Azacitidine Hikma
Hypomethylating agent for myelodysplastic syndromes and acute myeloid leukemia
Azacitidine Hikma is a prescription chemotherapy medication used to treat certain blood cancers and bone marrow disorders, including myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML). It works as a hypomethylating agent, restoring the function of genes that control normal blood cell growth. This medicine is administered by subcutaneous injection in a hospital or clinic setting under specialist supervision.
Quick Facts
Key Takeaways
- Azacitidine Hikma is a hypomethylating agent used primarily for myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) in adults who are not candidates for stem cell transplant.
- It is given as a subcutaneous injection, typically 75 mg/m² daily for 7 days in a 28-day cycle, for a minimum of 6 treatment cycles.
- Regular blood count monitoring is essential as myelosuppression (low blood counts) is the most common serious side effect.
- This medication must not be used during pregnancy or breastfeeding due to risk of serious harm to the fetus.
- Clinical trials have demonstrated that azacitidine significantly improves overall survival in higher-risk MDS compared to conventional care.
What Is Azacitidine Hikma and What Is It Used For?
Azacitidine Hikma contains the active substance azacitidine, which belongs to a group of medicines known as antineoplastic agents, specifically the class of pyrimidine analogues with hypomethylating activity. It is a generic formulation that is bioequivalent to the original branded product Vidaza, meaning it delivers the same therapeutic effect at the same dosage.
Myelodysplastic syndromes (MDS) are a group of bone marrow disorders in which the bone marrow does not produce enough healthy blood cells. This can lead to anemia (low red blood cells), neutropenia (low white blood cells leading to increased infection risk), and thrombocytopenia (low platelets leading to increased bleeding risk). In some patients, MDS can progress to acute myeloid leukemia (AML), a rapidly growing cancer of the blood and bone marrow.
Azacitidine works through a dual mechanism of action. At lower concentrations, it inhibits DNA methyltransferase enzymes, leading to hypomethylation of DNA. This process can reactivate tumor suppressor genes that have been silenced by abnormal methylation in cancer cells, restoring normal cell growth regulation and promoting differentiation of abnormal cells. At higher concentrations, azacitidine is directly cytotoxic to abnormal cells in the bone marrow, helping to reduce the burden of diseased cells.
The European Medicines Agency (EMA) has approved azacitidine for the treatment of adult patients with the following conditions who are not eligible for hematopoietic stem cell transplantation (HSCT):
- Intermediate-2 and high-risk myelodysplastic syndromes (MDS) according to the International Prognostic Scoring System (IPSS)
- Chronic myelomonocytic leukemia (CMML) with 10-29% marrow blasts without myeloproliferative disorder
- Acute myeloid leukemia (AML) with 20-30% blasts and multi-lineage dysplasia, according to the World Health Organization (WHO) classification
- AML with more than 30% marrow blasts according to the WHO classification, in elderly patients (65 years or older) who are not eligible for conventional induction chemotherapy
The landmark AZA-001 clinical trial, published in The Lancet Oncology in 2009, demonstrated that azacitidine significantly improved overall survival in patients with higher-risk MDS compared to conventional care regimens. The median overall survival was 24.5 months in the azacitidine group compared to 15.0 months in the conventional care group, representing a 42% reduction in the risk of death. This trial established azacitidine as a standard of care for higher-risk MDS patients who are not candidates for transplantation.
Azacitidine is included on the World Health Organization (WHO) Model List of Essential Medicines, reflecting its importance in the treatment of these hematological malignancies worldwide. It represents a significant advancement in the management of MDS and AML, particularly for older patients who cannot tolerate intensive chemotherapy regimens.
What Should You Know Before Taking Azacitidine Hikma?
Azacitidine Hikma is a potent chemotherapy medication that requires careful medical supervision. Before treatment begins, your healthcare team will conduct a thorough assessment to ensure that this medication is appropriate for you. Understanding the contraindications, warnings, and precautions is essential for safe and effective treatment.
Contraindications
Azacitidine Hikma must not be used in the following situations:
- Hypersensitivity: Known allergy to azacitidine or any of the excipients in the formulation (mannitol)
- Advanced malignant hepatic tumors: Patients with advanced liver cancers should not receive azacitidine
- Pregnancy: Azacitidine is teratogenic and must not be used during pregnancy
- Breastfeeding: Women should not breastfeed during treatment with azacitidine
Warnings and Precautions
Several important warnings apply to the use of azacitidine. Your healthcare team will monitor you closely throughout treatment to manage these risks effectively.
Azacitidine causes myelosuppression (suppression of bone marrow function), which can lead to severe decreases in blood cell counts. Complete blood counts must be performed before each treatment cycle and as clinically indicated to monitor for neutropenia, thrombocytopenia, and anemia. Dose delays and adjustments may be necessary based on blood count results.
- Hematological toxicity: Myelosuppression is the most common adverse effect. Patients should be monitored for signs of infection (fever, chills, sore throat), bleeding (unusual bruising, blood in urine or stool), and anemia (fatigue, shortness of breath, pallor).
- Hepatotoxicity: Liver function should be monitored before and during treatment. Cases of hepatic failure and hepatic coma have been reported, particularly in patients with pre-existing liver conditions or extensive tumor burden in the liver.
- Renal toxicity: Kidney function should be assessed before starting treatment and monitored regularly. Renal tubular acidosis (a decrease in serum bicarbonate to less than 20 mmol/L associated with alkaline urine and hypokalemia) has been reported. Dose reduction or discontinuation may be necessary if unexplained reductions in serum bicarbonate or increases in serum creatinine occur.
- Tumor lysis syndrome: Patients with a large tumor burden prior to treatment may be at risk of tumor lysis syndrome. Adequate hydration and monitoring of uric acid levels may be advisable.
- Cardiac disorders: Patients with pre-existing cardiac conditions should be monitored carefully as cardiac events including heart failure have been reported during azacitidine treatment.
- Injection site reactions: Local reactions at the injection site are common and may include redness, pain, induration, and rarely necrosis. Injection sites should be rotated, and symptomatic treatment may be applied as needed.
Pregnancy and Breastfeeding
Azacitidine Hikma poses significant risks during pregnancy and must not be used by pregnant women. Preclinical studies have shown that azacitidine is teratogenic (causes birth defects) and embryotoxic (harmful to the developing embryo). The following precautions are mandatory:
- Women of childbearing potential must use effective contraception during treatment and for 6 months after the last dose of azacitidine. A pregnancy test should be performed before starting treatment.
- Male patients must use effective contraception during treatment and for 3 months after the last dose, as azacitidine may affect sperm quality and fertility.
- Breastfeeding must be discontinued during treatment because it is unknown whether azacitidine or its metabolites are excreted in human breast milk.
- If pregnancy occurs during treatment, the patient should be informed of the potential hazard to the fetus and treatment should be discontinued.
Men are advised to seek counseling on sperm cryopreservation before starting treatment with azacitidine, as the drug may impair male fertility. The effects on female fertility have not been studied in humans, but animal data suggest potential adverse effects on fertility.
How Does Azacitidine Hikma Interact with Other Drugs?
Drug interactions with azacitidine can affect the safety and efficacy of treatment. While formal interaction studies are limited, several clinically significant interactions have been identified based on the pharmacological properties of azacitidine and post-marketing surveillance data. Your oncologist or hematologist will carefully review your medication list before starting treatment.
Azacitidine is primarily metabolized by spontaneous hydrolysis and by deamination mediated by cytidine deaminase. It does not appear to be a substrate of cytochrome P450 (CYP) enzymes and is unlikely to cause CYP-mediated drug interactions. However, interactions may occur through other mechanisms, particularly related to additive toxicities or immunosuppressive effects.
Major Interactions
| Interacting Drug/Class | Type of Interaction | Clinical Significance | Recommendation |
|---|---|---|---|
| Live vaccines (e.g., MMR, varicella, yellow fever) | Immunosuppressive effect | Risk of disseminated vaccine infection due to suppressed immune system | Contraindicated during treatment; use inactivated vaccines where possible |
| Other myelosuppressive agents (e.g., other chemotherapy, methotrexate) | Additive myelosuppression | Increased risk of severe neutropenia, thrombocytopenia, and anemia | Enhanced blood count monitoring; dose adjustments may be necessary |
| Hepatotoxic agents (e.g., acetaminophen/paracetamol at high doses, methotrexate, statins) | Additive hepatotoxicity | Increased risk of liver damage, potentially leading to hepatic failure | Monitor liver function closely; consider alternative medications |
| Nephrotoxic agents (e.g., NSAIDs, aminoglycosides, contrast agents) | Additive nephrotoxicity | Increased risk of renal tubular acidosis and kidney impairment | Monitor renal function and electrolytes; avoid if possible |
Minor Interactions
| Interacting Drug/Class | Type of Interaction | Recommendation |
|---|---|---|
| Anticoagulants (e.g., warfarin, heparin) | Increased bleeding risk due to thrombocytopenia | Monitor platelet counts and coagulation parameters closely |
| Antidiabetic agents (e.g., insulin, metformin) | Potential blood glucose fluctuations | Monitor blood glucose regularly during treatment cycles |
| Antihypertensives | Potential for hypotension, especially during nausea/vomiting episodes | Monitor blood pressure; adjust doses if needed |
It is essential that you inform your healthcare team about all medications you are currently taking, including prescription drugs, over-the-counter medications, vitamins, herbal supplements, and any complementary therapies. Some herbal products, such as St. John's wort or echinacea, may interact with chemotherapy agents and should be discussed with your oncologist before use.
What Is the Correct Dosage of Azacitidine Hikma?
Azacitidine Hikma dosing is calculated based on body surface area (BSA), which takes into account the patient's height and weight. The medication must be prepared and administered by a healthcare professional in a hospital or clinic setting. Dosing may need to be adjusted based on blood count results and the occurrence of adverse effects.
Adults
Standard Dosing Regimen
The recommended starting dose for all approved indications is 75 mg/m² body surface area, injected subcutaneously once daily for 7 consecutive days, followed by a rest period of 21 days. This constitutes one treatment cycle of 28 days. Treatment should be continued for a minimum of 6 cycles before assessing response.
Pre-medication with antiemetics (anti-nausea medications) may be given for the prevention of nausea and vomiting. The injection should be given at a different site each day to reduce injection site reactions. Injection sites should be rotated among the thigh, abdomen, and upper arm.
| Patient Group | Dose | Schedule | Duration |
|---|---|---|---|
| Adults (standard) | 75 mg/m² SC daily | Days 1-7 of each 28-day cycle | Minimum 6 cycles; continue until progression |
| Elderly (65+ years) | 75 mg/m² SC daily | Days 1-7 of each 28-day cycle | Same as adults; more frequent monitoring recommended |
| Renal impairment | 75 mg/m² (no initial adjustment needed) | Standard schedule; monitor renal function closely | Dose reduce by 50% if serum bicarbonate <20 mmol/L |
| Hepatic impairment | 75 mg/m² (mild-moderate) | Standard schedule; monitor liver function | Contraindicated in advanced hepatic tumors |
Dose Adjustments for Hematological Toxicity
Dose modifications are commonly required during azacitidine treatment due to myelosuppression. The following guidelines are used for dose adjustments based on blood count nadir values (the lowest point blood counts reach during a cycle):
If blood counts have not recovered to acceptable levels (absolute neutrophil count ≥1.0 x 10&sup9;/L and platelet count ≥50 x 10&sup9;/L) by Day 28, the next cycle should be delayed until recovery. If recovery takes more than 14 additional days, the dose should be reduced by 50% for the next cycle. If blood counts fall below certain thresholds during a cycle, the dose for subsequent cycles should be reduced according to the prescribing physician's judgment.
Children and Adolescents
The safety and efficacy of azacitidine in children and adolescents below 18 years of age have not been established. There are currently no data available to support the use of azacitidine in the pediatric population. Therefore, azacitidine is not recommended for use in patients under 18 years of age.
Elderly Patients
No specific dose adjustment is required for elderly patients. However, as elderly patients are more likely to have decreased renal function, it may be useful to monitor renal function more frequently. Elderly patients may also be more susceptible to adverse effects such as fatigue, infections, and bleeding, and may require more intensive supportive care during treatment.
Missed Dose
As azacitidine is administered in a clinical setting by healthcare professionals, missed doses are rare. However, if a scheduled dose is missed, it should be administered as soon as possible. The treating physician will determine whether to extend the treatment days within the cycle or adjust the schedule for subsequent cycles. Patients should not receive a double dose to make up for a missed injection.
Overdose
There is limited experience with overdose of azacitidine. In clinical trials, one case of overdose was reported in which a patient received approximately 290 mg/m² (nearly 4 times the recommended dose) intravenously. The adverse events observed were diarrhea, nausea, and vomiting, and the patient recovered without clinical sequelae.
In the event of an overdose, the patient should be monitored with appropriate blood counts and should receive supportive treatment as necessary. There is no specific antidote for azacitidine overdose. Hemodialysis is unlikely to be effective due to the rapid tissue distribution and metabolism of the drug.
What Are the Side Effects of Azacitidine Hikma?
Like all chemotherapy medications, Azacitidine Hikma can cause side effects. Not everyone will experience all of these effects, and their severity can vary between individuals. Your healthcare team will monitor you closely and can provide treatments to help manage many of these side effects. It is important to report any new or worsening symptoms to your doctor promptly.
The side effects listed below are categorized by frequency according to the convention used by the European Medicines Agency (EMA). Understanding the frequency can help you distinguish between common expected effects and rarer events that may require immediate medical attention.
Very Common Side Effects
- Anemia (low red blood cells) - fatigue, shortness of breath, pallor
- Neutropenia (low white blood cells) - increased risk of infections
- Thrombocytopenia (low platelets) - bruising, bleeding
- Febrile neutropenia - fever with low white blood cell count
- Nausea - feeling sick
- Vomiting
- Diarrhea
- Constipation
- Injection site reactions - redness, pain, swelling, bruising at injection site
- Fatigue and weakness
- Pyrexia (fever)
- Pneumonia and other respiratory infections
Common Side Effects
- Sepsis (blood infection) - including neutropenic sepsis
- Urinary tract infections
- Upper respiratory tract infections - nasopharyngitis, sinusitis
- Decreased appetite and weight loss
- Dizziness and headache
- Abdominal pain and stomatitis (mouth sores)
- Dyspnea (shortness of breath)
- Skin rash, pruritus (itching), petechiae (small red spots)
- Arthralgia (joint pain) and myalgia (muscle pain)
- Hypokalemia (low potassium) and other electrolyte disturbances
- Elevated liver enzymes (transaminases)
- Insomnia
Uncommon Side Effects
- Tumor lysis syndrome - rapid breakdown of cancer cells
- Renal tubular acidosis - kidney function disturbance
- Injection site necrosis - tissue death at injection site
- Allergic reactions - including hypersensitivity
- Sweet syndrome (acute febrile neutrophilic dermatosis)
- Pyoderma gangrenosum - ulcerative skin condition
Rare Side Effects
- Hepatic failure and hepatic coma (especially in patients with extensive liver tumor burden)
- Differentiation syndrome - potentially life-threatening condition
- Interstitial lung disease - progressive lung inflammation
- Necrotizing fasciitis - severe soft tissue infection
Contact your healthcare team immediately or go to the nearest emergency department if you experience: fever above 38°C (especially if accompanied by chills or signs of infection), unusual bleeding or bruising, severe abdominal pain, persistent vomiting or diarrhea, difficulty breathing, signs of allergic reaction (swelling of face/throat, severe rash, difficulty breathing), yellowing of skin or eyes (jaundice), or dark-colored urine.
Many side effects of azacitidine are related to its effect on blood cell production and are expected during treatment. Your healthcare team has experience managing these effects and can provide supportive treatments such as blood transfusions, growth factors (G-CSF for neutropenia), antibiotics for infections, and antiemetics for nausea. Dose adjustments or temporary treatment delays may also be used to manage toxicity while maintaining therapeutic benefit.
How Should You Store Azacitidine Hikma?
Proper storage of Azacitidine Hikma is essential to maintain the quality and effectiveness of the medication. As this is a hospital-administered medication, storage is typically handled by pharmacy and nursing staff. However, understanding the storage requirements can help ensure optimal treatment quality.
Unopened Vials
- Store below 25°C (77°F)
- Do not freeze
- Keep in the original packaging to protect from light
- Keep out of the sight and reach of children
- Do not use after the expiry date printed on the vial label and carton
Reconstituted Suspension
Once the powder has been mixed with sterile water for injection to create the suspension for administration:
- For immediate use: the reconstituted suspension should be administered within 45 minutes when stored below 25°C
- For delayed use: the reconstituted suspension may be placed in a refrigerator (2-8°C) for up to 8 hours
- If stored in the refrigerator, the suspension should be allowed to equilibrate to room temperature for approximately 30 minutes before injection
- If particles are visible in the suspension after gentle re-rolling between the palms, the vial should be discarded
Azacitidine is a cytotoxic medication. Any unused product, waste material, or equipment that has come into contact with azacitidine should be disposed of in accordance with local regulations for cytotoxic waste. Healthcare professionals should follow standard procedures for the handling and disposal of anticancer medicinal products.
What Does Azacitidine Hikma Contain?
Active Substance
The active ingredient in Azacitidine Hikma is azacitidine, a pyrimidine nucleoside analogue of cytidine. Each vial contains 100 mg of azacitidine as a white to off-white lyophilized (freeze-dried) powder. Azacitidine has the molecular formula C8H12N4O5 and a molecular weight of 244.20 g/mol.
Excipients (Inactive Ingredients)
The formulation contains a single excipient:
- Mannitol (E421): 100 mg per vial - used as a bulking agent and cryoprotectant during the freeze-drying process to ensure proper reconstitution characteristics
Reconstitution
When reconstituted with 4 ml of sterile water for injection, the resulting suspension contains 25 mg/ml azacitidine. The reconstituted product is a uniform, cloudy suspension free of agglomerates. Each vial is intended for single use only, and any remaining suspension should be discarded after the dose has been withdrawn.
Azacitidine Hikma is supplied as a Type I glass vial with a rubber stopper and aluminum seal with a flip-off cap. Each pack contains one vial. The product should appear as a white to off-white lyophilized powder or cake before reconstitution.
Frequently Asked Questions About Azacitidine Hikma
Azacitidine Hikma is used to treat adults with myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML) with 20-30% blasts and multi-lineage dysplasia. It is particularly indicated for patients who are not eligible for hematopoietic stem cell transplantation. It works by inhibiting DNA methylation, helping to restore normal cell growth control.
Azacitidine Hikma is given as a subcutaneous injection, typically administered by a healthcare professional in a hospital or clinic setting. The standard dose is 75 mg/m² body surface area, injected once daily for 7 consecutive days, followed by a rest period of 21 days (28-day treatment cycle). Injection sites should be rotated between the thigh, abdomen, and upper arm. Treatment should continue for at least 6 cycles before assessing response.
The most common side effects include blood count changes (anemia, neutropenia, thrombocytopenia), injection site reactions (redness, pain, bruising), gastrointestinal symptoms (nausea, vomiting, diarrhea, constipation), fatigue, and fever. Blood counts are regularly monitored during treatment, and dose adjustments may be necessary if counts drop too low. Most side effects are manageable with appropriate supportive care.
No, Azacitidine Hikma must not be used during pregnancy as it may cause serious birth defects or fetal death. Women of childbearing potential must use effective contraception during treatment and for 6 months after the last dose. Men must use effective contraception during treatment and for 3 months after the last dose. A pregnancy test should be performed before starting treatment. If pregnancy occurs during treatment, medical advice should be sought immediately.
Unopened vials should be stored below 25°C and protected from light. After reconstitution with sterile water, the suspension should be used within 45 minutes if kept at room temperature, or may be stored in a refrigerator (2-8°C) for up to 8 hours. If refrigerated, allow approximately 30 minutes to reach room temperature before injection.
Azacitidine Hikma contains the same active substance (azacitidine) as Vidaza and is approved as a generic equivalent. It has been demonstrated to be bioequivalent, meaning it delivers the same amount of active substance at the same rate and to the same extent. The choice between branded and generic versions is typically made by the prescribing physician or healthcare facility, often based on availability and cost considerations.
References
This article is based on the following peer-reviewed sources and international medical guidelines:
- Fenaux P, Mufti GJ, Hellstrom-Lindberg E, et al. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. The Lancet Oncology. 2009;10(3):223-232. doi:10.1016/S1470-2045(09)70003-8
- European Medicines Agency (EMA). Summary of Product Characteristics - Azacitidine. Available at: www.ema.europa.eu. Last updated 2024.
- National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Myelodysplastic Syndromes. Version 1.2024.
- World Health Organization. WHO Model List of Essential Medicines - 23rd List. 2023.
- Silverman LR, Demakos EP, Peterson BL, et al. Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the Cancer and Leukemia Group B. Journal of Clinical Oncology. 2002;20(10):2429-2440.
- Dombret H, Seymour JF, Butrym A, et al. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood. 2015;126(3):291-299.
- Greenberg PL, Tuechler H, Schanz J, et al. Revised International Prognostic Scoring System for myelodysplastic syndromes. Blood. 2012;120(12):2454-2465.
- British National Formulary (BNF). Azacitidine monograph. Available at: bnf.nice.org.uk. Accessed 2025.
Medical Editorial Team
This article has been written and reviewed by the iMedic Medical Editorial Team, comprising licensed physicians specializing in hematology, medical oncology, and clinical pharmacology. Our editorial process follows the GRADE evidence framework and adheres to international guidelines from the EMA, NCCN, and WHO.
All content is reviewed by board-certified physicians with clinical experience in hematology and oncology. Evidence level: 1A based on randomized controlled trials and systematic reviews.
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