Treatment of Shingles (Herpes Zoster) in Adults

First-Line Antiviral Therapy

For uncomplicated herpes zoster in immunocompetent adults, initiate oral valacyclovir 1 gram three times daily for 7–10 days, continuing until all lesions have completely scabbed. 1, 2

Alternative Oral Regimens

Acyclovir 800 mg orally five times daily for 7–10 days is equally effective but requires more frequent dosing, which may reduce adherence 1, 2, 3
Famciclovir 500 mg orally three times daily for 7 days offers comparable efficacy with better bioavailability than acyclovir 1, 3
Valacyclovir demonstrates superior pain reduction compared to acyclovir, particularly for zoster-associated pain and postherpetic neuralgia 3

Critical Timing Window

Treatment should ideally be initiated within 72 hours of rash onset for maximum efficacy in reducing acute pain, accelerating lesion healing, and preventing postherpetic neuralgia 1, 4, 5
Observational data suggest valacyclovir may retain benefit even when started beyond 72 hours, though earlier initiation remains optimal 3
The key clinical endpoint is complete scabbing of all lesions, not an arbitrary 7-day duration—extend treatment if active lesions persist 1, 2

Escalation to Intravenous Therapy

Switch to intravenous acyclovir 10 mg/kg every 8 hours when any of the following are present: 1, 2

Disseminated herpes zoster (≥3 dermatomes, visceral involvement, or hemorrhagic lesions)
Severe immunosuppression (active chemotherapy, HIV with low CD4 count, organ transplantation, high-dose corticosteroids >40 mg prednisone daily)
CNS complications (encephalitis, meningitis, Guillain-Barré syndrome)
Complicated facial/ophthalmic disease with risk of cranial nerve or vision-threatening complications
Lack of clinical improvement after 7–10 days of oral therapy, suggesting possible acyclovir resistance

Duration and Monitoring for IV Therapy

Continue IV acyclovir for a minimum of 7–10 days and until clinical resolution (all lesions scabbed, fever resolved) 1, 2
Obtain baseline renal function and monitor weekly (or twice weekly) during IV therapy; adjust dosing for renal impairment 1
Watch for thrombotic thrombocytopenic purpura/hemolytic uremic syndrome in immunocompromised patients receiving high-dose therapy 1
Switch to oral therapy once clinical improvement occurs to complete the treatment course 2

Management of Immunocompromised Patients

Immunocompromised patients with uncomplicated herpes zoster should receive oral valacyclovir 1 gram three times daily or acyclovir 800 mg five times daily, with close monitoring for dissemination. 1, 2

Special Considerations

For disseminated or invasive disease, initiate IV acyclovir 10 mg/kg every 8 hours immediately 1, 2
Temporarily reduce or discontinue immunosuppressive medications when clinically feasible in cases of disseminated/invasive herpes zoster 1, 2
Restart immunosuppression only after all vesicular lesions have crusted, fever has resolved, and the patient shows clinical improvement on antiviral therapy 1
Immunocompromised patients may require extended treatment beyond 7–10 days, as lesions develop over 7–14 days and heal more slowly 1
Prophylactic acyclovir 400 mg daily or valacyclovir should be considered for patients receiving proteasome inhibitor-based therapies (e.g., bortezomib) or B-cell depleting agents 1

Acyclovir-Resistant Herpes Zoster

For confirmed acyclovir-resistant VZV, switch to foscarnet 40 mg/kg IV every 8 hours until clinical resolution. 1, 2

Recognition and Confirmation

Suspect resistance when cutaneous lesions have not begun to resolve within 7–10 days of appropriate antiviral therapy 1
Obtain viral culture with susceptibility testing to confirm resistance 1
Acyclovir-resistant strains are rare in immunocompetent patients but occur in up to 7% of immunocompromised patients 1
All acyclovir-resistant strains are also resistant to valacyclovir, and most are resistant to famciclovir 1

Foscarnet Monitoring

Foscarnet requires close monitoring of renal function and electrolytes (hypocalcemia, hypophosphatemia, hypomagnesemia, hypokalemia) 2

Pain Management

Acute Neuropathic Pain

Initiate gabapentin as first-line therapy for acute zoster-associated neuropathic pain, titrating in divided doses up to 2400 mg daily. 1

Gabapentin improves sleep quality but causes somnolence in approximately 80% of patients—counsel accordingly 1
Pregabalin may be added for patients whose pain remains uncontrolled with gabapentin alone 1
Tricyclic antidepressants (amitriptyline, nortriptyline, desipramine) are effective alternatives, particularly for patients with sleep disturbance 5

Topical Therapies

A single application of 8% capsaicin patch (or 30-minute cream application) provides analgesia lasting at least 12 weeks for chronic peripheral neuropathic pain 1
Apply 4% lidocaine for 60 minutes before capsaicin to mitigate erythema and burning 1
Topical lidocaine patches are effective for localized PHN 5
Topical antivirals are substantially less effective than systemic therapy and should not be used 1

Adjunctive Analgesics

Over-the-counter analgesics (acetaminophen, ibuprofen) provide relief for acute pain in otherwise healthy adults 1
Opioid analgesics (tramadol, morphine, oxycodone) may be required for severe pain or PHN 6, 5
Application of topical ice or cold packs can reduce pain and swelling during the acute phase 1

Corticosteroid Use: Proceed with Extreme Caution

Corticosteroids may be considered as adjunctive therapy to antivirals in select cases of severe, widespread shingles, but carry significant risks that generally outweigh benefits. 1

Absolute Contraindications

Immunocompromised patients (HIV, cancer, chronic immunosuppression) should never receive corticosteroids during active shingles due to increased risk of disseminated infection 1
Patients with poorly controlled diabetes, history of steroid-induced psychosis, severe osteoporosis, or prior severe steroid toxicity should avoid prednisone 1

Risks in Elderly Patients

The elderly population most susceptible to shingles faces the highest risk of corticosteroid complications: infections, hypertension, myopathy, glaucoma, aseptic necrosis, cataracts, Cushing syndrome, weight gain, and osteopenia 1

Topical Corticosteroids

Never apply topical corticosteroids to active shingles lesions—this can increase viral replication, worsen infection, and promote dissemination 1

Vaccination for Prevention

The recombinant zoster vaccine (Shingrix) is strongly recommended for all adults aged ≥50 years, regardless of prior herpes zoster episodes. 1, 2

Timing and Efficacy

Shingrix provides >90% efficacy in preventing future herpes zoster episodes 1
Administer the two-dose series ideally before initiating immunosuppressive therapies 1
Vaccination can be given after recovery from an acute episode to prevent future recurrences 1
For patients on B-cell depleting therapy, administer Shingrix at least 4 weeks prior to the next scheduled dose to maximize immunogenicity 1

Contraindications

Live-attenuated vaccine (Zostavax) is contraindicated in immunocompromised patients due to risk of uncontrolled viral replication 1
Shingrix (recombinant vaccine) is not live and is under investigation for immunocompromised populations 1

Post-Exposure Prophylaxis

For varicella-susceptible patients exposed to active varicella zoster infection, administer varicella zoster immunoglobulin (VZIG) within 96 hours of exposure. 1, 2

High-Risk Populations Requiring VZIG

Pregnant women 1
Immunocompromised patients (HIV-infected, organ transplant recipients) 1
Premature newborns <28 weeks gestation or <1,000 g 1

Alternative if VZIG Unavailable

If immunoglobulin is unavailable or >96 hours have passed, initiate a 7-day course of oral acyclovir beginning 7–10 days after varicella exposure 1, 2

Infection Control Measures

Patients with active herpes zoster must avoid contact with susceptible individuals until all lesions have completely crusted. 1

Cover lesions with clothing or dressings to minimize transmission risk 1
Healthcare workers with herpes zoster should be excluded from duty until all lesions dry and crust 1
For disseminated zoster (≥3 dermatomes), implement both airborne and contact precautions in addition to standard precautions 1
Physical separation of at least 6 feet from other patients is recommended in healthcare settings 1

Renal Dosing and Safety

Measure serum creatinine and calculate creatinine clearance before initiating valacyclovir or acyclovir to identify patients requiring dose modification. 1

Valacyclovir Dose Adjustments

Creatinine Clearance	Recommended Dose
30–49 mL/min	500 mg–1 g every 12 hours
10–29 mL/min	500 mg–1 g every 24 hours
<10 mL/min	500 mg every 24 hours

Hydration and Monitoring

Ensure adequate hydration during therapy to reduce risk of crystalluria and obstructive nephropathy, which occurs in up to 20% of patients 1
For IV acyclovir, monitor renal function weekly (or twice weekly) throughout treatment 1

Common Pitfalls to Avoid

Do not discontinue antiviral therapy at exactly 7 days if lesions are still forming or have not completely scabbed—short-course therapy designed for genital herpes is inadequate for VZV infection 1
Do not rely on topical antivirals—they are substantially less effective than systemic therapy 1
Do not delay treatment waiting for the 72-hour window to close—initiate antivirals as soon as possible after rash onset 1, 4
Do not use standard oral dosing in severely immunocompromised patients—these patients require IV therapy 1, 2
Do not apply any topical products to active vesicular lesions—wait until lesions have crusted before using emollients 1

What is the appropriate treatment regimen for shingles in an adult, including antiviral dosing, pain control, management of immunocompromised patients, and prevention with vaccination?

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