What is the recommended treatment for painful herpes simplex?

Treatment of Painful Herpes Simplex

For painful herpes simplex infections, initiate oral antiviral therapy immediately with valacyclovir, famciclovir, or acyclovir, as these systemic agents are the most effective treatments for reducing pain and accelerating healing. 1

First-Line Treatment Options by Clinical Presentation

Herpes Labialis (Cold Sores)

• Valacyclovir 2g twice daily for 1 day is the preferred first-line treatment, reducing median episode duration by 1.0 day compared to placebo 2, 3
• Famciclovir 1500mg as a single dose is equally effective, offering convenient single-day dosing and significantly reducing healing time of primary lesions 1, 2, 4
• Acyclovir 400mg five times daily for 5 days is an alternative but requires more frequent dosing 1, 5

Critical timing consideration: Treatment must be initiated at the first sign of prodrome (tingling, itching, burning, pain) or within 24 hours of lesion onset for maximum efficacy, as peak viral titers occur in the first 24 hours 2, 3

Genital Herpes - First Episode

• Acyclovir 400mg orally three times daily for 7-10 days, OR 1
• Acyclovir 200mg orally five times daily for 7-10 days, OR 1
• Famciclovir 250mg orally three times daily for 7-10 days, OR 1
• Valacyclovir 1g orally twice daily for 7-10 days 1

Treatment may be extended if healing is incomplete after 10 days 1

Genital Herpes - Recurrent Episodes

• Acyclovir 400mg orally three times daily for 5 days, OR 1
• Acyclovir 200mg orally five times daily for 5 days, OR 1
• Acyclovir 800mg orally twice daily for 5 days, OR 1
• Famciclovir 125mg orally twice daily for 5 days, OR 1
• Valacyclovir 500mg orally twice daily for 5 days 1

Suppressive Therapy for Frequent Recurrences

Patients with six or more recurrences per year should receive daily suppressive therapy, which reduces recurrence frequency by ≥75% 1, 2

Recommended Suppressive Regimens

• Acyclovir 400mg orally twice daily (documented safety for up to 6 years), OR 1, 2
• Famciclovir 250mg orally twice daily (documented safety for 1 year), OR 1, 2
• Valacyclovir 500mg once daily (can increase to 1000mg once daily for very frequent recurrences ≥10 episodes/year) 1, 2

After 1 year of continuous suppressive therapy, discontinuation should be discussed to reassess recurrence rate, as frequency decreases over time in many patients 1, 2

Severe Disease Requiring Hospitalization

IV acyclovir 5-10 mg/kg body weight every 8 hours for 5-7 days should be provided for patients with severe disease or complications necessitating hospitalization, such as disseminated infection, pneumonitis, hepatitis, or CNS complications (meningitis or encephalitis) 1

Special Populations

HIV-Infected Patients

• Famciclovir 500mg twice daily for 7 days for recurrent orolabial or genital herpes 4
• Treatment should be initiated within 48 hours of symptom onset 4
• Higher doses or longer treatment durations may be required 3
• Acyclovir resistance rates are higher (7% vs <0.5% in immunocompetent patients) 2, 3

Immunocompromised Patients

• Episodes are typically longer and more severe, potentially involving the oral cavity or extending across the face 2
• Higher doses or longer treatment durations may be required 3
• For confirmed acyclovir-resistant HSV, IV foscarnet 40mg/kg three times daily is the treatment of choice 2, 3

Comparative Efficacy and Practical Considerations

Valacyclovir and famciclovir offer superior convenience due to less frequent dosing compared to acyclovir, which may improve adherence, though they are more expensive 3, 5, 6, 7

All three oral antivirals (acyclovir, valacyclovir, famciclovir) are comparable in clinical outcomes, with common side effects including headache (<10%), nausea (<4%), and diarrhea, which are typically mild to moderate 2, 3

Critical Pitfalls to Avoid

• Never rely solely on topical antivirals: Topical therapy with acyclovir is substantially less effective than systemic drugs and its use is discouraged 1, 2
• Do not delay treatment: Efficacy decreases significantly when treatment is initiated after lesions have fully developed 2, 3
• Do not underdose: Ensure appropriate dosing for the specific indication (e.g., herpes labialis requires higher single doses than genital herpes) 1, 2, 4
• Adjust for renal impairment: Dosage reduction is mandatory in patients with renal disease to prevent acute renal failure 4
• Do not overlook suppressive therapy: Failing to consider suppressive therapy in patients with ≥6 recurrences per year who could significantly benefit 2

Patient Counseling Points

• Patients should identify and avoid personal triggers including UV light exposure, fever, psychological stress, and menstruation 2
• Patients should be provided with antiviral medication or a prescription so treatment can be initiated at the first sign of prodrome 1
• Suppressive therapy reduces but does not eliminate asymptomatic viral shedding 1, 2
• Resistance to oral antivirals when used episodically in immunocompetent patients is unlikely (<0.5%) 2