Treatment of Cold Sores
Oral valacyclovir 2g twice daily for 1 day is the most effective treatment for cold sores, especially when started at the first sign of symptoms. 1
First-Line Treatment Options
Oral Antiviral Therapy
- Preferred regimen: Valacyclovir 2g twice daily for 1 day 1, 2
- Alternative valacyclovir regimen: 2g twice daily on day 1, then 1g twice daily on day 2 1
- Alternative oral antivirals:
Oral valacyclovir is superior to other treatments due to its better bioavailability compared to acyclovir, providing 3-5 times higher systemic concentrations 2. Clinical trials have demonstrated that the 1-day valacyclovir regimen reduces the median duration of cold sore episodes by approximately 1 day compared to placebo 2.
Timing of Treatment
Treatment should be initiated as early as possible, ideally during the prodromal stage (tingling, burning sensation) before visible lesions appear. The FDA label notes that "efficacy of VALTREX initiated after the development of clinical signs of a cold sore has not been established" 3, highlighting the importance of early intervention.
Topical Treatment Options
- Acyclovir 5% cream applied 5 times daily for 4 days (modest effect) 1
- Docosanol can be used as an alternative if oral medication is unavailable 1
Treatment by Stage of Cold Sore
Prodromal Stage (tingling/burning):
- Immediate oral antiviral therapy (valacyclovir or famciclovir)
- This is the optimal time to start treatment for maximum effectiveness
Vesicular Stage (blister formation):
- Continue oral antiviral therapy if started early
- Avoid touching or breaking blisters to prevent secondary infection
Crusting Stage:
- Focus on moisturizing with white soft paraffin
- Keep the area clean to prevent secondary infection
Healing Stage:
- Continue moisturizing until completely healed
- Protect from sun exposure with SPF 15+
Symptomatic Relief
- Apply white soft paraffin ointment every 2 hours to prevent cracking and bleeding 1
- Pain management options:
- Benzydamine hydrochloride oral rinse/spray every 3 hours
- Topical lidocaine 2% for severe pain
- Mixture of Maalox and diphenhydramine for pain relief 1
- Antiseptic oral rinse twice daily (0.2% chlorhexidine) to prevent secondary infection 1
Special Populations
Pregnant Patients
- Acyclovir 400mg orally three times daily for 5-7 days is preferred due to its established safety profile 1
Immunocompromised Patients
- Higher doses of acyclovir (400mg five times daily) and longer treatment duration (7-10 days) 1
- For severe cases: IV acyclovir 5-10 mg/kg every 8 hours until lesions heal 1
- In cases of acyclovir-resistant HSV (rare but more common in immunocompromised patients), consider foscarnet 40mg/kg three times daily 1, 4
Prevention of Recurrence
- Use sunscreen (SPF 15+) to prevent UV-triggered recurrences 1, 5
- Avoid known triggers: UV radiation, fever, psychological stress, and local trauma 1
- For frequent recurrences, suppressive therapy may be considered
Common Pitfalls and Caveats
Delayed treatment: Starting treatment after lesions appear significantly reduces effectiveness. Patients should be educated to recognize prodromal symptoms and start treatment immediately.
Inadequate dosing: Using lower doses than recommended (especially with valacyclovir) reduces efficacy. The high-dose, short-duration regimen is specifically designed for cold sores.
Treatment resistance: While rare in immunocompetent patients, acyclovir-resistant HSV can occur in immunocompromised individuals. If lesions don't improve after 7-10 days of treatment, consider resistance and alternative therapies like topical trifluridine or intravenous foscarnet 1, 4.
Confusing cold sores with other conditions: Ensure proper diagnosis, as angular cheilitis, impetigo, or allergic contact dermatitis can mimic cold sores but require different treatments.
The treatment landscape for cold sores has evolved, with a trend toward using newer antiviral medications like valacyclovir over acyclovir due to better bioavailability and more convenient dosing 6.