Foscarnet
From IDWiki
Background
- Inhibits DNA polymerase in human herpesviruses
- Indications: CMV after hematopoietic stem cell transplantation, CMV after solid organ transplantation, Cytomegalovirus, Herpes simplex virus, Herpesviridae, Post-transplant acute limbic encephalitis
Spectrum of Activity
- Active against all human herpesviruses
Mechanism of Action
- Acts as a pyrophosphate analogue that competitively and reversibly inhibits herpesvirus DNA polymerase, causing premature chain termination of DNA
Pharmacokinetics and Pharmacodynamics
- CSF penetration 66% of serum levels
Dosing
Adult Dosing
- CMV esophagitis and CMV colitis: 60 mg/kg/dose every 8 hours or 90 mg/kg/dose every 12 hours
- CMV retinitis: induction with 60 mg/kg/dose every 8 hours or 90 mg/kg/dose every 12 hours, for 14 to 21 days, followed by maintenance with 90 to 120 mg/kg/dose once daily for 3 to 6 months or longer
- Acyclovir-resistant mucocutaneous herpes simplex: 40 mg/kg/dose every 8 to 12 hours
Pediatric Dosing
- Induction: foscarnet 60 mg/kg IV q8h or 90 mg/kg IV q12h
- Maintenance: foscarnet 90 to 120 mg/kg IV q24h
Administration
- Infusion rate not to exceed 1 mg/kg/min, with adult doses of 60 mg/kg typically infused over 1 hour, and doses of 90 to 120 mg/kg infused over 2 hours
Safety
Adverse Events
- Most common AEs include infusion-related nausea, electrolyte abnormalities, and acute kidney injury
- Renal tubular nephrotoxicity is common, dose-dependent, and usually reversible if drug is stopped early
- Crystal glomerular nephropathy also occurs
- Electrolyte abnormalities, including hypocalcemia, hypophosphatemia, hyperphosphatemia, hypomagnesemia, and hypokalemia
- Nausea is very common, and can be debilitating
- Minimize with concurrent IV and oral hydration, antiemetics, and slowing the infusion rate1
- Other AEs include:
- Seizure, usually in patients with concurrent CNS pathology
- Genital ulcers, which slowly heal once the drug is stopped
- Anemia
- Nephrogenic diabetes insipidus
Monitoring
- Close monitoring of electrolytes and creatinine is required
References
- ^ Dushyantha T. Jayaweera. Minimising the Dosage-Limiting Toxicities of Foscarnet Induction Therapy. Drug Safety. 1997;16(4):258-266. doi:10.2165/00002018-199716040-00003.