What is the recommended dose of Foscarnet (Foscarnet) for the treatment of Cytomegalovirus (CMV) infections?

Foscarnet Dosing for CMV Infections

For CMV retinitis and disseminated disease, administer foscarnet 60 mg/kg IV every 8 hours (or 90 mg/kg every 12 hours) for 14-21 days as induction therapy, followed by 90 mg/kg IV once daily for maintenance. 1, 2

Induction Therapy Dosing

Standard CMV Disease:

• Administer 60 mg/kg IV every 8 hours for 14-21 days, with each dose infused over 1-2 hours 1, 2
• Alternative regimen: 90 mg/kg IV every 12 hours (infused over 1.5-2 hours) achieves similar efficacy 1, 2
• The every-8-hour regimen is more commonly cited in pediatric HIV guidelines, though both achieve comparable outcomes 1

CMV Encephalitis (Severe Disease):

• Mandatory combination therapy: foscarnet 60 mg/kg IV every 8 hours PLUS ganciclovir 5 mg/kg IV every 12 hours for 3 weeks 1, 3
• This combination achieves improvement or stabilization in 74% of HIV patients with CMV encephalitis or myelitis 1, 3
• Monotherapy with either agent frequently fails in CNS disease 3

Maintenance Therapy

• Start with 90 mg/kg IV once daily as the initial maintenance dose 1, 2
• Escalate to 120 mg/kg IV once daily if early retinitis progression occurs during maintenance 1, 2
• The superiority of 120 mg/kg/day has not been established in controlled trials, and higher doses correlate with increased toxicity 2
• Maintenance therapy must be lifelong, as CMV disease is not cured with current antiviral agents 1, 3

Critical Administration Requirements

Infusion Rate:

• Never infuse faster than 1 mg/kg/minute; use an infusion pump to control the rate 1, 2
• All doses require 1-2 hour infusions to minimize acute toxicity 1, 2

Hydration Protocol:

• Aggressive saline hydration both before and during treatment is mandatory to establish diuresis and minimize nephrotoxicity 1, 2
• This is the single most important intervention to prevent renal toxicity 1

Renal Function Monitoring and Dose Adjustment

• Decreased renal function occurs in up to 30% of patients due to acute tubular toxicity 1
• Dose modification is required for renal insufficiency; use manufacturer's nomograms based on creatinine clearance 2
• If creatinine clearance falls below 0.4 mL/min/kg, discontinue foscarnet, hydrate the patient, and monitor daily until renal function resolves 2
• Foscarnet is not recommended in patients undergoing hemodialysis, as dosage guidelines have not been established 2

Metabolic Monitoring Requirements

Essential Laboratory Monitoring:

• Monitor calcium, phosphorus, magnesium, and potassium levels regularly, as metabolic abnormalities occur in approximately one-third of patients 1
• Monitor serum creatinine at baseline and throughout therapy 2
• Fluctuations in serum calcium and phosphorus (both increases and decreases) are frequent adverse reactions 4

Clinical Indications and Special Considerations

When to Use Foscarnet:

• First-line alternative when ganciclovir-induced myelosuppression is prohibitive 1
• First-line therapy for ganciclovir-resistant CMV strains 1, 4
• Preferred in patients requiring concurrent zidovudine or trimethoprim/sulfamethoxazole, as foscarnet lacks myelosuppressive effects 5

Common Pitfalls:

• Penile ulcerations may occur from mucocutaneous direct toxicity of foscarnet eliminated in urine 4
• Hyperphosphatemia is clinically benign and reflects foscarnet incorporation into bone 4
• Most clinical symptoms relate to decreased ionized calcium levels, not total calcium 4