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Azacitidine is a chemotherapy drug used for myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and chronic myelomonocytic leukemia (CMML). It works as a hypomethylating agent, which is a chemical nucleoside analog. The drug targets abnormal DNA methylation, which cancer cells rely on to survive. By integrating into cancer cell DNA, Azacitidine blocks DNA methyltransferase. This reversal of abnormal methylation reactivates essential tumor suppressor genes. As a result, cancer growth slows. 

Azacitidine also disrupts RNA. It interferes with RNA synthesis, which affects protein production in malignant cells. This interference causes metabolic disruptions. Eventually, it triggers apoptosis or cell death. However, the drug does more than just kill cancer cells. 

It also helps alleviate anemia, bleeding, and infection risks by improving bone marrow function. Azacitidine restores normal methylation patterns, changing the tumor environment. This effect can make cancer cells more sensitive to other treatments. 

Treatment spans multiple cycles to ensure the best therapeutic response. Its dual impact on the DNA and RNA of cancer cells enhances its effectiveness in managing blood cancers.

Azacitidine Usage 

Azacitidine is frequently used to treat various blood-related cancers, particularly those arising from abnormal bone marrow activity:

• Myelodysplastic Syndromes (MDS): Azacitidine targets abnormal bone marrow cells in MDS by interfering with the abnormal DNA methylation patterns that drive the disease. This action helps restore normal blood cell production, lowering the need for transfusions and reducing symptoms like fatigue and infections.

• Acute Myeloid Leukemia (AML): In AML, Azacitidine incorporates itself into the DNA of leukemic cells, disrupting their replication. It forces these rapidly dividing cells into apoptosis, which slows disease progression and can extend survival, especially in older or high-risk patients who are not candidates for intensive chemotherapy.

• Chronic Myelomonocytic Leukemia (CMML): Azacitidine helps control the abnormal proliferation of white blood cells in CMML by inhibiting DNA methylation. This reduces leukemic cells and improves blood counts, offering symptomatic relief and improved quality of life for patients with this disease.

Azacitidine Dosage

Azacitidine tablets are taken at 300 mg once daily for 14 days in a 28-day cycle. This is for adults with acute myeloid leukemia (AML) who are in their first remission but can't have intense treatments. You can take the tablet with or without food, but don’t crush or chew it. To help with nausea, your doctor might suggest taking an antiemetic 30 minutes before each dose, especially during the first two cycles.

Treatment continues until the disease gets worse or side effects become too much, with regular blood tests to check for problems. If you miss a dose, take it as soon as you remember. If it's close to the next dose, skip the missed one.

Don’t take two doses at once. If you vomit after taking a dose, don’t take another one that day—just continue with the next dose.

Azacitidine Side Effects

• Myelosuppression: Azacitidine suppresses bone marrow function, decreasing the production of red and white blood cells and platelets. This increases the risk of infections, anemia, and bleeding.

• Nausea and Vomiting: Gastrointestinal side effects are common with Azacitidine, including persistent nausea and vomiting, often requiring antiemetic medication for relief.

• Fatigue: Severe fatigue is frequent, particularly during prolonged cycles of treatment.

• Fever: A rise in body temperature is common during treatment, which can be linked to low white blood cell counts.

• Renal Impairment: Kidney function may decline in some patients, leading to increased monitoring and potential dosage adjustments.

• Diarrhea: Azacitidine can irritate the digestive tract, causing diarrhea in many patients during treatment.

• Liver Toxicity: Azacitidine may impair liver function, particularly in patients with pre-existing liver disease. Monitoring liver enzymes is crucial to avoid further damage.

Precautions

To reduce any reactions that might cause you harm, you must do the following before and after treatment:

• Before you begin Azacitidine, it's essential to give your doctor a complete list of all your medications and supplements. This helps identify any potential interactions, especially with blood thinners.

• Regular blood tests are needed while on Azacitidine to monitor your blood counts. This drug can affect your bone marrow, increasing the risk of infections and bleeding.

• Stay hydrated during your treatment with Azacitidine. Drinking enough fluids can help reduce side effects like nausea and fatigue.

• Be vigilant for infection symptoms, such as fever or chills, while on Azacitidine. This drug can weaken your immune system, making you more vulnerable to infections.

• Discuss any planned vaccinations with your doctor before starting Azacitidine. Some vaccines might not be safe during treatment.

• Avoid NSAIDs (non-steroidal anti-inflammatory drugs) while on Azacitidine. These can increase the risk of bleeding, especially if your blood counts are low.

• If you experience significant fatigue, let your healthcare provider know. Azacitidine can cause fatigue that may affect your daily activities and quality of life.

• Notify your doctor about any new medications or supplements you want to take during treatment. Even common supplements can interact with Azacitidine and lead to complications.

• Monitor for any skin changes or rash during treatment. Some patients may experience skin reactions to Azacitidine, which should be reported to your healthcare provider.

• Maintain good oral hygiene and report any mouth sores. Azacitidine can cause mucositis, leading to painful sores in the mouth. It’s important to address any discomfort early.

Price and Availability

Azacitidine’s high cost stems from its complex synthesis as a nucleoside analog. The production process involves multiple steps to replicate natural nucleotides, which require advanced chemical techniques. Strict quality control, coupled with the need for specialized equipment, further increases manufacturing costs.

The cold chain logistics necessary to preserve its stability during transport also contribute to Azacitidine’s price. In the Philippines and Malaysia, added import taxes and distribution fees raise the overall cost.

Azacitidine Safety Advice

Alcohol

Limit alcohol consumption while taking Azacitidine, as it may increase dizziness. Alcohol worsens side effects.

Pregnancy

Azacitidine is highly teratogenic, posing severe risks to an unborn child. Use reliable contraception, and immediately inform your doctor if pregnancy occurs during treatment.

Breastfeeding

Breastfeeding should be discontinued during Azacitidine treatment due to potential harm to the infant. Consult your doctor for alternatives.

Driving

Azacitidine may cause dizziness and fatigue, affecting your ability to drive or use machinery safely. Assess your alertness before performing these tasks.

Liver

Azacitidine can affect liver enzymes, particularly if you have pre-existing liver conditions. Regular liver function monitoring is crucial to detect potential issues during treatment.

Doctor Advice

Your doctor will schedule regular check-ups to monitor blood counts and liver function. Close monitoring ensures effective treatment and helps manage side effects.