What is the recommended dose and usage of cidofovir (antiviral medication) in pediatric patients with impaired renal function?

Cidofovir Dosing in Pediatric Patients with Impaired Renal Function

Cidofovir is not recommended for pediatric patients with impaired renal function due to its significant nephrotoxicity risk and lack of established dosing guidelines in this population. 1

Standard Dosing in Pediatric Patients with Normal Renal Function

When cidofovir must be used in pediatric patients with normal renal function (for life-threatening viral infections):

• Induction treatment: 5 mg/kg IV once weekly for 2 consecutive weeks 2, 1
• Maintenance treatment: 5 mg/kg IV once every 2 weeks 2, 1

Renal Function Parameters for Cidofovir Use

Cidofovir is contraindicated in patients with:

• Serum creatinine >1.5 mg/dL
• Calculated creatinine clearance ≤55 mL/min
• Urine protein ≥100 mg/dL (equivalent to ≥2+ proteinuria) 1

Modified Dosing Approaches for Pediatric Patients

While not FDA-approved, recent research suggests alternative dosing strategies for select cases:

• Modified low-dose protocol: 1 mg/kg three times weekly 3
  • Shows reduced nephrotoxicity (4%) compared to conventional dosing (15%)
• Alternative approach: 1 mg/kg every other day or three times a week for 4 weeks 4
  • Used successfully in pediatric lung transplant recipients

Required Nephroprotective Measures

For any cidofovir administration, the following must be implemented:

1. Probenecid administration:

   • 2 g orally 3 hours before cidofovir
   • 1 g orally 2 hours after cidofovir
   • 1 g orally 8 hours after cidofovir 1

2. IV hydration:

   • At least 1 liter of 0.9% saline solution infused over 1-2 hours immediately before cidofovir
   • A second liter may be administered during or after cidofovir infusion 1

Monitoring Requirements

• Renal function (serum creatinine and urine protein) must be monitored within 48 hours prior to each dose 1
• Neutrophil count should be monitored throughout therapy 1
• Intraocular pressure should be monitored during therapy 1
• Serum electrolytes should be monitored for metabolic acidosis 1

Dose Adjustments for Changes in Renal Function

• Reduce maintenance dose from 5 mg/kg to 3 mg/kg if serum creatinine increases by 0.3-0.4 mg/dL above baseline
• Discontinue cidofovir if serum creatinine increases ≥0.5 mg/dL above baseline or if ≥3+ proteinuria develops 1

Cautions and Contraindications

• Cidofovir should not be administered with other nephrotoxic agents (aminoglycosides, amphotericin B, foscarnet, IV pentamidine, vancomycin, NSAIDs) 1
• Cidofovir has not been well studied in pediatric patients with CMV disease 2
• The drug produces proximal tubular dysfunction including Fanconi syndrome and acute renal failure 2
• Metabolic acidosis in association with liver dysfunction and pancreatitis resulting in death has been reported 1

Recent Evidence on Safety in Pediatric Populations

Recent research suggests cidofovir-related nephrotoxicity may be lower than previously reported in immunocompetent children (4.3%) 5, but remains a significant concern in immunocompromised patients. The pharmacokinetics of cidofovir in children appear similar to adults, though with a longer half-life (9.5 hours versus adult values) 6.

Given the significant risks and limited pediatric data, cidofovir should only be used in children with impaired renal function when absolutely necessary for life-threatening viral infections, and only after careful consideration of benefit-risk ratio and with intensive monitoring.

AI: I need to make a clearer recommendation about cidofovir use in pediatric patients with impaired renal function.