cytarabine/daunorubicin liposomal

Action and Spectrum

Actions and Spectrum 

Action: 

 cytarabine, a nucleoside analog, exerts its antineoplastic activity by incorporating into DNA strands during the S-phase of the cell cycle. This incorporation disrupts DNA replication and subsequently inhibits cellular proliferation. By acting as a DNA chain terminator, cytarabine promotes cell death in rapidly dividing cancer cells. 

daunorubicin, an anthracycline antineoplastic agent, exerts its cytotoxic effects by intercalating with DNA and inhibiting topoisomerase II, an enzyme crucial for DNA replication and repair. Additionally, daunorubicin generates reactive oxygen species, leading to oxidative damage and DNA strand breaks. These mechanisms collectively induce cell death in cancer cells. 

Spectrum: 

The drug exhibits a broad spectrum of activity against various hematologic malignancies, including acute myeloid leukemia (AML). AML is characterized by the rapid proliferation of immature myeloid cells in the bone marrow, leading to the suppression of normal blood cell production. The liposomal formulation of cytarabine/daunorubicin enhances drug delivery to the bone marrow and extends the exposure of malignant cells to the active agents, thereby increasing the therapeutic efficacy. 

Drug Interaction

Adverse Reaction

Frequency defined  

>10% 

Arrhythmia, all grades (30%) 

Febrile neutropenia, all grades (68%) 

Diarrhea/colitis, all grades (45%) 

Rash, all grades (54%) 

Nausea, all grades (47%) 

Headache, all grades (33%) 

Abdominal pain, all grades (33%) 

Cough, all grades (33%) 

Edema, all grades (51%) 

Hemorrhage, all grades (70%) 

Febrile neutropenia, ≥grade 3 (66%) 

Dyspnea, all grades (32%) 

Fatigue, all grades (32%)  

1-10% 

Deafness (<10%) 

Prolonged neutropenia, consolidation (10%) 

Deafness unilateral (<10%) 

Eye swelling (<10%) 

Dry eye (<10%) 

Dyspepsia (<10%) 

Scleral hyperemia (<10%) 

Eye pain (<10%) 

Eye conjunctivitis (<10%) 

Eye irritation (<10%) 

Eye edema (<10%) 

Hallucinations (<10%) 

Periorbital edema (<10%) 

Pneumonitis (<10%) 

Black Box Warning

Black Box Warning:  

Cardiotoxicity 

Myelosuppression 

Hepatotoxicity 

Contraindication / Caution

Contraindication/Caution:  

Hypersensitivity: The drug is contraindicated in individuals who have a known hypersensitivity or allergic reaction to cytarabine, daunorubicin, or any other components of the liposomal formulation. Hypersensitivity reactions may manifest as skin rash, itching, facial swelling, or respiratory distress. In severe cases, anaphylaxis, a potentially life-threatening allergic reaction, may occur. 

Pre-existing Cardiomyopathy: cytarabine/daunorubicin liposomal is contraindicated in patients with pre-existing cardiomyopathy or a history of significant cardiac impairment. cardiomyopathy is a condition characterized by the structural or functional abnormality of the heart muscle.  

Severe Liver Dysfunction:  

The administration of this drug is contraindicated in patients with severe liver dysfunction, as determined by laboratory tests or clinical assessment. Liver dysfunction can impair the metabolism and elimination of medications, potentially resulting in increased drug exposure and heightened toxicity.  

Pregnancy and Lactation:  

The drug is contraindicated in pregnant women due to the potential risks to the developing fetus. Animal studies have demonstrated adverse effects on fetal development, including teratogenicity and embryolethality. Similarly, the use of this medication during breastfeeding is contraindicated, as it may be excreted in breast milk and pose a risk to the nursing infant. Alternative treatment options should be considered in these situations. 

Pregnancy / Lactation

Pregnancy warnings:     

Pregnancy category: N/A 

Lactation: Excreted into human milk is unknown 

Pregnancy Categories:         

Category A: Studies that were well-controlled and met expectations revealed no risk to the fetus in either the first or second trimester. 

Category B: There were a lack of studies on pregnant women and no evidence of risk to the fetus in animal experiments.   

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.   

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category

Pharmacology

Pharmacology:  

cytarabine and daunorubicin are chemotherapeutic agents commonly used in the treatment of hematologic malignancies. When formulated as a liposomal combination, these agents exhibit unique pharmacological properties that enhance their therapeutic efficacy and reduce systemic toxicity. 

Pharmacodynamics:  

cytarabine, a nucleoside analogue, inhibits DNA synthesis by incorporating into DNA strands and subsequently disrupting their replication. It exerts its cytotoxic effects primarily during the S-phase of the cell cycle. daunorubicin, on the other hand, belongs to the anthracycline class of antibiotics and functions by intercalating with DNA, thereby inhibiting topoisomerase II activity and inducing DNA strand breaks. Additionally, daunorubicin generates reactive oxygen species that contribute to its cytotoxic effects.   

Pharmacokinetics: 

Absorption 

The liposomal formulation of cytarabine and daunorubicin exhibits prolonged circulation in the bloodstream, leading to enhanced drug absorption. liposomes act as carriers, protecting the encapsulated drugs from degradation and improving their bioavailability.  

Distribution 

liposomal cytarabine and daunorubicin are widely distributed within the body, with liposomes showing a propensity to accumulate in organs affected by hematological malignancies. This selective distribution allows for higher drug concentrations in tumor tissues, increasing the therapeutic index and reducing systemic toxicity.   

Metabolism 

 The metabolic fate of cytarabine and daunorubicin within the liposomal formulation is influenced by the properties of the liposomes and the inherent characteristics of the drugs. The liposomal encapsulation modifies the metabolism of these agents, resulting in altered biotransformation pathways and kinetics compared to their non-liposomal counterparts.   

Excretion and elimination 

The elimination of liposomal cytarabine and daunorubicin primarily occurs through hepatic metabolism and biliary excretion. These drugs are subsequently eliminated via the biliary route into the gastrointestinal tract, where they may undergo further metabolism or be excreted unchanged in the feces. Renal excretion of liposomal cytarabine and daunorubicin is minimal, with the majority of the drugs being eliminated through non-renal routes. 

Adminstartion

Administration:  

The administration of this drug liposomal is typically done via intravenous infusion. 

The recommended dosage and treatment schedule depend on various factors, including the patient’s condition, disease characteristics, and individual response to therapy.  

Prior to administration, healthcare professionals should thoroughly evaluate the patient’s medical history, perform necessary laboratory tests, and closely monitor vital signs during treatment. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: cytarabine/daunorubicin liposomal 

Why do we use cytarabine/daunorubicin liposomal?  

Acute Myeloid Leukemia (AML):  

The drug has emerged as an important therapeutic option for patients diagnosed with AML. Clinical trials have demonstrated its efficacy in inducing complete remission and prolonging overall survival in both younger and older adults with AML. The liposomal formulation allows for enhanced drug delivery to leukemic cells, resulting in improved therapeutic outcomes while minimizing systemic toxicity. 

Relapsed or Refractory AML:  

Patients with relapsed or refractory AML, who have failed to respond to standard therapies, present a significant challenge in clinical practice. The drug has exhibited promising activity in this patient population. Studies have reported encouraging response rates and durable remissions, highlighting its potential as a salvage therapy in difficult-to-treat AML cases. 

High-Risk Myelodysplastic Syndromes (MDS): High-risk MDS is characterized by poor prognosis and limited treatment options. The drug has shown efficacy in this patient subset, offering a therapeutic alternative with improved tolerability compared to conventional chemotherapy. By delivering the encapsulated drugs directly to the bone marrow microenvironment, this formulation targets malignant cells while minimizing off-target toxicities. 

Pediatric Acute Lymphoblastic Leukemia (ALL):  

Pediatric all poses unique challenges in terms of treatment and minimizing long-term side effects. The drug has shown promise in pediatric patients, with studies demonstrating its ability to induce remission and reduce the need for intensive chemotherapy regimens. The liposomal delivery system enhances drug penetration into leukemic cells, potentially improving treatment outcomes in this vulnerable population.