Foscarnet

CMV Retinitis FOSCAVIR is indicated for the treatment of CMV retinitis in patients with acquired immunodeficiency syndrome (AIDS). Combination therapy with FOSCAVIR and ganciclovir is indicated for patients who have relapsed after monotherapy with either drug. SAFETY AND EFFICACY OF FOSCAVIR HAVE NOT BEEN ESTABLISHED FOR TREATMENT OF OTHER CMV INFECTIONS (e.g., PNEUMONITIS, GASTROENTERITIS), CONGENITAL OR NEONATAL CMV DISEASE, OR NONIMMUNOCOMPROMISED INDIVIDUALS. Mucocutaneous Acyclovir Resistant HSV Infections FOSCAVIR is indicated for the treatment of acyclovir-resistant mucocutaneous HSV infections in immunocompromised patients. SAFETY AND EFFICACY OF FOSCAVIR HAVE NOT BEEN ESTABLISHED FOR TREATMENT OF OTHER HSV INFECTIONS (e.g., RETINITIS, ENCEPHALITIS), CONGENITAL OR NEONATAL HSV DISEASE, OR HSV IN NONIMMUNOCOMPROMISED INDIVIDUALS.

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.

CAUTION - DO NOT ADMINISTER FOSCAVIR BY RAPID OR BOLUS INTRAVENOUS INJECTION. THE TOXICITY OF FOSCAVIR 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.

FOSCAVIR is contraindicated in patients with clinically significant hypersensitivity to foscarnet sodium.

WARNING 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. SEIZURES, RELATED TO ALTERATIONS IN PLASMA MINERALS AND ELECTROLYTES, HAVE BEEN ASSOCIATED WITH FOSCAVIR TREATMENT. THEREFORE, PATIENTS MUST BE CAREFULLY MONITORED FOR SUCH CHANGES AND THEIR POTENTIAL SEQUELAE. Renal Impairment THE MAJOR TOXICITY OF FOSCAVIR IS RENAL IMPAIRMENT. Renal impairment is most likely to become clinically evident during the second week of induction therapy, but may occur at any time during FOSCAVIR treatment. Renal function should be monitored carefully during both induction and maintenance therapy. Elevations in serum creatinine are usually, but not always, reversible following discontinuation or dose adjustment of FOSCAVIR.

THE MAJOR TOXICITY OF FOSCAVIR IS RENAL IMPAIRMENT. Approximately 33% of 189 patients with AIDS and CMV retinitis who received FOSCAVIR (60 mg/kg TID), without adequate hydration, developed significant impairment of renal function (serum creatinine ≥ 2.0 mg/dL). The incidence of renal impairment in subsequent clinical trials in which 1000 mL of normal saline or 5% dextrose solution was given with each infusion of FOSCAVIR was 12% (34/280). FOSCAVIR has been associated with changes in serum electrolytes including hypocalcemia (15–30%), hypophosphatemia (8–26%) and hyperphosphatemia (6%), hypomagnesemia (15–30%), and hypokalemia (16–48%). The higher percentages were derived from those patients receiving hydration. FOSCAVIR treatment was associated with seizures in 18/189 (10%) AIDS patients in the initial five controlled studies.

A possible drug interaction of FOSCAVIR and intravenous pentamidine has been described. Concomitant treatment of four patients in the United Kingdom with FOSCAVIR and intravenous pentamidine may have caused hypocalcemia, one patient died with severe hypocalcemia. Toxicity associated with concomitant use of aerosolized pentamidine has not been reported. Because FOSCAVIR can reduce serum levels of ionized calcium, extreme caution is advised when used concurrently with other drugs known to influence serum calcium levels (e.g., intravenous pentamidine). Renal impairment and symptomatic hypocalcemia have been observed during concurrent treatment with FOSCAVIR and intravenous pentamidine.

Store between 20° and 25°C (68° and 77°F). Protect from excessive heat (above 40°C) and from freezing. If refrigerated or exposed to temperatures below the freezing point, precipitation may occur. By keeping the bottle or infusion bag at room temperature with repeated shaking, the precipitate can be brought into solution again.