Foscarnet

Serious side effects have been reported with foscarnet including the following:

• a decline in kidney function. Toxicity from foscarnet may occur with kidney dysfunction. Your doctor may want to monitor your kidney functions with certain blood tests as well. Tell your healthcare provider right away right away if you have any of the following symptoms of kidney dysfunction:
  • swelling of face, ankles, hands, or feet
  • fatigue
  • paleness of skin
  • decreased urination
  • shortness of breath
  • change in blood pressures
• mineral and electrolyte abnormalities. Your doctor may monitor the levels of certain electrolytes in your blood while using this medication. Tell your doctor if you experience numbness in the extremities, dizziness, or seizures.
• seizures. If seizure or any of the above side effects should occur during the infusion, the dose may need to be adjusted or the medication may need to be stopped entirely.
• low red blood cell count (anemia). Tell your doctor if you have any of the following signs of anemia during treatment with foscarnet: feeling weak tired, or tiring easily, you look pale, you feel short of breath.
• low white blood cell count (neutropenia). A low white blood cell count can cause you to get infections, which may be serious. Serious illness or death can happen if it is not treated right away when white blood cell counts are very low. Tell your doctor right away if you have any of the following signs or symptoms of an infection: fever, shortness of breath, pain or burning on urination, chills, or cough. 
• nerve damage (neuropathy). This drug can cause nerve damage that can cause you to have tingling, burning, or painful sensations in your extremities. Tell your doctor right away if you experience pain or numbness in your hands or feet.
• changes in vision. Tell your healthcare provider right away if you experience any changes in vision.
• anxiety. Tell your healthcare provider right away if you feel more nervous, anxious, or notice any changes in mood.
• depression. Tell your healthcare provider right away if you notice any changes in mood.
• confusion. Tell your doctor right away if you feel more confused or notice any changes in mood.
• rash.
• increased sweating.

Do not take foscarnet if you are allergic to foscarnet or to any of its ingredients.

Keep all your appointments with your doctor and laboratory. Your doctor will likely order blood tests to check your kidney function while you are being treated.

You should not use foscarnet if you are allergic to it.

To make sure foscarnet is safe for you, tell your doctor if you have:

• kidney disease;

• heart disease, heart rhythm disorder;

• personal or family history of long QT syndrome;

• an electrolyte imbalance (such as low levels of calcium, potassium, or magnesium in your blood);

• epilepsy or other seizure disorder; or

• if you are on a low salt diet.

It is not known whether this medicine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

It is not known whether foscarnet passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given as an infusion into a vein over a period of time.
• Drink lots of noncaffeine liquids unless told to drink less liquid by your doctor.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about foscarnet, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about foscarnet. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using foscarnet.

Review Date: October 4, 2017

CAUTIONDO NOT ADMINISTER Foscarnet SODIUM BY RAPID OR BOLUS INTRAVENOUS INJECTION. THE TOXICITY OF Foscarnet SODIUM 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.

Foscarnet sodium injection, 24 mg/mL for intravenous infusion, is supplied in glass bottles as follows:

Foscarnet sodium injection should be used only if the bottle and seal are intact, a vacuum is present, and the solution is clear and colorless.

Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature]. Protect from excessive heat (above 40°C) and from freezing.

Revised: 7/2015

                                                                            EN-3981

Hospira, Inc., Lake Forest, IL 60045 USA                                                                            

See tables.

Table has been converted to the following text.

Induction Dosing of Foscarnet in Patients With Abnormal Renal Function

CrCl <0.4 mL/minute/kg: Not recommended

CrCl ≥0.4 to 0.5 mL/minute/kg:

• HSV: 20 mg/kg every 24 hours (equivalent to 40 mg/kg every 12 hours)

• HSV: 35 mg/kg every 24 hours (equivalent to 40 mg/kg every 8 hours)

• CMV: 50 mg/kg every 24 hours (equivalent to 60 mg/kg every 8 hours)

• CMV: 50 mg/kg every 24 hours (equivalent to 90 mg/kg every 12 hours)

CrCl >0.5 to 0.6 mL/minute/kg:

• HSV: 25 mg/kg every 24 hours (equivalent to 40 mg/kg every 12 hours)

• HSV: 40 mg/kg every 24 hours (equivalent to 40 mg/kg every 8 hours)

• CMV: 60 mg/kg every 24 hours (equivalent to 60 mg/kg every 8 hours)

• CMV: 60 mg/kg every 24 hours (equivalent to 90 mg/kg every 12 hours)

CrCl >0.6 to 0.8 mL/minute/kg:

• HSV: 35 mg/kg every 24 hours (equivalent to 40 mg/kg every 12 hours)

• HSV: 25 mg/kg every 12 hours (equivalent to 40 mg/kg every 8 hours)

• CMV: 40 mg/kg every 12 hours (equivalent to 60 mg/kg every 8 hours)

• CMV: 80 mg/kg every 24 hours (equivalent to 90 mg/kg every 12 hours)

CrCl >0.8 to 1 mL/minute/kg:

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

• HSV: 35 mg/kg every 12 hours (equivalent to 40 mg/kg every 8 hours)

• CMV: 50 mg/kg every 12 hours (equivalent to 60 mg/kg every 8 hours)

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

CrCl >1 to 1.4 mL/minute/kg:

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

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

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

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

CrCl >1.4 mL/minute/kg:

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

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

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

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

Table has been converted to the following text.

Maintenance Dosing for CMV in Patients With Abnormal Renal Function

CrCl <0.4 mL/minute/kg: Not recommended

CrCl ≥0.4 to 0.5 mL/minute/kg:

• 50 mg/kg every 48 hours (equivalent to 90 mg/kg every 24 hours)

• 65 mg/kg every 48 hours (equivalent to 120 mg/kg every 24 hours)

CrCl >0.5 to 0.6 mL/minute/kg:

• 60 mg/kg every 48 hours (equivalent to 90 mg/kg every 24 hours)

• 80 mg/kg every 48 hours (equivalent to 120 mg/kg every 24 hours)

CrCl >0.6 to 0.8 mL/minute/kg:

• 80 mg/kg every 48 hours (equivalent to 90 mg/kg every 24 hours)

• 105 mg/kg every 48 hours (equivalent to 120 mg/kg every 24 hours)

CrCl >0.8 to 1 mL/minute/kg:

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

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

CrCl >1 to 1.4 mL/minute/kg:

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

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

CrCl >1.4 mL/minute/kg:

• 90 mg/kg every 24 hours (equivalent to 90 mg/kg every 24 hours)

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

Hemodialysis:

Foscarnet is highly removed by hemodialysis (up to ~38% in 2.5 hours HD with high-flux membrane) (Aweeka 1999)

Doses of 45 to 60 mg/kg/dose posthemodialysis (3 times/week) 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 (Aweeka 1999; Jayasekara 1999; MacGregor 1991)

Peritoneal dialysis: HSV infection (localized or disseminated): IV: 60 mg/kg/dose every 48 to 72 hours; higher doses may be necessary for herpes encephalitis or herpes zoster infection (Jayasekara 1999)

Some products may contain sodium.

>10%:

Central nervous system: Headache (26%)

Endocrine & metabolic: Hypokalemia (16% to 48%), hypocalcemia (15% to 30%), hypomagnesemia (15% to 30%), hypophosphatemia (8% to 26%)

Gastrointestinal: Nausea (47%), diarrhea (30%), vomiting (26%)

Hematologic & oncologic: Anemia (33%), granulocytopenia (17%)

Renal: Renal insufficiency (27%)

Miscellaneous: Fever (65%)

1% to 10%:

Cardiovascular: Chest pain (1% to 5%; including transient chest pain as part of infusion reactions), edema (1% to 5%), facial edema (1% to 5%), first degree atrioventricular block (1% to 5%), flushing (1% to 5%), hypertension (1% to 5%), hypotension (1% to 5%), palpitations (1% to 5%), sinus tachycardia (1% to 5%), ST segment changes on ECG (1% to 5%), thrombosis (1% to 5%)

Central nervous system: Seizure (10%), anxiety (≥5%), confusion (≥5%), depression (≥5%), dizziness (≥5%), fatigue (≥5%), hypoesthesia (≥5%), malaise (≥5%), neuropathy (≥5%), pain (≥5%), paresthesia (≥5%), rigors (≥5%), abnormal electroencephalogram (1% to 5%), aggressive behavior (1% to 5%), agitation (1% to 5%), amnesia (1% to 5%), aphasia (1% to 5%), ataxia (1% to 5%), cerebrovascular disease (1% to 5%), dementia (1% to 5%), hallucination (1% to 5%), insomnia (1% to 5%), meningitis (1% to 5%), nervousness (1% to 5%), sensory disturbance (1% to 5%), somnolence (1% to 5%), stupor (1% to 5%)

Dermatologic: Diaphoresis (≥5%), skin rash (≥5%), dermal ulcer (1% to 5%), erythematous rash (1% to 5%), maculopapular rash (1% to 5%), pruritus (1% to 5%), seborrhea (1% to 5%), skin discoloration (1% to 5%)

Endocrine & metabolic: Hyperphosphatemia (6%), electrolyte disturbance (≥5%), abnormal albumin-Globulin ratio (1% to 5%), acidosis (1% to 5%), albuminuria (1% to 5%), cachexia (1% to 5%), hyponatremia (1% to 5%), increased lactate dehydrogenase (1% to 5%), increased thirst (1% to 5%), weight loss (1% to 5%)

Gastrointestinal: Abdominal pain (≥5%), anorexia (≥5%), aphthous stomatitis (1% to 5%), cachexia (1% to 5%), constipation (1% to 5%), dysgeusia (1% to 5%), dyspepsia (1% to 5%), dysphagia (1% to 5%), flatulence (1% to 5%), melena (1% to 5%), pancreatitis (1% to 5%), xerostomia (1% to 5%)

Genitourinary: Nephrotoxicity (8%), dysuria (1% to 5%), nocturia (1% to 5%), urinary retention (1% to 5%), urinary tract infection (1% to 5%)

Hematologic & oncologic: Bone marrow suppression (10%), leukopenia (≥5%), mineral abnormalities (≥5%), neutropenia (≥5%), abnormal white cell differential (1% to 5%), altered platelet function (1% to 5%), lymphadenopathy (1% to 5%), pseudolymphoma (1% to 5%), rectal hemorrhage (1% to 5%), sarcoma (1% to 5%), thrombocytopenia (1% to 5%)

Hepatic: Abnormal hepatic function tests (1% to 5%), increased lactate dehydrogenase (1% to 5%), increased serum alkaline phosphatase (1% to 5%), increased serum ALT (1% to 5%), increased serum AST (1% to 5%)

Infection: Infection (≥5%), sepsis (≥5%), abscess, bacterial infection (1% to 5%), fungal infection (1% to 5%)

Local: Inflammation at injection site (1% to 5%), pain at injection site (1% to 5%)

Neuromuscular & skeletal: Muscle spasm (≥5%), neuropathy (peripheral; ≥5%), weakness (≥5%), arthralgia (1% to 5%), back pain (1% to 5%), leg cramps (1% to 5%), myalgia (1% to 5%), tremor (1% to 5%)

Ophthalmic: Visual disturbance (≥5%), conjunctivitis (1% to 5%), eye pain (1% to 5%)

Renal: Decreased creatinine clearance (≥5%), increased serum creatinine (≥5%), acute renal failure (1% to 5%), increased blood urea nitrogen (1% to 5%), polyuria (1% to 5%)

Respiratory: Cough (≥5%), dyspnea (≥5%), bronchospasm (1% to 5%), flu-like symptoms (1% to 5%), hemoptysis (1% to 5%), pharyngitis (1% to 5%), pneumonia (1% to 5%), pneumothorax (1% to 5%), pulmonary infiltrates (1% to 5%), respiratory failure (1% to 5%), respiratory insufficiency (1% to 5%), rhinitis (1% to 5%), sinusitis (1% to 5%), stridor (1% to 5%)

<1%, postmarketing, and/or case reports: Coma, dehydration, diabetes insipidus (usually nephrogenic), erythema multiforme, esophageal ulcer, extravasation, Fanconi syndrome, gastrointestinal hemorrhage, glomerulonephritis, hematuria, hypercalcemia, hypersensitivity reaction (including anaphylactic shock, angioedema, urticaria), hypoproteinemia, increased amylase, increased creatine phosphokinase, increased gamma-glutamyl transferase, increased serum lipase, local irritation (genitals), localized edema, myasthenia, myopathy, myositis, nephrolithiasis, nephrotic syndrome, pancytopenia, penile ulceration, prolonged Q-T interval on ECG, proteinuria, renal disease (crystal-induced), renal tubular acidosis, renal tubular necrosis, rhabdomyolysis, SIADH, status epilepticus, Stevens-Johnson syndrome, torsades de pointes, toxic epidermal necrolysis, vaginal ulcer, ventricular arrhythmia

Induction therapy: 90 mg/kg IV (90- to 120-minute infusion) every 12 hours or 60 mg/kg IV (minimum 1-hour infusion) every 8 hours over 2 to 3 weeks depending on clinical response
Maintenance therapy: 90 to 120 mg/kg IV (2-hour infusion) once a day

Comments:
-Maintenance therapy dose should be individualized for renal function.
-Most patients should be started on maintenance therapy at 90 mg/kg/day; escalation to 120 mg/kg/day may be considered should early reinduction be required due to retinitis progression.
-Some patients who show excellent tolerance to this drug may benefit from starting maintenance therapy at 120 mg/kg/day earlier in their treatment.
-Patients who have retinitis progression during foscarnet maintenance therapy may be retreated with the induction and maintenance regimens in combination with ganciclovir; this drug must not be mixed with ganciclovir due to physical incompatibility.

Uses: For the treatment of CMV retinitis in patients with AIDS; in combination with ganciclovir for patients who relapse after monotherapy with either drug

US CDC, National Institutes of Health (NIH), and Infectious Diseases Society of America (IDSA) Recommendations for HIV-infected Patients:
For sight-threatening lesions (adjacent to optic nerve or fovea):
-Intravitreal injections: 2.4 mg as an intravitreal injection for 1 to 4 doses over 7 to 10 days
-Systemic therapy: 60 mg/kg IV every 8 hours or 90 mg/kg IV every 12 hours for 14 to 21 days, then 90 to 120 mg/kg IV every 24 hours

For peripheral lesions: 60 mg/kg IV every 8 hours or 90 mg/kg IV every 12 hours for 14 to 21 days, then 90 to 120 mg/kg IV every 24 hours

Chronic maintenance therapy (secondary prophylaxis): 90 to 120 mg/kg IV once a day

Comments:
-Intravitreal injections plus a systemic antiviral agent should be used for sight-threatening lesions.
-Recommended as alternative systemic therapy

US BOXED WARNINGS:
-RENAL IMPAIRMENT: The major toxicity is renal impairment. Serum creatinine should be monitored frequently, adjusting dose accordingly for renal function changes. Adequate hydration with administration is essential.
-SEIZURES: Seizures related to plasma mineral and electrolyte changes reported. Monitoring for such changes (and potential sequelae) is recommended. Mineral and electrolyte supplementation may be needed.
-INDICATIONS: Indicated for use only in immunocompromised patients with CMV retinitis and mucocutaneous acyclovir-resistant HSV infections.

Safety and efficacy have not been established in patients younger than 18 years; this drug should only be used after careful evaluation and only if benefits outweigh risks.

Consult WARNINGS section for additional precautions.

Hemodialysis: Not recommended.

AU, UK: Use is not recommended. US: This drug should be used during pregnancy only if clearly needed. AU TGA pregnancy category: B3 US FDA pregnancy category: C Comments: -Female patients of childbearing potential should use effective contraception during therapy. -Male patients should not father a child during therapy and for up to 6 months after the last dose. -Local protocol should be consulted regarding contraception timing.

Animal studies have revealed evidence of teratogenicity (skeletal abnormalities). There are no controlled data in human pregnancy. AU TGA pregnancy category B3: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans. US FDA pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.