FOSCARNET- Antiviral drug

                                           

Generic Name: foscarnet (fos-KAR-net)

Brand Name: Foscavir

MECHANISM OF ACTION-

Foscarnet exerts its antiviral activity by a selective inhibition at the pyrophosphate binding site on virus-specific DNA polymerases at concentrations that do not affect cellular DNA polymerases. 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.

USES-

* 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.

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.

SIDE EFFECT-

* 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.

DRUG INTRACTION-

*FOSCARNET + ACICLOVER - Foscarnet may increase the nephrotoxic activities of Aciclovir.

*FOSCARNET + FRAMYCETIN –Foscarnet may increase the nephrotoxic activities of Framycetin.

*FOSCARNET + NEOMYCIN-Foscarnet may increase the nephrotoxic activities of Neomycin.

REFERENCE-

Tripathi K.D,"Essentials of medical pharmacology",7th edition,page no- 801.