Daunorubicin (HCl)

Daunorubicin (HCl) is antineoplastic agent. Daunorubicin (HCl) is anthracycline antibiotic, isolated from Streptomyces peuceticus var caesius. Daunorubicin (HCl) is the first agent in this class to be isolated. Daunorubicin (HCl) is structurally almost identical to doxorubicin, lacking only a hydroxyl moiety. Daunorubicin (HCl) is among the most useful cytotoxic anticancerous drugs. Daunorubicin (HCl) is effective in the treatment of different cancers such as acute myelocytic leukemia in adults and is used in combination with different anticancerous drugs to obtain the best therapeutic results and to minimize side effects or toxicities.

Daunorubicin (HCl) is primarily indicated in conditions like Acute granulocytic leukemia, Acute leukemia, Acute lymphocytic leukemia, Acute Nonlymphocytic leukemia, Kaposi's sarcoma.

Daunorubicin (HCl) is contraindicated in conditions like Heart failure, Chickenpox infection, Hypersensitivity, Active infection.

The severe or irreversible adverse effects of Daunorubicin (HCl), which give rise to further complications include Thrombophlebitis, Tissue necrosis, Radiation recall, Arrhythmias. Daunorubicin (HCl) produces potentially life-threatening effects which include Congestive heart failure, Bone marrow suppression, Cardiac arrhythmia, Neutropenia, Cardiomyopathy, ECG abnormalities, which are responsible for the discontinuation of Daunorubicin (HCl) therapy. The symptomatic adverse reactions produced by Daunorubicin (HCl) are more or less tolerable and if they become severe, they can be treated symptomatically, these include Nausea, Vomiting, Alopecia, Mucositis, Red urine, Alopecia, GI ulceration, Diarrhea, Urticaria, Pruritus, Fever, Flushing, Stomatitis.

Myelosuppression, manifested principally by severe leukopenia and thrombocytopenia, occurs in all patients receiving therapeutic dosages of conventional daunorubicin hydrochloride; infection or hemorrhage may occur. Leukocyte and platelet nadirs usually occur within 10–14 days after administration, with return to normal levels during the third week. In patients with AIDS-related Kaposi’s sarcoma receiving liposomal daunorubicin citrate, myelosuppression, mainly granulocytopenia (possibly severe and/or associated with fever; infection may result), is principal dose-limiting toxicity; lesser effect observed on platelets and erythroid cells. Carefully monitor hematologic status during therapy; determine leukocyte, platelet, and erythrocyte counts prior to and at frequent intervals during therapy. Evaluate bone marrow function to guide treatment and allow sufficient time for bone marrow recovery between courses of conventional daunorubicin. If absolute granulocyte count <750/mm 3 before scheduled dose of liposomal daunorubicin, withhold therapy until counts exceed this level. Persistent, severe myelosuppression may result in superinfection or hemorrhage. Severe hematologic toxicity may require supportive therapy, antibiotics for infections, and blood product transfusions. Carefully observe patients with HIV infection and immunosuppression for intercurrent or opportunistic infections. Do not initiate conventional daunorubicin in patients with preexisting drug-induced myelosuppression unless treatment benefit warrants risk. Risk of cardiotoxicity during or months to years after therapy; requires special attention and long-term periodic evaluation of cardiac function. Preexisting cardiac disease and/or previous anthracycline (e.g., doxorubicin, epirubicin) therapy increase risk of daunorubicin-induced cardiotoxicity; carefully consider risks before initiation of therapy. Infants and children appear to be at greater risk of anthracycline-induced cardiotoxicity. Impaired left ventricular systolic performance, reduced contractility, CHF, or death reported in pediatric patients receiving anthracycline therapy; appear to be dose-dependent and aggravated by thoracic irradiation. Potentially fatal CHF may occur during therapy or months to years after termination of therapy. With conventional daunorubicin, incidence of myocardial toxicity (e.g., CHF) is increased at cumulative dosages >550 mg/m 2 (>400 mg/m 2 in patients who have received radiation that encompassed the heart), >300 mg/m 2 in children >2 years of age, or >10 mg/kg in children <2 years of age. With liposomal daunorubicin, CHF reported at cumulative dose of 340 mg/m 2 in at least 1 patient with AIDS-related Kaposi’s sarcoma; in a limited number of patients, decreases in left ventricular ejection fraction occurred at median cumulative dose of 320 mg/m 2 (range: 200–2100 mg/m 2 ). Other serious adverse cardiac effects reported with liposomal daunorubicin include pericardial effusion, pericardial tamponade, ventricular extrasystoles, cardiac arrest, sinus tachycardia, atrial fibrillation, pulmonary hypertension, MI, supraventricular tachycardia, and angina pectoris. Further study and experience needed to determine relative risk of anthracycline-induced cardiotoxicity associated with liposomal versus conventional daunorubicin. Previous therapy with anthracyclines (doxorubicin >300 mg/m 2 or equivalent) may increase risk of cardiotoxicity with liposomal daunorubicin. Early clinical diagnosis of drug-induced CHF and prompt initiation of treatment are essential for optimizing response to supportive therapy. In determining total daunorubicin dose in adults and children, consider any previous or concomitant therapy with other anthracyclines (e.g., doxorubicin) or with other potentially cardiotoxic drugs. Do not use daunorubicin in patients who have previously received maximum recommended cumulative dose of doxorubicin or daunorubicin. (See Doxorubicin under Interactions.) No completely reliable method exists to predict which patients will develop drug-induced CHF. ECG and/or determination of ejection fraction recommended before each course of conventional daunorubicin; if decrease ≥30% in limb lead QRS voltage in ECG (associated with substantial risk of drug-induced cardiomyopathy) or decrease in systolic ejection fraction from pretreatment baseline occurs, weigh benefits against cardiac risks. The manufacturer of liposomal daunorubicin recommends evaluation of cardiac function (e.g., history of previous cardiac disease, physical examination) before each course of therapy and determination of left ventricular ejection fraction at total cumulative doses of 320 mg/m 2 and every 160 mg/m 2 thereafter (before therapy and every 160 mg/m 2 in patients with preexisting cardiac disease and/or those who have received previous anthracycline therapy [doxorubicin >300 mg/m 2 or equivalent] or radiation that encompassed the heart). Pericarditis-myocarditis, unrelated to dose, reported rarely. May cause fetal harm. Avoid pregnancy during therapy. Because of potential benefits, use during pregnancy may be acceptable in certain conditions (e.g., life-threatening situations, severe disease for which safer drugs cannot be used or are ineffective) despite possible risks to the fetus. If used during pregnancy or patient becomes pregnant, apprise of potential fetal hazard. Conventional daunorubicin hydrochloride: Extravasation during infusion may cause severe local tissue necrosis, severe cellulitis, thrombophlebitis, or painful induration; usually accompanied by immediate burning sensation at injection site. Liposomal daunorubicin citrate: Injection site inflammation reported rarely; tissue necrosis associated with extravasation not reported to date. If extravasation occurs, aspirate as much infiltrated drug as possible; may minimize local reaction by promptly infiltrating area with hydrocortisone sodium succinate injection (50–100 mg hydrocortisone) and/or sodium bicarbonate (5 mL of 8.4% injection) and applying cold compresses. Liposomal daunorubicin citrate: Triad of back pain, flushing, and chest tightness reported in about 14% of patients in clinical trials; generally occurs during first 5 minutes of infusion, subsides with infusion interruption, and generally does not recur if infusion resumed at slower rate. Symptoms appear to be related to lipid component since also reported with other liposomal preparations. Secondary leukemias reported in patients exposed to topoisomerase II inhibitors when used concomitantly with other antineoplastic agents or radiation therapy. Conventional daunorubicin hydrochloride: Rash, contact dermatitis, urticaria reported rarely. Conventional daunorubicin hydrochloride: Anaphylactoid reactions reported rarely. Liposomal daunorubicin citrate: Allergic reactions and pruritus reported. Administer only under the supervision of a qualified clinician experienced in the use of cancer chemotherapy agents. Closely observe patient and frequently determine CBC; evaluate cardiac, renal, and hepatic function prior to each course of treatment. Take appropriate measures to control systemic infections before beginning therapy; however, in some patients with acute leukemia, treatment of underlying malignancy in addition to other therapy (e.g., antibiotics) may be necessary before systemic infections can be controlled. Conventional daunorubicin hydrochloride: Possible hyperuricemia secondary to extensive purine catabolism accompanying rapid cellular destruction; monitor serum uric acid concentrations. Minimize or prevent by administering allopurinol prior to initiation of antileukemic therapy. Category D. (See Fetal/Neonatal Morbidity and Mortality under Cautions.) Not known whether daunorubicin is distributed into human milk. Discontinue nursing because of potential risk to nursing infants. Conventional daunorubicin hydrochloride: Although appropriate studies not performed, cardiotoxicity may be more frequent and occur at lower cumulative doses compared with adults. Liposomal daunorubicin citrate: Safety and efficacy not established. Conventional daunorubicin hydrochloride: Although appropriate studies not performed, cardiotoxicity may be more frequent and occur at lower cumulative doses compared with younger adults. Use with caution in patients with age-related bone marrow reserve inadequacies; consider dosage adjustment in patients with age-related renal impairment. Liposomal daunorubicin citrate: Safety and efficacy not established. Possible enhanced toxicity; dosage adjustment recommended. (See Hepatic Impairment under Dosage and Administration.) Limited clinical experience with liposomal daunorubicin citrate in patients with hepatic impairment; reduce dosage based on experience with conventional daunorubicin. Possible enhanced toxicity; dosage adjustment recommended. (See Renal Impairment under Dosage and Administration.) Limited clinical experience with liposomal daunorubicin citrate in patients with renal impairment; reduce dosage based on experience with conventional daunorubicin.

Myelosuppression, manifested principally by severe leukopenia and thrombocytopenia, occurs in all patients receiving therapeutic dosages of conventional daunorubicin hydrochloride; infection or hemorrhage may occur. Leukocyte and platelet nadirs usually occur within 10–14 days after administration, with return to normal levels during the third week. In patients with AIDS-related Kaposi’s sarcoma receiving liposomal daunorubicin citrate, myelosuppression, mainly granulocytopenia (possibly severe and/or associated with fever; infection may result), is principal dose-limiting toxicity; lesser effect observed on platelets and erythroid cells. Carefully monitor hematologic status during therapy; determine leukocyte, platelet, and erythrocyte counts prior to and at frequent intervals during therapy. Evaluate bone marrow function to guide treatment and allow sufficient time for bone marrow recovery between courses of conventional daunorubicin. If absolute granulocyte count <750/mm 3 before scheduled dose of liposomal daunorubicin, withhold therapy until counts exceed this level. Persistent, severe myelosuppression may result in superinfection or hemorrhage. Severe hematologic toxicity may require supportive therapy, antibiotics for infections, and blood product transfusions. Carefully observe patients with HIV infection and immunosuppression for intercurrent or opportunistic infections. Do not initiate conventional daunorubicin in patients with preexisting drug-induced myelosuppression unless treatment benefit warrants risk. Risk of cardiotoxicity during or months to years after therapy; requires special attention and long-term periodic evaluation of cardiac function. Preexisting cardiac disease and/or previous anthracycline (e.g., doxorubicin, epirubicin) therapy increase risk of daunorubicin-induced cardiotoxicity; carefully consider risks before initiation of therapy. Infants and children appear to be at greater risk of anthracycline-induced cardiotoxicity. Impaired left ventricular systolic performance, reduced contractility, CHF, or death reported in pediatric patients receiving anthracycline therapy; appear to be dose-dependent and aggravated by thoracic irradiation. Potentially fatal CHF may occur during therapy or months to years after termination of therapy. With conventional daunorubicin, incidence of myocardial toxicity (e.g., CHF) is increased at cumulative dosages >550 mg/m 2 (>400 mg/m 2 in patients who have received radiation that encompassed the heart), >300 mg/m 2 in children >2 years of age, or >10 mg/kg in children <2 years of age. With liposomal daunorubicin, CHF reported at cumulative dose of 340 mg/m 2 in at least 1 patient with AIDS-related Kaposi’s sarcoma; in a limited number of patients, decreases in left ventricular ejection fraction occurred at median cumulative dose of 320 mg/m 2 (range: 200–2100 mg/m 2 ). Other serious adverse cardiac effects reported with liposomal daunorubicin include pericardial effusion, pericardial tamponade, ventricular extrasystoles, cardiac arrest, sinus tachycardia, atrial fibrillation, pulmonary hypertension, MI, supraventricular tachycardia, and angina pectoris. Further study and experience needed to determine relative risk of anthracycline-induced cardiotoxicity associated with liposomal versus conventional daunorubicin. Previous therapy with anthracyclines (doxorubicin >300 mg/m 2 or equivalent) may increase risk of cardiotoxicity with liposomal daunorubicin. Early clinical diagnosis of drug-induced CHF and prompt initiation of treatment are essential for optimizing response to supportive therapy. In determining total daunorubicin dose in adults and children, consider any previous or concomitant therapy with other anthracyclines (e.g., doxorubicin) or with other potentially cardiotoxic drugs. Do not use daunorubicin in patients who have previously received maximum recommended cumulative dose of doxorubicin or daunorubicin. (See Doxorubicin under Interactions.) No completely reliable method exists to predict which patients will develop drug-induced CHF. ECG and/or determination of ejection fraction recommended before each course of conventional daunorubicin; if decrease ≥30% in limb lead QRS voltage in ECG (associated with substantial risk of drug-induced cardiomyopathy) or decrease in systolic ejection fraction from pretreatment baseline occurs, weigh benefits against cardiac risks. The manufacturer of liposomal daunorubicin recommends evaluation of cardiac function (e.g., history of previous cardiac disease, physical examination) before each course of therapy and determination of left ventricular ejection fraction at total cumulative doses of 320 mg/m 2 and every 160 mg/m 2 thereafter (before therapy and every 160 mg/m 2 in patients with preexisting cardiac disease and/or those who have received previous anthracycline therapy [doxorubicin >300 mg/m 2 or equivalent] or radiation that encompassed the heart). Pericarditis-myocarditis, unrelated to dose, reported rarely. May cause fetal harm. Avoid pregnancy during therapy. Because of potential benefits, use during pregnancy may be acceptable in certain conditions (e.g., life-threatening situations, severe disease for which safer drugs cannot be used or are ineffective) despite possible risks to the fetus. If used during pregnancy or patient becomes pregnant, apprise of potential fetal hazard. Conventional daunorubicin hydrochloride: Extravasation during infusion may cause severe local tissue necrosis, severe cellulitis, thrombophlebitis, or painful induration; usually accompanied by immediate burning sensation at injection site. Liposomal daunorubicin citrate: Injection site inflammation reported rarely; tissue necrosis associated with extravasation not reported to date. If extravasation occurs, aspirate as much infiltrated drug as possible; may minimize local reaction by promptly infiltrating area with hydrocortisone sodium succinate injection (50–100 mg hydrocortisone) and/or sodium bicarbonate (5 mL of 8.4% injection) and applying cold compresses. Liposomal daunorubicin citrate: Triad of back pain, flushing, and chest tightness reported in about 14% of patients in clinical trials; generally occurs during first 5 minutes of infusion, subsides with infusion interruption, and generally does not recur if infusion resumed at slower rate. Symptoms appear to be related to lipid component since also reported with other liposomal preparations. Secondary leukemias reported in patients exposed to topoisomerase II inhibitors when used concomitantly with other antineoplastic agents or radiation therapy. Conventional daunorubicin hydrochloride: Rash, contact dermatitis, urticaria reported rarely. Conventional daunorubicin hydrochloride: Anaphylactoid reactions reported rarely. Liposomal daunorubicin citrate: Allergic reactions and pruritus reported. Administer only under the supervision of a qualified clinician experienced in the use of cancer chemotherapy agents. Closely observe patient and frequently determine CBC; evaluate cardiac, renal, and hepatic function prior to each course of treatment. Take appropriate measures to control systemic infections before beginning therapy; however, in some patients with acute leukemia, treatment of underlying malignancy in addition to other therapy (e.g., antibiotics) may be necessary before systemic infections can be controlled. Conventional daunorubicin hydrochloride: Possible hyperuricemia secondary to extensive purine catabolism accompanying rapid cellular destruction; monitor serum uric acid concentrations. Minimize or prevent by administering allopurinol prior to initiation of antileukemic therapy. Category D. (See Fetal/Neonatal Morbidity and Mortality under Cautions.) Not known whether daunorubicin is distributed into human milk. Discontinue nursing because of potential risk to nursing infants. Conventional daunorubicin hydrochloride: Although appropriate studies not performed, cardiotoxicity may be more frequent and occur at lower cumulative doses compared with adults. Liposomal daunorubicin citrate: Safety and efficacy not established. Conventional daunorubicin hydrochloride: Although appropriate studies not performed, cardiotoxicity may be more frequent and occur at lower cumulative doses compared with younger adults. Use with caution in patients with age-related bone marrow reserve inadequacies; consider dosage adjustment in patients with age-related renal impairment. Liposomal daunorubicin citrate: Safety and efficacy not established. Possible enhanced toxicity; dosage adjustment recommended. (See Hepatic Impairment under Dosage and Administration.) Limited clinical experience with liposomal daunorubicin citrate in patients with hepatic impairment; reduce dosage based on experience with conventional daunorubicin. Possible enhanced toxicity; dosage adjustment recommended. (See Renal Impairment under Dosage and Administration.) Limited clinical experience with liposomal daunorubicin citrate in patients with renal impairment; reduce dosage based on experience with conventional daunorubicin.

30 to 45 mg/sq.meter (38 (37.5)) 24 hourly IV — For 3 Days

25 mg/sq.meter (46 (46)) As recommended. Intra Venous — Once a week.For acute lyphoblastic leukaemia in combination regiments.

1 mg/sq.meter (2 (2)) As recommended. Intra Venous — As Required

Daunorubicin (HCl) is known to interact with other drugs, the details of drug interactions is as follows:DrugDetailsSeverityOnsetManagementCytarabine (HCl)Mercaptopurine (Monohydrate) These interactions are sometimes beneficial and sometimes may pose threats to life. Always consult your physician for the change of dose regimen or an alternative drug of choice that may strictly be required.

Inj (reconstituted soln) Store at room temperature or refrigerator. Protect from Sunlight. Use within 2 days if refrigerated and within 24 hrs if kept at room temperature.