Foscarnet Sodium
Loading...Foscarnet Sodium Recall
Get an alert when a recall is issued.
Questions & Answers
Side Effects & Adverse Reactions
Renal Impairment: THE MAJOR TOXICITY OF FOSCARNET SODIUM IS RENAL IMPAIRMENT (see ADVERSE REACTIONS section). Renal impairment is most likely to become clinically evident during the second week of induction therapy, but may occur at any time during foscarnet sodium treatment. Renal function should be monitored carefully during both induction and maintenance therapy (see PATIENT MONITORING section). Elevations in serum creatinine are usually, but not always, reversible following discontinuation or dose adjustment of foscarnet sodium injection. Safety and efficacy data for patients with baseline serum creatinine levels greater than 2.8 mg/dL or measured 24-hour creatinine clearances <50 mL/min are limited.
SINCE FOSCARNET SODIUM HAS THE POTENTIAL TO CAUSE RENAL IMPAIRMENT, DOSE ADJUSTMENT BASED ON SERUM CREATININE IS NECESSARY. Hydration may reduce the risk of nephrotoxicity. It is recommended that 750 to 1000 mL of 0.9% sodium chloride injection or 5% dextrose solution should be given prior to the first infusion of foscarnet sodium to establish diuresis. With subsequent infusions, 750 to 1000 mL of hydration fluid should be given with 90 to 120 mg/kg of foscarnet sodium, and 500 mL with 40 to 60 mg/kg of foscarnet sodium. Hydration fluid may need to be decreased if clinically warranted.
After the first dose, the hydration fluid should be administered concurrently with each infusion of foscarnet sodium.
Mineral and Electrolyte Abnormalities: Foscarnet sodium has been associated with changes in serum electrolytes including hypocalcemia, hypophosphatemia, hyperphosphatemia, hypomagnesemia, and hypokalemia (see ADVERSE REACTIONS section). Foscarnet sodium may also be associated with a dose-related decrease in ionized serum calcium which may not be reflected in total serum calcium. This effect is likely to be related to chelation of divalent metal ions such as calcium by foscarnet. Patients should be advised to report symptoms of low ionized calcium such as perioral tingling, numbness in the extremities and paresthesias. Particular caution and careful management of serum electrolytes is advised in patients with altered calcium or other electrolyte levels before treatment and especially in those with neurologic or cardiac abnormalities and those receiving other drugs known to influence minerals and electrolytes (see PATIENT MONITORING and Drug Interactions sections). Physicians should be prepared to treat these abnormalities and their sequelae such as tetany, seizures or cardiac disturbances. The rate of foscarnet sodium infusion may also affect the decrease in ionized calcium. Therefore, an infusion pump must be used for administration to prevent rapid intravenous infusion (see DOSAGE AND ADMINISTRATION section). Slowing the infusion rate may decrease or prevent symptoms.
Seizures: Seizures related to mineral and electrolyte abnormalities have been associated with foscarnet sodium treatment (see WARNING section; Mineral and Electrolyte Abnormalities). Several cases of seizures were associated with death. Risk factors associated with seizures included impaired baseline renal function, low total serum calcium, and underlying CNS conditions.
Legal Issues
There is currently no legal information available for this drug.
FDA Safety Alerts
There are currently no FDA safety alerts available for this drug.
Manufacturer Warnings
There is currently no manufacturer warning information available for this drug.
FDA Labeling Changes
There are currently no FDA labeling changes available for this drug.
Uses
CMV Retinitis: Foscarnet sodium injection is indicated for the treatment of CMV retinitis in patients with acquired immunodeficiency syndrome (AIDS). Combination therapy with foscarnet sodium and ganciclovir is indicated for patients who have relapsed after monotherapy with either drug. SAFETY AND EFFICACY OF FOSCARNET SODIUM HAVE NOT BEEN ESTABLISHED FOR TREATMENT OF OTHER CMV INFECTIONS (e.g., PNEUMONITIS, GASTROENTERITIS); CONGENITAL OR NEONATAL CMV DISEASE; OR NON-IMMUNOCOMPROMISED INDIVIDUALS.
Mucocutaneous Acyclovir-Resistant HSV Infections: Foscarnet sodium injection is indicated for the treatment of acyclovir-resistant mucocutaneous HSV infections in immunocompromised patients. SAFETY AND EFFICACY OF FOSCARNET SODIUM HAVE NOT BEEN ESTABLISHED FOR TREATMENT OF OTHER HSV INFECTIONS (e.g., RETINITIS, ENCEPHALITIS); CONGENITAL OR NEONATAL HSV DISEASE; OR HSV IN NON-IMMUNOCOMPROMISED INDIVIDUALS.
History
There is currently no drug history available for this drug.
Other Information
The chemical name of foscarnet sodium is phosphonoformic acid, trisodium salt. Foscarnet sodium is a white, crystalline powder containing 6 equivalents of water of hydration with a molecular formula of Na3CO5P•6 H2O and a molecular weight of 300.1. The structural formula is:
Foscarnet sodium has the potential to chelate divalent metal ions, such as calcium and magnesium, to form stable coordination compounds. Foscarnet sodium injection is a sterile, isotonic aqueous solution for intravenous administration only. The solution is clear and colorless. Each milliliter of foscarnet sodium injection contains 24 mg of foscarnet sodium hexahydrate in Water for Injection, USP. Hydrochloric acid and/or sodium hydroxide may have been added to adjust the pH of the solution to 7.4. Foscarnet sodium injection contains no preservatives.
VIROLOGY
Mechanism of Action: Foscarnet sodium is an organic analogue of inorganic pyrophosphate that inhibits replication of herpesviruses in vitro including cytomegalovirus (CMV) and herpes simplex virus types 1 and 2 (HSV-1 and HSV-2).
Foscarnet sodium 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 sodium does not require activation (phosphorylation) by thymidine kinase or other kinases and therefore is active in vitro against HSV TK deficient mutants and CMV UL97 mutants. Thus, HSV strains resistant to acyclovir or CMV strains resistant to ganciclovir may be sensitive to foscarnet sodium. However, acyclovir or ganciclovir resistant mutants with alterations in the viral DNA polymerase may be resistant to foscarnet sodium and may not respond to therapy with foscarnet sodium. The combination of foscarnet sodium and ganciclovir has been shown to have enhanced activity in vitro.
Antiviral Activity in vitro and in vivo : The quantitative relationship between the in vitro susceptibility of human cytomegalovirus (CMV) or herpes simplex virus 1 and 2 (HSV-1 and HSV-2) to foscarnet sodium and clinical response to therapy has not been established and virus sensitivity testing has not been standardized. Sensitivity test results, expressed as the concentration of drug required to inhibit by 50% the growth of virus in cell culture (IC50), vary greatly depending on the assay method used, cell type employed and the laboratory performing the test. A number of sensitive viruses and their IC50 values are listed below (Table 1).
| TABLE 1 |
|
|---|---|
| FOSCARNET Inhibition of virus multiplication in cell culture |
|
| Virus |
IC50 (μM) |
| CMV |
50-800* |
| HSV-1, HSV-2 |
10-130 |
| Ganciclovir resistant CMV |
190 |
| HSV-TK negative mutant |
67 |
| HSV-DNA polymerase mutants |
5-443 |
| * Mean = 269 μM |
|
Statistically significant decreases in positive CMV cultures from blood and urine have been demonstrated in two studies (FOS-03 and ACTG-015/915) of patients treated with foscarnet sodium. Although median time to progression of CMV retinitis was increased in patients treated with foscarnet sodium, reductions in positive blood or urine cultures have not been shown to correlate with clinical efficacy in individual patients.
| TABLE 2 |
|||
|---|---|---|---|
| Blood and Urine Culture Results from CMV Retinitis Patients* |
|||
| Blood |
+CMV |
-CMV |
|
| Baseline |
27 |
34 |
|
| End of Induction ** |
1 |
60 |
|
| Urine |
+CMV |
-CMV |
|
| Baseline |
52 |
6 |
|
| End of Induction** |
21 |
37 |
|
| * A total of 77 patients was treated with foscarnet sodium in two clinical trials (FOS-03 and ACTG-015/915). Not all patients had blood or urine cultures done and some patients had results from both cultures. ** (60 mg/kg foscarnet sodium injection TID for 2 to 3 weeks). |
|||
Resistance: Strains of both HSV and CMV that are resistant to foscarnet sodium can be readily selected in vitro by passage of wild type virus in the presence of increasing concentrations of the drug. All foscarnet sodium resistant mutants are known to be generated through mutation in the viral DNA polymerase gene. CMV strains with double mutations conferring resistance to both foscarnet sodium and ganciclovir have been isolated from patients with AIDS. The possibility of viral resistance should be considered in patients who show poor clinical response or experience persistent viral excretion during therapy.
Sources
Foscarnet Sodium Manufacturers
-
Hospira, Inc.
![Foscarnet Sodium Injection, Solution [Hospira, Inc.]](/wp-content/themes/bootstrap/assets/img/loading2.gif)
Foscarnet Sodium | Hospira, Inc.
CAUTION—DO NOT ADMINISTER FOSCARNET SODIUM BY RAPID OR BOLUS INTRAVENOUS INJECTION. THE TOXICITY OF FOSCARNET SODIUM MAY BE INCREASED AS A RESULT OF EXCESSIVE PLASMA LEVELS. CARE SHOULD BE TAKEN TO AVOID UNINTENTIONAL OVERDOSE BY CAREFULLY CONTROLLING THE RATE OF INFUSION. THEREFORE, AN INFUSION PUMP MUST BE USED. IN SPITE OF THE USE OF AN INFUSION PUMP, OVERDOSES HAVE OCCURRED.
Login To Your Free Account