What is the optimal management of herpes zoster in an adult, including first‑line oral antiviral selection and dosing (with renal function adjustment), pain control strategies, treatment recommendations for immunocompromised patients, vaccination guidance, and infection‑control precautions?

Optimal Management of Herpes Zoster in Adults

First-Line Oral Antiviral Therapy

Valacyclovir 1000 mg three times daily for 7 days is the preferred first-line oral antiviral for herpes zoster in immunocompetent adults, offering superior convenience and pain reduction compared to acyclovir. 1, 2

Standard Oral Antiviral Options:

• Valacyclovir 1000 mg orally three times daily for 7 days – preferred due to better bioavailability, less frequent dosing, and faster resolution of zoster-associated pain and postherpetic neuralgia compared to acyclovir 1, 3, 2, 4
• Famciclovir 500 mg orally three times daily for 7 days – equivalent efficacy to valacyclovir with similar dosing convenience 1, 2, 5
• Acyclovir 800 mg orally five times daily for 7-10 days – effective but requires more frequent dosing, which may reduce adherence 1, 4, 6

Critical Timing:

• Initiate antiviral therapy within 72 hours of rash onset for optimal efficacy in reducing acute pain, accelerating lesion healing, and preventing postherpetic neuralgia 1, 4, 6, 7
• Treatment may still provide benefit when started after 72 hours, particularly for pain reduction, though earlier initiation is strongly preferred 2

Treatment Duration Endpoint:

• Continue antiviral therapy until all lesions have completely scabbed, not just for an arbitrary 7-day period 1
• Immunocompromised patients may require extended treatment beyond 7-10 days as lesions develop over longer periods (7-14 days) and heal more slowly 1

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Renal Dose Adjustments

All oral antivirals require mandatory dose reduction in renal impairment to prevent acute renal failure and drug accumulation. 1

Valacyclovir Renal Dosing:

• CrCl ≥50 mL/min: 1000 mg three times daily
• CrCl 30-49 mL/min: 1000 mg twice daily
• CrCl 10-29 mL/min: 1000 mg once daily
• CrCl <10 mL/min: 500 mg once daily 1

Famciclovir Renal Dosing:

• CrCl ≥60 mL/min: 500 mg every 8 hours
• CrCl 40-59 mL/min: 500 mg every 12 hours
• CrCl 20-39 mL/min: 500 mg every 24 hours
• CrCl <20 mL/min: 250 mg every 24 hours 1

Acyclovir Renal Dosing:

• CrCl >25 mL/min: 800 mg five times daily
• CrCl 10-25 mL/min: 800 mg every 8 hours
• CrCl <10 mL/min: 800 mg every 12 hours 1

Monitoring:

• Ensure adequate hydration during systemic antiviral therapy to reduce risk of crystalluria and acyclovir-induced nephropathy 1
• Assess baseline renal function and monitor at least once or twice weekly during intravenous acyclovir therapy 1

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Pain Control Strategies

Acute Phase Pain Management (Stepped Approach):

For mild to moderate pain, initiate acetaminophen up to 3000-4000 mg/day in divided doses, progressing to opioids for moderate-severe pain, with early addition of gabapentin to prevent postherpetic neuralgia. 3

Step 1: Mild Pain

• Acetaminophen up to 3000-4000 mg/day in divided doses – preferred due to lower adverse effect profile in older adults 3
• Over-the-counter analgesics such as ibuprofen may be used but with extreme caution in elderly patients due to gastrointestinal toxicity, renal issues, hypertension, and heart failure risk 1, 3

Step 2: Moderate to Severe Pain

• Opioids starting at low doses with gradual titration – use scheduled dosing for frequent or continuous pain 3
• Anticipate and manage opioid-related adverse effects including sedation, cognitive impairment, falls, and constipation 3

Step 3: Adjuvant Neuropathic Pain Therapy (Start Early)

• Gabapentin 100-300 mg at bedtime, gradually titrating to 300-600 mg three times daily as tolerated – first-line oral agent for acute neuropathic pain and prevention of postherpetic neuralgia 1, 3
• Counsel patients that somnolence occurs in approximately 80% of treated individuals 1
• Pregabalin may be added for patients whose pain remains uncontrolled with gabapentin alone 1

Step 4: Topical Therapies

• Lidocaine 5% patch applied to affected area for 12 hours daily (up to 3 patches) – particularly valuable for localized neuropathic pain with minimal systemic absorption and no drug interactions 1, 3
• The 5% prescription strength is preferred over 4% over-the-counter formulation for optimal efficacy 3
• Capsaicin 8% patch (single application) or 30-minute cream application provides analgesia lasting at least 12 weeks, though often poorly tolerated 1, 3

Medications to Avoid:

• Topical acyclovir is substantially less effective than systemic therapy and is not recommended 8, 1
• Muscle relaxants (cyclobenzaprine, carisoprodol) due to significant anticholinergic effects and increased fall risk 3
• Benzodiazepines due to sedation, cognitive impairment, and increased fall risk 3

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Treatment in Immunocompromised Patients

Immunocompromised patients with herpes zoster require intravenous acyclovir 10 mg/kg every 8 hours for disseminated or invasive disease, with temporary reduction in immunosuppressive medications when clinically feasible. 1

Indications for Intravenous Therapy:

• Disseminated herpes zoster (≥3 dermatomes, visceral involvement, or hemorrhagic lesions) 1
• Severe immunosuppression (active chemotherapy, HIV with low CD4 count, organ transplant, B-cell depleting therapies) 1
• CNS complications (encephalitis, meningitis, Guillain-Barré syndrome) 1
• Complicated ocular/facial disease 1
• Failure to improve on oral therapy within 7-10 days 1

IV Acyclovir Dosing:

• 10 mg/kg intravenously every 8 hours for severely immunocompromised hosts 1
• Continue for minimum 7-10 days and until clinical resolution (all lesions completely scabbed) 1
• Adjust dose for renal impairment 1

Management of Immunosuppression:

• Temporarily reduce or discontinue immunosuppressive medications in cases of disseminated or invasive herpes zoster when clinically feasible 1
• Re-introduce immunosuppressive agents only after all vesicular lesions have crusted, fever has resolved, and patient shows clinical improvement on antiviral therapy 1
• Initiation or continuation of immunomodulatory therapy during active herpes zoster is contraindicated 1

Special Populations:

• Kidney transplant recipients with uncomplicated herpes zoster: oral acyclovir or valacyclovir with renal dose adjustment 1
• Patients on B-cell depleting therapies (ocrelizumab, rituximab, ofatumumab): consider IV acyclovir even for apparently uncomplicated disease due to highest risk of severe herpes zoster 1
• HIV-positive patients: may require higher oral doses (acyclovir 800 mg 5-6 times daily) or IV therapy for severe disease 1

Prophylaxis:

• Acyclovir 400 mg twice daily or valacyclovir prophylaxis for patients receiving proteasome inhibitor-based therapies (e.g., bortezomib) 1
• Consider long-term prophylaxis (acyclovir 400 mg 2-3 times daily) for HIV-positive patients with frequent recurrences 1

Monitoring in Immunocompromised Patients:

• Assess for thrombotic thrombocytopenic purpura/hemolytic uremic syndrome during high-dose IV therapy 1
• Monitor for visceral dissemination including respiratory symptoms (pneumonia), hepatic enzyme elevation (hepatitis), or neurological changes (CNS involvement) 1

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Acyclovir-Resistant Herpes Zoster

For confirmed acyclovir-resistant VZV, switch to foscarnet 40 mg/kg intravenously every 8 hours until clinical resolution. 1

Recognition of Resistance:

• Suspect resistance when cutaneous lesions have not begun to resolve within 7-10 days after starting therapy 1
• Acyclovir resistance is extremely rare in immunocompetent patients but occurs in up to 7% of immunocompromised patients 1
• Obtain viral culture with susceptibility testing to confirm resistance 1

Treatment:

• Foscarnet 40 mg/kg IV every 8 hours until clinical resolution – treatment of choice for proven or suspected acyclovir-resistant herpes zoster 1
• All acyclovir-resistant strains are also resistant to valacyclovir, and most are resistant to famciclovir 1
• Topical cidofovir gel 1% applied once daily for 5 consecutive days may be an alternative option 1

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Vaccination Guidance

The recombinant zoster vaccine (Shingrix) is strongly recommended for all adults aged ≥50 years, providing >90% efficacy in preventing herpes zoster and should be administered regardless of prior herpes zoster episodes. 8, 1, 9

Vaccine Selection:

• Shingrix (recombinant zoster vaccine, RZV) is preferred over Zostavax due to superior efficacy (97% vs 70%) and safety in immunocompromised patients 8, 1, 9
• Shingrix contains only viral protein fragment (glycoprotein E) with adjuvant AS01B, eliminating risk of live virus reactivation 9
• Zostavax efficacy declines dramatically over time to only 14.1% within 10 years 9

Dosing Schedule:

• Two-dose series: first dose followed by second dose 2-6 months later (minimum interval 4 weeks if necessary) 1, 9

Timing Recommendations:

• Ideally administer before initiating immunosuppressive therapies 1
• For patients already on B-cell depleting therapy, give at least 4 weeks prior to next scheduled dose to maximize immunogenicity 1
• For patients with history of herpetic keratitis, administer when keratitis is completely quiescent for at least 2-3 months 9
• Vaccination is recommended even after recovery from acute herpes zoster to prevent future episodes 8, 1

Special Populations:

• Autoimmune inflammatory rheumatic diseases: herpes zoster vaccination may be considered when less severely immunosuppressed 8
• Administer only to patients seropositive for varicella zoster antibodies to prevent primary varicella infection with vaccine strain 8
• Live attenuated vaccine (Zostavax) is contraindicated in immunocompromised patients due to risk of uncontrolled viral replication 1

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Infection Control Precautions

Patients with herpes zoster must avoid contact with susceptible individuals until all lesions have crusted, as lesions are contagious to those who have not had chickenpox or vaccination. 1

Standard Precautions:

• Cover lesions with clothing or dressings to minimize transmission risk 1
• Maintain physical separation of at least 6 feet from other patients in healthcare settings 1
• Healthcare workers with herpes zoster should be excluded from duty until all lesions dry and crust 1

Enhanced Precautions for High-Risk Cases:

• Disseminated zoster (lesions in >3 dermatomes): implement both airborne and contact precautions in addition to standard precautions 1
• Immunocompromised patients with herpes zoster: implement airborne and contact precautions due to higher risk of dissemination 1

Post-Exposure Prophylaxis:

• Varicella-zoster immune globulin (VZIG) within 96 hours of exposure for varicella-susceptible patients, including pregnant women, immunocompromised patients, and premature newborns <28 weeks gestation or <1,000 g 1
• VZIG provides maximum benefit when administered as soon as possible after exposure 1
• If VZIG unavailable or >96 hours have passed: 7-day course of oral acyclovir beginning 7-10 days after varicella exposure 1
• Varicella vaccine within 3-5 days of exposure may modify disease if infection has not yet occurred 1