Comparison of Famciclovir, Valaciclovir, and Brivudine Treatments in Adult Immunocompetent Patients With Herpes Zoster

Herpes zoster (HZ) is a common disease characterized by the recurrence of varicella zoster, which remains dormant in sensory ganglia. The primary aim of this study was to compare the effectiveness of famciclovir, valaciclovir, and brivudine in providing pain relief to HZ patients. Medical records from patients diagnosed with acute HZ at the Dermatology Clinic of a university hospital between 2012 and 2014 were retrospectively analyzed. Treatment decisions were made by attending physicians based on clinical judgment, prescribing valaciclovir (VACV), famciclovir (FCV), or brivudine (BRV). All three medications were found effective in treating pain associated with acute HZ.

There was no significant difference in treatment outcomes among patients with mild or moderate HZ. However, among those with severe cases, a substantial reduction in pain was observed as early as day 3 in the BRV group, by day 7 in the FCV group, and within 2 to 3 weeks in the VACV group. No notable side effects were recorded in any treatment group. These findings suggest that brivudine could be the preferred option for managing severe HZ due to its earlier pain control and convenient once-daily dosage.

Introduction

Herpes zoster (HZ) is caused by reactivation of varicella zoster virus, remaining latent in sensory ganglia. It affects around 25% of the population and can occur at any age, with incidence rates increasing with age. It affects both men and women equally. Pain is the most prevalent complication and significantly impacts quality of life in immunocompetent individuals.

Postherpetic neuralgia (PHN) is a common long-term complication of HZ. Risk factors include advanced age, severe acute herpetic pain (AHP), extensive rash, and prodromal dermatomal pain. PHN may persist for up to six months in 50% to 75% of patients with these risk factors. Timely antiviral therapy is essential, particularly for elderly patients, to control AHP and minimize complications.

Effective HZ treatment focuses on expediting recovery, controlling pain, and minimizing complications. Antiviral therapy initiated early in the course of the disease speeds up rash resolution and reduces the severity of symptoms. Famciclovir, valaciclovir, and brivudine are preferred over aciclovir due to higher efficacy and lower dosing requirements.

Despite the common use of these drugs, few studies have directly compared all three. This study aimed to retrospectively evaluate the pain-relieving effects of famciclovir, valaciclovir, and brivudine in immunocompetent patients with acute HZ.

Materials and Methods

Patient records from 2012 to 2014 at the Dermatology Clinic were reviewed. Ethical approval was obtained. Treatment regimens included VACV (1000 mg three times daily), FCV (500 mg three times daily), or BRV (125 mg once daily). Patients were assigned to groups based on the prescribed antiviral.

Exclusion criteria included patients younger than 20, immunocompromised individuals, patients with rash present for more than five days, use of analgesic or anti-inflammatory medications other than flurbiprofen, and incomplete medical records. Of 150 patients, 89 met the criteria.

Patients were assessed at days 0, 3, 7, and 2–3 weeks. They completed a questionnaire evaluating pain, allodynia, and hyperesthesia using a visual analog scale (VAS). Data collected included demographic information, onset time of rash, treatment initiation, comorbidities, affected dermatome, lesion severity, and any medication side effects.

Patients were categorized based on the affected dermatome into trigeminal, cervical, upper thoracic, lower thoracic, and lumbosacral groups. Lesion involvement was classified as mild (<30%), moderate (30–70%), or severe (>70%).

Statistical Analysis

Data analysis utilized NCSS 2007 and PASS 2008 software. Statistical tests included the Mann-Whitney U, one-way ANOVA, Tukey HSD, Welch ANOVA, Kruskal–Wallis, and Chi-square tests. General linear mixed models were applied to assess factors affecting VAS scores. Significance was determined at P < 0.01 and P < 0.05.

Results

Among the 89 patients, 41.6% were male and 58.4% female, with a mean age of 55 years (range 24–88). There were no significant differences in age, gender, rash onset time, affected dermatome, or lesion severity among treatment groups.

VAS Changes

There were no significant differences in initial VAS scores among the three groups. However, all groups showed significant reductions in VAS scores over time. BRV, FCV, and VACV each led to marked pain reduction at days 3, 7, and 2–3 weeks.

Duration of Rash

In patients treated within three days of rash onset, significant pain reduction was observed in all groups by days 3, 7, and 2–3 weeks. Similar trends were noted in patients treated after three days, with no significant intergroup differences.

HZ Severity

For mild and moderate cases, all groups experienced significant pain reduction at each follow-up, with no intergroup differences. In severe HZ, BRV showed significant pain reduction by day 3, FCV by day 7, and VACV by 2–3 weeks.

Age Groups

Both age groups (<50 and ≥50 years) experienced significant pain reduction in all treatment arms. No intergroup differences were found based on age.

Crusting and Lesion Healing

All groups showed similar progression in crusting and lesion resolution. No significant correlation was found between pain score changes and crusting.

Pain Frequency

A significant decrease in pain frequency was observed in all groups from baseline through follow-up. The BRV group showed earlier reductions.

Allodynia Frequency

No significant intergroup differences were observed in allodynia at any time point. However, within-group comparisons showed significant reductions in allodynia over time in all three treatment arms.

General Linear Mixed Model

Model analysis confirmed that lesion severity significantly impacted VAS scores, while treatment group and age did not. The interaction between group, age, and severity was significant.

Discussion

All three antiviral agents—BRV, FCV, and VACV—demonstrated efficacy in reducing acute herpetic pain. BRV appeared to provide faster pain relief, particularly in severe HZ, potentially due to its once-daily dosing and ease of administration.

Previous studies have shown comparable effectiveness of FCV and BRV. The BRV group showed earlier pain control, and lesion healing was similar among treatments. Tyring et al. and Ono et al. found no major differences between FCV and VACV, although FCV had a faster onset of action in some cases.

In our study, differences in pain relief among treatments became more apparent in severe HZ cases. BRV led to pain reduction as early as day 3, while FCV showed results by day 7 and VACV by 2–3 weeks. All treatments were well tolerated with minimal side effects.

Study limitations include its retrospective design and relatively small sample size. Larger, randomized controlled studies are needed to confirm these findings.

Conclusion

BRV, FCV, and VACV are effective antiviral treatments for acute HZ pain. In mild and moderate cases, all three provide similar benefits. In severe HZ, BRV may offer faster pain relief and more convenient dosing, making it a potential first-line option. No significant side effects were noted with any treatment.