Foscarnet

The rate of controlled intravenous infusion must be no more than 1 mg/kg/minute. An individualized dose of foscarnet sodium injection should be calculated on the basis of body weight (mg/kg), renal function, indication of use and dosing frequency (refer to DOSAGE subsection). To reduce the risk of nephrotoxicity, creatinine clearance (mL/min/kg) should be calculated even if serum creatinine is within the normal range, and doses should be adjusted accordingly.

If accidental contact occurs, the exposed area should be flushed with water. DOSAGE THE RECOMMENDED DOSAGE, FREQUENCY, OR INFUSION RATES SHOULD NOT BE EXCEEDED. ALL DOSES MUST BE INDIVIDUALIZED FOR PATIENTS’ RENAL FUNCTION. Induction Treatment The recommended initial dose of foscarnet sodium injection for patients with normal renal function is: For CMV retinitis patients, either 90 mg/kg (1-1/2 to 2 hour infusion) every twelve hours or 60 mg/kg (minimum one hour infusion) every eight hours over 2 to 3 weeks depending on clinical response.

Maintenance Treatment Following induction treatment the recommended maintenance dose of foscarnet sodium injection for CMV retinitis is 90 mg/kg/day to 120 mg/kg/day (individualized for renal function) given as an intravenous infusion over 2 hours. Because the superiority of the 120 mg/kg/day has not been established in controlled trials, and given the likely relationship of higher plasma foscarnet levels to toxicity, it is recommended that most patients be started on maintenance treatment with a dose of 90 mg/kg/day.

Because of physical incompatibility, foscarnet sodium injection and ganciclovir must NOT be mixed. Use in Patients with Abnormal Renal Function Foscarnet sodium injection should be used with caution in patients with abnormal renal function because reduced plasma clearance of foscarnet will result in elevated plasma levels (see CLINICAL PHARMACOLOGY ).

In addition, foscarnet sodium injection has the potential to further impair renal function (see WARNINGS ). 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. Renal function must be monitored carefully at baseline and during induction and maintenance therapy with appropriate dose adjustments for foscarnet sodium injection as outlined below (see Dose Adjustment and PATIENT MONITORING ).

During foscarnet sodium injection therapy if creatinine clearance falls below the limits of the dosing nomograms (0.4 mL/min/kg), foscarnet sodium injection should be discontinued, the patient hydrated, and monitored daily until resolution of renal impairment is ensured. Foscarnet sodium injection is not recommended in patients undergoing hemodialysis because dosage guidelines have not been established.

Dose Adjustment Foscarnet sodium injection dosing must be individualized according to the patient’s renal function status. Refer to Table 13 below for recommended doses and adjust the dose as indicated. Even patients with serum creatinine in the normal range may require dose adjustment; therefore, the dose should be calculated at baseline and frequently thereafter.

To use this dosing guide, actual 24-hour creatinine clearance (mL/min) must be divided by body weight (kg), or the estimated creatinine clearance in mL/min/kg can be calculated from serum creatinine (mg/dL) using the following formula (modified Cockcroft and Gault equation): TABLE 13: Foscarnet sodium injection Dosage Guide Induction [See table below.] Maintenance [See table below.] < means “less than”.

PATIENT MONITORING The majority of patients will experience some decrease in renal function due to foscarnet sodium injection administration. Therefore, it is recommended that creatinine clearance, either measured or estimated using the modified Cockcroft and Gault equation based on serum creatinine, be determined at baseline, 2 to 3 times per week during induction therapy and once weekly during maintenance therapy, with foscarnet sodium injection dose adjusted accordingly (see Dose Adjustment ).

More frequent monitoring may be required for some patients. It is also recommended that a 24-hour creatinine clearance be determined at baseline and periodically thereafter to ensure correct dosing (assuming verification of an adequate collection using creatinine index). Foscarnet sodium injection should be discontinued if creatinine clearance drops below 0.4 mL/min/kg.

DOSAGE AND ADMINISTRATION CAUTION - DO NOT ADMINISTER FOSCARNET SODIUM INJECTION BY RAPID OR BOLUS INTRAVENOUS INJECTION. THE TOXICITY OF FOSCARNET SODIUM INJECTION 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. ADMINISTRATION Instructions for Administration and Preparation Foscarnet sodium injection is administered by controlled intravenous infusion, either by using a central venous line or with dilution by using a peripheral vein.

An individualized dose at the required concentration (24 mg/mL or 12 mg/mL) for the route of administration (central line or peripheral line) needs to be aseptically prepared prior to dispensing. The standard 24 mg/mL solution may be used with or without dilution when using a central venous catheter for infusion. When a peripheral vein catheter is used, the 24 mg/mL injection must be diluted to a 12 mg/mL concentration with 5% dextrose in water or with a normal saline solution prior to administration to avoid local irritation of peripheral veins.

Dilutions and/or removals of excess quantities should be accomplished under aseptic conditions. Solutions thus prepared should be used within 24 hours of first entry into a sealed bottle or infusion bag. Hydration Hydration may reduce the risk of nephrotoxicity. Clinically dehydrated patients should have their condition corrected before initiating foscarnet sodium injection therapy.

It is recommended that 750 to 1,000 mL of normal saline or 5% dextrose solution should be given prior to the first infusion of foscarnet sodium injection to establish diuresis. With subsequent infusions, 750 to 1,000 mL of hydration fluid should be given with 90 mg/kg to 120 mg/kg of foscarnet sodium injection, and 500 mL with 40 mg/kg to 60 mg/kg of foscarnet sodium injection.

Hydration fluid may need to be decreased if clinically warranted. Oral rehydration with similar regimens may be considered in certain patients. After the first dose, the hydration fluid should be administered concurrently with each infusion of foscarnet sodium injection. Compatibility With Other Solutions/Drugs Other drugs and supplements can be administered to a patient receiving foscarnet sodium injection.

However, care must be taken to ensure that foscarnet sodium injection is only administered with normal saline or 5% dextrose solution and that no other drug or supplement is administered concurrently via the same catheter. Foscarnet has been reported to be chemically incompatible with 30% dextrose, amphotericin B, and solutions containing calcium such as Ringer’s lactate and TPN.

Physical incompatibility with other intravenous drugs has also been reported including acyclovir sodium, ganciclovir, trimetrexate glucuronate, pentamidine isethionate, vancomycin, trimethoprim/sulfamethoxazole, diazepam, midazolam, digoxin, phenytoin, leucovorin, and proclorperazine. Because of foscarnet’s chelating properties, a precipitate can potentially occur when divalent cations are administered concurrently in the same catheter.

Parenteral drug products must be inspected visually for particulate matter and discoloration prior to administration whenever the solution and container permit. Solutions that are discolored or contain particulate matter should not be used. Accidental Exposure Accidental skin and eye contact with foscarnet sodium solution may cause local irritation and burning sensation.

For acyclovir-resistant HSV patients, 40 mg/kg (minimum one hour infusion) either every 8 or 12 hours for 2 to 3 weeks or until healed. An infusion pump must be used to control the rate of infusion. Adequate hydration is recommended to establish a diuresis (see Hydration for recommendation ), both prior to and during treatment to minimize renal toxicity (see WARNINGS ), provided there are no clinical contraindications.

Escalation to 120 mg/kg/day may be considered should early re-induction be required because of retinitis progression. Some patients who show excellent tolerance to foscarnet sodium injection may benefit from initiation of maintenance treatment at 120 mg/kg/day earlier in their treatment. An infusion pump must be used to control the rate of infusion with all doses.