foscarnet sodium - Medications

Foscarnet Sodium Injection is the brand name for foscarnet sodium. The chemical name of foscarnet sodium is phosphonoformic acid, trisodium salt. Foscarnet sodium is a white to almost white crystalline powder containing 6 equivalents of water of hydration with an empirical formula of Na 3 CO 5 P•6 H 2 O and a molecular weight of 300.04. The structural formula is: Foscarnet Sodium Injection 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 may have been added to adjust the pH of the solution to 7.4. Foscarnet Sodium Injection contains no preservatives. Structural Formula

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 an empirical formula of Na 3 CO 5 P•6 H 2 O 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 may have been added to adjust the pH of the solution to 7.4. Foscarnet sodium injection contains no preservatives. structural formula

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 an empirical formula of Na3CO5P·6H2O and a molecular weight of 300.1. The structural formula is: Foscarnet sodium injection 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 may have been added to adjust the pH of the solution to 7.4. Foscarnet sodium injection contains no preservatives. Foscarnet Structural Formula

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 an empirical formula of Na 3 CO 5 P · 6H 2 O and a molecular weight of 300.1. The structural formula is: Foscarnet sodium injection 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 may have been added to adjust the pH of the solution to 7.4. Foscarnet sodium injection contains no preservatives. Structural Formula

The chemical name of foscarnet sodium is phosphonoformic acid, trisodium salt. Foscarnet sodium, USP is a white to almost white, crystalline powder containing 6 equivalents of water of hydration with an empirical formula of Na 3 CO 5 P.6H 2 O and a molecular weight of 300.04. The structural formula is: Foscarnet sodium injection 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, clear, colorless solution for intravenous administration only. Each milliliter of foscarnet sodium injection contains 24 mg of foscarnet sodium hexahydrate in water for injection, USP. Hydrochloric acid may have been added to adjust the pH of the solution to 7.4. Foscarnet sodium injection contains no preservatives. 1

The chemical name of foscarnet sodium is phosphonoformic acid, trisodium salt, hexahydrate. Foscarnet sodium is a white to almost white, crystalline powder containing 6 equivalents of water of hydration with an empirical formula of Na 3 CO 5 P•6 H 2 O and a molecular weight of 300.04. 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 may have been added to adjust the pH of the solution to 7.4. Foscarnet sodium injection contains no preservatives. structure

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 an empirical formula of Na 3 CO 5 P·6H 2 O and a molecular weight of 300.1. The structural formula is: Foscarnet sodium Injection 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 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 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 does not require activation (phosphorylation) by thymidine kinase or other kinases. Antiviral Activity in Cell Culture The quantitative relationship between the cell culture susceptibility of human cytomegalovirus (CMV) or herpes simplex virus 1 and 2 (HSV-1 and HSV-2) to foscarnet 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 (EC 50 ), vary greatly depending on the assay method used, cell type employed and the laboratory performing the test. A number of sensitive viruses and their EC 50 values are listed below (Table 1). The combination antiviral activity of foscarnet and ganciclovir or acyclovir are not antagonistic in cell culture. TABLE 1 Foscarnet Inhibition of Virus Replication in Cell Culture Virus EC 50 value (µM) CMV Ganciclovir resistant CMV HSV-1, HSV-2 HSV-TK negative mutant HSV-DNA polymerase mutants 50 - 800* 190 10 -130 67 5 - 443 *Mean = 269 µM Antiviral Activity in vivo Statistically significant decreases in positive CMV cultures from blood and urine have been demonstrated in two studies (FOS-03 and ACTG-015/915) of subjects treated with foscarnet sodium Injection. Although median time to progression of CMV retinitis was increased in subjects treated with foscarnet sodium Injection, reductions in positive blood or urine cultures have not been shown to correlate with clinical efficacy in individual subjects (Table 2). TABLE 2 Blood and Urine Culture Results from CMV Retinitis Patients* Blood +CMV -CMV Baseline End of Induction† 27 1 34 60 Urine +CMV -CMV Baseline End of Induction† 52 21 6 37 *A total of 77 subjects were treated with foscarnet sodium Injection in two clinical trials (FOS-03 and ACTG-015/915). Not all subjects had blood or urine cultures done and some subjects had results from both cultures. †(60 mg/kg foscarnet sodium Injection TID for 2-3 weeks). Resistance Cell culture: CMV and HSV isolates with reduced susceptibility to foscarnet have been selected in cell culture by passage of wild type virus in the presence of increasing concentrations of the drug. All foscarnet resistant isolates are known to be generated through amino acid substitutions in the viral DNA polymerase pUL54 (CMV) or pUL30 (HSV) (Table 3). TABLE 3 Summary of Foscarnet Resistance-associated DNA Polymerase Amino Acid Substitutions in Cell Culture CMV pUL54 T419M, T552N, S585A, F595I, Q807A, M844T/V, V946L HSV-1 pUL30 Y577H, E597D, A605V, L702H, V714M, L774F, L788M, D780N, L782I, P797T, L802F, V813M, V817M, Y818C, T821M, R842S, S889A, F891C, V892M, D907V, A910V, SRA914-916LCV, V958L, R959H HSV-2 pUL30 _ In vivo: Limited clinical data are available on the development of clinical resistance to foscarnet and many pathways to resistance likely exist. Substitutions documented in the literature in treated patients as associated with foscarnet resistance, are listed in Table 4. TABLE 4 Summary of Foscarnet Resistance-associated Amino Acid Substitutions Observed in Treated Patients CMV pUL54 N495K, Q578H/L, D588E/N, T700A, V715M, E756D/K/Q, L773V, L776M, V781I, V787L, L802M, A809V, V812L, T813S, T821I, A834P, T838A, G841A/S, del 981-982 HSV-1 pUL30 S599L, D672N, R700G, V715G, A719T/V, S724N, E798K, G841C/S, A910T, Y941H HSV-2 pUL30 A724T, S725G, S729N, Q732R, L783M, D785N, T844I, L850I, D912V Note: Many additional pathways to foscarnet resistance likely exist The possibility of viral resistance should be considered in patients who show poor clinical response or experience persistent viral excretion during therapy. Cross-Resistance: The amino acid substitutions that resulted in reduced susceptibility to foscarnet and either ganciclovir, acyclovir and/or cidofovir are summarized in Tables 5 and 6. TABLE 5 Summary of CMV DNA polymerase Amino Acid Substitutions Conferring Foscarnet Resistance with Cross-Resistance to Ganciclovir and/or Cidofovir Cross-resistant to ganciclovir CMV pUL54 Q578H, D588N, E756K, L773V, L776M, V781I, V787L, L802M, A809V, V812L, T813S, T821I, A834P, G841A/S, del 981-982 Cross-resistant tocidofovir CMV pUL54 Q578H, D588N, E756K, L773V, V812L, T813S, A834P, G841A, del 981-982 TABLE 6 Summary of HSV DNA polymerase Amino Acid Substitutions Conferring Foscarnet Resistance with Cross-Resistance to Acyclovir and/or Cidofovir Cross-resistant to acyclovir HSV-1 pUL30 E597D, S599L, A605V, D672N, R700G, L702H, V714M, V715G, A719T/V, S724N, L774F, L778M, D780N, L782I, P797T, E798K, L802F, V813M, V817M, Y818C, T821M, G841C/S, R842S, S889A, F891C/Y, V892M, D907V, A910V/T, SRA914-916LCV, Y941H, V958L, V959H HSV-2 pUL30 A724T, S725G, S729N, Q732R, L783M, D785N, T844I, D912V Marginally cross-resistant to cidofovir HSV-1 pUL30 V714M, A719V, S724N, L778M, L802F, Y818C, T821M, G841S HSV-2 pUL30 L783M Foscarnet-SPL-Structure

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 containing 6 equivalents of water of hydration with an empirical formula of Na 3 CO 5 P• 6 H 2 O and a molecular weight of 300.1. The structural formula is: FOSCAVIR has the potential to chelate divalent metal ions, such as calcium and magnesium, to form stable coordination compounds. FOSCAVIR INJECTION is a sterile, isotonic aqueous solution for intravenous administration only. The solution is clear and colorless. Each milliliter of FOSCAVIR contains 24 mg of foscarnet sodium hexahydrate in Water for Injection, USP. Hydrochloric acid may have been added to adjust the pH of the solution to 7.4. FOSCAVIR INJECTION contains no preservatives. structural formula

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 containing 6 equivalents of water of hydration with an empirical formula of Na 3 CO 5 P•6 H 2 O and a molecular weight of 300.1. The structural formula is: FOSCAVIR has the potential to chelate divalent metal ions, such as calcium and magnesium, to form stable coordination compounds. FOSCAVIR INJECTION is a sterile, isotonic aqueous solution for intravenous administration only. The solution is clear and colorless. Each milliliter of FOSCAVIR contains 24 mg of foscarnet sodium hexahydrate in Water for Injection, USP. Hydrochloric acid may have been added to adjust the pH of the solution to 7.4. FOSCAVIR INJECTION contains no preservatives. structural formula