Daunorubicin
When ATH:
L01DB02
Characteristic.
The anthracycline antibiotic, produced Streptomyces coeruleorubidus. Molecular weight 563,99. Hygroscopic crystalline powder or porous mass of red colors. Soluble in water and ethanol, pH of an aqueous solution in concentration 5 mg/ml — 4.5–6.5.
It is used as the hydrochloride salt (por.d / in.) citrate, or (konc.d / info.), encapsulated in liposomes (Average diameter 45 nm, consisting of a lipid bilayer (distearoylphosphatidylcholine and cholesterol in a molar ratio 2:1).
Pharmacological action.
Antitumor.
Application.
Acute leukemia, blast crisis of chronic myeloid leukemia, lymphosarcoma, horionepitelioma uterus, malignant gistotsitoz (in adults and children); soft tissue sarcoma, sympathicoblastoma (children). Used in combination with other anticancer agents in the composition of programs remission induction.
Contraindications.
Hypersensitivity, suppression of bone marrow function, kaxeksija, terminal stage of tumor, metastases in the bone marrow, leukopenia, thrombocytopenia, viral infections (enable vetryanaya, shingles), organic heart disease, expressed human liver and kidneys, gastric ulcer and duodenal ulcer in the acute stage, pregnancy, lactation.
Restrictions apply.
Advanced age (increased risk of cardiotoxicity and bone marrow suppression), gout or renal calculi in history (the risk of hyperuricemia).
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.)
Breastfeeding is not recommended because of the possible risk to infants (Adverse Effects, mutagenic and carcinogenic effects).
Side effects.
Cardio-vascular system and blood (hematopoiesis, hemostasis): cardiotoxicity in the form of congestive heart failure (tachycardia, breathlessness, swelling of feet and ankles) and in the form of pericarditis, myocarditis, leukopenia, thrombocytopenia (usually asymptomatic), anemia, granulocytopenia; rarely - unusual bleeding or hemorrhage.
From the digestive tract: nausea, vomiting (observed shortly after administration and last 24-48 hours), esophagitis, stomatitis or (appear 3-7 days after treatment), oropharyngeal candidiasis, anorexia, diarrhea, ulceration of the mucous membranes of the gastrointestinal tract, tenesmus.
With the genitourinary system: giperurikemiya or nephropathy, associated with increased production of uric acid (joint pain, lower back or side), most often it occurs in the initial period of treatment; reddish coloration of urine (disappears within 48 no), cystitis.
For the skin: hair loss (obratimoe), darkening or redness of the skin, pannykulyt, cellulitis.
Allergic reactions: rarely - skin rash or itching, edema, fever or chills.
Other: headache, opportunistic infections; extravasates, necrosis, phlebitis at the injection site.
Cooperation.
Other anti-cancer drugs and radiation therapy to potentiate the effect of the additive and depress bone marrow function; Cyclophosphamide may enhance cardiotoxicity (particularly in patients with disorders of the cardiovascular system). It reduces the effectiveness of allopurinol protivopodagricakih, colchicine and sulfinpirazona. With the introduction of live virus vaccines vaccine virus replication and increased side effects, Inactivated vaccines - reducing production of antiviral antibodies.
The data on the interaction of liposomal form of daunorubicin citrate with other drugs no.
Overdose.
Symptoms: manifestations of cardiotoxicity (precordial pain, tachycardia, ECG changes, low blood pressure, miokardit), severe myelosuppression (granulocytopenia), weakness, nausea, vomiting.
Treatment: symptomatic.
Dosing and Administration.
B /. Daunorubicin hydrochloride is dissolved in isotonic sodium chloride solution and administered at a dose of 30–60 mg/m2 (0,8-1.5 mg/kg) daily for 3 days or at a dose of 20–40 mg/m2 (0,6-1 mg/kg) during 5 days. The total course dose - up to 15 mg / kg. After 7-15 days repeat the course. Intermittent administration is possible - 30-60 mg / m2 once in 5-7 days (kursovaya dose 7 mg/kg or more) or a single dose 180 mg / m2 (re-introduction - not earlier than after 1 Months). Children - 20-30 mg / m2 by the same scheme.
Daunorubicin citrate divorce 5% glucose solution in the ratio 1:1 and is administered for 60 min dose 40 mg / m2 1 once every 2 Sun.
If abnormal liver function and kidney dose daunorubicin reduced to 3/4 (at the level of bilirubin 20,5-51,3 mmol / l) or 1/2 (at the level of bilirubin above 51,3 mmol / L or creatinine 0,3 mmol / l).
Precautions.
The use of daunorubicin should be under the strict control of blood parameters. Before each course of treatment should be evaluated cardiac function, kidney and liver.
To prevent secondary hyperuricemia recommended early application of allopurinol and adequate fluid intake during treatment.
To use caution in patients with poor bone marrow reserve.
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 require immediate doctor's advice.
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). In the course of treatment must be careful when using toothbrushes, threads or toothpicks.
Avoid getting the solution under the skin or soft tissue. On education infiltration (local tissue damage and scarring), redness, pain or swelling at the injection site you must inform the doctor.
In the formation of extravasates (burning or severe pain at the injection site) administration should be discontinued immediately and restart in another vein until a full dose.
During the period of treatment is not recommended vaccination virus vaccines.
Cautions.
Using daunorubicin should be performed by qualified medical personnel in compliance with established precautions when preparing and diluting injections (in a sterile box with the use of disposable surgical gloves and masks), Destruction of needles, syringes, bottles, ampoules and the remainder of the unused product.
In case of accidental contact with the powder or solution to the skin or mucous membranes they should be thoroughly washed with soap and water.
Liposomal form of daunorubicin citrate can be mixed only 5% glucose solution; should not be mixed with saline, bacteriostatic agents (benzyl alcohol) and any other solutions. Liposomal form (translucent liposome dispersion, to some extent scatters light) can not be used, if it becomes opaque, or it there is precipitation or foreign matter.
