Drug Profile

FOSCARNET

Generic name: Foscavir or Foscavir Injection (foscarnet sodium)

Other commonly used names: PFA, phosphonoformic acid, trisodium phosphonoformate

Manufacturer: Astra USA

Foscarnet is indicated in the treatment of:

• Cytomegalovirus (CMV) retinitis in patients with acquired immunodeficiency syndrome (AIDS.)
• CMV disease that is severe and life-threatening, including CMV pneumonia, CMV gastrointestinal disease, and disseminated CMV infections in immunocompromised patients.
• Mucocutaneous herpes simplex virus infections that are acyclovir-resistant in immunocompromised patients.
• Varicella-zoster infection that is acyclovir-resistant in immunocompromised patients.

Foscarnet is not active against bacteria or mycoplasma.

Mechanism of action

Foscarnet blocks, through non-competitive inhibition, of the pyrophosphate binding site of viral DNA polymerase, thereby preventing the cleavage of pyrophosphate from deoxynucleoside triphosphate and elongation of the viral DNA chain. Foscarnet does not require viral thymidine kinase for activation, and viral replication resumes after foscarnet is discontinued.

In vitro studies reveal foscarnet to inhibit the viral replication of all known herpes viruses. It can also non-competitively inhibit human immunodeficiency virus (HIV) reverse transcriptase and hepapitis B virus DNA polymerase. However, full evaluations of the use of this drug in clinical practice for many of these infections have not yet been conducted.

Foscarnet also inhibits competitively the sodium-phosphate cotransport by renal cortical brush border membrane vesicles. This drug is dose-dependent and specific for phosphate, possibly decreasing tubular reabsorption and thus increasing phosphate-renal excretion.

Absorption

Oral administration of foscarnet is poorly absorbed, and bioavailability ranges from 12 to 22%.

Renal Elimination

About 80-87% of the drug was excreted unchanged in urine. Tubular reabsorption could possibly occur, and apparent extrarenal clearance could indicate the uptake of foscarnet into bone matrix.

Side Effects

• The major dose-limiting side effect is impairment of renal function.
• The most common type of nephrotoxicity (kidney damage) is acute tubular necrosis.
• Nephrogenic diabetes insipidus and foscarnet crystal formation in the glomerular capillary lumen have been described.
• Patients treated with the drug may have abnormal blood electrolyte levels or seizures.

Nephrotoxic effects have been alleviated with hydration using 0.5 to 1 liter of 0.9% sodium chloride per dose throughout the course of foscarnet treatment.

Recommended dosage

• The recommended intial osage of foscarnet intreating HSV infections in immunocompromised patients is 40 mg/kg either 2 or 3 times a day.
• The dosage for CMV retinits is 60 mg/kg every 8 hours for 2 to 3 weeks.
• The dosage should be individually tailored according to changes in renal function.
• The drug must be administered by controlled infusion through a central venous catheter or pheripheral venous line.
• The rate of infusion should not exceed 1 mg/kg/min.
• Treatment should commence between 7 to 10 days of failure of acyclovir therapy and should last 2 to 3 weeks or until the lesions are healed.

Foscavir is available in 250 and 500 mL bottles containing 24 mg foscarnet sodium/mL. It should be storeed at room temperature (15 to 30 degree C).

Patients with acyclovir-resistant mucocutaneous HSV infections who lack insurance coverage can participate in the Foscavir Assistance and Information on Reimbursement program by calling 1-800-488-3247 (FDA Reports 1995; p T&G1-2.)