Allopathy
Prescription Required
DCGI (Drugs Controller General of India)
Schedule H
India, the United States, Canada, countries within the European Union, Australia, Japan and South Korea.
Azacitidine is an antineoplastic agent belonging to the pharmacological class of demethylation agents, specifically DNA Methylation inhibitors.
The FDA approves Azacitidine to treat myelodysplastic syndromes (MDS) and Acute Myeloid Leukemia (AML).
When absorbed subcutaneously (SC), Azacitidine is quickly and completely absorbed. It has an extensive distribution (76 ± 26 L), is metabolized by the liver, and is primarily eliminated through urine.
The most common side effects of Azacitidine include injection site reactions (pain, swelling, redness), vomiting, weakness, and nausea.
Azacitidine is available as a tablet and powder for injection.
The molecule is available in India, the United States, Canada, countries within the European Union, Australia, Japan and South Korea.
Azacitidine is an antineoplastic agent belonging to the pharmacological class of demethylation agents, specifically DNA Methylation inhibitors.
Azacitidine is a synthetic pyrimidine nucleoside analogue of cytidine that is thought to cause DNA hypomethylation by inhibiting DNA methyltransferase. This enzyme methylates newly synthesized DNA in mammalian cells and directly harms aberrant hematopoietic cells in the bone marrow.
When administered subcutaneously, Azacitidine achieves a peak plasma concentration of 750 ng/mL.
Azacitidine administered subcutaneously reaches peak plasma time within 0.5 hours.
Azacitidine administered orally achieves peak plasma time within 1 hour.
Azacitidine is available as a tablet and powder for injection.
- Powder for injection: To be administered parenterally, as applicable.
- Tablets: To be swallowed whole with water/liquid. Do not chew, crush or break it.
As prescribed by the physician, take the medication with or without meals.
- Acute Myeloid Leukemia
- Treatment of Myelodysplastic syndrome
- Juvenile Myelomonocytic Leukemia
- Acute Myeloid Leukemia: When treating Acute Myeloid Leukemia (AML), Azacitidine inhibits DNA methylation, encourages the differentiation of leukemic cells, and induces apoptosis for effective management.
- Treatment of Myelodysplastic syndrome: Myelodysplastic syndrome is a group of disorders where the bone marrow fails to produce enough healthy blood cells and instead produces blood cells with aberrant structure and function. Azacitidine is used to treat this condition.Azacitidine inhibits the growth and multiplication of cancer cells as well as their death. It functions by preventing DNA methylation, encouraging healthy cell division, and triggering the death of aberrant cells. It lessens symptoms and lowers the chance of developing acute leukemia by enhancing blood cell production.
- Juvenile Myelomonocytic Leukemia: Azacitidine can be beneficial in treating juvenile myelomonocytic leukaemia (JMML) because it affects DNA methylation, may change abnormal gene expression, and promotes cellular differentiation. Rare childhood cancer JMML is characterized by abnormal proliferation of myeloid cells, decreased production of blood cells, and increased risk of leukaemia. The mode of action of Azacitidine in this particular form of leukaemia helps in its therapeutic effects.
- Indicated for patients with the following French-American-British (FAB) subtypes when treating myelodysplastic syndromes: Refractory anaemia (RA), RA with ringed sideroblasts (if transfusion-requiring or associated with neutropenia or thrombocytopenia), RAEB, RAEB-T, and chronic myelomonocytic leukaemia (CMMoL).
- Indicated for adults with acute myeloid leukaemia who are unable to finish intensive curative therapy after achieving first complete remission (CR) or CR with incomplete blood count recovery after intensive induction chemotherapy.
- In paediatrics, Individuals newly diagnosed with juvenile myelomonocytic leukaemia (JMML) are at least one month of age.
- Parenterally: To achieve a homogeneous suspension, vigorously roll the dosing syringe between the palms immediately before administration until a uniform, cloudy suspension is obtained. Administer Azacitidine suspension subcutaneously, rotating injection sites (thigh, abdomen, or upper arm) at least one inch apart. Avoid tender, bruised, red, or hard areas. For intravenous administration, administer the dose over 10 - 40 minutes, completing the process within 1 hour of reconstituting the Azacitidine vial.
- Orally: Tablets should not be chewed, split, or crushed. Take each dose every day at around the same time. Avoid substituting SC or IV Azacitidine; the indications and dosage requirements differ. Give an antiemetic half an hour before starting each dose for the first two cycles; if vomiting and nausea don't happen, stop taking it after that. Take only one dose on the same day; if missed, take it as soon as possible and return to the usual routine. Don't take another dose the same day if you vomit; instead, get back to the usual routine the next day.
The dosage and duration of treatment should be as per the treating physician's clinical judgment.
- Powder for injection: 100mg/single-dose vial
- Tablets: 200 mg, 300 mg.
Azacitidine is available as a tablet and powder for injection.
Dose Adjustment in Adult Patients:
Myelodysplastic Syndromes
Repeat every four weeks. 75 mg/m2 IV or SC qDay for seven days.
The dose can be raised to 100 mg/m2 if no improvement is seen after two treatment cycles and if there is no toxicity other than dizziness or nausea.
4-6 cycles of treatment are the minimum.
As long as the patient is still improving, continue to treat them.
Acute Myeloid Leukemia
Each cycle lasts for 28 days.
On Days 1 to 14, 300 mg PO qDay
Continue till the disease worsens or the toxicity becomes intolerable.
There are no specific dietary requirements when taking Azacitidine. When taking Azacitidine, avoid smoking and alcohol. Include vegetables and fruits, and avoid fast food, fried food, processed meats, refined carbs, and added sugar. Stay hydrated and maintain a balanced diet.
The dietary restriction should be individualized as per patient requirements.
- Hypersensitivity to Azacitidine, mannitol or its components.
- Advanced malignant hepatic tumours.
- Pregnancy and lactation.
- It is advised not to Substitute Injectable Azacitidine for Oral Azacitidine as it can lead to unintended consequences; always use the prescribed form.
- Frequent monitoring of complete blood counts (CBC) is essential to detect and manage blood-related issues.
- Patients with severe preexisting hepatic impairment are at a heightened risk of toxicity; closely monitor hepatic function.
- Regularly monitor patients with renal impairment, as Azacitidine and its metabolites are primarily excreted through the kidneys.
- Azacitidine may induce severe or fatal tumour lysis syndrome, especially in patients with myelodysplastic syndromes (MDS). It is advised to assess baseline risk and monitor/treat accordingly.
- Azacitidine also poses a risk of fetal harm. Inform female patients and male patients with female partners of reproductive potential about the potential risk to a fetus. Advise the use of effective contraception.
Alcohol Warning
Breast Feeding Warning
Pregnancy Warning
Food Warning
Consume fruits and vegetables. Limit fast food and processed meat.
The adverse reactions related to Azacitidine can be categorized as:
- Common Adverse Effects: Anemia, neutropenia, and thrombocytopenia, affecting blood cell counts.
- Less Common Adverse Effects: Hepatotoxicity
- Rare Adverse Effects: Severe skin disorders, Stevens-Johnson syndrome, toxic epidermal necrolysis, and severe infections.
Reports on Postmarketing
Pericardial effusion
The pericarditis
Hepatotoxicity
The common side effects of Azacitidine include
Injection site reactions (pain, swelling, redness)
Vomiting
Weakness
Nausea
Decreased potassium level in blood
Decreased platelet, white blood, and red blood cell counts
Bruise
Lightheadedness
Fever and Chills
Diarrhea
Constipation
Headache
Fatigue
Pneumonia
- Pregnancy
Pregnancy Category D (FDA): Use in cases where no safer medication is available and life is in danger. Positive evidence of prenatal risk in humans.
Fetal harm may result from its administration to pregnant women, according to studies on its mechanism of action and on animals.
There is not enough information on drug use in pregnant women to assess any risks.
Before starting therapy, ascertain whether females who are capable of reproducing are pregnant.
Animal data
In animals, Azacitidine at doses below the recommended human dose was teratogenic and resulted in embryofetal lethality.
Inform expectant mothers about possible fetal risks.
Contraception ( IV or SC)
Use effective contraception during the period of treatment and for six months following the last dosage.
Men who have female partners who may become pregnant should be advised to use effective contraception while taking this medication and for three months following the last dose.
Potentially fertile females(PO): During treatment and for at least six months following the last dosage, use an effective form of contraception.
Males who are sexually attracted to women who are capable of having children should use effective contraception both during and for at least three months following their last dosage.
Infertility(PO)
Male and female fertility may be compromised, according to data from animals.
- Nursing Mothers
No information is available about the presence of Azacitidine in human milk, how therapy affects breastfed infants, or how therapy affects the amount of milk produced.
IV or SC: Advise patients not to breastfeed during treatment and for one week following the last dosage because many medications are excreted in human milk; Azacitidine has been shown in animal studies to have tumorigenicity, and breastfeeding may result in severe adverse reactions.
PO: Tell patients not to nurse while receiving therapy and for a week following the last dosage.
- Pediatric Use
In pediatric patients, Azacitidine's safety and effectiveness are unknown. Careful assessment and clinical considerations should guide the use of Azacitidine in this population.
Dose adjustment
Juvenile Myelomonocytic Leukemia
≥From one month to one year OR less than ten kilograms: During seven days of a 28-day cycle, administer 2.5 mg/kg IV daily.
≥1 year AND ≥10 kg: 75 mg/m2 IV qDay for 7 days in a 28-day cycle
Treat for no more than three cycles, not six cycles.
The dose may be postponed for up to 14 days for nonhematologic toxicities.
If the patient continues to benefit, the course of treatment may be extended for up to six cycles.
Dose Adjustment in Kidney Impairment Patients:
No dosage adjustment is required for mild-to-severe (CrCl 15-89 mL/min).
Increased dosage modifications should be made for adverse reactions in patients with severe renal impairment (CrCl 15–29 mL/min).
Dose Adjustment in Hepatic Impairment Patients:
Mild: No dosage adjustment is required if total bilirubin is ≤ULN and AST is >ULN or if total bilirubin is 1-1.5x ULN and any AST.
Moderate (bilirubin total >1.5–3 times ULN): No established recommended dosage
Severe: Unstudied (total bilirubin >3x ULN)
The physician should be vigilant about the knowledge pertaining to identifying and treating overdosage of Azacitidine.
Signs and Symptoms
Overconsumption of Erlotinib could lead to nausea, vomiting, diarrhoea
Management
The management of Azacitidine overdose involves supportive measures. There isn't a specific antidote, and the drug is not removed by hemodialysis in case of overdose. Monitor hematologic parameters, liver function, and renal function. If severe adverse reactions occur, consider dose reduction or discontinuation of Azacitidine.
Pharmacodynamic
The amount of Azacitidine needed to inhibit DNA methylation in vitro maximally does not significantly suppress DNA synthesis, and hypomethylation may allow genes essential for differentiation and proliferation to function normally again. Following the initial azacitidine treatment cycle (75 mg/m2 or 2.5 mg/kg), patients with juvenile myelomonocytic leukaemia showed a reduction in genome-wide DNA methylation levels in bone marrow granulocytes, indicating that Azacitidine has DNA-hypomethylating properties.
Pharmacokinetics
- Absorption: When administered subcutaneously (SC), Azacitidine shows quick and thorough absorption with a high bioavailability of about 89%. Thirty minutes (SC) is a very short time to reach peak plasma concentration.
- Distribution: Azacitidine shows a 76 ± 26 L volume after intravenous (IV) administration, showing extensive distribution throughout the body.
- Metabolism: Azacitidine is mainly metabolized in the liver by cytidine deaminase-mediated spontaneous hydrolysis and deamination. Numerous metabolites are produced as a result of this process.
- Excretion: The primary method of excretion for azacitidine is urine, which accounts for between 50% (SC) and 85% (IV) of the material excreted, mainly metabolites. Less than 1% of the total is expelled through the faeces. With a half-life of about 4 hours, the drug's elimination is relatively short.
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