What is the recommended dose of Foscarnet (Foscarnet) for treating resistant Herpes Simplex Virus (HSV) mucositis and blood infection?

Foscarnet Dosing for Acyclovir-Resistant HSV Mucositis and Bloodstream Infection

For acyclovir-resistant HSV mucositis and disseminated infection, administer foscarnet 40 mg/kg intravenously every 8 hours (or every 12 hours as an alternative) for 2-3 weeks or until complete clinical resolution and lesion healing is achieved. 1, 2

Induction Dosing Regimen

Standard dosing for acyclovir-resistant HSV:

• 40 mg/kg IV every 8 hours is the primary recommended regimen 1, 2
• 40 mg/kg IV every 12 hours is an acceptable alternative dosing schedule 1, 2
• Each infusion must be administered over a minimum of 1 hour using an infusion pump 2
• Continue treatment for 2-3 weeks or until complete healing of all lesions 1, 2

The FDA label explicitly states these two dosing options are equivalent (80 mg/kg/day total when dosed every 12 hours, or 120 mg/kg/day total when dosed every 8 hours), providing flexibility based on clinical circumstances and patient tolerance 2.

Critical Treatment Considerations

Hydration requirements:

• Establish adequate diuresis both before and during foscarnet therapy to minimize nephrotoxicity 2
• This is mandatory unless clinical contraindications exist 2

When to suspect acyclovir resistance:

• If mucocutaneous HSV lesions fail to begin resolving within 7-10 days of standard acyclovir therapy 1
• Obtain viral culture with susceptibility testing to confirm resistance before initiating foscarnet 1

Disseminated/bloodstream infection considerations:

• For severe disease with systemic involvement (bloodstream infection), hospitalization should be strongly considered 1
• The same dosing regimen (40 mg/kg every 8 hours) applies to both mucocutaneous and disseminated disease 1, 2

Renal Dose Adjustments

Foscarnet requires careful dose modification based on creatinine clearance 2:

For the 40 mg/kg every 12 hours regimen (equivalent to 80 mg/kg/day total):

• CrCl >1.4 mL/min/kg: 40 mg/kg every 12 hours 2
• CrCl >1.0-1.4: 30 mg/kg every 12 hours 2
• CrCl >0.8-1.0: 20 mg/kg every 12 hours 2
• CrCl >0.6-0.8: 35 mg/kg every 24 hours 2
• CrCl >0.5-0.6: 25 mg/kg every 24 hours 2
• CrCl >0.4-0.5: 20 mg/kg every 24 hours 2
• CrCl <0.4: Not recommended - discontinue foscarnet, hydrate patient, and monitor daily until renal function improves 2

For the 40 mg/kg every 8 hours regimen (equivalent to 120 mg/kg/day total):

• CrCl >1.4 mL/min/kg: 40 mg/kg every 8 hours 2
• CrCl >1.0-1.4: 30 mg/kg every 8 hours 2
• CrCl >0.8-1.0: 35 mg/kg every 12 hours 2
• CrCl >0.6-0.8: 25 mg/kg every 12 hours 2
• CrCl >0.5-0.6: 40 mg/kg every 24 hours 2
• CrCl >0.4-0.5: 35 mg/kg every 24 hours 2
• CrCl <0.4: Not recommended 2

Calculate creatinine clearance using the modified Cockcroft-Gault equation: (140 - age) × 0.85 for females / (serum creatinine × 72) = mL/min/kg 2

Monitoring Requirements

Renal function monitoring is essential:

• Check creatinine clearance at baseline 2
• Monitor once or twice weekly during treatment 1, 2
• If CrCl falls below 0.4 mL/min/kg, discontinue foscarnet immediately, provide hydration, and monitor daily until renal function recovers 2

Electrolyte monitoring:

• Monitor serum calcium and phosphorus levels regularly, as foscarnet causes frequent fluctuations 3
• Most clinical symptoms relate to decreased ionized calcium levels 3
• Hyperphosphatemia is common but clinically benign, reflecting foscarnet incorporation into bone 3

Clinical Efficacy Data

Evidence supporting foscarnet for acyclovir-resistant HSV:

• In controlled trials, lesions healed in 11-25 days in patients randomized to foscarnet 2
• A second trial showed healing in 11-72 days with no difference between every 8-hour versus every 12-hour dosing 2
• An uncontrolled trial using 60 mg/kg every 8 hours (higher dose) showed dramatic improvement with marked clearing of mucocutaneous lesions in all four AIDS patients treated 4

The evidence consistently demonstrates that both the every 8-hour and every 12-hour regimens are effective, though the every 8-hour schedule provides higher total daily exposure 2, 5.

Common Pitfalls and How to Avoid Them

Nephrotoxicity prevention:

• The major adverse effect is reversible acute tubular toxicity 3
• Mandatory hyperhydration during treatment can partially prevent this complication 3
• Never exceed recommended infusion rates or doses 2

Penile ulcerations:

• These may result from direct mucocutaneous toxicity of foscarnet eliminated in urine 3
• Ensure adequate hydration and consider protective measures

Cross-resistance:

• All acyclovir-resistant strains are also resistant to valacyclovir 6, 7
• Most are resistant to famciclovir 7
• Do not waste time trying these alternatives once acyclovir resistance is confirmed 6, 7

Hemodialysis patients:

• Foscarnet is not recommended in patients undergoing hemodialysis because dosage guidelines have not been established 2

Alternative Topical Therapy for Accessible Lesions

For mucocutaneous lesions on external surfaces:

• Topical trifluridine, cidofovir, or imiquimod can be used as adjuncts 1
• These require prolonged application for 21-28 days or longer 1
• Topical cidofovir gel 1% applied once daily for 5 consecutive days may be effective for localized lesions 7

However, for disseminated disease or bloodstream infection, systemic IV foscarnet remains the treatment of choice and topical therapy is insufficient 1.

Maintenance Therapy Considerations

For recurrent acyclovir-resistant HSV:

• Preliminary evidence supports foscarnet maintenance therapy in delaying recurrence 5
• However, relapses frequently occur after a few months of maintenance therapy 3
• Some initial recurrences may be due to acyclovir-sensitive HSV, suggesting potential utility of acyclovir maintenance following foscarnet induction 5