Cytarabine

When ATH:
L01BC01

Characteristic.

Antimetaʙolit, pyrimidine antagonist. Synthetic nucleoside, containing arabinose carbohydrate moiety.

White or off-white crystalline powder without smell, soluble in water, slightly soluble in ethanol and chloroform. Molecular weight - 243,22.

Pharmacological action.
Antitumor, immunosuppressive.

Application.

Lymfoblastnыy and myeloblastnыy leukemia, chronic myelogenous leukemia (blastnыy crisis), erythroleukemia, limfogranulematoz, nehodzhkinskaya lymphoma, dysplasia of the bone marrow (myelodysplastic syndrome).

Contraindications.

Hypersensitivity, aplasia or suppression of bone marrow function (due to radiation or chemotherapy, incl. history), lack of liver and kidney function, acute infectious diseases, enable vetryanaya, shingles.

Pregnancy and breast-feeding.

Contraindicated in pregnancy (especially in the I trimester).

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: less frequently (≤10% of patients) - Toxic effects on the CNS, cerebellum or brain, peripheral neuropathy (feeling of numbness or tingling in the fingers, leg or facial; unusual tiredness); seldom - a headache (after intrathecal), alarm, hemorrhagic conjunctivitis, toxic effects on the cornea (obratimoe).

Cardio-vascular system and blood (hematopoiesis, hemostasis): suppression of bone marrow function, leukopenia, thrombocytopenia; REER - megaloblastnaя anemia, arrhythmia, tromboflebit (pain at the injection site).

From the respiratory system: bronchospasm; rarely - pulmonary edema or diffuse interstitial pneumonitis (cough, breathlessness).

From the digestive tract: more often (at 15-100% of patients) - Nausea, vomiting, loss of appetite, stomatitis, abdominal pain; less often - diarrhea; rarely - bleeding in the gastrointestinal tract, esophagitis, hepatotoxic effects (yellow skin or sclera).

With the genitourinary system: less frequently (≤10% of patients) - Giperurikemiya or nephropathy (associated with increased production of uric acid); rarely - urinary retention.

Other: less frequently (≤10% of patients) - Itching, the appearance of spots on the skin, rarely (≤ 2% patients ) - Pannykulyt, "Tsitarabinovy ​​syndrome" (pain in the bones or muscles, chest pain, fever, general feeling of discomfort, faintness, or weakness, red eyes, skin rash), hair loss.

Cooperation.

Chance of a synergistic cytotoxic effect of methotrexate. It inhibits the absorption of digoxin in the gastrointestinal tract.

Increased risk of infection while the use of other immunosuppressants (azathioprine, chlorambucil, tsiklofosfamida, cyclosporine, mercaptopurine, gljukokortikoidami).

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

Preparations, causing myelosuppression, increase due to cytarabine leukopenia and / or thrombocytopenia.

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.

Pharmaceutical incompatible with heparin, insulinom, ftoruracilom, oxacillin, penicillin, methylprednisolone.

Overdose.

Symptoms: treatment with high doses accompanied by a pronounced toxic effects with possible fatal, including reversible toxic effects on the cornea, and hemorrhagic conjunctivitis, CNS dysfunction (confusion, fatigue, memory loss, seizures), dysfunction of the cerebellum (difficulty in speaking, while standing or walking; tremor), ulceration in the gastrointestinal tract, peritonitis (including cystic intestinal pneumatosis, leading to peritonitis), sepsis due to the accession of secondary infection on a background of leukopenia, pulmonary edema, liver damage with hyperbilirubinemia, bowel necrosis, nekroticheskiy colitis, each eruption, leading to desquamation, cardiomyopathy, respiratory distress syndrome, progressing to pulmonary edema and cardiomegaly, as well as motor and sensory peripheral neuropathy.

12-kratnaya in / in infusion (during 1 no) cytarabine dose 4,5 g / m² every 12 h causes irreversible changes in the central nervous system and death.

Treatment: symptomatic, There is no specific antidote.

Dosing and Administration.

B / (infusion or slow bolus), n / a, intrathecal (intralyumbalno). The mode set individually; also used in combination with other anticancer drugs (cyclophosphamide, vynkrystyn, thioguanine et al.) and prednisone in different schemes.

The daily dose - 100 mg / m², Heading dose for all routes of administration - 500-1000 mg. Elderly patients or those with lower reserves of hematopoiesis is prescribed in doses of 50-75 mg / m².

Immediately before use, the contents of a bottle dissolve isotonic sodium chloride solution or water for injection (for I / administration 400 ml, for n / a and in intrathecal 1 ml).

B / (drop), 100 mg / m² /day in two infusions 3 h intervals 10 h or continuously 24 h for 4-7 days (The maximum single dose - 3 g / m²).

P /, by 20 mg / m² 23 times a day for 3-10 days (no more).

Intrathecal, 20 mg / m² (usually in combination with methotrexate 12,5 mg / m²) every 3 days for 2 Sun.

Spend 4-7 courses with an interval of 10-14 days.

Precautions.

The use of cytarabine should be under the strict control of the number of leukocytes (daily or every other day), hematopoietic function of bone marrow (before and after each course of therapy), liver function (at least once a week), renal excretory function (before and after the course of therapy). By reducing the number of leukocytes below 1x10⁹/l or the platelet count below 50h10⁹/l cytarabine may be canceled before the restoration of laboratory indices of blood, Further administered at a lower dose.

Special precautions (the rejection of the / m injection, a urine test, feces and secret occult blood, refusal to take acetylsalicylic acid, potential platelet transfusions, etc..) must be observed in the case of thrombocytopenia; when leukopenia - carefully monitor the development of infections. Patients with neutropenia with an increase in body temperature of antibiotics should be started empirically.

Elderly patients may require a dose reduction (more likely to age renal dysfunction).

Dental procedures should be completed before the start of therapy or deferred until the normalization of the blood picture (may increase the risk of microbial infection, slowing the healing process, krovotochivosty right). During treatment caution when using toothbrushes, threads or toothpicks.

Exercise caution in combination therapy; each product must be taken in due time.

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 virus vaccines, should avoid contact with people, received the vaccine against polio, patients with bacterial infections. Use live virus vaccine in patients with leukemia in remission should not be at least 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.

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.

Use caution to avoid accidental cuts with sharp objects (safety razor, scissors), Avoid contact sports or other situations, which are likely to hemorrhage or trauma.

For the preparation of drugs for use in infants is not recommended to use solvents, containing benzyl alcohol. Use of solvents, containing benzyl alcohol, It should also be avoided when preparing solutions, for the treatment of high doses and for intrathecal.

During treatment is recommended to use contraception.

Cautions.

The use of cytarabine should be done by specially trained medical personnel in compliance with established precautions when preparing and diluting injections (in sterile box, with the use of disposable surgical gloves and masks) and disposal of needles, syringes, bottles, ampoules and the remainder of the unused product.

Cooperation