- The medication should be administered under the guidance of a medical professional skilled in leukaemia chemotherapy. The ability to react quickly to severe hemorrhagic conditions or severe infections is a requirement for physicians.
- Give daunorubicin via an IV infusion that circulates quickly. If there is extravasation, there will be severe local tissue necrosis. Never administer SC or IM.
- When administered at therapeutic doses, severe myelosuppression that could cause infection or bleeding might happen.
- Congestive heart failure and other severe and possibly fatal myocardial toxicity can arise from cumulative dosages exceeding 400 to 550 mg/m² in adults, 300 mg/m² in children under the age of two, or 10 mg/kg in children under the age of two. These effects can happen during therapy or months or years after treatment.
Allopathy
Prescription Required
DCGI (Drugs Controller General of India)
Schedule H
Daunorubicin is an antineoplastic agent belonging to the pharmacological class of anthracycline antibiotics.
Daunorubicin is approved by the FDA to be used alone or with other drugs to treat AIDS-related Kaposi's sarcoma and in various blood cancers, including Acute Nonlymphocytic/Lymphocytic Leukemia.
When administered intravenously, Daunorubicin is absorbed through the vein, dispersed throughout the tissues, metabolized mainly in the liver, and excreted mostly through the kidneys and liver.
The most common side effects of Daunorubicin include nausea, vomiting, low platelet count, ulcer, loss of appetite and difficulty breathing.
Daunorubicin is available as an injectable solution and powder for injections.
The molecule is available in India, the United States, Canada, countries within the European Union, Australia, Japan and South Korea.
Daunorubicin is an antineoplastic agent belonging to the pharmacological class of anthracycline antibiotics.
Daunorubicin exhibits cytotoxic and antimitotic properties via a variety of possible modes of action. Daunorubicin intercalates between base pairs to form complexes with DNA. Maintaining the stability of the DNA-topoisomerase II complex stops topoisomerase II from catalyzing the religation step of the ligation-religation reaction, thereby inhibiting topoisomerase II activity. DNA breaks into single and double strands occur.
Moreover, daunorubicin hydrochloride may disrupt gene expression regulation, inhibit polymerase activity, and cause DNA damage from free radicals. Daunorubicin hydrochloride has antitumor properties against various animal tumours, including spontaneous and grafted ones.
- Acute Lymphocytic Leukemia
- Acute Nonlymphocytic Leukemia
- AIDS-related Kaposi's sarcoma
- In Blood Cancer: Blood cancer, also known as leukaemia, is a type of cancer that affects the tissues that make blood. It weakens the immune system and is especially common in Acute Nonlymphocytic Leukemia (ANLL) and Acute Lymphocytic Leukemia (ALL), where Daunorubicin either kills or stops the growth of the cancer cells or prevents them from increasing by preventing DNA and RNA synthesis. Intravenous administration of this drug is vital for chemotherapy regimens as it induces apoptosis and improves remission rates, thereby improving survival outcomes for patients with certain leukaemias.
- AIDS-related Kaposi's sarcoma: AIDS-related Kaposi's sarcoma is an immunocompromised person's cancer caused by the human herpesvirus-8. By interfering with the synthesis of DNA and RNA, Daunorubicin prevents the growth of cancer cells. Intravenous daunorubicin administration helps in the regression of Kaposi's sarcoma lesions, providing an alternative therapy for the treatment of this AIDS-related cancer.
- Daunorubicin is indicated for the induction of remission in adult myelogenous, monocytic, erythroid acute nonlymphocytic leukaemia as well as adult and pediatric acute lymphocytic leukaemia.
- It can also be used when combined with other chemotherapy drugs to treat other cancers, like Kaposi's sarcoma, which is associated with AIDS.
Parenterally: Never administer Daunorubicin subcutaneously or intramuscularly. Avoid injecting near joints and tendons, small veins, or swollen extremities. Before and after administration, dilute in 100 mL of D5W or NS, infuse over 30 to 45 minutes, and flush with 5 to 10 mL of IV solution. If extravasation occurs, immediately stop the injection, aspirate, and use a cold pack for 15 to 20 minutes every six hours for a total of 24 to 48 hours. After 48 hours of elevation, return the site to normal operations. Less than 1-2 mL of extravasation usually heal independently; more than 3 mL may result in ulceration. If after 48 hours there is still pain, redness, or swelling, one should consult a plastic surgeon promptly for advice and perhaps even debridement.
The dosage and duration of treatment should be as per the treating physician's clinical judgment.
Injectable solution: 5mg/mL
Powder for injection: 20mg
Daunorubicin is available as an injectable solution and powder for injections.
Dose Adjustment in Adult Patients:
Acute Nonlymphocytic Leukemia
In addition to cytarabine 100 mg/m³/day IV for the first seven days of the course and the next five days.
<60 years old: 45 mg/m² IVP on days 1, 2, and 3 of the initial course; days 1, 2 of the following courses
>60 years old: 30 mg/m² IVP on days 1, 2, and 3 of the initial course; days 1, 2 of the following courses
Continue to monitor the liver, kidney, and heart functions.
Acute Lymphocytic Leukemia
45 mg/m² IVP on days 1, 2, and 3.
Continue to monitor the liver, kidney, and heart functions.
AIDS-related Kaposi's sarcoma
The liposomal formulation was initially administered once every two weeks at a dose of 40 mg/m2, diluted in 5% glucose to a concentration of 0.2-1 mg/ml, and given over a period of 30 to 60 minutes.
Follow the dietary guidelines while taking Daunorubicin; in particular, avoid grapefruit and its juice because of possible drug interactions. When taking heart-related medications, proceed with caution. A balanced diet should include nutrient-dense fruits and vegetables and low-fat proteins like fish, poultry, and lean meats. Drink lots of water every day because some cancer treatments, like Daunorubicin, can cause dehydration. To ensure optimal health during treatment, actively stop smoking and drink in moderation.
The dietary restriction should be individualized as per patient requirements.
Patients with preexisting myelosuppression from other drug treatments;
severe hepatic impairment;
IM/SC administration;
Heart failure
recent myocardial infarction or severe myocardial insufficiency; severe arrhythmias;
active infection;
pregnancy;
lactation;
Hypersensitivity to Daunorubicin, its excipients, or other anthracyclines or anthracenediones.
- Before initiating daunorubicin therapy, address infections. If a patient develops fever during daunorubicin treatment, regardless of neutrophil count, promptly administer broad-spectrum antibiotics.
- Daunorubicin induces medullary aplasia and leukopenia. Ensure infection protection during aplasia.
- Daunorubicin may induce hyperuricemia due to tumour lysis syndrome. Manage elevated uric acid with allopurinol and encourage urine excretion, exercising caution in renal insufficiency.
- Observe cases of colitis, enterocolitis, and neutropenic enterocolitis (typhlitis). Cease treatment and promptly seek appropriate medical intervention.
- Exercise caution in injecting Daunorubicin to prevent tissue necrosis.
- When combining Daunorubicin with other anticancer agents, reduce each dosage to minimize overall toxic effects.
- Cumulative doses of 25 mg/kg may lead to cardiotoxicity and congestive heart failure. Avoid exceeding this dose, especially in patients with myocardial lesions or those over 75 years old.
- Before starting Daunorubicin treatment, conduct a physical examination, appropriate x-rays, and ECG. Repeat regularly, especially when the cumulative dose reaches 15 mg/kg.
- Use Daunorubicin solely for inducing remission, avoiding its use as maintenance therapy.
Alcohol Warning
Breast Feeding Warning
Pregnancy Warning
Food Warning
Avoid grapefruit, monitor heart meds, have a balanced diet, hydrate, and quit smoking.
The adverse reactions related to Daunorubicin can be categorized as:
- Common Adverse Effects: Nausea, vomiting, arrhythmias, discolouration of urine
- Less Common Adverse Effects: Injection site skin flare, hyperuricemia, GI ulceration, diarrhoea.
- Rare Adverse Effects: Arrhythmia, cardiomyopathy, bilirubin increased, pruritus, urticaria
The clinically relevant drug interactions of Daunorubicin are briefly summarized here.
When used with cyclophosphamide, there is an increased risk of cardiotoxicity. Increased potential for hepatic toxicity when combined with hepatotoxic medications, such as high-dose methotrexate.
Possibly Lethal: Getting immunized with live vaccines is not advised. Increased radiation reaction may result from concurrent radiation.
The common side effects of Daunorubicin include
- Nausea
- Vomiting
- Arrhythmias
- Discoloration of urine
- Alopecia
- Pregnancy
Pregnancy Category D (FDA): Use in cases where no safer medication is available and life is in danger. Positive evidence of prenatal risk in humans.
When given to a pregnant woman, Daunorubicin can harm the developing fetus. Pregnant women have not been the subject of sufficient, carefully monitored studies. Patients who are to take Daunorubicin while pregnant or who become pregnant while receiving therapy should be informed of the possible risks to the developing foetus. Daunorubicin's extended half-life needs to be taken into account if pregnancy develops during the first few months of treatment. It is advisable to counsel women who could become pregnant while undergoing daunorubicin treatment.
- Nursing Mothers
It is unknown if this medication is eliminated in human milk. Mothers should stop nursing before taking Daunorubicin because it can cause severe adverse reactions in nursing infants. This is because many drugs, including anthracyclines, are excreted in human milk.
- Pediatric Use
The safety and effectiveness of Daunorubicin in pediatric patients have not been established.
Dose Adjustments
Acute Nonlymphocytic Leukemia
<0.5 m² BSA or younger than 2 years old: 1 mg/kg IVP every week
Over the age of two or 0.5 m² BSA: 25 mg/m² IVP every week
Note: Hepatic, renal, and cardiac functions
Acute Lymphocytic Leukemia
<0.5 m² BSA or younger than 2 years old: 1 mg/kg IVP every week
Over the age of two or 0.5 m² BSA: 25 mg/m² IVP every week
Dose Adjustment in Kidney Impairment Patients:
>3 mg/dL serum creatinine: 50% standard dosage should be given.
Dose Adjustment in Hepatic Impairment Patients:
Serum bilirubin level < 1.2 mg/dL due to hepatic impairment: no dose modification is required.
Serum bilirubin level: 1.2–3 mg/dL; 75% of the recommended dosage
> Serum bilirubin > 3 mg/dL: 50% of standard dosage
The physician should be vigilant about the knowledge pertaining to identifying and treating overdosage of Daunorubicin.
Signs and Symptoms
Overconsumption of Daunorubicin could lead to severe myelosuppression and cardiotoxicity with or without transient reversible ECG changes leading to CHF.
Management
There isn't a known antidote for daunorubicin overdose. If an overdose occurs, stop taking Daunorubicin immediately and start getting supportive and symptomatic care promptly. Gastric lavage and activated charcoal may be an immediate intervention to prevent additional absorption. Monitoring blood counts, cardiac function, and vital signs is essential. Supportive interventions such as blood product transfusions, antibiotics, and antiemetics may be used when necessary. It is advised to consult a medical toxicologist or oncologist in severe cases. Though their effectiveness is limited, enhanced elimination techniques such as hemoperfusion or hemodialysis can be investigated. Assessing organ function and providing supportive interventions when needed continuously is essential.
- Absorption: In a 90-minute infusion, Daunorubicin demonstrated a maximum concentration (Cmax) of 24.8 μg/mL and a time to reach maximum concentration (Tmax) of two hours following the liposomal formulation at a dose of 44 mg/m2.
- Distribution: Daunorubicin penetrates all tissues in the body, passing through the placenta and finding its way into breastfeeding. The drug has a volume of distribution (Vd) ranging from 20 to 39.2 L/kg, and between 50 and 60 per cent of it is protein-bound.
- Metabolism: Daunorubicin gets broken down by the liver into its active metabolite, daunorubicinol.
- Excretion: The primary route of daunorubicin elimination is hepatic. About 25% of it remains active in the urine as either daunorubicinol or daunorubicinol, while the remaining 40% is eliminated in the bile. The active metabolite daunorubicinol has a longer elimination half-life of 26.7 hours compared to 18.5 hours for Daunorubicin.
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- https://www.ncbi.nlm.nih.gov/books/NBK559073/
- https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209401s000lbl.pdf
- Therapeutic Goods Administration (TGA): Department of Health [Internet]. Governmet of Australia; Package leaflet information for the user; Daunorubicin (daunorubicin hydrochloride)
