FOSCAVIR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for FOSCAVIR (FOSCAVIR).
Foscarnet is a pyrophosphate analog that selectively inhibits viral DNA polymerase and reverse transcriptase by binding to the pyrophosphate binding site, preventing the cleavage of pyrophosphate from deoxynucleotide triphosphates, thereby inhibiting viral DNA synthesis. It does not require activation by viral thymidine kinase, making it active against acyclovir-resistant HSV and VZV, and ganciclovir-resistant CMV.
| Metabolism | Foscarnet is not metabolized in humans. It is eliminated primarily by the kidneys via glomerular filtration and tubular secretion, with approximately 80-90% of an intravenous dose excreted unchanged in the urine within 48 hours. |
| Excretion | Primarily renal excretion (>80% as unchanged drug) via glomerular filtration and tubular secretion; minimal biliary/fecal elimination (<5%). |
| Half-life | Terminal elimination half-life is approximately 3-5 hours in patients with normal renal function; can extend to 48-120 hours in severe renal impairment (CrCl <20 mL/min), requiring dose adjustment and therapeutic drug monitoring. |
| Protein binding | 14-17% bound to plasma proteins (primarily albumin). |
| Volume of Distribution | Volume of distribution at steady state (Vss) is 0.3-0.7 L/kg, indicating distribution primarily into extracellular fluid and limited tissue penetration (excluding CSF at therapeutic levels). |
| Bioavailability | Oral bioavailability is negligible (<5%); intravenous administration only. |
| Onset of Action | Intravenous administration: time to clinical effect (antiviral activity) is rapid, with peak serum concentrations achieved by end of infusion; time to maximum plasma concentration (Tmax) is at infusion end. |
| Duration of Action | Duration of antiviral activity is approximately 8-12 hours post-dose, but depends on renal clearance; trough levels must be maintained above 2-4 times the EC50 for HIV to prevent resistance. Clinical effect persists as long as serum concentrations remain above inhibitory levels. |
Induction: 60 mg/kg IV every 8 hours for 2-3 weeks, then maintenance: 90-120 mg/kg IV once daily. Administer as a 2-hour infusion via central line.
| Dosage form | SOLUTION |
| Renal impairment | Base on creatinine clearance (CrCl): CrCl >1.0 mL/min/kg: full dose; CrCl 0.8-1.0: 45 mg/kg q8h induction, 70 mg/kg q24h maintenance; CrCl 0.6-0.8: 40 mg/kg q12h induction, 50 mg/kg q24h maintenance; CrCl 0.5-0.6: 50 mg/kg q24h induction, 80 mg/kg q48h maintenance; CrCl 0.4-0.5: 50 mg/kg q48h induction, 50 mg/kg q48h maintenance; CrCl <0.4: not recommended. |
| Liver impairment | No dose adjustment recommended for hepatic impairment. |
| Pediatric use | Children: Induction 60 mg/kg IV q8h for 2-3 weeks; maintenance 90-120 mg/kg IV once daily. Adjust dose for renal function per adult guidelines, using weight-based CrCl calculation. |
| Geriatric use | Elderly patients are more likely to have decreased renal function; base dose on renal function assessment (CrCl). Start with lower end of dosing range and monitor renal function frequently. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for FOSCAVIR (FOSCAVIR).
| Breastfeeding | No human data on excretion in breast milk; M/P ratio unknown. Foscarnet is present in animal milk. Because of potential for serious adverse reactions (e.g., renal toxicity, electrolyte disturbances) in nursing infants, breastfeeding is not recommended during therapy. |
| Teratogenic Risk | Pregnancy category C. First trimester: Animal studies show developmental toxicity (embryotoxicity, skeletal abnormalities) at clinically relevant doses; human data insufficient. Second and third trimesters: Foscarnet crosses placenta; risk of fetal nephrotoxicity due to accumulation in fetal kidneys. Overall, use only if benefit outweighs risk. |
■ FDA Black Box Warning
Foscarnet is indicated only for immunocompromised patients with CMV retinitis and acyclovir-resistant HSV infections. Nephrotoxicity occurs to some degree in most patients. Renal impairment is dose-limiting. Use with other nephrotoxic drugs increases risk. Electrolyte disturbances (e.g., hypocalcemia, hypomagnesemia, hypokalemia, hypophosphatemia) are common and may be severe. Seizures have been reported, often associated with electrolyte abnormalities.
| Serious Effects |
["Hypersensitivity to foscarnet or any component of the formulation","Severe renal impairment (CrCl < 0.4 mL/min/kg) unless the benefit clearly outweighs the risk"]
| Precautions | ["Renal impairment: Monitor renal function closely; dose adjustments required; risk of acute renal failure.","Electrolyte abnormalities: Monitor serum calcium, magnesium, potassium, and phosphate; correct before and during therapy.","Seizures: Increased risk with electrolyte disturbances; use caution in patients with CNS disorders.","Anemia: Monitor hemoglobin levels; may require transfusion.","Granulocytopenia: Monitor neutrophil counts.","Administration: Must be given via slow IV infusion; avoid rapid infusion or bolus to reduce nephrotoxicity.","Carcinogenesis: Not studied in humans.","Use in pregnancy: Category C; use only if benefit outweighs risk.","Use in elderly: Greater risk of renal impairment due to age-related decline in renal function."] |
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| Fetal Monitoring | Monitor maternal renal function (serum creatinine, BUN, electrolytes including calcium, magnesium, phosphorus, potassium) at baseline and at least twice weekly; adjust dose for renal impairment. Monitor fetal growth and amniotic fluid volume with ultrasound due to potential nephrotoxicity. Consider fetal renal ultrasound if prolonged therapy. |
| Fertility Effects | In animal studies, foscarnet caused testicular atrophy and impaired fertility in males; effects on human fertility unknown. No specific human fertility studies available. Potential for reversible impairment of spermatogenesis. |