What are alternative medications to Valtrex (valacyclovir) for preventing genital herpes?

Alternative Medications to Valtrex for Genital Herpes Prevention

For suppressive therapy of recurrent genital herpes, acyclovir 400 mg orally twice daily and famciclovir 250 mg orally twice daily are the two CDC-recommended alternatives to valacyclovir. 1

First-Line Alternative: Acyclovir

Acyclovir 400 mg orally twice daily is the most established alternative for daily suppressive therapy, with documented safety and efficacy for up to 5 years of continuous use. 2, 3 This regimen reduces recurrence frequency by at least 75% in patients with frequent recurrences (≥6 episodes per year). 2, 1

Alternative Acyclovir Dosing Options

• Lower-dose regimens of acyclovir 200 mg orally 3-5 times daily can be used to identify the minimum effective dose for individual symptom control. 2
• After 1 year of continuous suppressive therapy, acyclovir should be discontinued temporarily to reassess the patient's natural recurrence rate. 2, 1

Key Advantages of Acyclovir

• Longest track record of safety data among all antivirals for genital herpes 2
• Significantly lower cost compared to valacyclovir 4
• Multiple dosing options allow flexibility 2, 3

Critical Limitation

• Requires twice-daily dosing minimum (compared to valacyclovir's once-daily option), which may reduce adherence. 4, 5

Second Alternative: Famciclovir

Famciclovir 250 mg orally twice daily is equally effective to acyclovir and valacyclovir for suppressive therapy. 1 This is a penciclovir prodrug with high bioavailability similar to valacyclovir. 4

Famciclovir Advantages

• Comparable efficacy to valacyclovir in reducing recurrence frequency 4, 6
• Better bioavailability than acyclovir, allowing less frequent dosing than standard acyclovir regimens 4
• Well-tolerated safety profile 6

Dosing Adjustments for Renal Impairment

All three medications require dose adjustment in renal impairment to prevent toxicity. 3

• For acyclovir 400 mg twice daily: reduce to 200 mg twice daily if creatinine clearance is 0-10 mL/min 3
• Close monitoring of renal function is mandatory during therapy 7

Critical Pitfalls to Avoid

• Never use topical acyclovir for genital herpes suppression—it is substantially less effective than oral therapy and is not recommended. 2, 1
• Avoid valacyclovir 8 g/day in immunocompromised patients due to risk of hemolytic uremic syndrome/thrombotic thrombocytopenic purpura. 1, 8
• Suppressive therapy does not eliminate asymptomatic viral shedding or completely prevent transmission, so patients must still use barrier protection and disclose their status to partners. 2, 1

When to Suspect Antiviral Resistance

• If lesions fail to begin resolving within 7-10 days of appropriate therapy, suspect acyclovir resistance. 1, 7
• Acyclovir-resistant strains are cross-resistant to valacyclovir and usually to famciclovir as well. 7
• For proven or suspected resistance, foscarnet 40 mg/kg IV every 8 hours is the treatment of choice. 1

Special Population Considerations

• HIV-infected patients may require higher doses or longer treatment courses, though the standard suppressive regimens (acyclovir 400 mg twice daily or famciclovir 250 mg twice daily) are generally effective. 2, 8
• Pregnant patients: routine suppressive therapy is not recommended during pregnancy, though the safety of acyclovir and valacyclovir has not been definitively established. 1