A 32-year-old woman presents with painful vesicular lesions on the lower lip and surrounding skin for 3 days. She has a history of recurrent herpes simplex labialis. What is the drug of choice for treatment?

Explanation

## First-Line Antiviral for Herpes Simplex Labialis **Key Point:** Acyclovir is the gold-standard, first-line antiviral for herpes simplex virus (HSV) infection of the skin, including recurrent labial herpes. ### Mechanism of Action Acyclovir is a nucleoside analogue that: 1. Undergoes phosphorylation by viral thymidine kinase (TK) 2. Forms acyclovir triphosphate 3. Inhibits viral DNA polymerase and causes chain termination 4. Achieves selective toxicity because viral TK phosphorylates it ~200× more efficiently than cellular kinases ### Dosing for Recurrent Labial Herpes - **Topical:** 5% cream applied 5–6 times daily for 5–7 days (best if started within 48 hours of symptom onset) - **Oral:** 400 mg 5 times daily for 5 days (for more severe or disseminated disease) ### Comparative Antiviral Efficacy | Drug | Bioavailability | Dosing Frequency | Indication | Notes | |------|-----------------|------------------|-----------|-------| | Acyclovir | 15–20% (oral) | 5× daily | HSV-1/2, VZV (all types) | First-line; most experience | | Valacyclovir | 54% (oral) | 2–3× daily | HSV-1/2, VZV | Prodrug of acyclovir; better oral absorption | | Famciclovir | 77% (oral) | 2–3× daily | HSV-1/2, VZV | Prodrug of penciclovir; good for immunocompromised | | Penciclovir | Limited (topical) | 2 hourly | Labial HSV only | Topical only; shorter duration of viral shedding | **High-Yield:** Acyclovir remains the gold standard for initial and recurrent HSV skin infections due to: - Decades of clinical experience and safety data - Lowest cost - Efficacy when started early (within 48–72 hours) - Oral and topical formulations available **Clinical Pearl:** Valacyclovir and famciclovir are prodrugs with superior oral bioavailability and less frequent dosing, making them preferred in immunocompromised patients or when compliance is a concern. However, for straightforward recurrent labial herpes in an immunocompetent patient, acyclovir remains first-line. **Warning:** Penciclovir is topical-only and has no systemic bioavailability; it is not appropriate for systemic HSV infection or severe labial disease.