What is the recommended dose of famciclovir (famciclovir) for an adult patient with normal renal function and impaired renal function?

Famciclovir Dosing Recommendations

Standard Dosing for Normal Renal Function

For adult patients with normal renal function, famciclovir dosing varies by indication: 500 mg orally three times daily for 7 days for herpes zoster, 125 mg orally twice daily for 5 days for recurrent genital herpes, and 1500 mg as a single dose for herpes labialis. 1, 2, 3

Herpes Zoster (Shingles)

• 500 mg orally three times daily for 7 days 1, 3
• Alternative regimens with comparable efficacy include 750 mg once daily or 500 mg twice daily for 7 days 4
• Treatment should be initiated within 72 hours of rash onset for optimal effectiveness 4

Recurrent Genital Herpes

• 125 mg orally twice daily for 5 days for episodic treatment 3
• For HIV-infected patients, higher doses may be beneficial: 500 mg twice daily 1

Herpes Labialis (Cold Sores)

• 1500 mg as a single dose (three 500 mg tablets) 2
• Treatment should be initiated within 1 hour of symptom onset for maximum benefit 2
• Note: This single-dose regimen showed limited efficacy in adolescents when treatment was delayed beyond 1 hour 2

Renal Dose Adjustments

Famciclovir requires significant dose reduction in renal impairment because penciclovir (the active metabolite) is predominantly eliminated by the kidneys, with renal clearance decreasing linearly as creatinine clearance declines. 1, 5

Creatinine Clearance 20-39 mL/min

• 500 mg every 24 hours (instead of 500 mg three times daily for herpes zoster) 1

Creatinine Clearance <20 mL/min

• 250 mg every 24 hours 1

Hemodialysis Patients

• 250 mg after each dialysis session 1
• Hemodialysis effectively clears penciclovir from plasma 5

Pharmacokinetic Rationale

The elimination half-life of penciclovir increases dramatically with renal impairment: from 2.3 hours in normal renal function to 13.4 hours when creatinine clearance is <20 mL/min 2. Renal clearance drops from 30.1 L/hr in normal function to just 1.6 L/hr in severe impairment 2.

Special Populations

Elderly Patients

• No dose adjustment needed based on age alone if renal function is normal or only mildly impaired 2, 3
• However, age-related decline in renal function is common, so calculate creatinine clearance and adjust dose accordingly 2
• Elderly patients tolerate famciclovir well despite slower elimination 5

Hepatic Impairment

• No dose adjustment required for mild to moderate hepatic impairment 2
• Severe hepatic impairment has not been studied, but conversion of famciclovir to penciclovir may be impaired, potentially reducing efficacy 2

HIV-Infected Patients

• Higher doses may be needed: 500 mg twice daily for recurrent genital herpes 1
• All acyclovir-resistant HSV strains are resistant to famciclovir 1

Safety Profile

Famciclovir is generally well tolerated with minimal adverse events, primarily headache (<10% of patients) and nausea (<4% of patients), which are mild to moderate in intensity. 1

Common Adverse Effects

• Headache and gastrointestinal upset are most frequent 3
• Adverse event rates are similar to placebo in controlled trials 1
• No serious adverse events reported in major clinical trials 1

Resistance

• HSV-1 resistance remains very low: <0.5% in immunocompetent hosts 1
• In immunocompromised patients, penciclovir resistance is 2.1% (compared to 7% for acyclovir) 1

Clinical Pearls and Pitfalls

Critical Considerations

• Always calculate creatinine clearance before prescribing, especially in elderly patients, as age-related renal decline may not be reflected in serum creatinine alone 2
• For herpes labialis, the single 1500 mg dose is only effective when initiated within 1 hour of symptom onset; delayed treatment shows minimal benefit 2
• Adequate hydration should be maintained, particularly in patients with borderline renal function 5

Advantages Over Acyclovir

• Less frequent dosing: three times daily versus five times daily for acyclovir 4, 3
• Better oral bioavailability: 77% for penciclovir from famciclovir versus lower absorption for acyclovir 6, 3
• Prolonged intracellular half-life: penciclovir-triphosphate persists 9-14 hours in VZV-infected cells versus 0.8 hours for acyclovir-triphosphate 6

When to Suspect Treatment Failure

• If lesions persist despite treatment, consider acyclovir resistance, which confers cross-resistance to famciclovir 1
• Foscarnet 40 mg/kg IV every 8 hours is the treatment of choice for resistant HSV 1