Fludaraʙin

When ATH:
L01BB05

Characteristic.

Antimetaʙolit, relatively resistant to deamination of adenosine deaminase. It is used in the form of fludarabine phosphate, is a water soluble precursor of fludaraʙina. The molecular weight of fludarabine phosphate - 365,2.

Pharmacological action.
Antitumor, cytostatic.

Application.

Chronic lymphocytic leukemia B-cell (KhLL), non-Hodgkin's lymphoma, low-grade (NHL NZ).

Contraindications.

Hypersensitivity, impairment of renal function (Cl creatinine less than 30 ml / min), dekompensirovannaya gemoliticheskaya anemia, Pregnancy and lactation.

Pregnancy and breast-feeding.

Contraindicated in pregnancy.

Category actions result in FDA - D. (There is evidence of the risk of adverse effects of drugs on the human fetus, obtained in research or practice, However, the potential benefits, associated with drugs in pregnant, may justify its use, in spite of the possible risk, if the drug is needed in life-threatening situations or severe disease, when safer agents should not be used or are ineffective.)

At the time of treatment should stop breastfeeding.

Side effects.

From the nervous system and sensory organs: fatiguability, weakness, anxiety, impairment of consciousness and / or view, peripheral neuropathy; in rare cases - optic neuritis, zritelynaya neyropatiya or blindness.

Cardio-vascular system and blood (hematopoiesis, hemostasis): mielosuprescia (neutropenia, thrombocytopenia, anemia); in rare cases - heart failure, arrhythmia.

From the respiratory system: pulmonary edema or diffuse interstitial pneumonitis Hypersensitivity (cough, fever, breathlessness).

From the digestive tract: nausea, vomiting, anorexia, diarrhea, gastrointestinal bleeding; less frequently - stomatitis, or inflammation of the oral mucosa.

Metabolism: rarely - tumor lysis syndrome (hyperuricemia, hematuria, frequent urination, giperfosfatemiя, hypocalcemia), metabolic acidosis, hyperkalemia, kristallurija, renal failure.

With the genitourinary system: rarely - hemorrhagic cystitis.

For the skin: skin rash; in rare cases - Stevens - Johnson and toxic epidermal necrolysis (Lyell's syndrome).

Other: sometimes - lower tolerance to infections, swelling (swelling of feet and ankles); less frequently - Hair Loss.

Cooperation.

Adenosine reuptake inhibitors (dipyridamole, and others.) reduce efficiency.

It reduces the effectiveness of allopurinol protivopodagricakih, colchicine and sulfinpirazona.

Other drugs, causing depression of bone marrow function, or potentiate the effect of radiation therapy and additive depress bone marrow function. When administered live virus vaccines can intensify vaccine virus replication and increased side effects or reducing the production of antibodies in the patient's body in response to the vaccine, inactivated vaccines - reduction of production of antiviral antibodies.

Overdose.

Symptoms: with high doses of (higher 96 mg / m²/daily for 5-7 days) irreversible changes in the central nervous system (loss of sight, coma, can be fatal); mielosuprescia (thrombocytopenia and neytropeniya).

Treatment: elimination of the drug from the body, symptomatic and supportive therapy. Spetsificheskiy antidote unknown.

Dosing and Administration.

B /, infusion, during 30 m, slow bolus. The contents of the vial is dissolved in 2 ml water for injection. The resulting solution was further diluted 0,9% sodium chloride solution: for in / bolus - in 10 ml, for in / infusion - in 100 ml.

The recommended dose of fludarabine phosphate is 25 mg / m² body surface area daily for 5 every day 28 at days / introduction.

The duration of treatment depends on the effect and tolerability.

Patients with chronic lymphocytic leukemia fludarabine should be appointed until the maximum response (complete or partial remission, usually - 6 cycles), after which the treatment should be discontinued.

Patients with NHL NC fludarabine treatment is recommended to achieve maximum response (complete or partial remission). After reaching the maximum effect should discuss the need for two cycles of consolidation. According to clinical trials in NHL NC, most of the patients received no more 8 treatment cycles.

In the treatment of a form of oral fludarabine (tablets) the recommended dose is 40 mg / m² body surface area daily for 5 every day 28 days.

Patients with impaired renal function (the Cl creatinine 30-70 ml / min) and older persons 70 years to reduce the dose 50%.

Precautions.

The use of fludarabine should be under the supervision of a qualified physician, has experience in anticancer therapy.

The treatment requires periodic monitoring of peripheral blood, uric acid level in blood plasma, laboratory parameters of renal function. In the case of hemolysis therapy is stopped. Patients at risk for tumor lysis syndrome requires systematic monitoring physician, especially during the first week of treatment.

Elderly patients may require a dose reduction (more likely to age renal dysfunction). Fludarabine prescribed with caution after a careful assessment of risk / benefit to patients in a weakened state, Patients with a marked decrease in bone marrow function, Immunodeficiency, opportunistic infections, Children and patients with liver failure (efficacy and safety in children, and in patients with hepatic impairment has not been studied).

Patients, who received or are receiving fludarabine, requiring transfusion, should only irradiated blood transfusions, in order to avoid reaction "graft versus host".

Be wary appoint patients, previously treated with cytotoxic drugs or radiation therapy.

Care should be taken when signs of bone marrow suppression. Special precautions should be observed in the case of thrombocytopenia (the rejection of the / m injection, a urine test, feces and secret occult blood, refusal to take acetylsalicylic acid, caution when using toothbrushes, threads or toothpicks). You may need a transfusion of platelets.

Care should be taken to avoid accidental cuts with sharp objects (incl. safety razor, scissors). Avoid contact sports or other situations, which are likely to hemorrhage or trauma.

The appearance of signs of depression of bone marrow function, unusual bleeding or hemorrhage, black tarry stools, blood in the urine or feces or point of red spots on the skin requires immediate doctor's advice. When leukopenia should carefully monitor the development of infections. Patients with neutropenia with an increase in body temperature of antibiotics should be started empirically.

For the prevention of hyperuricemia in process is important enough fluid intake and urine output for subsequent amplification providing uricosuric, in some cases the use of allopurinol.

During the period of treatment is not recommended vaccination live virus vaccines. Apply live virus vaccine in patients with leukemia in remission should not be within 3 months after the last cycle of chemotherapy. Immunization of oral polio vaccine people, It is in close contact with the patient, especially family members, should be postponed.

At the time of treatment, as well as for 6 months after it should use birth control to prevent pregnancy.

Cautions.

Observe the necessary rules for the use and destruction of the drug. Breeding fludarabine should be performed by trained personnel in specially equipped place (in special cabinets with hood), using the protective garment (disposable gloves, goggles, masks), observing precautions in the preparation of injectable solutions and disposal of needles, syringes, ampoules and the remainder of the unused product.

Loose or stay drug burn. In case of accidental contact with the solution of the drug to the skin must be immediately wash the affected area with soap and water, Eye contact - rinse thoroughly with plenty of water. Avoid inhalation of the drug. During pregnancy, the medical staff is not allowed to work.

Avoid inadvertent intravascular contact with the drug.

Cooperation