What are the clinical indications for foscarnet in an immunocompromised patient, possibly with a history of HIV/AIDS or a transplant recipient?

Foscarnet Clinical Indications

Foscarnet is indicated for treatment of CMV retinitis in AIDS patients and acyclovir-resistant mucocutaneous HSV infections in immunocompromised patients, with additional off-label use for CMV encephalitis and other CMV end-organ diseases when ganciclovir fails or cannot be tolerated. 1

FDA-Approved Indications

CMV Retinitis in AIDS Patients

• Foscarnet is FDA-approved as monotherapy for CMV retinitis in AIDS patients at 60 mg/kg IV every 8 hours (or 90 mg/kg every 12 hours) for 14-21 days induction, followed by 90-120 mg/kg once daily for maintenance. 1, 2
• Combination therapy with ganciclovir and foscarnet is FDA-approved for patients who have relapsed after monotherapy with either drug alone. 1
• The combination regimen uses ganciclovir 5 mg/kg IV every 12 hours plus foscarnet 60 mg/kg IV every 8 hours (or 90 mg/kg every 12 hours). 3, 4

Acyclovir-Resistant HSV Infections

• Foscarnet is FDA-approved for acyclovir-resistant mucocutaneous HSV infections in immunocompromised patients only. 1
• This indication does not extend to HSV retinitis, encephalitis, congenital/neonatal HSV disease, or HSV in immunocompetent individuals. 1

Off-Label Guideline-Supported Indications

CMV Encephalitis in Immunocompromised Patients

• Combination ganciclovir (5 mg/kg IV every 12 hours) plus foscarnet (60 mg/kg IV every 8 hours or 90 mg/kg every 12 hours) for 3 weeks is recommended for CMV encephalitis, particularly in HIV-infected patients. 3
• This combination led to improvement or stabilization in 74% of 31 patients with CMV encephalitis or myelitis. 3
• Monotherapy with either ganciclovir or foscarnet alone has not improved survival in CMV encephalitis, making combination therapy the preferred approach. 3

CMV Colitis and Gastrointestinal Disease

• Foscarnet is recommended as an alternative for CMV colitis in cases of ganciclovir resistance, ganciclovir intolerance, or first-line therapy failure at 60 mg/kg IV every 8 hours (or 90 mg/kg every 12 hours) for 14-21 days. 2
• This applies to HIV-infected patients, solid organ transplant recipients, hematopoietic stem cell transplant recipients, and IBD patients with CMV superinfection. 2
• Improvement occurs in over 67% of immunocompromised patients with CMV gastrointestinal infections treated with foscarnet. 5

Ganciclovir-Resistant CMV Infections

• Foscarnet retains activity against ganciclovir-resistant CMV strains and should be used when CMV isolates demonstrate in vitro resistance (ED50 >6 μmol ganciclovir). 6, 5
• In two patients with ganciclovir-resistant CMV retinitis (ED50 9.5-14.5 μmol), foscarnet stabilized retinitis for 12 and 25 weeks after ganciclovir failure. 6

Critical Administration Requirements

Nephrotoxicity Prevention

• Saline fluid loading with 1 liter normal saline during each infusion is essential to minimize nephrotoxicity, which occurs in 7-30% of patients. 7, 2
• Infusion must occur over 1-2 hours, no faster than 1 mg/kg/minute. 7, 2
• Serum creatinine monitoring is mandatory at baseline and at least twice weekly during therapy, with immediate dose modification if renal function deteriorates. 7, 2

Electrolyte Monitoring

• Electrolyte disturbances (calcium, magnesium, potassium, phosphorus) occur in approximately one-third of patients and require monitoring at least twice weekly. 7, 2
• These abnormalities can lead to seizures and cardiac dysrhythmias. 7

Key Clinical Considerations

When to Choose Foscarnet Over Ganciclovir

• Use foscarnet when ganciclovir causes dose-limiting neutropenia or thrombocytopenia, as foscarnet does not cause myelosuppression. 3, 8
• Foscarnet is preferred when concurrent zidovudine therapy is needed in HIV patients, as ganciclovir potentiates zidovudine's myelosuppression. 5, 9
• In one trial, AIDS patients with CMV retinitis receiving foscarnet survived significantly longer than those receiving ganciclovir, possibly due to foscarnet's inherent anti-HIV activity. 5

Combination Therapy Indications

• Consider combination ganciclovir plus foscarnet for sight-threatening CMV retinitis, clinically resistant disease despite sustained single-drug induction therapy, or CMV encephalitis. 3, 8, 4
• All nine patients with clinically resistant CMV retinitis showed favorable response to combination therapy, with complete healing in 12 of 14 eyes. 4

Limitations

• Foscarnet is NOT indicated for CMV pneumonitis, congenital/neonatal CMV disease, or CMV infections in immunocompetent individuals, as safety and efficacy have not been established in these populations. 1
• Foscarnet has poor CNS penetration, making effective concentrations difficult to achieve in CSF for neurologic infections. 3