Foscarnet warnings and precautions

# Warnings And Precautions

## WARNINGS

### Renal Impairment
THE MAJOR TOXICITY OF FOSCAVIR 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 FOSCAVIR 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 FOSCAVIR. 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 FOSCAVIR 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 7501000 mL of normal saline or 5% dextrose solution should be given prior to the first infusion of FOSCAVIR to establish diuresis. With subsequent infusions, 7501000 mL of hydration fluid should be given with 90-120 mg/kg of FOSCAVIR, and 500 mL with 4060 mg/kg of FOSCAVIR. 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 FOSCAVIR.

### Mineral and Electrolyte Abnormalities
FOSCAVIR has been associated with changes in serum electrolytes including hypocalcemia, hypophosphatemia, hyperphosphatemia, hypomagnesemia, and hypokalemia (see ADVERSE REACTIONS section). FOSCAVIR 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 FOSCAVIR 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 FOSCAVIR 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.

## PRECAUTIONS

### General
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 (seeDOSAGE AND ADMINISTRATION). 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. Adequate hydration with close attention to personal hygiene may minimize the occurrence of such events.

### Hemopoietic System
Anemia has been reported in 33% of patients receiving FOSCAVIR in controlled studies. Granulocytopenia has been reported in 17% of patients receiving FOSCAVIR in controlled studies; however, only 1% (2/189) were terminated from these studies because of neutropenia.

### Information for Patients
CMV Retinitis: Patients should be advised that FOSCAVIR is not a cure for CMV retinitis, and that they may continue to experience progression of retinitis during or following treatment. They should be advised to have regular ophthalmologic examinations.
Mucocutaneous Acyclovir-Resistant HSV Infections: Patients should be advised that FOSCAVIR is not a cure for HSV infections. While complete healing is possible, relapse occurs in most patients. Because relapse may be due to acyclovir-sensitive HSV, sensitivity testing of the viral isolate is advised. In addition, repeated treatment with FOSCAVIR has led to the development of resistance associated with poorer response. In the case of poor therapeutic response, sensitivity testing of the viral isolate also is advised.
General: Patients should be informed that the major toxicities of foscarnet are renal impairment, electrolyte disturbances, and seizures, and that dose modifications and possibly discontinuation may be required. The importance of close monitoring while on therapy must be emphasized. Patients should be advised of the importance of reporting to their physicians symptoms of perioral tingling, numbness in the extremities or paresthesias during or after infusion as possible symptoms of electrolyte abnormalities. Should such symptoms occur, the infusion of FOSCAVIR should be stopped, appropriate laboratory samples for assessment of electrolyte concentrations obtained, and a physician consulted before resuming treatment. The rate of infusion must be no more than 1 mg/kg/minute. The potential for renal impairment may be minimized by accompanying FOSCAVIR administration with hydration adequate to establish and maintain a diuresis during dosing.