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THE MAJOR TOXICITY OF FOSCAVIR IS RENAL IMPAIRMENT (see WARNINGS section). Approximately 33% of 189 patients with AIDS and CMV retinitis who received FOSCAVIR (foscarnet sodium injection) (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 (foscarnet sodium injection) was 12% (34/280).
FOSCAVIR (foscarnet sodium injection) 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%) (see WARNINGS section). The higher percentages were derived from those patients receiving hydration.
FOSCAVIR (foscarnet sodium injection) treatment was associated with seizures in 18/189 (10%) AIDS patients in the initial five controlled studies (see WARNINGS section). Risk factors associated with seizures included impaired baseline renal function, low total serum calcium, and underlying CNS conditions predisposing the patient to seizures. The rate of seizures did not increase with duration of treatment. Three cases were associated with overdoses of FOSCAVIR (see OVERDOSAGE section).
In five controlled U.S. clinical trials the most frequently reported adverse events in patients with AIDS and CMV retinitis are shown in Table 5. These figures were calculated without reference to drug relationship or severity.
TABLE 5: Adverse Events Reported in Five Controlled US Clinical
|n = 189||n = 189|
|Fever||65%||Abnormal Renal Function||27%|
From the same controlled studies, adverse events categorized by investigator as "severe" are shown in Table 6. Although death was specifically attributed to FOSCAVIR (foscarnet sodium injection) in only one case, other complications of FOSCAVIR (foscarnet sodium injection) (ie, renal impairment, electrolyte abnormalities, and seizures) may have contributed to patient deaths (see WARNINGS section).
TABLE 6 - Severe Adverse Events
|n = 189|
|Abnormal Renal Function||14%|
From the five initial U.S. controlled trials of FOSCAVIR (foscarnet sodium injection) , the following list of adverse events has been compiled regardless of causal relationship to FOSCAVIR (foscarnet sodium injection) . Evaluation of these reports was difficult because of the diverse manifestations of the underlying disease and because most patients received numerous concomitant medications.
Incidence 5% or Greater
Metabolic and Nutritional: mineral and electrolyte imbalances (see WARNINGS) including hypokalemia, hypocalcemia, hypomagnesemia, hypophosphatemia, hyperphosphatemia
Respiratory System: coughing, dyspnea
Skin and Appendages: rash, increased sweating
Urinary: alterations in renal function including increased serum creatinine, decreased creatinine clearance, and abnormal renal function (see WARNINGS)
Special Senses: vision abnormalities
Incidence between 1% and 5%
Application Site: injection site pain, injection site inflammation
Cardiovascular: hypertension, palpitations, ECG abnormalities including sinus tachycardia, first degree AV block and non-specific ST-T segment changes, hypotension, flushing, cerebrovascular disorder (see WARNINGS)
Central and Peripheral Nervous System: tremor, ataxia, dementia, stupor, generalized spasms, sensory disturbances, meningitis, aphasia, abnormal coordination, leg cramps, EEG abnormalities (see WARNINGS)
Liver and Biliary: abnormal A-G ratio, abnormal hepatic function, increased SGPT, increased SGOT
Neoplasms: lymphoma-like disorder, sarcoma
Special Senses:taste perversions, eye abnormalities, eye pain, conjunctivitis
Selected adverse events occurring at a rate of less than 1% in the five initial U.S. controlled clinical trials of FOSCAVIR (foscarnet sodium injection) include: syndrome of inappropriate antidiuretic hormone secretion, pancytopenia, hematuria, dehydration, hypoproteinemia, increases in amylase and creatinine phosphokinase, cardiac arrest, coma, and other cardiovascular and neurologic complications.
Selected adverse event data from the Foscarnet vs. Ganciclovir CMV Retinitis Trial (FGCRT), performed by the Studies of the Ocular Complications of AIDS (SOCA) Research Group, are shown in Table 7 (see Clinical Trials section).
TABLE 7: FGCRT: SELECTED ADVERSE EVENTS*
|No. of Events||No. of Patients||Rates†||No. of Events||No. of Patients||Rates†|
|Absolute neutrophil count decreasing to < 0.50 x 109 per liter||63||41||1.30||31||17||0.72|
|Serum creatinine increasing to > 260 µmol per liter (> 2.9 mg/dL)||6||4||0.12||13||9||0.30|
|*Values for the treatment groups refer only to patients who
completed at least one follow-up visit - ie, 113 to 119 patients in the
ganciclovir group and 93 to 100 in the foscarnet group. "Events"
denotes all events observed and "patients" the number of patients
with one or more of the indicated events.
†Per person-year at risk
‡Final frozen SOCA I database dated October 1991.
Selected adverse events from ACTG Study 228 (CRRT) comparing combination therapy with FOSCAVIR (foscarnet sodium injection) or ganciclovir monotherapy are shown in Table 8. The most common reason for a treatment change in patients assigned to either FOSCAVIR (foscarnet sodium injection) or ganciclovir was retinitis progression. The most frequent reason for a treatment change in the combination treatment group was toxicity.
TABLE 8: CRRT: Selected Adverse Events
|No. Events||No. Pts.*||Rate†||No. Events||No. Pts.*||Rate†||No. Events||No. Pts.*||Rate†|
|Anemia(Hgb < 70 g/L)||11||7||0.20||9||7||0.14||19||15||0.33|
|ANC < 0.75 x 109 cells/L||86||32||1.53||95||41||1.51||107||51||1.91|
|ANC < 0.50 x 109 cells/L||50||25||0.91||49||28||0.80||50||28||0.85|
|Platelets < 50 x 109/L||28||14||0.50||19||8||0.43||40||15||0.56|
|Platelets < 20 x 109/L||1||1||0.01||6||2||0.05||7||6||0.18|
|Creatinine > 260 µmol/L (> 2.9 mg/dL)||9||7||0.15||10||7||0.17||11||10||0.20|
|*Pts. = patients with event;
†Rate = events/person/year;
‡ANC = absolute neutrophil count
Adverse events that have been reported in post-marketing surveillance include: ventricular arrhythmia, prolongation of QT interval, gamma GT increased, diabetes insipidus (usually nephrogenic), renal calculus, and muscle disorders including myopathy, myositis, muscle weakness and rare cases of rhabdomyolysis. Cases of vesiculobullous eruptions including erythema multiforme, toxic epidermal necrolysis, and Stevens-Johnson Syndrome have been reported. In most cases, patients were taking other medications that have been associated with toxic epidermal necrolysis or Stevens-Johnson Syndrome.
Read the Foscavir (foscarnet sodium injection) Side Effects Center for a complete guide to possible side effects
A possible drug interaction of FOSCAVIR (foscarnet sodium injection) and intravenous pentamidine has been described. Concomitant treatment of four patients in the United Kingdom with FOSCAVIR (foscarnet sodium injection) 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.
Since FOSCAVIR (foscarnet sodium injection) decreases serum concentrations of ionized calcium, concurrent treatment with other drugs known to influence serum calcium concentrations should be used with particular caution. Fatalities have been reported in post-marketing surveillance during concomitant therapy with FOSCAVIR (foscarnet sodium injection) and Pentamidine.
Because of foscarnet's tendency to cause renal impairment, the use of FOSCAVIR (foscarnet sodium injection) should be avoided in combination with potentially nephrotoxic drugs such as aminoglycosides, amphotericin B and intravenous pentamidine (see above) unless the potential benefits outweigh the risks to the patient.
Abnormal renal function has been observed in clinical practice during the use of FOSCAVIR (foscarnet sodium injection) and ritonavir, or FOSCAVIR, ritonavir, and saquinavir. (See DOSAGE AND ADMINISTRATION.)
Ganciclovir: The pharmacokinetics of foscarnet and ganciclovir were not altered in 13 patients receiving either concomitant therapy or daily alternating therapy for maintenance of CMV disease.
Read the Foscavir Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 9/11/2008
This monograph has been modified to include the generic and brand name in many instances.
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