Foscarnet Dosing for CMV Colitis
For CMV colitis, foscarnet should be administered at 60 mg/kg intravenously every 8 hours (or alternatively 90 mg/kg every 12 hours) for 14-21 days, infused slowly over 1-2 hours with concurrent saline hydration to minimize nephrotoxicity. 1
Primary Indication for Foscarnet
Foscarnet is reserved as an alternative agent for CMV colitis in specific clinical scenarios 1:
- Ganciclovir resistance (documented by viral genotyping showing UL97 or UL54 mutations) 1
- Ganciclovir intolerance, particularly severe myelosuppression with neutropenia 1
- First-line therapy failure after standard ganciclovir treatment 1
Ganciclovir (5 mg/kg IV twice daily) remains the preferred first-line treatment for CMV colitis, with foscarnet serving as the backup option 1.
Dosing Regimens
Induction Therapy
Two equivalent dosing schedules are recommended 1:
- 60 mg/kg IV every 8 hours (three times daily) for 14-21 days 1
- 90 mg/kg IV every 12 hours (twice daily) for 14-21 days 1
Administration Requirements
Critical administration parameters to prevent toxicity 1:
- Infusion rate: Administer over 1-2 hours, no faster than 1 mg/kg/minute 1
- Hydration: Concurrent saline fluid loading (1 liter normal saline with each infusion) is mandatory to minimize renal toxicity 1, 2
- Central access: Central venous catheter is typically required for prolonged therapy 3
Maintenance Therapy
Maintenance dosing considerations 1:
- 90-120 mg/kg IV once daily may be used for long-term suppression in HIV-infected patients with concurrent CMV retinitis 1
- For isolated CMV colitis without retinitis, maintenance therapy may not be required after successful induction, particularly in patients who achieve complete clinical and endoscopic resolution 2
Renal Dose Adjustment
Doses must be modified in patients with renal insufficiency 1. Baseline creatinine clearance should guide initial dosing, with frequent monitoring during therapy. If creatinine rises during treatment, dose reduction or temporary discontinuation may be necessary 4.
Expected Clinical Response
Efficacy Data
Response rates from clinical studies 5, 2, 3:
- Complete response: 57-80% of patients with CMV colitis achieve complete symptom resolution 5, 2, 3
- Time to response: Median 7.5 days (range 1-12 days) for clinical improvement 5
- Histopathologic improvement: 60-67% show clearance of CMV inclusions on repeat biopsy 5, 3
Relapse Rates
Relapse patterns differ by site 2, 3:
- CMV esophagitis: Lower relapse rate (approximately 20%) with longer disease-free intervals 2, 3
- CMV colitis: Higher relapse rate with shorter disease-free periods, though most respond to retreatment 2, 3
Critical Toxicity Monitoring
Nephrotoxicity (Most Common)
Renal dysfunction occurs in 7-30% of patients 1, 6:
- Monitor serum creatinine at baseline, then at least twice weekly during therapy 1
- Acute tubular necrosis is the mechanism; toxicity is usually reversible with dose reduction or discontinuation 6, 4
- Aggressive hydration is the primary preventive strategy 1, 2
Electrolyte Disturbances (Very Common)
Metabolic abnormalities occur in approximately one-third of patients 1:
- Hypocalcemia (most frequent): Monitor ionized calcium levels, as foscarnet chelates divalent cations 1, 6
- Hypomagnesemia, hypokalemia, hypophosphatemia or hyperphosphatemia all reported 1, 6
- Severe electrolyte imbalances can precipitate seizures and cardiac dysrhythmias 1
- Check electrolytes (calcium, magnesium, potassium, phosphorus) at least twice weekly during therapy 1
Other Adverse Effects
Additional toxicities to monitor 1, 6:
- Penile ulcerations: Occur in 6% of patients due to direct mucocutaneous toxicity from urinary excretion 6, 2
- Elevated liver transaminases 1
- CNS symptoms (headache, tremor) 1
Common Pitfalls to Avoid
Inadequate Hydration
Failure to provide concurrent saline hydration is the most common preventable cause of foscarnet nephrotoxicity 1, 2. Each dose should be accompanied by 500-1000 mL normal saline.
Rapid Infusion
Infusing foscarnet too quickly increases the risk of acute electrolyte disturbances and renal toxicity 1. Always infuse over 1-2 hours minimum.
Insufficient Monitoring
Weekly laboratory monitoring is inadequate; twice-weekly assessment of renal function and electrolytes is necessary to detect toxicity early 1.
Premature Discontinuation
Stopping therapy before 14 days increases relapse risk 5, 2. The full 14-21 day course should be completed unless prohibitive toxicity develops.
Special Populations
HIV-Infected Patients
In HIV-infected patients with CMV colitis 1:
- Consider discontinuing or reducing immunosuppressive therapy if feasible, as immune reconstitution improves outcomes 1
- Maintenance therapy may be necessary to prevent relapse, particularly if CD4 count remains very low 1
- Foscarnet has been associated with increased survival compared to ganciclovir in some HIV cohorts 1
Transplant Recipients
For solid organ or hematopoietic stem cell transplant recipients 7, 4:
- Reduction of immunosuppression should be attempted when treating CMV colitis 7
- High-dose valganciclovir may be an alternative if foscarnet causes acute kidney injury in a transplant recipient with baseline renal dysfunction 4
Inflammatory Bowel Disease Patients
In IBD patients with CMV colitis superinfection 1: