Foscarnet (Foscavir) - Uses, Dose, Side effects, MOA, Brands

Foscarnet (Foscavir) is an antiviral medicine that is used primarily in the treatment of ganciclovir-resistant cytomegalovirus infection and Acyclovir-resistant herpes simplex and varicella zoster infections.

Foscarnet Uses:

  • Treatment of Cytomegalovirus ophthalmic disease (retinitis):

    • Used in the treatment of cytomegalovirus (CMV) retinitis in persons with AIDS
  • Herpes simplex virus:

    • Used in the treatment of acyclovir-resistant mucocutaneous herpes simplex virus (HSV) infection in immunocompromised persons (eg, with advanced AIDS)
  • Off Label Use of Foscarnet in Adults:

    • Used in cytomegalovirus prevention in patients with allogeneic hematopoietic cell transplant recipients
    • Used in CMV treatment, gastrointestinal diseases such as esophagitis or colitis.
    • Used in the treatment of CMV neurological disease
    • Used in varicella-zoster virus infection of the eyes, progressive outer retinal necrosis

Foscarnet Dose in Adults

Foscarnet Dose in the treatment of Cytomegalovirus (CMV):

  • Dose as an alternative agent in the treatment of Gastrointestinal disease (esophagitis, colitis) (off-label):
    • IV: 60 mg per kg per dose every 8 hours or 90 mg per kg per dose every 12 hours for 21 to 42 days or until symptom resolution.
  • Dose in the treatment of Neurological disease (off-label):
    • IV: 60 mg per kg per dose every 8 hours or 90 mg per kg per dose every 12 hours in combination with ganciclovir; optimal duration not established.
  • Dose in the treatment of Ophthalmic disease (retinitis):
    • IV (alternative agent):
      • Induction treatment:
        • 60 mg per kg per dose every 8 hours for 14 to 21 days or 90 mg per kg per dose every 12 hours for 14 to 21 days; for immediate sight-threatening lesions, administered in combination with intravitreal therapy.
      • Maintenance therapy:
        • 90 to 120 mg per kg per dose once in a day; due to lower toxicity, begin with 90 mg per kg per dose once in a day, may escalate to 120 mg per kg per dose once in a day if lower dose tolerated or for retinitis progression (manufacturer’s labeling).
        • Duration of maintenance therapy is ≥3 to 6 months and until lesions are inactive and until CD4 count is more than 100 cells per mm³ for 3 to 6 months in response to antiretroviral therapy in HIV-infected patients.
    • Intravitreal (off-label route):
      • Induction treatment:
        • 4 mg per 0.1 mL injected into vitreum (Diaz-Llopis 1994; HHS [OI adult 2019]) for 1 to 4 doses administered over 7 to 10 days for immediate sight-threatening lesions; must be used in combination with systemic antiviral therapy.

Foscarnet Dose as an alternative agent in the prevention of CMV infection in allogeneic hematopoietic cell transplant (HCT) recipients (off-label):

  • Preemptive therapy: IV:

    • <100 days post-transplant:
      • Induction: 60 mg per kg per dose every 12 hours for 7 to 14 days, followed by
      • maintenance therapy: 90 mg per kg per dose once in a day if CMV is still detectable and declining, continue until indicator test is negative.
      • The minimum total duration (induction and maintenance) is 2 weeks.
    • >100 days post-transplant:
      • 60 mg per kg per dose every 12 hours for 14 days, continue treatment with 90 mg per kg per dose once in a day for 7 to 14 days until the indicator test is negative.
  • Prophylactic therapy:

    • IV: 60 mg per kg per dose every 12 hours for 7 days, followed by 90 to 120 mg/kg/dose once a day until day 100 after HCT.

Foscarnet Dose in the treatment of Herpes simplex infection (acyclovir-resistant):

  • Induction:

    • IV: 40 mg per kg per dose every 8 to 12 hours for 14 to 21 days.

Foscarnet Dose in the treatment of Varicella zoster virus (VZV) infection of the eyes, progressive outer retinal necrosis (PORN) (off-label):

  • IV:
    • 90 mg per kg per dose every 12 hours (with or without IV ganciclovir) plus intravitreal antiviral therapy. Duration is based on virologic, clinical, and immunologic responses in consultation with an ophthalmologist.
  • Intravitreal (off-label route):
    • 1.2 mg per 0.05 mL injected in the vitreum twice in a weak; must be used in combination with systemic antiviral therapy.

Foscarnet Dose in Children

Foscarnet Dose in the treatment of Cytomegalovirus (CMV) infection (HIV-exposed/-positive):

  • Treatment induction:
    • In addition to antiviral therapy, antiretroviral therapy (ART) should be optimized.
  • Dose in the treatment of CNS, neurological disease in children:
    • IV: 180 mg per kg per day in divided doses every 8 or 12 hours;
    • Use in combination with ganciclovir; begin treatment promptly and continue until symptom improvement; follow with chronic suppression
  • Dose in the treatment of GI disease (esophagitis or colitis) in patients with ganciclovir-intolerant or ganciclovir-resistance:
    • IV: 180 mg per kg per day in divided doses every 8 or 12 hours for 21 to 42 days or until resolution of symptoms.
  • Dose in the treatment of Retinitis: Use as a component of initial therapy if immediate, sight-threatening lesions are present.
    • Infants and Children: 
      • IV: 180 mg per kg per day in divided doses every 8 or 12 hours;
      • Continue the treatment for 14 to 21 days.
      • Use in combination with ganciclovir if monotherapy fails or in sight-threatening illnesses. Follow treatment with chronic suppression.
    • Adolescents:
      • Combination therapy with intravitreal and intravenous antiviral therapy recommended; follow treatment/induction with chronic suppression.
      • IV: 180 mg per kg per day in divided doses every 8 or 12 hours for 14 to 21 days
      • Intravitreal: 2.4 mg per dose for 1 to 4 doses administered over 7 to 10 days in combination with valganciclovir (oral), foscarnet (IV), ganciclovir (IV),  or cidofovir (IV)
  • Dose in the maintenance therapy of Chronic suppressive:
    • Secondary prophylaxis (following treatment for prior disseminated disease, retinitis, or neurologic disease or GI disease with relapse):
    • Infants, Children, and Adolescents:
      • IV: 90 to 120 mg per kg per dose once in a day;
      • The duration of therapy dependent on multiple factors (eg, age, CD4 cell count, infection, and response) and is typically several months.
  • Dose as an alternate agent in the treatment of Cytomegalovirus (CMV) infection after stem cell transplantation (HSCT) in children:
    • Preemptive therapy:

      • Induction:
        • less than 100 days post-transplant:
          • Induction: 60 mg per kg per dose every 12 hours for 7 to 14 days; follow with maintenance therapy if CMV is still detectable and declining
        • >100 days post-transplant:
          • 60 mg per kg per dose every 12 hours for 14 days; follow with maintenance therapy
      • Maintenance:
        • 90 mg per kg per dose once in a day; duration dependent on post-transplant days:
        • less than 100 days post-transplant:
          • Minimum duration is at least in a weak and continue daily until CMV indicator test is negative
        • more than 100 days post-transplant:
          • Continue for 7 to 14 days or until CMV indicator test is negative
    • Prophylactic therapy:

      • Engraftment to <100 days post-transplant:
        • 60 mg per kg per dose every 12 hours for a weak, followed by 90 to 120 mg per kg per dose once daily until day 100 after HSCT

Foscarnet Dose in the treatment of acyclovir-resistant Herpes simplex virus (HSV) infection; (HIV-exposed/positive):

  • Infants and Children:

    • IV: 120 mg per kg per day in divided doses every 8 or 12 hours;
    • The duration of treatment depends on the site of the infection.
  • Adolescents:

    • IV: 80 to 120 mg per kg per day in divided doses every 8 or 12 hours;
    • continue until clinical response.

Foscarnet Dose in the treatment of Varicella zoster virus (VZ) infection (HIV-exposed/-positive):

  • Treatment of Chickenpox not responding to acyclovir:

    • Infants and Children:
      • IV: 120 to 180 mg per kg per day in divided doses every 8 hours for 7 to 10 days or until no new lesions have appeared for 48 hours.
  • Treatment of Zoster: Progressive outer retinal necrosis:

    • Infants, Children, and Adolescents:
    • Note: In addition to antiviral therapy, optimize ART.
      • IV:
        • 90 mg per kg per dose every 12 hours in combination with ganciclovir (systemic, IV) and intravitreal foscarnet and/or ganciclovir
      • Intravitreal:
        • 1.2 mg per 0.05 mL per dose two times in a weak  in combination with systemic foscarnet and ganciclovir and/or intravitreal ganciclovir

Foscarnet Pregnancy Category: C

  • Limited information is available on the use of pregnancy.
  • To detect oligohydramnios, it is recommended to monitor the amniotic fluid volume by ultrasound every 20 weeks.

Foscarnet use during breastfeeding:

  • Foscarnet may be present in breast milk, but it is unknown.
  • To reduce the risk of HIV transmission, pregnant women with HIV should stop breastfeeding.
  • The manufacturer is concerned about the possibility of serious adverse reactions in breastfeeding infants and recommends that a decision be made regarding whether to discontinue breastfeeding or discontinue using the drug.
  • This consideration will also take into account the importance to the mother.

Foscarnit Dose in Kidney disease:

Note: Renal function may be estimated by dividing actual 24-hour CrCl (mL/minute) by body weight (kg) or by using the modified Cockcroft-Gault formula ([140 − age]/[serum creatinine in mg/dL × 72] [× 0.85 for females]) for dosage adjustment purposes.

Induction Dosing of Foscarnet in Patients With Abnormal Renal Function

CrCl (mL/min/kg) HSV HSV CMV CMV
Equivalent to 40 mg/kg every 12 hours Equivalent to 40 mg/kg every 8 hours Equivalent to 60 mg/kg every 8 hours Equivalent to 90 mg/kg every 12 hours
<0.4 Not recommended Not recommended Not recommended Not recommended
≥0.4-0.5 20 mg/kg every 24 hours 35 mg/kg every 24 hours 50 mg/kg every 24 hours 50 mg/kg every 24 hours
>0.5-0.6 25 mg/kg every 24 hours 40 mg/kg every 24 hours 60 mg/kg every 24 hours 60 mg/kg every 24 hours
>0.6-0.8 35 mg/kg every 24 hours 25 mg/kg every 12 hours 40 mg/kg every 12 hours 80 mg/kg every 24 hours
>0.8-1 20 mg/kg every 12 hours 35 mg/kg every 12 hours 50 mg/kg every 12 hours 50 mg/kg every 12 hours
>1-1.4 30 mg/kg every 12 hours 30 mg/kg every 8 hours 45 mg/kg every 8 hours 70 mg/kg every 12 hours
>1.4 40 mg/kg every 12 hours 40 mg/kg every 8 hours 60 mg/kg every 8 hours 90 mg/kg every 12 hours

Maintenance Dosing of Foscarnet in Patients With Abnormal Renal Function

CrCl (mL/min/kg) CMV CMV
Equivalent to 90 mg/kg every 24 hours Equivalent to 120 mg/kg every 24 hours
<0.4 Not recommended Not recommended
≥0.4-0.5 50 mg/kg every 48 hours 65 mg/kg every 48 hours
>0.5-0.6 60 mg/kg every 48 hours 80 mg/kg every 48 hours
>0.6-0.8 80 mg/kg every 48 hours 105 mg/kg every 48 hours
>0.8-1 50 mg/kg every 24 hours 65 mg/kg every 24 hours
>1-1.4 70 mg/kg every 24 hours 90 mg/kg every 24 hours
>1.4 90 mg/kg every 24 hours 120 mg/kg every 24 hours
  • Hemodialysis:

    • Foscarnet is highly removed by hemodialysis (up to ~38 percent in 2.5 hours HD with high-flux membrane).
    • Doses of 45 to 60 mg per kg per dose post hemodialysis (thrice in a weak) with the monitoring of weekly plasma concentrations to maintain peak plasma concentrations in the range of 500 to 800 micromolar for the treatment of CMV infection have been recommended.
  • Peritoneal dialysis:

    • HSV infection (localized or disseminated): IV:
      • 60 mg per kg per dose every 48 to 72 hours;
      • higher doses may be necessary for herpes encephalitis or herpes zoster infection.

Dose in Liver disease:

The manufacturer’s labeling hasn't provided any dosage adjustments.

Common Side Effects of Foscarnet:

  • Central Nervous System:

    • Headache
  • Endocrine & Metabolic:

    • Hypocalcemia
    • Hypomagnesemia
    • Hypokalemia
    • Hypophosphatemia
  • Gastrointestinal:

    • Nausea
    • Diarrhea
    • Vomiting
  • Hematologic & Oncologic:

    • Anemia
    • Granulocytopenia
  • Renal:

    • Renal Insufficiency
  • Miscellaneous:

    • Fever

Less Common Side Effects Of Foscarnet:

  • Cardiovascular:

    • First Degree Atrioventricular Block
    • Flushing
    • Hypertension
    • Hypotension
    • Chest Pain
    • Edema
    • Facial Edema
    • Palpitations
    • Sinus Tachycardia
    • ST Segment Changes On ECG
    • Thrombosis
  • Central Nervous System:

    • Dizziness
    • Fatigue
    • Hypoesthesia
    • Malaise
    • Neuropathy
    • Pain
    • Paresthesia
    • Seizure
    • Anxiety
    • Confusion
    • Depression
    • Rigors
    • Abnormal Electroencephalogram
    • Aggressive Behavior
    • Agitation
    • Amnesia
    • Aphasia
    • Ataxia
    • Cerebrovascular Disease
    • Dementia
    • Hallucination
    • Insomnia
    • Meningitis
    • Nervousness
    • Sensory Disturbance
    • Somnolence
    • Stupor
  • Dermatologic:

    • Erythematous Rash
    • Maculopapular Rash
    • Pruritus
    • Seborrhea
    • Diaphoresis
    • Skin Rash
    • Dermal Ulcer
    • Skin Discoloration
  • Endocrine & Metabolic:

    • Electrolyte Disturbance
    • Abnormal Albumin-Globulin Ratio
    • Acidosis
    • Albuminuria
    • Cachexia
    • Hyponatremia
    • Hyperphosphatemia
    • Increased Lactate Dehydrogenase
    • Increased Thirst
    • Weight Loss
  • Gastrointestinal:

    • Aphthous Stomatitis
    • Cachexia
    • Constipation
    • Dysgeusia
    • Dyspepsia
    • Dysphagia
    • Flatulence
    • Melena
    • Abdominal Pain
    • Anorexia
    • Pancreatitis
    • Xerostomia
  • Genitourinary:

    • Nephrotoxicity
    • Dysuria
    • Nocturia
    • Urinary Retention
    • Urinary Tract Infection
  • Hematologic & Oncologic:

    • Mineral Abnormalities
    • Neutropenia
    • Abnormal White Cell Differential
    • Altered Platelet Function
    • Lymphadenopathy
    • Pseudolymphoma
    • Bone Marrow Suppression
    • Leukopenia
    • Rectal Hemorrhage
    • Sarcoma
    • Thrombocytopenia
  • Hepatic:

    • Abnormal Hepatic Function Tests
    • Increased Lactate Dehydrogenase
    • Increased Serum Alkaline Phosphatase
    • Increased Serum ALT
    • Increased Serum AST
  • Infection:

    • Infection
    • Sepsis
    • Abscess
    • Bacterial Infection
    • Fungal Infection
  • Local:

    • Inflammation At Injection Site
    • Pain At Injection Site
  • Neuromuscular & Skeletal:

    • Weakness
    • Arthralgia
    • Back Pain
    • Leg Cramps
    • Myalgia
    • Muscle Spasm
    • Neuropathy
    • Tremor
  • Ophthalmic:

    • Visual Disturbance
    • Conjunctivitis
    • Eye Pain
  • Renal:

    • Increased Serum Creatinine
    • Acute Renal Failure
    • Increased Blood Urea Nitrogen
    • Decreased Creatinine Clearanc
    • Polyuria
  • Respiratory:

    • Hemoptysis
    • Pharyngitis
    • Pneumonia
    • Pneumothorax
    • Pulmonary Infiltrates
    • Respiratory Failure
    • Respiratory Insufficiency
    • Rhinitis
    • Sinusitis
    • Cough
    • Dyspnea
    • Bronchospasm
    • Flu-Like Symptoms
    • Stridor

Contraindications to Foscarnet:

Clinically significant hypersensitivity to foscarnet and any component of this formulation.

Warnings and precautions

  • Dental effects:

    • Foscarnet can be found in the teeth and bones of young animals. It has negatively affected the development of tooth enamel in rats.
  • Electrolyte imbalance:

    • Imbalance of serum electrolytes or minerals occurs in at least 15 percent of patients (hyper/hypophosphatemia, hypocalcemia, low ionized calcium, hypomagnesemia, or hypokalemia); reducing infusion rate may decrease or prevent the symptoms.
    • Low ionized calcium patients may experience perioral discomfort, paresthesias and tetany.
    • Before initiating therapy, ensure that your electrolytes are correct.
    • Patients with electrolyte imbalances or neurologic problems, as well as those taking calcium-dependent medications, should be cautious.
    • Patients with electrolyte imbalance symptoms or signs should seek immediate medical attention.
    • Be careful when you are taking any medications that can cause electrolyte imbalances.
  • Hematologic effects

    • It can cause anemia or granulocytopenia.
  • Hypersensitivity

    • There have been reports of severe hypersensitivity reactions including angioedema or anaphylactic shock.
    • If you experience an acute reaction, stop immediately and seek medical treatment.
  • Renal impairment: [US-Boxed Warning]

    • Foscarnet can cause some renal impairment in a majority of patients.;
    • It is possible to develop renal impairment at any time, though it usually occurs during the second week induction therapy.
    • However, many patients have died from renal failure in less than 4 weeks after stopping foscarnet. Therefore, both maintenance and induction therapy should be closely monitored for renal function.
    • For renal dysfunction, dosage adjustments are recommended.
    • Safety and efficacy are not guaranteed for patients with serum creatinine levels greater than 2.8 mg/dL or CrCl lower than 50 mL/minute.
    • To avoid overdosing, calculate CrCl before treatment begins.
    • It is not recommended for patients with CrCl below 0.4 mL/kg per minute.
    • A good hydration can reduce the risk of nephrotoxicity.
  • Extension of QT

    • Reports of QT prolongation have been made, including torsades es.
    • Some reports were also reported in patients with confounding risks factors, such as electrolyte abnormalities, concomitant medication, or underlying cardiac disease.
    • Patients with a history or increased risk of QT prolongation should be cautious.
  • Seizures: [US Boxed Warning]:

    • Possible seizures due to mineral imbalance and plasma electrolyte may occur
    • The incidence of HIV has been reported in as high as 10% of HIV-positive patients.
    • Low total serum calcium, impaired baseline renal function and an underlying CNS condition are all risk factors for seizures.
    • Patients who have had seizures in the past have sometimes been able stop or start again after receiving foscarnet treatment.
    • This is usually after their electrolyte or mineral abnormality has been corrected or their underlying condition treated.
  • Vascular irritant:

    • To avoid tissue irritation and ulceration, only administer into a vein that has adequate blood flow.
    • There have been reports of genital vascular tissue injury; it is important to hydrate properly.
  • Heart failure:

    • Patients with heart disease should be cautious when using this product due to its sodium content.

Foscarnet: Drug Interaction

Risk Factor C (Monitor therapy)

Haloperidol

QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTcprolonging effect of Haloperidol.

QT-prolonging Agents (Highest Risk)

QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.

Talimogene Laherparepvec

Antiherpetic Antivirals may diminish the therapeutic effect of Talimogene Laherparepvec.

Risk Factor D (Consider therapy modification)

Loop Diuretics

May increase the serum concentration of Foscarnet.

Pentamidine (Systemic)

May enhance the adverse/toxic effect of Foscarnet. The specific toxicities may include hypocalcemia, renal failure, and QT-prolongation. Management: Consider alternatives to this combination when possible. If this combination must be used, monitor patients more closely for hypocalcemia, renal dysfunction, and QT interval prolongation.

Risk Factor X (Avoid combination)

Acyclovir-Valacyclovir

Foscarnet may enhance the nephrotoxic effect of Acyclovir-Valacyclovir.

Aminoglycosides

Foscarnet may enhance the nephrotoxic effect of Aminoglycosides.

Amphotericin B

Foscarnet may enhance the nephrotoxic effect of Amphotericin B.

CycloSPORINE (Systemic)

Foscarnet may enhance the nephrotoxic effect of CycloSPORINE (Systemic).

Methotrexate

Foscarnet may enhance the nephrotoxic effect of Methotrexate.

Tacrolimus (Systemic)

Foscarnet may enhance the nephrotoxic effect of Tacrolimus (Systemic).

 

Monitoring parameters:

  • 24-hour creatinine clearance,
  • ECG, and electrolytes at baseline and periodically thereafter (when clinically appropriate).

During induction therapy:

  • Obtain complete blood counts, and electrolytes (including calcium, magnesium, potassium, serum creatinine, and phosphorus) twice a week and then 7 days during maintenance therapy.
  • More frequent monitoring may be required in some patients. Check hydration status before and after infusion.

How to administer Foscarnet?

IV:

  • Foscarnet is administered by intravenous infusion, using an infusion pump, at a rate not exceeding 1 mg per kg per minute.
  • Adult induction doses of 60 mg per kg are administered over 1 hour.
  • Adult maintenance doses of 90 to 120 mg per kg are infused over 2 hours.
  • Undiluted (24 mg per mL) solution can be administered without further dilution when using a central venous catheter for infusion.
  • For peripheral vein administration, the solution must be diluted to a final concentration not to exceed 12 mg per mL.
  • The manufacturer recommends 750 to 1,000 mL of NS or D5W be administered prior to the first infusion to establish diuresis.
  • With subsequent infusions of 90 to 120 mg per kg, this volume would be repeated.
  • If the dose were 40 to 60 mg per kg, then the volume could be reduced to 500 mL.
  • After the first dose, the hydration fluid should be administered concurrently with foscarnet.

Intravitreal: Off-label route:

  • Withdraw solution directly from infusion bottle as it is already diluted to the appropriate concentration for intravitreal administration. Pass through 0.22-micron filter prior to injection.

Mechanism of action of Foscarnet:

  • A pyrophosphate analog acts as a noncompetitive inhibitor of many viral DNA polymerases and viral RNA. 
  • Foscarnet, which is similar to ganciclovir and a virostatic drug, can be used. Foscarnet doesn't require activation via thymidinekinase.

Protein binding:

  • 14 percent to 17 percent

Metabolism:

  • Biotransformation does not occur.

Half-life elimination:

  • Elimination: ~3 to 4 hours;
  • Terminal: ~88 hours (due to bone deposition)

Excretion:

  • Urine (≤28 percent  as unchanged drug)

International Brand Names of Foscarnet:

  • Foscarnet Elea
  • Foscarnet Filaxis
  • Foscarnet Richmond
  • Foscavir
  • Fu Shi Ling
  • Terap
  • Foscavir
  • Carnet
  • Triapten

Foscarnet Brand Names in Pakistan:

There is no brand available in Pakistan.