Fludarabine phosphate

What is Fludarabine phosphate?

• Fludarabine phosphate is a nucleotide metabolic inhibitor used to treat B-cell chronic lymphocytic leukemia (CLL) that has not responded to treatment with other anticancer drugs or that has gotten worse.

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Fludarabine phosphate

Fludarabine ball-and-stick

What are the uses of this medicine?

• Fludarabine phosphate is used as a single agent for the treatment of adult patients with B-cell chronic lymphocytic leukemia (CLL) whose disease has not responded to or has progressed during or after treatment with at least one standard alkylating-agent containing regimen.

How does this medicine work?

• Fludarabine phosphate (2F-ara-AMP) is a synthetic purine nucleotide antimetabolite agent.
• Upon administration, it is rapidly dephosphorylated in the plasma to 2F-ara-A, which then enters into the cell.
• Intracellularly, 2F-ara-A is converted to the 5'-triphosphate, 2-fluoro-ara-ATP (2F-ara-ATP).
• 2F-ara-ATP competes with deoxyadenosine triphosphate for incorporation into DNA.
• Once incorporated into DNA, 2F-ara-ATP functions as a DNA chain terminator, inhibits DNA polymerase alpha, gamma, and delta, and inhibits ribonucleoside diphosphate reductase.
• 2F-ara-A also inhibits DNA primase and DNA ligase I.
• Fludarabine is converted intracellularly to the active triphosphate, which competes with adenine triphosphate for use by DNA polymerase leading to inhibition of DNA synthesis.
• Therfore, fludarabine phosphate blocks cells from making DNA and may kill cancer cells.

Who Should Not Use this medicine ?

• This medicine have no usage limitations.

What drug interactions can this medicine cause?

• The use of fludarabine phosphate in combination with pentostatin is not recommended due to the risk of severe pulmonary toxicity.

Is this medicine FDA approved?

• Fludarabine was approved for medical use in the United States in 1991.

How should this medicine be used?

Recommended dosage: Chronic Lymphocytic Leukemia (CLL):

• The oral dose is different than the intravenous dose.

Fludarabine Phosphate tablets:

• The recommended adult dose is 40 mg/m2 administered daily for five consecutive days by the oral route.
• Begin each 5-day course of treatment every 28 days.

Renal Impairment:

• Reduce dose by 20% in patients with mild to moderate renal impairment (creatinine clearance 30 to 70 mL/min/1.73 m2).
• Reduce dose by 50% in patients with severe renal impairment (creatinine clearance < 30 mL/min/1.73 m2).

Fludarabine Phosphate Injection:

• The recommended adult dose of Fludarabine Phosphate Injection, USP is 25 mg/m 2 administered intravenously over a period of approximately 30 minutes daily for five consecutive days.
• Each 5 day course of treatment should commence every 28 days.

Renal Impairment:

• Adult patients with moderate impairment of renal function (creatinine clearance 30 to 70 mL/min/1.73 m 2) should have a 20% dose reduction of Fludarabine Phosphate Injection, USP.

Administration:

• Fludarabine phosphate film-coated tablets can be taken either on an empty stomach or with food.
• The tablets have to be swallowed whole with water; they should not be chewed or broken.
• Fludarabine Phosphate Injection, USP is administered intravenously over a period of approximately 30 minutes.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• Fludarabine is available as a powder or solution for injection.
• Oral formulations are also available as 10 milligram film-coated tablets.

This medicine is available in fallowing brand namesː

• Fludara; Oforta

What side effects can this medication cause?

The most common side effects of this medicine include:

• myelosuppression (neutropenia, thrombocytopenia and anemia)
• Fever
• weakness
• infection
• pain
• cough
• anorexia

What special precautions should I follow?

• Severe bone marrow suppression, notably anemia, thrombocytopenia and neutropenia, has been reported in patients treated with fludarabine phosphate. Monitor blood counts before and during treatment.
• Infections may occur. Monitor for signs or symptoms of infection.
• Dose-dependent neurotoxicity has been observed with fludarabine phosphate. Physicians should consider delaying or discontinuing the drug if neurotoxicity occurs.
• A high incidence of fatal pulmonary toxicity was observed in a clinical investigation using fludarabine phosphate in combination with pentostatin (deoxycoformycin). Therefore, the use of fludarabine phosphate in combination with pentostatin is not recommended.
• Tumor lysis syndrome associated with fludarabine phosphate treatment has been reported. precautions should be taken in those patients at risk of developing this complication.
• Transfusion-associated graft-versus-host disease has been observed rarely after transfusion of non-irradiated blood in fludarabine phosphate treated patients. Consideration should, therefore, be given to the use of irradiated blood products in those patients requiring transfusions while undergoing treatment with fludarabine phosphate.
• Fludarabine phosphate dose should be adjusted in patients with mild to moderate (creatinine clearance 30 to 70 mL/min/1.73 m2) or severe (creatinine clearance < 30 mL/min/1.73 m2) renal impairment.
• Based on its mechanism of action, fludarabine phosphate can cause fetal harm when administered to a pregnant woman. Women of childbearing potential and fertile males must take contraceptive measures during and at least for 6 months after the cessation of therapy.

What to do in case of emergency/overdose?

Symptoms of overdosage may include:

• delayed blindness
• coma
• death
• thrombocytopenia
• neutropenia

Management of overdosage:

• There is no known specific antidote for fludarabine phosphate overdosage.
• Treatment consists of drug discontinuation and supportive therapy.

Can this medicine be used in pregnancy?

• Based on its mechanism of action, fludarabine phosphate can cause fetal harm when administered to a pregnant woman.
• There are no adequate and well-controlled studies of fludarabine phosphate in pregnant women.
• Women of childbearing potential should be advised to avoid becoming pregnant.
• Women of childbearing potential and fertile males must take contraceptive measures during and at least for 6 months after the cessation of therapy.

Can this medicine be used in children?

• Safety and effectiveness in pediatric patients have not been established.

What are the active and inactive ingredients in this medicine?

Active ingredient:

• FLUDARABINE PHOSPHATE

Inactive ingredients:

• microcrystalline cellulose
• lactose monohydrate
• colloidal anhydrous silicon dioxide
• croscarmellose sodium
• magnesium stearate
• hypromellose
• talc
• titanium dioxide
• ferric oxide pigment

Who manufactures and distributes this medicine?

Fludarabine Phosphate tablets:

• Manufactured for: Antisoma Research Limited, Cambridge, MA 02139
• Manufactured by: Bayer Schering Pharma AG, Berlin, Germany

What should I know about storage and disposal of this medication?

Fludarabine Phosphate Injection:

• REFRIGERATE AT: 2° to 8°C (36° to 46°F).
• The container closure is not made with natural rubber latex.

Fludarabine phosphate tablets:

• Store under normal lighting conditions at 25°C (77°F); excursions permitted to 15-30°C (59-86°F).

Handling and Disposal:

• Procedures for proper handling and disposal should be considered.
• Consideration should be given to handling and disposal according to guidelines issued for cytotoxic drugs.
• Several guidelines on this subject have been published.
• Caution should be exercised in the handling of fludarabine phosphate.
• Do not crush tablets.
• Avoid exposure by direct contact of the skin or mucous membranes or by inhalation.
• If contact occurs, wash thoroughly with soap and water or wash the eyes immediately with gently flowing water for at least 15 minutes.

• Dailymed label info on Fludarabine phosphate
• FDA Fludarabine phosphate

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