cytarabine

Action and Spectrum

Actions and spectrum: 

cytarabine is a potent chemotherapy drug that acts as a nucleoside analog that inhibits DNA synthesis. It is converted into its active triphosphate form within cells, where it competes with natural nucleosides for incorporation into DNA. This incorporation disrupts DNA replication and repair, leading to cell death. 

cytarabine has broad-spectrum activity against different types of leukemia, including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and chronic myeloid leukemia (CML). 

Drug Interaction

Adverse Reaction

Frequency defined 

1-10% 

Nausea 

Diarrhea 

Thrombophlebitis 

Myelosuppression 

Fever 

Anorexia 

Vomiting 

Oral/anal inflammation 

Bleeding 

Rash 

Hepatic dysfunction  

Frequency not defined 

Neuropathy 

Pericarditis 

Anemia 

Leukopenia 

Kidney disease 

Sepsis 

Skin ulcers 

Urinary retention 

Jaundice 

Headache 

Chest pain 

Pneumonia 

Bleeding 

Thrombocytopenia 

Infectious disease 

cytarabine syndrome 

Cellulitis 

Neuritis 

Anaphylaxis 

Black Box Warning

Black Box Warning: 

cytarabine does not have a specific black box warning. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• Hypersensitivity: cytarabine is contraindicated in individuals who have a known allergic or hypersensitivity reaction to cytarabine or any of its components.  
• Pregnancy and breastfeeding: cytarabine can cause harm to developing fetus and has the potential to be excreted in breast milk. It is contraindicated during pregnancy and breastfeeding.  
• Severe liver or kidney dysfunction: cytarabine should be used under caution in patients with liver or kidney impairment due to the potential for increased toxicity and impaired drug elimination.  
• Active infection: cytarabine is contraindicated in patients with active infections, especially those affecting the blood or central nervous system. The use of cytarabine may further compromise the immune system and increase the risk of severe infections. 
• Pre-existing bone marrow suppression: cytarabine can cause bone marrow suppression, and it is contraindicated in individuals with pre-existing bone marrow suppression, such as severe anemia, leukopenia, or thrombocytopenia.

Caution: 

• Bone marrow suppression: cytarabine can cause bone marrow suppression, leading to a decrease in the production of blood cells. Closely monitoring the blood cell counts is necessary to assess bone marrow function and adjust the dose if needed. 
• Hepatic and renal impairment: cytarabine may affect liver and kidney function. Patients with pre-existing liver or kidney impairment may require dose adjustments or close monitoring during treatment. 
• Infection risk: cytarabine can increase the risk of infections due to its effect on the immune system. Patients should be monitored closely for the signs of infection and appropriate prophylactic measures should be taken. 
• Neurological toxicity: cytarabine may cause neurological side effects, including confusion, seizures, and cerebellar dysfunction. Patients with a history of neurological disorders or compromised neurological function should be closely monitored during treatment. 
• GI toxicity: cytarabine can cause gastrointestinal (GI) toxicity, including nausea, vomiting, and diarrhea. Adequate supportive care should be provided to manage these symptoms and prevent dehydration. 
• Allergic reactions: Allergic reactions from mild to severe, can occur with cytarabine. Patients with a known hypersensitivity to cytarabine.

Comorbidities: 

• Cardiovascular disease: Patients with leukemia, especially older adults, may have comorbidities such as hypertension, coronary artery disease, or heart failure. These cardiovascular conditions can pose additional risks during cytarabine treatment. 
• Renal dysfunction: cytarabine can affect kidney function, and patients with pre-existing renal impairment may experience further deterioration.  
• Hepatic dysfunction: Liver dysfunction may be present in some patients with leukemia, and cytarabine can potentially exacerbate this condition.  
• Pulmonary disease: Patients with leukemia may have pre-existing conditions like COPD or pulmonary infections. cytarabine treatment may increase the risk of pulmonary toxicity, and close monitoring of respiratory function is important. 
• Immune system disorders: Some patients with leukemia may have underlying immune system disorders or compromised immune function. cytarabine can further suppress the immune system, increasing the risk of infections and other immune-related complications. 
• Hematological disorders: Patients with leukemia may have pre-existing hematological disorders, such as anemia, thrombocytopenia, or coagulopathy. cytarabine can worsen these conditions and necessitate careful monitoring of blood cell counts and appropriate supportive care. 

Pregnancy / Lactation

Pregnancy consideration: US FDA pregnancy category: D 

Lactation: N/A  

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• 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 exerts its pharmacological effects by inhibiting DNA synthesis and repair, leading to the disruption of DNA replication and cell division. cytarabine is converted into its active triphosphate form (ara-CTP) intracellularly. Ara-CTP competes with natural deoxycytidine triphosphate (dCTP) for incorporation into the growing DNA chain. Once incorporated, cytarabine inhibits DNA polymerase and results in premature chain termination, preventing further DNA synthesis.  

Pharmacodynamics: 

• Cell cycle specificity: cytarabine exhibits cell cycle-specific activity, primarily targeting cells in the S-phase (DNA synthesis phase) of the cell cycle. 
• Antimetabolite effect: cytarabine acts as a nucleoside analogue, disrupting the normal structure and function of DNA, leading to inhibition of DNA replication and cell division. 
• Cytotoxicity: cytarabine induces apoptosis in rapidly dividing cells, including cancer cells.

Pharmacokinetics: 

Absorption 

cytarabine is administered intravenously or subcutaneously and achieves rapid systemic distribution. 

Distribution 

It penetrates the blood-brain barrier and can enter the cerebrospinal fluid when administered intrathecally. 

Metabolism 

cytarabine is metabolized by intracellular enzymes to its active form (ara-CTP). 

Elimination and excretion 

cytarabine undergoes rapid clearance primarily through intracellular deamination and cytidine deaminase-mediated metabolism. The metabolites are excreted through kidneys. 

Adminstartion

Administration: 

• Intravenous (IV) Administration: cytarabine is often given as an IV infusion. It is diluted in a compatible IV solution and administered slowly into a vein over a specific duration of time. The infusion rate and duration may vary depending on the dose, patient factors, and treatment protocol. 
• Subcutaneous (SC) Administration: In some cases, cytarabine may be administered subcutaneously. It involves injecting the medication under the skin, usually in the abdomen or upper thigh. The injection site may be rotated to minimize discomfort. 
• Intrathecal (IT) Administration: cytarabine can be administered directly into the cerebrospinal fluid (CSF) through a lumbar puncture or Ommaya reservoir for the treatment or prevention of central nervous system (CNS) involvement in leukemia or lymphoma. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: cytarabine 

Pronounced: (sye-TAR-uh-been)  

Why do we use cytarabine? 

• Acute Myeloid Leukemia (AML): cytarabine is a key component of induction therapy for AML, a type of blood and bone marrow cancer. 
• Acute Lymphoblastic Leukemia (ALL): cytarabine may be used in the treatment of ALL, a cancer of the lymphocytes. It is typically included in multi-agent chemotherapy regimens for both induction and consolidation therapy. 
• Non-Hodgkin Lymphoma (NHL): cytarabine is used in the treatment of NHL, a group of cancers affecting the lymphatic system. It is often combined with other chemotherapy drugs in specific regimens for different subtypes of NHL. 
• Chronic Myeloid Leukemia (CML): In certain cases of CML, cytarabine may be used as part of a treatment regimen to control the disease, particularly during blast crisis or in combination with other targeted therapies. 
• Meningeal Leukemia or Lymphoma: cytarabine can be administered intrathecally (into the cerebrospinal fluid) to treat leukemia or lymphoma that has spread to the central nervous system.