FOSCARNET - ANTIVIRAL DRUG AND ITS INDICATIONS .pptx

DETAIL EXPLANATIONS ON FOSCARNET - AN ANTIVIRAL DRUG

1. Foscarnet Antiviral Dr. Shekhar Yadav Dr. Sudha Murthy Doctor of pharmacy

2. INTROUCTION FOSCAVIR is the brand name for foscarnet sodium. The chemical name of foscarnet sodium is phosphonoformic acid, trisodium salt. Foscarnet sodium is a white, crystalline powder FOSCAVIR INJECTION is a sterile, isotonic aqueous solution for intravenous administration only. The solution is clear and colourless. Each millilitre of FOSCAVIR contains 24 mg of foscarnet sodium hexahydrate in Water for Injection. Foscarnet is an FDA-approved antiviral therapy used to treat cytomegalovirus and CMV-associated ophthalmic retinitis in individuals diagnosed with AIDS and who are unable to tolerate ganciclovir or as salvage therapy for those who have drug-resistant CMV and fail ganciclovir. If ganciclovir shows strong side effects in a patient, foscarnet is used as monotherapy in its place.  It also has approval for use as a treatment option in immunocompromised patients with the herpes simplex virus (HSV) who exhibit resistance to acyclovir, the gold standard therapy for HSV. Foscarnet is a medication used to manage and treat CMV, HSV, and VZV viral infections in AIDS and immunocompromised patients.

3. INDICATION

4. MECHANISM OF ACTION Inhibits activity of pyrophosphate binding site on virus-specific DNA polymerases and reverse transcriptases ; active against CMV, HSV-1, and HSV-2

5. Pharmacokinetics Bioavailability: peak concentration: 589 u M(60mg/kg q8hr) 623 u M(90mg/kg q12hr). Distribution: 14 – 17% of foscarnet is protein bound. Metabolism: not metabolized. Elimination: half-life- 4hrs(60mg), 3.3hrs(90mg) .

6. DOSAGE The dosing and rate of administration are determined based on the patient's age and weight and the specific viral infection. CMV Retinitis Induction: 60 mg/kg q8hr IV x14-21 days; infuse IV over at least 60 min Maintenance: 90-120 mg/kg IV qDay ; infuse IV over at least 60-90 min  HERPES SIMPLEX Indicated for Herpes simplex in patients with acyclovir resistance who are immunocompromised Option 1: 40 mg/kg IV q8hr x14-21 days; infuse IV over at least 60 min Option 2: 40-60 mg/kg IV q12hr x14-21 days; infuse IV over at least 60 min GANCICLOVIR-RESITANT CMV (off label) Induction: 90mg/kg/dose IV for a minimum of 2 weeks, alternately 60 mg/kg/dose IV every 8 hours for a minimum of 2 weeks. Maintenance treatment: 90 mg/kg/dose IV every 24 hours or 120 mg/kg/dose IV every 24 hour

7. PREGNANCY category C NURSING : in lactating administered 75 mg/kg, FOSCAVIR was excreted in maternal milk at concentrations three times higher than peak maternal blood concentrations. PEDIATRIC: FOSCAVIR is deposited in teeth and bone and deposition is greater in younger age. FOSCAVIR has been demonstrated to adversely affect development of tooth enamel. Since deposition in human bone has also been shown to occur, it is likely that it does so to a greater degree in developing bone in pediatric patients. Administration to pediatric patients should be undertaken only after careful evaluation and only if the potential benefits for treatment outweigh the risks. GERIATRIC : the risk of toxic reactions to this drug may be greater in elderly patients with impaired renal function, care should be taken in dose selection.

8. Administration Foscarnet is not an orally administered drug due to poor bioavailability, possibly due to the poor metabolism of the drug and its inclination to deposit within bone and cartilage. the duration of therapy is dependent on the patient's immune status and the progress of the lesions. While the IV route is the most used method, intravitreal administration is also used on occasions for ophthalmic complications of viral pathogens. Administer by slow IV infusion Pre hydrate with 750-1000 mL NS or D5W before first infusion to decrease risk for nephrotoxicity See prescribing information for dose adjustments for CrCl <1.4 mL/min/kg. The rate of FOSCAVIR infusion may also affect the decrease in ionized calcium. Therefore, an infusion pump must be used for administration to prevent rapid intravenous infusion , s lowing the infusion rate may decrease or prevent symptoms.

9. STABILITY For Single Use Only. IV Preparation Should be diluted in D5W or NS & transferred to PVC containers For peripheral line administration, dilute to 12 mg/ mL with D5W or NS For central line administration, may administer undiluted IV Administration Use an infusion pump, not exceeding 1 mg/kg/min Adult induction doses of 60 mg/kg are administered over a minimum 1 hr Adult maintenance doses of 90-120 mg are infused over 2 hr Storage: Store between 20° and 25°C, protect from excessive heat (above 40°C) and from freezing. FOSCAVIR INJECTION should be used only if the bottle and seal are intact, a vacuum is present, and the solution is clear and colourless.

10. Side effects

11. Warning/ precautions Renal impairment is the major toxicity of foscavir . Frequent monitoring of serum creatinine, with dose adjustment for changes in renal function, and adequate hydration with administration of foscavir is imperative. It is recommended that 750–1000 mL of normal saline or 5% dextrose solution should be given prior to the first infusion of FOSCAVIR to establish diuresis. After the first dose, the hydration fluid should be administered concurrently with each infusion of FOSCAVIR. P atients should be advised to report symptoms of low ionized calcium such as perioral tingling, numbness in the extremities and paresthesias . Care must be taken to infuse solutions containing FOSCAVIR only into veins with adequate blood flow to permit rapid dilution and distribution to avoid local irritation. Local irritation and ulcerations of penile epithelium have been reported in male patients receiving FOSCAVIR, possibly related to the presence of drug in the urine. Cases of male and female genital irritation/ulceration have been reported in patients receiving FOSCAVIR. Accidental skin and eye contact with foscarnet sodium solution may cause local irritation and burning sensation. If accidental contact occurs, the exposed area should be flushed with water.

12. Monitoring

13. TOXICITY Renal toxicity is one of the major concerns around administering foscarnet. The risk is reducible by concurrent administration of 0.9% normal saline (about 0.5 L to 1.0 L) or dextrose 5% water solution. While a history of chronic renal disease can increase the risk of foscarnet toxicity, withhold the administration of other potentially nephrotoxic drugs such as ACE inhibitors, angiotensin II receptor blockers amphotericin B, vancomycin, or aminoglycosides to reduce the risk of additional renal damage. While there is no particular antidote for foscarnet overdose, it can be prevented by adequate prophylactic hydration or urgent hemodialysis to decrease drug plasma levels.    

14. Contraindication

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