Cytarabine And Daunorubicin

Cytarabine And Daunorubicin Uses, Dosage, Side Effects, Food Interaction and all others data.

Cytarabine inhibits deoxyribonucleic acid (DNA) synthesis specifically at the S-phase of the cell cycle. It also has an antiviral and immunosuppressant activity.

Cytarabine is an antineoplastic anti-metabolite used in the treatment of several forms of leukemia including acute myelogenous leukemia and meningeal leukemia. Anti-metabolites masquerade as purine or pyrimidine - which become the building blocks of DNA. They prevent these substances becoming incorporated in to DNA during the "S" phase (of the cell cycle), stopping normal development and division. Cytarabine is metabolized intracellularly into its active triphosphate form (cytosine arabinoside triphosphate). This metabolite then damages DNA by multiple mechanisms, including the inhibition of alpha-DNA polymerase, inhibition of DNA repair through an effect on beta-DNA polymerase, and incorporation into DNA. The latter mechanism is probably the most important. Cytotoxicity is highly specific for the S phase of the cell cycle.

Daunorubicin forms a stable complex with DNA and interferes with the nucleic acid synthesis. It is a cell-cycle nonspecific agent, but its cytotoxic effects are mostly marked in the S-phase. It also has immunosuppressant and antibacterial effects.

Daunorubicin is an antineoplastic in the anthracycline class. General properties of drugs in this class include: interaction with DNA in a variety of different ways including intercalation (squeezing between the base pairs), DNA strand breakage and inhibition with the enzyme topoisomerase II. Most of these compounds have been isolated from natural sources and antibiotics. However, they lack the specificity of the antimicrobial antibiotics and thus produce significant toxicity. The anthracyclines are among the most important antitumor drugs available. Doxorubicin is widely used for the treatment of several solid tumors while daunorubicin and idarubicin are used exclusively for the treatment of leukemia. Daunorubicin may also inhibit polymerase activity, affect regulation of gene expression, and produce free radical damage to DNA. Daunorubicin possesses an antitumor effect against a wide spectrum of tumors, either grafted or spontaneous. The anthracyclines are cell cycle-nonspecific.

Cytarabine And Daunorubicin
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Cytarabine And Daunorubicin
Generic	Cytarabine + daunorubicin
Weight	100mg + 44mg
Type	Intravenous powder for injection, liposomal
Therapeutic Class
Manufacturer
Available Country	United States
Last Updated:	September 19, 2023 at 7:00 am

Uses

Cytarabine is used for Leukaemic meningitis, Induction and maintenance of remission in acute leukaemias

Daunorubicin in combination with other approved anticancer drugs is used for remission induction in acute nonlymphocytic leukemia (myelogenous, monocytic, erythroid) of adults and for remission induction in acute lymphocytic leukemia of children and adults.

Cytarabine And Daunorubicin is also used to associated treatment for these conditions: Acute Lymphocytic Leukemia (ALL), Acute Myeloid Leukemia (AML), Acute Promyelocytic Leukemia (APL), Leptomeningeal Metastases, Meningeal leukemia, Non-Hodgkin's Lymphoma (NHL), Blast phase Chronic myelocytic leukemiaAcute Lymphocytic Leukemia (ALL), Acute Myeloid Leukemia (AML), Acute Myeloid Leukemia With Myelodysplasia-Related Changes, Acute erythroid leukemia, Acute monocytic leukaemia, Newly diagnosed Therapy-Related Acute Myeloid Leukemia

How Cytarabine And Daunorubicin works

Cytarabine acts through direct DNA damage and incorporation into DNA. Cytarabine is cytotoxic to a wide variety of proliferating mammalian cells in culture. It exhibits cell phase specificity, primarily killing cells undergoing DNA synthesis (S-phase) and under certain conditions blocking the progression of cells from the G1 phase to the S-phase. Although the mechanism of action is not completely understood, it appears that cytarabine acts through the inhibition of DNA polymerase. A limited, but significant, incorporation of cytarabine into both DNA and RNA has also been reported.

Daunorubicin has antimitotic and cytotoxic activity through a number of proposed mechanisms of action: Daunorubicin forms complexes with DNA by intercalation between base pairs, and it inhibits topoisomerase II activity by stabilizing the DNA-topoisomerase II complex, preventing the religation portion of the ligation-religation reaction that topoisomerase II catalyzes.

Dosage

Cytarabine And Daunorubicin dosage

Intrathecal (Adult)-

Leukaemic meningitis:5-75 mg/m2 or 30-100 mg once every 2-7 days to once daily for 4 or 5 days.
For lymphomatous meningitis: 50 mg every 2 wk for 5 doses, then every 4 wk for 5 doses.

Parenteral (Adult)-Induction and maintenance of remission in acute leukaemias:

As monotherapy: 200 mg/m2 daily by continuous IV infusion for 5 days, at intervals of approx 2 wk.
In combination therapy: 100 mg/m2 bid by rapid IV inj or 100 mg/m2 daily by continuous IV infusion both for 7 days. Maintenance: 1-1.5 mg/kg once or twice wkly via IV or SC.

Intravenous-

Acute leukaemias:

Adult:30-45 mg/m2BSA daily on days 1-3 of the induction course and days 1 and 2 for the subsequent courses. Admin as a solution in 0.9% sodium chloride into a fast-running infusion of sodium chloride or glucose. May repeat course 3-6 wk later. Max (total cumulative dose): 550 mg/m2in patients without risk factors for cardiotoxicity and 400 mg/m2in patients who have received chest radiotherapy.
Child:For acute lymphoblastic leukaemia: 25 mg/m2BSA once wkly in combination with other regimens. <2 yr old or BSA <0.5 m2: 1 mg/kg once wkly. Max (total cumulative dose): 300 mg/m2and in children <2 yr: 10 mg/kg.

AIDS-related Kaposi's sarcoma:

Adult:As the liposomal formulation: Initially, 40 mg/m2once every 2 wk, diluted in glucose 5% to a concentration of 0.2-1 mg/ml and given over 30-60 minutes. May continue for as long as disease control can be maintained.

Intravenous: Reconstitute with bacteriostatic water for inj (standard-dose), further dilute in 250-1,000 ml NaCl 0.9% or dextrose 5% in water for infusion.

Intrathecal: Reconstitute with preservative free NaCl 0.9%, further dilute with Elliot’s B soln, NaCl 0.9% or lactated Ringer’s inj to preferred final vol (up to 12 ml).

Side Effects

Nausea, vomiting, fever, rash, diarrhoea, anorexia, oral and anal inflammation or ulceration, hepatic dysfunction, headache, weakness, confusion, thrombocytopenia, fatigue.

GI disturbances; stomatitis; alopoecia and dermatological reactions. Extravasation of daunorubicin may cause severe local tissue necrosis damaging surrounding muscles, tendons and nerves. IV infusion, back pain, flushing and chest tightness.

Toxicity

Cytarabine syndrome may develop - it is characterized by fever, myalgia, bone pain, occasionally chest pain, maculopapular rash, conjunctivitis, and malaise.

LD₅₀=20 mg/kg (mice, IV); LD₅₀=13 mg/kg (rat, IV)

Precaution

Patient with previous drug-induced bone marrow suppression. Renal or hepatic impairment. Pregnancy and lactation.

Regular blood count and ECG monitoring; elderly, children. Hepatic or renal impairment may increase risk of toxicity. Pre-existing cardiac disease and previous treatment with doxorubicin. Myocardial toxicity leading to potentially fatal congestive heart failure may occur during therapy or mth to yr after therapy cessation. Incidence of myocardial toxicity increases after total cumulative dose exceeds 400-550 mg/m2in adults, 300 mg/m2 in children >2 yr, or 10 mg/kg in children <2 yr. Risk of severe myelosuppression leading to infection or haemorrhage.

Interaction

May reduce efficacy of 5-fluorocytosine, digoxin, gentamicin. May increase risk of neurotoxicity with other cytotoxic agents (intrathecal).

Increased risk of cardiotoxicity when used with cyclophosphamide. Increased risk of hepatic toxicity when used with hepatotoxic drugs e.g. high-dose methotrexate.

Elimination Route

Less than 20% of the orally administered dose is absorbed from the gastrointestinal tract.

Half Life

10 minutes

18.5 hours

Elimination Route

The primary route of elimination of cytarabine is metabolism to the inactive compound ara-U, followed by urinary excretion of ara-U.

Twenty-five percent of an administered dose of daunorubicin hydrochloride is eliminated in an active form by urinary excretion and an estimated 40% by biliary excretion.

Pregnancy & Breastfeeding use

Pregnancy Category D. There is positive evidence of human foetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).

Contraindication

Patient with active meningeal infection.

Heart failure. Pregnancy, lactation.

Special Warning

Renal Impairment: Based on serum-creatinine concentrations: 105-265 micromoles/l: 75% of the usual dose; >265 micromoles/l: 50% of the usual dose.

Hepatic Impairment: Based on serum bilirubin concentrations of 12-30 mcg/ml: 75% of the usual dose; >30 mcg/ml: 50% of the usual dose.

Acute Overdose

Symptoms: Irreversible CNS toxicity and death. Severe arachnoiditis including encephalopathy.

Management: Therapy cessation followed by treatment of ensuing bone marrow depression including whole blood or platelet transfusion and antibiotics. Maintain vital functions.

Severe myelosupression, cardiotoxicity with or without transient reversible ECG changes leading to CHF. Treatment is supportive and symptomatic.