UCSF Medical Center: Foscarnet Dosing and Monitoring

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Foscarnet

Dosing & Monitoring Guidelines for Management of Invasive CMV Disease

Indications:

-Foscarnet is used for the treatment of invasive CMV disease among patients with suspected or documented ganciclovir-resistant CMV.

Dosing:

-Careful attention to dosing is required given the dose-related toxicities of foscarnet. Foscarnet doses are based on renal function according to the adjusted Cockroft-Gault equation:

-Note that weight is not a factor in the adjusted Cockroft-Gault equation. Examples of estimates of corresponding non-adjusted creatinine clearance for a typical 70kg male are in parentheses to provide a comparison.

-Foscarnet dosing is weight-based; whether total or ideal/adjusted body weight should be used in obese patients is not known.

Foscarnet Dosing Guidelines

Indication

Adjusted CrCl (ml/min/kg)

[Non-adjusted CrCl for 70kg male (ml/min)]

>1.4

[>98]

1.0-1.4

0.8-1.0

0.6-0.8

0.5-0.6

0.4-0.5

<0.4

Intermittent

HD

[70-98]

[56-70]

[42-56]

[35-42]

[28-35]

[<28]

Induction

90mg/kg

q12h

70mg/kg q12h

50mg/kg q12h

80mg/kg q24h

60mg/kg q24h

50mg/kg q24h

NR*

60mg/kg pHD

Maintenance/ Secondary Prophylaxis

90-120 mg/kg q24h

70-90 mg/kg q24h

50-65 mg/kg q24h

80-105 mg/kg q48h

60-80 mg/kg q48h

50-65 mg/kg q48h

NR*

40-60 mg/kg pHD*

*Not FDA-approved dosing; NR=not recommended by manufacturer – consult ID pharmacy for recommendations

Important considerations for foscarnet administration:

-Infusion rate: infusion of foscarnet over <2h has been associated with symptomatic hypocalcemia (e.g. circumoral paresthesias). Initial doses should be infused over 2 hours. Reduction of infusion duration to no less than 1 hour may be attempted with careful monitoring.

-Infusion site: Infusion through a central line is recommended when available. If infusing through a peripheral line, the solution must be diluted to £12 mg/ml.

-Hydration: Ensuring adequate hydration is essential to mitigating the nephrotoxicity of foscarnet.Before the initial dose, administer 750-1000ml of D5 or NS over 1 hour. With subsequent doses, administer 500-1000ml of D5 or NS concurrently with the foscarnet. In patients with fluid overload, less (but not none) hydration may be given, recognizing the associated increased risk of nephrotoxicity.

Monitoring parameters:

-Renal function: Dose-related nephrotoxicity occurs in a substantial proportion of foscarnet recipients. Renal dysfunction usually (though not always) resolves 1-5 weeks after discontinuing foscarnet. During initial therapy and during hospitalization, serum creatinine should be monitored daily. Sustained (e.g. on 2 separate occasions) changes in serum creatinine of 0.4 mg/dl or more should warrant consideration for dose adjustment. For patients receiving foscarnet in an outpatient setting, serum creatinine should be monitored at least twice weekly. If creatinine increases substantially (e.g. >0.4mg/dl), consideration should be given to re-checking serum creatinine before infusion of next dose to determine if dose adjustment is necessary.

-Electrolytes: Depletion of Ca, K, Mg, Phos is common during foscarnet infusions. These electrolytes should be monitored 2-3 times weekly during the induction phase of foscarnet therapy (1-2 times weekly during maintenance therapy) and repleted as necessary. If electrolyte depletion is problematic, pretreatment with oral Ca, K, Mg or addition of electrolytes to hydration fluid (administered through a separate line from the foscarnet infusion), should be considered. Special caution should be used in patients with cardiac or seizure disorders.

-Hematologic: Anemia has been frequently described in association with foscarnet therapy in AIDS patients. A complete blood count should be obtained at least once weekly during therapy.

-Symptomatic: Nausea and vomiting may occur with foscarnet therapy. Pre-medication with anti-emetics may reduce the risk. Genital ulcerations occurring from excretion of foscarnet have been described; increased personal hygienic measures may be necessary. Symptoms of electrolyte abnormalities (tingling, paresthesias, arrhythmias, etc) should be monitored on follow-up visits.