No

Antiviral Agent

Herpesvirus infections suspected to be caused by acyclovir - (HSV, VZV) or ganciclovir - (CMV) resistant strains (this occurs almost exclusively in immunocompromised persons, eg, with advanced AIDS), who have received prolonged treatment for a herpesvirus infection

CMV retinitis in persons with AIDS

Other CMV infections in persons unable to tolerate ganciclovir; may be given in combination with ganciclovir in patients who relapse after monotherapy with either drug

C

Hypersensitivity to foscarnet, Cl_cr <0.4 mL/minute/kg during therapy

Renal impairment occurs to some degree in the majority of patients treated with foscarnet; renal impairment may occur at any time and is usually reversible within 1 week following dose adjustment or discontinuation of therapy, however, several patients have died with renal failure within 4 weeks of stopping foscarnet; therefore, renal function should be closely monitored. Foscarnet is deposited in teeth and bone of young, growing animals; it has adversely affected tooth enamel development in rats; safety and effectiveness in children have not been studied. Imbalance of serum electrolytes or minerals occurs in 6% to 18% of patients (hypocalcemia, low ionized calcium, hypo- or hyperphosphatemia, hypomagnesemia or hypokalemia).

>10%:

Central nervous system: Fever (65%), headache (26%), seizures (10%)

Gastrointestinal: Nausea (47%), diarrhea (30%), vomiting

Hematologic: Anemia (33%)

Renal: Abnormal renal function/decreased creatinine clearance (27%)

1% to 10%:

Central nervous system: Fatigue, malaise, dizziness, hypoesthesia, depression/confusion/anxiety ( greater than or equal to 5%)

Dermatologic: Rash

Endocrine & metabolic: Electrolyte imbalance (especially potassium, calcium, magnesium, and phosphorus)

Gastrointestinal: Anorexia

Hematologic: Granulocytopenia, leukopenia ( greater than or equal to 5%), thrombocytopenia, thrombosis

Local: Injection site pain

Neuromuscular & skeletal: Paresthesia, involuntary muscle contractions, rigors, neuropathy (peripheral), weakness

Ocular: Vision abnormalities

Respiratory: Coughing, dyspnea ( greater than or equal to 5%)

Miscellaneous: Sepsis, diaphoresis (increased)

<1%: Cardiac failure, bradycardia, arrhythmias, cerebral edema, leg edema, peripheral edema, syncope, substernal chest pain, hypothermia, abnormal crying, malignant hyperpyrexia, vertigo, coma, speech disorders, gynecomastia, decreased gonadotropins, cholecystitis, cholelithiasis, hepatitis, hepatosplenomegaly, ascites, abnormal gait, dyskinesia, hypertonia, nystagmus, vocal cord paralysis

Symptoms of overdose include seizures, renal dysfunction, perioral or limb paresthesias, hypocalcemia

Treatment is supportive; I.V. calcium salts for hypocalcemia

Increased toxicity: Pentamidine increases hypocalcemia; concurrent use with ciprofloxacin increases seizure potential; acute renal failure (reversible) has been reported with cyclosporin due most likely to toxic synergistic effect; other nephrotoxic drugs (amphotericin B, I.V. pentamidine, aminoglycosides, etc) should be avoided, if possible, to minimize additive renal risk with foscarnet

Foscarnet injection is a clear, colorless solution; it should be stored at room temperature and protected from temperatures >40°C and from freezing

Foscarnet should be diluted in D₅W or NS and transferred to PVC containers; stable for 24 hours at room temperature or refrigeration

For peripheral line administration, foscarnet must be diluted to 12 mg/mL with D₅W or NS

For central line administration, foscarnet may be administered undiluted

Incompatible with dextrose 30%, I.V. solutions containing calcium, magnesium, vancomycin, TPN

Pyrophosphate analogue which acts as a noncompetitive inhibitor of many viral RNA and DNA polymerases as well as HIV reverse transcriptase. Similar to ganciclovir, foscarnet is a virostatic agent. Foscarnet does not require activation by thymidine kinase.

Absorption: Oral: Poorly absorbed; I.V. therapy is needed for the treatment of viral infections in AIDS patients

Distribution: Up to 28% of cumulative I.V. dose may be deposited in bone

Metabolism: Biotransformation does not occur

Half-life: ~3 hours

Elimination: Up to 28% excreted unchanged in urine

Adolescents and Adults: I.V.:

Induction treatment: 60 mg/kg/dose every 8 hours or 100 mg/kg every 12 hours for 14-21 days

Maintenance therapy: 90-120 mg/kg/day as a single infusion

Acyclovir-resistant HSV induction treatment: 40 mg/kg/dose every 8-12 hours for 14-21 days

Dosage adjustment in renal impairment:

Induction and maintenance dosing schedules based on creatinine clearance (mL/minute/kg):

Induction Dosing:

Cl_cr <0.4: Not recommended

Cl_cr greater than or equal to 0.4-0.5:

HSV: 20 mg/kg every 24 hours (equivalent to 40 mg/kg q12h)

HSV: 35 mg/kg every 24 hours (equivalent to 40 mg/kg q8h)

CMV: 50 mg/kg every 24 hours (equivalent to 60 mg/kg q8h)

CMV: 50 mg/kg every 24 hours (equivalent to 90 mg/kg q12h)

Cl_cr >0.5-0.6:

HSV: 25 mg/kg every 24 hours (equivalent to 40 mg/kg q12h)

HSV: 40 mg/kg every 24 hours (equivalent to 40 mg/kg q8h)

CMV: 60 mg/kg every 24 hours (equivalent to 60 mg/kg q8h)

CMV: 60 mg/kg every 24 hours (equivalent to 90 mg/kg q12h)

Cl_cr >0.6-0.8:

HSV: 35 mg/kg every 24 hours (equivalent to 40 mg/kg q12h)

HSV: 25 mg/kg every 12 hours (equivalent to 40 mg/kg q8h)

CMV: 40 mg/kg every 12 hours (equivalent to 60 mg/kg q8h)

CMV: 80 mg/kg every 24 hours (equivalent to 90 mg/kg q12h)

Cl_cr >0.8-1.0:

HSV: 20 mg/kg every 12 hours (equivalent to 40 mg/kg q12h)

HSV: 35 mg/kg every 12 hours (equivalent to 40 mg/kg q8h)

CMV: 50 mg/kg every 12 hours (equivalent to 60 mg/kg q8h)

CMV: 50 mg/kg every 12 hours (equivalent to 90 mg/kg q12h)

Cl_cr >1.0-1.4:

HSV: 30 mg/kg every 12 hours (equivalent to 40 mg/kg q12h)

HSV: 30 mg/kg every 8 hours (equivalent to 40 mg/kg q8h)

CMV: 45 mg/kg every 8 hours (equivalent to 60 mg/kg q8h)

CMV: 70 mg/kg every 12 hours (equivalent to 90 mg/kg q12h)

Cl_cr >1.4:

HSV: 40 mg/kg every 12 hours (equivalent to 40 mg/kg q12h)

HSV: 40 mg/kg every 8 hours (equivalent to 40 mg/kg q8h)

CMV: 60 mg/kg every 8 hours (equivalent to 60 mg q8h)

CMV: 90 mg/kg every 12 hours (equivalent to 90 mg/kg q12h)

Maintenance Dosing for CMV

Cl_cr <0.4: Not recommended

Cl_cr greater than or equal to 0.4-0.5:

50 mg/kg every 48 hours (equivalent to 90 mg/kg q24h);

65 mg/kg every 48 hours (equivalent to 120 mg/kg q24h)

Cl_cr >0.5-0.6:

60 mg/kg every 48 hours (equivalent to 90 mg/kg q24h);

80 mg/kg every 48 hours (equivalent to 120 mg/kg q24h)

Cl_cr >0.6-0.8:

80 mg/kg every 48 hours (equivalent to 90 mg/kg q24h);

105 mg/kg every 48 hours (equivalent to 120 mg/kg q24h)

Cl_cr >0.8-1.0:

50 mg/kg every 24 hours (equivalent to 90 mg/kg q24h);

65 mg/kg every 24 hours (equivalent to 120 mg/kg q24h)

Cl_cr >1.0-1.4:

70 mg/kg every 24 hours (equivalent to 90 mg/kg q24h);

90 mg/kg every 24 hours (equivalent to 120 mg/kg q24h)

Cl_cr >1.4:

90 mg/kg every 24 hours (equivalent to 90 mg/kg q24h);

120 mg/kg every 24 hours (equivalent to 120 mg/kg q24h)

Hemodialysis:

Foscarnet is highly removed by hemodialysis (30% in 4 hours HD)

Doses of 50 mg/kg/dose posthemodialysis have been found to produce similar serum concentrations as doses of 90 mg/kg twice daily in patients with normal renal function

Doses of 60-90 mg/kg/dose loading dose (posthemodialysis) followed by 45 mg/kg/dose posthemodialysis (3 times/week) with the monitoring of weekly plasma concentrations to maintain peak plasma concentrations in the range of 400-800 mMolar has been recommended by some clinicians

Continuous arteriovenous or venovenous hemodiafiltration (CAVH) effects: Dose as for Cl_cr 10-50 mL/minute

Dizziness, anxiety, confusion, and depression are common; may rarely produce abnormal crying

Leukopenia is common; use caution with clozapine and carbamazepine

No information available to require special precautions

No effects or complications reported

Foscarnet is not a cure for the disease; progression may occur during or following therapy. Regular ophthalmic examinations will be necessary. While on the therapy it is important to maintain adequate nutrition and hydration (2-3 L/day of fluids unless instructed to restrict fluid intake); small frequent meals may help. Do not use alcohol or OTC medications without consulting prescriber. You may experience dizziness or confusion; use caution when driving or engaging in tasks that require alertness until response to drug is known. Report unresolved diarrhea or vomiting, unusual fever, chills, sore throat, unhealed sores, swollen lymph glands or extreme, or malaise. Barrier contraceptives are recommended to reduce transmission of disease. Breast-feeding precautions: Do not breast-feed.

Do not administer by rapid or bolus injection; follow administration guidelines carefully

Injection: 24 mg/mL (250 mL, 500 mL)

Butler KM, DeSmet MD, Husson RN, et al, "Treatment of Aggressive Cytomegalovirus Retinitis With Ganciclovir in Combination With Foscarnet in a Child Infected With Human Immunodeficiency Virus," J Pediatr, 1992, 120(3):483-6.

Calligaro KD, Stern J, and DeLaurentis DA, "Foscarnet: A Possible Cause of Ulnar Artery Thrombosis in a Patient With AIDS," J Vasc Surg, 1994, 20(6):1007-8.

Chrisp P and Clissold SP, "Foscarnet. A Review of Its Antiviral Activity, Pharmacokinetic Properties and Therapeutic Use in Immunocompromised Patients With Cytomegalovirus Retinitis," Drugs, 1991, 41(1):104-29.

Deray G, Martinez F, Katlama C, et al, "Foscarnet Nephrotoxicity: Mechanism, Incidence and Prevention," Am J Nephrol, 1989, 9:316-21.

"Drugs for Non-HIV Viral Infections," Med Lett Drugs Ther, 1994, 36(919):27.

Jacobson MA, "Review of the Toxicities of Foscarnet," J Acquir Immune Defic Syndr, 1992, 5(Suppl 1):S11-7.

Jayaweera DT, "Minimizing the Dosage-Limiting Toxicities of Foscarnet Induction Therapy," Drug Saf, 1997, 16(4):258-66.

Keating MR, "Antiviral Agents," Mayo Clin Proc, 1992, 67(2):160-78.

Morales JM, Munoz MA, Fernandez Zatarain G, et al, "Reversible Acute Renal Failure Caused by the Combined Use of Foscarnet and Cyclosporin in Organ Transplanted Patients," Nephrol Dial Transplant, 1995, 10(6):882-3.

Polis MA, "Foscarnet and Ganciclovir in the Treatment of Cytomegalovirus Retinitis," J Acquir Immune Defic Syndr, 1992, 5(Suppl 1):S3-10.

Whitley RJ, Jacobson MA, Friedberg DN, et al, "Guidelines for the Treatment of Cytomegalovirus Diseases in Patients With AIDS in the Era of Potent Antiretroviral Therapy: Recommendations of an International Panel. International AIDS Society-USA," Arch Intern Med, 1998, 158(9):957-69.