Foscarnet Dosing for CMV Infections
For CMV retinitis and disseminated disease, administer foscarnet 60 mg/kg IV every 8 hours for 14-21 days as induction therapy, followed by 90-120 mg/kg IV once daily for chronic suppression. 1, 2
Induction Therapy Dosing
Standard CMV Retinitis/Disseminated Disease
- 60 mg/kg IV every 8 hours for 14-21 days, with each dose infused over 1-2 hours (no faster than 1 mg/kg/minute) 1, 2
- Alternative FDA-approved regimen: 90 mg/kg IV every 12 hours for 2-3 weeks (infused over 1.5-2 hours) 2
- Both regimens achieve similar efficacy; the every-8-hour dosing is more commonly cited in pediatric HIV guidelines 1
CMV Encephalitis (Severe CNS Disease)
- Combination therapy required: Foscarnet 60 mg/kg IV every 8 hours PLUS ganciclovir 5 mg/kg IV every 12 hours, continued until symptoms improve 1
- This combination achieves improvement or stabilization in 74% of HIV patients with CMV encephalitis or myelitis 3
- Monotherapy frequently fails for CNS disease 1
Acyclovir-Resistant HSV
- 40 mg/kg IV every 8 or 12 hours for 2-3 weeks or until healed 2
Maintenance (Chronic Suppression) Therapy
- Start with 90 mg/kg IV once daily as the recommended initial maintenance dose 1, 2
- May escalate to 120 mg/kg IV once daily if early reinduction is required due to retinitis progression 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 3
Critical Administration Requirements
Infusion Rate and Hydration
- Never infuse faster than 1 mg/kg/minute (typically 1-2 hour infusion for each dose) 1, 2
- Mandatory use of infusion pump to control rate 2
- Aggressive hydration with saline both before and during treatment to establish diuresis and minimize nephrotoxicity 1, 2
Renal Function Monitoring and Dose Adjustment
- Monitor serum creatinine at baseline and during therapy with appropriate dose adjustments 1, 2
- Up to 30% of patients experience increased serum creatinine levels 1
- 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 hemodialysis patients due to lack of established dosing guidelines 2
Major Toxicities to Monitor
Nephrotoxicity (Most Common)
- Decreased renal function occurs in up to 30% of patients due to acute tubular toxicity 1, 4
- Can be partially prevented by hyperhydration during treatment 4
- Dose modification required for renal insufficiency 1
Electrolyte Abnormalities
- Foscarnet binds divalent metal ions (calcium, magnesium, phosphorus, potassium) causing metabolic abnormalities in approximately one-third of patients 1
- Monitor calcium, phosphorus, magnesium, and potassium levels regularly 1
- Can lead to secondary seizures, cardiac dysrhythmias, and CNS symptoms 1
Other Adverse Effects
- Abnormal liver transaminases 1
- Penile ulcerations (from direct mucocutaneous toxicity of foscarnet eliminated in urine) 4
- Muscle twitching, nausea, proteinuria 5
Clinical Pearls and Pitfalls
When to Use Foscarnet
- Alternative to ganciclovir when myelosuppression is prohibitive 1, 6
- First-line for ganciclovir-resistant CMV strains 1
- Mandatory for CMV encephalitis (in combination with ganciclovir) 1, 3
- Foscarnet has been associated with increased survival compared to ganciclovir in HIV-infected adults when used for suppression 1
Combination Therapy Indications
- Sight-threatening CMV retinitis as initial therapy 1
- Retinitis that has relapsed on single-agent therapy 1
- CMV encephalitis or neurologic disease 1
- Delays progression of retinitis in patients failing monotherapy 1
Pharmacokinetic Considerations
- Mean plasma half-life: 3.4-5 hours 7, 4
- Peak plasma levels with 60 mg/kg every 8 hours: approximately 500 μM 7
- Trough levels: 98-126 μM 7
- Clearance correlates directly with renal function 7
- Low oral bioavailability (12-22%) necessitates IV administration 4