brivudine and Pain

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

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

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