug of aciclovir, and famciclovir, the prodrug of penciclovir, in the treatment of herpes genitalis and acute herpes zoster has been well documented in large clinical trials. Both drugs are effective on zoster-associated pain. Brivudin and sorivudine which are the most active compounds against varicella-zoster virus (VZV) in cell culture have also been successful in the treatment of herpes zoster. Aciclovir is still the standard therapy of severe herpes simplex virus (HSV) and varicella virus infections. In patients treated with aciclovir, the mortality of herpes encephalitis has been reduced to about 25%. The development of resistance against aciclovir and the other nucleoside analogues has not been a problem to date in the treatment of immunocompetent individuals. However, in immunocompromised patients, aciclovir-resistant HSV strains often emerge. In such cases, intravenous foscarnet is the current treatment of choice.

Topics: 2-Aminopurine; Acyclovir; Administration, Oral; Antiviral Agents; Arabinofuranosyluracil; Bromodeoxyuridine; Chickenpox; Drug Resistance, Microbial; Encephalitis, Viral; Famciclovir; Herpes Genitalis; Herpes Labialis; Herpes Simplex; Herpes Zoster; Humans; Immunocompromised Host; Prodrugs; Simplexvirus; Valacyclovir; Valine

We now have a basis for a more rational approach to rapid evaluation and development of antiviral drugs by screening for activity in vitro, testing for toxicity and efficacy in animals, and clinical testing in humans. Acyclovir is a prototype of this improved process. Interferon has a beneficial effect against CMV infection in renal transplant patients and has promising results in the treatment of papillomas and rhinovirus infections. It does not seem to be as effective against genital herpes or varicella zoster as acyclovir. Ribavirin is effective against respiratory syncytial virus infections and Lassa fever. Varicella-zoster virus is highly sensitive to bromovinyl deoxyuridine in vitro. Phosphonoformate is effective in herpes simplex in animals but of little clinical benefit topically in human recurrent A2 herpes. Zidovudine may decrease mortality rates and infectious complications in patients with acquired immunodeficiency syndrome. DHPG (9-(1,3-dihydroxy-2-propoxymethyl]guanine is useful in treatment of cytomegalovirus and infection in immunocompromised patients. The prodrug of acyclovir results in high blood levels of acyclovir and shows promise in the treatment of varicella-zoster infections. Many halogenated pyrimidine nucleoside analogs are being developed. Buciclovir is another acyclic guanosine analog effective against herpes simplex virus in vitro. 2'-nor-cyclic guanosine monophosphate has a broad antiviral spectrum of action. Interleukin-2 is being investigated. Combined therapies of two or more antiviral drugs or antiviral drugs and other treatments are being studied.

Topics: Acyclovir; Animals; Antiviral Agents; Bromodeoxyuridine; Cytomegalovirus Infections; Foscarnet; Ganciclovir; Herpes Simplex; Herpes Zoster; Humans; Interferons; Phosphonoacetic Acid; Ribavirin; Thymidine; Zidovudine

Herpes viruses are among the most common and troublesome opportunistic pathogens infecting patients with neoplastic diseases. The recent development of partially effective and relatively nontoxic antiviral agents offers promise for the prophylaxis or therapy of these infections in high-risk groups. Vidarabine and acyclovir have shown efficacy in several herpes virus infections and are now licensed in the United States. Alpha interferon may also be useful in the prophylaxis or early therapy of certain herpes virus infections. Newer antiviral agents and combination therapies are under study. Early and rapid diagnosis of such infections is critical to the development of effective therapy.

Topics: Acyclovir; Antineoplastic Agents; Antiviral Agents; Bone Marrow Transplantation; Bromodeoxyuridine; Cloning, Molecular; Cytomegalovirus Infections; Herpes Simplex; Herpes Zoster; Herpesviridae Infections; Humans; Infectious Mononucleosis; Interferons; Kidney Transplantation; Leukemia; Lymphopenia; Neoplasms; Pulmonary Fibrosis; Vidarabine

Progress in antiviral chemotherapy has taken place as a logical strategy for the design of antiviral agents has emerged. The second-generation nucleoside analogues, led by acyclovir, have proved their worth against herpesviruses and should now become a standard part of medical practice. Meanwhile, recombinant DNA technology has lowered the cost of interferons to the point at which the several human subtypes of these naturally occurring hormones can be subjected individually to controlled clinical trials against the viral diseases in the treatment of which they show promise. Yet, optimism about the future of antiviral chemotherapy must be tempered by the observation that most of the agents discussed in this review are described more accurately as promising rather than proven, and several of these have not yet been released in Australia at the time of writing.

Topics: Acyclovir; Amantadine; Animals; Antiviral Agents; Bromodeoxyuridine; Female; Hepatitis B; Herpes Genitalis; Herpes Simplex; Herpes Zoster; Humans; Idoxuridine; In Vitro Techniques; Interferons; Male; Neoplasms; Papillomaviridae; Respiratory Tract Infections; Ribavirin; Rimantadine; Tumor Virus Infections; Vidarabine

Topics: Acyclovir; Antiviral Agents; Bromodeoxyuridine; Chickenpox; Herpes Zoster; Herpesviridae Infections; Herpesvirus 4, Human; Humans; Immune Tolerance; Interferon Type I; Interferons; Vidarabine

Herpes zoster neural injury was assessed by determining cutaneous nerve density in skin biopsies from the affected dermatomes of 35 adult patients with herpes zoster in the acute phase and 3 months post-treatment, using protein gene product 9.5 immunohistochemistry. In contrast to the significant increase in subepidermal nerve fibre density (11.77 ± 4.88/mm vs. 13.29 ± 5.74/mm, p = 0.045) after 3 months, no differences were found in epidermal free nerve endings (2.43 ± 2.35/mm and 2.8 ± 2.86/mm, p = 0.168). Patients with post-herpetic neuralgia had significantly lower subepidermal nerve fibre densities (9.7 ± 2.05/mm vs. 14.72 ± 6.13/mm, p = 0.011) compared with non-post-herpetic neuralgia patients. No differences in cutaneous nerve density were found in relation to antiviral therapy. In conclusion, 3 months after acute infection, no sign of epidermal innervation recovery is observed, while the increased subepidermal nerve fibre density in the affected dermatomes probably reflects nerve regeneration that is not affected by antiviral agent type. Subepidermal nerve fibre density is decreased in patients with post-herpetic neuralgia 3-months post-acute herpes zoster infection.

Topics: 2-Aminopurine; Acyclovir; Antiviral Agents; Biomarkers; Biopsy; Bromodeoxyuridine; Famciclovir; Female; Herpes Zoster; Humans; Immunohistochemistry; Male; Middle Aged; Nerve Fibers; Neuralgia, Postherpetic; Skin; Ubiquitin Thiolesterase; Valacyclovir; Valine

This was a double-blind, randomized multicentre trial comparing efficacy and safety of brivudin (125 mg, once a day) and famciclovir (250 mg, three times a day), both given orally for 7 days, in the treatment of herpes zoster.. A total of 2027 immunocompetent zoster patients>or=50 years with zoster-related pain at presentation were included. Outcome measures embraced prevalence of postherpetic neuralgia (PHN), defined as at least moderate pain 3 months after treatment initiation, duration of PHN, prevalence and duration of zoster-associated pain (ZAP), duration of vesicle formation and rash healing.. The prevalence of PHN at month 3 was 11.3% with brivudin and 9.6% with famciclovir [per-protocol (PP) population]. Equivalence of the two drugs could be demonstrated (P=0.01, PP and intention-to-treat analysis). The median duration of PHN was 46.5 days with brivudin and 58 days with famciclovir (P=0.54, PP analysis). Prevalence and duration of ZAP did not differ significantly between treatment groups. The prevalence of PHN was higher in patients>or=65 years (brivudin: 16.4%, famciclovir: 16.4%), and in patients with severe rash (brivudin: 13.4%, famciclovir: 15.7%), without significant differences between treatment groups. In patients>or=65 years, median duration of PHN was shorter with brivudin than with famciclovir (39.5 vs. 57.5 days), although the difference was not statistically significant. The two drugs had equivalent efficacy in being able to accelerate the stop of vesicle formation, and lesion healing. Adverse events were similar in nature and prevalence among groups.. The study demonstrated equivalent efficacy of brivudin and famciclovir in the treatment of herpes zoster regarding the prevention of chronic pain and the resolution of signs and symptoms of acute herpes zoster. Compared with famciclovir, brivudin provides equivalent efficacy and safety at a more convenient once-daily dose schedule.

Topics: 2-Aminopurine; Acute Disease; Administration, Oral; Aged; Antiviral Agents; Bromodeoxyuridine; Chronic Disease; Double-Blind Method; Europe; Famciclovir; Female; Herpes Zoster; Humans; Male; Middle Aged; Pain; Pain Measurement; Prospective Studies; Treatment Outcome

Brivudin [(E)-5-(2-bromovinyl)-2'-deoxyuridine] is a nucleoside analogue with a high and selective antiviral activity against varicella-zoster virus (VZV) and herpes simplex virus type 1 (HSV-1). The double-blind, randomized study presented here compared efficacy and safety of oral brivudin 1 x 125 mg and acyclovir 5 x 800 mg, both for 7 days, in 1227 immunocompetent patients with herpes zoster. Main results were as follows: brivudin was superior to acyclovir in accelerating the "time to last formation of new vesicles" (primary parameter; risk ratio(ITT): 1.13, P=0.014). Equivalent effects of brivudin and acyclovir were observed for the secondary parameters "time to first crust" (RR(ITT): 0.93, P=0.004), "time to full crusting" (risk ratio(ITT): 1.03, P<0.001), and "time to loss of crusts" (RR(ITT): 0.95, P=0.002). The incidence of potentially treatment-related adverse events was similar under brivudin (7.7%) and acyclovir (10.0%). In conclusion, brivudin proved to be more effective than acyclovir in terminating vesicle formation, the parameter which reflects the end of viral replication, thus confirming, in the clinical setting, the greater in vitro antiviral activity of brivudin. Compared with acyclovir, brivudin provides a similar safety profile and a significant improvement in efficacy.

Topics: Acyclovir; Adult; Aged; Antiviral Agents; Bromodeoxyuridine; Double-Blind Method; Female; Herpes Zoster; Herpesvirus 3, Human; Humans; Immunocompetence; Male; Middle Aged; Pain; Skin; Virus Replication

This concerns a double-blind survey study on 608 herpes zoster patients treated with 1x 125 mg oral brivudin (n=309) or 5x 800 mg acyclovir (n=299), both for 7 days, during two prospective, randomised clinical herpes zoster trials. The survey aimed at evaluating the outcome of the two treatment regimens on postherpetic neuralgia (PHN). During a follow-up ranging from 8 to 17 months after start of treatment, former study participants aged >/=50 years were interviewed for the occurrence of PHN. Neither the investigators nor the patients were aware of which treatment the patients received during acute herpes zoster. The incidence of PHN, defined as zoster-associated pain occurring or persisting after rash healing was significantly lower in brivudin recipients (32.7%) than in acyclovir recipients (43.5%, P=0.006). Mean duration of PHN was similar with brivudin (173 days) and acyclovir (164 days, P=0.270). Despite some methodological disadvantages common to this type of study, the present survey provides for the first evidence that brivudin treatment during acute herpes zoster favourably affects the incidence of PHN in immunocompetent elderly herpes zoster patients.

Topics: Acyclovir; Adult; Aged; Antiviral Agents; Bromodeoxyuridine; Double-Blind Method; Female; Follow-Up Studies; Herpes Zoster; Humans; Male; Middle Aged; Neuralgia; Prospective Studies

The efficacy of oral brivudin vs. intravenous acyclovir was compared in a randomized multicentered study under double-blind conditions using the double-dummy technique. Forty-eight patients with a herpes zoster rash less than 72 hours in duration were entered in the study. Brivudin was given as one 125-mg tablet every 6 hours. Acyclovir was infused over 1 hour at a dose of 10 mg/kg every 8 hours. Treatment was continued for 5 days. There was no significant difference between the treatment groups when analyzed in terms of new lesion formation, increase in the area of rash within the primary dermatome, cutaneous dissemination, and affection of mucous membranes or visceral organs. Both treatment regimes were also equally effective in the time to full crusting of lesions. Oral brivudin and intravenous acyclovir were well tolerated by most patients. There was no need to interrupt the treatment in any case. As effective as intravenous acyclovir in the treatment of herpes zoster, oral brivudin offers the potential for outpatient treatment of herpes zoster in immunocompromised patients.

Topics: Acyclovir; Administration, Oral; Adolescent; Adult; Antibodies, Viral; Antiviral Agents; Bromodeoxyuridine; Double-Blind Method; Female; Herpes Zoster; Herpesvirus 3, Human; Humans; Immunocompromised Host; Injections, Intravenous; Male; Treatment Outcome

After a discussion of the principles of antiviral chemotherapy, treatment and chemoprophylaxis of the following virus infections are reviewed in detail: the various manifestations of herpes simplex virus infections, varicella-zoster, cytomegalovirus infections, Epstein-Barr virus infections, laryngeal papillomas, and influenza A. Special reference is made to the treatment of immunocompromized patients. Acycloguanosine (acyclovir) has been found particularly useful in the treatment of herpes simplex virus and varicella zoster virus infections in immunocompromized patients and for herpesencephalitis. Varicella-zoster can also be treated effectively with bromovinyldeoxyuridine (BVDU). Toxicity of the currently used antiviral drugs is discussed as well as the problem of drug resistance.

Topics: Acyclovir; Antiviral Agents; Bromodeoxyuridine; Chickenpox; Child; Clinical Trials as Topic; Cytomegalovirus Infections; Double-Blind Method; Encephalitis; Female; Herpes Genitalis; Herpes Simplex; Herpes Zoster; Humans; Immunologic Deficiency Syndromes; Infant, Newborn; Pemphigoid Gestationis; Pregnancy; Vidarabine; Virus Diseases

Twenty-five patients with haematological diseases were treated orally with the highly potent and selective anti-herpes agent, bromovinyldeoxyuridine (BVDU), in a dosage of 7.5 mg/kg/day (divided over three or four doses a day) for 5 days for an intercurrent mucocutaneous herpesvirus infection. Of these 25 patients, 8 were severely granulocytopenic at the time of the viral infection, and 12 recently had undergone bone-marrow transplantation; 5 were under cytotoxic therapy for a lymphoproliferative disorder; 13 had herpes simplex virus type 1 (HSV-1); 1 had herpes simplex virus type 2 (HSV-2); and 11 had varicella-zoster virus (VZV) infection. In all but two patients, BVDU arrested progression of the HSV or VZV infection within 1-2 days after treatment was started. One of the two patients who failed to respond to BVDU had an HSV-2 infection. The other had an HSV-1 infection, which was highly sensitive to BVDU in vitro; BVDU may have failed in this patient because of incomplete drug intake or profuse diarrhoea, or both. The results of this preliminary uncontrolled clinical trial suggest that BVDU may be an effective and safe drug for the oral treatment of HSV-1 and VZV infections in severely immunosuppressed patients.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Antiviral Agents; Bromodeoxyuridine; Child; Child, Preschool; Clinical Trials as Topic; Female; Herpes Simplex; Herpes Zoster; Humans; Immunosuppression Therapy; Leukemia; Lymphoma; Male; Middle Aged

Topics: Acyclovir; Administration, Intravenous; Aged; Antiviral Agents; Bromodeoxyuridine; Female; Herpes Zoster; Humans; Paresis; Physical Therapy Modalities

Topics: Aged; Antimetabolites, Antineoplastic; Antiviral Agents; Bromodeoxyuridine; Diagnostic Errors; Drug Interactions; Fatal Outcome; Fluorouracil; Herpes Zoster; Humans; Male

Topics: Antiviral Agents; Bromodeoxyuridine; Coronary Vasospasm; Herpes Zoster; Humans; Male; Middle Aged; Syndrome

The alphaherpesvirus varicella-zoster virus (VZV) causes chickenpox and shingles. Current treatments are acyclovir (ACV) and its derivatives, foscarnet and brivudine (BVdU). Additional antiviral compounds with increased potency and specificity are needed to treat VZV, especially to treat post-herpetic neuralgia. We evaluated β-l-1-[5-(E-2-bromovinyl)-2-(hydroxymethyl)-1,3-(dioxolan-4-yl)] uracil (l-BHDU, 1) and 5'-O-valyl-l-BHDU (2) in three models of VZV replication: primary human foreskin fibroblasts (HFFs), skin organ culture (SOC) and in SCID-Hu mice with skin xenografts. The efficacy of l-BHDU in vivo and its drug-drug interactions were previously not known. In HFFs, 200μM l-BHDU was noncytotoxic over 3days, and l-BHDU treatment reduced VZV genome copy number and cell to cell spread. The EC50 in HFFs for l-BHDU and valyl-l-BHDU were 0.22 and 0.03μM, respectively. However, l-BHDU antagonized the activity of ACV, BVdU and foscarnet in cultured cells. Given its similar structure to BVdU, we asked if l-BHDU, like BVdU, inhibits 5-fluorouracil catabolism. BALB/c mice were treated with 5-FU alone or in combination with l-BHDU or BVdU. l-BHDU did not interfere with 5-FU catabolism. In SCID-Hu mice implanted with human skin xenografts, l-BHDU and valyl-l-BHDU were superior to ACV and valacyclovir. The maximum concentration (Cmax) levels of l-BHDU were determined in mouse and human tissues at 2h after dosing, and comparison of concentration ratios of tissue to plasma indicated saturation of uptake at the highest dose. For the first time, an l-nucleoside analog, l-BHDU, was found to be effective and well tolerated in mice.

Topics: Acyclovir; Animals; Antiviral Agents; Bromodeoxyuridine; Cell Line; Chickenpox; Dioxolanes; Drug Therapy, Combination; Fluorouracil; Foscarnet; Herpes Zoster; Herpesvirus 3, Human; Humans; Mice; Mice, Inbred BALB C; Mice, SCID; Nucleosides; Organ Culture Techniques; Skin; Uracil; Virus Replication

Mielitis cervicodorsal secundaria a infeccion por el virus varicela zoster en un paciente inmunocompetente.

Topics: Acyclovir; Antiviral Agents; Arm; Athetosis; Bromodeoxyuridine; Drug Therapy, Combination; Herpes Zoster; Herpesvirus 3, Human; Humans; Hyperalgesia; Immunocompetence; Male; Methylprednisolone; Middle Aged; Movement Disorders; Myelitis; Neck; Neuralgia, Postherpetic; Somatosensory Disorders; Thorax; Virus Activation

Brivudin is an oral antiviral agent used to treat herpes zoster infections. Common side effects of brivudin include nausea and headache. This report describes delirium in a patient who used brivudin for herpes zoster treatment, which consequently remitted after drug cessation on the fourth day of medication use. To our knowledge, no such side effect has been reported to date. However, it is important that clinicians who prescribe brivudin are aware that treatment cessation is likely to result in total clinical recovery.

Topics: Antiviral Agents; Bromodeoxyuridine; Delirium; Drug Monitoring; Herpes Zoster; Humans; Male; Middle Aged; Neurotoxicity Syndromes; Treatment Outcome

The treatment of varicella-zoster virus (VZV) reactivation is based on nucleoside analogues acyclovir (ACV) and bromevinyldeoxyuridine (BVdU) and a phosphonic acid derivative (PFA). Drug-resistant mutants of 3 wild-type (WT) VZV strains were obtained by exposure of human retinal pigment epithelial (hRPE) cells inoculated with cell-free WT virus at increasing concentrations of ACV, BVdU, and PFA. In addition to single-drug resistance, a cross-resistance of isolates vs. ACV was observed for PFA-resistant strains. Single-nucleotide (nt) exchanges resulting in amino acid (aa) substitutions were observed within the DNA polymerase (ORF 28) and/or thymidine kinase (ORF 36) of 3 of 3 ACV-, 2 of 3 BVdU-, and 3 of 3 PFA-resistant strains. Interestingly, aa substitutions were also observed within the immediate-early regulatory protein and major transactivator IE 62 (ORF 62), and the envelope glycoprotein (g) I (ORF 67) of the BVdU-resistant mutant of strain PP. No aa substitutions were observed in the protein sequences of gene products encoded by ORF 5 (gK, a glycoprotein arranging exocytosis of viral-loaded vacuoles), ORF 14 (gC), ORF 31 (gB), ORF 37 (gH), ORF 47 (protein kinase, involved in major phosphorylating processes), ORF 60 (gL, important for syncytia forming of infected cells in combination with gH), ORF 63 (major transactivator, part of the tegument), and ORF 68 (gE, triggers fusion of viral loaded vacuoles with cell membranes by heterodimerizing with gI). Phenotypic analysis revealed a slow-growth phenotype and a formation of smaller plaques of resistant mutants. Future studies should prove the presence of those resistant mutants in herpes zoster patients and the potential consequences of their putative reduced fitness on the success of therapeutical interventions.

Topics: Acyclovir; Amino Acid Substitution; Antiviral Agents; Bromodeoxyuridine; Cell Line; Drug Resistance, Viral; Evolution, Molecular; Foscarnet; Genes, Viral; Herpes Zoster; Herpesvirus 3, Human; Humans; Inhibitory Concentration 50; Microbial Sensitivity Tests; Mutation; Open Reading Frames; Thymidine Kinase; Virus Replication

Topics: Acyclovir; Antineoplastic Agents; Antiviral Agents; Bromodeoxyuridine; Diagnosis, Differential; Esophageal Neoplasms; Exanthema; Herpes Zoster; Humans; Leg; Lymphoma, Mantle-Cell; Male; Middle Aged; Paraneoplastic Syndromes; Vasculitis, Leukocytoclastic, Cutaneous

Topics: Adverse Drug Reaction Reporting Systems; Aged, 80 and over; Antimetabolites, Antineoplastic; Antiviral Agents; Bromodeoxyuridine; Capecitabine; Colorectal Neoplasms; Deoxycytidine; Drug Interactions; Drug-Related Side Effects and Adverse Reactions; Fatal Outcome; Female; Fluorouracil; Herpes Zoster; Humans; Switzerland

The synthesis of original imidazo[1,2-a]pyridines bearing a thioether side chain at the 3 position and diversely substituted on the 6 or 8 position, and their antiviral activities are reported. From the synthesized compounds, the imidazo[1,2-a]pyridines bearing a 5 membered heterocycle (thiophene, furane or pyrrole) in the 6 position or a phenylthio group in the 6 or 8 position were the most potent against human cytomegalovirus (CMV) and varicella-zoster virus (VZV), whereas several other congeners, while less potent, were more selective in their inhibitory activity against VZV and CMV. These compounds showed similar activity against thymidine kinase competent (TK+) and deficient (TK-) VZV strains, demonstrating a mechanism of action independent of the viral thymidine kinase.

Topics: Antiviral Agents; Cell Survival; Cells, Cultured; Cytomegalovirus; Cytomegalovirus Infections; Herpes Zoster; Herpesvirus 3, Human; Humans; Imidazoles; Lung; Molecular Structure; Pyridines; Structure-Activity Relationship

Herpes zoster results from the reactivation of latent varicella-zoster virus (VZV) from the dorsal root ganglion of sensory nerves. It is rarely described in the pediatric population. We report the case of an 8-year-old immunocompetent boy with a painful lumbosacral herpes zoster that was treated with brivudin and achieved rapid and sustained improvement in the absence of muco-cutaneous or pharmacological side effects.

Topics: Antiviral Agents; Bromodeoxyuridine; Child; Herpes Zoster; Humans; Male

We report the case of a human immunodeficiency virus-positive patient presenting linear Darier disease with varicella-zoster virus superinfection following the lines of Blaschko. The lesions healed after treatment with brivudine.

Topics: Antiviral Agents; Bromodeoxyuridine; Darier Disease; Herpes Zoster; Humans; Male; Middle Aged; Superinfection

Varicella zoster virus (VZV) causes varicella (chickenpox), remains dormant in dorsal root and cranial nerve ganglia and can be reactivated as a consequence of declining VZV-specific cellular immunity leading to herpes zoster (shingles). Patients older than 50 years of age affected by herpes zoster may suffer a significant decrease of quality of life. These patients and immunocompromised individuals are at increased risks for severe complications, involving the eye, the peripheral and the central nervous system (prolonged pain, postherpetic neuralgia). Such complications occur with and without cutaneous symptoms. The German Dermatology Society (DDG) has released guidelines in order to guarantee updated management to anyone affected by herpes zoster. Diagnosis is primarily clinical. The gold standard of laboratory diagnosis comprises PCR and direct identification of VZV in cell cultures. Detection of IgM- and IgA-anti VZV antibodies may be helpful in immunocompromised patients. Therapy has become very effective in the last years. Systemic antiviral therapy is able to shorten the healing process of acute herpes zoster, to prevent or to alleviate pain and other acute and chronic complications, particularly, when given within 48 h to a maximum of 72 h after onset of the rash. Systemic antiviral therapy is urgently indicated in patients beyond the age of 50 years and in patients at any age with herpes zoster in the head and neck area, especially in patients with zoster ophthalmicus. Further urgent indications are severe herpes zoster on the trunk and on the extremities, herpes zoster in immunosuppressed patients and in patients with severe atopic dermatitis and severe ekzema. Only relative indications for antiviral therapy exist in patients younger than 50 years with zoster on the trunk and on the extremities. In Germany acyclovir, valacyclovir, famciclovir and brivudin are approved for the systemic antiviral treatment of herpes zoster. These compounds are all well tolerated by the patients and do not differ with regard to efficacy and safety. Brivudin has a markedly higher anti-VZV potency than oral acyclovir, valacyclovir and famciclovir and thus offers a simpler dosing regimen. It must be given only once daily during 7 days in comparison to three and five times dosing per day of valacyclovir, famciclovir and acyclovir, respectively. Brivudin is an antiviral agent with no nephrotoxic properties, which is an advantage when compared to acyclovir. The most impo

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aged; Analgesics; Antiviral Agents; Bone Marrow Diseases; Bromodeoxyuridine; Child; Child, Preschool; Contraindications; Drug Resistance, Viral; Drug Therapy, Combination; Female; Germany; Herpes Zoster; Herpes Zoster Ophthalmicus; Herpes Zoster Oticus; Herpesvirus 3, Human; Humans; Immunocompromised Host; Incidence; Male; Middle Aged; Neuralgia; Pain; Paresthesia; Pregnancy; Pregnancy Complications, Infectious; Severity of Illness Index; Virus Activation

Topics: Aged; Animals; Antiviral Agents; Bromodeoxyuridine; Carcinogenicity Tests; Dermatology; Germany; Guidelines as Topic; Herpes Zoster; Herpesvirus 3, Human; Humans; Mice; Middle Aged; Rats; Societies, Medical

Topics: Antiviral Agents; Bromodeoxyuridine; Dose-Response Relationship, Drug; Drug Administration Schedule; Herpes Zoster; Herpesvirus 3, Human; Humans; Virus Replication

The animal model of necrotic hepatitis caused by HSV-1 infection in juvenile mice was used to compare the efficacies of the oral antiherpes agents famciclovir (FCV), valaciclovir (VACV) and brivudin (BVDU). The experimental infection allows the measurement of viral replication in the liver by macroscopic lesions and the evaluation of mortality from encephalitis. Mice intravenously inoculated with a highly virulent clinical HSV-1 isolate were orally treated by gavage over a period of 3 days starting on day 2 post infection. The reference drug acyclovir (ACV) was administered subcutaneously. Necrotic hepatitis was significantly (p < 0.01) reduced by treatment with FCV, VACV and ACV at a dose of 50 mg/kg per day divided into 3 doses. No significant effect was achieved with BVDU at 200 mg/kg per day. Treatment with FCV at 50 mg/kg per day, ACV at 100 mg/kg per day, and VACV at 200 mg/kg per day significantly (p < 0.001) decreased mortality in mice. BVDU treatment at 200 mg/kg per day did not reduce mortality but significantly prolonged (p < 0.05) the survival time.

Topics: 2-Aminopurine; Acyclovir; Animals; Antiviral Agents; Bromodeoxyuridine; Cell Line; Disease Models, Animal; Famciclovir; Hepatitis, Animal; Herpes Zoster; Herpesvirus 1, Human; Liver; Mice; Mice, Inbred BALB C; Valacyclovir; Valine; Viral Plaque Assay; Virus Replication

Herpes zoster (HZ) is one of the most common complications after bone marrow transplantation (BMT) in children. Apart from treatment with antiviral drugs, effective prevention by active immunization with varicella-zoster virus (VZV) appears to be possible. In this study 15 patients were vaccinated with a live attenuated VZV vaccine (Varilrix) 12-23 months after BMT. The vaccine was well tolerated without adverse reactions. Chickenpox or HZ were not observed for up to 2 years after immunization. Eight out of nine seronegative patients seroconverted and in six virus-specific IgG could still be demonstrated 2 years later. The incidence of VZV diseases in 133 non-immunized children after BMT was 26.3%. Infections usually occurred within 18 months after BMT.

Topics: Adolescent; Antibodies, Viral; Antiviral Agents; Bone Marrow Transplantation; Bromodeoxyuridine; Chickenpox; Chickenpox Vaccine; Child; Child, Preschool; Dose-Response Relationship, Drug; Follow-Up Studies; Herpes Zoster; Humans; Immune Tolerance; Immunoglobulin G; Retrospective Studies; Vaccination

In December 1995, a 70-years old male was referred to us because of rapid visual loss in the right eye, one month after a central retinal artery occlusion in the left eye. This renal transplant patient, with limited renal function, was on immunosuppressive therapy. The diagnosis of bilateral progressive outer retinal necrosis (PORN) due to varicella-zoster virus (VZV) was confirmed by polymerase chain reaction (PCR) detection of VZV DNA in the aqueous fluid. As retinitis progressed despite of intravenous acyclovir administration, the antiviral therapy was switched to oral bromovinyldeoxyuridine (BVDU). This case-report demonstrates that oral BVDU can be a good alternative to acyclovir for the treatment of VZV retinal infections.

Topics: Administration, Oral; Aged; Antiviral Agents; Bromodeoxyuridine; Fluorescein Angiography; Herpes Zoster; Humans; Immunocompromised Host; Kidney Transplantation; Male; Retinal Necrosis Syndrome, Acute

BVDU [(E)-5-(2-bromovinyl)-2'-deoxyuridine] has proved effective in the treatment of varicella-zoster virus diseases in patients with malignancies. In 13 out of 20 patients a prompt cessation of new vesicle formation accompanied by rapid resolution of fever, crusting and complete epithelialisation of cutaneous lesions were noted. Only in few cases a prolonged recovery from the severe zoster occurred. When starting the treatment later than 48 hours after the onset of initial rash the dissemination of epithelial lesions could not be prevented. BVDU was well tolerated. Laboratory abnormalities were observed only in some cases and did not result in interruption of treatment.

Topics: Adolescent; Adult; Aged; Antiviral Agents; Bromodeoxyuridine; Female; Herpes Zoster; Herpesvirus 3, Human; Humans; Immunoglobulin G; Immunoglobulin M; Male; Middle Aged; Neoplasms; Opportunistic Infections

Topics: Acyclovir; Antigens, Viral; Antiviral Agents; Bone Marrow Transplantation; Bromodeoxyuridine; Cytomegalovirus; DNA, Viral; Ganciclovir; Herpes Simplex; Herpes Zoster; Herpesvirus 4, Human; Humans; Simplexvirus

Topics: Aminopterin; Antiviral Agents; Bromodeoxyuridine; Cell Line; Chickenpox; DNA Replication; DNA-Directed DNA Polymerase; DNA, Viral; Drug Resistance, Microbial; Herpes Zoster; Herpesvirus 3, Human; Humans; Immunoenzyme Techniques; In Vitro Techniques; Kinetics; Mutation; Thymidine Kinase; Viral Plaque Assay; Virus Replication

In the period June 1980-April 1983, 21 children with malignant disease were admitted because of an intercurrent varicella or zoster infection. They were treated with the new antiviral drug BVDU [(E)-5-(2-bromovinyl)-2'-deoxyuridine]. The drug was administered orally at a dose of 15 mg/kg per day for 5 days. All our patients responded promptly to BVDU treatment and recovered completely from their varicella or zoster infections without complications. No toxic side-effects due to the drug were observed.

Topics: Administration, Oral; Adolescent; Animals; Antiviral Agents; Bromodeoxyuridine; Chickenpox; Child; Child, Preschool; Female; Herpes Zoster; Humans; Male; Neoplasms

For immunocompromised patients virus infections represent a definite risk, particularly infections with measles virus and viruses of the herpes group (primary infections or reactivations). Vidarabine, acyclovir and bromovinyldeoxyuridine are therapeutically active against varicella, zoster, and herpes simplex, provided they are administered early in the course of disease. For zoster at least, the efficacy of interferon has been documented in controlled studies. No convincing therapy is so far available for the severe cytomegalovirus infections. Interferons obtained with DNA recombinant techniques are of significant promise in the near future.

Topics: Acyclovir; Antiviral Agents; Bromodeoxyuridine; Chickenpox; Cytomegalovirus Infections; Herpes Simplex; Herpes Zoster; Humans; Immune System Diseases; Vidarabine; Virus Diseases

BVDU [(E)-5-(2-bromovinyl)-2'-deoxyuridine] is a highly potent and selective anti-herpes drug. It is particularly active against Varicella zoster virus, as demonstrated in cell culture and animals (monkeys). BVDU has been administered orally, at a dose of 7.5 mg/kg/day for 5 days, to 20 patients with severe localised or disseminated Herpes zoster. All patients had a malignant disorder for which they had been given intensive chemo- or radiotherapy. Upon BVDU treatment a rapid cessation of the acute Herpes zoster episode was noted in all but one patient. In the majority of patients progression of the infection was arrested within 1 day of starting treatment. No toxic side-effects could be attributed to the drug at the dosage used.

Topics: Administration, Oral; Adolescent; Adult; Aged; Antiviral Agents; Bromodeoxyuridine; Drug Evaluation; Female; Fever; Herpes Zoster; Humans; Male; Middle Aged; Neoplasms; Time Factors

Topics: Antiviral Agents; Bromodeoxyuridine; Herpes Zoster; Humans; Neoplasms

The in vitro susceptibility of eight strains of varicella-zoster virus (VZV) to E-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) was examined in human embryonic fibroblasts by the following techniques: inhibition of focus formation by either cell-free VZV (4-day assay) or cell-associated VZV (2-day assay), inhibition of viral antigen formation (2-day assay), and inhibition of viral cytopathogenicity (15-day assay). The 50% inhibitory dose (ID50) of BVDU ranged from 0.001 microgram/ml (2-day assay) to 0.01 microgram/ml (15-day assay). BVDU appeared highly selective in its anti-VZV activity since even at concentrations as high as 100 micrograms/ml, BVDU did not markedly affect the viability of the host cells. The ID50 of BVDU for VZV was comparable to that of IVDU (E-5-(2-iodovinyl)-2'-deoxyuridine). Both drugs inhibited the replication of VZV at a much lower concentration than did other antiviral compounds such as iododeoxyuridine, ethyldeoxyuridine, arabinosylcytosine, arabinosyladenine, phosphonoacetic acid, iododeoxycytidine, and acycloguanosine. BVDU and IVDU were virtually inactive against a thymidine kinase-deficient VZV mutant, suggesting that phosphorylation by the viral enzyme is responsible, at least in part, for the selective anti-VZV activity of the compounds.

Topics: Antiviral Agents; Bromodeoxyuridine; Herpes Zoster; Herpesvirus 3, Human; Humans; Microbial Sensitivity Tests; Phosphorylation

Topics: Administration, Oral; Aged; Antiviral Agents; Bromodeoxyuridine; Female; Herpes Zoster; Humans; Male; Middle Aged