Foscarnet: Difference between revisions

Latest revision as of 12:55, 18 October 2023

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.

@@ Line 1: / Line 1: @@
+==Background==
-* Inhibits DNA polymerase in [[human herpesviruses]]
-* Indications: {{#ask: [[Is treated by::foscarnet]] | default=none}}
+*Inhibits DNA polymerase in [[human herpesviruses]]
+*Indications: {{#ask: [[Is treated by::foscarnet]] | default=none}}
+===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 virus|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 rate[[CiteRef::jayaweera1997mi]]
+*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
 [[Category:Antivirals]]