Action and Spectrum

Action and Spectrum: 

azacitidine is a nucleoside analogue that is used as a chemotherapy drug for the treatment of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). It works by causing DNA hypomethylation, leading to abnormal gene expression and inhibition of cell division, causing the death of rapidly dividing cells. 

azacitidine is used to treat MDS and AML, particularly in patients who are not eligible for more intensive chemotherapy regimens. It can be administered orally or intravenously. The spectrum of activity of azacitidine includes the ability to induce differentiation and apoptosis of cancer cells, leading to a reduction in the size of the cancer cell population.

Drug Interaction

Adverse Reaction

Frequency defined: 

>10%: 

Chest pain 

Erythema of skin 

Skin rash 

Abdominal pain 

Constipation 

Nausea 

Vomiting 

Anemia 

Leukopenia 

Anxiety 

Dizziness 

Limb pain 

Arthralgia 

Dyspnea 

Pneumonia 

Fever  

1%-10% 

Atrial fibrillation 

Hypertension 

Orthostatic hypotension 

Septic shock  

Frequency not defined: 

Hepatic coma 

rigors 

Black Box Warning

Black Box Warning: 

The black box warning for azacitidine states that the drug may cause severe and sometimes fatal liver problems, severe infections, and low levels of red and white blood cells and platelets, which can lead to bleeding, infections, and death. 

Contraindication / Caution

Contraindication/Caution: 

azacitidine is contraindicated in patients with a known hypersensitivity reaction to the drug or any of its components. It is also contraindicated in women who are pregnant or breastfeeding. 

Patients with a history of severe bone marrow suppression or significant liver or kidney problems should use caution when receiving azacitidine. Additionally, patients taking medications that affect bone marrow function or who have a compromised immune system should also be cautious. 

azacitidine can interact with several medications, including anticoagulants, anti-inflammatory drugs, and drugs that affect the immune system, so it is important for patients to inform their healthcare provider of all medications they are taking. 

Pregnancy / Lactation

Pregnancy consideration: based on animal studies, it may cause harm to patients who can become pregnant. 

Lactation: excretion of azacitidine in breast milk is not known.  

Pregnancy category: 

• Category A: Satisfactory and well-controlled studies show no risk to the fetus in the first or later trimester. 
• Category B: There is no evidence of risk to the fetus found in animal reproduction studies and there are not enough studies on pregnant women. 
• Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for an effect in humans, care must be taken for potential risks in pregnant women 
• Category D: There is adequate data available with sufficient evidence of human fetal risk from various platforms, but despite potential risks may be used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh risks over benefits These category drugs should be prohibited for pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

azacitidine is a nucleoside analogue and antineoplastic agent that acts as a DNA methyltransferase inhibitor. DNA methylation is a critical epigenetic modification that regulates gene expression and can contribute to the development and progression of cancer. 

Pharmacodynamics: 

azacitidine interferes with the normal functioning of DNA methyltransferases, leading to the accumulation of unmodified DNA and the activation of normally silenced genes. This leads to the induction of cellular differentiation and apoptosis in cancer cells, resulting in their destruction. 

In addition, azacitidine has been shown to enhance the immune response to cancer cells and improve the effectiveness of chemotherapy drugs. 

Pharmacokinetics: 

Absorption 

azacitidine is administered intravenously (IV) and is rapidly absorbed 

Distribution 

It is widely distributed in the body and is rapidly metabolized 

Metabolism 

It is metabolized in the liver to its active form, decitabine, which is then eliminated from the body 

Elimination and excretion 

azacitidine is eliminated from the body primarily in the urine. The half-life of azacitidine is approximately 2 hours 

Adminstartion

Administration: 

azacitidine is a medication used in the treatment of certain blood and bone marrow cancers, such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). It is typically administered intravenously (IV) in a hospital or clinic setting. 

The medication is given as an IV infusion over a period of 1-5 hours, usually once per day for 5-7 consecutive days. This cycle of treatment is repeated every 4-6 weeks. The dose and duration of treatment is determined by the patient’s condition, health status, and response to the medication. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: Azacitidine 

Pronounced: aza-sy-ti-din 

Why do we use azacitidine? 

azacitidine is used for treating myelodysplastic syndrome (MDS), including VEXAS syndrome, because it works by blocking the activity of DNA methyltransferases, enzymes that play a role in gene expression regulation. By inhibiting these enzymes, azacitidine helps to reactivate normal gene expression and promotes cell growth, which can lead to a reduction in the number of abnormal cells in the bone marrow. This leads to improved blood counts and reduced symptoms in patients with MDS, including VEXAS syndrome.