Drug information of Fludarabine phosphate

Mechanism of effect

Fludarabine phosphate is rapidly dephosphorylated to 2-fluoro-ara-A and then phosphorylated intracellularly by deoxycytidine kinase to the active triphosphate, 2-fluoro-ara-ATP. This metabolite appears to act by inhibiting DNA polymerase alpha, ribonucleotide reductase and DNA primase, thus inhibiting DNA synthesis. The mechanism of action of this antimetabolite is not completely characterized and may be multi-faceted.

Pharmacodynamic

Fludarabine is a chemotherapy drug used in the treatment of chronic lymphocytic leukemia. It acts at DNA polymerase alpha, ribonucleotide reductase and DNA primase, results in the inhibition of DNA synthesis, and destroys the cancer cells.

Pharmacokinetics

• Peak plasma time: 2 hr
• Vd: 96-98 L/sq.meter
• Protein bound: 19-29%
• Metabolites: 2-fluoro-ara-ATP
• Clearance: 8.9 L/hr/sq.meter
• Excretion: urine

Drug indications

chronic lymphocytic leukemia

Dosage

Usual Adult Dose for Chronic Lymphocytic Leukemia

IV:
25 mg/m2 IV once over 30 minutes for 5 days every 28 days. Following a maximal tumor response, 3 additional cycles are recommended.

Oral:
40 mg/m2 once daily for 5 days every 28 days

Usual Adult Dose for non-Hodgkin's Lymphoma

25 mg/m2/day for 5 days every 28 days

Usual Pediatric Dose for Malignant Disease

Solid tumors: 7 to 9 mg/m2 IV bolus followed by 20 to 27 mg/m2/day continuous IV infusion for 5 days

Usual Pediatric Dose for Leukemia

Acute leukemia: 10 mg/m2 IV once over 15 minutes followed by continuous IV infusion of 30.5 mg/m2/day for 5 days or 10.5 mg/m2 IV once over 15 minutes followed by continuous IV infusion of 30.5 mg/m2/day for 2 days followed by cytarabine.

Usual Pediatric Dose for Stem Cell Transplant Conditioning

Reduced-intensity conditioning regimen prior to allogenic hematopoietic stem cell transplantation: 30 mg/m2/day for 5 days

Drug contraindications

hypersensitivity to drug or its components.

Side effects

anemia , Infection , Pain , Diarrhea , Headache , edema , nausea , vomiting , asthenia , Peripheral edema , fever , myalgia , Flu-like symptoms , anorexia , pneumonia , tiredness , shortness of breath , Abdominal pain , Leukopenia , thrombocytopenia , Rash , gastrointestinal hemorrhage

Interactions

Trastuzumab , Dipyridamole , Fingolimod , Hydroxy urea , Tobramycin inhalation , denosumab , Altretamine , Palifermin , Acalabrutinib , olaparib , Pentostatin , Meningococcal Vaccines , Belatacept , Vitamin A , Vitamin E , Adenovirus types 4 and 7 live, oral , Meningococcal conjugate vaccine , dichlorphenamide , sirukumab

Alerts

• Bone marrow depression, renal impairment, elderly
• Allopurinol and hydration recommended for patients newly diagnosed with CLL or those at risk of tumor lysis syndrome
• Very high doses (and rarely, normal doses) have caused irreversible or fatal neurotoxicity manifesting after 21-60 days
• Risk of potentially fatal autoimmune hemolytic anemia
• Avoid pregnancy
• No efficacy in children
• Black Box Warnings
• The drug should be administered under the supervision of an experienced cancer chemotherapy physician
• Bone marrow suppression may occur. Fludarabine has been associated with severe neurologic effects, including blindness, coma when high doses were used in patients with acute leukemia. Agitation, coma, confusion, and seizures have been reported in patients treated at recommended doses for the treatment of chronic lymphocytic leukemia
• If one or more cycles of treatment with fludarabine administered, autoimmune phenomena including acquired hemophilia, autoimmune thrombocytopenia/thrombocytopenic purpura, Evan syndrome, and hemolytic anemia may occur. Monitor patients closely for hemolysis
• Fludarabine in combination with pentostatin (deoxycoformycin) for the treatment of refractory chronic lymphocytic leukemia is not recommended due to a high incidence of fatal pulmonary toxicity

Points of recommendation

oral

Fludarabine is usually taken daily for 5 days in a row every 28 days. Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended. Your doctor will determine how long to treat you with fludarabine.

Take this medicine with a full glass of water. You may take fludarabine with or without food.

Do not crush or chew a fludarabine tablet. Swallow it whole. The medicine from a crushed or broken pill can be dangerous if it gets in your eyes, mouth, or nose, or on your skin. If you accidentally touch a broken tablet, wash your skin with soap and water. Call your doctor if you develop a skin rash or severe irritation.

If the powder from a broken tablet gets in your eyes, rinse them with water for at least 15 minutes.

Fludarabine can lower blood cells that help your body fight infections and help your blood to clot. This can make it easier for you to bleed from an injury or get sick from being around others who are ill. Serious and sometimes fatal infections may occur during treatment. Your blood will need to be tested often. Your nerve function may also need to be checked.

If you need to have a blood transfusion, tell your caregivers ahead of time that you are taking fludarabine.

Store at room temperature away from moisture and heat. Keep each tablet in the foil blister package until you are ready to take it.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Injection

Avoid driving and doing other tasks or actions that call for you to be alert or have clear eyesight until you see how fludarabine injection affects you.

You may have more chance of getting an infection. Wash hands often. Stay away from people with infections, colds, or flu.

You may bleed more easily. Be careful and avoid injury. Use a soft toothbrush and an electric razor.

Talk with your doctor before getting any vaccines while you take fludarabine injection and after you stop taking it. Vaccine use with fludarabine injection may either raise the chance of an infection or make the vaccine not work as well. Talk with your doctor.

Patients with cancer who take fludarabine injection may be at a greater risk of getting a bad health problem called tumor lysis syndrome (TLS). Sometimes, this has been deadly. Call your doctor right away if you have a fast heartbeat or a heartbeat that does not feel normal; any passing out; trouble passing urine; muscle weakness or cramps; upset stomach, throwing up, loose stools, or not able to eat; or feel sluggish.

A very bad brain problem called progressive multifocal leukoencephalopathy (PML) has happened with fludarabine injection. It may cause disability or can be deadly. Tell your doctor right away if you have signs like confusion, memory problems, low mood (depression), change in the way you act, change in strength on 1 side is greater than the other, trouble speaking or thinking, change in balance, or change in eyesight.

If you have taken fludarabine injection and you are getting a blood transfusion, talk with your doctor.

This medicine may affect sperm in men. This may affect being able to father a child. Talk with the doctor.

If you are a man and have sex with a female who could get pregnant, protect her from pregnancy during care and for some time after care ends. Use birth control that you can trust. Talk with your doctor to see how long to use birth control after you stop fludarabine injection.

If you are a man and your sex partner gets pregnant while you take fludarabine injection or within several months after your last dose, call your doctor right away.

This medicine may cause harm to the unborn baby if you take it while you are pregnant.

Use birth control that you can trust to prevent pregnancy during care and for some time after care ends. Talk with your doctor to see how long to use birth control after you stop fludarabine injection.

If you get pregnant while taking fludarabine injection or within several months after the last dose, call your doctor right away.

Pregnancy level

D

Related drugs

Thioguanine , Cytarabine , Hydroxy urea , Capecitabine , mercaptopurine , Clofarabine , Pralatrexate , Decitabine , Floxuridine , Nelarabine , Methotrexate , Pemetrexed