What is the recommended oral antiviral (antiviral medication taken by mouth) treatment for herpes simplex?

Oral Antiviral Treatment for Herpes Simplex

For herpes simplex infections, the recommended first-line oral antivirals are valacyclovir, famciclovir, or acyclovir, with valacyclovir and famciclovir offering superior convenience due to less frequent dosing compared to acyclovir. 1

Treatment Regimens by Clinical Presentation

Herpes Labialis (Cold Sores)

Episodic Treatment:

• Valacyclovir 2g twice daily for 1 day is the preferred first-line treatment, reducing median episode duration by 1.0 day compared to placebo 1
• Famciclovir 1500mg as a single dose is equally effective, offering convenient single-day dosing 1
• Acyclovir 400mg five times daily for 5 days is an alternative but requires more frequent dosing 1
• Treatment must be initiated at the earliest sign of prodrome (tingling, itching, burning) or within 24 hours of symptom onset for maximum efficacy 1

Suppressive Therapy (for ≥6 recurrences per year):

• Valacyclovir 500mg once daily (can increase to 1000mg once daily for very frequent recurrences) 1
• Famciclovir 250mg twice daily 1
• Acyclovir 400mg twice daily 1
• Daily suppressive therapy reduces recurrence frequency by ≥75% 1

Genital Herpes

Initial Episode:

• Acyclovir 400mg orally three times daily for 7-10 days 1
• Valacyclovir 1g twice daily for 10 days 1

Recurrent Episodes:

• Valacyclovir 500mg twice daily for 3 days (3-day course is FDA-approved for episodic treatment) 1, 2
• Famciclovir 1000mg twice daily for 1 day 1
• Acyclovir 400mg three times daily for 3-5 days 3

Suppressive Therapy:

• Valacyclovir 500-1000mg once daily 1, 4
• Famciclovir 250mg twice daily 1
• Acyclovir 400mg twice daily 1, 4

Herpes Simplex Keratitis/Conjunctivitis

When corneal involvement is present:

• Acyclovir 200-400mg five times per day 5
• Valacyclovir 500mg two or three times per day 5
• Famciclovir 250mg twice daily 5
• Must be combined with topical antiviral therapy (ganciclovir 0.15% gel or trifluridine 1% solution) 5
• Topical corticosteroids potentiate HSV infection and should be avoided unless treating secondary stromal keratitis, in which case they must be used in conjunction with oral antivirals 5

Duration of Suppressive Therapy

• Acyclovir has documented safety and efficacy for up to 6 years of continuous use 1
• Valacyclovir and famciclovir have documented safety for 1 year of continuous use 1
• After 1 year of suppressive therapy, consider a trial off medication to reassess recurrence frequency, as disease activity naturally decreases over time in many patients 1

Special Populations

Immunocompromised Patients

• Episodes are typically longer and more severe, potentially involving the oral cavity or extending across the face 1
• Higher doses or longer treatment durations may be required 1
• Acyclovir resistance rates are 7% in immunocompromised patients versus <0.5% in immunocompetent hosts 1
• For confirmed acyclovir-resistant HSV, IV foscarnet 40mg/kg three times daily is the treatment of choice 1, 6

Neonates

• Require prompt consultation with pediatrician or primary care physician, as systemic HSV infection is life-threatening 5

Critical Timing Considerations

• Peak viral titers occur in the first 24 hours after lesion onset, making early intervention essential for blocking viral replication 1
• Treatment efficacy decreases significantly when initiated after lesions have fully developed 1
• Patient-initiated episodic therapy at first symptoms may prevent lesion development in some cases 1

Common Pitfalls to Avoid

• Relying solely on topical antivirals, which provide only modest clinical benefit and cannot reach the site of viral reactivation in dorsal root ganglia 1, 7
• Failing to consider suppressive therapy in patients with ≥6 recurrences per year who could significantly benefit 1
• Starting treatment too late after symptom onset 1
• Using inadequate dosing regimens (e.g., not using short-course, high-dose therapy which is more effective than traditional longer courses) 1
• Not discussing potential triggers (UV light exposure, stress, fever, menstruation) that patients should avoid even while on suppressive therapy 1

Safety Profile

• All oral antivirals (acyclovir, valacyclovir, famciclovir) are generally well-tolerated with minimal adverse events 1
• Common side effects include headache (<10%), nausea (<4%), and diarrhea, which are typically mild to moderate 1
• Despite increasing use, the incidence of resistant HSV-1 strains remains low (<0.5% in immunocompetent hosts) 1
• Development of resistance with episodic use in immunocompetent patients is unlikely (<0.5%) 1

Key Patient Counseling Points

• Oral antivirals are not a cure for herpes simplex and do not eliminate asymptomatic viral shedding 1, 8
• Patients should avoid contact with lesions and practice safer sex, as transmission can occur even during asymptomatic periods 8
• Identify and avoid personal triggers including UV light exposure, fever, psychological stress, and menstruation 1
• For episodic therapy, patients should initiate treatment at the earliest sign of prodrome 1, 8