Usage
Cytarabine is primarily used to treat various types of leukemia, including acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), and meningeal leukemia. It is classified as an antimetabolite antineoplastic agent. Cytarabine works by interfering with DNA synthesis, thereby inhibiting the growth of rapidly dividing cancer cells.
Alternate Names
Cytarabine is also known as cytosine arabinoside and Ara-C. Brand names include Cytosar-U®, DepoCyte®, and Tarabine PFS®.
How It Works
Pharmacodynamics: Cytarabine’s primary effect is the inhibition of DNA polymerase, which disrupts DNA synthesis and leads to cell death, particularly in the S-phase of the cell cycle.
Pharmacokinetics:
- Absorption: Cytarabine is poorly absorbed orally and thus usually administered intravenously, subcutaneously, or intrathecally.
- Metabolism: Primarily metabolized in the liver to its inactive form, uracil arabinoside (ara-U), by cytidine deaminase.
- Elimination: Excreted primarily through the kidneys.
Mechanism of Action: Cytarabine is transported into cells and phosphorylated into its active metabolite, cytarabine triphosphate (ara-CTP). Ara-CTP competes with deoxycytidine triphosphate for incorporation into DNA. Once incorporated, ara-CTP inhibits DNA polymerase, leading to chain termination and blocking DNA synthesis. This disruption primarily affects rapidly dividing cells, such as cancer cells.
Dosage
Standard Dosage
Adults:
- Induction of remission (AML):
- Continuous infusion: 100-200 mg/m²/day for 5-10 days. A second course may be initiated 2-4 weeks after the initial therapy if needed.
- Intermittent IV: 3-5 mg/kg daily for 5 consecutive days. Repeat cycle after 2-9 days.
- Maintenance therapy: 1 mg/kg IV or subcutaneously once or twice weekly.
Children:
Children generally tolerate higher doses than adults. Specific pediatric dosing should be consulted within established protocols.
Special Cases:
- Elderly Patients: No specific dose adjustments are recommended, but monitor closely for toxicity due to age-related decline in organ function.
- Patients with Renal Impairment: Use cautiously; dose reductions might be necessary in cases of severe impairment.
- Patients with Hepatic Dysfunction: Use cautiously; dose reduction is often required.
- Patients with Comorbid Conditions: Carefully consider comorbidities and adjust dosage accordingly.
Clinical Use Cases
Dosing recommendations for specific clinical settings vary widely based on the disease state, patient characteristics, and concurrent therapies. Always refer to updated protocols and expert guidance when administering cytarabine in clinical settings, particularly for:
- Intubation: Dosage adjustments are not typically necessary.
- Surgical Procedures: No specific dosage adjustments based on procedure.
- Mechanical Ventilation: Dosage adjustments are not usually necessary.
- Intensive Care Unit (ICU) Use: Dosage adjustments are not usually necessary.
- Emergency Situations: Dosage adjustments are not typically necessary.
Side Effects
Common Side Effects:
Nausea, vomiting, diarrhea, loss of appetite, mouth sores, hair loss, bone pain, fever, and injection site reactions. Myelosuppression (decreased blood cell counts) is common and expected.
Rare but Serious Side Effects:
Severe myelosuppression with increased risk of infection and bleeding, liver dysfunction, kidney problems, lung inflammation or fluid buildup, neurological toxicity (including confusion, seizures, and paralysis), eye problems, and allergic reactions.
Long-Term Effects: Prolonged use can lead to chronic complications such as organ damage.
Adverse Drug Reactions (ADR): Serious ADRs include anaphylaxis, severe myelosuppression, and organ damage.
Contraindications
Hypersensitivity to cytarabine. Active meningeal infections (for liposomal cytarabine).
Drug Interactions
Cytarabine may interact with digoxin, hormonal contraceptives, cyclosporine, and rifampin. Consult a comprehensive drug interaction resource for a complete list.
Pregnancy and Breastfeeding
Cytarabine is contraindicated in pregnancy, especially during the first trimester. It is also not recommended during breastfeeding.
Drug Profile Summary
- Mechanism of Action: Inhibits DNA polymerase, disrupting DNA synthesis.
- Side Effects: Myelosuppression, nausea, vomiting, diarrhea, hair loss.
- Contraindications: Hypersensitivity, active meningeal infection (liposomal).
- Drug Interactions: Digoxin, hormonal contraceptives, cyclosporine, rifampin.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: Varies depending on indication and patient factors; see detailed dosage guidelines.
- Monitoring Parameters: Complete blood counts, liver and kidney function tests, and neurological assessments.
Popular Combinations
Cytarabine is often combined with other chemotherapeutic agents, such as daunorubicin or idarubicin for the treatment of AML and other leukemias.
Precautions
- General Precautions: Closely monitor blood counts, liver function, and kidney function.
- Specific Populations: Contraindicated during pregnancy and lactation. Use cautiously in elderly and patients with pre-existing organ dysfunction.
- Lifestyle Considerations: No specific lifestyle considerations apart from adhering to the recommended treatment plan.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Cytarabine?
A: Dosage varies widely depending on the indication, patient characteristics (age, weight, organ function), and treatment protocols. Refer to the detailed dosage guidelines above and consult with a hematology-oncology expert.
Q2: What are the most common side effects of Cytarabine?
A: Myelosuppression (decreased blood cell counts), nausea, vomiting, diarrhea, and hair loss.
Q3: How does Cytarabine work?
A: It is an antimetabolite that interferes with DNA synthesis, leading to cell death primarily in rapidly dividing cells.
Q4: Is Cytarabine safe during pregnancy?
A: No, cytarabine is contraindicated during pregnancy due to the risk of fetal harm.
Q5: How is Cytarabine administered?
A: Intravenously, subcutaneously, or intrathecally. It is not effective orally.
Q6: What should I monitor in patients receiving Cytarabine?
A: Complete blood counts, liver and kidney function tests, and neurological assessments.
Q7: Can Cytarabine be used to treat all types of leukemia?
A: It is commonly used in the treatment of AML, ALL, and meningeal leukemia but may not be suitable for all types.
Q8: What are the signs of Cytarabine toxicity?
A: Severe myelosuppression, liver dysfunction, kidney problems, neurotoxicity, eye problems, and allergic reactions.
Q9: What if a patient experiences severe side effects from Cytarabine?
A: Immediately discontinue treatment and implement supportive care as necessary. Dose reductions or treatment modifications may be necessary.
Q10: Are there any drug interactions I should be aware of with Cytarabine?
A: Yes, cytarabine interacts with several drugs, including some antibiotics, antifungals, and other chemotherapy agents. Refer to drug interaction databases and consult with a pharmacist.
