What is the recommended intravenous acyclovir regimen, dosing adjustments, and monitoring for a patient with a severe genital herpes outbreak (e.g., immunocompromised with extensive mucocutaneous involvement or systemic symptoms)?

Intravenous Acyclovir for Severe Genital Herpes Outbreaks

For severe genital herpes requiring hospitalization—including immunocompromised patients with extensive mucocutaneous disease or systemic complications—administer intravenous acyclovir 5–10 mg/kg every 8 hours for 5–7 days or until clinical resolution. 1, 2

Indications for IV Therapy

Escalate to intravenous acyclovir when any of the following are present:

• Severe disease requiring hospitalization (e.g., extensive mucocutaneous involvement, inability to tolerate oral medications) 1
• Disseminated infection involving visceral organs such as hepatitis, pneumonitis, or encephalitis 1, 3
• Immunocompromised status (HIV infection, transplant recipients, chemotherapy patients) where prolonged episodes with extensive disease are common 1, 2
• Complications such as urinary retention, extragenital lesions, or systemic symptoms 4

Dosing Regimen

• Standard dose: Acyclovir 5–10 mg/kg IV every 8 hours 1, 2, 3
• Duration: Continue for 5–7 days or until clinical improvement is achieved 1, 2
• Administration: Infuse over 1 hour to minimize nephrotoxicity 3

The FDA label documents that steady-state peak concentrations with 5 mg/kg every 8 hours average 9.8 mcg/mL (range 5.5–13.8), while 10 mg/kg achieves 22.9 mcg/mL (range 14.1–44.1). 3 Clinical trials demonstrate that IV acyclovir substantially decreases symptoms, duration of lesions, and complications of primary genital herpes, reducing median viral shedding from 13 days (placebo) to 2 days (acyclovir). 4

Renal Dose Adjustments

Acyclovir is primarily renally excreted (62–91% unchanged), making dose adjustment mandatory in renal impairment. 3

• CrCl >80 mL/min: No adjustment needed; half-life 2.5 hours 3
• CrCl 50–80 mL/min: Half-life increases to 3 hours; consider dose reduction 3
• CrCl 15–50 mL/min: Half-life 3.5 hours; reduce dose or extend interval 3
• Anuric patients: Half-life 19.5 hours; substantial dose reduction required 3
• Hemodialysis: Peak levels of 8.5 mcg/mL and trough of 0.7 mcg/mL were observed in severe renal failure patients receiving 2.5 mg/kg 3

Monitoring Requirements

• Ensure adequate hydration before and during infusion to prevent crystalline nephropathy 2
• Monitor serum creatinine daily, especially in patients with baseline renal impairment or receiving concurrent nephrotoxic agents 3
• Watch for proteinuria as a sign of nephrotoxicity 5
• Assess for neutropenia, the most common hematologic toxicity in children 2
• Evaluate clinical response daily; transition to oral therapy once lesions begin to regress 2

Transition to Oral Therapy

Once clinical improvement is evident (lesion regression, resolution of systemic symptoms), transition to oral acyclovir:

• Acyclovir 400 mg orally 3 times daily until complete healing 1, 2
• Alternative: Acyclovir 200 mg orally 5 times daily 1
• Immunocompromised patients may require higher doses (400 mg 3–5 times daily) and longer duration (14 days or until complete resolution) 2

Special Considerations for Immunocompromised Patients

HIV-infected and other immunocompromised patients require more aggressive therapy and closer monitoring. 1

• Prolonged episodes with extensive disease are common 1
• Higher doses may be necessary (consider 10 mg/kg rather than 5 mg/kg) 2, 3
• Extended duration beyond 7 days is often required until complete resolution 2
• Vigilance for acyclovir resistance is essential if lesions persist despite adequate therapy 2, 6

Management of Acyclovir-Resistant HSV

If lesions fail to respond after 7–10 days of appropriate IV acyclovir therapy in an immunocompromised patient, suspect resistance:

• Foscarnet 40 mg/kg IV every 8 hours or 60 mg/kg IV every 12 hours is the treatment of choice for acyclovir-resistant HSV 2, 7, 6
• Acyclovir resistance is an increasing problem in HIV-infected patients and those on prolonged suppressive therapy 6, 5

Common Pitfalls to Avoid

• Do not use topical acyclovir for severe or systemic disease; it is substantially less effective than systemic therapy and provides no improvement in systemic symptoms 1, 6
• Do not underdose in obese patients; calculate based on actual body weight 3
• Do not infuse rapidly; administer over 1 hour to minimize nephrotoxicity 3
• Do not forget hydration; inadequate fluid administration increases crystalline nephropathy risk 2
• Do not continue IV therapy unnecessarily; transition to oral once clinical improvement allows 2