Oral antivirals revisited in the treatment of herpes zoster: what do they accomplish?

Oral antiviral agents currently represent the most important therapeutic keystone in the treatment of herpes zoster. Three oral antiviral agents are available for the treatment of herpes zoster: acyclovir, its derivative valacyclovir, and famciclovir. Meta-analysis of published data has shown that oral acyclovir significantly reduces various herpes zoster-related symptoms as well as the duration, intensity and prevalence of zoster-associated pain (ZAP). However, this drug does not influence postherpetic neuralgia. The newer agents famciclovir and valacyclovir exhibit a better oral bioavailability than acyclovir. These agents have demonstrated similar efficacy to acyclovir with ZAP and they require less frequent administration. When initiated within 72 hours, oral antiviral therapy of herpes zoster is beneficial in selected, elderly immunocompetent patients, reducing the duration and intensity of ZAP and providing more rapid skin lesion healing. Oral antivirals are also of benefit in immunocompromised patients with uncomplicated herpes zoster. However, signs of cutaneous and visceral dissemination should be monitored; if signs occur, intravenous antiviral therapy is indicated.     

Treatment of postherpetic neuralgia

Postherpetic neuralgia (PHN) is a serious complication of herpes zoster that has a predilection for older individuals. PHN is often associated with significant morbidity, and it can cause insomnia, fatigue, depression and interference with daily activities in affected individuals. Treatment for PHN is initiated with antivirals during the acute herpes zoster outbreak. Acyclovir (Zoviraxr, GlaxoSmithKline), valacyclovir (Valtrex, GlaxoSmithKline) or famciclovir (Famvir, Novartis) can be used to treat herpes zoster, and all three have been shown to reduce the duration of the herpetic rash and zoster-associated pain. These antivirals are most effective when used within the first 72 hours of the onset of the rash. Side-effects of these antivirals are low and include nausea, vomiting, abdominal pain and headache. Other treatment options for PHN include topical analgesics, opioid analgesics, tricyclic antidepressants and gabapentin. Because of the complexity of PHN, most patients require a combination of treatment modalities for adequate pain relief.     

Valacyclovir in the Treatment of Herpes Simplex,Herpes Zoster,and Other Viral Infections

BACKGROUND: Genital herpes and herpes labialis are prevalent, physically and psychologically painful, and often disabling. Herpes zoster is often very painful and may result in months or years of postherpetic neuralgia (PHN). Over the past two decades, the treatment of these conditions has been transformed by guanosine nucleoside antivirals such as valacyclovir (Valtrex, a highly bioavailable prodrug of acyclovir (Zovirax, and famciclovir (Famvir), a highly bioavailable prodrug of penciclovir (Denavir). OBJECTIVE: We describe the pharmacology, pharmacokinetics, and clinical efficacy of valacyclovir for the treatment of herpes simplex, herpes zoster, and other viral infections. Valacyclovir is also compared with acyclovir and famciclovir. METHODS: All published literature containing the word "valacyclovir" was reviewed and summarized. RESULTS: Valacyclovir is the only oral antiviral agent approved for therapy of herpes labialis, the only antiviral drug approved for a 3-day course in the episodic treatment of recurrent genital herpes, as well as the only antiviral drug approved for once daily dosing for suppressive therapy. In herpes zoster, valacyclovir is more effective than acyclovir and equally effective as famciclovir at hastening the healing of zoster-associated pain and PHN. CONCLUSION: Valacyclovir is safe and effective in the therapy of patients with herpes simplex and herpes zoster and may be useful in other viral infections.     

The effects of famciclovir and epidural block in the treatment of herpes zoster.

In our previous study, we concluded that an epidural blockade combined with intravenous acyclovir is very effective in treating the acute pain in herpes zoster and postherpetic neuralgia. We evaluated the efficacy of oral famciclovir and epidural blockade on the pain of herpes zoster, compared to acyclovir administered intravenously and epidural blockade. For this purpose, we examined a new group treated with famciclovir and epidural blockade to compare with the group treated with acyclovir and epidural blockade in our previously study. The changes in the intensity of pain, the number of days required for relief of pain, and the total duration of pain were checked. We compared the days required for relief of pain (DRP) and the total duration of pain (TDP) of this group with those of the previous studied group treated with acyclovir and epidural blockade. DRP was significantly less, but TDP was similar. DRP and TDP were significantly lower, if the patients were treated within 7 days of symptom onset. The patients had a shorter DRP regardless of pain type than the previously studied group treated with acycolvir and epidural blockade. For the severe and moderate pain grades, there was a shorter DRP from 100 to 10. TDP was not significantly different for the groups regardless of pain type or grade. We believe that famciclovir and epidural blockade are very effective in treating the pain of herpes zoster, with a view to shortening the period of acute pain, providing similar effects on the prevention of postherpetic neuralgia, and being convenient to administer, compared to intravenous acyclovir and epidural blockade in our previous study.     

泛昔洛韦与阿昔洛韦治疗带状疱疹临床对比观察

目的 评价泛昔洛韦治疗带状疱疹的疗效和安全性。方法 将60例带状疱疹患者随机分为治疗组泛昔洛韦250mg一日三次和对照组阿昔洛韦200mg一日五次。治疗后第1,3,5,7,8天观察记录。结果 治疗组与对照组在水疱干涸时间和疱疹缓解开始时间比较有显著性差异（P＜0．01）,在水疱停止出现时间和完全结痂时间比较无显著性差异（P＞0．05）。两组病例不良反应相似且轻微。结论 泛昔洛韦是治疗带状疱疹的安全有效药物。     

Open-label study of valacyclovir 1.5 g twice daily for the treatment of uncomplicated herpes zoster in immunocompetent patients 18 years of age or older

BACKGROUND: Herpes zoster (shingles) is a common disease caused by a reactivation of the latent varicella-zoster virus (chickenpox), which resides in the dorsal root ganglia. Valacyclovir HCl, the L-valyl ester of acyclovir, is an antiviral drug that is used to accelerate the resolution of the herpes zoster rash and associated pain and reduce the duration of postherpetic neuralgia. OBJECTIVE: To demonstrate the safety and efficacy of oral valacyclovir 1.5 g twice daily (bid) for the treatment of uncomplicated herpes zoster in immunocompetent patients over 18 years of age. The dosing schedule of bid versus three times daily is desirable for enhancing patient compliance and to subsequently reduce the incidence of viral resistance. METHODS: One treatment group of 125 patients was administered oral valacyclovir 1.5 g bid for 7 days. Administration of the first dose occurred within 72 hours after onset of rash. Patients were seen and assessed for cutaneous healing, zoster-associated pain (ZAP), and/or zoster-associated abnormal sensations (ZAAS). Patients under 50 years of age were followed for 4 weeks and patients 50 years of age and older were followed for a total of 24 weeks. Patients >or= 50 years were also asked to record a daily diary on pain and abnormal sensations throughout the 24-week study period. Responses to resource use and quality of life questions were also collected. Safety was monitored by means of routine hematologic and biochemical assessments and reporting of adverse experiences. RESULTS: Data from this study were compared with historical control groups both for three times daily antiviral therapy and for placebo. The results showed that twice-daily dosing was as safe and effective as three times daily dosing for the reduction of ZAP and ZAAS. Adverse-effect profiles were similar between the two different regimens, and both treatment groups showed better outcomes than the historical placebo group. Because it is standard of care to administer antivirals for the treatment of acute herpes zoster, a placebo-controlled trial is not possible, necessitating the use of historical controls. CONCLUSION: Oral valacyclovir 1.5 g bid is safe and effective for the treatment of uncomplicated herpes zoster in immunocompetent patients over 18 years of age. Twice-daily dosing may help increase patient compliance and therefore increase the effectiveness of treatment of the acute herpes zoster rash and the prevention of ZAP.     

万乃洛韦联合小剂量泼尼松治疗老年人带状疱疹的临床疗效观察

目的:了解盐酸万乃洛韦与小剂量泼尼松联合用药治疗老年人带状疱疹的临床疗效.方法:84例老年带状疱疹患者随机分为两组,研究组联用盐酸万乃洛韦与小剂量泼尼松,对照组单纯用盐酸万乃洛韦,用药后第3、7、14、30天观察记录治疗效果.结果:研究组发疹停止时间、疼痛缓解时间、痊愈时间及后遗神经痛发生率与对照组比较均有显著性差异,两组均无不良反应发生.结论:万乃洛韦联合小剂量泼尼松治疗老年人带状疱疹起效快、病程短并能减少后遗症神经痛的发生率.     

Brivudin compared with famciclovir in the treatment of herpes zoster: effects in acute disease and chronic pain in immunocompetent patients. A randomized, double-blind, multinational study

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.     

Efficacy of low dose gabapentin in acute herpes zoster for preventing postherpetic neuralgia: a prospective controlled study

Postherpetic neuralgia (PHN) is a sequela of herpes zoster that adversely affects quality of life seriously. The risk factors for PHN are well known but the effective interventions that reduce the incidence of PHN are less studied. The objective of this study is to evaluate the efficacy of treatment with gabapentin in patients with acute herpes zoster for preventing PHN. We performed a prospective randomized controlled study of 120 participants diagnosed with acute herpes zoster, aged 50 and over and complaining moderate to severe pain. All patients were treated with valacyclovir and acetaminophen. Half of the participants were assigned to the gabapentin group and received gabapentin 300 mg three times a day additionally. The intensity of pain at every visit and the incidence of PHN in both groups were measured. Total 52 and 49 patients in the gabapentin group and the control group, respectively, had completed 12 weeks of follow‐up period. Although the incidence of PHN was higher in the control group, the difference was not statistically significant (6.1% vs. 3.8%, p = 0.67). Our results indicate that the use of low‐dose gabapentin in acute herpes zoster seems not effective in the prevention of PHN.     

带状疱疹后遗神经痛相关危险因素分析

目的：明确带状疱疹后遗神经痛(postherpetic neuralgia,PHN)的危险因素。方法：分析潍坊医学院附属医院2017年9月至2019年2月带状疱疹住院患者的临床资料,依据发病后1个月是否有PHN,分为病例组和对照组。对两组患者进行单因素及多元logistic回归分析。结果：共筛选出513例患者,其中111例发生PHN（21.6%）。单因素分析示年龄、吸烟史、部位、皮疹面积、临床分型、前驱症状、早期治疗时间、使用糖皮质激素、糖尿病与PHN的发生有关。多因素Logistic回归分析结果显示,PHN的危险因素有年龄≥60岁、有吸烟史、发病诱因为精神/焦虑、初始治疗时间＞7天、急性期重度疼痛和糖尿病史(OR=6.013、3.391、6.800、22.071、21.996、3.163, 95％CI：1.694～21.341、1.219～9.436、1.310～35.296、4.049～120.314、2.864～168.946、1.281～7.811,均P＜0.05)。结论：年龄＞60岁、有吸烟史、发病诱因为精神/焦虑、早期治疗时间＞7天、重度急性期疼痛、糖尿病是PHN发生的危险因素。     

盐酸伐昔洛韦治疗带状疱疹临床疗效观察

目的:评价盐酸伐昔洛韦治疗带状疱疹的临床疗效。方法:将入选患者随机分为两组,治疗组患者给予盐酸伐昔洛韦0.3g,每日2次口服;对照组患者给予阿昔洛韦0.2g,每日5次口服。疗程均为10d,并于用药后观察记录临床症状和体征改善情况。结果:盐酸伐昔洛韦的平均止痛、止疱、结痂时间均比阿昔洛韦短,治疗组有效率为91.4%,对照组有效率为54.3%,两组有效率比较,差异有显著性意义(P0.01)。结论:盐酸伐昔洛韦治疗带状疱疹疗效好,不良反应少,是一个安全有效的药物。     

三种方法治疗带状疱疹疗效观察

目的寻找更安全、有效、经济的治疗带状疱疹及神经痛的方法。方法91例患者随机分为三组进行对比观察.分别于疗程第5,10天观察症状及体征的变化和不良反应。A组口服泛昔洛韦250mg,3次/d,复方甘草酸苷片75mg,3次/d;B组口服泛昔洛韦250mg,3次/d;C组口服复方甘草酸苷片75mg,3次/d。结果三组在结痂起始、止痛起效、疼痛消失时间上有显著性差异;有效率分别为96.77%,86.67%和73.33%;不良反应分别为3.2%,3.3%和0。结论泛昔洛韦和复方甘草酸苷联合应用是治疗带状疱疹和神经痛的一种安全、有效、也较为经济的方法。     

右旋酮洛芬氨丁三醇治疗带状疱疹神经痛疗效观察

目的观察右旋酮洛芬氨丁三醇在治疗带状疱疹神经痛中的疗效和安全性。方法将入选的132例带状疱疹患者随机分为试验组(71例)和对照组(61例),试验组口服阿昔洛韦0.2g,5次/d,右旋酮洛芬氨丁三醇25mg,3次/d;对照组口服阿昔洛韦0.2g,5次/d,布洛芬0.3g,3次/d,分别在治疗第3、5和7天时观察疗效及其不良反应。结果右旋酮洛芬氨丁三醇联合阿昔洛韦能明显改善患者的疼痛症状,两组有效率比较,差异无显著性意义(P>0.05)。试验组不良反应发生率为7.46%,对照组为20.33%,两者差异有显著性意义(P<0.05)。结论右旋酮洛芬氨丁三醇联合阿昔洛韦治疗。能有效缓解带状疱疹神经痛,且不良反应率低。     

带状疱疹及其后遗神经痛治疗与预防

带状疱疹及带状疱疹后遗神经痛是皮肤科引起神经性疼痛的常见原因,其治疗和预防是常见临床问题.抗病毒药物能够降低疱疹严重程度、缩短疱疹持续时间,但对带状疱疹后遗神经痛的作用尚不明确.糖皮质激素、三环类抗抑郁药、抗惊厥剂、镇痛药等均能减轻带状疱疹相关疼痛.抗惊厥剂、麻醉性镇痛药、三环类抗抑郁药及局部用利多卡因贴剂和辣椒素软膏均对带状疱疹后遗神经痛有效.接种水痘一带状疱疹疫苗对带状疱疹及带状疱疹后遗神经痛的发病率有重要影响.     

溴夫定治疗带状疱疹的疗效和安全性评价

目的 评价溴夫定125mg每天1次和每天4次治疗带状疱疹的疗效和安全性.方法 多中心、随机、双盲、平行对照临床试验.226例带状疱疹患者分别接受溴夫定125mg每天1次(112例)或每天4次(114例)治疗,疗程7d,再随访3周.结果 新水疱停止出现时间,单次剂量组平均为3.88d,4次剂量组为3.79d,两组比较,差异无统计学意义.水疱完全消退时间、开始结痂时间、全部结痂时间、开始脱痂时间、全部脱痂时间、疼痛开始减轻时间和疼痛完全消失时间两组比较,差异均无统计学意义.单次剂量组有34.5%、4次剂量组有30.4%的患者皮损痊愈后仍存在疱疹相关疼痛.药物相关不良反应发生率分别为5.4%和9.6%.结论 溴夫定125mg每天1次和每天4次治疗带状疱疹同样有效,但单次剂量组更方便、安全.     

Famciclovir for the treatment of recurrent genital and labial herpes lesions

Famciclovir (Famvir, Novartis) is an effective treatment for herpes zoster and herpes simplex. Two separate studies recently examined the effectiveness of single high doses of famciclovir for treating recurrent genital herpes and labial herpes (cold sores). In the randomized, placebo-controlled studies, patients initiated treatment at the first onset of symptoms. For the treatment of genital herpes, a 1,000 mg b.i.d. dose of famciclovir had significant advantages over the placebo, reducing the time required to heal the lesions, preventing the development of lesions beyond the papule stage, and improving the time to resolution of all symptoms. For the treatment of labial herpes, a single 1,500 mg dose of famciclovir shortened the lesion healing time, shortened the time to normal skin, and resulted in faster resolution of pain and tenderness.     

Rash severity in herpes zoster: correlates and relationship to postherpetic neuralgia

Baseline and follow-up data from 4 samples of immunocompetent patients with herpes zoster who participated in clinical trials of the antiviral agent famciclovir were examined (N = 1778). In both univariate and multivariate analyses, severe rash (ie, >50 lesions, defined as papules, vesicles, or crusted vesicles) was significantly associated with older age, male sex, severe pain, primary involvement of nontrigeminal dermatomes, and a greater number of affected dermatomes. In addition, severe rash predicted the presence of pain 3 months later. The results indicate that severe rash is more common in patients with herpes zoster who are older and who have more severe acute pain and confirm that severe rash is a risk factor for prolonged pain.     

Amenamevir,a novel helicase–primase inhibitor,for treatment of herpes zoster: A randomized,double‐blind,valaciclovir‐controlled phase 3 study

Amenamevir is a potent helicase–primase inhibitor and a novel class of antiviral agent other than nucleoside compounds, such as aciclovir, valaciclovir and famciclovir. This study is the first randomized, double‐blind, valaciclovir‐controlled phase 3 study to evaluate the efficacy and safety of amenamevir in Japanese patients with herpes zoster when treated within 72 h after onset of rash. A total of 751 patients were randomly assigned to receive either amenamevir 400 mg or 200 mg p.o. once daily or valaciclovir 1000 mg three times daily (daily dose, 3000 mg) for 7 days. The primary efficacy end‐point was the proportion of cessation of new lesion formation by day 4 (“day 4 cessation proportion”). The day 4 cessation proportions for amenamevir 400 and 200 mg and valaciclovir were 81.1% (197/243), 69.6% (172/247) and 75.1% (184/245), respectively. Non‐inferiority of amenamevir 400 mg to valaciclovir was confirmed by a closed testing procedure. Days to cessation of new lesion formation, complete crusting, healing, pain resolution and virus disappearance were evaluated as secondary end‐points. No significant differences were observed in any of the treatment groups. Amenamevir 400 and 200 mg were well tolerated as well as valaciclovir. The proportions of patients who experienced drug‐related adverse events were 10.0% (25/249), 10.7% (27/252) and 12.0% (30/249) with amenamevir 400 and 200 mg and valaciclovir, respectively. In conclusion, amenamevir 400 mg appears to be effective and well tolerated for treatment of herpes zoster in immunocompetent Japanese patients.     

Cutaneous infections in the elderly: diagnosis and management

Over the past several years there have been many advances in the diagnosis and treatment of cutaneous infectious diseases. This review focuses on the three major topics of interest in the geriatric population: herpes zoster and postherpetic neuralgia (PHN), onychomycosis, and recent advances in antibacterial therapy. Herpes zoster in adults is caused by reactivation of the varicella-zoster virus (VZV) that causes chickenpox in children. For many years acyclovir was the gold standard of antiviral therapy for the treatment of patients with herpes zoster. Famciclovir and valacyclovir, newer antivirals for herpes zoster, offer less frequent dosing. PHN refers to pain lasting > or = 2 months after an acute attack of herpes zoster. The pain may be constant or intermittent and may occur spontaneously or be caused by seemingly innocuous stimuli such as a light touch. Treatment of established PHN through pharmacologic and nonpharmacologic therapy will be discussed. In addition, therapeutic strategies to prevent PHN will be reviewed. These include the use of oral corticosteroids, nerve blocks, and treatment with standard antiviral therapy. Onychomycosis, or tinea unguium, is caused by dermatophytes in the majority of cases, but can also be caused by Candida and nondermatophyte molds. Onychomycosis is found more frequently in the elderly and in more males than females. There are four types of onychomycosis: distal subungual onychomycosis, proximal subungual onychomycosis, white superficial onychomycosis, and candidal onychomycosis. Over the past several years, new treatments for this disorder have emerged which offer shorter courses of therapy and greater efficacy than previous therapies. The treatment of bacterial skin and skin structure infections in the elderly is an important issue. There has been an alarming increase in the incidence of gram-positive infections, including resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) and drug-resistant pneumococci. While vancomycin has been considered the drug of last defense against gram-positive multidrug-resistant bacteria, the late 1980s saw an increase in vancomycin-resistant bacteria, including vancomycin-resistant enterococci (VRE). More recently, strains of vancomycin-intermediate resistant S. aureus (VISA) have been isolated. Gram-positive bacteria, such as S. aureus and Streptococcus pyogenes are often the cause of skin and skin structure infections, ranging from mild pyodermas to complicated infections including postsurgical wound infections, severe carbunculosis, and erysipelas. With limited treatment options, it has become critical to identify antibiotics with novel mechanisms of activity. Several new drugs have emerged as possible therapeutic alternatives, including linezolid and quinupristin/dalfopristin.     

带状疱疹抗病毒药物的合理选择

抗病毒治疗是带状疱疹治疗的核心, 本文结合最新研究、共识和指南, 探讨抗病毒药物种类和剂量的合理选择。伐昔洛韦口服生物利用度高, 且用药更方便, 一般是口服抗病毒药物的首选;而对于一些特殊情况, 如免疫力低下患者, 应酌情选择静脉滴注阿昔洛韦。对于严重肾功能不全的患者, 溴夫定往往是更好的选择;对阿昔洛韦耐药的患者应考虑使用泛昔洛韦或者其他抗病毒药物治疗;而对于免疫力低下同时合并阿昔洛韦耐药的患者可选择静脉滴注膦甲酸钠。使用口服抗病毒药应达到足够的剂量。选择合适的抗病毒药物及剂量能有效缓解患者急性期症状, 同时降低发生带状疱疹后神经痛的可能性。