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Foscarnet

Class: Antivirals, Miscellaneous
VA Class: AM800
Chemical Name: Dihydroxyphosphinecarboxylic acid oxide trisodium salt
Molecular Formula: CNa3O5P
CAS Number: 63585-09-1
Brands: Foscavir

Medically reviewed by Drugs.com. Last updated on Aug 19, 2019.

Warning

  • Major toxicity is renal impairment.1 Adequate hydration, frequent monitoring of Scr, and dosage adjustments based on changes in renal function are imperative.1 (See Dosage and Administration.)

  • Seizures related to alterations in plasma minerals and electrolytes may occur.1 Carefully monitor for such changes and their potential sequelae.1 Mineral and electrolyte supplementation may be required.1

  • The only FDA-labeled indications are treatment of cytomegalovirus (CMV) retinitis in HIV-infected patients and treatment of mucocutaneous acyclovir-resistant herpes simplex virus (HSV) infections in immunocompromised patients.1

Introduction

Antiviral; organic analog of inorganic pyrophosphate; active against herpesviruses.1 2 3 4 85

Uses for Foscarnet

Cytomegalovirus (CMV) Retinitis

Initial treatment (induction therapy) and maintenance therapy (secondary prophylaxis) of CMV retinitis in HIV-infected adults, including those with acquired immunodeficiency syndrome (AIDS).1 2 3 4 33 155 Also used for management of CMV retinitis in HIV-infected pediatric patients.155 156

Safety and efficacy not established for treatment of CMV retinitis in immunocompetent individuals.1

Like other antivirals, foscarnet is not a cure for CMV retinitis; stabilization or improvement of ocular manifestations may occur, but relapse and/or progression of CMV retinitis possible during or following foscarnet therapy.1 2 3 4

Retinitis is the most common clinical manifestation of CMV end-organ disease in HIV-infected patients;155 156 ideally should be managed in consultation with an ophthalmologist familiar with diagnosis and treatment of retinal diseases.155 156

Select antiviral regimen for initial treatment of CMV retinitis in HIV-infected individuals based on location and severity of the CMV retinal lesions, severity of underlying immunosuppression, concomitant drug therapy, and patient’s ability to adhere to the treatment regimen.155 156 Select antiviral regimen for maintenance therapy based on location of CMV retinal lesions, vision in contralateral eye, patient's immunologic and virologic status, and patient's response to antiretroviral therapy.155 156

For management of immediate sight-threatening CMV retinal lesions (i.e., within 1.5 mm of the fovea) in HIV-infected adults and adolescents, CDC, NIH, and IDSA state that the preferred regimen is initial treatment (induction therapy) with intravitreal ganciclovir or intravitreal foscarnet (1–4 doses over 7–10 days) in conjunction with oral valganciclovir (twice daily for 14–21 days) followed by maintenance therapy (secondary prophylaxis) with oral valganciclovir (once daily).155 One alternative regimen recommended by these experts for sight-threatening CMV retinitis in HIV-infected adults and adolescents is intravitreal ganciclovir or intravitreal foscarnet (1–4 doses over 7–10 days) in conjunction with IV foscarnet (2 or 3 times daily for 2–3 weeks) followed by maintenance therapy (secondary prophylaxis) with IV foscarnet (once daily).155 Systemic antivirals (without an intravitreal antiviral) usually adequate for management of CMV retinitis in patients with only small peripheral lesions.155

For management of CMV retinitis in HIV-infected pediatric patients, CDC, NIH, IDSA, and others state that IV ganciclovir is drug of choice for initial treatment (induction therapy) and one of several options for maintenance therapy (secondary prophylaxis).156 These experts state that IV foscarnet is a preferred alternative for management of CMV retinitis in HIV-infected children and is recommended for infections known or suspected to be caused by ganciclovir-resistant CMV.156 These experts state that a regimen of IV ganciclovir and IV foscarnet can be considered for initial treatment (induction therapy) in HIV-infected children with sight-threatening CMV retinitis or when the infection failed to respond to or relapsed after monotherapy.156 Data are limited regarding use of intravitreal antivirals in children;156 intravitreal injections are impractical in most children.156

Because of risk of relapse, chronic maintenance therapy (secondary prophylaxis) of CMV retinitis usually continued until immune reconstitution occurs as a result of effective antiretroviral therapy.155 CDC, NIH, and IDSA state that discontinuance of maintenance therapy of CMV retinitis can be considered in HIV-infected adults and adolescents if CMV lesions have been treated for ≥3–6 months and are inactive and there has been a sustained (i.e., 3–6 months) increase in CD4+ T-cell count to >100/mm3 in response to antiretroviral therapy.155 156 Although safety of discontinuing maintenance therapy of CMV retinitis in HIV-infected pediatric patients not well studied, discontinuance of such therapy can be considered in those receiving antiretroviral therapy who have a sustained (i.e., >6 months) increase in CD4+ T-cell percentage to >15% (children <6 years of age) or increase in CD4+ T-cell count to >100/mm3 (children ≥6 years of age).156

If maintenance therapy of CMV retinitis is discontinued, continue regular ophthalmologic monitoring (optimally every 3–6 months) for early detection of CMV relapse or immune reconstitution uveitis.155 156 If CD4+ T-cell count decreases to <100/mm3 (adults, adolescents, children ≥6 years of age) or CD4+ T-cell percentage decreases to <15% (children <6 years of age), reinitiate CMV retinitis maintenance therapy.155 156

Extraocular CMV Infections

Safety and efficacy not established for management of extraocular CMV infections (e.g., pneumonitis, gastroenteritis) or for congenital or neonatal CMV disease.1

CDC, NIH, and IDSA state that IV ganciclovir usually is the preferred antiviral for initial management of CMV GI disease; however, IV foscarnet is a possible alternative for management of CMV esophagitis or colitis in HIV-infected adults who cannot receive ganciclovir or have infections caused by ganciclovir-resistant CMV.155

For management of well-documented CMV pneumonitis in HIV-infected adults, CDC, NIH, and IDSA state that either IV ganciclovir or IV foscarnet is a reasonable choice.155

Combination regimen of IV ganciclovir and IV foscarnet has been used for management of CMV neurologic disease (e.g., CMV encephalitis or myelitis)85 and is recommended by CDC, NIH, IDSA, and others for such infections in HIV-infected individuals.155 156

Prevention of CMV Infection and Disease

Has been used for prophylaxis or preemptive antiviral treatment of CMV infection and disease in hematopoietic stem cell transplant (HSCT) recipients.39 74 75 76 77 78 85

Although safety and efficacy not established, IV foscarnet is considered a second-line or alternative antiviral for prophylaxis or preemptive treatment of CMV infection in HSCT recipients; usually reserved for resistant and refractory CMV infections or when first-line antivirals cannot be used because of intolerance.74 75 76 78

Also recommended as a second-line or alternative antiviral for treatment of CMV infection in solid organ transplant recipients when first-line antivirals cannot be used because of resistance or intolerance.82

Mucocutaneous Herpes Simplex Virus (HSV) Infections

Management of mucocutaneous infections (e.g., orofacial, genital, digital) caused by acyclovir-resistant HSV types 1 and 2 (HSV-1 and HSV-2) in immunocompromised individuals, including those with AIDS.1 33 40 41 42 43 44 45 46 48 49 50 51 56 57 155 344

Safety and efficacy not established for treatment of other HSV infections (e.g., retinitis, encephalitis), congenital or neonatal HSV disease, or HSV infections in immunocompetent individuals.1

Drugs of choice for management of orolabial lesions or initial or recurrent genital lesions caused by HSV are valacyclovir, famciclovir, and acyclovir.155 156 344

For management of mucocutaneous lesions caused by acyclovir-resistant HSV in HIV-infected adults, adolescents, and children, CDC, NIH, IDSA, and others recommend IV foscarnet as drug of choice.155 156

Like other antivirals, foscarnet is not a cure for mucocutaneous HSV infections.1 While complete healing is possible, relapse occurs in most patients.1 Resistance may develop following repeated foscarnet treatment.1 In vitro susceptibility testing advised if there is a poor therapeutic response to the drug.1

Varicella-Zoster Virus (VZV) Infections

Management of acyclovir-resistant VZV infections in immunocompromised patients, including those with AIDS.52 53 70 85 156

Preferred antivirals for management of acute, localized herpes zoster (shingles) in HIV-infected adults and adolescents are acyclovir, famciclovir, and valacyclovir.155 For management of proven or suspected acyclovir-resistant VZV infections in HIV-infected adults or adolescents, CDC, NIH, and IDSA recommend IV foscarnet.155

In HIV-infected children, acyclovir is drug of choice for treatment of VZV infections and foscarnet is the preferred alternative for treatment of acyclovir-resistant VZV infections.156

Although optimal regimens for management of progressive outer retinal necrosis caused by VZV not identified, CDC, NIH, and IDSA recommend that HIV-infected adults and adolescents be treated with at least one IV antiviral (acyclovir, ganciclovir, foscarnet, cidofovir) used in conjunction with at least one intravitreal antiviral (ganciclovir or foscarnet).155 Prognosis for visual preservation in patients with progressive outer retinal necrosis caused by VZV is poor;155 such infections should be managed in consultation with an ophthalmologist.155

Foscarnet Dosage and Administration

General

  • Renal function must be assessed prior to initiation of foscarnet and monitored during therapy with the drug.1

  • To reduce risk of foscarnet-associated nephrotoxicity, patients must receive adequate hydration prior to and during treatment with the drug.1

  • Must not exceed recommended foscarnet dosage and recommended frequency and rate of administration.1

Hydration

  • Correct hydration status in clinically dehydrated patients prior to initiating foscarnet.1

  • Prior to first foscarnet dose, administer 750–1000 mL of 0.9% sodium chloride or 5% dextrose solution to establish diuresis.1

  • With each subsequent foscarnet dose, administer 750–1000 mL of IV hydration fluid concurrently with each foscarnet dose of 90–120 mg/kg or administer 500 mL of IV hydration fluid concurrently with each foscarnet dose of 40–60 mg/kg.1

  • Volume of IV hydration fluid may be decreased if clinically appropriate.1

  • Oral rehydration using similar regimens may be considered in some patients.1 37

Administration

Administer by slow IV infusion using a controlled-infusion device (e.g., pump).1 Do not administer by rapid IV infusion or direct IV injection since potentially toxic plasma foscarnet concentrations may result.1

Has been administered by intravitreal injection;79 80 86 155 85 a preparation of foscarnet specifically for intravitreal administration not commercially available in US.

IV Infusion

Must be administered using a controlled-infusion device (e.g., pump);1 rate of administration must be carefully controlled to avoid adverse effects and unintentional overdosage.1

Commercially available as a solution for IV infusion containing 24 mg/mL.1

If a central venous line used for IV infusion, the commercially available foscarnet solution can be administered either undiluted or diluted.1

If a peripheral vein used for IV infusion, the commercially available foscarnet solution must be diluted prior to administration with a compatible infusion solution to a concentration of 12 mg/mL.1 In addition, take care to select a vein that will provide adequate blood flow for rapid dilution and distribution of the drug.1

Foscarnet solutions should appear clear and colorless; do not use if discolored or contains particles.1

Do not admix foscarnet or administer through the same catheter as other drugs.1

Exercise caution when preparing and administering foscarnet solutions.1 Accidental skin and eye contact with the drug may cause local irritation and burning sensation.1 If accidental contact occurs, flush exposed area with water.1

Dilution

When a diluted solution of foscarnet is indicated for IV infusion (e.g., for infusion via a peripheral vein), commercially available foscarnet solution containing 24 mg/mL must be diluted with 0.9% sodium chloride injection or 5% dextrose injection to a concentration of 12 mg/mL.1 4

Use diluted foscarnet solutions within 24 hours after first entry into the sealed bottle.1 (See Storage under Stability.)

Rate of Administration

IV infusions should be given at a constant rate and usually are given over 1–2 hours depending on dosage.1

IV infusion rate must not exceed 1 mg/kg per minute.1

Dosage

Available as the hydrated trisodium salt (i.e., foscarnet sodium);1 dosage is expressed in terms of foscarnet sodium.1

Pediatric Patients

CMV Retinitis in HIV-infected Pediatric Patients†
IV

Initial treatment (induction therapy): CDC, NIH, IDSA, and others recommend 60 mg/kg every 8 hours or 90 mg/kg every 12 hours for 14–21 days or until symptomatic improvement.156

Maintenance therapy (secondary prophylaxis): CDC, NIH, IDSA, and others recommend 90–120 mg/kg once daily.156

Make decisions regarding discontinuance of CMV retinitis maintenance therapy in consultation with an ophthalmologist.156 (See Cytomegalovirus [CMV] Retinitis under Uses.)

Disseminated CMV Infections in HIV-infected Pediatric Patients†
IV

Initial treatment (induction therapy): CDC, NIH, IDSA, and others recommend 60 mg/kg every 8 hours or 90 mg/kg every 12 hours until symptomatic improvement.156 Used with or without IV ganciclovir.156

Maintenance therapy (secondary prophylaxis): CDC, NIH, IDSA, and others recommend 90–120 mg/kg once daily.156

Mucocutaneous HSV Infections
Mucocutaneous Acyclovir-resistant HSV Infections in HIV-infected Pediatric Patients†
IV

CDC, NIH, IDSA, and others recommend 40 mg/kg every 8 hours or 60 mg/kg every 12 hours (by IV infusion over 2 hours).156

VZV Infections†
Acyclovir-resistant VZV Infections in HIV-infected Pediatric Patients†
IV

CDC, NIH, IDSA, and others recommend 40–60 mg/kg (by IV infusion over 2 hours) given 3 times daily for 7–10 days or until no new lesions have appeared for ≥48 hours.156

Progressive Outer Retinal Necrosis Caused by VZV in HIV-infected Pediatric Patients†
IV

CDC, NIH, IDSA, and others state 90 mg/kg every 12 hours (used with or without IV ganciclovir) in conjunction with intravitreal foscarnet (used with or without intravitreal ganciclovir) can be considered.156

Adults

CMV Retinitis in HIV-infected Adults
IV

Initial treatment (induction therapy): 60 mg/kg (by IV infusion over ≥1 hour) every 8 hours for 14–21 days1 2 4 33 155 or 90 mg/kg (by IV infusion over 1.5–2 hours) every 12 hours for 14–21 days.1 33 155 If patient has immediate sight-threatening CMV retinal lesions, CDC, NIH, and IDSA recommend that initial treatment also include an intravitreal antiviral.155 (See Cytomegalovirus [CMV] Retinitis under Uses.)

Maintenance therapy (secondary prophylaxis): 90–120 mg/kg (by IV infusion over 2 hours) once daily.1 2 3 4 33 155 Most patients should receive a dosage of 90 mg/kg daily initially since the higher dosage may be associated with increased toxicity;1 2 3 4 dosage may be increased up to 120 mg/kg daily if early reinduction therapy is required because of further progression of CMV retinitis.1 Some patients exhibiting excellent tolerance to foscarnet may benefit from early initiation of a maintenance dosage of 120 mg/kg daily.1

If relapse or progression of CMV retinitis occurs during maintenance therapy, retreat with foscarnet using usual dosages for initial treatment and maintenance therapy or, alternatively, consider combination therapy with foscarnet and ganciclovir.1 63 155

Make decisions regarding discontinuance of CMV retinitis maintenance therapy in consultation with an ophthalmologist.155 (See Cytomegalovirus [CMV] Retinitis under Uses.)

Extraocular CMV Infections in HIV-infected Adults†
CMV Esophagitis† or Colitis†
IV

CDC, NIH, and IDSA recommend 60 mg/kg every 8 hours or 90 mg/kg every 12 hours given for 21–42 days or until signs and symptoms of the infection resolve.155 Maintenance therapy (secondary prophylaxis) not usually necessary, but can be considered if relapse occurs.155

CMV Pneumonitis†
IV

CDC, NIH, and IDSA recommend same dosage used for management of CMV retinitis in HIV-infected adults.155 Optimal duration of treatment not established.155

CMV Neurologic Disease†
IV

CDC, NIH, and IDSA recommend same dosage used for management of CMV retinitis in HIV-infected adults.155 Optimal duration of treatment not established.155

Mucocutaneous HSV Infections
Mucocutaneous Acyclovir-resistant HSV Infections in Immunocompromised Adults
IV

40 mg/kg (by IV infusion over ≥1 hour) every 8 or 12 hours for 2–3 weeks or until clinical resolution.1 33 40 46

Genital herpes: CDC states 40–80 mg/kg every 8 hours until clinical resolution has been effective.344

HIV-infected adults: CDC, NIH, and IDSA recommend 80–120 mg/kg daily in 2 or 3 divided doses until clinical response.155

VZV Infections†
Acyclovir-resistant VZV Infections in Immunocompromised Adults†
IV

40–60 mg/kg every 8 hours for 10–21 days.33 52 53

Progressive Outer Retinal Necrosis Caused by VZV in HIV-infected Adults†
IV

CDC, NIH, and IDSA state 90 mg/kg every 12 hours (used with or without IV ganciclovir) in conjunction with intravitreal foscarnet (used with or without intravitreal ganciclovir) can be considered.155

Special Populations

Hepatic Impairment

Manufacturer makes no specific recommendation for dosage in patients with hepatic impairment;1 some clinicians state dosage adjustment not needed in such patients.85

Renal Impairment

Dosage must be modified based on degree of renal impairment.1 4 66

Consider that dosage adjustment may be required in patients with initially normal renal function since most patients experience a decrease in renal function during foscarnet therapy.1 2 4

Assess renal function (i.e., measured and estimated Clcr) prior to initiating foscarnet, 2 or 3 times weekly during induction therapy, and at least once every 1 or 2 weeks during maintenance therapy and adjust dosage accordingly.1 2 4 (See Table 1 and Table 2.)

Dosage adjustments are based on the patient’s measured or estimated Clcr.1 4 Calculate Clcr even if Scr is within the normal range.1

If Clcr declines to <0.4 mL/minute per kg during foscarnet therapy, discontinue the drug, hydrate patient, and monitor daily until resolution of renal impairment is ensured.1

Table 1. Recommended Foscarnet Sodium Dosage for Initial Treatment (Induction) of CMV Retinitis or HSV Infections in Adults Based on Patient’s Clcr1

Clcr (mL/minute per kg)

Induction Dosage for CMV (in mg/kg) Equivalent to 60 mg/kg Every 8 Hours

Induction Dosage for CMV (in mg/kg) Equivalent to 90 mg/kg Every 12 Hours

Induction Dosage for HSV (in mg/kg) Equivalent to 40 mg/kg Every 12 Hours

Induction Dosage for HSV (in mg/kg) Equivalent to 40 mg/kg Every 8 Hours

>1.4

60 every 8 hours

90 every 12 hours

40 every 12 hours

40 every 8 hours

>1–1.4

45 every 8 hours

70 every 12 hours

30 every 12 hours

30 every 8 hours

>0.8–1

50 every 12 hours

50 every 12 hours

20 every 12 hours

35 every 12 hours

>0.6–0.8

40 every 12 hours

80 every 24 hours

35 every 24 hours

25 every 12 hours

>0.5–0.6

60 every 24 hours

60 every 24 hours

25 every 24 hours

40 every 24 hours

≥0.4–0.5

50 every 24 hours

50 every 24 hours

20 every 24 hours

35 every 24 hours

<0.4

Not recommended

Not recommended

Not recommended

Not recommended

Table 2. Recommended Foscarnet Sodium Dosage for Maintenance Therapy of CMV Retinitis in Adults Based on Patient’s Clcr1

Clcr (mL/minute per kg)

Maintenance Dosage (mg/kg) Equivalent to 90 mg/kg Once Daily

Maintenance Dosage (in mg/kg) Equivalent to 120 mg/kg Once Daily

>1.4

90 every 24 hours

120 every 24 hours

>1–1.4

70 every 24 hours

90 every 24 hours

>0.8–1

50 every 24 hours

65 every 24 hours

>0.6–0.8

80 every 48 hours

105 every 48 hours

>0.5–0.6

60 every 48 hours

80 every 48 hours

≥0.4–0.5

50 every 48 hours

65 every 48 hours

<0.4

Not recommended

Not recommended

Hemodialysis patients: Dosage recommendations not available; foscarnet not recommended in such patients.1

Geriatric Patients

Select dosage with caution because of age-related decreases in renal function.1 (See Renal Impairment under Dosage and Administration.)

Cautions for Foscarnet

Contraindications

  • Hypersensitivity to foscarnet.1

Warnings/Precautions

Warnings

Renal Effects

Renal impairment and/or failure, manifested mainly as an increase in Scr and/or a decrease in Clcr, is the major toxicity of foscarnet; occurs to some degree in most patients.1 2 4 21 22 23 24 25 26

In initial clinical trials in HIV-infected patients with AIDS who received foscarnet for the treatment of CMV retinitis, 27% developed abnormal renal function.1 Based on measurement of Scr, renal impairment is most likely to become clinically evident during the second week of induction therapy at a dosage of 180 mg/kg daily; however, renal impairment may occur at any time during therapy.1 21 22 25

Foscarnet-induced increases in Scr usually (but not always) are reversible following dosage adjustment or discontinuance of the drug;1 2 21 22 maximum deterioration in renal function may not be apparent until several weeks after discontinuance.1 25

Hemodialysis may be useful in management of foscarnet-induced nephrotoxicity when elevated plasma concentrations are present and the degree of renal failure is severe.2 25

Adequate hydration is imperative before and during foscarnet therapy (i.e., to establish and maintain diuresis) since this decreases risk of foscarnet-induced renal impairment.1 2 7 9 21 22 23 24 (See Hydration under Dosage and Administration.)

Renal function must be assessed prior to initiation of foscarnet and it is imperative that renal function be monitored during foscarnet therapy and dosage modified as needed based on renal function.1 2 21 22 23 24 25 26 (See Renal Impairment under Dosage and Administration.)

Mineral and Electrolyte Imbalance

Alterations in serum electrolytes reported, including hypocalcemia, hypophosphatemia, hyperphosphatemia, hypomagnesemia, and hypokalemia.1 2 4 7 9 10

Dose-related decreases in ionized serum calcium may occur, which may not be reflected in total serum calcium.1

Decreased serum concentrations of ionized calcium may result in symptoms such as perioral tingling, numbness in the extremities, or paresthesias.1 Clinicians should be prepared to treat these or more severe manifestations such as tetany, seizures, or cardiac disturbances.1

Foscarnet-induced changes in serum concentrations of calcium or other electrolytes most likely result from the drug’s ability to chelate and form stable coordination compounds with divalent metal ions such as calcium and magnesium.1 2

The decrease in ionized calcium may be affected by the foscarnet IV infusion rate.1 An infusion pump must be used to prevent rapid IV infusion; slowing the infusion rate may decrease or prevent symptoms.1

Particular caution and careful management of serum electrolytes is advised in patients with altered serum calcium concentrations or other electrolyte levels at baseline prior to initiation of foscarnet, especially in those who have neurologic or cardiac abnormalities or are receiving other drugs known to influence minerals and electrolytes (especially calcium).1 7

Nervous System Effects

Seizures related to mineral and electrolyte abnormalities (see Mineral and Electrolyte Imbalance under Cautions) have occurred;1 some seizures resulted in death.1

Factors that may increase risk of seizures include renal impairment at baseline, low total serum calcium concentrations, and underlying CNS conditions.1

Close monitoring of plasma electrolytes and minerals and appropriate electrolyte and/or mineral supplementation is particularly important in patients predisposed to seizures.1

If symptoms of electrolyte abnormalities (e.g., perioral tingling, numbness in extremities or paresthesia) develop during IV infusion of foscarnet, stop the infusion at least temporarily.1

Cardiovascular Effects

Prolonged QT interval, which may increase risk of torsades de pointes, reported.1 Foscarnet-associated transient changes in serum concentrations of calcium or other electrolytes may contribute to risk of cardiac disturbances.1 (See Mineral and Electrolyte Imbalance under Cautions.)

Use with caution in patients with a history of QT-interval prolongation, patients receiving other drugs known to prolong the QT interval, and those with electrolyte abnormalities or other risk factors for QT-interval prolongation.1 Assess ECGs and electrolyte concentrations prior to and periodically during foscarnet therapy.1

If cardiovascular adverse effects occur, stop foscarnet infusion, determine electrolyte concentrations, and consult a clinician prior to resuming therapy.1

Selection and Use of Antivirals

Foscarnet is labeled only for treatment of CMV retinitis in HIV-infected patients and treatment of mucocutaneous acyclovir-resistant HSV infections in immunocompromised patients.1

Safety and efficacy not established for treatment of extraocular CMV infections (e.g., pneumonitis, gastroenteritis), congenital or neonatal CMV disease, or CMV disease in individuals not infected with HIV.1

Safety and efficacy not established for treatment of systemic HSV infections (e.g., retinitis, encephalitis), congenital or neonatal HSV disease, or HSV infections in immunocompetent individuals.1

When used for mucocutaneous HSV infections, repeated foscarnet treatment has led to development of resistance associated with poor response.1 In vitro susceptibility testing of the HSV isolate advised if there is a poor therapeutic response to the drug.1

Sensitivity Reactions

Serious acute hypersensitivity reactions (e.g., anaphylactic shock, urticaria, angioedema) reported.1

If an acute hypersensitivity reaction occurs, discontinue foscarnet therapy and immediately initiate appropriate medical therapy.1

General Precautions

Administration Precautions

To avoid local irritation, commercially available foscarnet preparation containing 24 mg/mL must be diluted before IV administration via a peripheral vein.1 In addition, particular care must be taken to select a vein with adequate blood flow to permit rapid dilution and distribution of the drug.1 (See Administration under Dosage and Administration.)

Because of potential for nephrotoxicity, patients must receive adequate hydration prior to initial dose of foscarnet and also receive a recommended hydration regimen with each subsequent dose of the drug.1 (See Hydration under Dosage and Administration.)

To avoid unintentional overdosage, foscarnet must be administered by slow IV infusion using a controlled-infusion device (e.g., pump) to carefully control infusion rate.1 (See Rate of Administration under Dosage and Administration.)

Genitourinary Effects

Local irritation and ulcerations of penile epithelium (resembling fixed drug eruption grossly but not histologically) reported in male patients;1 2 4 11 12 13 14 15 16 vulvovaginal ulcerations reported in at least one female.1 17

These local effects possibly are related to high concentrations of unchanged drug in urine.1 14 15 Use of adequate hydration with close attention to personal hygiene may minimize risk of these adverse effects.1 15

Hematologic Effects

Although foscarnet not usually myelosuppressive,2 4 8 18 19 20 38 anemia and granulocytopenia reported.1

Sodium Content

Commercially available foscarnet solution containing 24 mg/mL contains 5.5 mg (0.24 mEq) of sodium per mL.1

Avoid foscarnet in patients who may not tolerate large amounts of sodium or water (e.g., patients with cardiomyopathy) and in patients on a sodium-controlled diet.1

Specific Populations

Pregnancy

No adequate and well-controlled studies to date using foscarnet in pregnant women.1 Animal data inadequate to define the potential for teratogenicity at dosages used in humans.1

Use during pregnancy only when clearly needed.1

Lactation

Not known whether distributed into human milk;1 distributed into milk in rats.1

Discontinue nursing or the drug, taking into consideration the importance of the drug to the woman.1

Instruct HIV-infected women not to breast-feed because of risk of HIV transmission.1

Pediatric Use

Safety and efficacy not established in pediatric patients <18 years of age.1 5

Animal studies indicate foscarnet is deposited in teeth and bone in animals (particularly during early growth and development) and adversely affects tooth enamel development.1 Also deposited to an unknown extent in bone in humans.1

Manufacturer states use in children only after careful evaluation and only when potential benefits outweigh possible risks.1

Some experts state foscarnet is the preferred alternative for management of CMV retinitis in HIV-infected children and a drug of choice for management of acyclovir-resistant HSV infections in HIV-infected children.156

Geriatric Use

Safety and efficacy not specifically studied in geriatric patients ≥65 years of age.1

Adverse effects reported in adults ≥65 years of age are similar to those reported in younger adults.1

Substantially eliminated by kidneys; risk of toxicity may be greater in patients with impaired renal function.1 Select dosage with caution and assess renal function prior to and during therapy since geriatric patients are more likely to have renal impairment.1

Renal Impairment

Because renal impairment is the principal toxicity of foscarnet and occurs to some degree in most patients, foscarnet must be used with particular caution in those with a history of renal impairment.1 2 21 22 23 24 25 26

In patients with renal impairment, reduced plasma clearance of foscarnet will result in increased plasma concentrations; in addition, the drug potentially may further impair renal function in these patients.1

Renal function must be assessed prior to and frequently during therapy; adjust dosage for decreased baseline renal function and for changes in renal function that may occur during treatment.1 2 21 22 23 24 25 26 38 (See Renal Impairment under Dosage and Administration.)

In patients with renal impairment, dosage is adjusted based on Clcr (measured or calculated).1 In addition, a 24-hour Clcr should be determined at baseline and periodically thereafter to ensure appropriate dosing (assuming verification of an adequate urine collection using the creatinine index).1

If Clcr declines to <0.4 mL/minute per kg during foscarnet therapy, discontinue the drug, hydrate patient, and monitor daily until resolution of renal impairment is ensured.1

Data are limited regarding safety and efficacy in patients with baseline measured Clcr <50 mL/minute or baseline Scr >2.8 mg/dL.1

Not recommended in patients undergoing hemodialysis1 38 or peritoneal dialysis.38 Removed by hemodialysis.85

Common Adverse Effects

Fever, nausea, anemia, diarrhea, abnormal renal function, vomiting, headache, seizures.1

Interactions for Foscarnet

Specific Drugs

Drug

Interaction

Comments

Acyclovir

Possible increased nephrotoxicity1

No in vitro evidence of antagonistic antiviral effects1

Avoid concomitant use unless potential benefits outweigh risks1

Aminoglycosides

Possible increased nephrotoxicity1

Avoid concomitant use unless potential benefits outweigh risks1

Amphotericin B

Possible increased nephrotoxicity1

Avoid concomitant use unless potential benefits outweigh risks1

Antiarrhythmic agents (amiodarone, dofetilide, procainamide, quinidine, sotalol)

Class IA antiarrhythmics (procainamide, quinidine), class III antiarrhythmics (amiodarone, dofetilide, sotalol), and other antiarrhythmic agents: Possible increased risk of QT-interval prolongation and potential for torsades de pointes1

Class IA antiarrhythmics (procainamide, quinidine), class III antiarrhythmics (amiodarone, dofetilide, sotalol), and other antiarrhythmic agents: Avoid concomitant use1

Cidofovir

Possible increased risk of nephrotoxicity84

Concomitant use contraindicated;84 discontinue foscarnet ≥7 days prior to initiating cidofovir84

Diuretics

Loop diuretics: May impair elimination of foscarnet due to inhibition of renal tubular excretion;1 may lead to toxicity1

If concomitant use with a diuretic required, manufacturer recommends thiazide diuretics over loop diuretics1

Drugs affecting calcium

Foscarnet decreases ionized calcium concentrations1

Use concomitantly with extreme caution1

Fluoroquinolones

Fluoroquinolones with potential to prolong QT interval: Possible increased risk of QT-interval prolongation and potential for torsades de pointes1

Fluoroquinolones with potential to prolong QT interval: Avoid concomitant use1

Ganciclovir

No apparent effect on ganciclovir or foscarnet pharmacokinetics1

Physically incompatible1 85

No in vitro evidence of antagonistic antiviral effects;1 possible synergistic or additive antiviral effects against CMV85

Do not admix1 85

Immunosuppressive agents (cyclosporine, tacrolimus)

Cyclosporine, tacrolimus: Possible increased nephrotoxicity1

Cyclosporine, tacrolimus: Avoid concomitant use unless potential benefits outweigh risks1

Letermovir

No in vitro evidence of antagonistic antiviral effects83

Macrolides

Macrolides with potential to prolong QT interval: Possible increased risk of QT-interval prolongation and potential for torsades de pointes1

Macrolides with potential to prolong QT interval: Avoid concomitant use1

Methotrexate

Possible increased nephrotoxicity1

Avoid concomitant use unless potential benefits outweigh risks1

Pentamidine

Possible hypocalcemia or renal impairment when used with IV pentamidine;1 not reported to date with aerosolized pentamidine1

Avoid concomitant use unless potential benefits outweigh risks; 1 if used concomitantly, extreme caution and close renal function monitoring advised1 85

Phenothiazines

Possible increased risk of QT-interval prolongation and potential for torsades de pointes1

Avoid concomitant use1

Probenecid

No clinically important interactions1

Ritonavir

Possible abnormal renal function when used with ritonavir (with or without saquinavir)1

Tricyclic antidepressants

Possible increased risk of QT-interval prolongation and potential for torsades de pointes1

Avoid concomitant use1

Zidovudine

No clinically important pharmacokinetic interactions1 85

Foscarnet Pharmacokinetics

Absorption

Plasma Concentrations

Considerable interindividual variation in plasma concentrations attained after IV infusion.85

Distribution

Extent

Distributed into bone; extent of accumulation unknown.1

Distributed into CSF.1 85

Plasma Protein Binding

14–17%.1

Elimination

Metabolism

Not substantially metabolized.85

Elimination Route

Excreted principally unchanged in urine by glomerular filtration.85

Half-life

Adults with normal renal function: 1.9 hours.1

Terminal half-life determined by urinary excretion reported to be 87.5 hours,1 most likely due to slow release of foscarnet from bone.1 85

Special Populations

Renal impairment: Clearance decreased and half-life prolonged.1 Half-life is approximately 3, 13, or 25 hours in those with Clcr 50–80, 25–49, or 10–24 mL/minute, respectively.1

Stability

Storage

Parenteral

Injection, for IV Infusion

20–25°C.1 Protect from excessive heat (>40°C); protect from freezing.1 If refrigerated or exposed to freezing, precipitation may occur;1 precipitate may be brought into solution again if kept at room temperature with repeated shaking.1

Use diluted solutions within 24 hours after first entry into sealed bottle.1

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility1 HID

Compatible

Dextrose 5% in water

Sodium chloride 0.9%

Incompatible

Dextrose 5% in Ringer's injection

Dextrose 5% in Ringer's injection, lactated

Ringer's injection

Ringer's injection, lactated

Drug Compatibility
Admixture CompatibilityHID

Compatible

Potassium chloride

Y-Site Compatibility1HID

Compatible

Aldesleukin

Amikacin sulfate

Aminophylline

Ampicillin sodium

Aztreonam

Cefazolin sodium

Cefoxitin sodium

Ceftazidime

Ceftriaxone sodium

Cefuroxime sodium

Chloramphenicol sodium succinate

Clindamycin phosphate

Dexamethasone sodium phosphate

Dopamine HCl

Doripenem

Erythromycin lactobionate

Fluconazole

Furosemide

Gentamicin sulfate

Heparin sodium

Hydrocortisone sodium succinate

Hydromorphone HCl

Hydroxyzine HCl

Imipenem–cilastatin sodium

Metoclopramide HCl

Metronidazole

Morphine sulfate

Nafcillin sodium

Oxacillin sodium

Penicillin G potassium

Ranitidine HCl

Tobramycin sulfate

Incompatible

Acyclovir sodium

Amphotericin B

Diazepam

Digoxin

Diphenhydramine HCl

Dobutamine HCl

Droperidol

Ganciclovir sodium

Haloperidol lactate

Leucovorin calcium

Midazolam HCl

Pentamidine isethionate

Prochlorperazine edisylate

Promethazine HCl

Trimetrexate glucuronate

Variable

Co-trimoxazole

Lorazepam

Vancomycin HCl

Actions and Spectrum

  • Organic analog of inorganic pyrophosphate with antiviral activity.1 85

  • Viral DNA polymerase inhibitor.85 Mechanism of antiviral activity appears to involve selective inhibition at the pyrophosphate binding site on virus-specific DNA polymerases at concentrations that do not affect cellular DNA polymerases.1 85

  • Active against herpesviruses, including CMV,1 85 HSV-1 and HSV-2,1 85 and VZV.85

  • Active against some ganciclovir-resistant CMV and some acyclovir-resistant HSV.1

  • CMV and HSV resistant to foscarnet can be selected in vitro and may occur in vivo in patients who receive the drug.1

  • Certain foscarnet resistance-associated substitutions result in reduced susceptibility to other antivirals (e.g., acyclovir, cidofovir, ganciclovir).1

Advice to Patients

  • Advise patients that foscarnet is not a cure for CMV retinitis; progression and/or recurrence can occur, particularly during periods of immunosuppression.1 Regular ophthalmologic examinations are necessary.1

  • Advise patients that foscarnet is not a cure for HSV infection.1 Although complete healing of HSV lesions is possible, relapse occurs in most patients.1 Repeated treatment with foscarnet may lead to resistance and poor response; in vitro susceptibility testing may be necessary if there is a poor therapeutic response or if relapse occurs.1

  • Inform patients about the major toxicities of foscarnet (e.g., renal impairment, electrolyte disturbances, seizures) and that dosage adjustments and possible discontinuance of the drug may be necessary.1 Emphasize importance of close monitoring during foscarnet therapy.1

  • Advise patients of the importance of adequate hydration to establish and maintain diuresis and minimize risk of renal impairment during foscarnet therapy.1

  • Advise patients of the importance of informing clinicians if symptoms of electrolyte imbalance (perioral tingling, numbness in the extremities, paresthesias) or any cardiac symptoms occur during or after IV infusion of foscarnet.1 If such symptoms occur, the IV infusion should be stopped, electrolyte concentrations determined, and a clinician consulted before treatment with the drug is resumed.1

  • Advise patients that dizziness and convulsions may occur during foscarnet therapy.1 Patients who experience seizures, dizziness, somnolence, or other adverse reactions that could result in cognitive impairment should avoid driving or operating machinery.1

  • Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of advising patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Foscarnet Sodium

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for IV infusion only

24 mg/mL

Foscavir

Hospira

AHFS DI Essentials™. © Copyright 2021, Selected Revisions August 19, 2019. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Hospira. Foscavir (foscarnet sodium) injection prescribing information. Lake Forest, IL; 2017 Nov.

2. Chrisp P, Clissold SP. Foscarnet: a review of its antiviral activity, pharmacokinetic properties and therapeutic use in immunocompromised patients with cytomegalovirus retinitis. Drugs. 1991; 41:104-29. http://www.ncbi.nlm.nih.gov/pubmed/1706982?dopt=AbstractPlus

3. Polis MA. Foscarnet and ganciclovir in the treatment of cytomegalovirus retinitis. J Acquir Immune Defic Syndr. 1992; 5(Suppl 1):S3-10. http://www.ncbi.nlm.nih.gov/pubmed/1318365?dopt=AbstractPlus

4. Minor JR, Baltz JK. Foscarnet sodium. DICP. 1991; 25:41-7. http://www.ncbi.nlm.nih.gov/pubmed/1848959?dopt=AbstractPlus

5. Hwang SB (Astra Pharmaceutical, Westborough, MA): Personal communication; 1992 May 5.

7. Palestine AG, Polis MA, De Smet MD et al. A randomized, controlled trial of foscarnet in the treatment of cytomegalovirus retinitis in patients with AIDS. Ann Intern Med. 1991; 115:665-73. http://www.ncbi.nlm.nih.gov/pubmed/1656826?dopt=AbstractPlus

8. Studies of Ocular Complications of AIDS Research Group, in Collaboration with the AIDS Clinical Trials Group. Mortality in patients with the acquired immunodeficiency syndrome treated with either foscarnet or ganciclovir for cytomegalovirus retinitis. N Engl J Med. 1992; 326:213-20. http://www.ncbi.nlm.nih.gov/pubmed/1345799?dopt=AbstractPlus

9. Jacobson MA, Causey D, Polsky B et al. A dose-ranging study of daily maintenance intravenous foscarnet therapy for cytomegalovirus retinitis in AIDS. J Infect Dis. 1993; 168:444-8. http://www.ncbi.nlm.nih.gov/pubmed/8393058?dopt=AbstractPlus

10. Gearhart MO, Sorg TB. Foscarnet-induced severe hypomagnesemia and other electrolyte disorders. Ann Pharmacother. 1993; 27:285-9. http://www.ncbi.nlm.nih.gov/pubmed/8384030?dopt=AbstractPlus

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37. Reviewers’ comments (personal observations).

38. Astra, Westborough, MA: personal communication.

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52. Safrin S, Berger TG, Gilson I et al. Foscarnet therapy in five patients with AIDS and acyclovir-resistant varicella-zoster virus infection. Ann Intern Med. 1991; 115:19-21. http://www.ncbi.nlm.nih.gov/pubmed/1646585?dopt=AbstractPlus

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