Daunorubicin is an anthracycline chemotherapy agent indicated in combination with other anticancer agents for remission induction in acute nonlymphocytic leukemias (e.g., myelogenous, monocytic, and erythroid) in adults and for remission induction in acute lymphocytic leukemia in pediatric and adult patients. Dose-limiting cardiotoxicity and myelosuppression have been reported with daunorubicin therapy.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Hazardous Drugs Classification
-NIOSH 2016 List: Group 1
-NIOSH (Draft) 2020 List: Table 1
-Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
-Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.
-For accidental daunorubicin contact with the skin or mucosa, wash the area thoroughly with soap and water.
Emetic Risk
-Moderate
-Administer routine antiemetic prophylaxis prior to treatment.
Extravasation Risk
-Vesicant
-Administer drug through a central venous line.
Route-Specific Administration
Injectable Administration
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
-Daunorubicin is available as a sterile, single-dose 5 mg/mL solution vial.
-Do NOT administer intramuscularly or subcutaneously.
-Monitor the IV infusion site for signs or symptoms of extravasation.
Dilution:
-Add the calculated dose (volume) of daunorubicin to a syringe containing 10 to 15 mL of 0.9% Sodium Chloride injection.
-Storage: Store at room temperature (20 to 25 degrees C; 68 to 77 degrees F) for up to 24 hours protected from light; discard unused vial portion.
Intravenous Injection:
-Inject daunorubicin into the tubing or sidearm of a rapidly flowing IV infusion of 0.9% Sodium Chloride injection or 5% Dextrose injection.
-Do not mix with other drugs including heparin.
Bone marrow suppression (e.g., anemia, leukopenia, neutropenia, and thrombocytopenia) occurs frequently with IV daunorubicin therapy; hematologic toxicity is dose dependent and occurs at therapeutic doses. Complications such as infection (or superinfection) and bleeding may occur due to pancytopenia. Monitor complete blood counts frequently during daunorubicin therapy.
Acute cardiotoxicity may occur during the administration of IV daunorubicin. Cumulative, dose-dependent cardiotoxicity including congestive heart failure (CHF) has also been reported with daunorubicin therapy, usually at cumulative doses of 550 mg/m2 or greater (or 400 mg/m2 or more in patients who received radiotherapy involving the heart) in adults. The incidence of myocardial toxicity increases after a total daunorubicin cumulative dose of 300 mg/m2 in children older than 2 years or 10 mg/kg in children younger than 2 years. Pericarditis or myocarditis has occurred rarely with IV daunorubicin and does not appear to be dose related. Acute ECG changes are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as ventricular tachycardia, supraventricular tachycardia (SVT), and premature ventricular contractions (PVCs) have been reported. Other conduction abnormalities (e.g., AV block or bundle-branch block) have been reported rarely and are associated with delayed daunorubicin-induced cardiotoxicity. Daunorubicin-induced cardiomyopathy, decreases in left ventricular function (LVEF), and CHF can develop within one year after discontinuing daunorubicin chemotherapy and are associated with the cumulative dose of daunorubicin. At cumulative doses of conventional daunorubicin in adults of 550 mg/m2 the incidence of CHF is 1% to 2%, at 800 mg/m2 the incidence is 5% and at 950 mg/m2 the incidence is 10%. Recently, it has been reported that cancer survivors may have an increased cardiac morbidity and mortality due to previous anthracycline therapy. Monitor electrocardiograms and/or systolic ejection fraction prior to each course of daunorubicin therapy. Perform a risk/benefit analysis prior to continuing therapy in patients who develop cardiotoxicity with daunorubicin therapy. Due to the risk of long-term cardiotoxicity, it has been recommended that children treated with anthracyclines should undergo screening with electrocardiograms and echocardiograms every 2 years and 24-hour continuous electrocardiograms and radionuclide angiograms every 5 years.
Acute nausea and vomiting have been reported with IV daunorubicin therapy; most cases were mild in severity. The use of antiemetic agents may help to alleviate these symptoms. Mucositis (mucosal inflammation and oral ulceration) may occur 3 to 7 days after starting therapy. Additionally, abdominal pain and diarrhea have occurred occasionally with IV daunorubicin use.
Reversible alopecia occurs in almost all patients receiving IV daunorubicin therapy. The hair loss can be sudden and total. This involves all body hair including scalp, axilla and pubic regions. Regrowth of hair usually resumes 3 weeks after therapy has been discontinued.
Red urine (urine discoloration) may occur transiently with IV daunorubicin therapy. Nail discoloration, specifically a single white transverse band on each nail (Mees lines), has been reported in a 27-year-old woman who received daunorubicin and cytarabine as induction therapy for acute myelogenous leukemia.
Dermatological reactions have been reported with IV daunorubicin use. It is a vesicant and should not be administered as a subcutaneous or intramuscular injection. Rash (unspecified), contact dermatitis, and urticaria have been reported rarely with IV daunorubicin therapy. Injection site reaction such as extravasation may lead severe tissue necrosis, cellulitis, (thrombo) phlebitis, and painful skin induration. Patients should be closely observed for any injection site reaction during therapy with daunorubicin, especially, severe pain, swelling, and poor blood return. Symptoms of extravasation are usually immediate although extravasations into chest wall tissue are less acutely symptomatic. Application of ice packs has been shown to be effective in reducing skin lesions associated with doxorubicin extravasation and is the treatment of choice for daunorubicin extravasation. Surgical follow-up is indicated if pain and swelling at the site continues 2 weeks after the extravasation.
Hyperuricemia caused by tumor lysis syndrome (TLS) may occur with IV daunorubicin therapy, especially in patients with leukemia. Monitor uric acid levels. Prophylactic measures (e.g., hydration, allopurinol) may be warranted.
Anaphylactoid reactions, fever, and chills occur rarely with IV daunorubicin use.
New primary malignancy, including new primary leukemias, have been reported in patient who received topoisomerase II inhibitors, such as daunorubicin, in combination with other chemotherapy or radiation.
Daunorubicin is contraindicated in patients with known daunorubicin hypersensitivity; it is prudent to use with caution in patients with documented allergic reaction to other anthracycline medications (i.e., anthracycline hypersensitivity).
Severe bone marrow suppression is a relative contraindication to daunorubicin depending upon the etiology of the suppression. Patients with acute leukemia may require treatment with daunorubicin despite severe bone marrow suppression. Daunorubicin should be used cautiously in patients with bone marrow suppression, coagulopathy, or in those who have received previous myelosuppressive therapy such as chemotherapy or radiotherapy. Therefore, treatment with this drug requires an experienced clinician knowledgeable in the use of cancer chemotherapy, and administration of daunorubicin requires a specialized care setting, such as a hospital or treatment facility. Patients with preexisting marrow suppression, including neutropenia and/or thrombocytopenia, should be allowed to recover their counts prior to daunorubicin administration. Patients should be treated for any active infection prior to receiving daunorubicin. Patients with a history of varicella zoster, other herpes infection (e.g., herpes simplex), or other viral infection are at risk for reactivation of the infection when treated with chemotherapy.
Patients who have had previous radiation therapy may experience radiation recall reactions during daunorubicin therapy. Daunorubicin is a radiation sensitizer and should be used with caution in patients receiving concurrent radiation therapy.
Myelosuppressive effects of daunorubicin can increase the risk of infection or bleeding; therefore, dental work should be delayed until blood counts have returned to normal. Patients, especially those with dental disease, should be instructed in proper oral hygiene, including caution in use of regular toothbrushes, dental floss, and toothpicks.
Daunorubicin is considered a vesicant; avoid extravasation of daunorubicin infusions. Closely monitor patients for signs and symptoms of extravasation including pain, swelling, and decreased blood return. If extravasation occurs, stop the infusion and remove the tubing. Attempt to aspirate the drug prior to removing the needle. Elevate the affected area and treat with ice packs. As this can be a progressive injury, appropriate long-term follow-up is required. Avoid intramuscular administration and subcutaneous administration of daunorubicin due to severe skin and tissue necrosis which may occur.
Intramuscular injections should not be administered to patients with platelet counts < 50,000/mm3 who are receiving daunorubicin. IM injections may cause bleeding, bruising, or hematomas due to daunorubicin-induced thrombocytopenia.
Patients with hepatic disease and/or jaundice should receive daunorubicin cautiously. The dose should be adjusted for elevations in the total bilirubin because daunorubicin is significantly cleared through the biliary tree.
Daunorubicin is eliminated renally. Dosage adjustments are recommended in patients with renal impairment or renal failure to avoid toxicity.
Hyperkalemia, hyperphosphatemia, hyperuricemia, hypocalcemia, and decreased urine output may be indicative of daunorubicin-induced tumor lysis syndrome (TLS). Appropriate measures (e.g. aggressive hydration and allopurinol) must be taken to prevent severe electrolyte imbalances and renal toxicity during and following chemotherapy administration in patients with large chemosensitive tumors.
Severe cardiotoxicity including fatal congestive heart failure may occur during daunorubicin therapy or months to years after discontinuing therapy. Cardiotoxicity is dose related and the incidence increases after total cumulative doses exceeding 400 to 550 mg/m2 in adults, 300 mg/m2 in patients greater than 2 years of age, or 10 mg/kg in patients less than 2 years of age. The maximum cumulative lifetime dose of daunorubicin is 550 mg/m2 IV, or 400 mg/m2 IV in patients who have previously received mediastinal radiation. A history of cardiac disease and previous therapy with doxorubicin may increase the risk of daunorubicin-induced cardiotoxicity; perform a risk/benefit analysis prior to starting therapy in these patients. Monitor electrocardiogram and/or systolic ejection fraction prior to each course of daunorubicin therapy.
Females may have an increased risk of anthracycline-induced cardiotoxicity. Female patients had a significantly greater reduction in cardiac contractility compared with male patients based on echocardiogram evaluations in a study in 120 children and adults who had been treated with bolus doses of doxorubicin (cumulative doses of 244-550 mg/m2) in childhood.
The risk of anthracycline-induced cardiotoxicity appears to be increased in infants, children, and adolescents and may occur at lower cumulative doses. Cardiotoxicity is dose dependent and may be worse in patients who received thoracic irradiation. Impaired left ventricular systolic performance, reduced contractility, congestive heart failure, and death have been reported in pediatric patients who received anthracycline therapy, including daunorubicin. Children treated with anthracyclines may develop late cardiotoxicity. Due to the risk of long-term cardiotoxicity, it has been recommended that patients treated with anthracyclines should undergo screening with electrocardiograms and echocardiograms every 2 years and 24-hour continuous electrocardiograms and radionuclide angiograms every 5 years.
Infertility may occur in male patients who receive daunorubicin, based on information from animal studies.
Daunorubicin is classified as FDA pregnancy risk category D. It may cause fetal harm if administered during pregnancy, based on animal studies. Females of reproductive potential should avoid pregnancy during daunorubicin therapy. If a woman takes daunorubicin during pregnancy or becomes pregnant during therapy, she should be advised of the potential risks to the fetus. Fetal toxicity has been reported in animal studies at daunorubicin doses that were below the recommended human dose (based on mg/kg in rabbits or body surface area in rats).
It is unknown whether daunorubicin is excreted in breast-milk. Due to the potential for severe toxicity in the nursing infant, it is recommended women discontinue breast-feeding during daunorubicin therapy.
For the treatment of acute nonlymphocytic leukemia including acute myelogenous leukemia (AML):
-as remission induction therapy of acute nonlymphocytic leukemia, in combination with other anticancer agents:
Intravenous dosage:
Adults less than 60 years: initial induction therapy, 45 mg/m2 IV daily on days 1, 2, and 3 in combination with cytarabine 100 mg/m2 IV daily for 7 days. Following a bone marrow evaluation, up to 3 courses of induction therapy may be required. For subsequent induction therapy, give daunorubicin 45 mg/m2 IV daily on days 1 and 2 in combination with cytarabine 100 mg/m2 IV daily for 5 days. Higher daunorubicin doses of 60 mg/m2 IV and 90 mg/m2 IV for 3 days (off-label use) in combination with cytarabine have also been evaluated as initial induction therapy in patients with AML in randomized trials.
Adults 60 years or older: initial induction therapy, 30 mg/m2 IV daily on days 1, 2, and 3 in combination with cytarabine 100 mg/m2 IV daily for 7 days. Following a bone marrow evaluation, up to 3 courses of induction therapy may be required. For subsequent induction therapy, give daunorubicin 30 mg/m2 IV daily on days 1 and 2 in combination with cytarabine 100 mg/m2 IV daily for 5 days. Higher daunorubicin doses (initial induction, 45 mg/m2 IV daily on days 1, 2, and 3; subsequent induction, 45 mg/m2 IV daily on days 1 and 2) may be appropriate if optimal supportive care is available. High-dose daunorubicin 90 mg/m2 IV for 3 days (off-label use) in combination with cytarabine has also been evaluated as initial induction therapy in elderly patients aged 60 to 83 years with AML in a randomized, phase 3 trial.
For the treatment of acute lymphocytic leukemia (ALL):
-as remission induction therapy of ALL, in combination with other anticancer agents:
Intravenous dosage:
Adults: 45 mg/m2 IV daily on days 1, 2, and 3 in combination with vincristine 2 mg IV on days 1, 8, and 15; prednisone 40 mg/m2 orally daily on days 1 to 22 (then tapered between days 22 to 29); and L-asparaginase 500 international units/kg IV daily for 10 days on days 22 to 32.
Children 2 years and older and Adolescents: 25 mg/m2 (or 1 mg/kg in patients with a body surface area less than 0.5 m2) IV on day 1 every week in combination with vincristine 1.5 mg/m2 IV on day 1 every week and prednisone 40 mg/m2 orally daily. If a complete remission has not been achieved within 4 courses of therapy and the patient is in a partial remission, an additional 1 or 2 courses may be given.
Infants and Children less than 2 years: 1 mg/kg IV on day 1 every week in combination with vincristine 1.5 mg/m2 IV on day 1 every week and prednisone 40 mg/m2 orally daily. If a complete remission has not been achieved within 4 courses of therapy and the patient is in a partial remission, an additional 1 or 2 courses may be given.
Maximum Dosage Limits:
-Adults
45 mg/m2 IV, although doses up to 90 mg/m2 IV have been used off-label; maximum cumulative anthracycline dose is 550 mg/m2 (or 400 mg/m2 in patients who have received radiation therapy involving the heart area).
-Geriatric
45 mg/m2 IV, although doses up to 90 mg/m2 IV have been used off-label; maximum cumulative lifetime anthracycline dose is 550 mg/m2 (or 400 mg/m2 in patients who have received radiation therapy involving the heart area).
-Adolescents
25 mg/m2 IV weekly; maximum cumulative dose is 300 mg/m2 IV.
-Children
2 years or older: 25 mg/m2 (or 1 mg/kg in children with a body surface area less than 0.5 m2); maximum cumulative dose is 300 mg/m2 IV.
Less than 2 years: 1 mg/kg IV weekly label; maximum cumulative dose is 10 mg/kg.
-Infants
1 mg/kg IV weekly label; maximum cumulative dose is 10 mg/kg.
Patients with Hepatic Impairment Dosing
Serum bilirubin level of 1.2 to 3 mg/dL: decrease the daunorubicin dose by 25%.
Serum bilirubin level greater than 3 mg/dL: decrease the daunorubicin dose by 50%.
Patients with Renal Impairment Dosing
Serum creatinine level greater than 3 mg/dL: decrease the daunorubicin dose by 50%.
*non-FDA-approved indication
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Cyclophosphamide: (Moderate) Monitor for signs and symptoms of cardiac dysfunction if coadministration of cyclophosphamide with anthracyclines is necessary as there is an additive or potentially synergistic increase in the risk of cardiomyopathy.
Cyclosporine: (Major) Concurrent use of daunorubicin with other agents which cause bone marrow or immune suppression such as other immunosuppressants may result in additive effects. In addition, high doses of cyclosporine (starting at 16 mg/kg/day IV) may increase exposure to anthracyclines (e.g., daunorubicin) in cancer patients. Cyclosporine is a substrate and inhibitor of P-glycoprotein, an energy-dependent drug efflux pump encoded for by the multidrug resistance gene-1 (MDR1). Overexpression of this protein has been described as a mechanism of resistance to naturally-occurring (non-synthetic) chemotherapy agents. Cyclosporine can block MDR1-mediated resistance when given at much higher doses than those used in transplantation and may also enhance the efficacy of daunorubicin by inhibiting this protein. Valspodar is a cyclosporine analog with less renal and immunosuppressive effects than cyclosporine while retaining effects on MDR. The addition of cyclosporine or valspodar to daunorubicin therapy may result in increases in AUC for both daunorubicin and daunorubincinol possibly due to a decrease in clearance of parent drug, a decrease in metabolism of daunorubincinol, or an increase in intracellular daunorubicin concentrations.
Dengue Tetravalent Vaccine, Live: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the dengue virus vaccine. When feasible, administer indicated vaccines at least 2 weeks prior to initiating immunosuppressant medications. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Elbasvir; Grazoprevir: (Moderate) Administering daunorubicin with elbasvir; grazoprevir may result in elevated daunorubicin plasma concentrations. Daunorubicin is a substrate for the breast cancer resistance protein (BCRP); both elbasvir and grazoprevir are BCRP inhibitors.
Gadobenate Dimeglumine: (Moderate) Gadobenate dimeglumine is a substrate for the canalicular multi-specific organic anion transporter (MOAT). Use with other MOAT substrates, such as anthracyclines, may result in prolonged systemic exposure of the coadministered drug. Caution is advised if these drugs are used together.
Margetuximab: (Major) Avoid administration of anthracyclines during margetuximab therapy and for up to 4 months after the last dose of margetuximab due to the risk of increased cardiac dysfunction. If concomitant use is unavoidable, closely monitor cardiac function. This interaction has not been studied with margetuximab; however, clinical data from other HER2-directed antibodies warrants consideration.
Mycophenolate: (Major) Concurrent use of daunorubicin with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Pertuzumab; Trastuzumab; Hyaluronidase: (Major) Avoid coadministration of anthracyclines and trastuzumab products due to the risk of increased cardiac dysfunction; if possible, continue to avoid for up to 7 months after the last dose of trastuzumab. If concomitant use is unavoidable, carefully monitor cardiac function. Anthracycline treatment after therapy with trastuzumab product may increase the risk of cardiac dysfunction due to the long washout period of trastuzumab.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Adenovirus Vector Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) mRNA Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Recombinant Spike Protein Nanoparticle Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Trastuzumab: (Major) Avoid coadministration of anthracyclines and trastuzumab products due to the risk of increased cardiac dysfunction; if possible, continue to avoid for up to 7 months after the last dose of trastuzumab. If concomitant use is unavoidable, carefully monitor cardiac function. Anthracycline treatment after therapy with trastuzumab product may increase the risk of cardiac dysfunction due to the long washout period of trastuzumab.
Trastuzumab; Hyaluronidase: (Major) Avoid coadministration of anthracyclines and trastuzumab products due to the risk of increased cardiac dysfunction; if possible, continue to avoid for up to 7 months after the last dose of trastuzumab. If concomitant use is unavoidable, carefully monitor cardiac function. Anthracycline treatment after therapy with trastuzumab product may increase the risk of cardiac dysfunction due to the long washout period of trastuzumab.
Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.
Daunorubicin cytotoxicity occurs via mechanisms similar to other anthracyclines. Daunorubicin complexes with DNA by intercalating between DNA base pairs, causing the helix to change shape. This simple act of changing the conformation of DNA can interfere with strand elongation by inhibiting DNA polymerase and can inhibit protein synthesis due to affects on RNA polymerase. Daunorubicin also affects topoisomerase II, an enzyme responsible for DNA strand breaks during transcription. Daunorubicin stabilizes the initial DNA-enzyme complex leading to double-strand DNA breaks. Daunorubicin also undergoes reduction to form oxygen free radical intermediates. In the presence of oxygen and metal catalysts such as Fe2+, daunorubicin undergoes reduction to the semiquone radical. In the presence of oxygen, the semiqunone radical can form a superperoxide that in the presence of hydrogen peroxide forms hydroxyl radicals. Daunorubicin-derived radicals can induce membrane lipid peroxidation, DNA strand scission, and direct oxidation of purine or pyrimidine bases, thiols and amines. Daunorubicin cytotoxicity is cell cycle nonspecific, but the majority occurs in the S-phase.
Resistance to daunorubicin may occur through several mechanisms. One of the most important mechanisms of resistance is multidrug resistance (MDR) which is mediated through an overexpression of a P170-glycoprotein. This membrane protein functions as an energy-dependent drug efflux pump in resistance cells. Several compounds including cyclosporine, cyclosporine analogs and verapamil may block this protein and can reverse resistance. Other mechanisms of resistance include changes in topoisomerase II and glutathione activity.
Daunorubicin-induced free radical formation also contributes to its cardiotoxicity. Once daunorubicin enters cardiac cells, it is reduced to an anthracycline free radical that is rapidly oxidized with oxygen to form the original drug and superoxide anions. Normally, these superoxide radicals are converted back to oxygen via glutathione peroxidase (GP); however, the heart is essentially devoid of this enzyme. Consequently, H2O2 is forced to react with ferrous ions (Fe2+) to form the highly toxic superhydroxide free radical that causes severe lipid peroxidation leading to extensive mitochondrial destruction. Both cardiac and malignant cells are rich in mitochondria. Additionally, these free radicals crosslink sulfhydryl groups of calcium-release channels and inhibit Ca-ATPase which leads to extensive depletion of sarcoplasmic reticulum (SR) calcium stores and prevention of restoration of calcium stores in the SR, respectively.
Daunorubicin also has antibacterial and immunosuppressive effects.
Daunorubicin is administered intravenously. It is rapidly distributed throughout the body tissues, concentrating in the liver, lymph nodes, muscle, kidney, and heart; it also binds to cellular components (e.g., nucleic acids). Daunorubicin does not appear to cross the blood-brain barrier; however, it crosses the placental barrier. Following daunorubicin administration, the initial half-life is 45 minutes and the terminal half-life is 18.5 hours. Daunorubicin is extensively metabolized in the liver via demethylation and conjugation and in other tissues via cytoplasmic aldo-keto reductases. The active metabolite, daunorubicinol, has a half-life of 26.7 hours. Daunorubicinol accounts for 40% and 60% of the total drug in plasma at 30 minutes and 4 hours, respectively. Daunorubicin elimination occurs via biliary (40%) and urinary (25%) excretion.
Affected cytochrome P450 isoenzymes and drug transporters: P-gp
Daunorubicin is a substrate for the multi-drug resistance protein, P-glycoprotein (P-gp).