Treatment of Shingles in Adults
For uncomplicated shingles in immunocompetent adults, initiate oral valacyclovir 1000 mg three times daily or famciclovir 500 mg three times daily within 72 hours of rash onset, continuing until all lesions have completely scabbed; for severely immunocompromised patients or disseminated disease, switch immediately to intravenous acyclovir 10 mg/kg every 8 hours. 1
First-Line Oral Antiviral Therapy
Standard Dosing Regimens
Valacyclovir 1000 mg orally three times daily for 7–10 days is the preferred first-line agent due to superior bioavailability and less frequent dosing compared to acyclovir, improving patient adherence. 1, 2
Famciclovir 500 mg orally three times daily for 7–10 days offers equivalent efficacy to valacyclovir with similar dosing convenience. 1, 2
Acyclovir 800 mg orally five times daily for 7–10 days remains an effective alternative but requires more frequent dosing throughout the day. 1, 2, 3
Critical Timing and Duration
Treatment must be initiated within 72 hours of rash onset to achieve optimal efficacy in reducing acute pain, accelerating lesion healing, and preventing postherpetic neuralgia. 1
Continue antiviral therapy until all lesions have completely scabbed, not just for an arbitrary 7-day period—this is the key clinical endpoint. 1
Do not discontinue therapy at exactly 7 days if lesions are still forming or have not fully crusted; short-course regimens designed for genital herpes (1–3 days) are inadequate for varicella-zoster virus infection. 1
Renal Dose Adjustments
Assess baseline renal function before starting any oral antiviral, as all three agents are renally eliminated and can cause crystalluria and obstructive nephropathy. 1
For famciclovir, adjust dosing based on creatinine clearance: 500 mg every 8 hours for CrCl ≥60 mL/min, down to 250 mg every 24 hours for CrCl <20 mL/min. 1
Maintain adequate hydration throughout the treatment course to minimize nephrotoxicity risk. 1
Intravenous Acyclovir for Severe or Complicated Disease
Indications for IV Therapy
Switch to intravenous acyclovir 10 mg/kg every 8 hours when any of the following are present: 1
Disseminated herpes zoster: lesions in ≥3 dermatomes, visceral organ involvement (hepatitis, pneumonia, encephalitis), or hemorrhagic lesions 1
Severe immunosuppression: active chemotherapy, HIV with low CD4 count, organ transplant recipients, or chronic high-dose immunosuppressive therapy 1
Central nervous system complications: encephalitis, meningitis, or Guillain-Barré syndrome 1
Complicated facial or ophthalmic disease with risk of vision-threatening complications 1, 2
Lack of clinical improvement after 7–10 days of appropriate oral therapy, suggesting possible acyclovir resistance 1
IV Acyclovir Administration and Monitoring
Continue IV therapy for a minimum of 7–10 days and until all lesions have completely scabbed; immunocompromised patients may require extended courses. 1
Monitor renal function at treatment initiation and once or twice weekly during IV therapy to detect nephrotoxicity early. 1
Adjust dosing based on degree of renal impairment to prevent drug accumulation. 1
Watch for thrombotic thrombocytopenic purpura or hemolytic-uremic syndrome in immunocompromised patients receiving high-dose IV acyclovir. 1
Management of Immunosuppressive Medications
In patients with disseminated or invasive herpes zoster, temporarily reduce or discontinue immunosuppressive medications when clinically feasible. 1
Re-introduce immunosuppressive agents only after all vesicular lesions have crusted, fever has resolved, and the patient shows clinical improvement on antiviral therapy. 1
Initiation or continuation of immunomodulatory therapy during active herpes zoster infection is contraindicated. 1
Treatment of Acyclovir-Resistant Herpes Zoster
Recognition of Resistance
Suspect acyclovir resistance when cutaneous lesions have not begun to resolve within 7–10 days after starting appropriate therapy. 1
Confirmed acyclovir-resistant varicella-zoster virus is rare in immunocompetent adults but occurs in up to 7% of immunocompromised patients. 1
All acyclovir-resistant strains are also resistant to valacyclovir, and most are resistant to famciclovir. 1
Treatment of Confirmed Resistance
For laboratory-confirmed acyclovir-resistant VZV, switch to foscarnet 40 mg/kg intravenously every 8 hours until clinical resolution of lesions. 1
Obtain viral culture with susceptibility testing to confirm resistance before changing therapy. 1
Topical cidofovir gel 1% applied once daily for 5 consecutive days may be an alternative option, though foscarnet remains the treatment of choice. 1
Pain Management for Acute Herpes Zoster
First-Line Neuropathic Pain Therapy
Gabapentin is the first-line oral agent for acute neuropathic pain, titrated in divided doses up to 2400 mg per day. 1
Gabapentin improves sleep quality but causes somnolence in approximately 80% of treated individuals—counsel patients about this common adverse effect. 1
When a patient is already receiving amitriptyline for another indication, add gabapentin rather than another tricyclic antidepressant. 1
Adjunctive Systemic Therapies
Pregabalin may be added for patients whose pain remains uncontrolled with gabapentin alone, particularly in postherpetic neuralgia. 1
Serotonin-norepinephrine reuptake inhibitors (SNRIs) can be considered as adjuncts based on their efficacy in broader neuropathic pain populations. 1
Topical Therapies
A single application of an 8% capsaicin patch (or a 30-minute cream application) provides analgesia lasting at least 12 weeks for chronic peripheral neuropathic pain. 1
To mitigate the erythema and burning associated with capsaicin, apply a 4% lidocaine preparation for 60 minutes, then remove before capsaicin administration. 1
Simple Analgesics
Over-the-counter analgesics such as acetaminophen and ibuprofen are recommended to relieve acute pain in otherwise healthy adults. 1
Application of topical ice or cold packs can reduce pain and swelling of the rash during the acute phase. 1
Therapies to Avoid
Topical anesthetics provide minimal benefit and are not recommended as primary therapy for acute zoster pain management. 1
Topical antiviral therapy is substantially less effective than systemic therapy and is not recommended. 1
Vaccination with Recombinant Zoster Vaccine (Shingrix)
Primary Recommendation
The recombinant zoster vaccine (Shingrix) is recommended for all adults aged ≥50 years, regardless of prior herpes zoster episodes or previous Zostavax vaccination, administered as a two-dose series with the second dose given 2–6 months after the first. 1, 4
Dosing Schedule
Standard schedule for immunocompetent adults: second dose 2–6 months after the first dose, with a minimum interval of 4 weeks. 4
Modified schedule for immunocompromised adults aged ≥18 years: second dose 1–2 months after the first dose to achieve earlier protection. 4
If the second dose is delayed beyond 6 months, effectiveness is not impaired—do not restart the series, simply administer the second dose as soon as possible. 4
Efficacy and Duration of Protection
Shingrix demonstrates 97.2% efficacy against herpes zoster in adults aged ≥50 years, with consistent protection across all age groups. 4
Protection persists for at least 8 years with minimal waning, maintaining efficacy above 83.3% during this period. 4
Real-world vaccine effectiveness is 70.1% for the two-dose series and 56.9% for a single dose, emphasizing the importance of completing both doses. 5
Vaccination After a Shingles Episode
Administer Shingrix once acute symptoms have resolved, with a practical interval of at least 2 months commonly recommended to allow complete symptom resolution. 1, 4
Having one episode of shingles does not provide reliable protection against future recurrences—the 10-year cumulative recurrence risk is 10.3%. 1, 4
Vaccination After Prior Zostavax
Adults who previously received Zostavax should receive the full two-dose Shingrix series, as Zostavax efficacy wanes to only 14.1% by year 10. 4
Administer Shingrix at least 2 months after the last Zostavax dose. 4
Special Populations
Immunocompromised adults aged ≥18 years should receive Shingrix on the shortened 1–2 month schedule, including those with hematologic malignancies, solid organ or stem cell transplant recipients, HIV infection, and autoimmune diseases requiring immunosuppressive therapy. 4
For autologous hematopoietic stem cell transplant recipients, administer Shingrix 50–70 days post-transplantation. 4
Shingrix is safe for patients on low-dose glucocorticoids (prednisone equivalent <10 mg/day) without adversely impacting vaccine response. 4
Never use live-attenuated Zostavax in immunocompromised patients—only Shingrix is appropriate due to the risk of disseminated VZV infection with live vaccine. 4
Timing with Immunosuppressive Therapy
Ideally, complete the full two-dose Shingrix series before starting immunosuppressive therapies such as JAK inhibitors to maximize immune response. 4
If urgent therapy initiation is required, administer at least the first dose before starting treatment, with the second dose completed after therapy has begun. 4
Safety Profile
Injection-site reactions (pain, redness, swelling) are common, with 9.5% experiencing grade 3 reactions compared to 0.4% with placebo. 4
Systemic symptoms (fever, fatigue, myalgia) occur in 11.4% of vaccine recipients versus 2.4% in placebo recipients, typically resolving within 4 days. 4
No serious safety concerns have been identified in large clinical trials, with similar rates of serious adverse events between vaccine and placebo groups. 4
Common Pitfalls and Caveats
Do not delay antiviral therapy beyond 72 hours of rash onset—efficacy diminishes significantly after this window. 1
Do not use topical antivirals as primary therapy; they are substantially less effective than systemic treatment. 1, 3
Do not stop oral antivirals at exactly 7 days if lesions have not fully scabbed—continue until complete crusting occurs. 1
Do not use corticosteroids without concurrent systemic antiviral therapy in active herpes zoster, as steroids can potentiate viral replication and worsen disease. 1, 2
Do not confuse varicella (chickenpox) vaccination with herpes zoster vaccination—they are distinct vaccines for different indications. 4
Do not order VZV antibody titers before administering Shingrix to adults ≥50 years—guidelines explicitly recommend against serologic screening in this population. 4
Do not give a third dose of Shingrix under any circumstance—the series consists of only two doses. 4