What is the recommended management of herpes zoster in adults, including antiviral therapy, analgesia, and vaccination?

Management of Herpes Zoster (Shingles) in Adults

Antiviral Therapy

Initiate antiviral therapy within 72 hours of rash onset with either valacyclovir 1000 mg three times daily or famciclovir 500 mg every 8 hours for 7 days, as these agents are preferred over acyclovir due to superior bioavailability and more convenient dosing. 1

Key Points on Antiviral Selection and Timing

• Valacyclovir and famciclovir are the first-line agents for herpes zoster in adults, offering better oral bioavailability than acyclovir while requiring less frequent administration 1
• The 72-hour window is critical: early antiviral initiation reduces rash duration, acute pain intensity, and may decrease postherpetic neuralgia (PHN) risk 1, 2
• Acyclovir 800 mg five times daily for 7 days remains an acceptable alternative, though less convenient, and meta-analysis shows it reduces residual pain at 6 months by 46% when started within 72 hours 3
• For immunocompromised patients with uncomplicated herpes zoster, oral antivirals are beneficial, but monitor closely for signs of cutaneous or visceral dissemination requiring intravenous therapy 4

Renal Dosing Considerations

• Adjust doses for renal impairment, particularly critical in elderly patients who commonly have reduced creatinine clearance 5
• Famciclovir and valacyclovir both require dose reduction based on creatinine clearance 5

---

Pain Management: Stepped Analgesic Approach

Begin with acetaminophen (up to 3000-4000 mg/day in divided doses) for mild pain, escalate to opioids for moderate-severe pain with scheduled dosing, and initiate gabapentin early (starting 100-300 mg at bedtime, titrating to 300-600 mg three times daily) to prevent postherpetic neuralgia. 1

Acute Pain Management Algorithm

Step 1: Mild Pain

• Acetaminophen is preferred due to its lower adverse effect profile in older adults 1
• NSAIDs should be used with extreme caution due to gastrointestinal toxicity, renal dysfunction, hypertension, and heart failure risk 1
• If NSAIDs are necessary, monitor gastrointestinal symptoms, renal function, blood pressure, and drug interactions routinely 1

Step 2: Moderate to Severe Pain

• Initiate opioids at low doses with gradual titration 1
• Use scheduled dosing rather than as-needed for continuous or frequent pain 1
• Anticipate and manage opioid-related adverse effects: sedation, cognitive impairment, falls, and constipation (prophylactic bowel regimen essential) 1

Step 3: Adjuvant Therapy for Neuropathic Pain

• Gabapentin should be considered from the acute phase alongside conventional analgesics to prevent PHN 1
  • Start: 100-300 mg at bedtime
  • Titrate gradually to 300-600 mg three times daily as tolerated 1
• Nortriptyline (preferred over amitriptyline in older adults due to lower anticholinergic burden) 1
  • Start: 10-25 mg at bedtime
  • Titrate slowly based on response and tolerability 1

Topical Therapies

• Lidocaine 5% patch is highly effective for localized neuropathic pain 1
  • Apply up to 3 patches over affected area for 12 hours daily 1
  • Significantly more effective than lidocaine gel or cream, with sustained analgesia through gradual delivery 1
  • No systemic absorption or toxicity documented with proper use, making it exceptionally safe for elderly patients 1
  • Minimal drug interactions due to negligible systemic absorption 1
• Capsaicin topical therapy may benefit a small proportion but is often poorly tolerated 1
• Compounded amitriptyline 1-2% with ketamine 0.5% can be applied up to 3 times daily if lidocaine fails 1

Medications to Avoid in Older Adults

• Muscle relaxants (cyclobenzaprine, carisoprodol): significant anticholinergic effects and increased fall risk 1
• Benzodiazepines: sedation, cognitive impairment, and increased fall risk 1

Special Considerations in Elderly Patients

• Older adults have increased drug accumulation risk due to altered pharmacokinetics: increased fat-to-lean body mass ratio and slowed gastrointestinal transit 1
• Start all medications at lower doses and titrate slowly 1

---

Vaccination Strategies

All adults aged 50 years and older should receive the 2-dose Shingrix (recombinant zoster vaccine) series, with the second dose administered 2-6 months after the first dose, regardless of prior herpes zoster history or previous Zostavax vaccination. 6

Primary Vaccination Recommendations

• Shingrix demonstrates 97.2% efficacy in preventing herpes zoster in adults ≥50 years, with protection persisting at least 8 years with minimal waning (efficacy >83.3%) 6, 1
• Administer intramuscularly in the deltoid region 6, 7
• Standard schedule: second dose at 2-6 months after first dose (minimum interval 4 weeks if necessary) 6
• For immunocompromised adults ≥18 years: shortened schedule with second dose at 1-2 months after first dose 6

Vaccination After Herpes Zoster Episode

• Vaccinate once acute symptoms have resolved, typically waiting at least 2 months after the episode 6
• Prior herpes zoster does not provide reliable protection against recurrence (10.3% cumulative recurrence risk at 10 years) 6
• Vaccination after an episode is strongly recommended to prevent future recurrences 6

Revaccination After Previous Zostavax

• All adults who previously received Zostavax should receive the full 2-dose Shingrix series 6
• Zostavax efficacy declines dramatically to only 14.1% by year 10 6
• Minimum interval: at least 2 months after Zostavax, though most patients received Zostavax years ago 6
• Shingrix offers significantly higher efficacy across all age groups compared to Zostavax (70% in ages 50-59 vs. 18% in ≥80 years for Zostavax) 6

Special Populations

Immunocompromised Patients:

• Shingrix is preferred and safe for immunocompromised patients (unlike live-attenuated Zostavax which is contraindicated) 6
• Includes patients with autoimmune inflammatory rheumatic diseases, those on immunosuppressive therapy, cancer patients, and transplant recipients 6
• Use shortened 1-2 month interval between doses 6

Patients on Glucocorticoids:

• Shingrix can be safely administered to patients on low-dose glucocorticoids (<10 mg/day prednisone equivalent) without adversely impacting vaccine response 6
• Studies show only mild disease flares (4-17%) after vaccination with no serious adverse events 6

Patients on JAK Inhibitors (e.g., Tofacitinib):

• Complete the full 2-dose Shingrix series before starting tofacitinib whenever possible to maximize immune response 6
• If urgent tofacitinib initiation required: administer at least first dose before starting therapy, complete second dose after starting tofacitinib 6
• Never use live-attenuated Zostavax in patients on or about to start JAK inhibitors 6

Patients with History of Herpetic Keratitis:

• Use Shingrix exclusively, not Zostavax 8
• Administer first dose when keratitis is completely quiescent for at least 2-3 months 8
• Shingrix contains only viral protein fragment (glycoprotein E) with adjuvant, reducing theoretical risk of viral reactivation compared to Zostavax 8
• Benefits of vaccination generally outweigh rare risk of reactivation 8

Common Side Effects

• Injection-site reactions (pain, redness, swelling) are common: 9.5% experience grade 3 reactions vs. 0.4% with placebo 6
• Systemic symptoms in 11.4% vs. 2.4% in placebo recipients 6
• Most side effects resolve within 4 days 6
• No serious safety concerns identified in large clinical trials 6

Booster Recommendations

• No additional booster doses beyond the initial 2-dose series are currently recommended 6

Contraindications

• History of severe allergic reaction (anaphylaxis) to any vaccine component or after previous Shingrix dose 7

---

Key Clinical Pitfalls to Avoid

• Do not delay antiviral therapy beyond 72 hours—efficacy diminishes significantly after this window 1, 2
• Do not use Zostavax in immunocompromised patients—only Shingrix is appropriate 6, 8
• Do not assume prior herpes zoster provides adequate protection—vaccination is still strongly indicated 6
• Do not use muscle relaxants or benzodiazepines for pain management in older adults due to fall risk and cognitive impairment 1
• Do not use NSAIDs without careful monitoring in elderly patients—acetaminophen is safer 1
• Do not forget renal dose adjustments for antivirals in elderly patients 5
• Do not use corticosteroids alone for herpetic keratitis—always combine with systemic antivirals 8