Onureg (Azacitidine)
Oral antimetabolite for acute myeloid leukemia maintenance therapy
Quick Facts About Onureg
Key Takeaways
- Onureg (azacitidine) is the first oral maintenance therapy specifically approved for adults with acute myeloid leukemia (AML) in remission after intensive chemotherapy.
- The standard dosage is 300 mg once daily for 14 days followed by a 14-day rest period in each 28-day treatment cycle, continuing as long as the patient benefits.
- Regular blood tests are essential during treatment to monitor blood cell counts, liver function, and kidney function, as Onureg can cause significant cytopenias.
- The most common side effects include nausea, vomiting, diarrhea, fatigue, and low blood counts – anti-emetics are routinely prescribed to manage gastrointestinal symptoms.
- Onureg must not be used during pregnancy or breastfeeding, and effective contraception is required for both women (6 months post-treatment) and men (3 months post-treatment).
What Is Onureg and What Is It Used For?
Onureg (azacitidine) represents an important advancement in the treatment of acute myeloid leukemia (AML), one of the most common and aggressive forms of blood cancer in adults. AML affects the bone marrow and disrupts the normal production of blood cells, leading to a deficiency in healthy white blood cells, red blood cells, and platelets. Without appropriate treatment, AML progresses rapidly and can become life-threatening within weeks to months of diagnosis.
The primary role of Onureg is as a maintenance therapy for adult patients who have achieved first complete remission (CR) or complete remission with incomplete blood count recovery (CRi) following intensive induction chemotherapy, and who are not able to complete intensive curative therapy including hematopoietic stem cell transplantation. Maintenance therapy is a critical phase of AML treatment designed to sustain the remission achieved during initial chemotherapy and delay or prevent disease relapse.
Before the approval of Onureg, there was no widely established standard-of-care maintenance therapy for AML patients in first remission who were not undergoing stem cell transplantation. The QUAZAR AML-001 clinical trial, a landmark phase 3 randomized study, demonstrated that oral azacitidine significantly improved overall survival compared to placebo, with a median overall survival of 24.7 months versus 14.8 months. This represented a clinically meaningful improvement and led to regulatory approvals by the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA).
How Does Onureg Work?
Azacitidine, the active ingredient in Onureg, is a nucleoside analogue that works through a dual mechanism of action. It functions as a hypomethylating agent, meaning it alters the way cells activate and deactivate genes through a process called DNA methylation. In cancer cells, abnormal DNA methylation patterns can silence tumour suppressor genes, allowing malignant cells to grow unchecked. By inhibiting DNA methyltransferases, azacitidine reverses this abnormal methylation and restores normal gene function.
In addition to its epigenetic effects, azacitidine is incorporated directly into cellular DNA and RNA, which disrupts normal nucleic acid metabolism and reduces the production of new genetic material. This cytotoxic effect selectively targets rapidly dividing cancer cells. Together, these mechanisms work to block the growth and survival of leukemia cells in the bone marrow, helping to maintain the remission achieved through initial chemotherapy.
It is important to note that Onureg (oral azacitidine) has distinct pharmacokinetic properties compared to injectable azacitidine (marketed as Vidaza and other brand names). The oral formulation provides prolonged, lower-level exposure to the drug, which is believed to be more suitable for maintenance therapy, while the injectable form delivers higher peak concentrations appropriate for active disease treatment.
What Should You Know Before Taking Onureg?
Contraindications
There are specific situations in which Onureg must not be used. Understanding these contraindications is essential for patient safety. You should not take Onureg if:
- You are allergic (hypersensitive) to azacitidine or any of the other ingredients in the tablet (including lactose monohydrate, croscarmellose sodium, magnesium stearate, mannitol, or silicified microcrystalline cellulose).
- You are currently breastfeeding, as azacitidine may be excreted in breast milk and could harm the nursing infant.
If you have a known allergy to any component of Onureg, inform your healthcare provider immediately. An allergic reaction may present as skin rash, itching, swelling of the face or throat, difficulty breathing, or dizziness. In rare cases, severe anaphylactic reactions can occur and require emergency medical attention.
Warnings and Precautions
Onureg can significantly reduce blood cell counts, which may lead to serious infections, bleeding, or anaemia. Your doctor will perform regular blood tests before and during treatment to monitor your white blood cells, red blood cells, and platelets. Report any signs of infection (fever, chills), unusual bleeding or bruising, or severe fatigue to your doctor immediately.
Several important precautions should be observed during Onureg therapy. Your healthcare team will conduct regular blood tests both before treatment initiation and at periodic intervals throughout therapy. These tests are critical for monitoring:
- Complete blood counts – to check for neutropenia (low white blood cells), thrombocytopenia (low platelets), and anaemia (low red blood cells).
- Liver function tests – to ensure the liver is processing the medication appropriately.
- Kidney function tests – to verify that renal function remains adequate for drug clearance.
Contact your healthcare provider immediately if you experience any of the following during treatment:
- Bruising or bleeding – this may indicate thrombocytopenia (low platelet count).
- Fever – this could be a sign of infection due to neutropenia (low white blood cell count), which can be life-threatening if untreated.
- Diarrhea, vomiting, or nausea – while common side effects, severe gastrointestinal symptoms may require dose adjustment or treatment interruption.
Azacitidine can also cause a rare but serious immune reaction called differentiation syndrome, which may manifest as fever, cough, breathing difficulties, skin rash, decreased urine output, low blood pressure, swelling of the arms or legs, and rapid weight gain. If you experience any combination of these symptoms, seek medical attention immediately, as differentiation syndrome requires prompt treatment.
Your doctor may need to modify your treatment based on how you respond, including adjusting the dose, pausing treatment temporarily, or discontinuing Onureg entirely. Additional supportive medications may be prescribed to manage side effects.
Onureg is not recommended for use in children and adolescents under 18 years of age. The safety and efficacy of oral azacitidine have not been established in paediatric populations, and clinical trials have been conducted exclusively in adult patients.
Pregnancy and Breastfeeding
Onureg poses significant risks to reproductive health and must be used with extreme caution in patients of childbearing potential. The following guidelines apply:
Pregnancy: Onureg must not be taken during pregnancy. Based on its mechanism of action and preclinical data, azacitidine is expected to cause harm to the developing foetus, including potential birth defects and foetal loss. If you become pregnant while taking Onureg, inform your doctor immediately. A pregnancy test should be performed before starting treatment.
Contraception: Women of childbearing potential must use highly effective contraception during Onureg treatment and for at least 6 months after the final dose. Men with female partners of childbearing potential must use effective contraception during treatment and for at least 3 months after the last dose. Your doctor can advise on the most appropriate contraceptive methods.
Breastfeeding: Breastfeeding is contraindicated during Onureg treatment. It is not known whether azacitidine is excreted in human breast milk, but given the potential for serious adverse reactions in nursing infants, breastfeeding must be discontinued before starting therapy.
Fertility: Onureg may impair fertility in both men and women. If you wish to have children in the future, discuss fertility preservation options with your doctor before starting treatment. Sperm banking for men and oocyte or embryo cryopreservation for women may be considered.
Driving and Operating Machinery
Onureg may cause fatigue, weakness, or difficulty concentrating. If you experience these or other side effects that could impair your alertness, you should not drive vehicles or operate heavy machinery until you are confident that your abilities are not affected.
Important Information About Excipients
Onureg tablets contain lactose monohydrate. If you have been diagnosed with an intolerance to certain sugars (such as galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption), consult your doctor before taking this medicine.
Onureg contains less than 1 mmol (23 mg) of sodium per tablet, meaning it is essentially sodium-free and suitable for patients on sodium-restricted diets.
How Does Onureg Interact with Other Drugs?
Drug interactions can alter the effectiveness of Onureg or increase the risk of adverse effects. It is essential that you inform your healthcare provider about all medications you are currently taking, have recently taken, or are planning to take. This includes prescription medications, non-prescription drugs, vitamins, and herbal supplements.
While specific major drug-drug interactions with oral azacitidine have not been extensively characterized in dedicated interaction studies, several categories of medications warrant particular attention due to their potential to interact with Onureg or exacerbate its side effects.
Significant Interactions to Consider
| Drug / Class | Interaction Type | Clinical Significance |
|---|---|---|
| Other cytotoxic agents (e.g., cytarabine, methotrexate) | Additive myelosuppression | Increased risk of severe cytopenias; requires close blood count monitoring |
| Immunosuppressants (e.g., ciclosporin, tacrolimus) | Additive immunosuppression | Heightened infection risk; careful monitoring required |
| Live vaccines | Reduced immune response | Avoid live vaccines during treatment; inactivated vaccines may have reduced efficacy |
| Anticoagulants (e.g., warfarin, heparin) | Increased bleeding risk | Thrombocytopenia from Onureg may compound anticoagulant effects; monitor INR closely |
| Nephrotoxic drugs (e.g., aminoglycosides, NSAIDs) | Additive renal effects | May impair renal clearance of azacitidine; renal function monitoring advised |
Additional Considerations
Patients should also be aware that grapefruit and grapefruit juice can affect the metabolism of many medications, although a specific interaction with azacitidine has not been established. As a precaution, discuss consumption of grapefruit products with your doctor.
Over-the-counter medications that affect blood clotting, such as aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs), should be used with caution during Onureg treatment, as they may increase the risk of bleeding in patients with low platelet counts.
Herbal supplements, particularly those with anticoagulant properties (such as ginkgo biloba, garlic supplements, or fish oil), should be discussed with your oncologist, as they may potentiate the bleeding risk associated with thrombocytopenia.
What Is the Correct Dosage of Onureg?
Onureg should always be taken exactly as prescribed by your doctor. Do not change your dose or stop treatment without consulting your healthcare provider. The dosing regimen for Onureg follows a structured cycle designed to balance anticancer efficacy with tolerability.
Standard Adult Dosage
Recommended Dosing Schedule
- Standard dose: 300 mg orally, once daily
- Treatment days: Days 1 through 14 of each 28-day cycle
- Rest period: Days 15 through 28 (no medication)
- Reduced dose (if needed): 200 mg orally, once daily
- Duration: Treatment continues for as long as the patient benefits, or until disease progression or unacceptable toxicity
The 28-day cycle structure is fundamental to Onureg therapy. During the first 14 days, you take one tablet each day. This is followed by a 14-day treatment-free period during which your body recovers before the next cycle begins. This cyclical dosing approach is essential for managing the drug's effects on blood cell production while maintaining therapeutic benefit.
| Parameter | Standard Dose | Reduced Dose |
|---|---|---|
| Daily dose | 300 mg once daily | 200 mg once daily |
| Treatment days per cycle | Day 1–14 | Day 1–14 (or Day 1–7) |
| Cycle length | 28 days | 28 days |
| Administration | Oral, with or without food | Oral, with or without food |
| Anti-emetic pre-treatment | 30 min before, cycles 1–2 | 30 min before, cycles 1–2 |
Your doctor may decide to adjust your treatment in several ways, depending on how well you tolerate the medication and your clinical response:
- Extend treatment duration beyond 14 days within a cycle if clinically appropriate.
- Reduce the dose from 300 mg to 200 mg per day in the event of significant side effects.
- Shorten the treatment period to 7 days per cycle if dose reduction alone is insufficient.
- Temporarily pause treatment to allow blood counts to recover before resuming.
How to Take Onureg
Proper administration of Onureg is essential for both safety and efficacy. Follow these guidelines carefully:
- Take Onureg once daily at the same time each day to maintain consistent drug levels.
- Swallow the tablet whole with a full glass of water. Do not split, crush, dissolve, or chew the tablets, as this may alter the drug's release profile and increase the risk of side effects.
- Onureg can be taken with or without food.
- Take your prescribed anti-emetic medication 30 minutes before each Onureg dose during the first and second treatment cycles (and longer if directed by your doctor).
- If you vomit after taking a tablet, do not take a replacement dose that day. Resume your normal schedule the following day.
- If you get powder from a broken tablet on your skin, wash the area immediately with soap and water. If powder contacts your eyes, nose, or mouth, rinse thoroughly with water.
Missed Dose
If you forget to take Onureg at your usual time, take the missed dose as soon as you remember on the same day, then resume your normal schedule the next day. Do not take a double dose to compensate for a missed or vomited tablet. If you are unsure about what to do, contact your doctor or pharmacist for guidance.
Overdose
If you have taken more Onureg tablets than prescribed, contact your doctor or go to the nearest hospital emergency department immediately. If possible, bring the medication packaging and this information with you. An overdose of azacitidine may cause severe myelosuppression and gastrointestinal toxicity requiring urgent medical management.
Children and Elderly
Children and adolescents (under 18 years): Onureg is not approved for use in paediatric patients. Clinical data in this age group are not available.
Elderly patients: No specific dose adjustment is required based on age alone. However, elderly patients may be more susceptible to side effects, particularly cytopenias and infections. Closer monitoring may be warranted, and dose adjustments should be made based on individual tolerance and blood count results.
Do not stop taking Onureg unless your doctor tells you to do so. Premature discontinuation of maintenance therapy may increase the risk of disease relapse.
What Are the Side Effects of Onureg?
Like all medications, Onureg can cause side effects, although not everyone who takes it will experience them. Understanding the potential side effects, their frequency, and when to seek medical help is an important part of your treatment. Your healthcare team will monitor you closely for adverse reactions and can provide supportive care to help manage any side effects that arise.
Contact your healthcare provider or seek emergency care immediately if you experience: unusual bruising or bleeding, fever or signs of infection, severe diarrhea or vomiting, difficulty breathing, skin rash with fever, swelling of arms or legs, or rapid weight gain. These may indicate serious complications requiring prompt treatment.
Very Common Side Effects
- Nausea
- Vomiting
- Diarrhea
- Constipation
- Abdominal (stomach) pain
- Thrombocytopenia (low platelet count) – may cause bruising or bleeding
- Neutropenia (low white blood cell count) – may increase infection risk
- Upper respiratory tract infection (cold, sinusitis, sore throat)
- Pneumonia (lung infection)
- Fatigue or weakness
- Decreased appetite
- Pain in various body areas (arthralgia, myalgia)
- Joint stiffness
- Back pain
Common Side Effects
- Sepsis (blood infection caused by bacteria) – may be related to low white blood cell counts
- Influenza (flu)
- Urinary tract infection
- Allergic rhinitis (hay fever symptoms)
- Anxiety
- Weight loss
Frequency Not Known
- Differentiation syndrome – a serious immune reaction that may cause fever, cough, breathing difficulties, skin rash, decreased urine output, low blood pressure (hypotension), swelling in arms or legs, and rapid weight gain. This condition requires immediate medical treatment.
Managing Common Side Effects
Gastrointestinal symptoms: Nausea and vomiting are among the most frequently reported side effects of Onureg. Your doctor will prescribe anti-emetic (anti-nausea) medication to be taken 30 minutes before each dose during the first two treatment cycles, and potentially longer if needed. Eating small, frequent meals and staying well-hydrated can also help manage these symptoms. If diarrhea is persistent or severe, contact your doctor, as fluid and electrolyte replacement may be necessary.
Low blood counts: Cytopenias (low blood cell counts) are an expected pharmacological effect of Onureg. Your doctor will monitor your blood counts regularly and may adjust your dose, delay treatment cycles, or provide supportive care such as growth factor support or blood transfusions as needed. To reduce infection risk during periods of neutropenia, practise good hand hygiene, avoid close contact with people who are ill, and avoid crowded places when your white blood cell count is low.
Fatigue: Cancer-related fatigue is common during AML maintenance therapy. Gentle exercise, adequate rest, and maintaining a balanced diet can help manage fatigue. Discuss persistent or worsening fatigue with your healthcare team, as it may also be a sign of anaemia requiring treatment.
Reporting Side Effects
Reporting suspected side effects after a medicine has been authorised is important for ongoing safety monitoring. Healthcare professionals and patients are encouraged to report any suspected adverse reactions to their national regulatory authority. This helps ensure continuous monitoring of the medicine's benefit-risk balance.
How Should You Store Onureg?
Proper storage of Onureg is essential to maintain the integrity and effectiveness of the medication. Follow these storage guidelines:
- Keep Onureg out of the sight and reach of children at all times.
- Do not use Onureg after the expiry date stated on the blister pack and outer carton after "EXP." The expiry date refers to the last day of the stated month.
- No special storage conditions are required – store at room temperature.
- Keep the tablets in the original blister packaging to protect them from moisture and light until ready to use.
- Do not dispose of medications via wastewater or household waste. Ask your pharmacist how to properly dispose of unused or expired medicines. These measures help protect the environment.
If you notice any visible changes in the appearance of the tablets (such as discolouration, crumbling, or unusual odour), do not take them and consult your pharmacist for a replacement.
What Does Onureg Contain?
Active Ingredient
Each Onureg film-coated tablet contains either 200 mg or 300 mg of azacitidine as the active substance.
Inactive Ingredients (Excipients)
The tablet core contains the following excipients:
- Croscarmellose sodium (E468) – a disintegrant that helps the tablet break down in the digestive system
- Magnesium stearate (E572) – a lubricant used in tablet manufacturing
- Mannitol (E421) – a sugar alcohol used as a filler
- Silicified microcrystalline cellulose (E460, E551) – provides structural integrity to the tablet
Tablet Appearance
| Strength | Colour | Shape | Imprint |
|---|---|---|---|
| 200 mg | Pink | Oval | "200" on one side, "ONU" on the other |
| 300 mg | Brown | Oval | "300" on one side, "ONU" on the other |
The 200 mg tablet coating (Pink Opadry II) contains hypromellos (E464), titanium dioxide (E171), lactose monohydrate, polyethylene glycol/macrogol (E1521), triacetin (E1518), and red iron oxide (E172).
The 300 mg tablet coating (Brown Opadry II) contains hypromellos (E464), titanium dioxide (E171), lactose monohydrate, polyethylene glycol/macrogol (E1521), triacetin (E1518), red iron oxide (E172), yellow iron oxide (E172), and black iron oxide (E172).
The tablets are packaged in aluminium blisters. Each pack contains 7 or 14 film-coated tablets. Not all pack sizes may be marketed in all countries.
Marketing Authorisation
Marketing authorisation holder: Bristol-Myers Squibb Pharma EEIG, Plaza 254, Blanchardstown Corporate Park 2, Dublin 15, D15 T867, Ireland.
Manufacturer: Celgene Distribution B.V., Orteliuslaan 1000, 3528 BD Utrecht, Netherlands.
Other Azacitidine Brand Names
Azacitidine is also available under other brand names and formulations for different indications. These include injectable formulations for the treatment of myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), and AML:
- Vidaza – the original injectable azacitidine formulation
- Azacitidine STADA, Azacitidine Kabi, Azacitidine Mylan, Azacitidine betapharm, Azacitidine Zentiva, Azacitidine Sandoz – generic injectable versions
It is important to understand that these injectable formulations are not interchangeable with Onureg oral tablets. The different formulations have distinct pharmacokinetic profiles, approved indications, and dosing regimens. Always use the specific formulation prescribed by your doctor.
Frequently Asked Questions About Onureg
Onureg (azacitidine) is used as maintenance therapy for adult patients with acute myeloid leukemia (AML) who have achieved first complete remission (CR) or complete remission with incomplete blood count recovery (CRi) following intensive induction chemotherapy. Its purpose is to keep the disease in remission and delay or prevent relapse. It is not used as a first-line treatment for active AML, but rather as a follow-up therapy after initial chemotherapy has successfully reduced the cancer.
Onureg and Vidaza both contain azacitidine but are fundamentally different medications. Onureg is an oral tablet taken by mouth, while Vidaza is administered via injection (subcutaneous or intravenous). They are approved for different indications: Onureg for AML maintenance therapy, and Vidaza for treatment of myelodysplastic syndromes (MDS), CMML, and AML. The oral formulation provides prolonged, lower-level drug exposure compared to the injectable form's higher peak concentrations. They are not interchangeable and should never be substituted for one another.
If you miss a dose of Onureg, take it as soon as you remember on the same day, then take your next dose at the regular time the following day. Do not take two doses on the same day to make up for a missed dose. Similarly, if you vomit after taking a tablet, do not take a replacement dose – simply wait until the next day and resume your normal schedule. If you are unsure about what to do, contact your doctor or pharmacist for advice.
There is no specific contraindication regarding alcohol and Onureg. However, alcohol can irritate the stomach lining and may worsen gastrointestinal side effects such as nausea and vomiting, which are already common with Onureg. Additionally, alcohol can impair liver function, and your liver needs to be functioning well during cancer treatment. It is generally advisable to limit or avoid alcohol during chemotherapy. Discuss your alcohol consumption with your oncologist for personalised guidance.
Onureg treatment continues for as long as you benefit from the therapy, or until disease progression, unacceptable side effects, or your doctor decides to stop treatment. There is no fixed duration – some patients may take Onureg for many months or even years. In the QUAZAR AML-001 clinical trial, the median duration of treatment was approximately 12 cycles (about 12 months). Your doctor will regularly assess your response to treatment and decide on the most appropriate duration for your situation.
Regular blood tests are an essential part of Onureg therapy. Before starting treatment and throughout each cycle, your doctor will order complete blood counts (CBC) to monitor white blood cells, red blood cells, and platelets. Liver function tests and kidney function tests are also performed to ensure these organs are working properly. The frequency of blood tests is determined by your doctor based on your individual response to treatment, but they are typically performed before each new cycle and more frequently during the early cycles of therapy.
References
This article is based on the following peer-reviewed sources and regulatory documents:
- Wei AH, Döhner H, Pocock C, et al. Oral Azacitidine Maintenance Therapy for Acute Myeloid Leukemia in First Remission. N Engl J Med. 2020;383(26):2526-2537. doi:10.1056/NEJMoa2004444
- European Medicines Agency (EMA). Onureg (azacitidine) – Summary of Product Characteristics. Last updated January 2026.
- U.S. Food and Drug Administration (FDA). Onureg (azacitidine tablets) – Prescribing Information. Bristol-Myers Squibb.
- Döhner H, Wei AH, Appelbaum FR, et al. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood. 2022;140(12):1345-1377.
- National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology: Acute Myeloid Leukemia. Version 3.2025.
- World Health Organization (WHO). WHO Model List of Essential Medicines – 23rd List (2023).
- Döhner H, Estey E, Grimwade D, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129(4):424-447.
About the Medical Editorial Team
All content on iMedic is written and reviewed by a team of licensed physicians with expertise in the relevant medical specialty. Our editorial process follows the GRADE evidence framework, ensuring that all medical claims are supported by the highest available level of evidence. Content is regularly updated to reflect current clinical guidelines and regulatory information.
Medical Writers
Board-certified oncologists and clinical pharmacologists with expertise in haematological malignancies and anticancer drug therapy.
Medical Reviewers
Independent review by the iMedic Medical Review Board, comprising specialists who verify accuracy against international guidelines (EMA, FDA, NCCN, ELN).
Evidence Level: 1A – Based on systematic reviews of randomised controlled trials and international regulatory documents.
Guideline Adherence: EMA SmPC, FDA Prescribing Information, NCCN Guidelines, ELN Recommendations.
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